Adakitic magmas: modern analogues of Archaean granitoids

NASA Astrophysics Data System (ADS)

Martin, Hervé

1999-03-01

Both geochemical and experimental petrological research indicate that Archaean continental crust was generated by partial melting of an Archaean tholeiite transformed into a garnet-bearing amphibolite or eclogite. The geodynamic context of tholeiite melting is the subject of controversy. It is assumed to be either (1) subduction (melting of a hot subducting slab), or (2) hot spot (melting of underplated basalts). These hypotheses are considered in the light of modern adakite genesis. Adakites are intermediate to felsic volcanic rocks, andesitic to rhyolitic in composition (basaltic members are lacking). They have trondhjemitic affinities (high-Na 2O contents and K 2O/Na 2O˜0.5) and their Mg no. (0.5), Ni (20-40 ppm) and Cr (30-50 ppm) contents are higher than in typical calc-alkaline magmas. Sr contents are high (>300 ppm, until 2000 ppm) and REE show strongly fractionated patterns with very low heavy REE (HREE) contents (Yb≤1.8 ppm, Y≤18 ppm). Consequently, high Sr/Y and La/Yb ratios are typical and discriminating features of adakitic magmas, indicative of melting of a mafic source where garnet and/or hornblende are residual phases. Adakitic magmas are only found in subduction zone environments, exclusively where the subduction and/or the subducted slab are young (<20 Ma). This situation is well-exemplified in Southern Chile where the Chile ridge is subducted and where the adakitic character of the lavas correlates well with the young age of the subducting oceanic lithosphere. In typical subduction zones, the subducted lithosphere is older than 20 Ma, it is cool and the geothermal gradient along the Benioff plane is low such that the oceanic crust dehydrates before it reaches the solidus temperature of hydrated tholeiite. Consequently, the basaltic slab cannot melt. The released large ion lithophile element (LILE)-rich fluids rise up into the mantle wedge, inducing both its metasomatism and partial melting. Afterwards, the residue is made up of olivine

207Pb-206Pb zircon ages of eastern and western Dharwar craton, southern India : Evidence for contemporaneous Archaean crust

NASA Astrophysics Data System (ADS)

Maibam, B.; Goswami, J. N.; Srinivasan, R.

2009-04-01

Dharwar craton is one of the major Archaean crustal blocks in the Indian subcontinent. The craton is comprised of two blocks, western and eastern. The western domain is underlain by orthogneisses and granodiorites (ca. 2.9-3.3 Ga) collectively termed as Peninsular Gneiss [e.g., 1] interspersed with older tracts of metasedimentary and metamorphosed igneous suites (Sargur Group and Dharwar Group; [2]). The eastern part of the craton is dominated by Late Archaean (2.50-2.75 Ga) granitoids and their gneissic equivalents. They are interspersed with schist belts (also of Sargur Group and Dharwar Group), which are lithologically similar to the Dharwar Supergroup in the western block, but are in different metamorphic dress. Here we report 207Pb-206Pb age of zircons separated from the metasedimentary and gneissic samples from the two blocks to constrain the evolution of the Dharwar craton during the early Archaean. Detrital zircons of the metasedimentary rocks from both the blocks show a wide range of overlapping ages between ~2.9 to >3.5 Ga. Zircon ages of the orthogneisses from the two blocks showed that most of the analysed grains of the eastern Dharwar block are found to be of the age as old as the western Dharwar gneisses. Imprints of younger events could be discerned from the presence of overgrowths in zircons from the studied samples throughout the craton. Our data suggest that crust forming cycles in the two blocks of the Dharwar craton occurred contemporaneously during the Archaean. References [1] Beckinsale, R.D., Drury, S.A., Holt, R.W. (1980) Nature 283, 469-470. [2] Swami Nath J., Ramakrishnan M., Viswanatha M.N. (1976) Rec. Geol. Surv. Ind., 107, 149-175.

Mantle hydrous-fluid interaction with Archaean granite.

NASA Astrophysics Data System (ADS)

Słaby, E.; Martin, H.; Hamada, M.; Śmigielski, M.; Domonik, A.; Götze, J.; Hoefs, J.; Hałas, S.; Simon, K.; Devidal, J.-L.; Moyen, J.-F.; Jayananda, M.

2012-04-01

Water content/species in alkali feldspars from late Archaean Closepet igneous bodies as well as growth and re-growth textures, trace element and oxygen isotope composition have been studied (Słaby et al., 2011). Both processes growth and re-growth are deterministic, however they differ showing increasing persistency in element behaviour during interaction with fluids. The re-growth process fertilized domains and didn't change their oxygen-isotope signature. Water speciation showed persistent behaviour during heating at least up to 600oC. Carbonate crystals with mantle isotope signature are associated with the recrystallized feldspar domains. Fluid-affected domains in apatite provide evidence of halide exchange. The data testify that the observed recrystallization was a high-temperature reaction with fertilized, halide-rich H2O-CO2 mantle-derived fluids of high water activity. A wet mantle being able to generate hydrous plumes, which appear to be hotter during the Archean in comparison to the present time is supposed by Shimizu et al. (2001). Usually hot fluids, which can be strongly carbonic, precede asthenospheric mantle upwelling. They are supposed to be parental to most recognized compositions, which can be derived by their immiscible separation into saline aqueous-silicic and carbonatitic members (Klein-BenDavid et al., 2007). The aqueous fractions are halogen-rich with a significant proportion of CO2. Both admixed fractions are supposed to be fertile. The Closepet granite emplaced in a major shear zone that delimitates two different terrains. Generally such shear zones, at many places, are supposed to be rooted deep into the mantle. The drain, that favoured and controlled magma ascent and emplacement, seemed to remain efficient after granite crystallization. In the southern part of the Closepet batholiths an evidence of intensive interaction of a lower crust fluid (of high CO2 activity) is provided by the extensive charnockitization of amphibolite facies (St

The composite Archaean grey gneisses: Petrological significance, and evidence for a non-unique tectonic setting for Archaean crustal growth

NASA Astrophysics Data System (ADS)

Moyen, Jean-François

2011-04-01

The geodynamic context of formation of the Archaean continental crust is a matter of debate. The crust is largely made of grey gneiss complexes, a composite rock assemblage dominated by granitoids that are generally regarded as belonging to the TTG (tonalite-trondhjemite-granodiorite) series. Using a large database of published TTG and grey gneiss compositions, it is possible to show that the granitoids forming grey gneiss complexes actually belong to at least four main geochemical groups: (i) a potassic component made of granodiorites and formed by melting of existing crustal lithologies; and (ii) three sodic groups (TTG proper) that comprise low, medium and high pressure groups. The geochemistry of the low pressure group is consistent with derivation from a plagioclase and garnet-amphibolite; the medium pressure group was formed in equilibrium with a garnet-rich, plagioclase-poor amphibolite, whereas the high pressure group derived from a rutile-bearing eclogite. As the temperature of melting of metamafic rocks is largely independent from pressure, this corresponds to melting along a range of contrasting geothermal gradients, in turn reflecting a range of tectonic sites for the formation of the Archaean continental crust.

Implications of a reducing and warm (not hot) Archaean ambient mantle for ancient element cycles

NASA Astrophysics Data System (ADS)

Aulbach, Sonja

2016-04-01

There is considerable uncertainty regarding the oxygen partial pressure (fO2) and potential temperature (TP) of the ambient convecting mantle throughout Earth's history. Rare Archaean eclogite suites have elemental and isotopic compositions indicative of formation of crustal protoliths in oceanic spreading ridges, hence unaffected by continental sources. These include some eclogite xenoliths derived from cratonic mantle lithosphere and orogenic eclogites marking the exhumation of oceanic crust at Pacific-type margins. Their compositions may retain a memory of the thermal and redox state of the Archaean convecting mantle sources that gave rise to their low-pressure protoliths. Archaean eclogites have TiO2-REE relationships consistent with fractional crystallisation of olivine±plagioclase and cpx during formation of picritic protoliths from a melt that separated from a garnet-free peridotite source, implying intersection of the solidus at ≤2.5 to 3.0 GPa [1]. Low melt fractions (<0.25) inferred from samples with the least fractionated (lowest TiO2) protoliths further argue against deep intersection of the mantle solidus. This suggests a moderately elevated TP ~ 1420-1470 degrees C (lower than some estimates for the ambient convecting mantle at that time [2]), which would support an early onset of plate tectonics [3] and emergence of continents [4], heralding a transition to modern chemical cycles. Moderate TP further indicates that deep recycling of carbon and water, though reduced compared to today, may have been possible in the Archaean [5,6]. Carefully screened eclogites have V/Sc (reflecting the redox state of the ambient mantle during protolith formation [7]) corresponding to ΔFMQ corrected to 1 GPa as low as -1.7 at 3 Ga [1]. Such low oxygen fugacities have consequences for the location of the peridotite solidus and for the types of melts generated during redox melting [5,8]. They also modulate the redox state of volatiles liberated at oceanic spreading

Early Life on Earth: the Ancient Fossil Record

NASA Astrophysics Data System (ADS)

Westall, F.

2004-07-01

The evidence for early life and its initial evolution on Earth is lin= ked intimately with the geological evolution of the early Earth. The environment of the early Earth would be considered extreme by modern standards: hot (50-80=B0C), volcanically and hydrothermally active, a= noxic, high UV flux, and a high flux of extraterrestrial impacts. Habitats = for life were more limited until continent-building processes resulted in= the formation of stable cratons with wide, shallow, continental platforms= in the Mid-Late Archaean. Unfortunately there are no records of the first appearance of life and the earliest isotopic indications of the exist= ence of organisms fractionating carbon in ~3.8 Ga rocks from the Isua greenst= one belt in Greenland are tenuous. Well-preserved microfossils and micro= bial mats (in the form of tabular and domical stromatolites) occur in 3.5-= 3.3 Ga, Early Archaean, sedimentary formations from the Barberton (South Afri= ca) and Pilbara (Australia) greenstone belts. They document life forms that = show a relatively advanced level of evolution. Microfossil morphology inclu= des filamentous, coccoid, rod and vibroid shapes. Colonial microorganism= s formed biofilms and microbial mats at the surfaces of volcaniclastic = and chemical sediments, some of which created (small) macroscopic microbi= alites such as stromatolites. Anoxygenic photosynthesis may already have developed. Carbon, nitrogen and sulphur isotopes ratios are in the r= ange of those for organisms with anaerobic metabolisms, such as methanogenesi= s, sulphate reduction and photosynthesis. Life was apparently distribute= d widely in shallow-water to littoral environments, including exposed, evaporitic basins and regions of hydrothermal activity. Biomass in t= he early Archaean was restricted owing to the limited amount of energy t= hat could be produced by anaerobic metabolisms. Microfossils resembling o= xygenic photosynthesisers, such as cyanobacteria, probably first occurred in

Modulation of oxygen production in Archaean oceans by episodes of Fe(II) toxicity

NASA Astrophysics Data System (ADS)

Swanner, Elizabeth D.; Mloszewska, Aleksandra M.; Cirpka, Olaf A.; Schoenberg, Ronny; Konhauser, Kurt O.; Kappler, Andreas

2015-02-01

Oxygen accumulated in the surface waters of the Earth's oceans and atmosphere several hundred million years before the Great Oxidation Event between 2.4 and 2.3 billion years ago. Before the Great Oxidation Event, periods of enhanced submarine volcanism associated with mantle plume events supplied Fe(II) to sea water. These periods generally coincide with the disappearance of indicators of the presence of molecular oxygen in Archaean sedimentary records. The presence of Fe(II) in the water column can lead to oxidative stress in some organisms as a result of reactions between Fe(II) and oxygen that produce reactive oxygen species. Here we test the hypothesis that the upwelling of Fe(II)-rich, anoxic water into the photic zone during the late Archaean subjected oxygenic phototrophic bacteria to Fe(II) toxicity. In laboratory experiments, we found that supplying Fe(II) to the anoxic growth medium housing a common species of planktonic cyanobacteria decreased both the efficiency of oxygenic photosynthesis and their growth rates. We suggest that this occurs because of increasing intracellular concentrations of reactive oxygen species. We use geochemical modelling to show that Fe(II) toxicity in conditions found in the late Archaean photic zone could have substantially inhibited water column oxygen production, thus decreasing fluxes of oxygen to the atmosphere. We therefore propose that the timing of atmospheric oxygenation was controlled by the timing of submarine, plume-type volcanism, with Fe(II) toxicity as the modulating factor.

The composite TTG series: evidence for a non-unique tectonic setting for Archaean crustal growth.

NASA Astrophysics Data System (ADS)

Moyen, Jean-François

2010-05-01

The geodynamic context of formation of the Archaean TTG (tonalite-trondhjemite-granodiorite) series, the dominant component of the Archaean continental crust, is a matter of debate. The two end-member models for TTG formation are melting of the basaltic slab in a "hot subduction"; and intra-plate melting of basaltic rocks at the base of thick crust (oceanic plateau?). Both models do however predict strikingly different geothermal gradients, as in the modern Earth a typical subduction gradient is less than 10 °C/km compared to > 25-30 °C/km in the case of plateau melting. Using a large database of published TTG compositions, and filtering it to remove rocks that do not match the definition of TTG, it is possible to show that the TTG series is actually composite and made of a range of geochemically identifiable components that can be referred to as low-, medium- and high-pressure groups. The geochemistry of the low-pressure group (low Al, Na, Sr, relatively high Y and Nb) is consistent with derivation from a plagioclase and garnet- amphibolite; the medium-pressure group was formed in equilibrium with a garnet-rich, plagioclase-poor amphibolite, whereas the high pressure group derived from a rutile bearing eclogite. As the temperature of melting of metamafic rocks is largely independent from pressure, this corresponds to melting along a range of contrasting geothermal gradients. The low pressure group requires gradients of 10-12 °C/km, whereas the gradient required for the low pressure group can be as high as 25—30 °C/km. Regardless of the preferred tectonic model for the Archaean, such a range of gradients requires an equally large range of tectonic sites for the formation of the Archaean continental crust.

Asteroids and Archaean crustal evolution: Tests of possible genetic links between major mantle/crust melting events and clustered extraterrestrial bombardments

NASA Technical Reports Server (NTRS)

Glikson, A. Y.

1992-01-01

Since the oldest intact terrestrial rocks of ca. 4.0 Ga and oldest zircon xenocrysts of ca. 4.3 Ga measured to date overlap with the lunar late heavy bombardment, the early Precambrian record requires close reexamination vis a vis the effects of megaimpacts. The identification of microtektite-bearing horizons containing spinals of chondritic chemistry and Ir anomalies in 3.5-3.4-Ga greenstone belts provides the first direct evidence for large-scale Archaean impacts. The Archaean crustal record contains evidence for several major greenstone-granite-forming episodes where deep upwelling and adiabatic fusion of the mantle was accompanied by contemporaneous crustal anatexis. Isotopic age studies suggest evidence for principal age clusters about 3.5, 3.0, and 2.7 (+/- 0.8) Ga, relics of a ca. 3.8-Ga event, and several less well defined episodes. These peak events were accompanied and followed by protracted thermal fluctuations in intracrustal high-grade metamorphic zones. Interpretations of these events in terms of internal dynamics of the Earth are difficult to reconcile with the thermal behavior of silicate rheologies in a continuously convecting mantle regime. A triggering of these episodes by mantle rebound response to intermittent extraterrestrial asteroid impacts is supported by (1) identification of major Archaean impacts from microtektite and distal ejecta horizons marked by Ir anomalies; (2) geochemical and experimental evidence for mantle upwelling, possibly from levels as deep as the transition zone; and (3) catastrophic adiabatic melting required to generate peridotitic komatites. Episodic differentiation/accretion growth of sial consequent on these events is capable of resolving the volume problem that arises from comparisons between modern continental crust and the estimated sial produced by continuous two-stage mantle melting processes. The volume problem is exacerbated by projected high accretion rates under Archaean geotherms. It is suggested that

Chronology of early Archaean granite-greenstone evolution in the Barberton Mountain Land, South Africa, based on precise dating by single zircon evaporation

NASA Technical Reports Server (NTRS)

Kruener, Alfred; Byerly, Gary R.; Lowe, Donald R.

1991-01-01

Precise Pb-207/Pb-206 single zircon evaporating ages are reported for low-grade felsic metavolcanic rocks within the Onverwacht and Fig Tree Groups of the Barberton Greenstone Belt (BGB), South Africa, as well as for granitoid plutons bordering the belt. Dacitic tuffs of the Hooggenoeg Formation in the upper part of the Onverwacht Group are shown to yield ages between 3445 + or - 3 and 3416 + or - 5 Ma and to contain older crustal components represented by a 3504 + or - 4 Ma old zircon xenocryst. Fig Tree dacitic tuffs and agglomerates have euhedral zircons between 3259 + or - 3 Ma in age which are interpreted to reflect the time of crystallization. The comagmatic relationships between greenstone felsic volcanic units and the surrounding plutonic suites are keynoted. The data adduced show that the Onverwacht and Fig Tree felsic units have distinctly different ages and thus do not constitute a single, tectonically repeated unit as proposed by others. It is argued that conventional multigrain zircon dating may not accurately identify the time of felsic volcanic activity in ancient greenstones, and that the BGB in the Kaapval craton of southern Africa and greenstones in the Pilbara Block of Western Australia may have been part of a larger crustal unit in early Archaean times.

Extraterrestrial Impact Episodes and Archaean to Early Proterozoic (3.8 2.4 Ga) Habitats of Life

NASA Astrophysics Data System (ADS)

Glikson, Andrew

The terrestrial record is punctuated by major clustered asteroid and comet impacts, which affected the appearance, episodic extinction, radiation, and reemergence of biogenic habitats. Here I examine manifest and potential extraterrestrial impact effects on the onset and evolution of Archaean to early Proterozoic (3.8- 2.4-Ga) habitats, with reference to the Pilbara (Western Australia) and Kaapvaal (eastern Transvaal) Cratons. The range of extraterrestrial connections of microbial habitats includes cometary contribution of volatiles and amino acids, sterilization by intense asteroid and comet bombardment, supernova and solar flares, and impacttriggered volcanic and hydrothermal activity, tectonic modifications, and tsunami effects. Whereas cometary dusting of planetary atmosphere may contribute littlemodi fied extraterrestrial organic components, large impact effects result in both incineration of organic molecules and shock synthesis of new components. From projected impact incidence, ~1.3% of craters >100 km and ~3.8% of craters >250 km have to date been identified for post-3.8-Ga events, due to the mm-scale of impact spherules and the difficulty in their identification in the field - only the tip of the iceberg is observed regarding the effects of large impacts on the Precambrian biosphere, to date no direct or genetic relations between impacts and the onset or extinction of early Precambrian habitats can be confirmed. However, potential relations include (1) ~3.5-3.43 Ga - intermittent appearance of stromatolite-like structures of possible biogenic origin on felsic volcanic shoals representing intervals between mafic volcanic episodes in rapidly subsiding basins, a period during which asteroid impacts are recorded; (2) ~3.26-3.225 Ga - impact-triggered crustal transformation from mafic-ultramafic volcanic environments to rifted troughs dominated by felsic volcanics and turbidites, marked by a major magmatic peak, resulting in extensive hydrothermal activity and

Generation of continental crust in the northern part of the Borborema Province, northeastern Brazil, from Archaean to Neoproterozoic

NASA Astrophysics Data System (ADS)

de Souza, Zorano Sérgio; Kalsbeek, Feiko; Deng, Xiao-Dong; Frei, Robert; Kokfelt, Thomas Find; Dantas, Elton Luiz; Li, Jian-Wei; Pimentel, Márcio Martins; Galindo, Antonio Carlos

2016-07-01

(TZ). Early Neoproterozoic volcanism at 1091 Ma, and A-type plutonism, from 920 to 775 Ma, mark the intracontinental magmatism in the TZ. In the Seridó Domain, the Late Neoproterozoic registers several events of plutonism, at 600-593, 575-560, 548-533, 528-510, 495-450 Ma. These rocks cover ca. 15% of the area, while Neoproterozoic supracrustal rocks cover ca. 30%. The most important magmatic event is that at 575 Ma, consistent with the peak of widespread transpression and synchronous high temperature metamorphism. The Neoproterozoic rocks are mostly K-enriched alkaline or transitional to calc-alkaline. Inherited Archaean and Palaeoproterozoic zircons and Nd model ages, as well as moderate to strongly negative (-21 to -9) epsilon Nd, and persistent negative anomalies for Ta-Nb, Ti and P indicate significant crustal contributions in their genesis. While a convergent setting (subduction zone) could explain the Archaean and Palaeoproterozoic units, this is not so for the Neoproterozoic rocks which mimic the geochemical and isotopic features of the older sources. In the study area, the peak of juvenile accretion (mantle derived magmas) took place in the Archaean (3.4-2.7 Ga) and Palaeproterozoic (2.4-2.11 Ga), whereas crustal recycling predominated in the Neoproterozoic.

Chronology of early Archaean granite-greenstone evolution in the Barberton Mountain Land, South Africa, based on precise dating by single zircon evaporation.

PubMed

Krüner, A; Byerly, G R; Lowe, D R

1991-04-01

others. Unlike the late Archaean Abitibi greenstone belt in Canada, which formed over about 30 Ma. exposed rocks in the BGB formed over a period of at least 220 Ma. The complex zircon populations encountered in this study imply that conventional multigrain zircon dating may not accurately identify the time of felsic volcanic activity in ancient greenstones. A surprising similarity in rock types, tectonic evolution, and ages of the BGB in the Kaapvaal craton of southern Africa and greenstones in the Pilbara Block of Western Australia suggests that these two terrains may have been part of a larger crustal unit in early Archaean times.

Archaean ultra-depleted komatiites formed by hydrous melting of cratonic mantle.

PubMed

Wilson, A H; Shirey, S B; Carlson, R W

2003-06-19

Komatiites are ultramafic volcanic rocks containing more than 18 per cent MgO (ref. 1) that erupted mainly in the Archaean era (more than 2.5 gigayears ago). Although such compositions occur in later periods of Earth history (for example, the Cretaceous komatiites of Gorgona Island), the more recent examples tend to have lower MgO content than their Archaean equivalents. Komatiites are also characterized by their low incompatible-element content, which is most consistent with their generation by high degrees of partial melting (30-50 per cent). Current models for komatiite genesis include the melting of rock at great depth in plumes of hot, diapirically rising mantle or the melting of relatively shallow mantle rocks at less extreme, but still high, temperatures caused by fluxing with water. Here we report a suite of ultramafic lava flows from the Commondale greenstone belt, in the southern part of the Kaapvaal Craton, which represents a previously unrecognized type of komatiite with exceptionally high forsterite content of its igneous olivines, low TiO(2)/Al(2)O(3) ratio, high silica content, extreme depletion in rare-earth elements and low Re/Os ratio. We suggest a model for their formation in which a garnet-enriched residue left by earlier cratonic volcanism was melted by hydration from a subducting slab.

U-Pb Geochronology and Hf-isotope constrains on Formation of Archaean Crust From the Lewisian of NW Scotland, Great Britain

NASA Astrophysics Data System (ADS)

Crowley, Q. G.; Noble, S. R.; Key, R.

2006-12-01

The Lewisian complex of NW Scotland is dominantly composed of Archaean tonalitic to granodioritic gneisses, ultramafic bodies and minor metasedimentary components. Although the area is internationally well known and has been much studied for over a century, the precise timing of crustal forming events has proven difficult to ascertain. We present data from both in-situ laser ablation (LA) ICP-MS and an adaptation of a new U-Pb chemical abrasion ID-TIMS technique (Mattinson 2006) applied to multi-age component zircons from the Assynt block of this region. The new data reveal a previously unrecognised complexity and provide the first unequivocal proof of an Archean metamorphic event in the area. In a wider context the data also elucidate some of the processes involved in early global crust formation and plate tectonic events. In-situ LA-ICPMS U-Pb dating has indicated a ca 2.8Ga protolith age for a tonalite gneiss with evidence for a ca. 3.6Ga xenocrystic component (the oldest discovered in the UK). Non-conventional U-Pb ID-TIMS utilising a combination of high-temperature annealing followed by multi-step incremental dissolution on single grains has dated zircon growth at ca 2.7Ga (Badcallian) and 2.5Ga (Inverian) with later Pb-loss occurring at ca 1.9Ga and ca 1.7Ga (early and late Laxfordian respectively). This latter method combines a pseudo-spatial resolution normally associated with an in-situ technique but benefits from the high-precision analysis of ID-TIMS. Zircon Hf isotopes indicate that some rocks from the Assynt area are typical of Archaean continental crust (epsilon Hf ca -1. The tonalite gneisses however have strongly negative epsilon Hf values of -7 to -10 indicating a more complex history of derivation through partial melting of ancient crust with residual garnet as a long- lived control on Hf. Archaean events at ca. 3.6Ga, ca 2.8Ga and ca 2.7Ga have also been recorded in west Greenland (e.g. Mojzsis & Harrison 1999, Richards and Appel, 1987

The cellular immunity and oxidative stress markers in early pregnancy loss.

PubMed

Daglar, Korkut; Biberoglu, Ebru; Kirbas, Ayse; Dirican, Aylin Onder; Genc, Metin; Avci, Aslihan; Biberoglu, Kutay

2016-01-01

We investigated whether changes in cellular immunity and oxidative stress in pregnancy have any association with spontaneous miscarriage. Circulating adenosine deaminase (ADA) activity as a marker of cellular immunity and malondialdehyde (MDA) and catalase (CAT), glutathione peroxidase (GPx) as markers of T lymphocyte activation and parameters of oxidative stress and antioxidant defense were compared between 40 women with early pregnancy loss and another 40 women with ungoing healthy pregnancy. Women with miscarriage had higher serum ADA and GPx levels when compared with women with normal pregnancy (p = 0.034 and p < 0.001, respectively). Although serum MDA level was slightly higher in women with miscarriage, the difference was not significant (p = 0.083). CAT levels were alike in both groups. We have demonstrated an increased cellular immunity and perhaps a compensated oxidative stress related to increased antioxidant activation in women with early spontaneous pregnancy loss.

Constraining the potential temperature of the Archaean mantle: A review of the evidence from komatiites

NASA Astrophysics Data System (ADS)

Nisbet, E. G.; Cheadle, M. J.; Arndt, N. T.; Bickle, M. J.

1993-09-01

The maximum potential temperature of the Archaean mantle is poorly known, and is best constrained by the MgO contents of komatiitic liquids, which are directly related to eruptive temperatures. However, most Archaean komatiites are significantly altered and it is difficult to assess the composition of the erupted liquid. Relatively fresh lavas from the SASKMAR suite, Belingwe Greenstone Belt, Zimbabwe (2.7 Ga) include chills of 25.6 wt.% MgO, and olivines ranging to Fo 93.6, implying eruption at around 1520°C. A chill sample from Alexo Township, Ontario (also 2.7 Ga) is 28 wt.% MgO, and associated olivines range to Fo 94.1, implying eruption at 1560°C. However, inferences of erupted liquids containing 32-33 wt.% MgO, from lavas in the Barberton Greenstone Belt, South Africa (3.45 Ga) and from the Perseverance Complex, Western Australia (2.7 Ga) may be challenged on the grounds that they contain excess (cumulate) olivine, or were enriched in Mg during alteration or metamorphism. Re-interpretation of olivine compositions from these rocks shows that they most likely contained a maximum of 29 wt.% MgO corresponding to an eruption temperature of 1580°C. This composition is the highest liquid MgO content of an erupted lava that can be supported with any confidence. The hottest modern magma, on Gorgona Island (0.155 Ga) contained 18-20% MgO and erupted at circa 1400°C. If 1580°C is taken as the temperature of the most magnesian known eruption, then the source mantle from which the liquids rose would have been at up to 2200°C at pressures of 18 GPa corresponding to a mantle potential temperature of 1900°C. These temperatures are in excess of the mantle temperatures predicted by secular cooling models, and thus komatiites can only be formed in hot rising convective jets in the mantle. This result requires that Archaean mantle jets may have been 300°C hotter than the Archaean ambient mantle temperature. This temperature difference is similar to the 200-300�

Growth of early continental crust by partial melting of eclogite.

PubMed

Rapp, Robert P; Shimizu, Nobumichi; Norman, Marc D

2003-10-09

The tectonic setting in which the first continental crust formed, and the extent to which modern processes of arc magmatism at convergent plate margins were operative on the early Earth, are matters of debate. Geochemical studies have shown that felsic rocks in both Archaean high-grade metamorphic ('grey gneiss') and low-grade granite-greenstone terranes are comprised dominantly of sodium-rich granitoids of the tonalite-trondhjemite-granodiorite (TTG) suite of rocks. Here we present direct experimental evidence showing that partial melting of hydrous basalt in the eclogite facies produces granitoid liquids with major- and trace-element compositions equivalent to Archaean TTG, including the low Nb/Ta and high Zr/Sm ratios of 'average' Archaean TTG, but from a source with initially subchondritic Nb/Ta. In modern environments, basalts with low Nb/Ta form by partial melting of subduction-modified depleted mantle, notably in intraoceanic arc settings in the forearc and back-arc regimes. These observations suggest that TTG magmatism may have taken place beneath granite-greenstone complexes developing along Archaean intraoceanic island arcs by imbricate thrust-stacking and tectonic accretion of a diversity of subduction-related terranes. Partial melting accompanying dehydration of these generally basaltic source materials at the base of thickened, 'arc-like' crust would produce compositionally appropriate TTG granitoids in equilibrium with eclogite residues.

Witwatersrand gold deposits formed by volcanic rain, anoxic rivers and Archaean life

NASA Astrophysics Data System (ADS)

Heinrich, Christoph A.

2015-03-01

The Witwatersrand Basin in South Africa is one of the best-preserved records of fluvial sedimentation on an Archaean continent. The basin hosts the worlds biggest gold resource in thin pebble beds, but the process for gold enrichment is debated. Mechanical accumulation of gold particles from flowing river water is the prevailing hypothesis, yet there is evidence for hydrothermal mobilization of gold by fluids invading the metasedimentary rocks after their burial. Earth's atmosphere three billion years ago was oxygen free, but already sustained some of the oldest microbial life on land. Here I use thermodynamic modelling and mass-balance calculations to show that these conditions could have led to the chemical transport and precipitation of gold in anoxic surface waters, reconciling the evidence for fluvial deposition with evidence for hydrothermal-like chemical reactions. I suggest that the release of sulphurous gases from large volcanic eruptions created acid rain that enabled the dissolution and transport of gold in surface waters as sulphur complexes. Precipitation of the richest gold deposits could have been triggered by chemical reduction of the dissolved gold onto organic material in shallow lakes and pools. I conclude that the Witwatersrand gold could have formed only during the Archaean, after the emergence of continental life but before the rise of oxygen in the Earth's atmosphere.

Why Archaean TTG cannot be generated by MORB melting in subduction zones

NASA Astrophysics Data System (ADS)

Martin, Hervé; Moyen, Jean-François; Guitreau, Martin; Blichert-Toft, Janne; Le Pennec, Jean-Luc

2014-06-01

Until recently it was assumed that the Archaean continental crust (made of TTGs: tonalites, trondhjemites, and granodiorites) was generated through partial melting of MORB-like basalts in hot subduction environments, where the subducted oceanic crust melted at high pressure, leaving a garnet-bearing amphibolitic or eclogitic residue. However, recent geochemical models as well as basalt melting experiments have precluded MORB as a plausible source for TTGs. Rather, geochemical and experimental evidences indicate that formation of TTG required a LILE-enriched source, similar to oceanic plateau basalts. Moreover, subduction is a continuous process, while continental growth is episodic. Several “super-growth events” have been identified at ~ 4.2, ~ 3.8, ~ 3.2, ~ 2.7, ~ 1.8, ~ 1.1, and ~ 0.5 Ga, which is inconsistent with the regular pattern that would be expected from a subduction-driven process. In order to account for this periodicity, it has been proposed that, as subduction proceeds, descending residual slabs accumulate at the 660-km seismic discontinuity. When stored oceanic crust exceeds a certain mass threshold, it rapidly sinks into the mantle as a cold avalanche, which induces the ascent of mantle plumes that in turn produce large amounts of magmas resulting in oceanic plateaus. However, melting at the base of thick oceanic plateaus does not appear to be a realistic process that can account for TTG genesis. Modern oceanic plateaus contain only small volumes (≤ 5%) of felsic magmas generally formed by high degrees of fractional crystallization of basaltic magmas. The composition of these felsic magmas drastically differs from that of TTGs. In Iceland, the interaction between a mantle plume and the mid-Atlantic ridge gives rise to an anomalously (Archaean-like) high geothermal gradient resulting in thick basaltic crust able to melt at shallow depth. Even in this favorable context though, the characteristic Archaean TTG trace element signature is not being

Percolation of diagenetic fluids in the Archaean basement of the Franceville basin

NASA Astrophysics Data System (ADS)

Mouélé, Idalina Moubiya; Dudoignon, Patrick; Albani, Abderrazak El; Cuney, Michel; Boiron, Marie-Christine; Gauthier-Lafaye, François

2014-01-01

The Palaeoproterozoic Franceville basin, Gabon, is mainly known for its high-grade uranium deposits, which are the only ones known to act as natural nuclear fission reactors. Previous work in the Kiéné region investigated the nature of the fluids responsible for these natural nuclear reactors. The present work focuses on the top of the Archaean granitic basement, specifically, to identify and date the successive alteration events that affected this basement just below the unconformity separating it from the Palaeoproterozoic basin. Core from four drill holes crosscutting the basin-basement unconformity have been studied. Dating is based on U-Pb isotopic analyses performed on monazite. The origin of fluids is discussed from the study of fluid inclusion planes (FIP) in quartz from basement granitoids. From the deepest part of the drill holes to the unconformable boundary with the basin, propylitic alteration assemblages are progressively replaced by illite and locally by a phengite + Fe chlorite ± Fe oxide assemblage. Illitic alteration is particularly strong along the sediment-granitoid contact and is associated with quartz dissolution. It was followed by calcite and anhydrite precipitation as fracture fillings. U-Pb isotopic dating outlines three successive events: a 3.0-2.9-Ga primary magmatic event, a 2.6-Ga propylitic alteration and a late 1.9-Ga diagenetic event. Fluid inclusion microthermometry suggests the circulation of three types of fluids: (1) a Na-Ca-rich diagenetic brine, (2) a moderately saline (diagenetic + meteoric) fluid, and (3) a low-salinity fluid of probable meteoric origin. These fluids are similar to those previously identified within the overlying sedimentary rocks of the Franceville basin. Overall, the data collected in this study show that the Proterozoic-Archaean unconformity has operated as a major flow corridor for fluids circulation, around 1.9 Ga. highly saline diagenetic brines; hydrocarbon-rich fluids derived from organic matter

Stromatolites at ~3,500 Myr and a greenstone-granite unconformity in the Zimbabwean Archaean

NASA Astrophysics Data System (ADS)

Orpen, J. L.; Wilson, J. F.

1981-05-01

Two controversial areas of geological endeavour are the establishment of the antiquity of life and the tectonic setting of greenstone sequences. We record here the recent discoveries in the Fort Victoria greenstone belt of stromatolites in limestones assigned to ~3,500 Myr (minimum age) Sebakwian Group rocks of the Rhodesian Archaean Craton within Zimbabwe, and a nearby outcrop of a thin sedimentary formation, basal to a thick ~2,700 Myr volcanic pile, resting with definite unconformity on ~3,500 Myr Mushandike Granite.

Did the formation of D″ cause the Archaean-Proterozoic transition?

NASA Astrophysics Data System (ADS)

Campbell, Ian H.; Griffiths, Ross W.

2014-02-01

The MgO content of the highest MgO plume-related komatiites and picrites remained constant at 32±2.5% between 3.5 and 2.7 Ga, then fell to 21±3% by ca. 2.0 Ga, a value similar to the present day value. Because there is a linear relationship between the liquidus temperature of dry magmas and their MgO content this observation implies that the temperature of mantle plumes changed little between 3.5 and 2.7 Ga, and then fell by 200-250 °C between 2.7 and 2.0 Ga to a temperature similar to that of present plumes. We suggest that Archaean plumes originate from the core-mantle boundary and that their temperature remained constant because the temperature of the outer core was buffered by solidification of the Fe-Ni inner core. At about 2.7 Ga dense former basaltic crust began to accumulate at the core and eventually covered it to produce an insulating layer that reduced the heat flux out of the core and lowered the temperature of mantle plumes. The temperature of mantle plumes fell as the dense layer above the core thickened until it exceeded the critical thickness required for convection. Because heat is transferred rapidly across the convecting part of the insulating layer, any further increase in its thickness by the addition more basaltic material has no influence on the temperature at the top of the layer, which is the source of Post-Archaean mantle plumes. We equate the dense layer above the core with the seismically identified layer D″. Our analyses suggest the drop in plume temperatures produced by a dense insulating layer above the core will be about 40% once it starts to convect, which is consistent with the observed drop inferred from the decrease in the MgO content of komatiites and picrites at that time.

Feldspar palaeo-isochrons from early Archaean TTGs: Pb-isotope evidence for a high U/Pb terrestrial Hadean crust

NASA Astrophysics Data System (ADS)

Kamber, B. S.; Whitehouse, M. J.; Moorbath, S.; Collerson, K. D.

2001-12-01

Feldspar lead-isotope data for 22 early Archaean (3.80-3.82 Ga) tonalitic gneisses from an area south of the Isua greenstone belt (IGB),West Greenland, define a steep linear trend in common Pb-isotope space with an apparent age of 4480+/-77 Ma. Feldspars from interleaved amphibolites yield a similar array corresponding to a date of 4455+/-540 Ma. These regression lines are palaeo-isochrons that formed during feldspar-whole rock Pb-isotope homogenisation a long time (1.8 Ga) after rock formation but confirm the extreme antiquity (3.81 Ga) of the gneissic protoliths [1; this study]. Unlike their whole-rock counterparts, feldspar palaeo-isochrons are immune to rotational effects caused by the vagaries of U/Pb fractionation. Hence, comparison of their intercept with mantle Pb-isotope evolution models yields meaningful information regarding the source history of the magmatic precursors. The locus of intersection between the palaeo-isochrons and terrestrial mantle Pb-isotope evolution lines shows that the gneissic precursors of these 3.81 Ga gneisses were derived from a source with a substantially higher time-integrated U/Pb ratio than the mantle. Similar requirements for a high U/Pb source have been found for IGB BIF [2], IGB carbonate [3], and particularly IGB galenas [4]. Significantly, a single high U/Pb source that separated from the MORB-source mantle at ca. 4.3 Ga with a 238U/204Pb of ca. 10.5 provides a good fit to all these observations. In contrast to many previous models based on Nd and Hf-isotope evidence we propose that this reservoir was not a mantle source but the Hadean basaltic crust which, in the absence of an operating subduction process, encased the early Earth. Differentiation of the early high U/Pb basaltic crust could have occurred in response to gravitational sinking of cold mantle material or meteorite impact, and produced zircon-bearing magmatic rocks. The subchondritic Hf-isotope ratios of ca. 3.8 Ga zircons support this model [5] provided that

A Proposal for Formation of Archaean Stromatolites before the Advent of Oxygenic Photosynthesis.

PubMed

Allen, John F

2016-01-01

Stromatolites are solid, laminar structures of biological origin. Living examples are sparsely distributed and formed by cyanobacteria, which are oxygenic phototrophs. However, stromatolites were abundant between 3.4 and 2.4 Gyr, prior to the advent of cyanobacteria and oxygenic photosynthesis. Here I propose that many Archaean stromatolites were seeded at points of efflux of hydrogen sulfide from hydrothermal fields into shallow water, while their laminar composition arose from alternating modes of strictly anoxygenic photosynthetic metabolism. These changes were a redox regulatory response of gene expression to changing hydrogen sulfide concentration, which fluctuated with intermittent dilution by tidal action or by rainfall into surface waters. The proposed redox switch between modes of metabolism deposited sequential microbial mats. These mats gave rise to alternating carbonate sediments predicted to retain evidence of their origin in differing ratios of isotopes of carbon and sulfur and in organic content. The mats may have arisen either by replacement of microbial populations or by continuous lineages of protocyanobacteria in which a redox genetic switch selected between Types I and II photosynthetic reaction centers, and thus between photolithoautotrophic and photoorganoheterotrophic metabolism. In the latter case, and by 2.4 Gyr at the latest, a mutation had disabled the redox genetic switch to give simultaneous constitutive expression of both Types I and II reaction centers, and thus to the ability to extract electrons from manganese and then water. By this simple step, the first cyanobacterium had the dramatic advantage of emancipation from limiting supplies of inorganic electron donors, produced free molecular oxygen as a waste product, and initiated the Great Oxidation Event in Earth's history at the transition from the Archaean to the Paleoproterozoic.

High but balanced sedimentation and subsidence rates (Moodies Group, Barberton Greenstone Belt), followed by basin collapse: Implication for Archaean tectonics

NASA Astrophysics Data System (ADS)

Heubeck, Christoph; Lowe, Donald R.; Byerly, Gary R.

2010-05-01

top of the underlying Fig Tree Group (Schoongezicht Fm.; Byerly et al., 1996), implying that ca. 2000m of Moodies sandstones and subordinate siltstones and conglomerates were deposited in not more than a few (0-6) Ma. Their comparatively low degree of facies variation and lithological change implies a balance between rates of sediment supply and of subsidence, creating thick stacked units. Ferruginous shales and thin BIFs of the upper Moodies Group suggest that background 'Fig-Tree-style' sedimentation continued during Moodies time but was mostly overwhelmed by the apparently brief but massive influx of medium- to coarse-grained quartzose sediment. Because two progressive unconformities, marking Moodies basin uplift and onset of renewed overall BGB shortening, occur only 50 m above this dated unit, they are likely of a similar age and imply that dominant NW-SE-directed shortening in the BGB began shortly after 3230+-6 Ma. The combination of these new data with published information thus suggest that the Moodies Basin formed after 3225+-6 Ma (i.e., at the earliest at 3231) but was already largely filled and began to be deformed by 3231+-6 (i.e., at the latest by 3225). Moodies deposition thus happened geologically nearly instantaneously following the end of Fig Tree volcanism, took very little time and deposited large volumes of sediments on a rapidly subsiding basement just prior to large-scale BGB deformation. REFERENCES Byerly, G.R., Kroner, A., Lowe, D.R., Todt W., Walsh, M.M., 1996, Prolonged magmatism and time constraints for sediment deposition in the early Archean Barberton greenstone belt: Evidence from the Upper Onverwacht and Fig Tree groups: Precambrian Research, 78, p. 125-138. Eriksson, K.A., 1979, Marginal marine depositional processes from the Archaean Moodies Group, Barberton Mountain Land, South Africa: Evidence and significance: Precambrian Res., 8, p. 153-182. Heubeck, C. and Lowe, D.R., 1994, Depositional and tectonic setting of the Archaean

Helium in the Archaean komatiites revisited: significantly high 3He/4He ratios revealed by fractional crushing gas extraction

NASA Astrophysics Data System (ADS)

Matsumoto, T.; Seta, A.; Matsuda, J.; Chen, Y.; Arai, S.

2001-12-01

In order to provide constraints on 3He/4He ratios in the Archaean mantle source, we have analysed helium isotopic compositions in 2.7Ga old Archaean komatiites from the Abitibi green stone belt, Ontario, Canada. Two spinifex-textured komatiites yielded significantly high 3He/4He ratios of about 30Ra (where Ra denotes the atmospheric 3He/4He ratio) in fractions released by sequential crushing. These results are the first confirmation of the occurrence of high 3He/4He component in Archaean komatiites after the intriguing finding by [Richard et al., Science 273 (1996) 93-95] in komatiites from a nearby locality, Alexo. We also found that the crystal structure of the komatiites was significantly enriched in a radiogenic component (4He) and that the radiogenic 4He in the crystal structure was actually degassed by a crushing gas extraction, indicating that the nominal 3He/4He ratios measured by crushing are lower limits for the 3He/4He ratio of an intrinsic component. By constraining the release behaviour of radiogenic 4He by crushing, we have estimated the initial 3He/4He ratio of an inclusion-trapped component to be 73 (+7.8/-5.5) Ra. A mantle source with such a high 3He/4He ratio at 2.7Ga would, if evolved in a closed-system, have present-day 3He/4He ratio of 46-60Ra, indicating that the komatiites from Munro had been trapped their helium from a mantle reservoir with very high 3He/4He ratio in the context of the present-day value. However, whether or not such a source can be considered as the one that is equivalent to the primitive mantle source (such that sampled at hotspots) is highly model-dependent. If a closed-system evolution model were assumed, helium in the Munro komatiites is not likely to be derived from the MORB-source-like reservoir. However, the notion that the komatiites may be derived from a depleted reservoir in terms of trace elemental and isotopic geochemistry might requires an alternative view for the evolution of 3He/4He ratio in ancient mantle

Audio-magnetotelluric investigation of allochthonous iron formations in the Archaean Reguibat shield (Mauritania): structural and mining implications

NASA Astrophysics Data System (ADS)

Bronner, G.; Fourno, J. P.

1992-11-01

The M'Haoudat range, considered as an allochthonous unit amid the strongly metamorphosed Archaean basement (Tiris Group), belongs to the Lower Proterozoic Ijil Group, weakly metamorphosed, constituted mainly by iron quartzites including red jaspers and high grade iron ore. Audio-magnetotelluric (AMT) soundings (frequency range 1-7500 HZ) were performed together with the systematic survey of the range (SNIM mining company). The non-linear least squares method was used to perform a smoothness-constrained data model. The obvious AMT resistivity contrasts between the M'Haoudat Unit (150-3500 ohm. m) and the Archaean basement (20 000 ohm. m) allow to state precisely that the two thrust surfaces, on both sides of the range, join together at a depth which increases from North-West to South-East, as the ore bodies. Inside the steeply dipping M'Haoudat Unit, the main beds of iron quartzites (1500-3500 ohm. m), schists (1000-1500 ohm. m) and hematite ores (150-300 ohm. m) were distinguished when their thickness exceeded 30 to 50 m. The existence of an hydrostatic level (1-50 ohm. m) and the steeply dipping architecture, very likely responsible for the lack of resistivity contrast on the upper part of some profiles, complicate the interpretation at high frequencies the thin layers being poorly defined.

Elemental fingerprints of isotopic contamination of hebridean Palaeocene mantle-derived magmas by archaean sial

NASA Astrophysics Data System (ADS)

Thompson, R. N.; Dickin, A. P.; Gibson, I. L.; Morrison, M. A.

1982-06-01

One of the major puzzles presented by the geochemistry of the Palaeocene plateau lavas of Skye and Mull (N.W. Scotland) is that, although a very strong case can be made that the magmas are variably isotopically contaminated by Archaean Lewisian continental crust, little evidence has been gleaned to date from their major- and trace-element compositions to illuminate this hypothetical process. The combined results of published Sr-, Nd- and Pb-isotope studies of these lavas allow the basalts and hawaiites to be divided into three broad groups: essentially uncontaminated; contaminated with granulite-facies Archaean crust; contaminated with amphibolite-facies Archaean crust. Members of each group show distinctive chondrite-normalised incompatible-element patterns. The processes which gave rise to isotopic contamination of these lavas also affected the abundances and ratios of Ba, Rb, Th, K, Sr and light REE in the magmas, whilst having negligible effects on their abundances and ratios of Nb, Ta, P, Zr, Hf, Ti, Y and middle-heavy REE. Because such a wide range of elements were affected by the contamination process, it is postulated that the contaminant was a silicate melt of one or more distinctive crustal rock types, rather than an aqueous or similar fluid causing selective elemental movements from wall rocks into the magmas. As previous experimental and isotopic studies have shown that the Skye and Mull basic magmas were not constrained by cotectic equilibria at the time when they interacted with sial, the compositions of the contaminated lavas have been modelled in terms of simple magma-crust mixtures. Very close approximations to both the abundances and ratios of incompatible elements in the two groups of contaminated basalts may be obtained by adding 15% to 20% of Lewisian leucogneisses to uncontaminated Palaeocene basalt. Nevertheless, major-element constraints suggest that the maximum amount of granitic contaminant which has been added to these magmas lies between

Isotope composition and volume of Earth's early oceans.

PubMed

Pope, Emily C; Bird, Dennis K; Rosing, Minik T

2012-03-20

Oxygen and hydrogen isotope compositions of Earth's seawater are controlled by volatile fluxes among mantle, lithospheric (oceanic and continental crust), and atmospheric reservoirs. Throughout geologic time the oxygen mass budget was likely conserved within these Earth system reservoirs, but hydrogen's was not, as it can escape to space. Isotopic properties of serpentine from the approximately 3.8 Ga Isua Supracrustal Belt in West Greenland are used to characterize hydrogen and oxygen isotope compositions of ancient seawater. Archaean oceans were depleted in deuterium [expressed as δD relative to Vienna standard mean ocean water (VSMOW)] by at most 25 ± 5‰, but oxygen isotope ratios were comparable to modern oceans. Mass balance of the global hydrogen budget constrains the contribution of continental growth and planetary hydrogen loss to the secular evolution of hydrogen isotope ratios in Earth's oceans. Our calculations predict that the oceans of early Earth were up to 26% more voluminous, and atmospheric CH(4) and CO(2) concentrations determined from limits on hydrogen escape to space are consistent with clement conditions on Archaean Earth.

Growth of early continental crust by water-present eclogite melting in subduction zones

NASA Astrophysics Data System (ADS)

Laurie, A.; Stevens, G.

2011-12-01

The geochemistry of well preserved Paleo- to Meso-Archaean Tonalite-Trondhjemite-Granodiorite (TTG) suite rocks, such as the ca 3.45 Ga trondhjemites from the Barberton greenstone belt in South Africa, provides insight into the origins of Earth's early felsic continental crust. This is particularly well demonstrated by the high-Al2O3 variety of these magmas, such as the Barberton rocks, where the geochemistry requires that they are formed by high pressure (HP) melting of a garnet-rich metamafic source. This has been interpreted as evidence for the formation of these magmas by anatexis of the upper portions of slabs within Archaean subduction zones. Most of the experimental data relevant to Archaean TTG genesis has been generated by studies of fluid-absent melting of metabasaltic sources. However, water drives arc magmatism within Phanerozoic subduction zones and thus, understanding the behaviour of water in Archaean subduction zones, may have considerable value for understanding the genesis of these TTG magmas. Consequently, this study investigates the role of HP water-present melting of an eclogite-facies starting material, in the production of high-Al2O3 type TTG melts. Water-saturated partial melting experiments were conducted between 1.9 and 3.0GPa; and, 870°C and 900°C. The melting reaction is characterized by the breakdown of sodic Cpx, together with Qtz and H2O, to form melt in conjunction with a less sodic Cpx: Qtz + Cpx1 + Grt1 + H2O = Melt + Cpx2 + Grt2. In many of the experimental run products, melt segregated efficiently from residual crystals, allowing for the measurement of a full range of trace elements via Laser Ablation Inductively Coupled Plasma Mass Spectroscopy. The experimental glasses produced by this study have the compositions of peraluminous trondhjemites; and they are light rare earth element, Zr and Sr enriched; and heavy rare earth element, Y and Nb depleted. The compositions of the experimental glasses are similar to high-Al2O3 type

Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

PubMed Central

Huang, Li-Tung

2014-01-01

Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

An Archaean heavy bombardment from a destabilized extension of the asteroid belt.

PubMed

Bottke, William F; Vokrouhlický, David; Minton, David; Nesvorný, David; Morbidelli, Alessandro; Brasser, Ramon; Simonson, Bruce; Levison, Harold F

2012-05-03

The barrage of comets and asteroids that produced many young lunar basins (craters over 300 kilometres in diameter) has frequently been called the Late Heavy Bombardment (LHB). Many assume the LHB ended about 3.7 to 3.8 billion years (Gyr) ago with the formation of Orientale basin. Evidence for LHB-sized blasts on Earth, however, extend into the Archaean and early Proterozoic eons, in the form of impact spherule beds: globally distributed ejecta layers created by Chicxulub-sized or larger cratering events4. At least seven spherule beds have been found that formed between 3.23 and 3.47 Gyr ago, four between 2.49 and 2.63 Gyr ago, and one between 1.7 and 2.1 Gyr ago. Here we report that the LHB lasted much longer than previously thought, with most late impactors coming from the E belt, an extended and now largely extinct portion of the asteroid belt between 1.7 and 2.1 astronomical units from Earth. This region was destabilized by late giant planet migration. E-belt survivors now make up the high-inclination Hungaria asteroids. Scaling from the observed Hungaria asteroids, we find that E-belt projectiles made about ten lunar basins between 3.7 and 4.1 Gyr ago. They also produced about 15 terrestrial basins between 2.5 and 3.7 Gyr ago, as well as around 70 and four Chicxulub-sized or larger craters on the Earth and Moon, respectively, between 1.7 and 3.7 Gyr ago. These rates reproduce impact spherule bed and lunar crater constraints.

Two distinct cellular proteins interact with the EIa-responsive element of an adenovirus early promoter.

PubMed Central

Jansen-Durr, P; Wintzerith, M; Reimund, B; Hauss, C; Kédinger, C

1990-01-01

EIa-dependent transactivation of the adenovirus EIIa early (EIIaE) promoter is correlated with the activation of the cellular transcription factor E2F. In this study we identified a cellular protein, C alpha, that is distinct from E2F and that binds two sites in the EIIaE promoter, one of which overlaps with the proximal E2F binding site of the EIIaE promoter. The possible involvement of C alpha in the EIa responsiveness of this promoter is discussed. Images PMID:2139142

Isotope composition and volume of Earth’s early oceans

PubMed Central

Pope, Emily C.; Bird, Dennis K.; Rosing, Minik T.

2012-01-01

Oxygen and hydrogen isotope compositions of Earth’s seawater are controlled by volatile fluxes among mantle, lithospheric (oceanic and continental crust), and atmospheric reservoirs. Throughout geologic time the oxygen mass budget was likely conserved within these Earth system reservoirs, but hydrogen’s was not, as it can escape to space. Isotopic properties of serpentine from the approximately 3.8 Ga Isua Supracrustal Belt in West Greenland are used to characterize hydrogen and oxygen isotope compositions of ancient seawater. Archaean oceans were depleted in deuterium [expressed as δD relative to Vienna standard mean ocean water (VSMOW)] by at most 25 ± 5‰, but oxygen isotope ratios were comparable to modern oceans. Mass balance of the global hydrogen budget constrains the contribution of continental growth and planetary hydrogen loss to the secular evolution of hydrogen isotope ratios in Earth’s oceans. Our calculations predict that the oceans of early Earth were up to 26% more voluminous, and atmospheric CH4 and CO2 concentrations determined from limits on hydrogen escape to space are consistent with clement conditions on Archaean Earth. PMID:22392985

Facies architecture and sequence-stratigraphic features of the Tumbiana Formation: A depositional setting of late Archaean stromatolites in the Pilbara Craton, northwestern Australia

NASA Astrophysics Data System (ADS)

Sakurai, R.; Ueno, Y.; Kitajima, K.; Ito, M.; Maruyama, S.

2001-12-01

The Tumbiana Formation (ca. 2700 Ma) is a succession developed in response to late Archaean crustal extension in the Pilbara Craton, northwestern Australia. The formation is characterized by intercalations of stromatolite carbonates and provides a perspective of evolution of photosynthetic organisms that are interpreted to have been responsible for oxygenation of atmosphere. Here we investigated a depositional setting of the stromatolite limestone for better understanding of an environment that may have controlled early development of oxygenic photosynthesis. We studied lithofacies and sequence-stratigraphic features of the Tumbiana Formation in the Redmont area based upon three-dimensional analyses of onshore outcrops. The Tumbiana Formation, as much as 170 m thick, unconformably overlies the early Archaean basement rocks and is unconformably overlain by the Maddina Formation that consists of mafic tuffaceous sediments and basalt. The lower part of the Tumbiana Formation is characterized by planar- and trough-cross stratified conglomerates that are interpreted to be an alluvial-fan deposit shed from the northern hinterlands and developed mainly in local depressions of the basement rocks during an early transgressive stage. The base of the middle part is defined by a transgressive erosional surface overlain by conglomerates and/or breccia that pass upward to mafic tuffaceous mudstones and sandstones intercalated with accretionary lapilli, breccia, and basalt. Mudstones are commonly laminated and sandstones contain current- and wave ripple-lamination, parallel lamination, hummocky cross-stratification, and trough cross-stratification. In general, the middle part exhibits an overall fining- and coarsening-upward pattern and is interpreted to indicate transgressive and regressive shelf-to-coastal lithofacies successions. In particular, the uppermost horizon of the middle part is characterized by sandstone beds with herringbone structures and desiccation cracks and is

Identifying Provenance of Archaean Basal Conglomerates: An Evidence from Sigegudda and Bababudan Conglomerate Quartzites, India

NASA Astrophysics Data System (ADS)

Mitra, A.; Dey, S.

2017-12-01

Geochemical characteristics of clastic sedimentary rocks deposited and later preserved in ancient supracrustal sequences of Archaean terrain are competent representation of their source rocks in provenance. These rocks usually sample a wide geographic area and bear signature of subsequently destroyed and dismembered terrains. In this study the quartz pebble conglomerate-quartz sandstone association of Sigegudda and Bababudan belt of western Dharwar craton (WDC), Southern India have been studied to understand the nature of their provenance. Both Sigegudda and Bababudan belt represent younger (2.8-2.6 Ga) greenstone sequences of WDC. They start with a prominent band of conglomerate-quartzite lying over Palaeo to Meso Archaean Peninsular Gneiss (3.35-3.29 Ga) with older Sargur greentone (3.35-3.28 Ga) enclaves along an unconformity. Here, we present a comprehensive provenance (mainly source rock characterization) study of major and trace element composition of low to moderately metamorphosed basal siliciclastics of the younger greenstone sequences of WDC. Chemically they are enriched in Th, U, HFSE (Hf, Nb, Zr) and depleted in Sc, Co, Cr and Eu content with elevated La/Sc and Th/Sc values depicting a differentiated felsic source. This is further supported by fractionated LREE (10.64 - 14.66), significant negative Eu anomaly (0.67 - 0.55) and nearly flat HREE indicating granitoid rocks as source. In La-Th-Cr/100 and La-Th-Sc triangular diagram, quartz arenite field overlap with the Peninsular Gneiss and plotted far away from the mafic-ultramafics of Sargur. The chemical index of alteration (CIA) values of arenites of Sigegudda (71) and Bababudan (75), Peninsular Gneisses (avg-50) and Sargur group (avg-30) implies their derivation from the underlying gneisses associated with a prolonged weathering. The presence of a thick conglomerate-quartz sandstone association with differently sized quartz in their framework and matrix, depicts the development of a stable craton in

Archaean zircons in Miocene oceanic hotspot rocks establish ancient continental crust beneath Mauritius

PubMed Central

Ashwal, Lewis D.; Wiedenbeck, Michael; Torsvik, Trond H.

2017-01-01

A fragment of continental crust has been postulated to underlie the young plume-related lavas of the Indian Ocean island of Mauritius based on the recovery of Proterozoic zircons from basaltic beach sands. Here we document the first U–Pb zircon ages recovered directly from 5.7 Ma Mauritian trachytic rocks. We identified concordant Archaean xenocrystic zircons ranging in age between 2.5 and 3.0 Ga within a trachyte plug that crosscuts Older Series plume-related basalts of Mauritius. Our results demonstrate the existence of ancient continental crust beneath Mauritius; based on the entire spectrum of U–Pb ages for old Mauritian zircons, we demonstrate that this ancient crust is of central-east Madagascar affinity, which is presently located ∼700 km west of Mauritius. This makes possible a detailed reconstruction of Mauritius and other Mauritian continental fragments, which once formed part of the ancient nucleus of Madagascar and southern India. PMID:28140395

Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma.

PubMed

Sauer, C M; Haugg, A M; Chteinberg, E; Rennspiess, D; Winnepenninckx, V; Speel, E-J; Becker, J C; Kurz, A K; Zur Hausen, A

2017-08-01

Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by early metastases and poor survival. Although MCC is a rare malignancy, its incidence is rapidly increasing in the U.S. and Europe. The discovery of the Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its etiopathogenesis and biology. MCCs are characterized by trilinear differentiation, comprising the expression of neuroendocrine, epithelial and B-lymphoid lineage markers. To date, it is generally accepted that the initial assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed to their post-mitotic character, absence of MCPyV in MCs and discrepant protein expression pattern in comparison to MCC. Evidence from mouse models suggests that epidermal/dermal stem cells might be of cellular origin in MCC. The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression of early B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review we elaborate on the cellular ancestry of MCC, the identification of which could pave the way for novel and more effective therapeutic regimens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The evolution of early cellular systems viewed through the lens of biological interactions.

PubMed

Poole, Anthony M; Lundin, Daniel; Rytkönen, Kalle T

2015-01-01

The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts-list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the last universal common ancestor, as few genes trace back to this hypothetical ancestral state. However, the study of minimal cellular systems is the study of biological outliers where, by practical necessity, coevolutionary interactions are minimized or ignored. In this paper, we consider the biological context from which minimal genomes have been removed. For instance, some of the most reduced genomes are from endosymbionts and are the result of coevolutionary interactions with a host; few such organisms are "free-living." As few, if any, biological systems exist in complete isolation, we expect that, as with modern life, early biological systems were part of an ecosystem, replete with organismal interactions. We favor refocusing discussions of the evolution of cellular systems on processes rather than gene counts. We therefore draw a distinction between a pragmatic minimal cell (an interesting engineering problem), a distributed genome (a system resulting from an evolutionary transition involving more than one cell) and the looser coevolutionary interactions that are ubiquitous in ecosystems. Finally, we consider the distributed genome and coevolutionary interactions between genomic entities in the context of early evolution.

Organic-walled microfossils in 3.2-billion-year-old shallow-marine siliciclastic deposits.

PubMed

Javaux, Emmanuelle J; Marshall, Craig P; Bekker, Andrey

2010-02-18

Although the notion of an early origin and diversification of life on Earth during the Archaean eon has received increasing support in geochemical, sedimentological and palaeontological evidence, ambiguities and controversies persist regarding the biogenicity and syngeneity of the record older than Late Archaean. Non-biological processes are known to produce morphologies similar to some microfossils, and hydrothermal fluids have the potential to produce abiotic organic compounds with depleted carbon isotope values, making it difficult to establish unambiguous traces of life. Here we report the discovery of a population of large (up to about 300 mum in diameter) carbonaceous spheroidal microstructures in Mesoarchaean shales and siltstones of the Moodies Group, South Africa, the Earth's oldest siliciclastic alluvial to tidal-estuarine deposits. These microstructures are interpreted as organic-walled microfossils on the basis of petrographic and geochemical evidence for their endogenicity and syngeneity, their carbonaceous composition, cellular morphology and ultrastructure, occurrence in populations, taphonomic features of soft wall deformation, and the geological context plausible for life, as well as a lack of abiotic explanation falsifying a biological origin. These are the oldest and largest Archaean organic-walled spheroidal microfossils reported so far. Our observations suggest that relatively large microorganisms cohabited with earlier reported benthic microbial mats in the photic zone of marginal marine siliciclastic environments 3.2 billion years ago.

Constant average olivine Mg# in cratonic mantle reflects Archaean mantle melting to the exhaustion of orthopyroxene

NASA Astrophysics Data System (ADS)

Bernstein, S.; Kelemen, P. B.; Hanghoj, K.

2006-12-01

Shallow (garnet-free) cratonic mantle, occurring as xenoliths in kimberlites and alkaline basaltic lavas, has high Mg# (100x Mg/(Mg+Fe)>92) and is poor in Al and Ca compared to off-cratonic mantle. Many xenoliths show rhenium-depletion age of > 3 Ga, and are thus representative of depleted mantle peridotite that form an integral part of the stable nuclei of Archaean (2.5-3.8 Ga) cratons. Accordingly, the depleted composition of the xenolith suites is linked to Archaean melt extraction events. We have compiled data for many suites of shallow cratonic mantle xenoliths worldwide, including samples from cratons of Kaapvaal, Tanzania, Siberia, Slave, North China and Greenland, and encompassing both the classic orthopyroxene-rich peridotites of Kaapvaal and orthopyroxene-poor peridotites from Greenland. The suites show a remarkably small range in average olivine Mg# of 92.8 +/- 0.2. Via comparison with data for experimental melting of mantle peridotite compositions, we explain consistent olivine Mg# in the shallow cratonic mantle as the result of mantle melting and melt extraction to the point of orthopyroxene exhaustion, leaving a nearly monomineralic olivine, or dunitic, residue. Experimental data for peridotite melting at pressures less than 4 GPa and data on natural rocks suggest that mantle olivine has a Mg# of about 92.8 at the point of orthopyroxene exhaustion. If the melt extraction was efficient, no further melting could take place without a considerable temperature increase or melt/fluid flux through the dunite residue at high temperatures. While the high Mg#, dunite-dominated xenolith suites from e.g. Greenland represent simple residues from mantle melting, the orthopyroxene-rich xenolith suites with identical Mg# as known from e. g. Kaapvaal must reflect some additional processes. We envisage their derivation from dunite protoliths via subsequent melt/rock reaction with silica-rich melts or, in some cases, possibly as residues at higher average melting

Imaging eubacteria and archaean cell abundance and nitrification activity on marine snow particles collected from the South Pacific using microscopy and nanoSIMS

NASA Astrophysics Data System (ADS)

Foster, R.; Santoro, A. E.; Tienken, D.; Littman, S.; Berelson, W.; Kuypers, M. M. M.

2016-02-01

The abundance and nitrification activity by marine-snow associated eubacteria and archaea were measured on particles collected in the South Pacific. The particles were first collected from 24 hour floating sediment traps moored at 100 and 200 m and later amended and incubated with 13C-bicarbonate and 15NH4 for 48 hours. Enrichment for 13C and 15N in cells above natural abundance was quantified using a coupled halogenated in situ hybridization assay with nano-meter scale secondary ion mass spectrometry (HISH-SIMS). Approximately 82% ± 10 of the observed hybridized cells were Eubacterial, while 24% ± 5 were positively hybridized with the Archaean probe. There was high variability in 13C/12C and 15N/14N in both bacterial and archaeal cells. Complementary measurements of δ15NNO3 at the conclusion of the experiment indicated no detectible nitrification activity associated with the particles. Thin sections of the particles imaged with Transmission Electron Microscopy (TEM) showed that a higher abundance of degrading phytoplanktonic cells, including numerous empty radiolarian and diatom frustules were associated with the deeper moored tap, while the shallow trap collected intact bacterial cells, including small picocyanobacteria. Single cell imaging and observations such as those presented here can provide subtle insights and measurements of cellular activity that are often diluted by bulk approaches and that are directly applicable to modeling N and C cycling.

Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease.

PubMed

Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J

2016-01-01

Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task.

Early detection of disease program: Evaluation of the cellular immune response

NASA Technical Reports Server (NTRS)

Criswell, B. S.; Knight, V.; Martin, R. R.; Kasel, J. A.

1974-01-01

The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

Early impact basins and the onset of plate tectonics. Ph.D. Thesis - Maryland Univ.

NASA Technical Reports Server (NTRS)

Frey, H.

1977-01-01

The fundamental crustal dichotomy of the Earth (high and low density crust) was established nearly 4 billion years ago. Therefore, subductable crust was concentrated at the surface of the Earth very early in its history, making possible an early onset for plate tectonics. Simple thermal history calculations spanning 1 billion years show that the basin forming impact thins the lithosphere by at least 25%, and increases the sublithosphere thermal gradients by roughly 20%. The corresponding increase in convective heat transport, combined with the highly fractured nature of the thinned basin lithosphere, suggest that lithospheric breakup or rifting occurred shortly after the formation of the basins. Conditions appropriate for early rifting persisted from some 100,000,000 years following impact. We suggest a very early stage of high temperature, fast spreading "microplate" tectonics, originating before 3.5 billion years ago, and gradually stabilizing over the Archaean into more modern large plate or Wilson Cycle tectonics.

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

PubMed

Saraf, Rabya; Huang, Thomas; Mahmood, Feroze; Owais, Khurram; Bardia, Amit; Khabbaz, Kamal R; Liu, David; Senthilnathan, Venkatachalam; Lassaletta, Antonio D; Sellke, Frank; Matyal, Robina

2016-01-01

Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome. Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD). There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group. Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

Massive cellular disruption occurs during early imbibition of Cuphea seeds containing crystallized triacylglycerols.

PubMed

Volk, Gayle M; Crane, Jennifer; Caspersen, Ann M; Hill, Lisa M; Gardner, Candice; Walters, Christina

2006-11-01

The transition from anhydrobiotic to hydrated state occurs during early imbibition of seeds and is lethal if lipid reserves in seeds are crystalline. Low temperatures crystallize lipids during seed storage. We examine the nature of cellular damage observed in seeds of Cuphea wrightii and C. lanceolata that differ in triacylglycerol composition and phase behavior. Intracellular structure, observed using transmission electron microscopy, is profoundly and irreversibly perturbed if seeds with crystalline triacylglycerols are imbibed briefly. A brief heat treatment that melts triacylglycerols before imbibition prevents the loss of cell integrity; however, residual effects of cold treatments in C. wrightii cells are reflected by the apparent coalescence of protein and oil bodies. The timing and temperature dependence of cellular changes suggest that damage arises via a physical mechanism, perhaps as a result of shifts in hydrophobic and hydrophilic interactions when triacylglycerols undergo phase changes. Stabilizers of oil body structure such as oleosins that rely on a balance of physical forces may become ineffective when triacylglycerols crystallize. Recent observations linking poor oil body stability and poor seed storage behavior are potentially explained by the phase behavior of the storage lipids. These findings directly impact the feasibility of preserving genetic resources from some tropical and subtropical species.

The first 800 million years of earth's history

NASA Technical Reports Server (NTRS)

Smith, J. V.

1981-01-01

It is pointed out that there is no direct geological information on the first 750 Ma of earth history. Consequently the reported study is based on controversial inferences drawn from the moon, other planets and meteorites, coupled with backward extrapolation from surviving terrestrial rocks, especially those of Archaean age. Aspects of accretion are considered, taking into account cosmochemical and cosmophysical evidence, a new earth model, and convection systems. Attention is given to phase-equilibrium constraints, estimates of heat production, the bombardment history of the moon and implications for the earth, and the nature of the early crust. From a combination of physical, chemical, and petrological arguments, it is concluded that the earth's surface underwent intense volcanism in the pre-Archaean era, and that the rock types were chemically similar to those found in the early Archaean era.

An Archaean submarine volcanic debris avalanche deposit, Yilgarn Craton, western Australia, with komatiite, basalt and dacite megablocks. The product of dome collapse

NASA Astrophysics Data System (ADS)

Trofimovs, J.; Cas, R. A. F.; Davis, B. K.

2004-11-01

The Boorara Domain of the Kalgoorlie Terrane, Eastern Goldfields Superterrane, western Australia contains excellent exposure of Archaean felsic and ultramafic breccias characterised by facies associations interpreted to reflect a volcanic debris avalanche mode of deposition. Such Archaean volcanic deposits are typically difficult to identify due to poor preservation and exposure. However, primary volcanological and sedimentological features are preserved within the relatively low strain and low metamorphic grade (up to lower greenschist facies) Boorara Domain that allow accurate facies reconstruction. The breccia deposit is characterised by two clast populations. A 'block facies' comprised of metre- to decimetre-scale megablocks of dacite, basalt and komatiite is preserved within a 'mixed' matrix breccia facies of angular, coarse sand- to boulder-sized clasts. The megablocks preserve original stratigraphy and show fracturing and jigsaw-fit textures within the poorly sorted, unstratified, genetically related matrix. Overlying the volcanic debris avalanche deposit, are a series of stratified horizons. These deposits show evidence of hydraulic sorting within bedforms exhibiting normal grain-size grading and tractional scour and fill structures along their basal contacts. The stratified facies is interpreted to have been deposited by high concentration, high competency turbidity currents, triggered by slope stabilization slides in the source region. Primary contacts and volcanic textures preserved in decimetre-scale volcanic blocks allow reconstruction of the pre-collapse palaeovolcanological history of the source region. The volcanic debris avalanche deposit, together with the associated stratified sedimentary horizons, were produced by sector collapse of a submarine, dacitic volcanic dome. Contemporaneous komatiite intrusion into the dacite dome may have caused dome flank instability. However, the volcanic debris avalanche trigger is interpreted to be a post

Evidence for extreme mantle fractionation in early Archaean ultramafic rocks from northern Labrador

NASA Technical Reports Server (NTRS)

Collerson, Kenneth D.; Campbell, Lisa M.; Weaver, Barry L.; Palacz, Zenon A.

1991-01-01

Samarium-neodymium isotope data for tectonically interleaved fragments of lithospheric mantle and meta-komatiite from the North Atlantic craton provide the first direct record of mantle differentiation before 3,800 Myr ago. The results confirm the magnitude of light-rare-earth-element depletion in the early mantle, and also its depleted neodymium isotope composition. The mantle fragments were able to retain these ancient geochemical signatures by virtue of having been tectonically incorporated in buoyant felsic crust, thus escaping recycling and homogenization by mantle convection.

Coordination of cellular differentiation, polarity, mitosis and meiosis - New findings from early vertebrate oogenesis.

PubMed

Elkouby, Yaniv M; Mullins, Mary C

2017-10-15

A mechanistic dissection of early oocyte differentiation in vertebrates is key to advancing our knowledge of germline development, reproductive biology, the regulation of meiosis, and all of their associated disorders. Recent advances in the field include breakthroughs in the identification of germline stem cells in Medaka, in the cellular architecture of the germline cyst in mice, in a mechanistic dissection of chromosomal pairing and bouquet formation in meiosis in mice, in tracing oocyte symmetry breaking to the chromosomal bouquet of meiosis in zebrafish, and in the biology of the Balbiani body, a universal oocyte granule. Many of the major events in early oogenesis are universally conserved, and some are co-opted for species-specific needs. The chromosomal events of meiosis are of tremendous consequence to gamete formation and have been extensively studied. New light is now being shed on other aspects of early oocyte differentiation, which were traditionally considered outside the scope of meiosis, and their coordination with meiotic events. The emerging theme is of meiosis as a common groundwork for coordinating multifaceted processes of oocyte differentiation. In an accompanying manuscript we describe methods that allowed for investigations in the zebrafish ovary to contribute to these breakthroughs. Here, we review these advances mostly from the zebrafish and mouse. We discuss oogenesis concepts across established model organisms, and construct an inclusive paradigm for early oocyte differentiation in vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells.

PubMed

Jeon, Yoon; Ko, Eun; Lee, Kyung Yong; Ko, Min Ji; Park, Seo Young; Kang, Jeeheon; Jeon, Chang Hwan; Lee, Ho; Hwang, Deog Su

2011-02-18

TopBP1 plays important roles in chromosome replication, DNA damage response, and other cellular regulatory functions in vertebrates. Although the roles of TopBP1 have been studied mostly in cancer cell lines, its physiological function remains unclear in mice and untransformed cells. We generated conditional knock-out mice in which exons 5 and 6 of the TopBP1 gene are flanked by loxP sequences. Although TopBP1-deficient embryos developed to the blastocyst stage, no homozygous mutant embryos were recovered at E8.5 or beyond, and completely resorbed embryos were frequent at E7.5, indicating that mutant embryos tend to die at the peri-implantation stage. This finding indicated that TopBP1 is essential for cell proliferation during early embryogenesis. Ablation of TopBP1 in TopBP1(flox/flox) mouse embryonic fibroblasts and 3T3 cells using Cre recombinase-expressing retrovirus arrests cell cycle progression at the G(1), S, and G(2)/M phases. The TopBP1-ablated mouse cells exhibit phosphorylation of H2AX and Chk2, indicating that the cells contain DNA breaks. The TopBP1-ablated mouse cells enter cellular senescence. Although RNA interference-mediated knockdown of TopBP1 induced cellular senescence in human primary cells, it induced apoptosis in cancer cells. Therefore, TopBP1 deficiency in untransformed mouse and human primary cells induces cellular senescence rather than apoptosis. These results indicate that TopBP1 is essential for cell proliferation and maintenance of chromosomal integrity.

New concept: cellular senescence in pathophysiology of cholangiocarcinoma.

PubMed

Sasaki, Motoko; Nakanuma, Yasuni

2016-01-01

Cholangiocarcinoma, a malignant tumor arising in the hepatobiliary system, presents with poor prognosis because of difficulty in its early detection/diagnosis. Recent progress revealed that cellular senescence may be involved in the pathophysiology of cholangiocarcinoma. Cellular senescence is defined as permanent growth arrest caused by several cellular injuries, such as oncogenic mutations and oxidative stress. "Oncogene-induced" and/or stress-induced senescence may occur in the process of multi-step cholangiocarcinogenesis, and overexpression of a polycomb group protein EZH2 may play a role in the escape from, and/or bypassing of, senescence. Furthermore, senescent cells may play important roles in tumor development and progression via the production of senescence-associated secretory phenotypes. Cellular senescence may be a new target for the prevention, early diagnosis, and therapy of cholangiocarcinoma in the near future.

Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

PubMed

Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

2013-11-30

Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metal availability and the expanding network of microbial metabolisms in the Archaean eon

NASA Astrophysics Data System (ADS)

Moore, Eli K.; Jelen, Benjamin I.; Giovannelli, Donato; Raanan, Hagai; Falkowski, Paul G.

2017-09-01

Life is based on energy gained by electron-transfer processes; these processes rely on oxidoreductase enzymes, which often contain transition metals in their structures. The availability of different metals and substrates has changed over the course of Earth's history as a result of secular changes in redox conditions, particularly global oxygenation. New metabolic pathways using different transition metals co-evolved alongside changing redox conditions. Sulfur reduction, sulfate reduction, methanogenesis and anoxygenic photosynthesis appeared between about 3.8 and 3.4 billion years ago. The oxidoreductases responsible for these metabolisms incorporated metals that were readily available in Archaean oceans, chiefly iron and iron-sulfur clusters. Oxygenic photosynthesis appeared between 3.2 and 2.5 billion years ago, as did methane oxidation, nitrogen fixation, nitrification and denitrification. These metabolisms rely on an expanded range of transition metals presumably made available by the build-up of molecular oxygen in soil crusts and marine microbial mats. The appropriation of copper in enzymes before the Great Oxidation Event is particularly important, as copper is key to nitrogen and methane cycling and was later incorporated into numerous aerobic metabolisms. We find that the diversity of metals used in oxidoreductases has increased through time, suggesting that surface redox potential and metal incorporation influenced the evolution of metabolism, biological electron transfer and microbial ecology.

Geological constraints on detecting the earliest life on Earth: a perspective from the Early Archaean (older than 3.7 Gyr) of southwest Greenland

PubMed Central

Fedo, Christopher M; Whitehouse, Martin J; Kamber, Balz S

2006-01-01

At greater than 3.7 Gyr, Earth's oldest known supracrustal rocks, comprised dominantly of mafic igneous with less common sedimentary units including banded iron formation (BIF), are exposed in southwest Greenland. Regionally, they were intruded by younger tonalites, and then both were intensely dynamothermally metamorphosed to granulite facies (the highest pressures and temperatures generally encountered in the Earth's crust during metamorphism) in the Archaean and subsequently at lower grades until about 1500 Myr ago. Claims for the first preserved life on Earth have been based on the occurrence of greater than 3.8 Gyr isotopically light C occurring as graphite inclusions within apatite crystals from a 5 m thick purported BIF on the island of Akilia. Detailed geologic mapping and observations there indicate that the banding, first claimed to be depositional, is clearly deformational in origin. Furthermore, the mineralogy of the supposed BIF, being dominated by pyroxene, amphibole and quartz, is unlike well-known BIF from the Isua Greenstone Belt (IGB), but resembles enclosing mafic and ultramafic igneous rocks modified by metasomatism and repeated metamorphic recrystallization. This scenario parsimoniously links the geology, whole-rock geochemistry, 2.7 Gyr single crystal zircon ages in the unit, an approximately 1500 Myr age for apatites that lack any graphite, non-MIF sulphur isotopes in the unit and an inconclusive Fe isotope signature. Although both putative body fossils and carbon-12 enriched isotopes in graphite described at Isua are better explained by abiotic processes, more fruitful targets for examining the earliest stages in the emergence of life remain within greater than 3.7 Gyr IGB, which preserves BIF and other rocks that unambiguously formed at Earth's surface. PMID:16754603

Heat flow, heat production, and crustal temperatures in the Archaean Bundelkhand craton, north-central India: Implications for thermal regime beneath the Indian shield

NASA Astrophysics Data System (ADS)

Podugu, Nagaraju; Ray, Labani; Singh, S. P.; Roy, Sukanta

2017-07-01

Heat flow and heat production data sets constrain the crustal thermal structure in the 2.5-3.5 Ga Bundelkhand craton, the oldest cratonic core in northern Indian shield, for the first time and allow comparisons with the southern Indian shield. Temperature measurements carried out in 10 boreholes at five sites in the craton, combined with systematic thermal conductivity measurements on major rock types, yield low heat flow in the range of 32-41 mW m-2, which is distinct from the generally high heat flow reported from other parts of the northern Indian shield. Radioelemental measurements on 243 samples of drill cores and outcrops reveal both large variability and high average heat production for the Neo-Archaean to Palaeo-Proterozoic granites (4.0 ± 2.1 (SD) μW m-3) relative to the Meso-Archaean tonalite-trondhjemite-granodiorite (TTG) gneisses (2.0 ± 1.0 (SD) μW m-3). On the basis of new heat flow and heat production data sets combined with available geological and geophysical information, a set of steady state, heat flow-crustal heat production models representative of varying crustal scenarios in the craton are envisaged. Mantle heat flow and Moho temperatures are found to be in the range of 12-22 mW m-2 and 290-420°C, respectively, not much different from those reported for the similar age Dharwar craton in southern India. This study reveals similar mantle thermal regimes across the northern and southern parts of the Indian shield, in spite of varying surface heat flow regimes, implying that much of the intraprovince and interprovince variations in the Indian shield are explained by variations in upper crustal heat production.

Archaean and Palaeoproterozoic metamorphic events in the Orekhov-Pavlograd compressional zone, Ukrainian Shield

NASA Astrophysics Data System (ADS)

Yurchenko, A. V.

2012-04-01

The Orekhov-Pavlograd zone (OPZ) is located between the Mesoarchaean-Neoarchaean Middle Dnieper Province and the Mesoarchaean-Palaeoproterozoic Azov Province in the eastern Ukrainian Shield. The OPZ consists of Archaean and Palaeoproterozoic high-grade metamorphic rocks. According U-Pb isotope analyses Archaean methaigneous rocks have age of 3.5-3.3 Ga, and latest AR events dated form both individual grains and metamorphic rims in the tonalite and the granitic vein occurred at about 2.88 Ga ego. Paleoproterozoic zircons from a hornblende granulite have a concordia age of 2.08 Ga [1]. P-T conditions of the 3.5-3.3 Ga processes calculated from the Ti content in zircon are of 730-760°C. Metamorphic event dated as 2.88 Ga is more preserved and detected in some amphibolites after mafic dykes. According to different methods of hornblende-plagioclase geothermometry along with Al- and Ti-geobarometry of hornblende, the amphibolites have formed at temperature of 735-749 °C and pressure of 5.2 to 7.8 kbar. P-T conditions of Paleoproterozoic metamorphic processes have been calculated for a Paleoproterozoic high-Al paragneiss and mafic rocks. On the base of the computer software THERIAK-DOMINO [2], near-isothermal decompression from ca. 8.5 to 6.0 kbar at 650 °C and then to 5.8 kbar at 740 °C has been determined for small irregular garnet grains (grs 4-7% and XMg 0.36-0.37) associated with the same biotite and plagioclase. P-T conditions obtained by means of the P-T pseudosection calculation are identical within errors to those defined by the Grt + Bt + Pl + Ozt geothermometer by [3] and the geobarometer by [4], T = 675 °C and P = 5.6 kbar. Temperature and pressure calculated for assemblage Grt-Pl-Opx-Amph-Ilm-Ru (mafic rock) by using the TWEEQU method shows: 1) high values of pressure and temperature (ca. 7 kbar and 800 °C) are linked with the first metamorphic event with Opx-Cpx assemblage, 2) moderate values (ca. 5 kbar and ca. 600 °C) are referred to the second

Development of the earth-moon system with implications for the geology of the early earth

NASA Technical Reports Server (NTRS)

Smith, J. V.

1976-01-01

Established facts regarding the basic features of the earth and the moon are reviewed, and some important problems involving the moon are discussed (extent of melting, time of crustal differentiation and nature of bombardment, bulk chemical composition, and nature and source of mare basins), with attention given to the various existing theories concerning these problems. Models of the development of the earth-moon system from the solar nebula are examined, with particular attention focused on those that use the concept of capture with disintegration. Impact processes in the early crust of the earth are briefly considered, with attention paid to Green's (1972) suggestion that Archaean greenstone belts may be the terrestrial equivalent of lunar maria.

[Effect of early high fat diet on pancreatic β cellularity and insulin sensibility in young rats].

PubMed

Xie, Kun-Xia; Xiao, Yan-Feng; Xu, Er-Di; Yin, Chun-Yan; Yi, Xiao-Qing; Chang, Ming

2010-09-01

To study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic β cellularity in young rats. Sixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope. The high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet β-cells were observed in the high fat group after 6 weeks. Early high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in β-cells may be an early sign of β-cell damage due to obesity.

High-K calc-alkaline magmatism at the Archaean-Proterozoic boundary: implications for mantle metasomatism and continental crust petrogenesis. Example of the Bulai pluton (Central Limpopo Belt, South Africa)

NASA Astrophysics Data System (ADS)

Laurent, Oscar; Martin, Hervé; Doucelance, Régis; Moyen, Jean-François; Paquette, Jean-Louis

2010-05-01

The Neoarchaean Bulai pluton, intrusive within the supracrustal granulites of the Central Limpopo Belt (Limpopo Province, South Africa) is made up of large volumes of porphyritic granodiorites with subordinate enclaves and dykes which have monzodioritic and charno-enderbitic compositions. New U-Pb LA-ICP-MS dating on separated zircons yielded pluton emplacement ages ranging between 2.60 and 2.63 Ga, which are slightly older than previous proposed ages (~ 2.57-2.61 Ga). The whole-rock major- and trace-element composition of the Bulai pluton evidences unequivocal affinities with "high-Ti" late-Archaean sanukitoids. It belongs to a high-K calc-alkaline differentiation suite, with metaluminous affinities (0.7 < A/CNK < 1) and relatively high Mg# (0.4-0.6). These rocks have "juvenile" affinities, such as eNd ranging between -0.5 and 0.5, and in addition, are very rich in all incompatible trace elements, which is particularly obvious in monzodioritic enclaves and enderbites where primitive mantle-normalized LILE and LREE contents are up to 300. These characteristics point to an enriched mantle source for the Bulai batholith. Chondrite normalized, REE patterns are strongly fractionated ([La/Yb]N ~ 25-80), mainly due to high LREE contents (LaN ~ 250-630), and chiefly high HFSE contents (Nb ~ 15-45 ppm ; up to 770 ppm Zr) indicate that the metasomatic agent is a silicic melt rather than a hydrous fluid. Moreover, based on high Nb/Ta, Th/Rb, La/Rb and low Sr/Nd and Ba/La, we suggest that the metasomatic agent is a granitic melt generated by melting of terrigenous sediments. Interactions of this melt with mantle peridotites implies that sediments are located under a mantle slice; geometry which is easily achieved in subduction zone settings. This conclusion is supported by the fact that Bulai trace element patterns are very similar to those of sub-actual potassic magmas generated in magmatic arc environments by interactions between mantle and terrigenous sediments (e.g. Sunda

A Field Trip to the Archaean in Search of Darwin's Warm Little Pond.

PubMed

Damer, Bruce

2016-05-25

Charles Darwin's original intuition that life began in a "warm little pond" has for the last three decades been eclipsed by a focus on marine hydrothermal vents as a venue for abiogenesis. However, thermodynamic barriers to polymerization of key molecular building blocks and the difficulty of forming stable membranous compartments in seawater suggest that Darwin's original insight should be reconsidered. I will introduce the terrestrial origin of life hypothesis, which combines field observations and laboratory results to provide a novel and testable model in which life begins as protocells assembling in inland fresh water hydrothermal fields. Hydrothermal fields are associated with volcanic landmasses resembling Hawaii and Iceland today and could plausibly have existed on similar land masses rising out of Earth's first oceans. I will report on a field trip to the living and ancient stromatolite fossil localities of Western Australia, which provided key insights into how life may have emerged in Archaean, fluctuating fresh water hydrothermal pools, geological evidence for which has recently been discovered. Laboratory experimentation and fieldwork are providing mounting evidence that such sites have properties that are conducive to polymerization reactions and generation of membrane-bounded protocells. I will build on the previously developed coupled phases scenario, unifying the chemical and geological frameworks and proposing that a hydrogel of stable, communally supported protocells will emerge as a candidate Woese progenote, the distant common ancestor of microbial communities so abundant in the earliest fossil record.

Gold mineralisation throughout about 45 Ma of Archaean orogenesis: protracted flux of gold in the Golden Mile, Yilgarn craton, Western Australia

NASA Astrophysics Data System (ADS)

Bateman, Roger; Hagemann, Steffen

2004-10-01

Golden Mile Dolerite exerting a strong lithological control on gold mineralisation. Veins consist of quartz carbonate minor scheelite, and wall-rock alteration comprises chlorite destruction and growth of ferroan carbonate sericite pyrite native gold. Pyrite pyrrhotite is zoned on the scale of vein haloes and of the entire mine, giving a vertical temperature gradient of 50 100 °C over 1,000 vertical metres. The structural hydrothermal model proposed consists of four major stages: (1) D1 thrusting and formation of Fimiston-style lodes, (2) D2 reverse faulting and formation of Oroya-style lodes, (3) D3 faulting and dissecting of Fimiston- and Oroya-style lodes, and (4) D4 faulting and formation of Mt Charlotte-style sheeted quartz vein system. The giant accumulation of gold in the Golden Mile deposit was formed due to protracted gold mineralisation throughout episodes of an Archaean orogeny that spanned about 45 Ma. Fluid conduits formed early in the tectonic history and persisted throughout orogenesis with the plumbing system showing a rare high degree of focussing, efficiency and duration. In addition to the long-lasting fluid plumbing system, the wide variety of transient structural and geochemical traps, multiple fluid sources and precipitation mechanism contributed towards the richest golden mile in the world.

A Sm-Nd and Pb isotope study of Archaean greenstone belts in the southern Kaapvaal Craton, South Africa

NASA Technical Reports Server (NTRS)

Wilson, A. H.; Carlson, R. W.

1989-01-01

An Sm-Nd and Pb study on a wide variety of lithologies in Archaean greenstone belt fragments in the southern Kaapvaal Craton reveals a complex petrogenetic history. The fragments are important because they represent a 350 km transect through the craton south of Barberton to its southern margin. The Commondale greenstone belt yields a precise Sm-Nd age of 3334 + or - 18 Ma on an exceptionally well preserved peridotite suite of komatiitic affinity. The wide range of Sm/Nd from 0.6 to 1.0 is attributed to the unusual occurrence of orthopyroxene in the spinifex-bearing rocks. A considerably younger age of about 3.2 Ga is suggested for the Nondweni greenstone belt close to the southern margin of the craton on the basis of separate Sm-Nd isochrons on individual lithologies ranging from komatiite, through komatiitic basalt and basalt to felsic volcanic rocks. On the basis of the present study the greenstone belts appear to have been emplaced at progressively younger ages toward the southern margin of the craton.

An Archaean Tonalite-Trondhjemite-Granodiorite Association of the Kursk Block (Voronezh Massif): Composition, Age, and Correlation with the Ukrainian Shield

NASA Astrophysics Data System (ADS)

Savko, K. A.; Samsonov, A. V.; Larionov, A. N.; Korish, E. Kh.; Bazikov, N. S.

2018-01-01

Framing of the Archaean greenstone belts of the Kursk Block (KB) of the East Sarmatia preserves rocks of the TTG association: those do not form massifs with distinct boundaries, but occur as fields gradually transiting into gneisses and migmatites. According to Sm-Nd isotope-geochemical data, the TTG are characterized by positive values of ɛNd(2960) = +0.3…+1.6 and protolith model ages of T Nd( DM) = 3100-3200 Ma. Magmatic protoliths of the Kursk Block TTG were formed about 2960 Ma by melting from a juvenile basite source. These age estimates are significantly younger than heterochronous (3.19, 3.13 and 3.07 Ga) TTGs of the Middle Dnieper granite-greenstone terrane. On the other hand, the similarity of ɛNd(T) implies a single source of their protoliths. Consequently, the KB TTGs, apparently, are a result of transformation of an older sial crust preserved within the Middle Dnieper Block.

Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the human cytomegalovirus UL127 and major immediate-early genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee Jialing; Klase, Zachary; Gao Xiaoqi

An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal, P., 2000. Identification of a boundary domain adjacent to the potent human cytomegalovirus enhancer that represses transcription of the divergent UL127 promoter. J.more » Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski, M.F., 1999. A strong negative transcriptional regulatory region between the human cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73 (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was identified in the UR and found to play a key role in repression of the UL127 promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A., Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113-5123]. However, the cellular factors which associate with the UR and FOX-like region remain to be determined. We reported previously that pancreatic-duodenal homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao, S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell, J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111-16120]. Here we demonstrate that two additional cellular homeoproteins, special AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP), bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as a FOX-like binding

Petrology and isotopic geochemistry of the Archaean basement lithologies near Gardiner, Montana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guy, R.E.; Sinha, A.K.

1985-01-01

In an attempt to recognize potential source rocks for some of the rhyolites of the Yellowstone Rhyolite Plateau, four major exposures of Precambrian rocks have been analyzed for major and trace elements and isotopic composition. The terrain is characterized by granitic gneisses with subordinant mica schist, quartzite, amphibolite, and two-mica granite. The gneiss units from the northern (Yankee Jim Canyon) and eastern (Lamar Canyon) outcrops are characterized by k-feldspar augen in a gneissic groundmass of two-feldspar--quartz--mica--epidote. The feldspar compositions are Or/sub 95/ and An/sub 5-15/ indicating metamorphic re-equilibration. Mafic phases are iron-rich with Fe:Mg of 1.0 in epidote, 0.7 inmore » pyroxene, and 0.5 in biotite. Sr isotopic analyses yield present day values of 0.7201-0.7519 for Lamar Canyon, 0.7157-0.7385 for Yankee Jam Canyon, and 0.7200-0.7679 for mica schist from the western and northern outcrops. Rb-Sr whole-rock data indicate a complicated isotopic history with ages ranging from 2800 to 3600 my. The 2800 my ages are consistent with ages for the Tobacco Root and Ruby Mountains to the NW (James and Hedge, 1980) and the Beartooth Range to the NE (Nunes and Tilton, 1971) while the 3600 my age may be related to the formation of the protolith. The rhyolites of the northern Yellowstone Rhyolite Plateau (Sr/sub I/=0.7100) cannot be derived from the exposed Archaean rocks based on Sr isotopic and whole-rock chemistry, and must be derived from lithologies not exposed in the area. This study shows that care must be taken when using surface lithologies to model potential sources materials for volcanic rocks in an associated terrain.« less

Cord blood Streptococcus pneumoniae‐specific cellular immune responses predict early pneumococcal carriage in high‐risk infants in Papua New Guinea

PubMed Central

Francis, J. P.; Richmond, P. C.; Strickland, D.; Prescott, S. L.; Pomat, W. S.; Michael, A.; Nadal‐Sims, M. A.; Edwards‐Devitt, C. J.; Holt, P. G.; Lehmann, D.

2016-01-01

Summary In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high‐risk areas have pre‐existing pneumococcal‐specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA‐induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA‐specific interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐5, IL‐6, IL‐10 and IL‐13 responses, and lower dPly‐IL‐6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA‐IL‐5 and PspA‐IL‐13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly‐IL‐6 responses with a higher frequency of cord antigen‐presenting cells. In the PNG cohort, higher PspA‐specific IL‐5 and IL‐6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA‐IL‐10 CBMC responses. Pneumococcus‐specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease. PMID:27859014

Archaean greenstone belts of Sierra Leone with comments on the stratigraphy and metallogeny

NASA Astrophysics Data System (ADS)

Umeji, A. C.

Four belts of weakly metamorphosed volcano-sedimentary material, of about 2700 Ma, are enclosed by older granulites, gneisses and migmatites in the eastern part, and (i) a basal ultramafic unit followed by (ii) mafic to feldspathic differentiate and then (iii) a terminal sedimentary formation has been recognized in all the four belts and their average ratio is ultramafic: mafic (greenstone): sedimentary unit (2:5:3). The belts are linear and tightly folded along N-S to NE-SW axis which is also the regional grain of the structures in the older basement complex that engulfs them. Structural and geochronological evidences suggest that the deformation of these volcano-sedimentary supracrustals began during the Liberian tectonism ( c. 2700 Ma) and culminated at the beginning of the Eburnean (2200 Ma). Diapiric rise of K-rich younger Aechaean granites which sharphy trangressed all the earlier rocks and their structural trends, marked the last geotectonic event in the Archaean of this part of West Africa. Chromite cumulate and asbestiform deposits characterize the layered ultramafic unit. whilst gold and associated base metal sulphides which were derived from the volcanic units became hydrothermally concentrated close to the contact between the volcanic units and the overlying sediments, and also in the fault zones. Iron ore deposits are restricted to the sedimentary units where they occur as banded iron formation. It is only in the huge metasedimetary piles of the Sula-Kangari belt that deposits of iron ore occur in commercially viable quantities. The patterns of distribution, deformation and mineralization in these greenstone belts appear to fit closely into island arc model of plate tectonic theory.

Genomics and Metagenomics of Extreme Acidophiles in Biomining Environments

NASA Astrophysics Data System (ADS)

Holmes, D. S.

2015-12-01

Over 160 draft or complete genomes of extreme acidophiles (pH < 3) have been published, many of which are from bioleaching and other biomining environments, or are closely related to such microorganisms. In addition, there are over 20 metagenomic studies of such environments. This provides a rich source of latent data that can be exploited for understanding the biology of biomining environments and for advancing biotechnological applications. Genomic and metagenomic data are already yielding valuable insights into cellular processes, including carbon and nitrogen management, heavy metal and acid resistance, iron and sulfur oxido-reduction, linking biogeochemical processes to organismal physiology. The data also allow the construction of useful models of the ecophysiology of biomining environments and provide insight into the gene and genome evolution of extreme acidophiles. Additionally, since most of these acidophiles are also chemoautolithotrophs that use minerals as energy sources or electron sinks, their genomes can be plundered for clues about the evolution of cellular metabolism and bioenergetic pathways during the Archaean abiotic/biotic transition on early Earth. Acknowledgements: Fondecyt 1130683.

Generation of anti-porcine CD69 monoclonal antibodies and their usefulness to evaluate early activation of cellular immunity by flow cytometric analysis.

PubMed

Hayashi, Yumiko; Okutani, Mie; Ogawa, Shohei; Tsukahara, Takamitsu; Inoue, Ryo

2018-05-01

T cell-mediated cellular immunity and humoral immunity are equally important for the prevention of diseases. To assess activation of human and mouse cellular immunity, early activation markers of lymphocytes are often used in flow cytometry targeting expression of CD69 molecules. Response of humoral immunity against infection or vaccination has been well investigated in pigs, but that of cellular immunity has been largely neglected due to lack of direct evaluation tools. Thus, in pig research a proper assay of antibody reacted with porcine CD69 is still unavailable. In the present study, two anti-porcine CD69 mAb-producing mouse hybridomas, 01-14-22-51 (IgG2b-κ) and 01-22-44-102 (IgG2a-κ), both showing fine reactivity with phorbol 12-myristate 13-acetate (PMA) and ionomycin-stimulated porcine peripheral blood lymphocytes in flow cytometry, were established. When porcine peripheral blood lymphocytes were activated with PMA and ionomycin and analyzed by flow cytometry, it was found that both mAbs generated in this study stained about 70% of lymphocytes. In contrast, after an identical procedure, only 5% and 13.5% of lymphocytes were stained with anti-interferon-γ mAb and anti-tumor necrosis factor-α mAb, respectively. These results indicate that evaluation of cellular immunity activation turns more sensitive after using our newly generated mAbs. © 2018 Japanese Society of Animal Science.

The Kovdor-2015 experiment: study of the parameters of a conductive layer of dilatancy-diffusion nature (DD Layer) in the Archaean crystalline basement of the Baltic Shield

NASA Astrophysics Data System (ADS)

Zhamaletdinov, A. A.; Velikhov, E. P.; Shevtsov, A. N.; Kolobov, V. V.; Kolesnikov, V. E.; Skorokhodov, A. A.; Korotkova, T. G.; Ivonin, V. V.; Ryazantsev, P. A.; Birulya, M. A.

2017-06-01

This paper addresses the Kovdor-2015 Experiment involving frequency electromagnetic soundings of the Archaean basement of the Earth's crust in the southwestern part of the Kola Peninsula. Eleven soundings were carried out using two transmitting arrangements, 85 km apart. Each arrangement consisted of two mutually orthogonal grounded electric dipoles of 1.5 km long. The distances between the source and the receiver were 25 and 50 km. Interpretation of the results took into account the influence of displacement currents and static distortions. It is found that there is an intermediate conductive layer of the dilatancy-diffusion nature (DD layer) with a longitudinal conductivity of about one siemens at depths ranging from 1.5-2 to 5-7 km. The results are interpreted in the terms of geodynamics.

Magmatism during the accretion of the late Archaean Dharwar Craton (South India): sanukitoids and related rocks in their geological context.

NASA Astrophysics Data System (ADS)

Moyen, J.-F.; Martin, H.; Jayananda, M.; Peucat, J.-J.

2003-04-01

The South Indian Dharwar Craton assembled during the late-Archaean (ca. 2.5 Ga). This event was associated with intense granite genesis and emplacement. Based on petrography and geochemistry, 4 main types of late Archaean granitoids were distinguished: (1) Anatectic granites (and diatexites), formed by partial melting of TTG gneisses; (2) Classical TTGs; (3) Sanukitoids, generated by interaction between slab melts (TTG) and mantle peridotite; (4) The high HFSE Closepet granite, interpreted as derived from partial melting of a mantle metasomatized by slab melts (TTG). While the 3 later groups all are interpreted as resulting from slab melt/mantle wedge interactions, their differences are related to decreasing felsic melt/peridotite ratios during the ascent “slab melts” in the mantle wedge above an active subduction zone. Field data together with geochronology and isotope geochemistry allow to subdivide the Dharwar craton into three main domains: (1) The Western Dharwar Craton (WDC) is an old (3.3 2.9 Ga ), stable continental block with limited amounts of 2.5 Ga old anatectic granites. (2) The Eastern Dharwar Craton (EDC) is subdivided into two parts: (2a) West of Kolar Schist Belt, a region of 3.0-2.7 Ga old basement intruded by 2.5 Ga old anatectic granites; (2b) East of Kolar, an area featuring mainly 2.5 Ga old diatexites and granites, derived of partial melting of a newly accreted TTG crust. Anatectic granites are ubiquitous, and late in the cratonic evolution; they witnessed generalized melting of a juvenile crust. In contrast, deep-originated granites emplaced before this melting and are restricted to the boundaries between the blocks. This structure of distinct terranes separated by narrow bands operating as channels for deep-originated magmas provides independent evidences for a two-stage evolution: an arc accretion context for the TTG, sanukitoids and related rocks, immediately followed by high temperature reworking of the newly accreted craton

Telomere length and early severe social deprivation: linking early adversity and cellular aging

PubMed Central

Drury, SS; Theall, K; Gleason, MM; Smyke, AT; De Vivo, I; Wong, JYY; Fox, NA; Zeanah, CH; Nelson, CA

2012-01-01

Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity. PMID:21577215

The relationship between in vitro cellular aging and in vivo human age.

PubMed Central

Schneider, E L; Mitsui, Y

1976-01-01

Differences between early and late passage cell cultures on the organelle and macromolecular levels have been attributed to cellular "aging". However, concern has been expressed over whether changes in diploid cell populations after serial passage in vitro accurately reflect human cellular aging in vivo. Studies were therefore undertaken to determine if significant differences would be observed in the in vitro lifespans of skin fibroblast cultures from old and young normal, non-hospitalized volunteers and to examine if parameters that change with in vitro "aging" are altered as a function of age in vivo. Statistically signigificant (P less than 0.05) decreases were found in the rate of fibroblast migration, onset of cell culture senescence, in vitro lifespan, cell population replication rate, and cell number at confluency of fibroblast cultures derived from the old donor group when compared to parallel cultures from young donors. No significant differences were observed in modal cell volumes and cellular macromolecular contents. The differences observed in cell cultures from old and young donors were quantitatively and qualitatively distinct from those cellular alterations observed in early and late passage WI-38 cells (in vitro "aging"). Therefore, although early and late passage cultures of human diploid cells may provide an important cell system for examining loss of replicative potential, fibroblast cultures derived from old and young human donors may be a more appropriate model system for studying human cellular aging. PMID:1068470

Rifting an Archaean Craton: Insights from Seismic Anisotropy Patterns in E. Africa

NASA Astrophysics Data System (ADS)

Ebinger, C. J.; Tiberi, C.; Currie, C. A.; van Wijk, J.; Albaric, J.

2016-12-01

Few places worldwide offer opportunities to study active deformation of deeply-keeled cratonic lithosphere. The magma-rich Eastern rift transects the eastern edge of the Archaean Tanzania craton in northeastern Tanzania, which has been affected by a large-scale mantle upwelling. Abundant xenolith locales offer constraints on mantle age, composition, and physical properties. Our aim is to evaluate models for magmatic fluid-alteration (metasomatism) and deformation of mantle lithosphere along the edge of cratons by considering spatial variations in the direction and magnitude of seismic anisotropy, which is strongly influenced by mantle flow patterns along lithosphere-asthenosphere topography, fluid-filled cracks (e.g., dikes), and pre-existing mantle lithosphere strain fabrics. Waveforms of teleseismic earthquakes (SKS, SKKS) recorded on the 39-station CRAFTI-CoLiBREA broadband array in southern Kenya and northern Tanzania are used to determine the azimuth and amount of shear-wave splitting accrued as seismic waves pass through the uppermost mantle and lithosphere at the craton edge. Lower crustal earthquakes enable evaluation of seismic anisotropy throughout the crust along the rift flanks and beneath the heavily intruded Magadi and Natron basins, and the weakly intruded Manyara basin. Our results and those of earlier studies show a consistent N50E splitting direction within the craton, with delay times of ca. 1.5 s, and similar direction east of the rift in thinner Pan-African lithosphere. Stations within the rift zone are rotated to a N15-35E splitting, with the largest delay times of 2.5 s at the margin of the heavily intruded Magadi basin. The short length scale of variations and rift-parallel splitting directions are similar to patterns in the Main Ethiopian rift attributed to melt-filled cracks or oriented pockets rising from the base of the lithosphere. The widespread evidence for mantle metasomatism and magma intrusion to mid-crustal levels suggests that

Polyphase Neoproterozoic orogenesis within the east Africa- Antarctica orogenic belt in central and northern Madagascar

USGS Publications Warehouse

Key, R.M.; Pitfield, P.E.J.; Thomas, Ronald J.; Goodenough, K.M.; Waele, D.; Schofield, D.I.; Bauer, W.; Horstwood, M.S.A.; Styles, M.T.; Conrad, J.; Encarnacion, J.; Lidke, D.J.; O'connor, E. A.; Potter, C.; Smith, R.A.; Walsh, G.J.; Ralison, A.V.; Randriamananjara, T.; Rafahatelo, J.-M.; Rabarimanana, M.

2011-01-01

Our recent geological survey of the basement of central and northern Madagascar allowed us to re-evaluate the evolution of this part of the East Africa-Antarctica Orogen (EAAO). Five crustal domains are recognized, characterized by distinctive lithologies and histories of sedimentation, magmatism, deformation and metamorphism, and separated by tectonic and/or unconformable contacts. Four consist largely of Archaean metamorphic rocks (Antongil, Masora and Antananarivo Cratons, Tsaratanana Complex). The fifth (Bemarivo Belt) comprises Proterozoic meta-igneous rocks. The older rocks were intruded by plutonic suites at c. 1000 Ma, 820-760 Ma, 630-595 Ma and 560-520 Ma. The evolution of the four Archaean domains and their boundaries remains contentious, with two end-member interpretations evaluated: (1) all five crustal domains are separate tectonic elements, juxtaposed along Neoproterozoic sutures and (2) the four Archaean domains are segments of an older Archaean craton, which was sutured against the Bemarivo Belt in the Neoproterozoic. Rodinia fragmented during the early Neoproterozoic with intracratonic rifts that sometimes developed into oceanic basins. Subsequent Mid- Neoproterozoic collision of smaller cratonic blocks was followed by renewed extension and magmatism. The global 'Terminal Pan-African' event (560-490 Ma) finally stitched together the Mid-Neoproterozoic cratons to form Gondwana. ?? The Geological Society of London 2011.

Early changes in staurosporine-induced differentiated RGC-5 cells indicate cellular injury response to nonlethal blue light exposure.

PubMed

Zhang, Pei; Huang, Chen; Wang, Wei; Wang, Minshu

2015-06-01

damage of staurosporine-differentiated RGC-5 cells. These increases in oxidative stress and mitochondrial content were the early steps of the cellular response to the exposure of relatively low doses (10 J cm(-2)) of blue light.

Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR.

PubMed

Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

2015-08-01

Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue.

Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR

PubMed Central

Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

2015-01-01

Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue. PMID:26171232

Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models*

PubMed Central

Mochel, Fanny; Durant, Brandon; Meng, Xingli; O'Callaghan, James; Yu, Hua; Brouillet, Emmanuel; Wheeler, Vanessa C.; Humbert, Sandrine; Schiffmann, Raphael; Durr, Alexandra

2012-01-01

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in HdhQ111/+ mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. PMID:22123819

Overexpression of the base excision repair NTHL1 glycosylase causes genomic instability and early cellular hallmarks of cancer

PubMed Central

Limpose, Kristin L; Trego, Kelly S; Li, Zhentian; Leung, Sara W; Sarker, Altaf H; Shah, Jason A; Ramalingam, Suresh S; Werner, Erica M; Dynan, William S; Cooper, Priscilla K; Corbett, Anita H; Doetsch, Paul W

2018-01-01

Abstract Base excision repair (BER), which is initiated by DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. The NTHL1 glycosylase, which excises DNA base damage caused by reactive oxygen species, is thought to be a tumor suppressor. However, in addition to NTHL1 loss-of-function mutations, our analysis of cancer genomic datasets reveals that NTHL1 frequently undergoes amplification or upregulation in some cancers. Whether NTHL1 overexpression could contribute to cancer phenotypes has not yet been explored. To address the functional consequences of NTHL1 overexpression, we employed transient overexpression. Both NTHL1 and a catalytically-dead NTHL1 (CATmut) induce DNA damage and genomic instability in non-transformed human bronchial epithelial cells (HBEC) when overexpressed. Strikingly, overexpression of either NTHL1 or CATmut causes replication stress signaling and a decrease in homologous recombination (HR). HBEC cells that overexpress NTHL1 or CATmut acquire the ability to grow in soft agar and exhibit loss of contact inhibition, suggesting that a mechanism independent of NTHL1 catalytic activity contributes to acquisition of cancer-related cellular phenotypes. We provide evidence that NTHL1 interacts with the multifunctional DNA repair protein XPG suggesting that interference with HR is a possible mechanism that contributes to acquisition of early cellular hallmarks of cancer. PMID:29522130

The effect of human hair keratin hydrogel on early cellular response to sciatic nerve injury in a rat model.

PubMed

Pace, Lauren A; Plate, Johannes F; Smith, Thomas L; Van Dyke, Mark E

2013-08-01

Peripheral nerve injuries requiring surgery can be repaired by autograft, the clinical "gold standard", allograft, or nerve conduits. Most published clinical studies show the effectiveness of nerve conduits in small size defects in sensory nerves. Many preclinical studies suggest that peripheral nerve regeneration through conduits can be enhanced and repair lengths increased with the use of a biomaterial filler in the conduit lumen. We have previously shown that a luminal hydrogel filler derived from human hair keratin (HHK) can improve electrophysiological and histological outcomes in mouse, rabbit, and non-human primate nerve injury models, but insight into potential mechanisms has been lacking. Based on the premise that a keratin biomaterial (KOS) hydrogel provides an instantaneous structural matrix within the lumen, the current study compares the cellular behavior elicited by KOS hydrogel to Matrigel (MAT) and saline (SAL) conduit fillers in a 1 cm rat sciatic nerve injury model at early stages of regeneration. While there was little difference in initial cellular influx, the KOS group showed earlier migration of dedifferentiated Schwann cells (SC) from the proximal nerve end compared to the other groups. The KOS group also showed faster SC dedifferentiation and myelin debris clearance, and decreased macrophage infiltration during Wallerian degeneration of the distal nerve tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

Komatiite genesis in the Archaean mantle, with implications for the tectonics of Archaean greenstone belts

NASA Technical Reports Server (NTRS)

Elthon, D.

1986-01-01

The presence of ultramafic lavas (komatiites) associated with Archean greenstone belts has been suggested to indicate very high increments (50-80%) of partial melting of the Archean mantle. Such extensive melting of the Earth's mantle during the Archean might have profound effects on the early tectonic and chemical evolution of the planet, although problems associated with keeping the komatiite liquid in equilibrium with the residual mantle at such high increments of melting has cast doubt upon aspects of extensive melting. Two important aspects of the origin of komatiites are discussed below.

Differential Activation of Cellular DNA Damage Responses by Replication-Defective and Replication-Competent Adenovirus Mutants

PubMed Central

Prakash, Anand; Jayaram, Sumithra

2012-01-01

Adenovirus (Ad) mutants that lack early region 4 (E4) activate the phosphorylation of cellular DNA damage response proteins. In wild-type Ad type 5 (Ad5) infections, E1b and E4 proteins target the cellular DNA repair protein Mre11 for redistribution and degradation, thereby interfering with its ability to activate phosphorylation cascades important during DNA repair. The characteristics of Ad infection that activate cellular DNA repair processes are not yet well understood. We investigated the activation of DNA damage responses by a replication-defective Ad vector (AdRSVβgal) that lacks E1 and fails to produce the immediate-early E1a protein. E1a is important for activating early gene expression from the other viral early transcription units, including E4. AdRSVβgal can deliver its genome to the cell, but it is subsequently deficient for viral early gene expression and DNA replication. We studied the ability of AdRSVβgal-infected cells to induce cellular DNA damage responses. AdRSVβgal infection does activate formation of foci containing the Mdc1 protein. However, AdRSVβgal fails to activate phosphorylation of the damage response proteins Nbs1 and Chk1. We found that viral DNA replication is important for Nbs1 phosphorylation, suggesting that this step in the viral life cycle may provide an important trigger for activating at least some DNA repair proteins. PMID:23015708

Safe use of cellular telephones in hospitals: fundamental principles and case studies.

PubMed

Cohen, Ted; Ellis, Willard S; Morrissey, Joseph J; Bakuzonis, Craig; David, Yadin; Paperman, W David

2005-01-01

Many industries and individuals have embraced cellular telephones. They provide mobile, synchronous communication, which could hypothetically increase the efficiency and safety of inpatient healthcare. However, reports of early analog cellular telephones interfering with critical life-support machines had led many hospitals to strictly prohibit cellular telephones. A literature search revealed that individual hospitals now are allowing cellular telephone use with various policies to prevent electromagnetic interference with medical devices. The fundamental principles underlying electromagnetic interference are immunity, frequency, modulation technology, distance, and power Electromagnetic interference risk mitigation methods based on these principles have been successfully implemented. In one case study, a minimum distance between cellular telephones and medical devices is maintained, with restrictions in critical areas. In another case study, cellular telephone coverage is augmented to automatically control the power of the cellular telephone. While no uniform safety standard yet exists, cellular telephones can be safely used in hospitals when their use is managed carefully.

Dendritic cells are early cellular targets of Listeria monocytogenes after intestinal delivery and are involved in bacterial spread in the host.

PubMed

Pron, B; Boumaila, C; Jaubert, F; Berche, P; Milon, G; Geissmann, F; Gaillard, J L

2001-05-01

We studied the sequence of cellular events leading to the dissemination of Listeria monocytogenes from the gut to draining mesenteric lymph nodes (MLNs) by confocal microscopy of immunostained tissue sections from a rat ligated ileal loop system. OX-62-positive cells beneath the epithelial lining of Peyer's patches (PPs) were the first Listeria targets identified after intestinal inoculation. These cells had other features typical of dendritic cells (DCs): they were large, pleiomorphic and major histocompatibility complex class II(hi). Listeria were detected by microscopy in draining MLNs as early as 6 h after inoculation. Some 80-90% of bacteria were located in the deep paracortical regions, and 100% of the bacteria were present in OX-62-positive cells. Most infected cells contained more than five bacteria each, suggesting that they had arrived already loaded with bacteria. At later stages, the bacteria in these areas were mostly present in ED1-positive mononuclear phagocytes. These cells were also infected by an actA mutant defective in cell-to-cell spreading. This suggests that Listeria are transported by DCs from PPs to the deep paracortical regions of draining MLNs and are then transmitted to other cell populations by mechanisms independent of ActA. Another pathway of dissemination to MLNs was identified, probably involving free Listeria and leading to the infection of ED3-positive mononuclear phagocytes in the subcapsular sinus and adjacent paracortical areas. This study provides evidence that DCs are major cellular targets of L. monocytogenes in PPs and that DCs may be involved in the early dissemination of this pathogen. DCs were not sites of active bacterial replication, making these cells ideal vectors of infection.

Cellular Contraction and Polarization Drive Collective Cellular Motion.

PubMed

Notbohm, Jacob; Banerjee, Shiladitya; Utuje, Kazage J C; Gweon, Bomi; Jang, Hwanseok; Park, Yongdoo; Shin, Jennifer; Butler, James P; Fredberg, Jeffrey J; Marchetti, M Cristina

2016-06-21

Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Selection for Protein Kinetic Stability Connects Denaturation Temperatures to Organismal Temperatures and Provides Clues to Archaean Life

PubMed Central

Romero-Romero, M. Luisa; Risso, Valeria A.; Martinez-Rodriguez, Sergio; Gaucher, Eric A.; Ibarra-Molero, Beatriz; Sanchez-Ruiz, Jose M.

2016-01-01

The relationship between the denaturation temperatures of proteins (Tm values) and the living temperatures of their host organisms (environmental temperatures: TENV values) is poorly understood. Since different proteins in the same organism may show widely different Tm’s, no simple universal relationship between Tm and TENV should hold, other than Tm≥TENV. Yet, when analyzing a set of homologous proteins from different hosts, Tm’s are oftentimes found to correlate with TENV’s but this correlation is shifted upward on the Tm axis. Supporting this trend, we recently reported Tm’s for resurrected Precambrian thioredoxins that mirror a proposed environmental cooling over long geological time, while remaining a shocking ~50°C above the proposed ancestral ocean temperatures. Here, we show that natural selection for protein kinetic stability (denaturation rate) can produce a Tm↔TENV correlation with a large upward shift in Tm. A model for protein stability evolution suggests a link between the Tm shift and the in vivo lifetime of a protein and, more specifically, allows us to estimate ancestral environmental temperatures from experimental denaturation rates for resurrected Precambrian thioredoxins. The TENV values thus obtained match the proposed ancestral ocean cooling, support comparatively high Archaean temperatures, and are consistent with a recent proposal for the environmental temperature (above 75°C) that hosted the last universal common ancestor. More generally, this work provides a framework for understanding how features of protein stability reflect the environmental temperatures of the host organisms. PMID:27253436

Fossil Microorganisms in Archaean

NASA Technical Reports Server (NTRS)

Astafleva, Marina; Hoover, Richard; Rozanov, Alexei; Vrevskiy, A.

2006-01-01

Ancient Archean and Proterozoic rocks are the model objects for investigation of rocks comprising astromaterials. The first of Archean fossil microorganisms from Baltic shield have been reported at the last SPIE Conference in 2005. Since this confeence biomorphic structures have been revealed in Archean rocks of Karelia. It was determined that there are 3 types of such bion structures: 1. structures found in situ, in other words microorganisms even-aged with rock matrix, that is real Archean fossils biomorphic structures, that is to say forms inhabited early formed rocks, and 3. younger than Archean-Protherozoic minerali microorganisms, that is later contamination. We made attempt to differentiate these 3 types of findings and tried to understand of burial of microorganisms. The structures belongs (from our point of view) to the first type, or real Archean, forms were under examination. Practical investigation of ancient microorganisms from Green-Stone-Belt of Northern Karelia turns to be very perspective. It shows that even in such ancient time as Archean ancient diverse world existed. Moreover probably such relatively highly organized cyanobacteria and perhaps eukaryotic formes existed in Archean world.

Volcaniclastic habitats for early life on Earth and Mars: A case study from ˜3.5 Ga-old rocks from the Pilbara, Australia

NASA Astrophysics Data System (ADS)

Westall, Frances; Foucher, Frédéric; Cavalazzi, Barbara; de Vries, Sjoukje T.; Nijman, Wouter; Pearson, Victoria; Watson, Jon; Verchovsky, Alexander; Wright, Ian; Rouzaud, Jean-Noel; Marchesini, Daniele; Anne, Severine

2011-08-01

Within the context of present and future in situ missions to Mars to investigate its habitability and to search for traces of life, we studied the habitability and traces of past life in ˜3.5 Ga-old volcanic sands deposited in littoral environments an analogue to Noachian environments on Mars. The environmental conditions on Noachian Mars (4.1-3.7 Ga) and the Early Archaean (4.0-3.3 Ga) Earth were, in many respects, similar: presence of liquid water, dense CO 2 atmosphere, availability of carbon and bio-essential elements, and availability of energy. For this reason, information contained in Early Archaean terrestrial rocks concerning habitable conditions (on a microbial scale) and traces of past life are of relevance in defining strategies to be used to identify past habitats and past life on Mars. One such example is the 3.446 Ga-old Kitty's Gap Chert in the Pilbara Craton, NW. Australia. This formation consists of volcanic sediments deposited in a coastal mudflat environment and is thus a relevant analogue for sediments deposited in shallow water environments on Noachian Mars. Two main types of habitat are represented, a volcanic (lithic) habitat and planar stabilized sediment surfaces in sunlit shallow waters. The sediments hosted small (<1 μm in size) microorganisms that formed colonies on volcanic particle surfaces and in pore waters within the volcanic sediments, as well as biofilms on stabilised sediment surfaces. The microorganisms included coccoids, filaments and rare rod-shaped organisms associated with microbial polymer (EPS). The preserved microbial community was apparently dominated by chemotrophic organisms but some locally transported filaments and filamentous mat fragments indicate that possibly photosynthetic mats formed nearby. Both microorganisms and sediments were silicified during very early diagenesis. There are no macroscopic traces of fossilised life in these volcanic sediments and sophisticated instrumentation and specialized sample

The roles of cellular and molecular components of a hematoma at early stage of bone healing.

PubMed

Shiu, Hoi Ting; Leung, Ping Chung; Ko, Chun Hay

2018-04-01

Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the early healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and molecular components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an early hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.

Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

DOE PAGES

Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

2017-03-22

Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

Nipah virus matrix protein: expert hacker of cellular machines.

PubMed

Watkinson, Ruth E; Lee, Benhur

2016-08-01

Nipah virus (NiV, Henipavirus) is a highly lethal emergent zoonotic paramyxovirus responsible for repeated human outbreaks of encephalitis in South East Asia. There are no approved vaccines or treatments, thus improved understanding of NiV biology is imperative. NiV matrix protein recruits a plethora of cellular machinery to scaffold and coordinate virion budding. Intriguingly, matrix also hijacks cellular trafficking and ubiquitination pathways to facilitate transient nuclear localization. While the biological significance of matrix nuclear localization for an otherwise cytoplasmic virus remains enigmatic, the molecular details have begun to be characterized, and are conserved among matrix proteins from divergent paramyxoviruses. Matrix protein appropriation of cellular machinery will be discussed in terms of its early nuclear targeting and later role in virion assembly. © 2016 Federation of European Biochemical Societies.

Earth's early O2 cycle suppressed by primitive continents

NASA Astrophysics Data System (ADS)

Smit, Matthijs A.; Mezger, Klaus

2017-10-01

Free oxygen began to accumulate in Earth's surface environments between 3.0 and 2.4 billion years ago. Links between oxygenation and changes in the composition of continental crust during this time are suspected, but have been difficult to demonstrate. Here we constrain the average composition of the exposed continental crust since 3.7 billion years ago by compiling records of the Cr/U ratio of terrigenous sediments. The resulting record is consistent with a predominantly mafic crust prior to 3.0 billion years ago, followed by a 500- to 700-million-year transition to a crust of modern andesitic composition. Olivine and other Mg-rich minerals in the mafic Archaean crust formed serpentine minerals upon hydration, continuously releasing O2-scavenging agents such as dihydrogen, hydrogen sulfide and methane to the environment. Temporally, the decline in mafic crust capable of such process coincides with the first accumulation of O2 in the oceans, and subsequently the atmosphere. We therefore suggest that Earth's early O2 cycle was ultimately limited by the composition of the exposed upper crust, and remained underdeveloped until modern andesitic continents emerged.

Development of the Archaean Mallina Basin, Pilbara Craton, northwestern Australia; a study of detrital and inherited zircon ages

NASA Astrophysics Data System (ADS)

Smithies, R. H.; Nelson, D. R.; Pike, G.

2001-06-01

SHRIMP U-Pb zircon dates are combined with an examination of the age distribution patterns and provenance of both detrital zircons and of zircon xenocrysts in granites to investigate the development of the Archaean Mallina Basin, in the granite-greenstone terrain of the Pilbara Craton, northwestern Australia. The oldest dated components of the basin are c. 3010 Ma volcaniclastic rocks in the western part of the area. New data indicate that siliciclastic turbidites that dominate the southern and eastern part of the basin were deposited at or after c. 2970 Ma but before c. 2955 Ma. Linking both the detrital zircon populations as well as zircon xenocrysts from granites that intruded the Mallina Basin to well-dated areas of the Pilbara granite-greenstone terrane indicates that the sediment was derived from the south, north, northwest, and east. The basin probably evolved primarily in an intracontinental setting between two elevated land masses to the southeast and northwest. Most of the rocks within the basin were folded before intrusion of granites, the oldest of which has been dated at 2954±4 Ma. Evidence of a second depositional cycle is provided by a maximum depositional age of 2941±9 Ma, indicated by a detrital zircon population from a sample of wacke from the southeast part of the Mallina Basin. This second depositional phase may have been related to renewed extension, and recycling of sedimentary rocks within the basin.

Cellular Therapies Clinical Research Roadmap: lessons learned on how to move a cellular therapy into a clinical trial.

PubMed

Ouseph, Stacy; Tappitake, Darah; Armant, Myriam; Wesselschmidt, Robin; Derecho, Ivy; Draxler, Rebecca; Wood, Deborah; Centanni, John M

2015-04-01

A clinical research roadmap has been developed as a resource for researchers to identify critical areas and potential pitfalls when transitioning a cellular therapy product from the research laboratory, by means of an Investigational New Drug (IND) application, into early-phase clinical trials. The roadmap describes four key areas: basic and preclinical research, resource development, translational research and Good Manufacturing Practice (GMP) and IND assembly and submission. Basic and preclinical research identifies a new therapeutic concept and demonstrates its potential value with the use of a model of the relevant disease. During resource development, the appropriate specialists and the required expertise to bring this product into the clinic are identified (eg, researchers, regulatory specialists, GMP manufacturing staff, clinicians and clinical trials staff, etc). Additionally, the funds required to achieve this goal (or a plan to procure them) are identified. In the next phase, the plan to translate the research product into a clinical-grade therapeutic is developed. Finally regulatory approval to start the trial must be obtained. In the United States, this is done by filing an IND application with the Food and Drug Administration. The National Heart, Lung and Blood Institute-funded Production Assistance for Cellular Therapies program has facilitated the transition of a variety of cellular therapy products from the laboratory into Phase1/2 trials. The five Production Assistance for Cellular Therapies facilities have assisted investigators by performing translational studies and GMP manufacturing to ensure that cellular products met release specifications and were manufactured safely, reproducibly and at the appropriate scale. The roadmap resulting from this experience is the focus of this article. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Cellular Automata

NASA Astrophysics Data System (ADS)

Gutowitz, Howard

1991-08-01

Cellular automata, dynamic systems in which space and time are discrete, are yielding interesting applications in both the physical and natural sciences. The thirty four contributions in this book cover many aspects of contemporary studies on cellular automata and include reviews, research reports, and guides to recent literature and available software. Chapters cover mathematical analysis, the structure of the space of cellular automata, learning rules with specified properties: cellular automata in biology, physics, chemistry, and computation theory; and generalizations of cellular automata in neural nets, Boolean nets, and coupled map lattices. Current work on cellular automata may be viewed as revolving around two central and closely related problems: the forward problem and the inverse problem. The forward problem concerns the description of properties of given cellular automata. Properties considered include reversibility, invariants, criticality, fractal dimension, and computational power. The role of cellular automata in computation theory is seen as a particularly exciting venue for exploring parallel computers as theoretical and practical tools in mathematical physics. The inverse problem, an area of study gaining prominence particularly in the natural sciences, involves designing rules that possess specified properties or perform specified task. A long-term goal is to develop a set of techniques that can find a rule or set of rules that can reproduce quantitative observations of a physical system. Studies of the inverse problem take up the organization and structure of the set of automata, in particular the parameterization of the space of cellular automata. Optimization and learning techniques, like the genetic algorithm and adaptive stochastic cellular automata are applied to find cellular automaton rules that model such physical phenomena as crystal growth or perform such adaptive-learning tasks as balancing an inverted pole. Howard Gutowitz is

Continental emergence and growth on a cooling earth

NASA Astrophysics Data System (ADS)

Vlaar, N. J.

2000-07-01

Isostasy considerations are connected to a 1-D model of mantle differentiation due to pressure release partial melting to obtain a model for the evolution of the relative sea level with respect to the continent during the earth secular cooling. In this context, a new mechanism is derived for the selective exhumation of exposed ancient cratons. The model results in a quantitative scenario for sea-level fall due to the changing thicknesses of the oceanic basaltic crust and its harzburgite residual layer as a function of falling mantle temperature. It is also shown that the buoyancy of the harzburgite root of a stabilized continental craton has an important effect on sea-level and on the isostatic readjustment and exhumation of exposed continental surface during the earth's secular cooling. The model does not depend on the usual assumption of constant continental freeboard and crustal thickness and its application is not restricted to the post-Archaean. It predicts large-scale continental emergence near the end of the Archaean and the early Proterozoic. This provides an explanation for reported late Archaean emergence and the subsequent formation of late Archaean cratonic platforms and early Proterozoic sedimentary basins. For a period of secular cooling of 3.8 Ga, corresponding to the length of the geological record, the model predicts a fall of the ocean floor of some 4 km or more. For a constant ocean depth, this implies a sea-level fall of the same magnitude. A formula is derived that allows for an increasing ocean depth due to either the changing ratio of continental with respect to oceanic area, or to a possible increase of the oceanic volume during the geological history. Increasing ocean depth results in a later emergence of submarine ancient geological formations compared to the case when ocean depth is constant. Selective exhumation is studied for the case of constant ocean depth. It is shown that for this case, early exposed continental crust can be exhumed

Earth's oldest stable crust in the Pilbara Craton formed by cyclic gravitational overturns

NASA Astrophysics Data System (ADS)

Wiemer, Daniel; Schrank, Christoph E.; Murphy, David T.; Wenham, Lana; Allen, Charlotte M.

2018-05-01

During the early Archaean, the Earth was too hot to sustain rigid lithospheric plates subject to Wilson Cycle-style plate tectonics. Yet by that time, up to 50% of the present-day continental crust was generated. Preserved continental fragments from the early Archaean have distinct granite-dome/greenstone-keel crust that is interpreted to be the result of a gravitationally unstable stratification of felsic proto-crust overlain by denser mafic volcanic rocks, subject to reorganization by Rayleigh-Taylor flow. Here we provide age constraints on the duration of gravitational overturn in the East Pilbara Terrane. Our U-Pb ages indicate the emplacement of 3,600-3,460-million-year-old granitoid rocks, and their uplift during an overturn event ceasing about 3,413 million years ago. Exhumation and erosion of this felsic proto-crust accompanied crustal reorganization. Petrology and thermodynamic modelling suggest that the early felsic magmas were derived from the base of thick ( 43 km) basaltic proto-crust. Combining our data with regional geochronological studies unveils characteristic growth cycles on the order of 100 million years. We propose that maturation of the early crust over three of these cycles was required before a stable, differentiated continent emerged with sufficient rigidity for plate-like behaviour.

Emergence of silicic continents as the lower crust peels off on a hot plate-tectonic Earth

NASA Astrophysics Data System (ADS)

Chowdhury, Priyadarshi; Gerya, Taras; Chakraborty, Sumit

2017-09-01

The rock record and geochemical evidence indicate that continental recycling has been occurring since the early history of the Earth. The stabilization of felsic continents in place of Earth's early mafic crust about 3.0 to 2.0 billion years ago, perhaps due to the initiation of plate tectonics, implies widespread destruction of mafic crust during this time interval. However, the physical mechanisms of such intense recycling on a hotter, (late) Archaean and presumably plate-tectonic Earth remain largely unknown. Here we use thermomechanical modelling to show that extensive recycling via lower crustal peeling-off (delamination but not eclogitic dripping) during continent-continent convergence was near ubiquitous during the late Archaean to early Proterozoic. We propose that such destruction of the early mafic crust, together with felsic magmatism, may have caused both the emergence of silicic continents and their subsequent isostatic rise, possibly above the sea level. Such changes in the continental character have been proposed to influence the Great Oxidation Event and, therefore, peeling-off plate tectonics could be the geodynamic trigger for this event. A transition to the slab break-off controlled syn-orogenic recycling occurred as the Earth aged and cooled, leading to reduced recycling and enhanced preservation of the continental crust of present-day composition.

Evidence for Functional Differentiation among Drosophila Septins in Cytokinesis and Cellularization

PubMed Central

Adam, Jennifer C.; Pringle, John R.; Peifer, Mark

2000-01-01

The septins are a conserved family of proteins that are involved in cytokinesis and other aspects of cell-surface organization. In Drosophila melanogaster, null mutations in the pnut septin gene are recessive lethal, but homozygous pnut mutants complete embryogenesis and survive until the pupal stage. Because the completion of cellularization and other aspects of early development seemed likely to be due to maternally contributed Pnut product, we attempted to generate embryos lacking the maternal contribution in order to explore the roles of Pnut in these processes. We used two methods, the production of germline clones homozygous for a pnut mutation and the rescue of pnut homozygous mutant flies by a pnut+ transgene under control of the hsp70 promoter. Remarkably, the pnut germline-clone females produced eggs, indicating that stem-cell and cystoblast divisions in the female germline do not require Pnut. Moreover, the Pnut-deficient embryos obtained by either method completed early syncytial development and began cellularization of the embryo normally. However, during the later stages of cellularization, the organization of the actin cytoskeleton at the leading edge of the invaginating furrows became progressively more abnormal, and the embryos displayed widespread defects in cell and embryo morphology beginning at gastrulation. Examination of two other septins showed that Sep1 was not detectable at the cellularization front in the Pnut-deficient embryos, whereas Sep2 was still present in normal levels. Thus, it is possible that Sep2 (perhaps in conjunction with other septins such as Sep4 and Sep5) fulfills an essential septin role during the organization and initial ingression of the cellularization furrow even in the absence of Pnut and Sep1. Together, the results suggest that some cell-division events in Drosophila do not require septin function, that there is functional differentiation among the Drosophila septins, or both. PMID:10982405

Earth's first stable continents did not form by subduction

NASA Astrophysics Data System (ADS)

Johnson, Tim; Brown, Michael; Gardiner, Nicholas; Kirkland, Christopher; Smithies, Hugh

2017-04-01

The geodynamic setting in which Earth's first stable cratonic nuclei formed remains controversial. Most exposed Archaean continental crust comprises rocks of the tonalite-trondhjemite-granodiorite (TTGs) series that were produced from partial melting of low magnesium basaltic source rocks and have 'arc-like' trace element signatures that resemble continental crust produced in modern supra-subduction zone settings. The East Pilbara Terrane, Western Australia, is amongst the oldest fragments of preserved continental crust of Earth. Low magnesium basalts of the Paleoarchaean Coucal Formation, at the base of the Pilbara Supergroup, have trace element compositions consistent with the putative source rocks for TTGs. These basalts may be remnants of the ≥35 km-thick pre-3.5 Ga plateau-like basaltic crust that is predicted to have formed if mantle temperatures were much hotter than today. Using phase equilibria modelling of an average uncontaminated Coucal basalt, we confirm their suitability as TTG source rocks. The results suggest that TTGs formed by 20-30% melting along high geothermal gradients (≥700 °C/GPa), which accord with apparent geotherms recorded by >95% of Archaean rocks worldwide. Moreover, the trace element composition of the Coucal basalts demonstrates that they were derived from an earlier generation of mafic/ultramafic rocks, and that the arc-like signature in Archaean TTGs was inherited through an ancestral source lineage. The protracted multistage process required for production and stabilisation of Earth's first continents, coupled with the high geothermal gradients, are incompatible with modern-style subduction and favour a stagnant lid regime in the early Archaean.

Pluton emplacement within an extensional transfer zone during dextral strike-slip faulting: an example from the late Archaean Abitibi Greenstone Belt

NASA Astrophysics Data System (ADS)

Lacroix, S.; Sawyer, E. W.; Chown, E. H.

1998-01-01

The Lake Abitibi area within the late Archaean Abitibi Greenstone Belt exhibits an interlinked plutonic, structural and metamorphic evolution that may characterize segmented strike-slip faults at upper-to-mid-crustal levels. Along the major, southeastward propagating Macamic D2 dextral strike-slip fault, Theological and preexisting D1 structural heterogeneities induced the development of NNW-trending dextral-oblique splays which evolved into an extensional trailing fan and created an extensional, NNW-dipping stepover. Magma flowing upwards from deeper parts of the Macamic Fault spread towards the southeast at upper crustal levels along both the oblique-slip and extensional D2 splays, and built several plutons in a pull-apart domain between 2696 and 2690 Ma. Different emplacement and material transfer mechanisms operated simultaneously in different parts of the system, including fault dilation and wedging, lateral expansion, wall-rock ductile flow and stoping. Transfer of movement between D2 splays occurred under ductile conditions during syn-emplacement, amphibolite-grade metamorphism (500-700 °C). During cooling (< 2690 Ma), narrower brittle-ductile zones of greenschist-grade shearing were concentrated along the pluton-wall rock contacts, but the extensional stepover locked since both normal and reverse movements occurred along NNW-dipping faults. Pluton emplacement, contact metamorphism and propagation of D2 faults appear to have been closely linked during the Superior Province-wide late transpressional event.

[Incontinentia pigmenti with defect in cellular immunity].

PubMed

Zamora-Chávez, Antonio; Escobar-Sánchez, Argelia; Sadowinski-Pine, Stanislaw; Saucedo-Ramírez, Omar Josué; Delgado-Barrera, Palmira; Enríquez-Quiñones, Claudia G

Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal. We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient. The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Cellular Therapies Clinical Research Roadmap: Lessons learned on how to move a cellular therapy into a clinical trial

PubMed Central

Ouseph, Stacy; Tappitake, Darah; Armant, Myriam; Wesselschmidt, Robin; Derecho, Ivy; Draxler, Rebecca; Wood, Deborah; Centanni, John M.

2014-01-01

A clinical research roadmap has been developed as a resource for researchers to identify critical areas and potential pitfalls when transitioning a cellular therapy product from the research laboratory, via and Investigational New Drug (IND) application, into early phase clinical trials. The roadmap describes four key areas; basic and preclinical research, resource development, translational research and good manufacturing practice (GMP), and IND assembly and submission. Basic and preclinical research identifies a new therapeutic concept and demonstrates its potential value using a model of the relevant disease. During resource development the appropriate specialists and the required expertise to bring this product into the clinic are identified (e.g., researchers, regulatory specialists, GMP manufacturing staff, clinicians, and clinical trials staff, etc.). Additionally, the funds required to achieve this goal (or a plan to procure them) are identified. In the next phase the plan to translate the research product into a clinical grade therapeutic is developed. Finally regulatory approval to start the trial must be obtained. In the United States this is done by filing an IND application with the Food and Drug Administration. The NHLBI-funded Production Assistance for Cellular Therapies (PACT) program has facilitated the transition of a variety of cellular therapy products from the laboratory into Phase1/2 trials. The five PACT facilities have assisted investigators by performing translational studies and GMP manufacturing to ensure that cellular products met release specifications and were manufactured safely, reproducibly, and at the appropriate scale. The roadmap resulting from this experience is the focus of this article. PMID:25484311

Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

PubMed Central

Schreiner, Sabrina; Bürck, Carolin; Glass, Mandy; Groitl, Peter; Wimmer, Peter; Kinkley, Sarah; Mund, Andreas; Everett, Roger D.; Dobner, Thomas

2013-01-01

Death domain–associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein–protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling. PMID:23396441

Rock strength measurements on Archaean basement granitoids recovered from scientific drilling in the active Koyna seismogenic zone, western India

NASA Astrophysics Data System (ADS)

Goswami, Deepjyoti; Akkiraju, Vyasulu V.; Misra, Surajit; Roy, Sukanta; Singh, Santosh K.; Sinha, Amalendu; Gupta, Harsh; Bansal, B. K.; Nayak, Shailesh

2017-08-01

Reservoir triggered earthquakes have been occurring in the Koyna area, western India for the past five decades. Triaxial tests carried out on 181 core samples of Archaean granitoids underlying the Deccan Traps provide valuable constraints on rock strength properties in the Koyna seismogenic zone for the first time. The data include measurements on granite gneiss, granite, migmatitic gneiss and mylonitised granite gneiss obtained from boreholes KBH-3, KBH-4A, KBH-5 and KBH-7 located in the western and eastern margins of the seismic zone. Salient results are as follows. (i) Increase of rock strength with increasing confining pressure allow determination of the linearized failure envelopes from which the cohesive strength and angle of internal friction are calculated. (ii) Variable differential stresses at different depths are the manifestations of deformation partitioning in close association of fault zone(s) or localized fracture zones. (iii) Fractures controlled by naturally developed weak planes such as cleavage and fabric directly affect the rock strength properties, but the majority of failure planes developed during triaxial tests is not consistent with the orientations of pre-existing weak planes. The failure planes may, therefore, represent other planes of weakness induced by ongoing seismic activity. (iv) Stress-strain curves confirm that axial deformation is controlled by the varying intensity of pre-existing shear in the granitoids, viz., mylonite, granite gneiss and migmatitic gneiss. (v) Frequent occurrences of low magnitude earthquakes may be attributed to low and variable rock strength of the granitoids, which, in turn, is modified by successive seismic events.

Important cellular targets for antimicrobial photodynamic therapy.

PubMed

Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

2016-09-01

The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets.

Human Papillomavirus Types 16 and 18 Early-expressed Proteins Differentially Modulate the Cellular Redox State and DNA Damage

PubMed Central

Cruz-Gregorio, Alfredo; Manzo-Merino, Joaquín; Gonzaléz-García, María Cecilia; Pedraza-Chaverri, José; Medina-Campos, Omar Noel; Valverde, Mahara; Rojas, Emilio; Rodríguez-Sastre, María Alexandra; García-Cuellar, Claudia María; Lizano, Marcela

2018-01-01

Oxidative stress has been proposed as a risk factor for cervical cancer development. However, few studies have evaluated the redox state associated with human papillomavirus (HPV) infection. The aim of this work was to determine the role of the early expressed viral proteins E1, E2, E6 and E7 from HPV types 16 and 18 in the modulation of the redox state in an integral form. Therefore, generation of reactive oxygen species (ROS), concentration of reduced glutathione (GSH), levels and activity of the antioxidant enzymes catalase and superoxide dismutase (SOD) and deoxyribonucleic acid (DNA) damage, were analysed in epithelial cells ectopically expressing the viral proteins. Our research shows that E6 oncoproteins decreased GSH and catalase protein levels, as well as its enzymatic activity, which was associated with an increase in ROS production and DNA damage. In contrast, E7 oncoproteins increased GSH, as well as catalase protein levels and its activity, which correlated with a decrease in ROS without affecting DNA integrity. The co-expression of both E6 and E7 oncoproteins neutralized the effects that were independently observed for each of the viral proteins. Additionally, the combined expression of E1 and E2 proteins increased ROS levels with the subsequent increase in the marker for DNA damage phospho-histone 2AX (γH2AX). A decrease in GSH, as well as SOD2 levels and activity were also detected in the presence of E1 and E2, even though catalase activity increased. This study demonstrates that HPV early expressed proteins differentially modulate cellular redox state and DNA damage. PMID:29483822

Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis.

PubMed

Moeller, Marcus J; Soofi, Abdulsalaam; Hartmann, Inge; Le Hir, Michel; Wiggins, Roger; Kriz, Wilhelm; Holzman, Lawrence B

2004-01-01

Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin of glomerular crescents remains unresolved. A genetic cell lineage-mapping study with a novel transgenic mouse model was performed to investigate whether visceral glomerular epithelial cells, termed podocytes, are precursors of cells that populate cellular crescents. The podocyte-specific 2.5P-Cre mouse line was crossed with the ROSA26 reporter line, resulting in irreversible constitutive expression of beta-galactosidase in doubly transgenic 2.5P-Cre/ROSA26 mice. In these mice, crescentic glomerulonephritis was induced with a previously described rabbit anti-glomerular basement membrane antiserum nephritis approach. Interestingly, beta-galactosidase-positive cells derived from podocytes adhered to the parietal basement membrane and populated glomerular crescents during the early phases of cellular crescent formation, accounting for at least one-fourth of the total cell mass. In cellular crescents, the proliferation marker Ki-67 was expressed in beta-galactosidase-positive and beta-galactosidase-negative cells, indicating that both cell types contributed to the formation of cellular crescents through proliferation in situ. Podocyte-specific antigens, including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular crescents, suggesting that podocytes underwent profound phenotypic changes in this nephritis model.

Cellular autofluorescence imaging for early diagnosis of cancers

NASA Astrophysics Data System (ADS)

Steenkeste, Karine; Deniset, Ariane; Lecart, Sandrine; Leveque-Fort, Sandrine; Fontaine-Aupart, Marie-Pierre; Ferlicot, Sophie; Eschwege, Pascal

2005-08-01

Urinary cytology is employed in diagnostic guidelines of bladder cancer in anatomo-pathological laboratories mostly for its ability to diagnose non detectable cancers using cystoscopy, but also because it is a non-invasive and non-constraining technique for a regular follow-up of the more exposed populations. The impossibility to detect such cancers is mainly due to their localization either in the bladder or in the upper urinary tract and the prostate. However, urinary cytology lacks sensitivity, especially for the detection of low grade low stage tumors due to inherent limitation of morphological criteria to distinguish low grade tumor cells from normal urothelial cells. For this purpose, we developed, in addition to urinary cytology, an original screening of these cytological slides by using spectrally-resolved and time-resolved fluorescence as a contrast factor, without changing any parameters in the cytological slide preparation. This method takes advantage of a femtosecond Ti:sapphire laser, continuously tunable in the spectral range 700-950 nm allowing the observation of most endogenous cellular chromophores by biphotonic excitation. A commercial confocal microscope was also used in the measurements allowing an excitation of the samples between 458 nm and 633 nm. We observed that the fluorescence emission is differentially distributed in normal and pathological urothelial cells. Spectral- and time-resolved measurements attested this difference over about one hundred cases which have been tested to confirm the high accuracy of this non-invasive technique.

Time scale of diffusion in molecular and cellular biology

NASA Astrophysics Data System (ADS)

Holcman, D.; Schuss, Z.

2014-05-01

Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal.

PubMed

Putker, Marrit; O'Neill, John Stuart

2016-01-01

Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping.

Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal

PubMed Central

Putker, Marrit; O’Neill, John Stuart

2016-01-01

Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping. PMID:26810072

Navigating novel mechanisms of cellular plasticity with the NAD+ precursor and nutrient nicotinamide.

PubMed

Li, Faqi; Chong, Zhao Zhong; Maiese, Kenneth

2004-09-01

Interest in neuroprotectants for the central nervous system continues to garner significant attention. Nicotinamide, the amide form of niacin (vitamin B3), is the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD+) and is considered to be necessary for cellular function and metabolism. However, recent work has focused on the development of nicotinamide as a novel agent that is critical for modulating cellular plasticity, longevity, and inflammatory microglial function. The ability of nicotinamide to preserve both neuronal and vascular cell populations in the brain during injury is intriguing, but further knowledge of the specific cellular mechanisms that determine protection by this agent is required. The capacity of nicotinamide to govern not only intrinsic cellular integrity, but also extrinsic cellular inflammation rests with the modulation of a host of cellular targets that involve protein kinase B, glycogen synthase kinase-3 beta (GSK-3 beta), Forkhead transcription factors, mitochondrial dysfunction, poly(ADP-ribose) polymerase, cysteine proteases, and microglial activation. Intimately tied to the cytoprotection of nicotinamide is the modulation of an early and late phase of apoptotic injury that is triggered by the loss of membrane asymmetry. Identifying robust cytoprotective agents as nicotinamide in conjunction with the elucidation of the cellular mechanisms responsible for cell survival will continue to solidify the development of therapeutic strategies against neurodegenerative diseases

Expression of voltage-activated calcium channels in the early zebrafish embryo.

PubMed

Sanhueza, Dayán; Montoya, Andro; Sierralta, Jimena; Kukuljan, Manuel

2009-05-01

Increases in cytosolic calcium concentrations regulate many cellular processes, including aspects of early development. Calcium release from intracellular stores and calcium entry through non-voltage-gated channels account for signalling in non-excitable cells, whereas voltage-gated calcium channels (CaV) are important in excitable cells. We report the expression of multiple transcripts of CaV, identified by its homology to other species, in the early embryo of the zebrafish, Danio rerio, at stages prior to the differentiation of excitable cells. CaV mRNAs and proteins were detected as early as the 2-cell stages, which indicate that they arise from both maternal and zygotic transcription. Exposure of embryos to pharmacological blockers of CaV does not perturb early development significantly, although late effects are appreciable. These results suggest that CaV may have a role in calcium homeostasis and control of cellular process during early embryonic development.

Maize early endosperm growth and development: from fertilization through cell type differentiation.

PubMed

Leroux, Brian M; Goodyke, Austin J; Schumacher, Katelyn I; Abbott, Chelsi P; Clore, Amy M; Yadegari, Ramin; Larkins, Brian A; Dannenhoffer, Joanne M

2014-08-01

• Given the worldwide economic importance of maize endosperm, it is surprising that its development is not the most comprehensively studied of the cereals. We present detailed morphometric and cytological descriptions of endosperm development in the maize inbred line B73, for which the genome has been sequenced, and compare its growth with four diverse Nested Association Mapping (NAM) founder lines.• The first 12 d of B73 endosperm development were described using semithin sections of plastic-embedded kernels and confocal microscopy. Longitudinal sections were used to compare endosperm length, thickness, and area.• Morphometric comparison between Arizona- and Michigan-grown B73 showed a common pattern. Early endosperm development was divided into four stages: coenocytic, cellularization through alveolation, cellularization through partitioning, and differentiation. We observed tightly synchronous nuclear divisions in the coenocyte, elucidated that the onset of cellularization was coincident with endosperm size, and identified a previously undefined cell type (basal intermediate zone, BIZ). NAM founders with small mature kernels had larger endosperms (0-6 d after pollination) than lines with large mature kernels.• Our B73-specific model of early endosperm growth links developmental events to relative endosperm size, while accounting for diverse growing conditions. Maize endosperm cellularizes through alveolation, then random partitioning of the central vacuole. This unique cellularization feature of maize contrasts with the smaller endosperms of Arabidopsis, barley, and rice that strictly cellularize through repeated alveolation. NAM analysis revealed differences in endosperm size during early development, which potentially relates to differences in timing of cellularization across diverse lines of maize. © 2014 Botanical Society of America, Inc.

Cellular injury evidenced by impedance technology and infrared microspectroscopy

NASA Astrophysics Data System (ADS)

le Roux, K.; Prinsloo, L. C.; Meyer, D.

2015-03-01

Fourier Transform Infrared (FTIR) spectroscopy is finding increasing biological application, for example in the analysis of diseased tissues and cells, cell cycle studies and investigating the mechanisms of action of anticancer drugs. Cancer treatment studies routinely define the types of cell-drug responses as either total cell destruction by the drug (all cells die), moderate damage (cell deterioration where some cells survive) or reversible cell cycle arrest (cytostasis). In this study the loss of viability and related chemical stress experienced by cells treated with the medicinal plant, Plectranthus ciliatus, was investigated using real time cell electronic sensing (RT-CES) technology and FTIR microspectroscopy. The use of plants as medicines is well established and ethnobotany has proven that crude extracts can serve as treatments against various ailments. The aim of this study was to determine whether FTIR microspectroscopy would successfully distinguish between different types of cellular injury induced by a potentially anticancerous plant extract. Cervical adenocarcinoma (HeLa) cells were treated with a crude extract of Pciliatus and cells monitored using RT-CES to characterize the type of cellular responses induced. Cell populations were then investigated using FTIR microspectroscopy and statistically analysed using One-way Analysis of Variance (ANOVA) and Principal Component Analysis (PCA). The plant extract and a cancer drug control (actinomycin D) induced concentration dependent cellular responses ranging from nontoxic, cytostatic or cytotoxic. Thirteen spectral peaks (915 cm-1, 933 cm-1, 989 cm-1, 1192 cm-1, 1369 cm-1, 1437 cm-1, 1450 cm-1, 1546 cm-1, 1634 cm-1, 1679 cm-1 1772 cm-1, 2874 cm-1 and 2962 cm-1) associated with cytotoxicity were significantly (p value < 0.05, one way ANOVA, Tukey test, Bonferroni) altered, while two of the bands were also indicative of early stress related responses. In PCA, poor separation between nontoxic and cytostatic

Isotopic studies of the late Archean plutonic rocks of the Wind River Range, Wyoming.

USGS Publications Warehouse

Stuckless, J.S.; Hedge, C.E.; Worl, R.G.; Simmons, K.R.; Nkomo, I.T.; Wenner, D.B.

1985-01-01

Two late Archaean intrusive events were documented in the Wind River Range by isotopic studies of the Rb-Sr and U-Th-Pb systems in whole-rock samples and the U-Pb systematics for zircon. An age of approx 2630(20) m.y. for the Louis Lake batholith and apparent ages of 2504(40) to 2575(50) m.y. for the Bear Ears pluton were obtained. Post-magmatic hydrothermal events approximately Tertiary in age, lowered delta 18O values and disturbed parent-daughter relationships in most of the isotopic systems investigated. The two intrusive units apparently were derived from different protoliths. Initial isotopic ratios and petrochemistry for the Louis Lake batholith are consistent with an early Archaean trondhjemitic to tonalitic source. The protolith for the Bear Ears pluton must have been subjected to high-grade metamorphism that caused loss of Rb and U prior to magma generation. -L.C.H.

Deciphering the role of fluids in early stage rifting from full moment tensor inversion of East African earthquakes

NASA Astrophysics Data System (ADS)

Oliva, S. J. C.; Ebinger, C. J.; Keir, D.; Shillington, D. J.; Chindandali, P. R. N.

2016-12-01

The East African Rift splits around the Archaean Tanzania craton into the magmatic Eastern branch and the mostly amagmatic Western branch, which continues south of the craton. Temporary seismic networks recently deployed in three rift sectors allow for comparison and insights into the early stages of rifting, including areas with lower crustal earthquakes. We analyze earthquakes with ML > 3.5 in the area recorded by CRAFTI (northern Tanzania/Kenya), TANGA (Tanganyika rift), and/or SEGMeNT (Malawi rift) networks. For events not well enclosed by these arrays, nearby permanent stations are used to improve azimuthal coverage when possible. We present source mechanisms as well as better-constrained source depth estimates from moment tensor inversion using Dreger and Ford TDMT algorithm (Dreger, 2003; Minson & Dreger, 2008). Data and synthetic waveforms are bandpass filtered between 0.02 to 0.10 Hz, or a narrower frequency band within this range, depending on lake noise, which can interfere strongly on the lower end of this frequency range. Results suggest local stress reorientations as well as significant dilatation components on some events within magmatic rift sectors. The implications of these results for crustal rheology and magmatic modification will be discussed in light of the growing complementary data sets from the three projects to inform our understanding of early rifting as a whole.

Earth’s first stable continents did not form by subduction

NASA Astrophysics Data System (ADS)

Johnson, Tim E.; Brown, Michael; Gardiner, Nicholas J.; Kirkland, Christopher L.; Smithies, R. Hugh

2017-02-01

The geodynamic environment in which Earth’s first continents formed and were stabilized remains controversial. Most exposed continental crust that can be dated back to the Archaean eon (4 billion to 2.5 billion years ago) comprises tonalite-trondhjemite-granodiorite rocks (TTGs) that were formed through partial melting of hydrated low-magnesium basaltic rocks; notably, these TTGs have ‘arc-like’ signatures of trace elements and thus resemble the continental crust produced in modern subduction settings. In the East Pilbara Terrane, Western Australia, low-magnesium basalts of the Coucal Formation at the base of the Pilbara Supergroup have trace-element compositions that are consistent with these being source rocks for TTGs. These basalts may be the remnants of a thick (more than 35 kilometres thick), ancient (more than 3.5 billion years old) basaltic crust that is predicted to have existed if Archaean mantle temperatures were much hotter than today’s. Here, using phase equilibria modelling of the Coucal basalts, we confirm their suitability as TTG ‘parents’, and suggest that TTGs were produced by around 20 per cent to 30 per cent melting of the Coucal basalts along high geothermal gradients (of more than 700 degrees Celsius per gigapascal). We also analyse the trace-element composition of the Coucal basalts, and propose that these rocks were themselves derived from an earlier generation of high-magnesium basaltic rocks, suggesting that the arc-like signature in Archaean TTGs was inherited from an ancestral source lineage. This protracted, multistage process for the production and stabilization of the first continents—coupled with the high geothermal gradients—is incompatible with modern-style plate tectonics, and favours instead the formation of TTGs near the base of thick, plateau-like basaltic crust. Thus subduction was not required to produce TTGs in the early Archaean eon.

Earth's first stable continents did not form by subduction.

PubMed

Johnson, Tim E; Brown, Michael; Gardiner, Nicholas J; Kirkland, Christopher L; Smithies, R Hugh

2017-03-09

The geodynamic environment in which Earth's first continents formed and were stabilized remains controversial. Most exposed continental crust that can be dated back to the Archaean eon (4 billion to 2.5 billion years ago) comprises tonalite-trondhjemite-granodiorite rocks (TTGs) that were formed through partial melting of hydrated low-magnesium basaltic rocks; notably, these TTGs have 'arc-like' signatures of trace elements and thus resemble the continental crust produced in modern subduction settings. In the East Pilbara Terrane, Western Australia, low-magnesium basalts of the Coucal Formation at the base of the Pilbara Supergroup have trace-element compositions that are consistent with these being source rocks for TTGs. These basalts may be the remnants of a thick (more than 35 kilometres thick), ancient (more than 3.5 billion years old) basaltic crust that is predicted to have existed if Archaean mantle temperatures were much hotter than today's. Here, using phase equilibria modelling of the Coucal basalts, we confirm their suitability as TTG 'parents', and suggest that TTGs were produced by around 20 per cent to 30 per cent melting of the Coucal basalts along high geothermal gradients (of more than 700 degrees Celsius per gigapascal). We also analyse the trace-element composition of the Coucal basalts, and propose that these rocks were themselves derived from an earlier generation of high-magnesium basaltic rocks, suggesting that the arc-like signature in Archaean TTGs was inherited from an ancestral source lineage. This protracted, multistage process for the production and stabilization of the first continents-coupled with the high geothermal gradients-is incompatible with modern-style plate tectonics, and favours instead the formation of TTGs near the base of thick, plateau-like basaltic crust. Thus subduction was not required to produce TTGs in the early Archaean eon.

Synchrony of plant cellular circadian clocks with heterogeneous properties under light/dark cycles.

PubMed

Okada, Masaaki; Muranaka, Tomoaki; Ito, Shogo; Oyama, Tokitaka

2017-03-22

Individual cells in a plant can work independently as circadian clocks, and their properties are the basis of various circadian phenomena. The behaviour of individual cellular clocks in Lemna gibba was orderly under 24-h light/dark cycles despite their heterogeneous free-running periods (FRPs). Here, we reveal the entrainment habits of heterogeneous cellular clocks using non-24-h light/dark cycles (T-cycles). The cellular rhythms of AtCCA1::LUC under T = 16 h cycles showed heterogeneous entrainment that was associated with their heterogeneous FRPs. Under T = 12 h cycles, most cells showed rhythms having ~24-h periods. This suggested that the lower limit of entrainment to the light/dark cycles of heterogeneous cellular circadian clocks is set to a period longer than 12 h, which enables them to be synchronous under ~24-h daily cycles without being perturbed by short light/dark cycles. The entrainment habits of individual cellular clocks are likely to be the basis of the circadian behaviour of plant under the natural day-night cycle with noisy environmental fluctuations. We further suggest that modifications of EARLY FLOWERING3 (ELF3) in individual cells deviate the entrainability to shorter T-cycles possibly by altering both the FRPs and light responsiveness.

47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

Code of Federal Regulations, 2011 CFR

2011-10-01

...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition...

Cellular Imaging With MRI.

PubMed

Makela, Ashley V; Murrell, Donna H; Parkins, Katie M; Kara, Jenna; Gaudet, Jeffrey M; Foster, Paula J

2016-10-01

Cellular magnetic resonance imaging (MRI) is an evolving field of imaging with strong translational and research potential. The ability to detect, track, and quantify cells in vivo and over time allows for studying cellular events related to disease processes and may be used as a biomarker for decisions about treatments and for monitoring responses to treatments. In this review, we discuss methods for labeling cells, various applications for cellular MRI, the existing limitations, strategies to address these shortcomings, and clinical cellular MRI.

Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport.

PubMed

Pirkmajer, Sergej; Kirchner, Henriette; Lundell, Leonidas S; Zelenin, Pavel V; Zierath, Juleen R; Makarova, Kira S; Wolf, Yuri I; Chibalin, Alexander V

2017-07-15

Small transmembrane proteins such as FXYDs, which interact with Na + ,K + -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca 2+ -ATPase play fundamental roles in regulation of ion transport in vertebrates. Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions. We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage. We also identified 13 gene subfamilies of FXYDs and propose a revised, phylogeny-based FXYD classification that is consistent across vertebrate species. These findings provide an improved framework for investigating physiological and pathophysiological functions of small transmembrane regulators of ion transport. Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these are members of the FXYD family (FXYD1-12), which regulate Na + ,K + -ATPase, and phospholamban, sarcolipin, myoregulin and DWORF, which regulate the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies. Here we discovered that sea lamprey (Petromyzon marinus), a representative of extant jawless vertebrates (Cyclostomata), expresses an FXYD homologue, which strongly suggests that FXYDs predate the emergence of fishes and other jawed vertebrates (Gnathostomata). Using a combination of sequence-based phylogenetic analysis and conservation of local chromosome context, we determined that FXYDs markedly diversified in the lineages leading to cartilaginous fishes (Chondrichthyes) and bony

Cellular consequences of sleep deprivation in the brain.

PubMed

Cirelli, Chiara

2006-10-01

Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

Q fever in pregnant goats: humoral and cellular immune responses

PubMed Central

2013-01-01

Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. Both humoral and cellular immunity are important in the host defence against intracellular bacteria. Little is known about the immune response to C. burnetii infections in domestic ruminants even though these species are the major source of Q fever in humans. To investigate the goat’s immune response we inoculated groups of pregnant goats via inhalation with a Dutch outbreak isolate of C. burnetii. All animals were successfully infected. Phase 1 and Phase 2 IgM- and IgG-specific antibodies were measured. Cellular immune responses were investigated by interferon-gamma, enzyme-linked immunosorbent spot test (IFN-γ Elispot), lymphocyte proliferation test (LPT) and systemic cytokines. After two weeks post inoculation (wpi), a strong anti-C. burnetii Phase 2 IgM and IgG antibody response was observed while the increase in IgM anti-Phase 1 antibodies was less pronounced. IgG anti-Phase 1 antibodies started to rise at 6 wpi. Cellular immune responses were observed after parturition. Our results demonstrated humoral and cellular immune responses to C. burnetii infection in pregnant goats. Cell-mediated immune responses did not differ enough to distinguish between Coxiella-infected and non-infected pregnant animals, whereas a strong-phase specific antibody response is detected after 2 wpi. This humoral immune response may be useful in the early detection of C. burnetii-infected pregnant goats. PMID:23915213

Winding through the WNT pathway during cellular development and demise.

PubMed

Li, F; Chong, Z Z; Maiese, K

2006-01-01

In slightly over a period of twenty years, our comprehension of the cellular and molecular mechanisms that govern the Wnt signaling pathway continue to unfold. The Wnt proteins were initially implicated in viral carcinogenesis experiments associated with mammary tumors, but since this period investigations focusing on the Wnt pathways and their transmembrane receptors termed Frizzled have been advanced to demonstrate the critical nature of Wnt for the development of a variety of cell populations as well as the potential of the Wnt pathway to avert apoptotic injury. In particular, Wnt signaling plays a significant role in both the cardiovascular and nervous systems during embryonic cell patterning, proliferation, differentiation, and orientation. Furthermore, modulation of Wnt signaling under specific cellular influences can either promote or prevent the early and late stages of apoptotic cellular injury in neurons, endothelial cells, vascular smooth muscle cells, and cardiomyocytes. A number of downstream signal transduction pathways can mediate the biological response of the Wnt proteins that include Dishevelled, beta-catenin, intracellular calcium, protein kinase C, Akt, and glycogen synthase kinase-3beta. Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative, vascular, and cardiac disorders and may be closely integrated with the function of trophic factors. Identification of the critical elements that modulate the Wnt-Frizzled signaling pathway should continue to unlock the potential of Wnt pathway for the development of new therapeutic options against neurodegenerative and vascular diseases.

Biomechanics of cellular solids.

PubMed

Gibson, Lorna J

2005-03-01

Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

Cellular Reflectarray Antenna

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.

2010-01-01

The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

Electromagnetic cellular interactions.

PubMed

Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

2011-05-01

Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Mathematical Model to study the Dynamics of Epithelial Cellular Networks

PubMed Central

Abate, Alessandro; Vincent, Stéphane; Dobbe, Roel; Silletti, Alberto; Master, Neal; Axelrod, Jeffrey D.; Tomlin, Claire J.

2013-01-01

Epithelia are sheets of connected cells that are essential across the animal kingdom. Experimental observations suggest that the dynamical behavior of many single-layered epithelial tissues has strong analogies with that of specific mechanical systems, namely large networks consisting of point masses connected through spring-damper elements and undergoing the influence of active and dissipating forces. Based on this analogy, this work develops a modeling framework to enable the study of the mechanical properties and of the dynamic behavior of large epithelial cellular networks. The model is built first by creating a network topology that is extracted from the actual cellular geometry as obtained from experiments, then by associating a mechanical structure and dynamics to the network via spring-damper elements. This scalable approach enables running simulations of large network dynamics: the derived modeling framework in particular is predisposed to be tailored to study general dynamics (for example, morphogenesis) of various classes of single-layered epithelial cellular networks. In this contribution we test the model on a case study of the dorsal epithelium of the Drosophila melanogaster embryo during early dorsal closure (and, less conspicuously, germband retraction). PMID:23221083

An outline of cellular automaton universe via cosmological KdV equation

NASA Astrophysics Data System (ADS)

Christianto, V.; Smarandache, F.; Umniyati, Y.

2018-03-01

It has been known for long time that the cosmic sound wave was there since the early epoch of the Universe. Signatures of its existence are abound. However, such a sound wave model of cosmology is rarely developed fully into a complete framework. This paper can be considered as our second attempt towards such a complete description of the Universe based on soliton wave solution of cosmological KdV equation. Then we advance further this KdV equation by virtue of Cellular Automaton method to solve the PDEs. We submit wholeheartedly Robert Kuruczs hypothesis that Big Bang should be replaced with a finite cellular automaton universe with no expansion [4][5]. Nonetheless, we are fully aware that our model is far from being complete, but it appears the proposed cellular automaton model of the Universe is very close in spirit to what Konrad Zuse envisaged long time ago. It is our hope that the new proposed method can be verified with observation data. But we admit that our model is still in its infancy, more researches are needed to fill all the missing details.

Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

NASA Astrophysics Data System (ADS)

Pradhan, Prabhakar; Damania, Dhwanil; Joshi, Hrushikesh M.; Turzhitsky, Vladimir; Subramanian, Hariharan; Roy, Hemant K.; Taflove, Allen; Dravid, Vinayak P.; Backman, Vadim

2011-04-01

Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed. Originally submitted for the special focus issue on physical oncology.

Comparative studies on cellular behaviour of carnation (Dianthus caryophyllus Linn. cv. Grenadin) grown in vivo and in vitro for early detection of somaclonal variation.

PubMed

Yaacob, Jamilah Syafawati; Taha, Rosna Mat; Khorasani Esmaeili, Arash

2013-01-01

The present study deals with the cytological investigations on the meristematic root cells of carnation (Dianthus caryophyllus Linn.) grown in vivo and in vitro. Cellular parameters including the mitotic index (MI), chromosome count, ploidy level (nuclear DNA content), mean cell and nuclear areas, and cell doubling time (Cdt) were determined from the 2 mm root tip segments of this species. The MI value decreased when cells were transferred from in vivo to in vitro conditions, perhaps due to early adaptations of the cells to the in vitro environment. The mean chromosome number was generally stable (2n = 2x = 30) throughout the 6-month culture period, indicating no occurrence of early somaclonal variation. Following the transfer to the in vitro environment, a significant increase was recorded for mean cell and nuclear areas, from 26.59 ± 0.09  μm² to 35.66 ± 0.10  μm² and 142.90 ± 0.59  μm² to 165.05 ± 0.58  μm², respectively. However, the mean cell and nuclear areas of in vitro grown D. caryophyllus were unstable and fluctuated throughout the tissue culture period, possibly due to organogenesis or rhizogenesis. Ploidy level analysis revealed that D. caryophyllus root cells contained high percentage of polyploid cells when grown in vivo and maintained high throughout the 6-month culture period.

Adenovirus Type 5 Early Region 1B 55K Oncoprotein-Dependent Degradation of Cellular Factor Daxx Is Required for Efficient Transformation of Primary Rodent Cells▿

PubMed Central

Schreiner, Sabrina; Wimmer, Peter; Groitl, Peter; Chen, Shuen-Yuan; Blanchette, Paola; Branton, Philip E.; Dobner, Thomas

2011-01-01

Early region 1B 55K (E1B-55K) from adenovirus type 5 (Ad5) is a multifunctional regulator of lytic infection and contributes in vitro to complete cell transformation of primary rodent cells in combination with Ad5 E1A. Inhibition of p53 activated transcription plays a key role in processes by which E1B-55K executes its oncogenic potential. Nevertheless, additional functions of E1B-55K or further protein interactions with cellular factors of DNA repair, transcription, and apoptosis, including Mre11, PML, and Daxx, may also contribute to the transformation process. In line with previous results, we performed mutational analysis to define a Daxx interaction motif within the E1B-55K polypeptide. The results from these studies showed that E1B-55K/Daxx binding is not required for inhibition of p53-mediated transactivation or binding and degradation of cellular factors (p53/Mre11). Surprisingly, these mutants lost the ability to degrade Daxx and showed reduced transforming potential in primary rodent cells. In addition, we observed that E1B-55K lacking the SUMO-1 conjugation site (SCS/K104R) was sufficient for Daxx interaction but no longer capable of E1B-55K-dependent proteasomal degradation of the cellular factor Daxx. These results, together with the observation that E1B-55K SUMOylation is required for efficient transformation, provides evidence for the idea that SUMO-1-conjugated E1B-55K-mediated degradation of Daxx plays a key role in adenoviral oncogenic transformation. We assume that the viral protein contributes to cell transformation through the modulation of Daxx-dependent pathways. This further substantiates the assumption that further mechanisms for efficient transformation of primary cells can be separated from functions required for the inhibition of p53-stimulated transcription. PMID:21697482

Lithostratigraphy and structure of the early Archaean Doolena Gap Greenstone Belt, East Pilbara Terrane (EPT), Western Australia

NASA Astrophysics Data System (ADS)

Wiemer, D.; Schrank, C. E.; Murphy, D. T.

2014-12-01

We present a detailed lithostratigraphic and structural analysis of the Archean Doolena Gap greenstone belt to shed light on the tectonic evolution of the EPT. The study area is divided into four structural domains: i) marginal orthogneisses of the MGC (Muccan Granitoid Complex), ii) a dominantly mafic mylonitic shear zone (South Muccan Shear Zone, SMSZ) enveloping the MGC, iii) a Central Fold Belt of dominantly mafic greenschists (CFB), and iv) a lower greenschist- to sub-greenschist southern domain. Toward the dome margin, abrupt increases in deformation intensity occur across domain boundaries. Domain boundaries and intra-domain shear zones are marked by significant carbonate +/- quartz alteration and high-strain non-coaxial deformation with dome-up kinematics. The southern domain comprises pillow basalts of the Mount Ada Formation (MAF), conformably overlain by clastic sediments and minor pillow basalts of the Duffer Formation (DF). The MAF and DF are overlain by an up to 1km thick package of quartzite (Strelley Pool Formation) across an angular unconformity. Isoclinal folds (F2) within the CFB to the North deform an early foliation (S1) within dominantly mafic schists and associated carbonate veins. F2 folds are preserved within lozenges that are parallel to the axial planes of F2 folds in a regional E-W trending foliation (S2) and to the SMSZ. Lozenges are often bound by zones of significant carbonate alteration. The lozenges are folded recumbently (F3), with sub-vertical fold axes pointing towards the dome. The F3 axes are parallel to mineral stretching lineations on S2 indicating dome-up movement. The entire belt is cut by late NE-SW-striking faults that exhibit dominantly brittle deformation in the southern domain but ductile drag folding (F4) in the CFB. Therefore, the southern domain must have overlain the CFB during this D4 event. We propose a protracted structural history of the greenstone belt where successive deformation events relate to the episodic

Cellular and molecular perspectives in rheumatoid arthritis.

PubMed

Veale, Douglas J; Orr, Carl; Fearon, Ursula

2017-06-01

Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization, facilitating an influx of lymphocytes and monocytes that transform a typically acellular loose areolar membrane into an invasive tumour-like pannus. The microvasculature proliferates to form straight regularly-branching vessels; however, they are highly dysfunctional resulting in reduced oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are found at an early stage, often before arthritis has developed, and they have been implicated in the pathogenesis of RA. Abnormal cellular metabolism and mitochondrial dysfunction thus ensue and, in turn, through the increased production of reactive oxygen species actively induce inflammation. Key pro-inflammatory cytokines, chemokines and growth factors and their signalling pathways, including nuclear factor κB, Janus kinase-signal transducer, are highly activated when immune cells are exposed to hypoxia in the inflamed rheumatoid joint show adaptive survival reactions by activating. This review attempts to highlight those aberrations in the innate and adaptive immune systems including the role of genetic and environmental factors, autoantibodies, cellular alterations, signalling pathways and metabolism that are implicated in the pathogenesis of RA and may therefore provide an opportunity for therapeutic intervention.

Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

NASA Astrophysics Data System (ADS)

McCune, Matthew; Kosztin, Ioan

2013-03-01

Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level.

PubMed

Humphreys, Kathryn L; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A; Drury, Stacy S

2016-12-30

Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2-4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child's life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level

PubMed Central

Humphreys, Kathryn L.; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A.; Drury, Stacy S.

2016-01-01

Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2 to 4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child’s life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. PMID:27677058

Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

NASA Astrophysics Data System (ADS)

Gao, Ziyang

Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

Mechanisms for strain localization within Archaean craton: A structural study from the Bundelkhand Tectonic Zone, north-central India

NASA Astrophysics Data System (ADS)

Sarkar, Saheli; Patole, Vishal; Saha, Lopamudra; Pati, Jayanta Kumar; Nasipuri, Pritam

2015-04-01

The transformation of palaeo-continents involve breakup, dispersal and reassembly of cratonic blocks by collisional suturing that develop a network of orogenic (mobile) belts around the periphery of the stable cratons. The nature of deformation in the orogenic belt depends on the complex interaction of fracturing, plastic deformation and diffusive mass transfer. Additionally, the degree and amount of melting during regional deformation is critical as the presence of melt facilitates the rate of diffusive mass transfer and weakens the rock by reducing the effective viscosity of the deformed zone. The nature of strain localization and formation of ductile shear zones surrounding the cratonic blocks have been correlated with Proterozoic-Palaeozoic supercontinent assembly (Columbia, Rodinia and Gondwana reconstruction). Although, a pre-Columbia supercontinent termed as Kenorland has been postulated, there is no evidence that supports the notion due to lack of the presence of shear zones within the Archaean cratonic blocks. In this contribution, we present the detailed structural analysis of ductile shear zones within the Bundelkhand craton. The ductlile shear zone is termed as Bundelkhand Tectonic Zone (BTZ) that extends east-west for nearly 300 km throughout the craton with a width of two-three kilometer . In the north-central India, the Bundelkhand craton is exposed over an area of 26,000 sq. The craton is bounded by Central Indian Tectonic zone in the south, the Great Boundary fault in the west and by the rocks of Lesser Himalaya in the north. A series of tonalite-trondjhemite-granodiorite gneiss are the oldest rocks of the Bundelkhand craton that also contains a succession of metamorphosed supracrustal rocks comprising of banded iron formation, quartzite, calc-silicate and ultramafic rocks. K-feldspar bearing granites intrude the tonalite-trondjhemite-granodiorite and the supracrustal rocks during the time span of 2.1 to 2.5 Ga. The TTGs near Babina, in central

MSAT and cellular hybrid networking

NASA Astrophysics Data System (ADS)

Baranowsky, Patrick W., II

Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

Extracellular matrix motion and early morphogenesis

PubMed Central

Loganathan, Rajprasad; Rongish, Brenda J.; Smith, Christopher M.; Filla, Michael B.; Czirok, Andras; Bénazéraf, Bertrand

2016-01-01

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale ‘total’ cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. PMID:27302396

Cellular proliferation after experimental glaucoma filtration surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jampel, H.D.; McGuigan, L.J.; Dunkelberger, G.R.

1988-01-01

We used light microscopic autoradiography to determine the time course of cellular incorporation of tritiated thymidine (a correlate of cell division) following glaucoma filtration surgery in seven eyes of four cynomolgus monkeys with experimental glaucoma. Incorporation of tritiated thymidine was detected as early as 24 hours postoperatively. Peak incorporation occurred five days postoperatively and had returned to baseline levels by day 11. Cells incorporating tritiated thymidine included keratocytes, episcleral cells, corneal and capillary endothelial cells, and conjunctival and corneal epithelial cells. Transmission electron microscopy was correlated with the autoradiographic results to demonstrate that fibroblasts were dividing on the corneoscleral margin.more » These findings have potential clinical implications for the use of antiproliferative agents after filtration surgery.« less

Role of Mitochondrial Ca2+ in the Regulation of Cellular Energetics

PubMed Central

Glancy, Brian; Balaban, Robert S.

2012-01-01

Calcium is an important signaling molecule involved in the regulation of many cellular functions. The large free energy in the Ca2+ ion membrane gradients make Ca2+ signaling inherently sensitive to the available cellular free energy, primarily in the form of ATP. In addition, Ca2+ regulates many cellular ATP consuming reactions such as muscle contraction, exocytosis, biosynthesis and neuronal signaling. Thus, Ca2+ becomes a logical candidate as a signaling molecule to modulate ATP hydrolysis and synthesis during changes in numerous forms of cellular work. Mitochondria are the primary source of aerobic energy production in mammalian cells and also maintain a large Ca2+ gradient across their inner membrane providing a signaling potential for this molecule. The demonstrated link between cytosolic and mitochondrial [Ca2+], identification of transport mechanisms as well as proximity of mitochondria to Ca2+ release sites further supports the notion that Ca2+ can be an important signaling molecule in the energy metabolism interplay of the cytosol with the mitochondria. Here we review sites within the mitochondria where Ca2+ plays a role in the regulation of ATP generation and potentially contributes to the orchestration of the cellular metabolic homeostasis. Early work on isolated enzymes pointed to several matrix dehydrogenases that are stimulated by Ca2+, which were confirmed in the intact mitochondrion as well as cellular and in vivo systems. However, studies in these intact systems suggested a more expansive influence of Ca2+ on mitochondrial energy conversion. Numerous non-invasive approaches monitoring NADH, mitochondrial membrane potential, oxygen consumption and workloads suggest significant Ca2+ effects on other elements of NADH generation as well as downstream elements of oxidative phosphorylation including the F1FO-ATPase and the cytochrome chain. These other potential elements of Ca2+ modification of mitochondrial energy conversion will be the focus of this

Compound annotation with real time cellular activity profiles to improve drug discovery.

PubMed

Fang, Ye

2016-01-01

In the past decade, a range of innovative strategies have been developed to improve the productivity of pharmaceutical research and development. In particular, compound annotation, combined with informatics, has provided unprecedented opportunities for drug discovery. In this review, a literature search from 2000 to 2015 was conducted to provide an overview of the compound annotation approaches currently used in drug discovery. Based on this, a framework related to a compound annotation approach using real-time cellular activity profiles for probe, drug, and biology discovery is proposed. Compound annotation with chemical structure, drug-like properties, bioactivities, genome-wide effects, clinical phenotypes, and textural abstracts has received significant attention in early drug discovery. However, these annotations are mostly associated with endpoint results. Advances in assay techniques have made it possible to obtain real-time cellular activity profiles of drug molecules under different phenotypes, so it is possible to generate compound annotation with real-time cellular activity profiles. Combining compound annotation with informatics, such as similarity analysis, presents a good opportunity to improve the rate of discovery of novel drugs and probes, and enhance our understanding of the underlying biology.

Early cellular evolution.

NASA Technical Reports Server (NTRS)

Margulis, L.

1972-01-01

Study of the evolutionary developments that occurred subsequent to the origin of ancestral cells. Microbial physiology and ecology are potential sharp tools for shaping concepts of microbial evolution. Some popular unjustified assumptions are discussed. It is considered that certain principles derived mainly from the advances of molecular biology can be used to order the natural groups (genera) of extant prokaryotes and their patterns phylogenetically.

Cellular nanotechnology: making biological interfaces smarter.

PubMed

Mendes, Paula M

2013-12-21

Recently, there has been an outburst of research on engineered cell-material interfaces driven by nanotechnology and its tools and techniques. This tutorial review begins by providing a brief introduction to nanostructured materials, followed by an overview of the wealth of nanoscale fabrication and analysis tools available for their development. This background serves as the basis for a discussion of early breakthroughs and recent key developments in the endeavour to develop nanostructured materials as smart interfaces for fundamental cellular studies, tissue engineering and regenerative medicine. The review covers three major aspects of nanostructured interfaces - nanotopographical control, dynamic behaviour and intracellular manipulation and sensing - where efforts are continuously being made to further understand cell function and provide new ways to control cell behaviour. A critical reflection of the current status and future challenges are discussed as a conclusion to the review.

Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy.

PubMed

Izumi, Hiroto; Torigoe, Takayuki; Ishiguchi, Hiroshi; Uramoto, Hidetaka; Yoshida, Yoichiro; Tanabe, Mizuho; Ise, Tomoko; Murakami, Tadashi; Yoshida, Takeshi; Nomoto, Minoru; Kohno, Kimitoshi

2003-12-01

One of the major obstacles to the successful treatment of cancer is the complex biology of solid tumour development. Although regulation of intracellular pH has been shown to be critically important for many cellular functions, pH regulation has not been fully investigated in the field of cancer. It has, however, been shown that cellular pH is crucial for biological functions such as cell proliferation, invasion and metastasis, drug resistance and apoptosis. Hypoxic conditions are often observed during the development of solid tumours and lead to intracellular and extracellular acidosis. Cellular acidosis has been shown to be a trigger in the early phase of apoptosis and leads to activation of endonucleases inducing DNA fragmentation. To avoid intracellular acidification under such conditions, pH regulators are thought to be up-regulated in tumour cells. Four major types of pH regulator have been identified: the proton pump, the sodium-proton exchanger family (NHE), the bicarbonate transporter family (BCT) and the monocarboxylate transporter family (MCT). Here, we describe the structure and function of pH regulators expressed in tumour tissue. Understanding pH regulation in tumour cells may provide new ways of inducing tumour-specific apoptosis, thus aiding cancer chemotherapy.

In vivo cellular imaging with microscopes enabled by MEMS scanners

NASA Astrophysics Data System (ADS)

Ra, Hyejun

High-resolution optical imaging plays an important role in medical diagnosis and biomedical research. Confocal microscopy is a widely used imaging method for obtaining cellular and sub-cellular images of biological tissue in reflectance and fluorescence modes. Its characteristic optical sectioning capability also enables three-dimensional (3-D) image reconstruction. However, its use has mostly been limited to excised tissues due to the requirement of high numerical aperture (NA) lenses for cellular resolution. Microscope miniaturization can enable in vivo imaging to make possible early cancer diagnosis and biological studies in the innate environment. In this dissertation, microscope miniaturization for in vivo cellular imaging is presented. The dual-axes confocal (DAC) architecture overcomes limitations of the conventional single-axis confocal (SAC) architecture to allow for miniaturization with high resolution. A microelectromechanical systems (MEMS) scanner is the central imaging component that is key in miniaturization of the DAC architecture. The design, fabrication, and characterization of the two-dimensional (2-D) MEMS scanner are presented. The gimbaled MEMS scanner is fabricated on a double silicon-on-insulator (SOI) wafer and is actuated by self-aligned vertical electrostatic combdrives. The imaging performance of the MEMS scanner in a DAC configuration is shown in a breadboard microscope setup, where reflectance and fluorescence imaging is demonstrated. Then, the MEMS scanner is integrated into a miniature DAC microscope. The whole imaging system is integrated into a portable unit for research in small animal models of human biology and disease. In vivo 3-D imaging is demonstrated on mouse skin models showing gene transfer and siRNA silencing. The siRNA silencing process is sequentially imaged in one mouse over time.

Comparative Studies on Cellular Behaviour of Carnation (Dianthus caryophyllus Linn. cv. Grenadin) Grown In Vivo and In Vitro for Early Detection of Somaclonal Variation

PubMed Central

Yaacob, Jamilah Syafawati; Taha, Rosna Mat; Khorasani Esmaeili, Arash

2013-01-01

The present study deals with the cytological investigations on the meristematic root cells of carnation (Dianthus caryophyllus Linn.) grown in vivo and in vitro. Cellular parameters including the mitotic index (MI), chromosome count, ploidy level (nuclear DNA content), mean cell and nuclear areas, and cell doubling time (Cdt) were determined from the 2 mm root tip segments of this species. The MI value decreased when cells were transferred from in vivo to in vitro conditions, perhaps due to early adaptations of the cells to the in vitro environment. The mean chromosome number was generally stable (2n = 2x = 30) throughout the 6-month culture period, indicating no occurrence of early somaclonal variation. Following the transfer to the in vitro environment, a significant increase was recorded for mean cell and nuclear areas, from 26.59 ± 0.09 μm2 to 35.66 ± 0.10 μm2 and 142.90 ± 0.59 μm2 to 165.05 ± 0.58 μm2, respectively. However, the mean cell and nuclear areas of in vitro grown D. caryophyllus were unstable and fluctuated throughout the tissue culture period, possibly due to organogenesis or rhizogenesis. Ploidy level analysis revealed that D. caryophyllus root cells contained high percentage of polyploid cells when grown in vivo and maintained high throughout the 6-month culture period. PMID:23766703

Location and cellular stages of NK cell development

PubMed Central

Yu, Jianhua; Freud, Aharon G.; Caligiuri, Michael A

2013-01-01

The identification of distinct tissue-specific natural killer (NK) cell populations that apparently mature from local precursor populations has brought new insight into the diversity and developmental regulation of this important lymphoid subset. NK cells provide a necessary link between the early (innate) and late (adaptive) immune responses to infection. Gaining a better understanding of the processes that govern NK cell development should allow us to better harness NK cell functions in multiple clinical settings as well as to gain further insight into how these cells undergo malignant transformation. In this review, we summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice. PMID:24055329

Untangling the origin of viruses and their impact on cellular evolution.

PubMed

Nasir, Arshan; Sun, Feng-Jie; Kim, Kyung Mo; Caetano-Anollés, Gustavo

2015-04-01

The origin and evolution of viruses remain mysterious. Here, we focus on the distribution of viral replicons in host organisms, their morphological features, and the evolution of highly conserved protein and nucleic acid structures. The apparent inability of RNA viral replicons to infect contemporary akaryotic species suggests an early origin of RNA viruses and their subsequent loss in akaryotes. A census of virion morphotypes reveals that advanced forms were unique to viruses infecting a specific supergroup, while simpler forms were observed in viruses infecting organisms in all forms of cellular life. Results hint toward an ancient origin of viruses from an ancestral virus harboring either filamentous or spherical virions. Finally, phylogenetic trees built from protein domain and tRNA structures in thousands of genomes suggest that viruses evolved via reductive evolution from ancient cells. The analysis presents a complete account of the evolutionary history of cells and viruses and identifies viruses as crucial agents influencing cellular evolution. © 2015 New York Academy of Sciences.

78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... and Gene Therapy Products; Extension of Comment Period AGENCY: Food and Drug Administration, HHS...: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' that... sponsors of Investigational New Drug Applications for cellular therapy (CT) and gene therapy (GT) products...

Cellular genetic therapy.

PubMed

Del Vecchio, F; Filareto, A; Spitalieri, P; Sangiuolo, F; Novelli, G

2005-01-01

Cellular genetic therapy is the ultimate frontier for those pathologies that are consequent to a specific nonfunctional cellular type. A viable cure for there kinds of diseases is the replacement of sick cells with healthy ones, which can be obtained from the same patient or a different donor. In fact, structures can be corrected and strengthened with the introduction of undifferentiated cells within specific target tissues, where they will specialize into the desired cellular types. Furthermore, consequent to the recent results obtained with the transdifferentiation experiments, a process that allows the in vitro differentiation of embryonic and adult stem cells, it has also became clear that many advantages may be obtained from the use of stem cells to produce drugs, vaccines, and therapeutic molecules. Since stem cells can sustain lineage potentials, the capacity for differentiation, and better tolerance for the introduction of exogenous genes, they are also considered as feasible therapeutic vehicles for gene therapy. In fact, it is strongly believed that the combination of cellular genetic and gene therapy approaches will definitely allow the development of new therapeutic strategies as well as the production of totipotent cell lines to be used as experimental models for the cure of genetic disorders.

Cellular telephone interference with medical equipment.

PubMed

Tri, Jeffrey L; Severson, Rodney P; Firl, Allen R; Hayes, David L; Abenstein, John P

2005-10-01

To assess the potential electromagnetic interference (EMI) effects that new or current-generation cellular telephones have on medical devices. For this study, performed at the Mayo Clinic in Rochester, Minn, between March 9, 2004, and April 24, 2004, we tested 16 different medical devices with 6 cellular telephones to assess the potential for EMI. Two of the medical devices were tested with both new and old interface modules. The 6 cellular telephones chosen represent the different cellular technology protocols in use: Code Division Multiple Access (2 models), Global System for Mobile communications, Integrated Digital Enhanced Network, Time Division Multiple Access, and analog. The cellular telephones were tested when operating at or near their maximum power output. The medical devices, connected to clinical simulators during testing, were monitored by observing the device displays and alarms. Of 510 tests performed, the incidence of clinically important interference was 1.2%; EMI was Induced in 108 tests (21.2%). Interference occurred in 7 (44%) of the 16 devices tested. Cellular telephones can interfere with medical equipment. Technology changes in both cellular telephones and medical equipment may continue to mitigate or may worsen clinically relevant interference. Compared with cellular telephones tested in previous studies, those currently in use must be closer to medical devices before any interference is noticed. However, periodic testing of cellular telephones to determine their effects on medical equipment will be required.

Mathematical Modeling of Cellular Metabolism.

PubMed

Berndt, Nikolaus; Holzhütter, Hermann-Georg

Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

The Effect of Gravity Fields on Cellular Gene Expression

NASA Technical Reports Server (NTRS)

Hughes-Fulford, Millie

1999-01-01

Early theoretical analysis predicted that microgravity effects on the isolated cell would be minuscule at the subcellular level; however, these speculations have not proven true in the real world. Astronauts experience a significant bone and muscle loss in as little as 2 weeks of spaceflight and changes are seen at the cellular level soon after exposure to microgravity. Changes in biological systems may be primarily due to the lack of gravity and the resulting loss of mechanical stress on tissues and cells. Recent ground and flight studies examining the effects of gravity or mechanical stress on cells demonstrate marked changes in gene expression when relatively small changes in mechanical forces or gravity fields were made. Several immediate early genes (IEG) like c-fos and c-myc are induced by mechanical stimulation within minutes. In contrast, several investigators report that the absence of mechanical forces during space flight result in decreased sera response element (SRE) activity and attenuation of expression of IEGs such as c-fos, c-jun and cox-2 mRNAs. Clearly, these early changes in gene expression may have long term consequences on mechanically sensitive cells. In our early studies on STS-56, we reported four major changes in the osteoblast; 1) prostaglandin synthesis in flight, 2) changes in cellular morphology, 3) altered actin cytoskeleton and 4) reduced osteoblast growth after four days exposure to microgravity. Initially, it was believed that changes in fibronectin (FN) RNA, FN protein synthesis or subsequent FN matrix formation might account for the changes in cytoskeleton and/ or reduction of growth. However our recent studies on Biorack (STS-76, STS-81 and STS-84), using ground and in-flight 1-G controls, demonstrated that fibronectin synthesis and matrix formation were normal in microgravity. In addition, in our most recent Biorack paper, our laboratory has documented that relative protein synthesis and mRNA synthesis are not changed after 24

Extrinsic Embryonic Sensory Stimulation Alters Multimodal Behavior and Cellular Activation

PubMed Central

Markham, Rebecca G.; Shimizu, Toru; Lickliter, Robert

2009-01-01

Embryonic vision is generated and maintained by spontaneous neuronal activation patterns, yet extrinsic stimulation also sculpts sensory development. Because the sensory and motor systems are interconnected in embryogenesis, how extrinsic sensory activation guides multimodal differentiation is an important topic. Further, it is unknown whether extrinsic stimulation experienced near sensory sensitivity onset contributes to persistent brain changes, ultimately affecting postnatal behavior. To determine the effects of extrinsic stimulation on multimodal development, we delivered auditory stimulation to bobwhite quail groups during early, middle, or late embryogenesis, and then tested postnatal behavioral responsiveness to auditory or visual cues. Auditory preference tendencies were more consistently toward the conspecific stimulus for animals stimulated during late embryogenesis. Groups stimulated during middle or late embryogenesis showed altered postnatal species-typical visual responsiveness, demonstrating a persistent multimodal effect. We also examined whether auditory-related brain regions are receptive to extrinsic input during middle embryogenesis by measuring postnatal cellular activation. Stimulated birds showed a greater number of ZENK-immunopositive cells per unit volume of brain tissue in deep optic tectum, a midbrain region strongly implicated in multimodal function. We observed similar results in the medial and caudomedial nidopallia in the telencephalon. There were no ZENK differences between groups in inferior colliculus or in caudolateral nidopallium, avian analog to prefrontal cortex. To our knowledge, these are the first results linking extrinsic stimulation delivered so early in embryogenesis to changes in postnatal multimodal behavior and cellular activation. The potential role of competitive interactions between the sensory and motor systems is discussed. PMID:18777564

Extracellular matrix motion and early morphogenesis.

PubMed

Loganathan, Rajprasad; Rongish, Brenda J; Smith, Christopher M; Filla, Michael B; Czirok, Andras; Bénazéraf, Bertrand; Little, Charles D

2016-06-15

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale 'total' cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. © 2016. Published by The Company of Biologists Ltd.

Total cellular glycomics allows characterizing cells and streamlining the discovery process for cellular biomarkers.

PubMed

Fujitani, Naoki; Furukawa, Jun-ichi; Araki, Kayo; Fujioka, Tsuyoshi; Takegawa, Yasuhiro; Piao, Jinhua; Nishioka, Taiki; Tamura, Tomohiro; Nikaido, Toshio; Ito, Makoto; Nakamura, Yukio; Shinohara, Yasuro

2013-02-05

Although many of the frequently used pluripotency biomarkers are glycoconjugates, a glycoconjugate-based exploration of novel cellular biomarkers has proven difficult due to technical difficulties. This study reports a unique approach for the systematic overview of all major classes of oligosaccharides in the cellular glycome. The proposed method enabled mass spectrometry-based structurally intensive analyses, both qualitatively and quantitatively, of cellular N- and O-linked glycans derived from glycoproteins, glycosaminoglycans, and glycosphingolipids, as well as free oligosaccharides of human embryonic stem cells (hESCs), induced pluripotent stem cells (hiPSCs), and various human cells derived from normal and carcinoma cells. Cellular total glycomes were found to be highly cell specific, demonstrating their utility as unique cellular descriptors. Structures of glycans of all classes specifically observed in hESCs and hiPSCs tended to be immature in general, suggesting the presence of stem cell-specific glycosylation spectra. The current analysis revealed the high similarity of the total cellular glycome between hESCs and hiPSCs, although it was suggested that hESCs are more homogeneous than hiPSCs from a glycomic standpoint. Notably, this study enabled a priori identification of known pluripotency biomarkers such as SSEA-3, -4, and -5 and Tra-1-60/81, as well as a panel of glycans specifically expressed by hESCs and hiPSCs.

Quartz exposure, retention, and early silicosis in sheep.

PubMed

Bégin, R; Dufresne, A; Cantin, A; Possmayer, F; Sébastien, P; Fabi, D; Bilodeau, G; Martel, M; Bisson, D; Pietrowski, B

1989-05-01

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To

Molecular and Cellular Aspects of Calcific Aortic Valve Disease

PubMed Central

Towler, Dwight A.

2014-01-01

Calcific aortic valve disease (CAVD) increasingly afflicts our aging population. One-third of our elderly have echocardiographic or radiological evidence of aortic valve sclerosis (CAVS), an early and subclinical form of CAVD. Age, gender, tobacco use, hypercholesterolemia, hypertension, and type II diabetes all contribute to the risk of disease that has worldwide distribution. Upon progression to its most severe form --- calcific aortic stenosis (CAS) --- CAVD becomes debilitating and devastating, and 2% of individuals over age 60 suffer from CAS to the extent that surgical intervention is required. No effective pharmacotherapies exist for treating those at risk for clinical progression. It is becoming increasingly apparent that a diverse spectrum of cellular and molecular mechanisms converge to regulate valvular calcium load; this is evidenced not only in histopathologic heterogeneity of CAVD but also from the multiplicity of cell types that can participate in valve biomineralization. In this review, we highlight our current understanding of CAVD disease biology, emphasizing molecular and cellular aspects of its regulation. We end by pointing to important biological and clinical questions that must be answered to enable sophisticated disease staging and the development of new strategies to medically treat CAVD. PMID:23833294

Membrane-Based Functions in the Origin of Cellular Life

NASA Technical Reports Server (NTRS)

Chipot, Christophe; New, Michael H.; Schweighofer, Karl; Pohorille, Andrew; Wilson, Michael A.

1999-01-01

Our objective is to help explain how the earliest ancestors of contemporary cells (protocells) performed their essential functions employing only the molecules available in the protobiological milieu. Our hypothesis is that vesicles, built of amphiphilic, membrane-forming materials, emerged early in protobiological evolution and served as precursors to protocells. We further assume that the cellular functions associated with contemporary membranes, such as capturing and, transducing of energy, signaling, or sequestering organic molecules and ions, evolved in these membrane environments. An alternative hypothesis is that these functions evolved in different environments and were incorporated into membrane-bound structures at some later stage of evolution. We focus on the application of the fundamental principles of physics and chemistry to determine how they apply to the formation of a primitive, functional cell. Rather than attempting to develop specific models for cellular functions and to identify the origin of the molecules which perform these functions, our goal is to define the structural and energetic conditions that any successful model must fulfill, therefore providing physico-chemical boundaries for these models. We do this by carrying out large-scale, molecular level computer simulations on systems of interest.

Refining Raindrop Paleobarometry: A Satus Report

NASA Astrophysics Data System (ADS)

Zimmerman, J. K.; Som, S. M.

2016-12-01

In the late Archaean eon, a sun that was approximately 20% dimmer than today's was still able to warm the Earth to the point where there was liquid water. This is known as the `Faint Young Sun' paradox. Explanations of this paradox include a denser atmosphere rich in nitrogen1 or higher greenhouse gas concentrations. Recent work has suggested that the partial pressure of nitrogen in the late Archean was less than modern values, up to a maximum of 0.5 bar 2.7 billion years ago2. In the current work, we have compiled several global datasets on modern raindrop size and rainfall rate. Together with existing scaling on how raindrop size affects the size of resultant craters3, we use the full distribution of fossilized raindrop craters found in the Ventersdorp Supergroup, South Africa to draw conclusions about the difference in terminal velocity through the Archaean atmosphere as compared to today, in addition to inferences on rainfall rate that formed the Ventersdorp imprints. The calculated value of the terminal velocity places bounds on the range of possible densities of the Archaean atmosphere during Ventersdorp deposition. 1 Goldblatt, C., et al. "Nitrogen-enhanced greenhouse warming on early Earth." Nature Geoscience 2 (2009): 891-896. 2 Som, S., et al. "Earth's air pressure 2.7 billion years ago constrained to less than half of modern levels." Nature Geoscience (2016). 3 Som, S., et al. "Air density 2.7 billion years ago limited to less than twice modern levels by fossil raindrop imprints." Nature 484.7394 (2012): 359-362.

Cytomegalovirus: pathophysiological mechanisms of the cytomegalovirus-induced cellular responses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nokta, M.A.

1986-01-01

Cytomegalovirus (CMV) infection of fibroblasts of human origin is associated with a cascade of morphologic cellular responses which in other systems have been associated with regulation of intracellular free (IF) (Ca/sup + +/). In the present study, the relationship of specific ion fluxes (Ca/sup + +/, Na/sup +/) to the development of cytomegalovirus (CMV)-induced morphologic cellular responses was investigated. An influx of Ca/sup + +/ was observed by the first hour after CMV infection (PI), and total calcium sequestered by infected cells was enhanced by 5 hr Pl. A gradual rise in intracellular free (IF) (Ca/sup + +/) was observedmore » that continued through 48 hour postinfection (hr Pl). The IF (Ca/sup + +/) response to CMV infection was shown to be multiplicity dependent, require viable virus, and occur under conditions consistent with the expression of immediate early CMV genes. Development and progression of cytomegaly was found to be independent of CMV DNA synthesis and appeared to be dependent on the IF (Ca/sup + +/) response. Ca/sup + +/ influx blockers (e.g. verapamil) and cyclic nucleotide modulators (e.g. papaverine) inhibited both Ca/sup + +/ responses and cytomegaly. Quabain-sensitive /sup 86/Rb uptake and sequestering of Ca/sup + +/ increased in parallel with development of cytomegaly. There may be a relationship between Ca/sup + +/ influx, IF (Ca/sup + +/), activation of the Na/sup +//H/sup +/ exchanger, induction of Na/sup +/, Cl/sup -/, HCO/sub 3/ cotransport, Na/sup +/ entry, Na/sup +//K/sup +/ ATPase activity and development of CMV-induced morphologic cellular responses including cytomegaly.« less

Cellular Angiofibroma of the Nasopharynx.

PubMed

Erdur, Zülküf Burak; Yener, Haydar Murat; Yilmaz, Mehmet; Karaaltin, Ayşegül Batioğlu; Inan, Hakki Caner; Alaskarov, Elvin; Gozen, Emine Deniz

2017-11-01

Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

Transient inter-cellular polymeric linker.

PubMed

Ong, Siew-Min; He, Lijuan; Thuy Linh, Nguyen Thi; Tee, Yee-Han; Arooz, Talha; Tang, Guping; Tan, Choon-Hong; Yu, Hanry

2007-09-01

Three-dimensional (3D) tissue-engineered constructs with bio-mimicry cell-cell and cell-matrix interactions are useful in regenerative medicine. In cell-dense and matrix-poor tissues of the internal organs, cells support one another via cell-cell interactions, supplemented by small amount of the extra-cellular matrices (ECM) secreted by the cells. Here we connect HepG2 cells directly but transiently with inter-cellular polymeric linker to facilitate cell-cell interaction and aggregation. The linker consists of a non-toxic low molecular-weight polyethyleneimine (PEI) backbone conjugated with multiple hydrazide groups that can aggregate cells within 30 min by reacting with the aldehyde handles on the chemically modified cell-surface glycoproteins. The cells in the cellular aggregates proliferated; and maintained the cortical actin distribution of the 3D cell morphology while non-aggregated cells died over 7 days of suspension culture. The aggregates lost distinguishable cell-cell boundaries within 3 days; and the ECM fibers became visible around cells from day 3 onwards while the inter-cellular polymeric linker disappeared from the cell surfaces over time. The transient inter-cellular polymeric linker can be useful for forming 3D cellular and tissue constructs without bulk biomaterials or extensive network of engineered ECM for various applications.

Spreading continents kick-started plate tectonics.

PubMed

Rey, Patrice F; Coltice, Nicolas; Flament, Nicolas

2014-09-18

Stresses acting on cold, thick and negatively buoyant oceanic lithosphere are thought to be crucial to the initiation of subduction and the operation of plate tectonics, which characterizes the present-day geodynamics of the Earth. Because the Earth's interior was hotter in the Archaean eon, the oceanic crust may have been thicker, thereby making the oceanic lithosphere more buoyant than at present, and whether subduction and plate tectonics occurred during this time is ambiguous, both in the geological record and in geodynamic models. Here we show that because the oceanic crust was thick and buoyant, early continents may have produced intra-lithospheric gravitational stresses large enough to drive their gravitational spreading, to initiate subduction at their margins and to trigger episodes of subduction. Our model predicts the co-occurrence of deep to progressively shallower mafic volcanics and arc magmatism within continents in a self-consistent geodynamic framework, explaining the enigmatic multimodal volcanism and tectonic record of Archaean cratons. Moreover, our model predicts a petrological stratification and tectonic structure of the sub-continental lithospheric mantle, two predictions that are consistent with xenolith and seismic studies, respectively, and consistent with the existence of a mid-lithospheric seismic discontinuity. The slow gravitational collapse of early continents could have kick-started transient episodes of plate tectonics until, as the Earth's interior cooled and oceanic lithosphere became heavier, plate tectonics became self-sustaining.

Cellular retinoic acid bioavailability in various pathologies and its therapeutic implication.

PubMed

Osanai, Makoto

2017-06-01

Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling molecule in various cell types. We found that RA depletion caused by expression of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that the biological effect of RA on target cells is primarily determined by "cellular RA bioavailability", which is defined as the RA level in an individual cell, rather than by the serum concentration of RA. Consistently, stellate cells store approximately 80% of vitamin A in the body, and the state of cellular RA bioavailability regulates their function. Based on the similarities between stellate cells and astrocytes, we demonstrated that retinal astrocytes regulate tight junction-based endothelial integrity in a paracrine manner. Since diabetic retinopathy is characterized by increased vascular permeability in its early pathogenesis, RA normalized retinal astrocytes that are compromised in diabetes, resulting in suppression of vascular leakiness. RA also attenuated the loss of the epithelial barrier in murine experimental colitis. The concept of "cellular RA bioavailability" in various diseases will be directed at understanding various pathologies caused by RA insufficiency, implying the potential feasibility of a therapeutic strategy targeting the stellate cell system. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington's disease CAG knock-in mice across multiple genetic backgrounds.

PubMed

Ament, Seth A; Pearl, Jocelynn R; Grindeland, Andrea; St Claire, Jason; Earls, John C; Kovalenko, Marina; Gillis, Tammy; Mysore, Jayalakshmi; Gusella, James F; Lee, Jong-Min; Kwak, Seung; Howland, David; Lee, Min Young; Baxter, David; Scherler, Kelsey; Wang, Kai; Geman, Donald; Carroll, Jeffrey B; MacDonald, Marcy E; Carlson, George; Wheeler, Vanessa C; Price, Nathan D; Hood, Leroy E

2017-03-01

Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+  mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cellular senescence and organismal aging.

PubMed

Jeyapalan, Jessie C; Sedivy, John M

2008-01-01

Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

Cellular senescence and organismal aging

PubMed Central

Jeyapalan, Jessie C.; Sedivy, John M.

2012-01-01

Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging. PMID:18502472

Calcium movements and the cellular basis of gravitropism

NASA Astrophysics Data System (ADS)

Roux, S. J.; Biro, R. L.; Hale, C. C.

An early gravity-transduction event in oat coleoptiles which precedes any noticeable bending is the accumulation of calcium on their prospective slower-growing side. Sub-cellular calcium localization studies indicate that the gravity-stimulated redistribution of calcium results in an increased concentration of calcium in the walls of responding cells. Since calcium can inhibit the extension growth of plant cell walls, this selective accumulation of calcium in walls may play a role in inducing the asymmetry of growth which characterizes gravitropism. The active transport of calcium from cells into walls is performed by a calcium-dependent ATPase localized in the plasma membrane. Evidence is presented in support of the hypothesis that this calcium pump is regulated by a feed-back mechanism which includes the participation of calmodulin.

Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

PubMed

Jain, Shruti; Bhattacharyya, Kausik; Bakshi, Rachit; Narang, Ankita; Brahmachari, Vani

2017-04-01

The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cellular Homeostasis and Aging.

PubMed

Hartl, F Ulrich

2016-06-02

Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans.

Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis.

PubMed

Reithmair, Marlene; Buschmann, Dominik; Märte, Melanie; Kirchner, Benedikt; Hagl, Daniel; Kaufmann, Ines; Pfob, Martina; Chouker, Alexander; Steinlein, Ortrud K; Pfaffl, Michael W; Schelling, Gustav

2017-10-01

Septic shock is a common medical condition with a mortality approaching 50% where early diagnosis and treatment are of particular importance for patient survival. Novel biomarkers that serve as prompt indicators of sepsis are urgently needed. High-throughput technologies assessing circulating microRNAs represent an important tool for biomarker identification, but the blood-compartment specificity of these miRNAs has not yet been investigated. We characterized miRNA profiles from serum exosomes, total serum and blood cells (leukocytes, erythrocytes, platelets) of sepsis patients by next-generation sequencing and RT-qPCR (n = 3 × 22) and established differences in miRNA expression between blood compartments. In silico analysis was used to identify compartment-specific signalling functions of differentially regulated miRNAs in sepsis-relevant pathways. In septic shock, a total of 77 and 103 miRNAs were down- and up-regulated, respectively. A majority of these regulated miRNAs (14 in serum, 32 in exosomes and 73 in blood cells) had not been previously associated with sepsis. We found a distinctly compartment-specific regulation of miRNAs between sepsis patients and healthy volunteers. Blood cellular miR-199b-5p was identified as a potential early indicator for sepsis and septic shock. miR-125b-5p and miR-26b-5p were uniquely regulated in exosomes and serum, respectively, while one miRNA (miR-27b-3p) was present in all three compartments. The expression of sepsis-associated miRNAs is compartment-specific. Exosome-derived miRNAs contribute significant information regarding sepsis diagnosis and survival prediction and could serve as newly identified targets for the development of novel sepsis biomarkers. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

47 CFR 90.672 - Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part...

Code of Federal Regulations, 2011 CFR

2011-10-01

... MHz licensees from 800 MHz cellular systems or part 22 Cellular Radiotelephone systems, and within the... COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES... licensees from 800 MHz cellular systems or part 22 Cellular Radiotelephone systems, and within the 900 MHz...

Cellular registration without behavioral recall of olfactory sensory input under general anesthesia.

PubMed

Samuelsson, Andrew R; Brandon, Nicole R; Tang, Pei; Xu, Yan

2014-04-01

Previous studies suggest that sensory information is "received" but not "perceived" under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. One hundred seven rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. The olfactory sensory processing centers could distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Reexposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity, which was similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the "cellular memory," however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Histologically distinguishable registration of sensory processing continues to occur at the cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications.

A role for autophagic protein beclin 1 early in lymphocyte development.

PubMed

Arsov, Ivica; Adebayo, Adeola; Kucerova-Levisohn, Martina; Haye, Joanna; MacNeil, Margaret; Papavasiliou, F Nina; Yue, Zhenyu; Ortiz, Benjamin D

2011-02-15

Autophagy is a highly regulated and evolutionarily conserved process of cellular self-digestion. Recent evidence suggests that this process plays an important role in regulating T cell homeostasis. In this study, we used Rag1(-/-) (recombination activating gene 1(-/-)) blastocyst complementation and in vitro embryonic stem cell differentiation to address the role of Beclin 1, one of the key autophagic proteins, in lymphocyte development. Beclin 1-deficient Rag1(-/-) chimeras displayed a dramatic reduction in thymic cellularity compared with control mice. Using embryonic stem cell differentiation in vitro, we found that the inability to maintain normal thymic cellularity is likely caused by impaired maintenance of thymocyte progenitors. Interestingly, despite drastically reduced thymocyte numbers, the peripheral T cell compartment of Beclin 1-deficient Rag1(-/-) chimeras is largely normal. Peripheral T cells displayed normal in vitro proliferation despite significantly reduced numbers of autophagosomes. In addition, these chimeras had greatly reduced numbers of early B cells in the bone marrow compared with controls. However, the peripheral B cell compartment was not dramatically impacted by Beclin 1 deficiency. Collectively, our results suggest that Beclin 1 is required for maintenance of undifferentiated/early lymphocyte progenitor populations. In contrast, Beclin 1 is largely dispensable for the initial generation and function of the peripheral T and B cell compartments. This indicates that normal lymphocyte development involves Beclin 1-dependent, early-stage and distinct, Beclin 1-independent, late-stage processes.

The early cellular signatures of protective immunity induced by live viral vaccination.

PubMed

Kohler, Siegfried; Bethke, Nicole; Böthe, Matthias; Sommerick, Sophie; Frentsch, Marco; Romagnani, Chiara; Niedrig, Matthias; Thiel, Andreas

2012-09-01

Here, we have used primary vaccination of healthy donors with attenuated live yellow fever virus 17D (YFV-17D) as a model to study the generation of protective immunity. In short intervals after vaccination, we analyzed the induction of YFV-17D specific T- and B-cell immunity, bystander activation, dendritic cell subsets, changes in serum cytokine levels, and YFV-17D-specific antibodies. We show activation of innate immunity and a concomitant decline of numbers of peripheral blood T and B cells. An early peak of antigen-specific T cells at day 2, followed by mobilization of innate immune cells, preceded the development of maximal adaptive immunity against YFV-17D at day 14 after vaccination. Interestingly, potent adaptive immunity as measured by high titers of neutralizing YFV-17D-specific antibodies, correlated with early activation and recruitment of YFV-17D-specific CD4(+) T cells and higher levels of sIL-6R. Thus our data might provide new insights into the interplay of innate and adaptive immunity for the induction of protective immunity. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The ECM moves during primitive streak formation--computation of ECM versus cellular motion.

PubMed

Zamir, Evan A; Rongish, Brenda J; Little, Charles D

2008-10-14

Galileo described the concept of motion relativity--motion with respect to a reference frame--in 1632. He noted that a person below deck would be unable to discern whether the boat was moving. Embryologists, while recognizing that embryonic tissues undergo large-scale deformations, have failed to account for relative motion when analyzing cell motility data. A century of scientific articles has advanced the concept that embryonic cells move ("migrate") in an autonomous fashion such that, as time progresses, the cells and their progeny assemble an embryo. In sharp contrast, the motion of the surrounding extracellular matrix scaffold has been largely ignored/overlooked. We developed computational/optical methods that measure the extent embryonic cells move relative to the extracellular matrix. Our time-lapse data show that epiblastic cells largely move in concert with a sub-epiblastic extracellular matrix during stages 2 and 3 in primitive streak quail embryos. In other words, there is little cellular motion relative to the extracellular matrix scaffold--both components move together as a tissue. The extracellular matrix displacements exhibit bilateral vortical motion, convergence to the midline, and extension along the presumptive vertebral axis--all patterns previously attributed solely to cellular "migration." Our time-resolved data pose new challenges for understanding how extracellular chemical (morphogen) gradients, widely hypothesized to guide cellular trajectories at early gastrulation stages, are maintained in this dynamic extracellular environment. We conclude that models describing primitive streak cellular guidance mechanisms must be able to account for sub-epiblastic extracellular matrix displacements.

Origami interleaved tube cellular materials

NASA Astrophysics Data System (ADS)

Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-09-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

Perspectives and Open Problems in the Early Phases of Left-Right Patterning

PubMed Central

Vandenberg, Laura N.; Levin, Michael

2009-01-01

Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

Designing a new three-dimensional periodic cellular auxetic material

NASA Astrophysics Data System (ADS)

Zhou, Yiyi; Chen, Lianmen

2017-07-01

Auxetics are materials showing a negative Poisson’s ratio. Early research found several categories of auxetic materials in the chemical field. Later research identified the fundamental mechanism generating this behavior is rotation; a variety of two-dimensional auxetic material have been generated accordingly. Nevertheless, the successful example of three-dimensional auxetic material is still rare. This paper introduces a new design of three-dimensional periodic cellular auxetic material based on geometrical and mechanical methodology. The projections of the optimized periodic modules in two horizontal directions are geometrically same with auxetic hexahedral poem, so that the optimized periodic material can perform auxetic in both two horizontal directions under vertical compression. Parametric model is simulated to prove the design.

Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.

PubMed

Hashimoto, Kyoichi; Yamada, Yosuke; Semi, Katsunori; Yagi, Masaki; Tanaka, Akito; Itakura, Fumiaki; Aoki, Hitomi; Kunisada, Takahiro; Woltjen, Knut; Haga, Hironori; Sakai, Yoshiharu; Yamamoto, Takuya; Yamada, Yasuhiro

2017-01-24

The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an Apc Min/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion.

Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior

PubMed Central

Hashimoto, Kyoichi; Yamada, Yosuke; Semi, Katsunori; Yagi, Masaki; Tanaka, Akito; Itakura, Fumiaki; Aoki, Hitomi; Kunisada, Takahiro; Woltjen, Knut; Haga, Hironori; Sakai, Yoshiharu; Yamamoto, Takuya; Yamada, Yasuhiro

2017-01-01

The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an ApcMin/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion. PMID:28057861

Resveratrol Inhibition of Cellular Respiration: New Paradigm for an Old Mechanism

PubMed Central

Madrigal-Perez, Luis Alberto; Ramos-Gomez, Minerva

2016-01-01

Resveratrol (3,4′,5-trihydroxy-trans-stilbene, RSV) has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1) decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2) increases adenosine monophosphate/adenosine diphosphate (AMP/ADP) ratio that can lead to AMP protein kinase (AMPK) activation, which is related to its health effects, and (3) increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol. PMID:26999118

Activation of cellular immune response in acute pancreatitis.

PubMed Central

Mora, A; Pérez-Mateo, M; Viedma, J A; Carballo, F; Sánchez-Payá, J; Liras, G

1997-01-01

BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity. PMID:9245935

Microfossils of the Early Archean Apex chert - New evidence of the antiquity of life

NASA Technical Reports Server (NTRS)

Schopf, J. W.

1993-01-01

Eleven taxa (including eight heretofore undescribed species) of cellularly preserved filamentous microbes, among the oldest fossils known, have been discovered in a bedded chert unit of the Early Archean Apex Basalt of northwestern Western Australia. This prokaryotic assemblage establishes that trichomic cyanobacteriumlike microorganisms were extant and morphologically diverse at least as early as about 3465 million years ago and suggests that oxygen-producing photoautotrophy may have already evolved by this early stage in biotic history.

A basin on an unstable ground: Correlation of the Middle Archaean Moodies Basin, Barberton Greenstone Belt, South Africa

NASA Astrophysics Data System (ADS)

Ohnemueller, Frank; Heubeck, Christoph; Kirstein, Jens; Gamper, Antonia

2010-05-01

time and immediately predates the initiation of basin shortening. Basin compartmentalization was likely due to the movement along a group of major faults (Sheba, Haki, Barbrook, Saddleback Faults) between the present Saddleback and Eureka Synclines, creating at least two subbasins in late Moodies time. Even though sediment provenance thus became localized, intensive Archaean weathering likely contributed to generate petrographically similar quartz-rich sandstones in fault-bounded minibasins. The late-Moodies minibasins may have become connected occasionally, allowing concurrent deposition of thin BIFs. A similar phase of movement along the major transcurrent Inyoka Fault may be responsible for the distinct petrographic character of Moodies sandstones south of that fault.

Bridging Two Worlds: From the Archean to the Proterozoic

NASA Technical Reports Server (NTRS)

Schopf, J. William

2000-01-01

As now known, the Archean and Proterozoic appear to have been different worlds: the geology (tectonic style, basinal distribution, dominant rock types), atmospheric composition (O2, CO21, CH4), and surface environment (day-length, solar luminosity, ambient temperature) all appear to have changed over time. And virtually all paleobiologic indicators can be interpreted as suggesting there were significant biotic differences as well: (1) Stromatolites older than 2.5 Ga are rare relative to those of the Proterozoic; their biotic components are largely unknown; and the biogenicity of those older than approx. 3.2 Ga has been questioned. (2) Bona fide microfossils older than approx. 2.4 Ga are rare, poorly preserved, and of uncertain biological relations. Gaps of hundreds of millions of years in the known record make it impossible to show that Archean microorganisms are definitely part of the 2.4 Ga-to-present evolutionary continuum. and (3) In rocks older than approx. 2.2 Ga, the sulfur isotopic record is subject to controversy; phylogenetically distinctive bio-markers are unknown; and nearly a score of geologic units contain organic carbon anomalously light isotopically (relative to that of the Proterozoic and Phanerozoic) that may reflect the presence of Archaeans ("Archaebacteria of earlier classifications) but may not (since cellularly preserved Archean-age Archaeans have never been identified).

Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense oligonucleotides

PubMed Central

Wang, Shiyu; Allen, Nickolas; Vickers, Timothy A; Revenko, Alexey S; Sun, Hong; Liang, Xue-hai; Crooke, Stanley T

2018-01-01

Abstract Chemically modified antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages have been extensively studied as research and therapeutic agents. PS-ASOs can enter the cell and trigger cleavage of complementary RNA by RNase H1 even in the absence of transfection reagent. A number of cell surface proteins have been identified that bind PS-ASOs and mediate their cellular uptake; however, the mechanisms that lead to productive internalization of PS-ASOs are not well understood. Here, we characterized the interaction between PS-ASOs and epidermal growth factor receptor (EGFR). We found that PS-ASOs trafficked together with EGF and EGFR into clathrin-coated pit structures. Their co-localization was also observed at early endosomes and inside enlarged late endosomes. Reduction of EGFR decreased PS-ASO activity without affecting EGF-mediated signaling pathways and overexpression of EGFR increased PS-ASO activity in cells. Furthermore, reduction of EGFR delays PS-ASO trafficking from early to late endosomes. Thus, EGFR binds to PS-ASOs at the cell surface and mediates essential steps for active (productive) cellular uptake of PS-ASOs through its cargo-dependent trafficking processes which migrate PS-ASOs from early to late endosomes. This EGFR-mediated process can also serve as an additional model to better understand the mechanism of intracellular uptake and endosomal release of PS-ASOs. PMID:29514240

Protein accounting in the cellular economy.

PubMed

Vázquez-Laslop, Nora; Mankin, Alexander S

2014-04-24

Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the functional needs. Copyright © 2014 Elsevier Inc. All rights reserved.

Origins of cellular geometry

PubMed Central

2011-01-01

Cells are highly complex and orderly machines, with defined shapes and a startling variety of internal organizations. Complex geometry is a feature of both free-living unicellular organisms and cells inside multicellular animals. Where does the geometry of a cell come from? Many of the same questions that arise in developmental biology can also be asked of cells, but in most cases we do not know the answers. How much of cellular organization is dictated by global cell polarity cues as opposed to local interactions between cellular components? Does cellular structure persist across cell generations? What is the relationship between cell geometry and tissue organization? What ensures that intracellular structures are scaled to the overall size of the cell? Cell biology is only now beginning to come to grips with these questions. PMID:21880160

Epigenetics and Cellular Metabolism

PubMed Central

Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

2016-01-01

Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties.

PubMed

Katira, Parag; Bonnecaze, Roger T; Zaman, Muhammad H

2013-01-01

Malignant transformation, though primarily driven by genetic mutations in cells, is also accompanied by specific changes in cellular and extra-cellular mechanical properties such as stiffness and adhesivity. As the transformed cells grow into tumors, they interact with their surroundings via physical contacts and the application of forces. These forces can lead to changes in the mechanical regulation of cell fate based on the mechanical properties of the cells and their surrounding environment. A comprehensive understanding of cancer progression requires the study of how specific changes in mechanical properties influences collective cell behavior during tumor growth and metastasis. Here we review some key results from computational models describing the effect of changes in cellular and extra-cellular mechanical properties and identify mechanistic pathways for cancer progression that can be targeted for the prediction, treatment, and prevention of cancer.

Cellular regeneration strategies for macular degeneration: past, present and future.

PubMed

Chichagova, Valeria; Hallam, Dean; Collin, Joseph; Zerti, Darin; Dorgau, Birthe; Felemban, Majed; Lako, Majlinda; Steel, David H

2018-05-01

Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Early patterning and specification of cardiac progenitors in gastrulating mesoderm

PubMed Central

Devine, W Patrick; Wythe, Joshua D; George, Matthew; Koshiba-Takeuchi, Kazuko; Bruneau, Benoit G

2014-01-01

Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor ‘fields’ has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies. DOI: http://dx.doi.org/10.7554/eLife.03848.001 PMID:25296024

Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

PubMed

Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

2009-09-01

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

Early Archean (approximately 3.4 Ga) prokaryotic filaments from cherts of the apex basalt, Western Australia: The oldest cellularly preserved microfossils now known

NASA Technical Reports Server (NTRS)

Schopf, J. W.

1991-01-01

In comparison with that known from later geologic time, the Archean fossil record is miniscule: although literally hundreds of Proterozoic formations, containing more that 2800 occurrences of bona fide microfossils are now known, fewer than 30 units containing some 43 categories of putative microfossils (the vast majority of which are of questionable authenticity) have been reported from the Archean. Among the oldest known fossils are Early Archean filaments reported from cherts of the Towers Formation and the Apex Basalt of the 3.3-3.6 Ga-old Warrawoona Group of Western Australia. The paleobiologic significance of the Towers Formation microstructures is open to question: thin aggregated filaments are properly regarded as dubiomicrofossils (perhaps biogenic, but perhaps not); therefore, they cannot be regarded as firm evidence of Archean life. Although authentic, filamentous microfossiles were reported from a second Towers Formation locality, because the precise layer containing the fossiliferous cherts was not relocated, this discovery can neither be reconfirmed by the original collector nor confirmed independently by other investigators. Discovery of microfossils in bedded cherts of the Apex Basalt, the stratigraphic unit immediately overlying the Towers Formation, obviates the difficulties stored above. The cellularly preserved filaments of the Apex Basalt meet all of the criteria required of a bona fide Archean microfossils. Recent studies indicate that the Apex assemblage includes at least six morphotypes of uniseriate filaments, composed of barrel-shaped, discoidal, or quadrate cells and exhibiting rounded or conical terminal cells and medial bifurcated and paired half-cells that reflect the occurrence of prokaryotic binary cell division. Interestingly, the majority of these morphotypes are morphologically more similar to extant cyanobacteria than to modern filamentous bacteria. Prokaryotes seem clearly to have been hypobradytelic, and the evidence suggests

New insights into typical Archaean structures in greenstone terranes of western Ontario

NASA Technical Reports Server (NTRS)

Schwerdtner, W. M.

1986-01-01

Ongoing detailed field work in selected granitoid complexes of the western Wabigoon and Wawa Subprovinces, southern Canadian Shield, has led to several new conclusions: (1) Prominent gneiss domes are composed of prestrained tonalite-granodiorite and represent dense hoods of magmatic granitoid diapirs; (2) the deformation history of the prestrained gneiss remains to be unraveled; (3) the gneiss lacked a thick cover of mafic metavolcanics or other dense rocks at the time of magmatic diaprisim; (4) the synclinoral structure of large greenstone belts is older than the late gneiss domes and may have been initiated by volcano-tectonic processes; (5) small greenstone masses within the gneiss are complexly deformed, together with the gneiss; and, (6) no compelling evidence has been found of ductile early thrusting in the gneiss terranes. Zones of greenstone enclaves occur in hornblende-rich contaminated tonalite and are apt to be deformed magmatic septa. Elsewhere, the tonalite gneiss is biotite-rich and hornblende-poor. These conclusions rest on several new pieces of structural evidence; (1) oval plutons of syenite-diorite have magmatic strain fabrics and sharp contacts that are parallel to an axial-plane foliation in the surrounding refolded gneiss; (2) gneiss domes are lithologically composite and contain large sheath-like structures which are deformed early plutons, distorted earlier gneiss domes, or early ductile nappes produced by folding of planar plutonic septa, and (3) the predomal attitudes of gneissosity varied from point to point.

Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

EPA Science Inventory

CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis

PubMed Central

Watanabe, Miki; Muraleedharan, Ranjithmenon; Lambert, Paul F.; Lane, Andrew N.; Romick-Rosendale, Lindsey E.; Wells, Susanne I.

2017-01-01

The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth. PMID:28558019

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis.

PubMed

Matrka, Marie C; Watanabe, Miki; Muraleedharan, Ranjithmenon; Lambert, Paul F; Lane, Andrew N; Romick-Rosendale, Lindsey E; Wells, Susanne I

2017-01-01

The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth.

Cellular Registration Without Behavioral Recall Of Olfactory Sensory Input Under General Anesthesia

PubMed Central

Samuelsson, Andrew R.; Brandon, Nicole R.; Tang, Pei; Xu, Yan

2014-01-01

Background Previous studies suggest that sensory information is “received” but not “perceived” under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. Methods 107 rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. Results The olfactory sensory processing centers can distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Re-exposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the “cellular memory,” however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Conclusions Histologically distinguishable registration of sensory process continues to occur at cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications. PMID:24694846

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

PubMed Central

2013-01-01

Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

PubMed

Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

2013-10-17

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding

Cellular-based preemption system

NASA Technical Reports Server (NTRS)

Bachelder, Aaron D. (Inventor)

2011-01-01

A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

47 CFR 22.923 - Cellular system configuration.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular system configuration. 22.923 Section 22.923 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations...

47 CFR 22.923 - Cellular system configuration.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular system configuration. 22.923 Section 22.923 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations...

Urban Flood Prevention and Early Warning System in Jinan City

NASA Astrophysics Data System (ADS)

Feng, Shiyuan; Li, Qingguo

2018-06-01

The system construction of urban flood control and disaster reduction in China is facing pressure and challenge from new urban water disaster. Under the circumstances that it is difficult to build high standards of flood protection engineering measures in urban areas, it is particularly important to carry out urban flood early warning. In Jinan City, a representative inland area, based on the index system of early warning of flood in Jinan urban area, the method of fuzzy comprehensive evaluation was adopted to evaluate the level of early warning. Based on the cumulative rainfall of 3 hours, the CAflood simulation results based on cellular automaton model of urban flooding were used as evaluation indexes to realize the accuracy and integration of urban flood control early warning.

Probabilistic Cellular Automata

PubMed Central

Agapie, Alexandru; Giuclea, Marius

2014-01-01

Abstract Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case—connecting the probability of a configuration in the stationary distribution to its number of zero-one borders—the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata. PMID:24999557

Probabilistic cellular automata.

PubMed

Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

2014-09-01

Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

Protective cellular responses to Burkholderia mallei infection.

PubMed

Rowland, Caroline A; Lever, M Stephen; Griffin, Kate F; Bancroft, Gregory J; Lukaszewski, Roman A

2010-10-01

Burkholderia mallei is a Gram-negative bacillus causing the disease glanders in humans. During intraperitoneal infection, BALB/c mice develop a chronic disease characterised by abscess formation where mice normally die up to 70 days post-infection. Although cytokine responses have been investigated, cellular immune responses to B. mallei infection have not previously been characterised. Therefore, the influx and activation status of splenic neutrophils, macrophages and T cells was examined during infection. Gr-1+ neutrophils and F4/80+ macrophages infiltrated the spleen 5 h post-infection and an increase in activated macrophages, neutrophils and T cells occurred by 24 h post-infection. Mice depleted of Gr-1+ cells were acutely susceptible to B. mallei infection, succumbing to the infection 5 days post-infection. Mice depleted of both CD4 and CD8 T cells did not succumb to the infection until 14 days post-infection. Infected μMT (B cell) and CD28 knockout mice did not differ from wildtype mice whereas iNOS-2 knockout mice began to succumb to the infection 30 days post-infection. The data presented suggests that Gr-1+ cells, activated early in B. mallei infection, are essential for controlling the early, innate response to B. mallei infection and T cells or nitric oxide are important during the later stages of infection. Crown Copyright © 2010. Published by Elsevier SAS. All rights reserved.

Lineage mapping and characterization of the native progenitor population in cellular allograft.

PubMed

Neman, Josh; Duenas, Vincent; Kowolik, Claudia; Hambrecht, Amanda; Chen, Mike; Jandial, Rahul

2013-02-01

Osteocalcin; and (3) enzyme-linked immunosorbent assays (ELISA) for BMP-2, Osteocalcin, RANKL, Osteoprotegrin, and Osteocalcin. Clonal analysis of cells from cellular allograft was performed utilizing advance lentivirus lineage mapping techniques and massive parallel sequencing. Alizarin Red, Alcian Blue, and Oil red O staining assessed tripotential differentiation capacity. Serial trypsinization of allograft cellular bone matrix yielded approximately 1×105 cells per mL with viability greater than 90%. Cells expressed a panel of 84 MSC-associated genes in a pattern similar to but not identical to pure MSCs; specifically, 59 of 84 genes showed less than a 2.5-fold change in both cell types. Protein analysis showed that cellular allograft -derived cells maintained in nondifferentiation media expressed the early osteo-progenitor markers BMP-2, SMADs, and Runx2. Corresponding flow cytometry data for MSC markers revealed the presence of Stro-1 (49%), CD44 (99%), CD90 (42%), and CD146 (97%). Lineage mapping indicated that 62% of clones persisted and generated progeny through 10 passages, strongly suggesting the presence of bona fide stem cells. Passage 10 clones also exhibited tri-lineage differentiation capacity into osteogenic (Alizarin Red with H&E counterstain), chondrogenic (Alcian Blue), and adipogenic (Oil red O). Cells that did not proliferate through 10 passages presumably differentiated along an osteo-progenitor lineage. These data indicate that cellular allograft (Osteocel Plus) contains a heterogeneous population of cells with most cells demonstrating the capacity for extensive self-renewal and multipotential differentiation, which are hallmarks of stem cells. Whether stem cell-enriched allografts function comparably to autograft will require further studies, and their efficacy in facilitating arthrodesis will depend on randomized clinical studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Tissue morphodynamics shaping the early mouse embryo.

PubMed

Sutherland, Ann E

2016-07-01

Generation of the elongated vertebrate body plan from the initially radially symmetrical embryo requires comprehensive changes to tissue form. These shape changes are generated by specific underlying cell behaviors, coordinated in time and space. Major principles and also specifics are emerging, from studies in many model systems, of the cell and physical biology of how region-specific cell behaviors produce regional tissue morphogenesis, and how these, in turn, are integrated at the level of the embryo. New technical approaches have made it possible more recently, to examine the morphogenesis of the mouse embryo in depth, and to elucidate the underlying cellular mechanisms. This review focuses on recent advances in understanding the cellular basis for the early fundamental events that establish the basic form of the embryo. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fabrication of cellular materials

NASA Astrophysics Data System (ADS)

Prud'homme, Robert K.; Aksay, Ilhan A.; Garg, Rajeev

1996-02-01

Nature uses cellular materials in applications requiring strength while, simultaneously, minimizing raw materials requirements. Minimizing raw materials is efficient both in terms of the energy expended by the organism to synthesize the structure and in terms of the strength- to-weight ratio of the structure. Wood is the most obvious example of cellular bio-materials, and it is the focus of other presentations in this symposium. The lightweight bone structure of birds is another excellent example where weight is a key criterion. The anchoring foot of the common muscle [Mytilus edulis] whereby it attaches itself to objects is a further example of a biological system that uses a foam to fill space and yet conserve on raw materials. In the case of the muscle the foam is water filled and the foot structure distributes stress over a larger area so that the strength of the byssal thread from which it is suspended is matched to the strength of interfacial attachment of the foot to a substrate. In these examples the synthesis and fabrication of the cellular material is directed by intercellular, genetically coded, biochemical reactions. The resulting cell sizes are microns in scale. Cellular materials at the next larger scale are created by organisms at the next higher level of integration. For example an African tree frog lays her eggs in a gas/fluid foam sack she builds on a branch overhanging a pond. The outside of the foam sack hardens in the sun and prevents water evaporation. The foam structure minimizes the amount of fluid that needs to be incorporated into the sack and minimizes its weight. However, as far as the developing eggs are concerned, they are in an aqueous medium, i.e. the continuous fluid phase of the foam. After precisely six days the eggs hatch, and the solidified outer wall re-liquefies and dumps the emerging tadpoles into the pond below. The bee honeycomb is an example of a cellular material with exquisite periodicity at millimeter length scales. The

Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

PubMed

Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

1995-02-06

EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy.

PubMed

Szalai, Eszter; Deák, Eszter; Módis, László; Németh, Gábor; Berta, András; Nagy, Annamária; Felszeghy, Eniko; Káposzta, Rita; Malik, Rayaz A; Csutak, Adrienne

2016-03-01

The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy. A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM). We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects. Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

47 CFR 22.901 - Cellular service requirements and limitations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and limitations. The licensee of each cellular system is responsible for ensuring that its cellular system operates in compliance with this section. (a) Each cellular system must provide either mobile service...

Pericentrin in cellular function and disease

PubMed Central

Delaval, Benedicte

2010-01-01

Pericentrin is an integral component of the centrosome that serves as a multifunctional scaffold for anchoring numerous proteins and protein complexes. Through these interactions, pericentrin contributes to a diversity of fundamental cellular processes. Recent studies link pericentrin to a growing list of human disorders. Studies on pericentrin at the cellular, molecular, and, more recently, organismal level, provide a platform for generating models to elucidate the etiology of these disorders. Although the complexity of phenotypes associated with pericentrin-mediated disorders is somewhat daunting, insights into the cellular basis of disease are beginning to come into focus. In this review, we focus on human conditions associated with loss or elevation of pericentrin and propose cellular and molecular models that might explain them. PMID:19951897

The iodine–plutonium–xenon age of the Moon–Earth system revisited

PubMed Central

Avice, G.; Marty, B

2014-01-01

Iodine–plutonium–xenon isotope systematics have been used to re-evaluate time constraints on the early evolution of the Earth–atmosphere system and, by inference, on the Moon-forming event. Two extinct radionuclides (129I, T1/2=15.6 Ma and 244Pu, T1/2=80 Ma) have produced radiogenic 129Xe and fissiogenic 131−136Xe, respectively, within the Earth, the related isotope fingerprints of which are seen in the compositions of mantle and atmospheric Xe. Recent studies of Archaean rocks suggest that xenon atoms have been lost from the Earth's atmosphere and isotopically fractionated during long periods of geological time, until at least the end of the Archaean eon. Here, we build a model that takes into account these results. Correction for Xe loss permits the computation of new closure ages for the Earth's atmosphere that are in agreement with those computed for mantle Xe. The corrected Xe formation interval for the Earth–atmosphere system is  Ma after the beginning of Solar System formation. This time interval may represent a lower limit for the age of the Moon-forming impact. PMID:25114317

Cellular phone use while driving at night.

PubMed

Vivoda, Jonathon M; Eby, David W; St Louis, Renée M; Kostyniuk, Lidia P

2008-03-01

Use of a cellular phone has been shown to negatively affect one's attention to the driving task, leading to an increase in crash risk. At any given daylight hour, about 6% of US drivers are actively talking on a hand-held cell phone. However, previous surveys have focused only on cell phone use during the day. Driving at night has been shown to be a riskier activity than driving during the day. The purpose of the current study was to assess the rate of hand-held cellular phone use while driving at night, using specialized night vision equipment. In 2006, two statewide direct observation survey waves of nighttime cellular phone use were conducted in Indiana utilizing specialized night vision equipment. Combined results of driver hand-held cellular phone use from both waves are presented in this manuscript. The rates of nighttime cell phone use were similar to results found in previous daytime studies. The overall rate of nighttime hand-held cellular phone use was 5.8 +/- 0.6%. Cellular phone use was highest for females and for younger drivers. In fact, the highest rate observed during the study (of 11.9%) was for 16-to 29-year-old females. The high level of cellular phone use found within the young age group, coupled with the increased crash risk associated with cellular phone use, nighttime driving, and for young drivers in general, suggests that this issue may become an important transportation-related concern.

Abundance and diversity of Archaea in heavy-metal-contaminated soils.

PubMed

Sandaa, R A; Enger, O; Torsvik, V

1999-08-01

The impact of heavy-metal contamination on archaean communities was studied in soils amended with sewage sludge contaminated with heavy metals to varying extents. Fluorescent in situ hybridization showed a decrease in the percentage of Archaea from 1.3% +/- 0.3% of 4', 6-diamidino-2-phenylindole-stained cells in untreated soil to below the detection limit in soils amended with heavy metals. A comparison of the archaean communities of the different plots by denaturing gradient gel electrophoresis revealed differences in the structure of the archaean communities in soils with increasing heavy-metal contamination. Analysis of cloned 16S ribosomal DNA showed close similarities to a unique and globally distributed lineage of the kingdom Crenarchaeota that is phylogenetically distinct from currently characterized crenarchaeotal species.

Visualization of self-delivering hydrophobically modified siRNA cellular internalization

PubMed Central

Ly, Socheata; Navaroli, Deanna M.; Didiot, Marie-Cécile; Cardia, James; Pandarinathan, Lakshmipathi; Alterman, Julia F.; Fogarty, Kevin; Standley, Clive; Lifshitz, Lawrence M.; Bellve, Karl D.; Prot, Matthieu; Echeverria, Dimas; Corvera, Silvia; Khvorova, Anastasia

2017-01-01

siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of asymmetric, chemically stabilized, cholesterol-modified siRNAs (sd-rxRNAs®) that efficiently enter cells and tissues without the need for formulation. We demonstrate that uptake is rapid with significant membrane association within minutes of exposure followed by the formation of vesicular structures and internalization. Furthermore, sd-rxRNAs are internalized by a specific class of early endosomes and show preferential association with epidermal growth factor (EGF) but not transferrin (Tf) trafficking pathways as shown by live cell TIRF and structured illumination microscopy (SIM). In fixed cells, we observe ∼25% of sd-rxRNA co-localizing with EGF and <5% with Tf, which is indicative of selective endosomal sorting. Likewise, preferential sd-rxRNA co-localization was demonstrated with EEA1 but not RBSN-containing endosomes, consistent with preferential EGF-like trafficking through EEA1-containing endosomes. sd-rxRNA cellular uptake is a two-step process, with rapid membrane association followed by internalization through a selective, saturable subset of the endocytic process. However, the mechanistic role of EEA1 is not yet known. This method of visualization can be used to better understand the kinetics and mechanisms of hydrophobic siRNA cellular uptake and will assist in further optimization of these types of compounds for therapeutic intervention. PMID:27899655

Inter-Cellular Exchange of Cellular Components via VE-Cadherin-Dependent Trans-Endocytosis

PubMed Central

Sakurai, Takashi; Woolls, Melissa J.; Jin, Suk-Won

2014-01-01

Cell-cell communications typically involve receptor-mediated signaling initiated by soluble or cell-bound ligands. Here, we report a unique mode of endocytosis: proteins originating from cell-cell junctions and cytosolic cellular components from the neighboring cell are internalized, leading to direct exchange of cellular components between two adjacent endothelial cells. VE-cadherins form transcellular bridges between two endothelial cells that are the basis of adherence junctions. At such adherens junction sites, we observed the movement of the entire VE-cadherin molecule from one endothelial cell into the other with junctional and cytoplasmic components. This phenomenon, here termed trans-endocytosis, requires the establishment of a VE-cadherin homodimer in trans with internalization proceeding in a Rac1-, and actomyosin-dependent manner. Importantly, the trans-endocytosis is not dependent on any known endocytic pathway including clathrin-dependent endocytosis, macropinocytosis or phagocytosis. This novel form of cell-cell communications, leading to a direct exchange of cellular components, was observed in 2D and 3D-cultured endothelial cells as well as in the developing zebrafish vasculature. PMID:24603875

Mechanical properties of porous and cellular materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sieradzki, K.; Green, D.J.; Gibson, L.J.

1991-01-01

This symposium successfully brought scientists together from a wide variety of disciplines to focus on the mechanical behavior of porous and cellular solids composed of metals, ceramics, polymers, or biological materials. For cellular materials, papers ranged from processing techniques through microstructure-mechanical property relationships to design. In an overview talk, Mike Ashby (Cambridge Univ.) showed how porous cellular materials can be more efficient than dense materials in designs that require minimum weight. He indicated that many biological materials have been able to accomplish such efficiency but there exists an opportunity to design even more efficient, manmade materials controlling microstructures at differentmore » scale levels. In the area of processing, James Aubert (Sandia National Laboratories) discussed techiques for manipulating polymersolvent phase equilibria to control the microstructure of microcellular foams. Other papers on processing discussed the production of cellular ceramics by CVD, HIPing and sol- gel techniques. Papers on the mechanical behavior of cellular materials considered various ceramics microcellular polymers, conventional polymer foams and apples. There were also contributions that considered optimum design procedures for cellular materials. Steven Cowin (City Univ. of New York) discussed procedures to match the discrete microstructural aspects of cellular materials with the continuum mechanics approach to their elastic behavior.« less

Predictability in Cellular Automata

PubMed Central

Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

2014-01-01

Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case. PMID:25271778

Predictability in cellular automata.

PubMed

Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

2014-01-01

Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

The mammary cellular hierarchy and breast cancer.

PubMed

Oakes, Samantha R; Gallego-Ortega, David; Ormandy, Christopher J

2014-11-01

Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

47 CFR 90.672 - Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part 22 Cellular Radiotelephone systems, and within the 900 MHz Business/Industrial Land Transportation Pool. 90.672 Section 90.672 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY...

Reprogramming cellular functions with engineered membrane proteins.

PubMed

Arber, Caroline; Young, Melvin; Barth, Patrick

2017-10-01

Taking inspiration from Nature, synthetic biology utilizes and modifies biological components to expand the range of biological functions for engineering new practical devices and therapeutics. While early breakthroughs mainly concerned the design of gene circuits, recent efforts have focused on engineering signaling pathways to reprogram cellular functions. Since signal transduction across cell membranes initiates and controls intracellular signaling, membrane receptors have been targeted by diverse protein engineering approaches despite limited mechanistic understanding of their function. The modular architecture of several receptor families has enabled the empirical construction of chimeric receptors combining domains from distinct native receptors which have found successful immunotherapeutic applications. Meanwhile, progress in membrane protein structure determination, computational modeling and rational design promise to foster the engineering of a broader range of membrane receptor functions. Marrying empirical and rational membrane protein engineering approaches should enable the reprogramming of cells with widely diverse fine-tuned functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biomechanical and ultrastructural comparison of cryopreservation and a novel cellular extraction of porcine aortic valve leaflets.

PubMed

Courtman, D W; Pereira, C A; Omar, S; Langdon, S E; Lee, J M; Wilson, G J

1995-12-01

Heart valve substitutes of biological origin often fail by degenerative mechanisms. Many authors have hypothesized that mechanical fatigue and structural degradation are instrumental to in vivo failure. Since the properties of the structural matrix at implantation may predetermine failure, we have examined the ultrastructure, fracture, mechanics, and uniaxial high-strain-rate viscoelastic properties of: (1) fresh, (2) cryopreserved, and (3) cellular extracted porcine aortic valve leaflets. The cellular extraction process is being developed in order to reduce immunological attack and calcification. Cryopreservation causes cellular disruption and necrotic changes throughout the tissue, whereas extraction removes all cells and lipid membranes. Both processes leave an intact collagen and elastin structural matrix and preserve the high-strain-rate viscoelastic characteristics of the fresh leaflets. Extraction does cause a 20% reduction in the fracture tension and increases tissue extensibility, with the percent strain at fracture rising to 45.3 +/- 4 (mean +/- SEM) from 31.5 +/- 3 for fresh leaflets. However, extraction does preserve matrix structure and mechanics over the physiological loading range. Glutaraldehyde fixation produces increased extensibility, increased elastic behavior, and, when applied to extracted leaflets, it causes a marked drop in fracture tension, to 50% of that for fresh leaflets. The combination of extraction and fixation may lead to early degenerative failure. The cellular extraction technique alone may be a useful alternative to glutaraldehyde fixation in preparing bioprosthetic heart valves.

The thermal regimes of the upper mantle beneath Precambrian and Phanerozoic structures up to the thermobarometry data of mantle xenoliths

NASA Astrophysics Data System (ADS)

Glebovitsky, V. A.; Nikitina, L. P.; Khiltova, V. Ya.; Ovchinnikov, N. O.

2004-05-01

The thermal state of the upper mantle beneath tectonic structures of various ages and types (Archaean cratons, Early Proterozoic accretionary and collisional orogens, and Phanerozoic structures) is characterized by geotherms and by thermal gradients (TG) derived from data on the P- T conditions of mineral equilibria in garnet and garnet-spinel peridotite xenoliths from kimberlites (East Siberia, Northeastern Europe, India, Central Africa, North America, and Canada) and alkali basalts (Southeastern Siberia, Mongolia, southeastern China, southeastern Australia, Central Africa, South America, and the Solomon and Hawaiian islands). The use of the same garnet-orthopyroxene thermobarometer (Theophrastus Contributions to Advanced Studies in Geology. 3: Capricious Earth: Models and Modelling of Geologic Processes and Objects 2000 44) for all xenoliths allowed us to avoid discrepancies in estimation of the P- T conditions, which may be a result of the mismatch between different thermometers and barometers, and to compare the thermal regimes in the mantle in various regions. Thus, it was established that (1) mantle geotherms and geothermal gradients, obtained from the estimation of P- T equilibrium conditions of deep xenoliths, correspond to the age of crust tectonic structures and respectively to the time of lithosphere stabilization; it can be suggested that the ancient structures of the upper mantle were preserved within continental roots; (2) thermal regimes under continental mantle between the Archaean cratons and Palaeoproterozoic belts are different today; (3) the continental mantle under Neoproterozoic and Phanerozoic belts is characterized by significantly higher values of geothermal gradient compared to the mantle under Early Precambrian structures; (4) lithosphere dynamics seems to change at the boundary between Early and Mezo-Neoproterozoic and Precambrian and Phanerozoic.

Cellular immunotherapy for patients with reactivation of JC and BK polyomaviruses after transplantation.

PubMed

Mani, Jiju; Jin, Nan; Schmitt, Michael

2014-10-01

Immunosuppression of patients after hematopoietic stem cell or kidney transplantation potentially leads to reactivation of JC and BK polyomaviruses. In hematopoietic stem cell transplantation, the reactivation rate of BKV can be up to 60%, resulting in severe complications of the urogenital tract, particularly hemorrhagic cystitis and renal dysfunction. After kidney transplantation, BKV reactivation can cause a loss of the graft. JCV can cause progressive multifocal leukoencephalopathy, a lethal disease. Adoptive transfer of donor-derived polyomavirus-specific T cells is an attractive and promising treatment that restores virus-specific cellular immunity. Pioneering work in the early 1990s on the reconstitution of cellular immunity against cytomegalovirus and recent development in the field of monitoring and isolation of antigen-specific T cells paved the way toward a personalized T-cell therapy. Multimer technology and magnetic beads are available to produce untouched T cells in a single-step, good manufacturing practice-compliant procedure. Another exciting aspect of T-cell therapy against polyomaviruses is the fact that both JCV and BKV can be targeted simultaneously because of their high sequence homology. Finally, "designer T cells" can be redirected to recognize polyomavirus antigens with high-affinity T-cell receptors. This review summarizes the state-of-the art technologies and gives an outlook of future developments in the field. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Characterizing heterogeneous cellular responses to perturbations.

PubMed

Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

2008-12-09

Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

Molecular and Cellular Mechanisms that Initiate Pain and Itch

PubMed Central

Luo, Jialie; Feng, Jing; Liu, Shenbin; Walters, Edgar T.

2015-01-01

Somatosensory neurons mediate our sense of touch. They are critically involved in transducing pain and itch sensations under physiological and pathological conditions, along with other skin resident cells. Tissue damage and inflammation can produce a localized or systemic sensitization of our senses of pain and itch, which can facilitate our detection of threats in the environment. Although acute pain and itch protect us from further damage, persistent pain and itch are debilitating. Recent exciting discoveries have significantly advanced our knowledge of the roles of membrane-bound G protein-coupled receptors and ion channels in the encoding of information leading to pain and itch sensations. This review focuses on molecular and cellular events that are important in early stages of the biological processing that culminates in our senses of pain and itch. PMID:25894692

Movies of cellular and sub-cellular motion by digital holographic microscopy.

PubMed

Mann, Christopher J; Yu, Lingfeng; Kim, Myung K

2006-03-23

Many biological specimens, such as living cells and their intracellular components, often exhibit very little amplitude contrast, making it difficult for conventional bright field microscopes to distinguish them from their surroundings. To overcome this problem phase contrast techniques such as Zernike, Normarsky and dark-field microscopies have been developed to improve specimen visibility without chemically or physically altering them by the process of staining. These techniques have proven to be invaluable tools for studying living cells and furthering scientific understanding of fundamental cellular processes such as mitosis. However a drawback of these techniques is that direct quantitative phase imaging is not possible. Quantitative phase imaging is important because it enables determination of either the refractive index or optical thickness variations from the measured optical path length with sub-wavelength accuracy. Digital holography is an emergent phase contrast technique that offers an excellent approach in obtaining both qualitative and quantitative phase information from the hologram. A CCD camera is used to record a hologram onto a computer and numerical methods are subsequently applied to reconstruct the hologram to enable direct access to both phase and amplitude information. Another attractive feature of digital holography is the ability to focus on multiple focal planes from a single hologram, emulating the focusing control of a conventional microscope. A modified Mach-Zender off-axis setup in transmission is used to record and reconstruct a number of holographic amplitude and phase images of cellular and sub-cellular features. Both cellular and sub-cellular features are imaged with sub-micron, diffraction-limited resolution. Movies of holographic amplitude and phase images of living microbes and cells are created from a series of holograms and reconstructed with numerically adjustable focus, so that the moving object can be accurately tracked

Cellular solidification in a monotectic system

NASA Technical Reports Server (NTRS)

Kaukler, W. F.; Curreri, P. A.

1987-01-01

Succinonitrile-glycerol, SN-G, transparent organic monotectic alloy is studied with particular attention to cellular growth. The phase diagram is determined, near the monotectic composition, with greater accuracy than previous studies. A solidification interface stability diagram is determined for planar growth. The planar-to-cellular transition is compared to predictions from the Burton, Primm, Schlichter theory. A new technique to determine the solute segregation by Fourier transform infrared spectroscopy is developed. Proposed models that involve the cellular interface for alignment of monotectic second-phase spheres or rods are compared with observations.

δ- and γ-Tocopherols Inhibit PhIP/DSS-induced Colon Carcinogenesis by Protection against Early Cellular and DNA Damages

PubMed Central

Chen, Jayson X.; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S.

2017-01-01

Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T) and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 weeks. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. PMID:27175800

Statistical geochemistry reveals disruption in secular lithospheric evolution about 2.5 Gyr ago.

PubMed

Keller, C Brenhin; Schoene, Blair

2012-05-23

The Earth has cooled over the past 4.5 billion years (Gyr) as a result of surface heat loss and declining radiogenic heat production. Igneous geochemistry has been used to understand how changing heat flux influenced Archaean geodynamics, but records of systematic geochemical evolution are complicated by heterogeneity of the rock record and uncertainties regarding selection and preservation bias. Here we apply statistical sampling techniques to a geochemical database of about 70,000 samples from the continental igneous rock record to produce a comprehensive record of secular geochemical evolution throughout Earth history. Consistent with secular mantle cooling, compatible and incompatible elements in basalts record gradually decreasing mantle melt fraction through time. Superimposed on this gradual evolution is a pervasive geochemical discontinuity occurring about 2.5 Gyr ago, involving substantial decreases in mantle melt fraction in basalts, and in indicators of deep crustal melting and fractionation, such as Na/K, Eu/Eu* (europium anomaly) and La/Yb ratios in felsic rocks. Along with an increase in preserved crustal thickness across the Archaean/Proterozoic boundary, these data are consistent with a model in which high-degree Archaean mantle melting produced a thick, mafic lower crust and consequent deep crustal delamination and melting--leading to abundant tonalite-trondhjemite-granodiorite magmatism and a thin preserved Archaean crust. The coincidence of the observed changes in geochemistry and crustal thickness with stepwise atmospheric oxidation at the end of the Archaean eon provides a significant temporal link between deep Earth geochemical processes and the rise of atmospheric oxygen on the Earth.

Cellular immunotherapy for malignant gliomas.

PubMed

Lin, Yi; Okada, Hideho

2016-10-01

Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy.

Potential Role of Lateral Gene Transfer in the Evolution of Biofilm Communities at the Lost City Hydrothermal Field and in the Earliest Stages of Cellular Evolution

NASA Astrophysics Data System (ADS)

Brazelton, W. J.; Mehta, M. P.; Baross, J. A.

2010-04-01

DNA sequencing and metabolic activity measurements show that lateral gene transfer promotes phenotypic diversity in single-species archaeal biofilms attached to hydrothermal chimneys. This system may be a useful model for early cellular evolution.

Forty years of TTG research

NASA Astrophysics Data System (ADS)

Moyen, Jean-François; Martin, Hervé

2012-09-01

TTGs (tonalite-trondhjemite-granodiorite) are one of the archetypical lithologies of Archaean cratons. Since their original description in the 1970s, they have been the subject of many studies and discussions relating to Archaean geology. In this paper, we review the ideas, concepts and arguments brought forward in these 40 years, and try to address some open questions — both old and new. The late 1960s and the 1970s mark the appearance of "grey gneisses" (TTG) in the scientific literature. During this period, most work was focused on the identification and description of this suite, and the recognition that it is a typical Archaean lithology. TTGs were already recognised as generated by melting of mafic rocks. This was corroborated during the next decade, when detailed geochemical TTG studies allowed us to constrain their petrogenesis (melting of garnet-bearing metamafic rocks), and to conclude that they must have been generated by Archaean geodynamic processes distinct from their modern counterparts. However, the geodynamic debate raged for the following 30 years, as many distinct tectonic scenarios can be imagined, all resulting in the melting of mafic rocks in the garnet stability field. The 1990s were dominated by experimental petrology work. A wealth of independent studies demonstrated that melting of amphibolites as well as of mafic eclogites can give rise to TTG liquids; whether amphibolitic or eclogitic conditions are more likely is still an ongoing debate. From 1990s onwards, one of the key questions became the comparison with modern adakites. As originally defined these arc lavas are reasonably close equivalents to Archaean TTGs. Pending issues largely revolve around definitions, as the name TTG has now been applied to most Archaean plutonic rocks, whether sodic or potassic, irrespective of their HREE contents. This leads to a large range of petrogenetic and tectonic scenarios; a fair number of which may well have operated concurrently, but are

Cellular La protein shields nonsegmented negative-strand RNA viral leader RNA from RIG-I and enhances virus growth by diverse mechanisms.

PubMed

Bitko, Vira; Musiyenko, Alla; Bayfield, Mark A; Maraia, Richard J; Barik, Sailen

2008-08-01

The La antigen (SS-B) associates with a wide variety of cellular and viral RNAs to affect gene expression in multiple systems. We show that La is the major cellular protein found to be associated with the abundant 44-nucleotide viral leader RNA (leRNA) early after infection with respiratory syncytial virus (RSV), a nonsegmented negative-strand RNA virus. Consistent with this, La redistributes from the nucleus to the cytoplasm in RSV-infected cells. Upon RNA interference knockdown of La, leRNA is redirected to associate with the RNA-binding protein RIG-I, a known activator of interferon (IFN) gene expression, and this is accompanied by the early induction of IFN mRNA. These results suggest that La shields leRNA from RIG-I, abrogating the early viral activation of type I IFN. We mapped the leRNA binding function to RNA recognition motif 1 of La and showed that while wild-type La greatly enhanced RSV growth, a La mutant defective in RSV leRNA binding also did not support RSV growth. Comparative studies of RSV and Sendai virus and the use of IFN-negative Vero cells indicated that La supports the growth of nonsegmented negative-strand RNA viruses by both IFN suppression and a potentially novel IFN-independent mechanism.

Integration of mobile satellite and cellular systems

NASA Technical Reports Server (NTRS)

Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

1993-01-01

By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

Integration of mobile satellite and cellular systems

NASA Astrophysics Data System (ADS)

Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

Cellular membrane collapse by atmospheric-pressure plasma jet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kangil; Sik Yang, Sang, E-mail: jsjlee@ajou.ac.kr, E-mail: ssyang@ajou.ac.kr; Jun Ahn, Hak

2014-01-06

Cellular membrane dysfunction caused by air plasma in cancer cells has been studied to exploit atmospheric-pressure plasma jets for cancer therapy. Here, we report that plasma jet treatment of cervical cancer HeLa cells increased electrical conductivity across the cellular lipid membrane and caused simultaneous lipid oxidation and cellular membrane collapse. We made this finding by employing a self-manufactured microelectrode chip. Furthermore, increased roughness of the cellular lipid membrane and sequential collapse of the membrane were observed by atomic force microscopy following plasma jet treatment. These results suggest that the cellular membrane catastrophe occurs via coincident altered electrical conductivity, lipid oxidation,more » and membrane roughening caused by an atmospheric-pressure plasma jet, possibly resulting in cellular vulnerability to reactive species generated from the plasma as well as cytotoxicity to cancer cells.« less

Quantum cellular automata

NASA Astrophysics Data System (ADS)

Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

1994-06-01

The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

Toxicity of pyrolysis gases from some cellular polymers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Machado, A. M.

1978-01-01

Various samples of cellular polymers were evaluated for toxicity of pyrolysis gases, using the screening test method developed at the University of San Francisco. The cellular polymer samples included polyimide, polymethacrylimide, polybismaleimide, polyurethane, polyisocyanurate, polyethylene, polychloroprene, polyvinyl chloride, polystyrene, polysiloxane, and polyphosphazene. The cellular polymers exhibited varying levels of toxicity under these test conditions. Among the rigid cellular polymers, times to death were shortest with the imide type foams and longest with polyvinyl chloride and polystyrene. Among the flexible cellular polymers, times to death were shortest with polyimide and polyester, and longest with polychloroprene and polysiloxane. Increased char yield was not necessarily associated with reduced toxicity.

Wavefront cellular learning automata.

PubMed

Moradabadi, Behnaz; Meybodi, Mohammad Reza

2018-02-01

This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

Wavefront cellular learning automata

NASA Astrophysics Data System (ADS)

Moradabadi, Behnaz; Meybodi, Mohammad Reza

2018-02-01

This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

Fracture mechanics of cellular glass

NASA Technical Reports Server (NTRS)

Zwissler, J. G.; Adams, M. A.

1981-01-01

The fracture mechanics of cellular glasses (for the structural substrate of mirrored glass for solr concentrator reflecting panels) are discussed. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials were developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region 1 may be slower, by orders of magnitude, than that found in dense glasses.

47 CFR 22.911 - Cellular geographic service area.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular geographic service area. 22.911 Section 22.911 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.911 Cellular geographic service area. The...

Average composition of the tonalite-trondhjemite-granodiorite association: Possibilities of application

NASA Astrophysics Data System (ADS)

Chekulaev, V. P.; Glebovitsky, V. A.

2017-01-01

The possibilities of using the average compositions of tonalite-trondhjemite-granodiorite association rocks (TTG), which make up a significant part of the Archaean continental crust, have been examined. The results of the TTG average compositions obtained by other researchers and the authors' data of the average compositions of TTG from the Baltic and Ukrainian shields and the entire Archaean crust are given. It is shown that the average compositions of the Archaean TTG of continental large crustal fragments (cratons or provinces) practically do not bear any information on their sources or conditions of their formation. The possibility of obtaining of such information by means of analysis of the average compositions of TTG, composing smaller fragments of the crust, exemplified by rocks of the Karelian subprovinces of the Baltic Shield has been demonstrated.

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

PubMed

Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

2017-01-01

Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity

PubMed Central

Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

2017-01-01

Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

Asynchronous adaptive time step in quantitative cellular automata modeling

PubMed Central

Zhu, Hao; Pang, Peter YH; Sun, Yan; Dhar, Pawan

2004-01-01

Background The behaviors of cells in metazoans are context dependent, thus large-scale multi-cellular modeling is often necessary, for which cellular automata are natural candidates. Two related issues are involved in cellular automata based multi-cellular modeling: how to introduce differential equation based quantitative computing to precisely describe cellular activity, and upon it, how to solve the heavy time consumption issue in simulation. Results Based on a modified, language based cellular automata system we extended that allows ordinary differential equations in models, we introduce a method implementing asynchronous adaptive time step in simulation that can considerably improve efficiency yet without a significant sacrifice of accuracy. An average speedup rate of 4–5 is achieved in the given example. Conclusions Strategies for reducing time consumption in simulation are indispensable for large-scale, quantitative multi-cellular models, because even a small 100 × 100 × 100 tissue slab contains one million cells. Distributed and adaptive time step is a practical solution in cellular automata environment. PMID:15222901

47 CFR 22.905 - Channels for cellular service.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Channels for cellular service. 22.905 Section 22.905 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.905 Channels for cellular service. The following...

47 CFR 22.905 - Channels for cellular service.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Channels for cellular service. 22.905 Section 22.905 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.905 Channels for cellular service. The following...

47 CFR 22.905 - Channels for cellular service.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Channels for cellular service. 22.905 Section 22.905 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.905 Channels for cellular service. The following...

Modems for emerging digital cellular-mobile radio system

NASA Technical Reports Server (NTRS)

Feher, Kamilo

1991-01-01

Digital modem techniques for emerging digital cellular telecommunications-mobile radio system applications are described and analyzed. In particular, theoretical performance, experimental results, principles of operation, and various architectures of pi/4-QPSK (pi/4-shifted coherent or differential QPSK) modems for second-generation US digital cellular radio system applications are presented. The spectral/power efficiency and performance of the pi/4-QPSK modems (American and Japanese digital cellular emerging standards) are studied and briefly compared to GMSK (Gaussian minimum-shift keying) modems (proposed for European DECT and GSM cellular standards). Improved filtering strategies and digital pilot-aided (digital channel sounding) techniques are also considered for pi/4-QPSK and other digital modems. These techniques could significantly improve the performance of digital cellular and other digital land mobile and satellite mobile radio systems. More spectrally efficient modem trends for future cellular/mobile (land mobile) and satellite communication systems applications are also highlighted.

Cellular metabolic energy modulation by tangeretin in 7,12-dimethylbenz(a) anthracene-induced breast cancer.

PubMed

Periyasamy, Kuppusamy; Sivabalan, Venkatachalam; Baskaran, Kuppusamy; Kasthuri, Kannayiram; Sakthisekaran, Dhanapal

2016-03-01

Breast cancer is the leading cause of death among women worldwide. Chemoprevention and chemotherapy play beneficial roles in reducing the incidence and mortality of cancer. Epidemiological and experimental studies showed that naturally-occurring antioxidants present in the diet may act as anticancer agents. Identifying the abnormalities of cellular energy metabolism facilitates early detection and management of breast cancer. The present study evaluated the effect of tangeretin on cellular metabolic energy fluxes in 7,12-dimethylbenz(a) anthracene (DMBA)-induced proliferative breast cancer. The results showed that the activities of glycolytic enzymes significantly increased in mammary tissues of DMBA-induced breast cancer bearing rats. The gluconeogenic tricarboxylic acid (TCA) cycle and respiratory chain enzyme activities significantly decreased in breast cancer-bearing rats. In addition, proliferating cell nuclear antigen (PCNA) was highly expressed in breast cancer tissues. However, the activities of glycolytic enzymes were significantly normalized in the tangeretin pre- and post-treated rats and the TCA cycle and respiratory chain enzyme activities were significantly increased in tangeretin treated rats. Furthermore, tangeretin down-regulated PCNA expression on breast cancer-bearing rats. Our study demonstrates that tangeretin specifically regulates cellular metabolic energy fluxes in DMBA-induced breast cancer-bearing rats. © 2016 by the Journal of Biomedical Research. All rights reserved.

Analysis of Human Mobility Based on Cellular Data

NASA Astrophysics Data System (ADS)

Arifiansyah, F.; Saptawati, G. A. P.

2017-01-01

Nowadays not only adult but even teenager and children have then own mobile phones. This phenomena indicates that the mobile phone becomes an important part of everyday’s life. Based on these indication, the amount of cellular data also increased rapidly. Cellular data defined as the data that records communication among mobile phone users. Cellular data is easy to obtain because the telecommunications company had made a record of the data for the billing system of the company. Billing data keeps a log of the users cellular data usage each time. We can obtained information from the data about communication between users. Through data visualization process, an interesting pattern can be seen in the raw cellular data, so that users can obtain prior knowledge to perform data analysis. Cellular data processing can be done using data mining to find out human mobility patterns and on the existing data. In this paper, we use frequent pattern mining and finding association rules to observe the relation between attributes in cellular data and then visualize them. We used weka tools for finding the rules in stage of data mining. Generally, the utilization of cellular data can provide supporting information for the decision making process and become a data support to provide solutions and information needed by the decision makers.

Terminal addition in a cellular world.

PubMed

Torday, J S; Miller, William B

2018-07-01

Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Copyright © 2017. Published by Elsevier Ltd.

Testicular cellular toxicity of cadmium : transmission electron microscopy examination.

PubMed

Haffor, A S; Abou-Tarboush, F M

2004-07-01

It is clear that environmental heavy metals influence life systems and reproductive system. In the present study histological investigation revealed that cadmium was testicular toxicant in mice. Here we compared the fine-structure of spermatogenesis in two groups of mice (SWR), experimental and control. The experimental group underwent cadmium ingestion at 1 mg/kg daily for 4 weeks. The control group underwent ingestion of distilled water with equal dosages, using the same type of injectors, for 4-weeks. After cadmium exposure period both control and experimental groups were killed and samples of the testes were processed for microscopic examination. Ultra sections were examined and photographed by Transmission Electron Microscope (JEOL- 100SX) at 80KV. Ultrastructure examination revealed, vascular endothelial, interstitial, and sertoli cells damages. Early impairments of germinal cellular differentiation resulted in deformations in all parts of late spermatid. There were dislocation of accrosomal granules, nuclear damage associated with chromatin heterogeneity, detached spermatid from the apical process of sertoli cell, disarrangement of the mitochondria, abnormal oriented tail piece, and abnormal microtubules complex. These ultra morphological abnormalities relate to cell injury and to the resulting physiological abnormality, necrobiosis. Based on the results of this investigation it can be concluded that cadmium ingestion at 1000 microg/kg caused testicular toxicity and abnormalities in early sperm development.

Characterization of Betula platyphylla gene transcripts associated with early development of male inflorescence.

PubMed

Xing, Lei; Liu, Xue-Mei

2012-02-01

Birch (Betula platyphylla), an eminent tree species in Northeast and Inner Mongolia of China, has been widely used in architecture, furniture, and paper making in recent years. In order to retrieve genes involved in early development of B. platyphylla male inflorescence, RNA populations extracted from early and late developmental stage were analyzed by cDNA-Amplified Fragment Length Polymorphism (cDNA-AFLP) technique. Following amplification of 256 pairs of primer combinations, ~7000 fragments were generated, of which 350 transcripts expressing more in early stage than late. Of 350 specific transcripts, 198 clear and reproducible electrophoresis bands were retrieved and sequenced successfully, 74 of them (37%) showing significant homologies to known genes after GO annotation. Majority of the predicted gene products were involved in metabolism (24.56%), cellular process (27.19%), response to stimulus (11.4%) and cell growth (8.7%). Transcripts ME56, ME108, ME206 and ME310, representing metabolism, cellular process, response to stimulus and cell growth, respectively, were selected for further study to validate cDNA-AFLP expression patterns via RT-PCR and qRT-PCR analysis. RT-PCR and qRT-PCR expression pattern results were consistent with cDNA-AFLP analysis results.

Exploration of cellular reaction systems.

PubMed

Kirkilionis, Markus

2010-01-01

We discuss and review different ways to map cellular components and their temporal interaction with other such components to different non-spatially explicit mathematical models. The essential choices made in the literature are between discrete and continuous state spaces, between rule and event-based state updates and between deterministic and stochastic series of such updates. The temporal modelling of cellular regulatory networks (dynamic network theory) is compared with static network approaches in two first introductory sections on general network modelling. We concentrate next on deterministic rate-based dynamic regulatory networks and their derivation. In the derivation, we include methods from multiscale analysis and also look at structured large particles, here called macromolecular machines. It is clear that mass-action systems and their derivatives, i.e. networks based on enzyme kinetics, play the most dominant role in the literature. The tools to analyse cellular reaction networks are without doubt most complete for mass-action systems. We devote a long section at the end of the review to make a comprehensive review of related tools and mathematical methods. The emphasis is to show how cellular reaction networks can be analysed with the help of different associated graphs and the dissection into modules, i.e. sub-networks.

Cellular immunotherapy for malignant gliomas

PubMed Central

Lin, Yi

2016-01-01

Introduction Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Areas covered Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. Expert opinion While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy. PMID:27434205

Early-life estrogen exposure and uterine pathogenesis: ?A model for gene-environment interactions

EPA Science Inventory

Aberrant cellular differentiation early in life can contribute to increased cancer risk later in life. In a classic model of this effect, female mice exposed on postnatal day (PND) 1-5 to the synthetic estrogen diethylstilbestrol (DES) have a high incidence of uterine carcinoma. ...

The concept of self-organization in cellular architecture

PubMed Central

Misteli, Tom

2001-01-01

In vivo microscopy has recently revealed the dynamic nature of many cellular organelles. The dynamic properties of several cellular structures are consistent with a role for self-organization in their formation, maintenance, and function; therefore, self-organization might be a general principle in cellular organization. PMID:11604416

Temporal and mechanistic tracking of cellular uptake dynamics with novel surface fluorophore-bound nanodiamonds.

PubMed

Schrand, Amanda M; Lin, Jonathan B; Hens, Suzanne Ciftan; Hussain, Saber M

2011-02-01

Nanoparticles (NPs) offer promise for a multitude of biological applications including cellular probes at the bio-interface for targeted delivery of anticancer substances, Raman and fluorescent-based imaging and directed cell growth. Nanodiamonds (NDs), in particular, have several advantages compared to other carbon-based nanomaterials - including a rich surface chemistry useful for chemical conjugation, high biocompatibility with little reactive oxygen species (ROS) generation, physical and chemical stability that affords sterilization, high surface area to volume ratio, transparency and a high index of refraction. The visualization of ND internalization into cells is possible via photoluminescence, which is produced by direct dye conjugation or high energy irradiation that creates nitrogen vacancy centers. Here, we explore the kinetics and mechanisms involved in the intracellular uptake and localization of novel, highly-stable, fluorophore-conjugated NDs. Examination in a neuronal cell line (N2A) shows ND localization to early endosomes and lysosomes with eventual release into the cytoplasm. The addition of endocytosis and exocytosis inhibitors allows for diminished uptake and increased accumulation, respectively, which further corroborates cellular behavior in response to NDs. Ultimately, the ability of the NDs to travel throughout cellular compartments of varying pH without degradation of the surface-conjugated fluorophore or alteration of cell viability over extended periods of time is promising for their use in biomedical applications as stable, biocompatible, fluorescent probes.

Effects of differentiation on the geodynamics of the early Earth

NASA Astrophysics Data System (ADS)

Piccolo, Andrea; Kaus, Boris; White, Richard; Johnson, Tim

2016-04-01

Archean geodynamic processes are not well understood, but there is general agreement that the mantle potential temperature was higher than present, and that as a consequence significant amounts of melt were produced both in the mantle and any overlying crust. This has likely resulted in crustal differentiation. An early attempt to model the geodynamic effects of differentiation was made by Johnson et al. (2014), who used numerical modeling to investigate the crust production and recycling in conjunction with representative phase diagrams (based on the inferred chemical composition of the primary melt in accordance with the Archean temperature field). The results of the simulations show that the base of the over-thickened primary basaltic crust becomes gravitational unstable due to the mineral assemblage changes. This instability leads to the dripping of dense material into the mantle, which causes an asthenospheric return flow, local partial melting and new primary crust generation that is rapidly recycled in to mantle. Whereas they gave important insights, the previous simulations were simplified in a number of aspects: 1) the rheology employed was viscous, and both elasticity and pressure-dependent plasticity were not considered; 2) extracted mantle melts were 100% transformed into volcanic rocks, whereas on the present day Earth only about 20-30% are volcanic and the remainder is plutonic; 3) the effect of a free surface was not studied in a systematic manner. In order to better understand how these simplifications affect the geodynamic models, we here present additional simulations to study the effects of each of these parameters. Johnson, T.E., Brown, M., Kaus, B., and VanTongeren, J.A., 2014, Delamination and recycling of Archaean crust caused by gravitational instabilities: Nature Geoscience, v. 7, no. 1, p. 47-52, doi: 10.1038/NGEO2019.

Numerical Mantle Convection Models of Crustal Formation in an Oceanic Environment in the Early Earth

NASA Astrophysics Data System (ADS)

van Thienen, P.; van den Berg, A. P.; Vlaar, N. J.

2001-12-01

The generation of basaltic crust in the early Earth by partial melting of mantle rocks, subject to investigation in this study, is thought to be a first step in the creation of proto-continents (consisting largely of felsic material), since partial melting of basaltic material was probably an important source for these more evolved rocks. In the early Archean the earth's upper mantle may have been hotter than today by as much as several hundred degrees centigrade. As a consequence, partial melting in shallow convective upwellings would have produced a layering of basaltic crust and underlying depleted (lherzolitic-harzburgitic) mantle peridotite which is much thicker than found under modern day oceanic ridges. When a basaltic crustal layer becomes sufficiently thick, a phase transition to eclogite may occur in the lower parts, which would cause delamination of this dense crustal layer and recycling of dense eclogite into the upper mantle. This recycling mechanism may have contributed significantly to the early cooling of the earth during the Archean (Vlaar et al., 1994). The delamination mechanism which limits the build-up of a thick basaltic crustal layer is switched off after sufficient cooling of the upper mantle has taken place. We present results of numerical modelling experiments of mantle convection including pressure release partial melting. The model includes a simple approximate melt segregation mechanism and basalt to eclogite phase transition, to account for the dynamic accumulation and recycling of the crust in an upper mantle subject to secular cooling. Finite element methods are used to solve for the viscous flow field and the temperature field, and lagrangian particle tracers are used to represent the evolving composition due to partial melting and accumulation of the basaltic crust. We find that this mechanism creates a basaltic crust of several tens of kilometers thickness in several hundreds of million years. This is accompanied by a cooling of

Theoretical aspects of cellular decision-making and information-processing.

PubMed

Kobayashi, Tetsuya J; Kamimura, Atsushi

2012-01-01

Microscopic biological processes have extraordinary complexity and variety at the sub-cellular, intra-cellular, and multi-cellular levels. In dealing with such complex phenomena, conceptual and theoretical frameworks are crucial, which enable us to understand seemingly different intra- and inter-cellular phenomena from unified viewpoints. Decision-making is one such concept that has attracted much attention recently. Since a number of cellular behavior can be regarded as processes to make specific actions in response to external stimuli, decision-making can cover and has been used to explain a broad range of different cellular phenomena [Balázsi et al. (Cell 144(6):910, 2011), Zeng et al. (Cell 141(4):682, 2010)]. Decision-making is also closely related to cellular information-processing because appropriate decisions cannot be made without exploiting the information that the external stimuli contain. Efficiency of information transduction and processing by intra-cellular networks determines the amount of information obtained, which in turn limits the efficiency of subsequent decision-making. Furthermore, information-processing itself can serve as another concept that is crucial for understanding of other biological processes than decision-making. In this work, we review recent theoretical developments on cellular decision-making and information-processing by focusing on the relation between these two concepts.

Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis

PubMed Central

Rabano, Miriam; Vivanco, Maria d M; Perrin, Florence Evelyne

2012-01-01

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective motoneurons degeneration. There is today no clear-cut pathogenesis sequence nor any treatment. However growing evidences are in favor of the involvement, besides neurons, of several partners such as glia and muscles. To better characterize the time course of pathological events in an animal model that recapitulates human ALS symptoms, we investigated functional and cellular characteristics of hSOD1G93A mice. Methods and Findings We have evaluated locomotor function of hSOD1G93A mice through dynamic walking patterns and spontaneous motor activity analysis. We detected early functional deficits that redefine symptoms onset at 60 days of age, i.e. 20 days earlier than previously described. Moreover, sequential combination of these approaches allows monitoring of motor activity up to disease end stage. To tentatively correlate early functional deficit with cellular alterations we have used flow cytometry and immunohistochemistry approaches to characterize neuromuscular junctions, astrocytes and microglia. We show that (1) decrease in neuromuscular junction's number correlates with motor impairment, (2) astrocytes number is not altered at pre- and early-symptomatic ages but intraspinal repartition is modified at symptoms onset, and (3) microglia modifications precede disease onset. At pre-symptomatic age, we show a decrease in microglia number whereas at onset of the disease two distinct microglia sub-populations emerge. Conclusions In conclusion, precise motor analysis updates the onset of the disease in hSOD1G93A mice and allows locomotor monitoring until the end stage of the disease. Early functional deficits coincide with alterations of neuromuscular junctions. Importantly, we identify different sets of changes in microglia before disease onset as well as at early-symptomatic stage. This finding not only brings a new sequence of cellular events in the natural

DNA Methylation: A Mechanism for Embedding Early Life Experiences in the Genome

ERIC Educational Resources Information Center

Szyf, Moshe; Bick, Johanna

2013-01-01

Although epidemiological data provide evidence that early life experience plays a critical role in human development, the mechanism of how this works remains in question. Recent data from human and animal literature suggest that epigenetic changes, such as DNA methylation, are involved not only in cellular differentiation but also in the…

Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer

PubMed Central

Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei

2014-01-01

Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer. PMID:25988156

In vitro characterization of MG-63 osteoblast-like cells cultured on organic-inorganic lyophilized gelatin sponges for early bone healing.

PubMed

Rodriguez, Isaac A; Saxena, Gunjan; Hixon, Katherine R; Sell, Scott A; Bowlin, Gary L

2016-08-01

The development of three-dimensional porous scaffolds with enhanced osteogenic and angiogenic potential would be beneficial for inducing early-stage bone regeneration. Previous studies have demonstrated the advantages of mineralized and nonmineralized acellular 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers. In this study, those same scaffolds were mineralized and dynamically seeded with MG-63 cells. Cell proliferation, protein/cytokine secretion, and compressive mechanical properties of scaffolds were evaluated. It was found that mineralization and the addition of growth factors increased cell proliferation compared to gelatin controls. Cells on all scaffolds responded in an appropriate bone regenerative fashion as shown through osteocalcin secretion and little to no secretion of bone resorbing markers. However, compressive mechanical properties of cellularized scaffolds were not significantly different from acellular scaffolds. The combined results of increased cellular attachment, infiltration, and bone regenerative protein/cytokine secretion on scaffolds support the need for the addition of a bone-like mineral surface. Cellularized scaffolds containing growth factors reported similar advantages and mechanical values in the range of native tissues present in the early stages of bone healing. These results suggest that the developed composite sponges exhibited cellular responses and mechanical properties appropriate for promoting early bone healing in various applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2011-2019, 2016. © 2016 Wiley Periodicals, Inc.

Diversity and three-dimensional structures of the alpha Mcr of the methanogenic Archaea from the anoxic region of Tucuruí Lake, in Eastern Brazilian Amazonia

PubMed Central

Santana, Priscila Bessa; Junior, Rubens Ghilardi; Alves, Claudio Nahum; Silva, Jeronimo Lameira; McCulloch, John Anthony; Schneider, Maria Paula Cruz; da Costa da Silva, Artur

2012-01-01

Methanogenic archaeans are organisms of considerable ecological and biotechnological interest that produce methane through a restricted metabolic pathway, which culminates in the reaction catalyzed by the Methyl-coenzyme M reductase (Mcr) enzyme, and results in the release of methane. Using a metagenomic approach, the gene of the α subunit of mcr (mcrα) was isolated from sediment sample from an anoxic zone, rich in decomposing organic material, obtained from the Tucuruí hydroelectric dam reservoir in eastern Brazilian Amazonia. The partial nucleotide sequences obtained were 83 to 95% similar to those available in databases, indicating a low diversity of archaeans in the reservoir. Two orders were identified - the Methanomicrobiales, and a unique Operational Taxonomic Unit (OTU) forming a clade with the Methanosarcinales according to low bootstrap values. Homology modeling was used to determine the three-dimensional (3D) structures, for this the partial nucleotide sequence of the mcrα were isolated and translated on their partial amino acid sequences. The 3D structures of the archaean Mcrα observed in the present study varied little, and presented approximately 70% identity in comparison with the Mcrα of Methanopyrus klanderi. The results demonstrated that the community of methanogenic archaeans of the anoxic C1 region of the Tucurui reservoir is relatively homogeneous. PMID:22481885

Initiating a regenerative response; cellular and molecular features of wound healing in the cnidarian Nematostella vectensis.

PubMed

DuBuc, Timothy Q; Traylor-Knowles, Nikki; Martindale, Mark Q

2014-03-26

Wound healing is the first stage of a series of cellular events that are necessary to initiate a regenerative response. Defective wound healing can block regeneration even in animals with a high regenerative capacity. Understanding how signals generated during wound healing promote regeneration of lost structures is highly important, considering that virtually all animals have the ability to heal but many lack the ability to regenerate missing structures. Cnidarians are the phylogenetic sister taxa to bilaterians and are highly regenerative animals. To gain a greater understanding of how early animals generate a regenerative response, we examined the cellular and molecular components involved during wound healing in the anthozoan cnidarian Nematostella vectensis. Pharmacological inhibition of extracellular signal-regulated kinases (ERK) signaling blocks regeneration and wound healing in Nematostella. We characterized early and late wound healing events through genome-wide microarray analysis, quantitative PCR, and in situ hybridization to identify potential wound healing targets. We identified a number of genes directly related to the wound healing response in other animals (metalloproteinases, growth factors, transcription factors) and suggest that glycoproteins (mucins and uromodulin) play a key role in early wound healing events. This study also identified a novel cnidarian-specific gene, for a thiamine biosynthesis enzyme (vitamin B synthesis), that may have been incorporated into the genome by lateral gene transfer from bacteria and now functions during wound healing. Lastly, we suggest that ERK signaling is a shared element of the early wound response for animals with a high regenerative capacity. This research describes the temporal events involved during Nematostella wound healing, and provides a foundation for comparative analysis with other regenerative and non-regenerative species. We have shown that the same genes that heal puncture wounds are also

Initiating a regenerative response; cellular and molecular features of wound healing in the cnidarian Nematostella vectensis

PubMed Central

2014-01-01

Background Wound healing is the first stage of a series of cellular events that are necessary to initiate a regenerative response. Defective wound healing can block regeneration even in animals with a high regenerative capacity. Understanding how signals generated during wound healing promote regeneration of lost structures is highly important, considering that virtually all animals have the ability to heal but many lack the ability to regenerate missing structures. Cnidarians are the phylogenetic sister taxa to bilaterians and are highly regenerative animals. To gain a greater understanding of how early animals generate a regenerative response, we examined the cellular and molecular components involved during wound healing in the anthozoan cnidarian Nematostella vectensis. Results Pharmacological inhibition of extracellular signal-regulated kinases (ERK) signaling blocks regeneration and wound healing in Nematostella. We characterized early and late wound healing events through genome-wide microarray analysis, quantitative PCR, and in situ hybridization to identify potential wound healing targets. We identified a number of genes directly related to the wound healing response in other animals (metalloproteinases, growth factors, transcription factors) and suggest that glycoproteins (mucins and uromodulin) play a key role in early wound healing events. This study also identified a novel cnidarian-specific gene, for a thiamine biosynthesis enzyme (vitamin B synthesis), that may have been incorporated into the genome by lateral gene transfer from bacteria and now functions during wound healing. Lastly, we suggest that ERK signaling is a shared element of the early wound response for animals with a high regenerative capacity. Conclusions This research describes the temporal events involved during Nematostella wound healing, and provides a foundation for comparative analysis with other regenerative and non-regenerative species. We have shown that the same genes that

Cellular Strategies of Protein Quality Control

PubMed Central

Chen, Bryan; Retzlaff, Marco; Roos, Thomas; Frydman, Judith

2011-01-01

Eukaryotic cells must contend with a continuous stream of misfolded proteins that compromise the cellular protein homeostasis balance and jeopardize cell viability. An elaborate network of molecular chaperones and protein degradation factors continually monitor and maintain the integrity of the proteome. Cellular protein quality control relies on three distinct yet interconnected strategies whereby misfolded proteins can either be refolded, degraded, or delivered to distinct quality control compartments that sequester potentially harmful misfolded species. Molecular chaperones play a critical role in determining the fate of misfolded proteins in the cell. Here, we discuss the spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation. PMID:21746797

Supporting performance and configuration management of GTE cellular networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Ming; Lafond, C.; Jakobson, G.

GTE Laboratories, in cooperation with GTE Mobilnet, has developed and deployed PERFFEX (PERFormance Expert), an intelligent system for performance and configuration management of cellular networks. PERFEX assists cellular network performance and radio engineers in the analysis of large volumes of cellular network performance and configuration data. It helps them locate and determine the probable causes of performance problems, and provides intelligent suggestions about how to correct them. The system combines an expert cellular network performance tuning capability with a map-based graphical user interface, data visualization programs, and a set of special cellular engineering tools. PERFEX is in daily use atmore » more than 25 GTE Mobile Switching Centers. Since the first deployment of the system in late 1993, PERFEX has become a major GTE cellular network performance optimization tool.« less

Cellularized Cellular Solids via Freeze-Casting.

PubMed

Christoph, Sarah; Kwiatoszynski, Julien; Coradin, Thibaud; Fernandes, Francisco M

2016-02-01

The elaboration of metabolically active cell-containing materials is a decisive step toward the successful application of cell based technologies. The present work unveils a new process allowing to simultaneously encapsulate living cells and shaping cell-containing materials into solid-state macroporous foams with precisely controlled morphology. Our strategy is based on freeze casting, an ice templating materials processing technique that has recently emerged for the structuration of colloids into macroporous materials. Our results indicate that it is possible to combine the precise structuration of the materials with cellular metabolic activity for the model organism Saccharomyces cerevisiae. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Imaging the morphological change of tissue structure during the early phase of esophageal tumor progression using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Xu, Jian; Kang, Deyong; Xu, Meifang; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

2012-12-01

Esophageal cancer is a common malignancy with a very poor prognosis. Successful strategies for primary prevention and early detection are critically needed to control this disease. Multiphoton microscopy (MPM) is becoming a novel optical tool of choice for imaging tissue architecture and cellular morphology by two-photon excited fluorescence. In this study, we used MPM to image microstructure of human normal esophagus, carcinoma in situ (CIS), and early invasive carcinoma in order to establish the morphological features to differentiate these tissues. The diagnostic features such as the appearance of cancerous cells, the significant loss of stroma, the absence of the basement membrane were extracted to distinguish between normal and cancerous esophagus tissue. These results correlated well with the paired histological findings. With the advancement of clinically miniaturized MPM and the multi-photon probe, combining MPM with standard endoscopy will therefore allow us to make a real-time in vivo diagnosis of early esophageal cancer at the cellular level.

Viral Activation of Cellular Metabolism

PubMed Central

Sanchez, Erica L.; Lagunoff, Michael

2015-01-01

To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways. PMID:25812764

47 CFR 22.923 - Cellular system configuration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 22.923 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations communicate with and through base transmitters only. Base transmitters communicate with mobile stations...

Functionalized graphene oxide/Fe3O4 hybrids for cellular magnetic resonance imaging and fluorescence labeling.

PubMed

Zhou, Chaohui; Wu, Hui; Wang, Mingliang; Huang, Chusen; Yang, Dapeng; Jia, Nengqin

2017-09-01

In this work, we developed a T 2 -weighted contrast agent based on graphene oxide (GO)/Fe 3 O 4 hybrids for efficient cellular magnetic resonance imaging (MRI). The GO/Fe 3 O 4 hybrids were obtained by combining with co-precipitation method and pyrolysis method. The structural, surface and magnetic characteristics of the hybrids were systematically characterized by transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), AFM, Raman, FT-IR and XRD. The GO/Fe 3 O 4 hybrids were functionalized by modifying with anionic and cationic polyelectrolyte through layer-by-layer assembling. The fluorescence probe fluorescein isothiocyanate (FITC) was further loaded on the surface of functionalized GO/Fe 3 O 4 hybrids to trace the location of GO/Fe 3 O 4 hybrids in cells. Functionalized GO/Fe 3 O 4 hybrids possess good hydrophilicity, less cytotoxicity, high MRI enhancement with the relaxivity (r 2 ) of 493mM -1 s -1 as well as cellular MRI contrast effect. These obtained results indicated that the functionalized GO/Fe 3 O 4 hybrids could have great potential to be utilized as cellular MRI contrast agents for tumor early diagnosis and monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

Cellular Automata Generalized To An Inferential System

NASA Astrophysics Data System (ADS)

Blower, David J.

2007-11-01

Stephen Wolfram popularized elementary one-dimensional cellular automata in his book, A New Kind of Science. Among many remarkable things, he proved that one of these cellular automata was a Universal Turing Machine. Such cellular automata can be interpreted in a different way by viewing them within the context of the formal manipulation rules from probability theory. Bayes's Theorem is the most famous of such formal rules. As a prelude, we recapitulate Jaynes's presentation of how probability theory generalizes classical logic using modus ponens as the canonical example. We emphasize the important conceptual standing of Boolean Algebra for the formal rules of probability manipulation and give an alternative demonstration augmenting and complementing Jaynes's derivation. We show the complementary roles played in arguments of this kind by Bayes's Theorem and joint probability tables. A good explanation for all of this is afforded by the expansion of any particular logic function via the disjunctive normal form (DNF). The DNF expansion is a useful heuristic emphasized in this exposition because such expansions point out where relevant 0s should be placed in the joint probability tables for logic functions involving any number of variables. It then becomes a straightforward exercise to rely on Boolean Algebra, Bayes's Theorem, and joint probability tables in extrapolating to Wolfram's cellular automata. Cellular automata are seen as purely deductive systems, just like classical logic, which probability theory is then able to generalize. Thus, any uncertainties which we might like to introduce into the discussion about cellular automata are handled with ease via the familiar inferential path. Most importantly, the difficult problem of predicting what cellular automata will do in the far future is treated like any inferential prediction problem.

A Study on Cognitive Radio Coexisting with Cellular Systems

NASA Astrophysics Data System (ADS)

Tandai, Tomoya; Horiguchi, Tomoya; Deguchi, Noritaka; Tomizawa, Takeshi; Tomioka, Tazuko

Cognitive Radios (CRs) are expected to perform more significant role in the view of efficient utilization of the spectrum resources in the future wireless communication networks. In this paper, a cognitive radio coexisting with cellular systems is proposed. In the case that a cellular system adopts Frequency Division Duplex (FDD) as a multiplexing scheme, the proposed CR terminals communicate in local area on uplink channels of the cellular system with transmission powers that don't interfere with base stations of the cellular system. Alternatively, in the case that a cellular system adopts Time Division Duplex (TDD), the CR terminals communicate on uplink slots of the cellular system. However if mobile terminals in the cellular system are near the CR network, uplink signals from the mobile terminals may interfere with the CR communications. In order to avoid interference from the mobile terminals, the CR terminal performs carrier sense during a beginning part of uplink slot, and only when the level of detected signal is below a threshold, then the CR terminal transmits a signal during the remained period of the uplink slot. In this paper, both the single carrier CR network that uses one frequency channel of the cellular system and the multicarrier CR network that uses multiple frequency channels of the cellular system are considered. The probabilities of successful CR communications, the average throughputs of the CR communications according to the positions of the CR network, and the interference levels from cognitive radio network to base stations of the cellular system are evaluated in the computer simulation then the effectiveness of the proposed network is clarified.

Dendritic cells modulate burn wound healing by enhancing early proliferation.

PubMed

Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

2016-01-01

Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

47 CFR 22.940 - Criteria for comparative cellular renewal proceedings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Criteria for comparative cellular renewal... CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.940 Criteria for comparative cellular renewal proceedings. This section sets forth criteria to be used in comparative cellular renewal...

47 CFR 22.940 - Criteria for comparative cellular renewal proceedings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Criteria for comparative cellular renewal... CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.940 Criteria for comparative cellular renewal proceedings. This section sets forth criteria to be used in comparative cellular renewal...

47 CFR 22.940 - Criteria for comparative cellular renewal proceedings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Criteria for comparative cellular renewal... CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.940 Criteria for comparative cellular renewal proceedings. This section sets forth criteria to be used in comparative cellular renewal...

47 CFR 22.940 - Criteria for comparative cellular renewal proceedings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Criteria for comparative cellular renewal... CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.940 Criteria for comparative cellular renewal proceedings. This section sets forth criteria to be used in comparative cellular renewal...

47 CFR 22.940 - Criteria for comparative cellular renewal proceedings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Criteria for comparative cellular renewal... CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.940 Criteria for comparative cellular renewal proceedings. This section sets forth criteria to be used in comparative cellular renewal...

Understanding cellular architecture in cancer cells

NASA Astrophysics Data System (ADS)

Bianco, Simone; Tang, Chao

2011-03-01

Understanding the development of cancer is an important goal for today's science. The morphology of cellular organelles, such as the nucleus, the nucleoli and the mitochondria, which is referred to as cellular architecture or cytoarchitecture, is an important indicator of the state of the cell. In particular, there are striking difference between the cellular architecture of a healthy cell versus a cancer cell. In this work we present a dynamical model for the evolution of organelles morphology in cancer cells. Using a dynamical systems approach, we describe the evolution of a cell on its way to cancer as a trajectory in a multidimensional morphology state. The results provided by this work may increase our insight on the mechanism of tumorigenesis and help build new therapeutic strategies.

The iodine-plutonium-xenon age of the Moon-Earth system revisited.

PubMed

Avice, G; Marty, B

2014-09-13

Iodine-plutonium-xenon isotope systematics have been used to re-evaluate time constraints on the early evolution of the Earth-atmosphere system and, by inference, on the Moon-forming event. Two extinct radionuclides ((129)I, T1/2=15.6 Ma and (244)Pu, T1/2=80 Ma) have produced radiogenic (129)Xe and fissiogenic (131-136)Xe, respectively, within the Earth, the related isotope fingerprints of which are seen in the compositions of mantle and atmospheric Xe. Recent studies of Archaean rocks suggest that xenon atoms have been lost from the Earth's atmosphere and isotopically fractionated during long periods of geological time, until at least the end of the Archaean eon. Here, we build a model that takes into account these results. Correction for Xe loss permits the computation of new closure ages for the Earth's atmosphere that are in agreement with those computed for mantle Xe. The corrected Xe formation interval for the Earth-atmosphere system is [Formula: see text] Ma after the beginning of Solar System formation. This time interval may represent a lower limit for the age of the Moon-forming impact. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Average sedimentary rock rare Earth element patterns and crustal evolution: Some observations and implications from the 3800 Ma ISUA supracrustal belt, West Greenland

NASA Technical Reports Server (NTRS)

Dymek, R. F.; Boak, J. L.; Gromet, L. P.

1983-01-01

Rare earth element (REE) data is given on a set of clastic metasediments from the 3800 Ma Isua Supracrustal belt, West Greenland. Each of two units from the same sedimentary sequence has a distinctive REE pattern, but the average of these rocks bears a very strong resemblance to the REE pattern for the North American Shale Composite (NASC), and departs considerably from previous estimates of REE patterns in Archaean sediments. The possibility that the source area for the Isua sediments resembled that of the NASC is regarded as highly unlikely. However, REE patterns like that in the NASC may be produced by sedimentary recycling of material yielding patterns such as are found at Isua. The results lead to the following tentative conclusions: (1) The REE patterns for Isua Seq. B MBG indicate the existence of crustal materials with fractionated REE and negative Eu anomalies at 3800 Ma, (2) The average Seq. B REE pattern resembles that of the North American Shale Composite (NASC), (3) If the Seq. B average is truly representative of its crustal sources, then this early crust could have been extensively differentiated. In this regard, a proper understanding of the NASC pattern, and its relationship to post-Archaean crustal REE reservoirs, is essential, (4) The Isua results may represent a local effect.

47 CFR 32.5003 - Cellular mobile revenue.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003 Cellular...

47 CFR 32.5003 - Cellular mobile revenue.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003 Cellular...

Early Passage Dependence of Mesenchymal Stem Cell Mechanics Influences Cellular Invasion and Migration.

PubMed

Spagnol, Stephen T; Lin, Wei-Chun; Booth, Elizabeth A; Ladoux, Benoit; Lazarus, Hillard M; Dahl, Kris Noel

2016-07-01

The cellular structures and mechanical properties of human mesenchymal stem cells (hMSCs) vary significantly during culture and with differentiation. Previously, studies to measure mechanics have provided divergent results using different quantitative parameters and mechanical models of deformation. Here, we examine hMSCs prepared for clinical use and subject them to mechanical testing conducive to the relevant deformability associated with clinical injection procedures. Micropipette aspiration of hMSCs shows deformation as a viscoelastic fluid, with little variation from cell to cell within a population. After two passages, hMSCs deform as viscoelastic solids. Further, for clinical applicability during stem cell migration in vivo, we investigated the ability of hMSCs to invade into micropillar arrays of increasing confinement from 12 to 8 μm spacing between adjacent micropillars. We find that hMSC samples with reduced deformability and cells that are more solid-like with passage are more easily able to enter the micropillar arrays. Increased cell fluidity is an advantage for injection procedures and optimization of cell selection based on mechanical properties may enhance efficacy of injected hMSC populations. However, the ability to invade and migrate within tight interstitial spaces appears to be increased with a more solidified cytoskeleton, likely from increased force generation and contractility. Thus, there may be a balance between optimal injection survival and in situ tissue invasion.

The cellular basis of the convergence and extension of the Xenopus neural plate.

PubMed

Keller, R; Shih, J; Sater, A

1992-03-01

There is great interest in the patterning and morphogenesis of the vertebrate nervous system, but the morphogenetic movements involved in early neural development and their underlying cellular mechanisms are poorly understood. This paper describes the cellular basis of the early neural morphogenesis of Xenopus laevis. The results have important implications for neural induction. Mapping the fate map of the midneurula (Eagleson and Harris: J. Neurobiol. 21:427-440, 1990) back to the early gastrula with time-lapse video recording demonstrates that the prospective hindbrain and spinal cord are initially very wide and very short, and thus at the beginning of gastrulation all their precursor cells lie within a few cell diameters of the inducing mesoderm. In the midgastrula, the prospective hindbrain and spinal cord undergo very strong convergence and extension movements in two phases: In the first phase they primarily undergo thinning in the radial direction and lengthening (extension) in the animal-vegetal direction, and the second phase is characterized primarily by mediolateral narrowing (convergence) and anterior-posterior lengthening (extension). These movements also occur in sandwich explants of the gastrula, thus demonstrating the local autonomy of the forces producing them. Tracing cell movements with fluorescein dextran-labeled cells in embryos or explants shows that the initial thinning and extension occurs by radial intercalation of deep cells to form fewer layers of greater area, all of which is expressed as increased length. The subsequent convergence and extension occurs by mediolateral intercalation of deep cells to form a longer, narrower array. These results establish that a similar if not identical sequence of radial and mediolateral cell intercalations underlie convergence and extension of the neural and the mesoderm tissues (Wilson and Keller: Development, 112:289-300, 1991). Moreover, these results establish that radial and mediolateral

Phase separation and the formation of cellular bodies

NASA Astrophysics Data System (ADS)

Xu, Bin; Broedersz, Chase P.; Meir, Yigal; Wingreen, Ned S.

Cellular bodies in eukaryotic cells spontaneously assemble to form cellular compartments. Among other functions, these bodies carry out essential biochemical reactions. Cellular bodies form micron-sized structures, which, unlike canonical cell organelles, are not surrounded by membranes. A recent in vitro experiment has shown that phase separation of polymers in solution can explain the formation of cellular bodies. We constructed a lattice-polymer model to capture the essential mechanism leading to this phase separation. We used both analytical and numerical tools to predict the phase diagram of a system of two interacting polymers, including the concentration of each polymer type in the condensed and dilute phase.

47 CFR 22.917 - Emission limitations for cellular equipment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Emission limitations for cellular equipment. 22.917 Section 22.917 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.917 Emission limitations for cellular...

47 CFR 22.917 - Emission limitations for cellular equipment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Emission limitations for cellular equipment. 22.917 Section 22.917 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.917 Emission limitations for cellular...

Cellular proliferation, cellular viability, and biocompatibility of HA-ZnO composites.

PubMed

Saha, Naresh; Dubey, Ashutosh K; Basu, Bikramjit

2012-01-01

One of the important issues in the development of hydroxyapatite (HA)-based biomaterials is the prosthetic infection, which limits wider use of monolithic HA despite superior cellular response. Recently, we reported that ZnO addition to HA can induce bactericidal property. It is therefore important to assess how ZnO addition influences the cytotoxicity property and cell adhesion/proliferation on HA-ZnO composite surfaces in vitro. In the above perspective, the objective of this study is to investigate the cell type and material composition dependent cellular proliferation and viability of pressureless sintered HA-ZnO composites. The combination of cell viability data as well as morphological observations of cultured human osteoblast-like SaOS2 cells and mouse fibroblast L929 cells suggests that HA-ZnO composites containing 10 Wt % or lower ZnO exhibit the ability to support cell adhesion and proliferation. Both SaOS2 and L929 cells exhibit extensive multidirectional network of actin cytoskeleton and cell flattening on the lower ZnO containing (≤10 Wt %) HA-ZnO composites. The in vitro results illustrate how variation in ZnO content can influence significantly the cell vitality, as evaluated using MTT biochemical assay. Also, the critical statistical analysis reveals that ZnO addition needs to be carefully tailored to ensure good in vitro cytocompatibility. The underlying reasons for difference in biological properties are analyzed. It is suggested that surface wettability as well as dissolution of ZnO, both contribute to the observed differences in cellular viability and proliferation. Copyright © 2011 Wiley Periodicals, Inc.

Mechanisms for Variation of Cellular P Stoichiometry: Diverse Cellular Phosphorus Allocation Strategies Across Microbial Groups from the Sargasso Sea

NASA Astrophysics Data System (ADS)

Popendorf, K.; Duhamel, S.

2016-02-01

Phosphorus is the least abundant of the three major macronutrients that define the canonical Redfield ratio, but its place in the backbone of nucleic acids and as an energy trafficking molecule lays a lower bound of cellular phosphorus content that is essential for all life. In addition to forming DNA, RNA, and adenosine triphosphate (ATP), significant amounts of cellular phosphorus may also be allocated to the production of phospholipids and polyphosphate. These latter two biochemicals in particular may occur in significant but highly variable amounts across different microbial groups, and the variation in cellular allocation to these biochemicals may be a contributing factor in defining the elemental stoichiometry of microbes. We investigated this variation in cellular phosphorus allocation across the most abundant microbial groups in the P-depleted Sargasso Sea: Prochlorococcus, Synechococcus, and heterotrophic bacteria. By coupling radioisotope tracing of phosphate and ATP with cell sorting flow cytometry and subsequent biochemical extractions, we made novel measurements of the P allocation to DNA, phospholipids, and polyphosphate in individual microbial groups from environmental populations. These results provide new insights into the cellular mechanisms of variation in stoichiometry and different microbial strategies for adaptation to low-P environments.

Optimizing Cellular Networks Enabled with Renewal Energy via Strategic Learning.

PubMed

Sohn, Insoo; Liu, Huaping; Ansari, Nirwan

2015-01-01

An important issue in the cellular industry is the rising energy cost and carbon footprint due to the rapid expansion of the cellular infrastructure. Greening cellular networks has thus attracted attention. Among the promising green cellular network techniques, the renewable energy-powered cellular network has drawn increasing attention as a critical element towards reducing carbon emissions due to massive energy consumption in the base stations deployed in cellular networks. Game theory is a branch of mathematics that is used to evaluate and optimize systems with multiple players with conflicting objectives and has been successfully used to solve various problems in cellular networks. In this paper, we model the green energy utilization and power consumption optimization problem of a green cellular network as a pilot power selection strategic game and propose a novel distributed algorithm based on a strategic learning method. The simulation results indicate that the proposed algorithm achieves correlated equilibrium of the pilot power selection game, resulting in optimum green energy utilization and power consumption reduction.

Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

PubMed

Gill, Saar

2016-08-01

Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer.

"The Only 13-Year-Old on Planet Earth without a Cell Phone": Meanings of Cell Phones in Early Adolescents' Everyday Lives

ERIC Educational Resources Information Center

Blair, Bethany L.; Fletcher, Anne C.

2011-01-01

Cellular telephones have become an increasingly prevalent feature of contemporary American life, with usage often beginning during early adolescence. With this in mind, twenty 7th graders and their mothers participated in separate qualitative interviews regarding early adolescents' use of cell phones as well as perceived risks and benefits of such…

δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

PubMed

Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

2017-01-01

Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gravitational Effects on Cellular Flame Structure

NASA Technical Reports Server (NTRS)

Dunsky, C. M.; Fernandez-Pello, A. C.

1991-01-01

An experimental investigation has been conducted of the effect of gravity on the structure of downwardly propagating, cellular premixed propane-oxygen-nitrogen flames anchored on a water-cooled porous-plug burner. The flame is subjected to microgravity conditions in the NASA Lewis 2.2-second drop tower, and flame characteristics are recorded on high-speed film. These are compared to flames at normal gravity conditions with the same equivalence ratio, dilution index, mixture flow rate, and ambient pressure. The results show that the cellular instability band, which is located in the rich mixture region, changes little under the absence of gravity. Lifted normal-gravity flames near the cellular/lifted limits, however, are observed to become cellular when gravity is reduced. Observations of a transient cell growth period following ignition point to heat loss as being an important mechanism in the overall flame stability, dominating the stabilizing effect of buoyancy for these downwardly-propagating burner-anchored flames. The pulsations that are observed in the plume and diffusion flame generated downstream of the premixed flame in the fuel rich cases disappear in microgravity, verifying that these fluctuations are gravity related.

Alternative Ways to Think about Cellular Internal Ribosome Entry*

PubMed Central

Gilbert, Wendy V.

2010-01-01

Internal ribosome entry sites (IRESs) are specialized mRNA elements that allow recruitment of eukaryotic ribosomes to naturally uncapped mRNAs or to capped mRNAs under conditions in which cap-dependent translation is inhibited. Putative cellular IRESs have been proposed to play crucial roles in stress responses, development, apoptosis, cell cycle control, and neuronal function. However, most of the evidence for cellular IRES activity rests on bicistronic reporter assays, the reliability of which has been questioned. Here, the mechanisms underlying cap-independent translation of cellular mRNAs and the contributions of such translation to cellular protein synthesis are discussed. I suggest that the division of cellular mRNAs into mutually exclusive categories of “cap-dependent” and “IRES-dependent” should be reconsidered and that the implications of cellular IRES activity need to be incorporated into our models of cap-dependent initiation. PMID:20576611

Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

NASA Astrophysics Data System (ADS)

Johnson, Lee James

2001-08-01

The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is

The Emergence of Predators in Early Life: There was No Garden of Eden

PubMed Central

de Nooijer, Silvester; Holland, Barbara R.; Penny, David

2009-01-01

Background Eukaryote cells are suggested to arise somewhere between 0.85∼2.7 billion years ago. However, in the present world of unicellular organisms, cells that derive their food and metabolic energy from larger cells engulfing smaller cells (phagocytosis) are almost exclusively eukaryotic. Combining these propositions, that eukaryotes were the first phagocytotic predators and that they arose only 0.85∼2.7 billion years ago, leads to an unexpected prediction of a long period (∼1–3 billion years) with no phagocytotes – a veritable Garden of Eden. Methodology We test whether such a long period is reasonable by simulating a population of very simple unicellular organisms - given only basic physical, biological and ecological principles. Under a wide range of initial conditions, cellular specialization occurs early in evolution; we find a range of cell types from small specialized primary producers to larger opportunistic or specialized predators. Conclusions Both strategies, specialized smaller cells and phagocytotic larger cells are apparently fundamental biological strategies that are expected to arise early in cellular evolution. Such early predators could have been ‘prokaryotes’, but if the earliest cells on the eukaryote lineage were predators then this explains most of their characteristic features. PMID:19492046

Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

PubMed Central

Liu, Pei; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

2015-01-01

Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response. PMID:25720653

Viral and Cellular Determinants of the Hepatitis C Virus Envelope-Heparan Sulfate Interaction▿

PubMed Central

Barth, Heidi; Schnober, Eva K.; Zhang, Fuming; Linhardt, Robert J.; Depla, Erik; Boson, Bertrand; Cosset, Francois-Loic; Patel, Arvind H.; Blum, Hubert E.; Baumert, Thomas F.

2006-01-01

Cellular binding and entry of hepatitis C virus (HCV) are the first steps of viral infection and represent a major target for antiviral antibodies and novel therapeutic strategies. We have recently demonstrated that heparan sulfate (HS) plays a key role in the binding of HCV envelope glycoprotein E2 to target cells (Barth et al., J. Biol. Chem. 278:41003-41012, 2003). In this study, we characterized the HCV-HS interaction and analyzed its inhibition by antiviral host immune responses. Using recombinant envelope glycoproteins, virus-like particles, and HCV pseudoparticles as model systems for the early steps of viral infection, we mapped viral and cellular determinants of HCV-HS interaction. HCV-HS binding required a specific HS structure that included N-sulfo groups and a minimum of 10 to 14 saccharide subunits. HCV envelope binding to HS was mediated by four viral epitopes overlapping the E2 hypervariable region 1 and E2-CD81 binding domains. In functional studies using HCV pseudoparticles, we demonstrate that HCV binding and entry are specifically inhibited by highly sulfated HS. Finally, HCV-HS binding was markedly inhibited by antiviral antibodies derived from HCV-infected individuals. In conclusion, our results demonstrate that binding of the viral envelope to a specific HS configuration represents an important step for the initiation of viral infection and is a target of antiviral host immune responses in vivo. Mapping of viral and cellular determinants of HCV-HS interaction sets the stage for the development of novel HS-based antiviral strategies targeting viral attachment and entry. PMID:16928753

Asymmetric cellular memory in bacteria exposed to antibiotics.

PubMed

Mathis, Roland; Ackermann, Martin

2017-03-09

The ability to form a cellular memory and use it for cellular decision-making could help bacteria to cope with recurrent stress conditions. We analyzed whether bacteria would form a cellular memory specifically if past events are predictive of future conditions. We worked with the asymmetrically dividing bacterium Caulobacter crescentus where past events are expected to only be informative for one of the two cells emerging from division, the sessile cell that remains in the same microenvironment and does not migrate. Time-resolved analysis of individual cells revealed that past exposure to low levels of antibiotics increases tolerance to future exposure for the sessile but not for the motile cell. Using computer simulations, we found that such an asymmetry in cellular memory could be an evolutionary response to situations where the two cells emerging from division will experience different future conditions. Our results raise the question whether bacteria can evolve the ability to form and use cellular memory conditionally in situations where it is beneficial.

High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium.

PubMed

Lu, Zhongyan; Shen, Hong; Shen, Zanming

2018-01-01

In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. These results indicated that the alterations of cellular metabolism promote the alterations in cellular

Primary cellular meningeal defects cause neocortical dysplasia and dyslamination

PubMed Central

Hecht, Jonathan H.; Siegenthaler, Julie A.; Patterson, Katelin P.; Pleasure, Samuel J.

2010-01-01

Objective Cortical malformations are important causes of neurological morbidity, but in many cases their etiology is poorly understood. Mice with Foxc1 mutations have cellular defects in meningeal development. We use hypomorphic and null alleles of Foxc1 to study the effect of meningeal defects on neocortical organization. Methods Embryos with loss of Foxc1 activity were generated using the hypomorphic Foxc1hith allele and the null Foxc1lacZ allele. Immunohistologic analysis was used to assess cerebral basement membrane integrity, marginal zone heterotopia formation, neuronal overmigration, meningeal defects, and changes in basement membrane composition. Dysplasia severity was quantified using two measures. Results Cortical dysplasia resembling cobblestone cortex, with basement membrane breakdown and lamination defects, is seen in Foxc1 mutants. As Foxc1 activity was reduced, abnormalities in basement membrane integrity, heterotopia formation, neuronal overmigration, and meningeal development appeared earlier in gestation and were more severe. Surprisingly, the basement membrane appeared intact at early stages of development in the face of severe deficits in meningeal development. Prominent defects in basement membrane integrity appeared as development proceeded. Molecular analysis of basement membrane laminin subunits demonstrated that loss of the meninges led to changes in basement membrane composition. Interpretation Cortical dysplasia can be caused by cellular defects in the meninges. The meninges are not required for basement membrane establishment but are needed for remodeling as the brain expands. Specific changes in basement membrane composition may contribute to subsequent breakdown. Our study raises the possibility that primary meningeal defects may cortical dysplasia in some cases. PMID:20976766

Production, properties, and applications of hydrocolloid cellular solids.

PubMed

Nussinovitch, Amos

2005-02-01

Many common synthetic and edible materials are, in fact, cellular solids. When classifying the structure of cellular solids, a few variables, such as open vs. closed cells, flexible vs. brittle cell walls, cell-size distribution, cell-wall thickness, cell shape, the uniformity of the structure of the cellular solid and the different scales of length are taken into account. Compressive stress-strain relationships of most cellular solids can be easily identified according to their characteristic sigmoid shape, reflecting three deformation mechanisms: (i) elastic distortion under small strains, (ii) collapse and/or fracture of the cell walls, and (iii) densification. Various techniques are used to produce hydrocolloid (gum) cellular solids. The products of these include (i) sponges, obtained when the drying gel contains the occasionally produced gas bubbles; (ii) sponges produced by the immobilization of microorganisms; (iii) solid foams produced by drying foamed solutions or gels containing oils, and (iv) hydrocolloid sponges produced by enzymatic reactions. The porosity of the manufactured cellular solid is subject to change and depends on its composition and the processing technique. The porosity is controlled by a range of methods and the resulting surface structures can be investigated by microscopy and analyzed using fractal methods. Models used to describe stress-strain behaviors of hydrocolloid cellular solids as well as multilayered products and composites are discussed in detail in this manuscript. Hydrocolloid cellular solids have numerous purposes, simple and complex, ranging from dried texturized fruits to carriers of vitamins and other essential micronutrients. They can also be used to control the acoustic response of specific dry food products, and have a great potential for future use in countless different fields, from novel foods and packaging to medicine and medical care, daily commodities, farming and agriculture, and the environmental, chemical

Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

PubMed Central

Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

2013-01-01

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

47 CFR 32.5003 - Cellular mobile revenue.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular mobile revenue. 32.5003 Section 32... mobile revenue. This account shall include message revenue derived from cellular mobile telecommunications systems connected to the public switched network placed between mobile units and other stations...

At a glance: cellular biology for engineers.

PubMed

Khoshmanesh, K; Kouzani, A Z; Nahavandi, S; Baratchi, S; Kanwar, J R

2008-10-01

Engineering contributions have played an important role in the rise and evolution of cellular biology. Engineering technologies have helped biologists to explore the living organisms at cellular and molecular levels, and have created new opportunities to tackle the unsolved biological problems. There is now a growing demand to further expand the role of engineering in cellular biology research. For an engineer to play an effective role in cellular biology, the first essential step is to understand the cells and their components. However, the stumbling block of this step is to comprehend the information given in the cellular biology literature because it best suits the readers with a biological background. This paper aims to overcome this bottleneck by describing the human cell components as micro-plants that form cells as micro-bio-factories. This concept can accelerate the engineers' comprehension of the subject. In this paper, first the structure and function of different cell components are described. In addition, the engineering attempts to mimic various cell components through numerical modelling or physical implementation are highlighted. Next, the interaction of different cell components that facilitate complicated chemical processes, such as energy generation and protein synthesis, are described. These complex interactions are translated into simple flow diagrams, generally used by engineers to represent multi-component processes.

Endoplasmic reticulum mediated signaling in cellular microdomains

PubMed Central

Biwer, Lauren; Isakson, Brant E

2016-01-01

The endoplasmic reticulum (ER) is a prime mediator of cellular signaling due to its functions as an internal cellular store for calcium, as well as a site for synthesis of proteins and lipids. Its peripheral network of sheets and tubules facilitate calcium and lipid signaling, especially in areas of the cell that are more distant to the main cytoplasmic network. Specific membrane proteins shape the peripheral ER architecture and influence the network stability in order to project into restricted spaces. The signaling microdomains are anatomically separate from the cytoplasm as a whole and exhibit localized protein, ion channel and cytoskeletal element expression. Signaling can also occur between the ER and other organelles, such as the Golgi or mitochondria. Lipids made in the ER membrane can be sent to the Golgi via specialized transfer proteins and specific phospholipid synthases are enriched at ER-mitochondria junctions to more efficiently expedite phospholipid transfer. As a hub for protein and lipid synthesis, a store for intracellular calcium [Ca2+]i, and a mediator of cellular stress, the ER is an important cellular organelle. Its ability to organize into tubules and project into restricted spaces allows for discrete and temporal signaling, which is important for cellular physiology and organism homeostasis. PMID:26973141

Early Effects of Salinity on Water Transport in Arabidopsis Roots. Molecular and Cellular Features of Aquaporin Expression1

PubMed Central

Boursiac, Yann; Chen, Sheng; Luu, Doan-Trung; Sorieul, Mathias; van den Dries, Niels; Maurel, Christophe

2005-01-01

Aquaporins facilitate the uptake of soil water and mediate the regulation of root hydraulic conductivity (Lpr) in response to a large variety of environmental stresses. Here, we use Arabidopsis (Arabidopsis thaliana) plants to dissect the effects of salt on both Lpr and aquaporin expression and investigate possible molecular and cellular mechanisms of aquaporin regulation in plant roots under stress. Treatment of plants by 100 mm NaCl was perceived as an osmotic stimulus and induced a rapid (half-time, 45 min) and significant (70%) decrease in Lpr, which was maintained for at least 24 h. Macroarray experiments with gene-specific tags were performed to investigate the expression of all 35 genes of the Arabidopsis aquaporin family. Transcripts from 20 individual aquaporin genes, most of which encoded members of the plasma membrane intrinsic protein (PIP) and tonoplast intrinsic protein (TIP) subfamilies, were detected in nontreated roots. All PIP and TIP aquaporin transcripts with a strong expression signal showed a 60% to 75% decrease in their abundance between 2 and 4 h following exposure to salt. The use of antipeptide antibodies that cross-reacted with isoforms of specific aquaporin subclasses revealed that the abundance of PIP1s decreased by 40% as early as 30 min after salt exposure, whereas PIP2 and TIP1 homologs showed a 20% to 40% decrease in abundance after 6 h of treatment. Expression in transgenic plants of aquaporins fused to the green fluorescent protein revealed that the subcellular localization of TIP2;1 and PIP1 and PIP2 homologs was unchanged after 45 min of exposure to salt, whereas a TIP1;1-green fluorescent protein fusion was relocalized into intracellular spherical structures tentatively identified as intravacuolar invaginations. The appearance of intracellular structures containing PIP1 and PIP2 homologs was occasionally observed after 2 h of salt treatment. In conclusion, this work shows that exposure of roots to salt induces changes in

Calcification and Silicification: Fossilization Potential of Cyanobacteria from Stromatolites of Niuafo‘ou's Caldera Lakes (Tonga) and Implications for the Early Fossil Record

PubMed Central

Kazmierczak, Józef; Łukomska-Kowalczyk, Maja; Kempe, Stephan

2012-01-01

Abstract Calcification and silicification processes of cyanobacterial mats that form stromatolites in two caldera lakes of Niuafo‘ou Island (Vai Lahi and Vai Si‘i) were evaluated, and their importance as analogues for interpreting the early fossil record are discussed. It has been shown that the potential for morphological preservation of Niuafo‘ou cyanobacteria is highly dependent on the timing and type of mineral phase involved in the fossilization process. Four main modes of mineralization of cyanobacteria organic parts have been recognized: (i) primary early postmortem calcification by aragonite nanograins that transform quickly into larger needle-like crystals and almost totally destroy the cellular structures, (ii) primary early postmortem silicification of almost intact cyanobacterial cells that leave a record of spectacularly well-preserved cellular structures, (iii) replacement by silica of primary aragonite that has already recrystallized and obliterated the cellular structures, (iv) occasional replacement of primary aragonite precipitated in the mucopolysaccharide sheaths and extracellular polymeric substances by Al-Mg-Fe silicates. These observations suggest that the extremely scarce earliest fossil record may, in part, be the result of (a) secondary replacement by silica of primary carbonate minerals (aragonite, calcite, siderite), which, due to recrystallization, had already annihilated the cellular morphology of the mineralized microbiota or (b) relatively late primary silicification of already highly degraded and no longer morphologically identifiable microbial remains. Key Words: Stromatolites—Cyanobacteria—Calcification—Silicification—Niuafo‘ou (Tonga)—Archean. Astrobiology 12, 535–548. PMID:22794297

Alzheimer's as a Systems-Level Disease Involving the Interplay of Multiple Cellular Networks.

PubMed

Castrillo, Juan I; Oliver, Stephen G

2016-01-01

sequence of events underlying AD. Indeed, studies of models of AD in simple organisms, differentiated cells in culture and rodents are beginning to offer hope that the onset and progression of AD, if detected at an early stage, may be stopped, delayed, or even reversed, by activating or modulating networks involved in proteostasis and the clearance of toxic species. In practice, the incorporation of next-generation neuroimaging, high-throughput and computational approaches are opening the way towards early diagnosis well before irreversible cell death. Thus, the presence or co-occurrence of: (a) accumulation of toxic Aβ oligomers and tau species; (b) altered splicing and transcriptome patterns; (c) impaired redox, proteostatic, and metabolic networks together with, (d) compromised homeostatic capacities may constitute relevant 'AD hallmarks at the cellular level' towards reliable and early diagnosis. From here, preventive lifestyle changes and tailored therapies may be investigated, such as combined strategies aimed at both lowering the production of toxic species and potentiating homeostatic responses, in order to prevent or delay the onset, and arrest, alleviate, or even reverse the progression of the disease.

Paleoenvironmental signals and paleoclimatic condition of the Early Maastrichtian oil shales from Central Eastern Desert, Egypt

NASA Astrophysics Data System (ADS)

Fathy, Douaa; Wagreich, Michael; Zaki, Rafat; Mohamed, Ramadan S. A.

2016-04-01

Early Maastrichtian oil shales are hosted in the Duwi Formation of the Central Eastern Desert, Egypt. The examined member represents up to 20% of the total Duwi Formation. This interval is mainly composed of siliciclastic facies, phosphorites facies and carbonate facies. Oil shales microfacies is mainly composed of smectite, kaolinite, calcite, fluorapatite, quartz and pyrite. They are enriched in a number of major elements and trace metals in particular Ca, P, V, Ni, Cr, Sr, Zn, Mo, Nb, U and Y compared to the post-Archaean Australian shale (PAAS). Chondrite-normalized REEs patterns of oil shales for the studied area display light rare earth elements enrichment relatively to heavy rare earth elements with negative Ce/Ce* and Eu/Eu* anomalies. The most remarkable indicators for redox conditions are enrichments of V, Mo, Ni, Cr, U content and depletion of Mn content. Besides, V/V+Ni, V/Ni, U/Th, Ni/Co, authigentic uranium ratios with presence of framboidal shape of pyrite and its size are reflecting the deposition of these shales under marine anoxic to euxinic environmental conditions. Additionally, the ratio of Strontium (Sr) to Barium (Ba) Sr/Ba reflected highly saline water during deposition. Elemental ratios critical to paleoclimate and paleoweathering (Rb /Sr, Al2O3/TiO2), CIA values, binary diagram between (Al2O3+K2O+Na2O) and SiO2 and types of clay minerals dominated reflect warm to humid climate conditions prevailing during the accumulation of these organic-rich petroleum source rocks.

Cellular Restriction Factors of Feline Immunodeficiency Virus

PubMed Central

Zielonka, Jörg; Münk, Carsten

2011-01-01

Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors. PMID:22069525

Specific early fine structural changes in the lung following irradiation. [X rays; mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penney, D.P.; Rubin, P.

1977-01-01

The lungs of mice were irradiated with single and fractionated doses of 1000 R, 2000 R, and 3000 R and recovered 1 hr, 1 day, 1 week, and 1 month following exposure. Electron microscopy revealed early changes in the decrement of lamellar bodies of Type II pneumocytes and increased fibrous content and edema in the septal walls of all animals treated. Those lungs treated with fractionated doses of irradiation displayed more pronounced cellular damage than did singly-dosed lungs. It is proposed that these early changes may predict for subsequent atelectasis.

Early diagnosis of tongue malignancy using laser induced fluorescence spectroscopy technique

NASA Astrophysics Data System (ADS)

Patil, Ajeetkumar; Unnikrishnan V., K.; Ongole, Ravikiran; Pai, Keerthilatha M.; Kartha, V. B.; Chidangil, Santhosh

2015-07-01

Oral cancer together with pharyngeal cancer is the sixth most common malignancy reported worldwide and one with high mortality ratio among all malignancies [1]. Worldwide 450,000 new cases are estimated in 2014[2]. About 90% are a type of cancer called squamous cell carcinoma (SCC). SCC of the tongue is the most common oral malignancy accounting for approximately 40% of all oral carcinomas. One of the important factors for successful therapy of any malignancy is early diagnosis. Although considerable progress has been made in understanding the cellular and molecular mechanisms of tumorigenesis, lack of reliable diagnostic methods for early detection leading to delay in therapy is an important factor responsible for the increase in the mortality rate in various types of cancers. Spectroscopy techniques are extremely sensitive for the analysis of biochemical changes in cellular systems. These techniques can provide a valuable information on alterations that occur during the development of cancer. This is especially important in oral cancer, where "tumor detection is complicated by a tendency towards field cancerization, leading to multi-centric lesions" and "current techniques detect malignant change too late" [3], and "biopsies are not representative of the whole premalignant lesion". [4

Marine molluscs in environmental monitoring. I. Cellular and molecular responses

NASA Astrophysics Data System (ADS)

Bresler, Vladimir; Abelson, Avigdor; Fishelson, Lev; Feldstein, Tamar; Rosenfeld, Michael; Mokady, Ofer

2003-10-01

levels of biological organization—the molecular and cellular level—the parameters measured may have the capacity not only for biomonitoring environmental quality, but also for early warning.

TRIENNIAL GROWTH AND DEVELOPMENT SYMPOSIUM: Factors influencing bovine intramuscular adipose tissue development and cellularity.

PubMed

Albrecht, E; Schering, L; Liu, Y; Komolka, K; Kühn, C; Wimmers, K; Gotoh, T; Maak, S

2017-05-01

Appearance, distribution, and amount of intramuscular fat (IMF), often referred to as marbling, are highly variable and depend on environmental and genetic factors. On the molecular level, the concerted action of several drivers, including hormones, receptors, transcription factors, etc., determines where clusters of adipocytes arise. Therefore, the aim of future studies remains to identify such factors as biological markers of IMF to increase the ability to identify animals that deposit IMF early in age to increase efficiency of high-quality meat production. In an attempt to unravel the cellular development of marbling, we investigated the abundance of markers for adipogenic differentiation during fattening of cattle and the transcriptome of muscle and dissected IMF. Markers of different stages of adipogenic differentiation are well known from cell culture experiments. They are usually transiently expressed, such as delta-like homolog 1 (DLK1) that is abundant in preadipocytes and absent during differentiation to mature adipocytes. It is even a greater challenge to detect those markers in live animals. Within skeletal muscles, hyperplasia and hypertrophy of adipocytes can be observed throughout life. Therefore, development of marbling requires, on the cellular level, recruitment, proliferation, and differentiation of adipogenic cells to store excess energy in the form of lipids in new cells. In a recent study, we investigated the localization and abundance of early markers of adipogenic differentiation, such as DLK1, in bovine muscle tissue. An inverse relationship between IMF content and number of DLK1-positive cells in bovine muscle was demonstrated. Considering the cellular environment of differentiating adipocytes in muscle and the secretory action of adipocytes and myocytes, it becomes obvious that cross talk between cells via adipokines and myokines may be important for IMF development. Secreted proteins can act on other cells, inhibiting or stimulating

Dynamics of Cellular Responses to Radiation

PubMed Central

Wodarz, Dominik; Sorace, Ron; Komarova, Natalia L.

2014-01-01

Understanding the consequences of exposure to low dose ionizing radiation is an important public health concern. While the risk of low dose radiation has been estimated by extrapolation from data at higher doses according to the linear non-threshold model, it has become clear that cellular responses can be very different at low compared to high radiation doses. Important phenomena in this respect include radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive responses, low dose exposure can protect against subsequent challenges, and two mechanisms have been suggested: an intracellular mechanism, inducing cellular changes as a result of the priming radiation, and induction of a protected state by inter-cellular communication. We use mathematical models to examine the effect of these mechanisms on cellular responses to low dose radiation. We find that the intracellular mechanism can account for the occurrence of radioadaptive responses. Interestingly, the same mechanism can also explain the existence of the HRS and IRR phenomena, and successfully describe experimentally observed dose-response relationships for a variety of cell types. This indicates that different, seemingly unrelated, low dose phenomena might be connected and driven by common core processes. With respect to the inter-cellular communication mechanism, we find that it can also account for the occurrence of radioadaptive responses, indicating redundancy in this respect. The model, however, also suggests that the communication mechanism can be vital for the long term survival of cell populations that are continuously exposed to relatively low levels of radiation, which cannot be achieved with the intracellular mechanism in our model. Experimental tests to address our model predictions are proposed. PMID:24722167

Diversity of burial rates in convergent settings decreased as Earth aged.

PubMed

Nicoli, Gautier; Moyen, Jean-François; Stevens, Gary

2016-05-24

The evolution and the growth of the continental crust is inextricably linked to the evolution of Earth's geodynamic processes. The detrital zircon record within the continental crust, as well as the isotopic composition of this crust, indicates that the amount of juvenile felsic material decreased with time and that in geologically recent times, the generation of new crust is balanced by recycling of the crust back into the mantle within subduction zones. However it cannot always have been so; yet the nature of the crust and the processes of crustal reworking in the Precambrian Earth are not well constrained. Here we use both detrital zircon ages and metamorphic pressure-temperature-time (P-T-t) information from metasedimentary units deposited in proposed convergent settings from Archaean, Proterozoic and Phanerozoic terrains to characterize the evolution of minimum estimates of burial rate (km.Ma(-1)) as a function of the age of the rocks. The demonstrated decrease in burial rate correlates positively with a progressive decrease in the production of juvenile felsic crust in the Archaean and Proterozoic. Burial rates are also more diverse in the Archaean than in modern times. We interpret these features to reflect a progressive decrease in the diversity of tectonic processes from Archaean to present, coupled with the emergence of the uniquely Phanerozoic modern-style collision.

Diversity of burial rates in convergent settings decreased as Earth aged

PubMed Central

Nicoli, Gautier; Moyen, Jean-François; Stevens, Gary

2016-01-01

The evolution and the growth of the continental crust is inextricably linked to the evolution of Earth’s geodynamic processes. The detrital zircon record within the continental crust, as well as the isotopic composition of this crust, indicates that the amount of juvenile felsic material decreased with time and that in geologically recent times, the generation of new crust is balanced by recycling of the crust back into the mantle within subduction zones. However it cannot always have been so; yet the nature of the crust and the processes of crustal reworking in the Precambrian Earth are not well constrained. Here we use both detrital zircon ages and metamorphic pressure-temperature-time (P-T-t) information from metasedimentary units deposited in proposed convergent settings from Archaean, Proterozoic and Phanerozoic terrains to characterize the evolution of minimum estimates of burial rate (km.Ma−1) as a function of the age of the rocks. The demonstrated decrease in burial rate correlates positively with a progressive decrease in the production of juvenile felsic crust in the Archaean and Proterozoic. Burial rates are also more diverse in the Archaean than in modern times. We interpret these features to reflect a progressive decrease in the diversity of tectonic processes from Archaean to present, coupled with the emergence of the uniquely Phanerozoic modern-style collision. PMID:27216133

Reliable Cellular Automata with Self-Organization

NASA Astrophysics Data System (ADS)

Gács, Peter

2001-04-01

In a probabilistic cellular automaton in which all local transitions have positive probability, the problem of keeping a bit of information indefinitely is nontrivial, even in an infinite automaton. Still, there is a solution in 2 dimensions, and this solution can be used to construct a simple 3-dimensional discrete-time universal fault-tolerant cellular automaton. This technique does not help much to solve the following problems: remembering a bit of information in 1 dimension; computing in dimensions lower than 3; computing in any dimension with non-synchronized transitions. Our more complex technique organizes the cells in blocks that perform a reliable simulation of a second (generalized) cellular automaton. The cells of the latter automaton are also organized in blocks, simulating even more reliably a third automaton, etc. Since all this (a possibly infinite hierarchy) is organized in "software," it must be under repair all the time from damage caused by errors. A large part of the problem is essentially self-stabilization recovering from a mess of arbitrary size and content. The present paper constructs an asynchronous one-dimensional fault-tolerant cellular automaton, with the further feature of "self-organization." The latter means that unless a large amount of input information must be given, the initial configuration can be chosen homogeneous.

Design, synthesis and cellular metabolism study of 4'-selenonucleosides.

PubMed

Yu, Jinha; Sahu, Pramod K; Kim, Gyudong; Qu, Shuhao; Choi, Yoojin; Song, Jayoung; Lee, Sang Kook; Noh, Minsoo; Park, Sunghyouk; Jeong, Lak Shin

2015-01-01

4'-seleno-homonucleosides were synthesized as next-generation nucleosides, and their cellular phosphorylation was studied to confirm the hypothesis that bulky selenium atom can sterically hinder the approach of cellular nucleoside kinase to the 5'-OH for phosphorylation. 4'-seleno-homonucleosides (n = 2), with one-carbon homologation, were synthesized through a tandem seleno-Michael addition-SN2 ring cyclization. LC-MS analysis demonstrated that they were phosphorylated by cellular nucleoside kinases, resulting in anticancer activity. The bulky selenium atom played a key role in deciding the phosphorylation by cellular nucleoside kinases. [Formula: see text].

Cellular Factors Required for Lassa Virus Budding

PubMed Central

Urata, Shuzo; Noda, Takeshi; Kawaoka, Yoshihiro; Yokosawa, Hideyoshi; Yasuda, Jiro

2006-01-01

It is known that Lassa virus Z protein is sufficient for the release of virus-like particles (VLPs) and that it has two L domains, PTAP and PPPY, in its C terminus. However, little is known about the cellular factor for Lassa virus budding. We examined which cellular factors are used in Lassa virus Z budding. We demonstrated that Lassa Z protein efficiently produces VLPs and uses cellular factors, Vps4A, Vps4B, and Tsg101, in budding, suggesting that Lassa virus budding uses the multivesicular body pathway functionally. Our data may provide a clue to develop an effective antiviral strategy for Lassa virus. PMID:16571837

Failover in Cellular Automata

NASA Astrophysics Data System (ADS)

Kumar, Shailesh; Rao, Shrisha

This paper studies a phenomenon called failover, and shows that this phenomenon (in particular, stateless failover) can be modeled by Game of Life cellular automata. This is the first time that this sophisticated real-life system behavior has been modeled in abstract terms. A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using the primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

Cellular and Molecular Biological Approaches to Interpreting Ancient Biomarkers

NASA Astrophysics Data System (ADS)

Newman, Dianne K.; Neubauer, Cajetan; Ricci, Jessica N.; Wu, Chia-Hung; Pearson, Ann

2016-06-01

Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of this progress. By way of example, we review how attempts to understand the biological function of 2-methylhopanoids in modern bacteria have changed our interpretation of what their molecular fossils tell us about the early history of life. They were once thought to be biomarkers of cyanobacteria and hence the evolution of oxygenic photosynthesis, but we now believe that 2-methylhopanoid biosynthetic capacity originated in the Alphaproteobacteria, that 2-methylhopanoids are regulated in response to stress, and that hopanoid 2-methylation enhances membrane rigidity. We present a new interpretation of 2-methylhopanes that bridges the gap between studies of the functions of 2-methylhopanoids and their patterns of occurrence in the rock record.

Adoptive cellular therapy of cancer: exploring innate and adaptive cellular crosstalk to improve anti-tumor efficacy.

PubMed

Payne, Kyle K; Bear, Harry D; Manjili, Masoud H

2014-08-01

The mammalian immune system has evolved to produce multi-tiered responses consisting of both innate and adaptive immune cells collaborating to elicit a functional response to a pathogen or neoplasm. Immune cells possess a shared ancestry, suggestive of a degree of coevolution that has resulted in optimal functionality as an orchestrated and highly collaborative unit. Therefore, the development of therapeutic modalities that harness the immune system should consider the crosstalk between cells of the innate and adaptive immune systems in order to elicit the most effective response. In this review, the authors will discuss the success achieved using adoptive cellular therapy in the treatment of cancer, recent trends that focus on purified T cells, T cells with genetically modified T-cell receptors and T cells modified to express chimeric antigen receptors, as well as the use of unfractionated immune cell reprogramming to achieve optimal cellular crosstalk upon infusion for adoptive cellular therapy.

Role of cellular adhesions in tissue dynamics spectroscopy

NASA Astrophysics Data System (ADS)

Merrill, Daniel A.; An, Ran; Turek, John; Nolte, David

2014-02-01

Cellular adhesions play a critical role in cell behavior, and modified expression of cellular adhesion compounds has been linked to various cancers. We tested the role of cellular adhesions in drug response by studying three cellular culture models: three-dimensional tumor spheroids with well-developed cellular adhesions and extracellular matrix (ECM), dense three-dimensional cell pellets with moderate numbers of adhesions, and dilute three-dimensional cell suspensions in agarose having few adhesions. Our technique for measuring the drug response for the spheroids and cell pellets was biodynamic imaging (BDI), and for the suspensions was quasi-elastic light scattering (QELS). We tested several cytoskeletal chemotherapeutic drugs (nocodazole, cytochalasin-D, paclitaxel, and colchicine) on three cancer cell lines chosen from human colorectal adenocarcinoma (HT-29), human pancreatic carcinoma (MIA PaCa-2), and rat osteosarcoma (UMR-106) to exhibit differences in adhesion strength. Comparing tumor spheroid behavior to that of cell suspensions showed shifts in the spectral motion of the cancer tissues that match predictions based on different degrees of cell-cell contacts. The HT-29 cell line, which has the strongest adhesions in the spheroid model, exhibits anomalous behavior in some cases. These results highlight the importance of using three-dimensional tissue models in drug screening with cellular adhesions being a contributory factor in phenotypic differences between the drug responses of tissue and cells.

Ultramafic Terranes and Associated Springs as Analogs for Mars and Early Earth

NASA Technical Reports Server (NTRS)

Blake, David; Schulte, Mitch; Cullings, Ken; DeVincezi, D. (Technical Monitor)

2002-01-01

Putative extinct or extant Martian organisms, like their terrestrial counterparts, must adopt metabolic strategies based on the environments in which they live. In order for organisms to derive metabolic energy from the natural environment (Martian or terrestrial), a state of thermodynamic disequilibrium must exist. The most widespread environment of chemical disequilibrium on present-day Earth results from the interaction of mafic rocks of the ocean crust with liquid water. Such environments were even more pervasive and important on the Archean Earth due to increased geothermal heat flow and the absence of widespread continental crust formation. The composition of the lower crust and upper mantle of the Earth is essentially the-same as that of Mars, and the early histories of these two planets are similar. It follows that a knowledge of the mineralogy, water-rock chemistry and microbial ecology of Earth's oceanic crust could be of great value in devising a search strategy for evidence of past or present life on Mars. In some tectonic regimes, cross-sections of lower oceanic crust and upper mantle are exposed on land as so-called "ophiolite suites." Such is the case in the state of California (USA) as a result of its location adjacent to active plate margins. These mafic and ultramafic rocks contain numerous springs that offer an easily accessible field laboratory for studying water/rock interactions and the microbial communities that are supported by the resulting geochemical energy. A preliminary screen of Archaean biodiversity was conducted in a cold spring located in a presently serpentinizing ultramafic terrane. PCR and phylogenetic analysis of partial 16s rRNA, sequences were performed on water and sediment samples. Archaea of recent phylogenetic origin were detected with sequences nearly identical to those of organisms living in ultra-high pH lakes of Africa.

Crustal formation and recycling in an oceanic environment in the early Earth

NASA Astrophysics Data System (ADS)

van Thienen, P.; van den Berg, A. P.; Vlaar, N. J.

2003-04-01

Several lines of evidence indicate higher mantle temperatures (by some hundreds of degrees) during the early history of the Earth. Due to the strong effect of temperature on viscosity as well as on the degree of melting, this enforces a geodynamic regime which is different from the present plate tectonics, and in which smaller scale processes play a more important role. Upwelling of a hotter mantle produces a thicker oceanic crust, of which the lower part may reside in the eclogite stability field. This facilitates delamination, making room for fresh mantle material which may partly melt and add new material to the crust (Vlaar et al., 1994). We present results of numerical thermo-chemical convection models including a simple approximate melt segregation mechanism in which we investigate this alternative geodynamic regime, and its effect on the cooling history and chemical evolution of the mantle. Our results show that the mechanism is capable of working on two scales. On a small scale, involving the lower boundary of the crust, delaminations and downward transport of eclogite into the upper mantle takes place. On a larger scale, involving the entire crustal column, (parts of) the crust may episodically sink into the mantle and be replaced by a fresh crust. Both are capable of significantly and rapidly cooling a hot upper mantle by driving partial melting and thus the generation of new crust. After some hundreds of millions of years, as the temperature drops, the mechanism shuts itself off, and the cooling rate significantly decreases. Vlaar, N.J., P.E. van Keken and A.P. van den Berg (1994), Cooling of the Earth in the Archaean: consequences of pressure-release melting in a hotter mantle, Earth and Planetary Science Letters, vol 121, pp. 1-18

The oxidation state of Hadean magmas and implications for early Earth's atmosphere.

PubMed

Trail, Dustin; Watson, E Bruce; Tailby, Nicholas D

2011-11-30

Magmatic outgassing of volatiles from Earth's interior probably played a critical part in determining the composition of the earliest atmosphere, more than 4,000 million years (Myr) ago. Given an elemental inventory of hydrogen, carbon, nitrogen, oxygen and sulphur, the identity of molecular species in gaseous volcanic emanations depends critically on the pressure (fugacity) of oxygen. Reduced melts having oxygen fugacities close to that defined by the iron-wüstite buffer would yield volatile species such as CH(4), H(2), H(2)S, NH(3) and CO, whereas melts close to the fayalite-magnetite-quartz buffer would be similar to present-day conditions and would be dominated by H(2)O, CO(2), SO(2) and N(2) (refs 1-4). Direct constraints on the oxidation state of terrestrial magmas before 3,850 Myr before present (that is, the Hadean eon) are tenuous because the rock record is sparse or absent. Samples from this earliest period of Earth's history are limited to igneous detrital zircons that pre-date the known rock record, with ages approaching ∼4,400 Myr (refs 5-8). Here we report a redox-sensitive calibration to determine the oxidation state of Hadean magmatic melts that is based on the incorporation of cerium into zircon crystals. We find that the melts have average oxygen fugacities that are consistent with an oxidation state defined by the fayalite-magnetite-quartz buffer, similar to present-day conditions. Moreover, selected Hadean zircons (having chemical characteristics consistent with crystallization specifically from mantle-derived melts) suggest oxygen fugacities similar to those of Archaean and present-day mantle-derived lavas as early as ∼4,350 Myr before present. These results suggest that outgassing of Earth's interior later than ∼200 Myr into the history of Solar System formation would not have resulted in a reducing atmosphere.

Cellular Factors Shape 3D Genome Landscape

Cancer.gov

Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper 3D positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities.

Identifying early Earth microfossils in unsilicified sediments

NASA Astrophysics Data System (ADS)

Javaux, Emmanuelle J.; Asael, Dan; Bekker, Andrey; Debaille, Vinciane; Derenne, Sylvie; Hofmann, Axel; Mattielli, Nadine; Poulton, Simon

2013-04-01

The search for life on the early Earth or beyond Earth requires the definition of biosignatures, or "indices of life". These traditionally include fossil molecules, isotopic fractionations, biosedimentary structures and morphological fossils interpreted as remnants of life preserved in rocks. This research focuses on traces of life preserved in unsilicified siliciclastic sediments. Indeed, these deposits preserve well sedimentary structures indicative of past aqueous environments and organic matter, including the original organic walls of microscopic organisms. They also do not form in hydrothermal conditions which may be source of abiotic organics. At our knowledge, the only reported occurrence of microfossils preserved in unsilicified Archean sediments is a population of large organic-walled vesicles discovered in shales and siltstones of the 3.2 Ga Moodies Group, South Africa. (Javaux et al, Nature 2010). These have been interpreted as microfossils based on petrographic and geochemical evidence for their endogenicity and syngeneity, their carbonaceous composition, cellular morphology and ultrastructure, occurrence in populations, taphonomic features of soft wall deformation, and the geological context plausible for life, as well as lack of abiotic explanation falsifying a biological origin. Demonstrating that carbonaceous objects from Archaean rocks are truly old and truly biological is the subject of considerable debate. Abiotic processes are known to produce organics and isotopic signatures similar to life. Spheroidal pseudofossils may form as self-assembling vesicles from abiotic CM, e.g. in prebiotic chemistry experiments (Shoztak et al, 2001), from meteoritic lipids (Deamer et al, 2006), or hydrothermal fluids (Akashi et al, 1996); by artifact of maceration; by migration of abiotic or biotic CM along microfractures (VanZuilen et al, 2007) or along mineral casts (Brasier et al, 2005), or around silica spheres formed in silica-saturated water (Jones and

Diurnal Regulation of Cellular Processes in the Cyanobacterium Synechocystis sp. Strain PCC 6803: Insights from Transcriptomic, Fluxomic, and Physiological Analyses

PubMed Central

Saha, Rajib; Liu, Deng; Hoynes-O’Connor, Allison; Liberton, Michelle; Yu, Jingjie; Bhattacharyya-Pakrasi, Maitrayee; Balassy, Andrea; Zhang, Fuzhong; Maranas, Costas D.

2016-01-01

ABSTRACT Synechocystis sp. strain PCC 6803 is the most widely studied model cyanobacterium, with a well-developed omics level knowledgebase. Like the lifestyles of other cyanobacteria, that of Synechocystis PCC 6803 is tuned to diurnal changes in light intensity. In this study, we analyzed the expression patterns of all of the genes of this cyanobacterium over two consecutive diurnal periods. Using stringent criteria, we determined that the transcript levels of nearly 40% of the genes in Synechocystis PCC 6803 show robust diurnal oscillating behavior, with a majority of the transcripts being upregulated during the early light period. Such transcripts corresponded to a wide array of cellular processes, such as light harvesting, photosynthetic light and dark reactions, and central carbon metabolism. In contrast, transcripts of membrane transporters for transition metals involved in the photosynthetic electron transport chain (e.g., iron, manganese, and copper) were significantly upregulated during the late dark period. Thus, the pattern of global gene expression led to the development of two distinct transcriptional networks of coregulated oscillatory genes. These networks help describe how Synechocystis PCC 6803 regulates its metabolism toward the end of the dark period in anticipation of efficient photosynthesis during the early light period. Furthermore, in silico flux prediction of important cellular processes and experimental measurements of cellular ATP, NADP(H), and glycogen levels showed how this diurnal behavior influences its metabolic characteristics. In particular, NADPH/NADP+ showed a strong correlation with the majority of the genes whose expression peaks in the light. We conclude that this ratio is a key endogenous determinant of the diurnal behavior of this cyanobacterium. PMID:27143387

Structure and biochemical characterization of proliferating cellular nuclear antigen from a parasitic protozoon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cardona-Felix, Cesar S.; Lara-Gonzalez, Samuel; Brieba, Luis G.

2012-02-08

Proliferating cellular nuclear antigen (PCNA) is a toroidal-shaped protein that is involved in cell-cycle control, DNA replication and DNA repair. Parasitic protozoa are early-diverged eukaryotes that are responsible for neglected diseases. In this work, a PCNA from a parasitic protozoon was identified, cloned and biochemically characterized and its crystal structure was determined. Structural and biochemical studies demonstrate that PCNA from Entamoeba histolytica assembles as a homotrimer that is able to interact with and stimulate the activity of a PCNA-interacting peptide-motif protein from E. histolytica, EhDNAligI. The data indicate a conservation of the biochemical mechanisms of PCNA-mediated interactions between metazoa, yeastmore » and parasitic protozoa.« less

Current status and perspectives in atomic force microscopy-based identification of cellular transformation

PubMed Central

Dong, Chenbo; Hu, Xiao; Dinu, Cerasela Zoica

2016-01-01

Understanding the complex interplay between cells and their biomechanics and how the interplay is influenced by the extracellular microenvironment, as well as how the transforming potential of a tissue from a benign to a cancerous one is related to the dynamics of both the cell and its surroundings, holds promise for the development of targeted translational therapies. This review provides a comprehensive overview of atomic force microscopy-based technology and its applications for identification of cellular progression to a cancerous phenotype. The review also offers insights into the advancements that are required for the next user-controlled tool to allow for the identification of early cell transformation and thus potentially lead to improved therapeutic outcomes. PMID:27274238

Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses.

PubMed

Wolferstätter, Michael; Schweneker, Marc; Späth, Michaela; Lukassen, Susanne; Klingenberg, Marieken; Brinkmann, Kay; Wielert, Ursula; Lauterbach, Henning; Hochrein, Hubertus; Chaplin, Paul; Suter, Mark; Hausmann, Jürgen

2014-12-01

Double-stranded RNA (dsRNA) is an important molecular pattern associated with viral infection and is detected by various extra- and intracellular recognition molecules. Poxviruses have evolved to avoid producing dsRNA early in infection but generate significant amounts of dsRNA late in infection due to convergent transcription of late genes. Protein kinase R (PKR) is activated by dsRNA and triggers major cellular defenses against viral infection, including protein synthesis shutdown, apoptosis, and type I interferon (IFN-I) production. The poxviral E3 protein binds and sequesters viral dsRNA and is a major antagonist of the PKR pathway. We found that the highly replication-restricted modified vaccinia virus Ankara (MVA) engineered to produce excess amounts of dsRNA early in infection showed enhanced induction of IFN-β in murine and human cells in the presence of an intact E3L gene. IFN-β induction required a minimum overlap length of 300 bp between early complementary transcripts and was strongly PKR dependent. Excess early dsRNA produced by MVA activated PKR early but transiently in murine cells and induced enhanced systemic levels of IFN-α, IFN-γ, and other cytokines and chemokines in mice in a largely PKR-dependent manner. Replication-competent chorioallantois vaccinia virus Ankara (CVA) generating excess early dsRNA also enhanced IFN-I production and was apathogenic in mice even at very high doses but showed no in vitro host range defect. Thus, genetically adjuvanting MVA and CVA to generate excess early dsRNA is an effective method to enhance innate immune stimulation by orthopoxvirus vectors and to attenuate replicating vaccinia virus in vivo. Efficient cellular sensing of pathogen-specific components, including double-stranded RNA (dsRNA), is an important prerequisite of an effective antiviral immune response. The prototype poxvirus vaccinia virus (VACV) and its derivative modified vaccinia virus Ankara (MVA) produce dsRNA as a by-product of viral

Breast cancer risk accumulation starts early: prevention must also.

PubMed

Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S

2014-06-01

Nearly one in four breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. This study follows the literature review methods and format. Exposures during childhood and adolescence affect a woman's long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors is related to breast cancer risk and risk of premalignant proliferative benign lesions. Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention.

The effects of storage and sterilization on de-cellularized and re-cellularized whole lung.

PubMed

Bonenfant, Nicholas R; Sokocevic, Dino; Wagner, Darcy E; Borg, Zachary D; Lathrop, Melissa J; Lam, Ying Wai; Deng, Bin; Desarno, Michael J; Ashikaga, Taka; Loi, Roberto; Weiss, Daniel J

2013-04-01

Despite growing interest on the potential use of de-cellularized whole lungs as 3-dimensional scaffolds for ex vivo lung tissue generation, optimal processing including sterilization and storage conditions, are not well defined. Further, it is unclear whether lungs need to be obtained immediately or may be usable even if harvested several days post-mortem, a situation mimicking potential procurement of human lungs from autopsy. We therefore assessed effects of delayed necropsy, prolonged storage (3 and 6 months), and of two commonly utilized sterilization approaches: irradiation or final rinse with peracetic acid, on architecture and extracellular matrix (ECM) protein characteristics of de-cellularized mouse lungs. These different approaches resulted in significant differences in both histologic appearance and in retention of ECM and intracellular proteins as assessed by immunohistochemistry and mass spectrometry. Despite these differences, binding and proliferation of bone marrow-derived mesenchymal stromal cells (MSCs) over a one month period following intratracheal inoculation was similar between experimental conditions. In contrast, significant differences occurred with C10 mouse lung epithelial cells between the different conditions. Therefore, delayed necropsy, duration of scaffold storage, sterilization approach, and cell type used for re-cellularization may significantly impact the usefulness of this biological scaffold-based model of ex vivo lung tissue regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cellular Immune Response to Cytomegalovirus Infection After Renal Transplantation

PubMed Central

Linnemann, Calvin C.; Kauffman, Carol A.; First, M. Roy; Schiff, Gilbert M.; Phair, John P.

1978-01-01

A prospective study of 15 patients who received renal transplants defined the effect of renal transplantation on the cellular immune response to cytomegalovirus infection. Of 15 patients, 14 developed cytomegalovirus infection, usually in the first 2 months after transplantation, and all infections were accompanied by a normal humoral immune response. After the initiation of immunosuppressive therapy and transplantation, there was a general depression of lymphocyte transformation, as reflected in the response to phytohemagglutinin, accompanied by a specific defect in cellular immunity, as indicated by lymphocyte transformation to cytomegalovirus antigen. Eleven patients had cellular immunity to cytomegalovirus before transplantation, and all of these became negative in the first month after transplantation. In subsequent months, only 6 of the 14 study patients with cytomegalovirus infection developed specific cellular immune responses to cytomegalovirus. This occurred most often in patients who had severe febrile illnesses in association with infection. The specific cellular immune response which developed in the posttransplant period did not persist in three of the patients. This study demonstrates the dissociation of the humoral and cellular immune response to cytomegalovirus infection in renal transplant patients and indicates the importance of the loss of cellular immunity in the appearance of infection. Previously infected patients lost their cell-mediated immunity and had reactivation infections despite the presence of serum antibody. PMID:215541

AGCVIII Kinases: at the crossroads of cellular signaling

USDA-ARS?s Scientific Manuscript database

AGCVIII kinases regulate diverse developmental and cellular processes in plants. As putative mediators of secondary messengers, AGCVIII kinases potentially integrate developmental and environmental cues into specific cellular responses through substrate phosphorylation. Here we discuss the functiona...

Cellular structures with interconnected microchannels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaefer, Robert Shahram; Ghoniem, Nasr M.; Williams, Brian

A method for fabricating a cellular tritium breeder component includes obtaining a reticulated carbon foam skeleton comprising a network of interconnected ligaments. The foam skeleton is then melt-infiltrated with a tritium breeder material, for example, lithium zirconate or lithium titanate. The foam skeleton is then removed to define a cellular breeder component having a network of interconnected tritium purge channels. In an embodiment the ligaments of the foam skeleton are enlarged by adding carbon using chemical vapor infiltration (CVI) prior to melt-infiltration. In an embodiment the foam skeleton is coated with a refractory material, for example, tungsten, prior to meltmore » infiltration.« less

Comparison between reflectance confocal microscopy and two-photon microscopy in early detection of cutaneous radiation injury in a mouse model in-vivo.

PubMed

Jang, Won Hyuk; Kwon, Soonjae; Shim, Sehwan; Jang, Won-Suk; Myung, Jae Kyung; Yang, Sejung; Park, Sunhoo; Kim, Ki Hean

2018-05-12

Cutaneous radiation injury (CRI) is a skin injury caused by high dose exposure of ionizing radiation (IR). For proper treatment, early detection of CRI before clinical symptoms is important. Optical microscopic techniques such as reflectance confocal microscopy (RCM) and two-photon microscopy (TPM) have been tested as the early diagnosis method by detecting cellular changes. In this study, RCM and TPM were compared in the detection of cellular changes caused by CRI in an in-vivo mouse model. CRI was induced on the mouse hindlimb skin with various IR doses and the injured skin regions were imaged longitudinally by both modalities until the onset of clinical symptoms. Both RCM and TPM detected the changes of epidermal cells and sebaceous glands before clinical symptoms in different optical contrasts. RCM detected changes of cell morphology and scattering property based on light reflection. TPM detected detail changes of cellular structures based on autofluorescence of cells. Since both RCM and TPM were sensitive to the early-stage CRI by using different contrasts, the optimal method for clinical CRI diagnosis could be either individual methods or their combination. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cellular delivery of PEGylated PLGA nanoparticles.

PubMed

Pamujula, Sarala; Hazari, Sidhartha; Bolden, Gevoni; Graves, Richard A; Chinta, Dakshinamurthy Devanga; Dash, Srikanta; Kishore, Vimal; Mandal, Tarun K

2012-01-01

The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide-co-gycolide (PLGA) nanoparticles by breast cancer cells. Nanoparticles of PLGA containing various amounts of polyethylene glycol (PEG, 5%-15%) were prepared using a double emulsion solvent evaporation method. The nanoparticles were loaded with coumarin-6 (C6) as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Irrespective of the amount of PEG, all formulations yielded smooth spherical particles. However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1.2 µm filter to obtain target size particles (114-335 nm) with zeta potentials ranging from -2.8 mV to -26.2 mV. While PLGA-PEG di-block (15% PEG) formulation showed significantly higher 4T1 cellular uptake than all other formulations, there was no statistical difference in cellular uptake among PLGA, PLGA-PEG-PLGA tri-block (10% PEG), PLGA-PEG di-block (5% PEG) and PLGA-PEG di-block (10% PEG) nanoparticles. These preliminary findings indicated that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum cellular uptake due to it having the smallest particle size and lowest zeta potential. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Evolutionary tradeoffs in cellular composition across diverse bacteria

PubMed Central

Kempes, Christopher P; Wang, Lawrence; Amend, Jan P; Doyle, John; Hoehler, Tori

2016-01-01

One of the most important classic and contemporary interests in biology is the connection between cellular composition and physiological function. Decades of research have allowed us to understand the detailed relationship between various cellular components and processes for individual species, and have uncovered common functionality across diverse species. However, there still remains the need for frameworks that can mechanistically predict the tradeoffs between cellular functions and elucidate and interpret average trends across species. Here we provide a comprehensive analysis of how cellular composition changes across the diversity of bacteria as connected with physiological function and metabolism, spanning five orders of magnitude in body size. We present an analysis of the trends with cell volume that covers shifts in genomic, protein, cellular envelope, RNA and ribosomal content. We show that trends in protein content are more complex than a simple proportionality with the overall genome size, and that the number of ribosomes is simply explained by cross-species shifts in biosynthesis requirements. Furthermore, we show that the largest and smallest bacteria are limited by physical space requirements. At the lower end of size, cell volume is dominated by DNA and protein content—the requirement for which predicts a lower limit on cell size that is in good agreement with the smallest observed bacteria. At the upper end of bacterial size, we have identified a point at which the number of ribosomes required for biosynthesis exceeds available cell volume. Between these limits we are able to discuss systematic and dramatic shifts in cellular composition. Much of our analysis is connected with the basic energetics of cells where we show that the scaling of metabolic rate is surprisingly superlinear with all cellular components. PMID:27046336

Bioinspired Cellular Structures: Additive Manufacturing and Mechanical Properties

NASA Astrophysics Data System (ADS)

Stampfl, J.; Pettermann, H. E.; Liska, R.

Biological materials (e.g., wood, trabecular bone, marine skeletons) rely heavily on the use of cellular architecture, which provides several advantages. (1) The resulting structures can bear the variety of "real life" load spectra using a minimum of a given bulk material, featuring engineering lightweight design principles. (2) The inside of the structures is accessible to body fluids which deliver the required nutrients. (3) Furthermore, cellular architectures can grow organically by adding or removing individual struts or by changing the shape of the constituting elements. All these facts make the use of cellular architectures a reasonable choice for nature. Using additive manufacturing technologies (AMT), it is now possible to fabricate such structures for applications in engineering and biomedicine. In this chapter, we present methods that allow the 3D computational analysis of the mechanical properties of cellular structures with open porosity. Various different cellular architectures including disorder are studied. In order to quantify the influence of architecture, the apparent density is always kept constant. Furthermore, it is shown that how new advanced photopolymers can be used to tailor the mechanical and functional properties of the fabricated structures.

Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

PubMed

Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

2016-08-01

Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2015. Published by Elsevier B.V.

Design Optimization of Irregular Cellular Structure for Additive Manufacturing

NASA Astrophysics Data System (ADS)

Song, Guo-Hua; Jing, Shi-Kai; Zhao, Fang-Lei; Wang, Ye-Dong; Xing, Hao; Zhou, Jing-Tao

2017-09-01

Irregularcellular structurehas great potential to be considered in light-weight design field. However, the research on optimizing irregular cellular structures has not yet been reporteddue to the difficulties in their modeling technology. Based on the variable density topology optimization theory, an efficient method for optimizing the topology of irregular cellular structures fabricated through additive manufacturing processes is proposed. The proposed method utilizes tangent circles to automatically generate the main outline of irregular cellular structure. The topological layoutof each cellstructure is optimized using the relative density informationobtained from the proposed modified SIMP method. A mapping relationship between cell structure and relative densityelement is builtto determine the diameter of each cell structure. The results show that the irregular cellular structure can be optimized with the proposed method. The results of simulation and experimental test are similar for irregular cellular structure, which indicate that the maximum deformation value obtained using the modified Solid Isotropic Microstructures with Penalization (SIMP) approach is lower 5.4×10-5 mm than that using the SIMP approach under the same under the same external load. The proposed research provides the instruction to design the other irregular cellular structure.

Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

NASA Astrophysics Data System (ADS)

Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

2016-05-01

Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated.

33 CFR 183.516 - Cellular plastic used to encase fuel tanks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Cellular plastic used to encase....516 Cellular plastic used to encase fuel tanks. (a) Cellular plastic used to encase metallic fuel...-polyurethane cellular plastic used to encase metallic fuel tanks must have a compressive strength of at least...

1024-Pixel CMOS Multimodality Joint Cellular Sensor/Stimulator Array for Real-Time Holistic Cellular Characterization and Cell-Based Drug Screening.

PubMed

Park, Jong Seok; Aziz, Moez Karim; Li, Sensen; Chi, Taiyun; Grijalva, Sandra Ivonne; Sung, Jung Hoon; Cho, Hee Cheol; Wang, Hua

2018-02-01

This paper presents a fully integrated CMOS multimodality joint sensor/stimulator array with 1024 pixels for real-time holistic cellular characterization and drug screening. The proposed system consists of four pixel groups and four parallel signal-conditioning blocks. Every pixel group contains 16 × 16 pixels, and each pixel includes one gold-plated electrode, four photodiodes, and in-pixel circuits, within a pixel footprint. Each pixel supports real-time extracellular potential recording, optical detection, charge-balanced biphasic current stimulation, and cellular impedance measurement for the same cellular sample. The proposed system is fabricated in a standard 130-nm CMOS process. Rat cardiomyocytes are successfully cultured on-chip. Measured high-resolution optical opacity images, extracellular potential recordings, biphasic current stimulations, and cellular impedance images demonstrate the unique advantages of the system for holistic cell characterization and drug screening. Furthermore, this paper demonstrates the use of optical detection on the on-chip cultured cardiomyocytes to real-time track their cyclic beating pattern and beating rate.

Protective Cellular Immunity Against Influenza Virus Induced by Plasmid Inoculation of Newborn Mice

PubMed Central

Bot, Adrian; Bot, Simona; García-Sastre, Adolfo

1998-01-01

Neonate organisms display an intrinsic disability to mount effective immune responses to infectious agents or conventional vaccines. Whereas low. doses of antigens trigger a suboptimal response, higher doses are frequently associated with tolerance induction. We investigated the ability of a plasmid-expressing nucleoprotein of influenza virus to prime a specific cellular immune response when administered to newborn mice. We found that persistent exposure to antigen following plasmid inoculation of neonates leads to a vigorous priming of specific CTLs rather than tolerance induction. The CTLs were cross-reactive against multiple strains of type A influenza viruses and produced IFNγ but no IL-4. The immunity triggered by plasmid inoculation of neonates was protective in terms of pulmonary virus clearance as well as survival rate following lethal challenge with influenza virus. Whereas the persistence of the plasmid at the site of injection was readily demonstrable in adult mice at 3 months after inoculation, mice immunized as newborns displayed no plasmid at 3 months and very little at 1 month after injection. Thus, DNA-based immunization of neonates may prove an effective and safe vaccination strategy for induction of cellular immunity against microbes that cause serious infectious diseases in the early period of life. PMID:9851359

Single cell RNA Seq reveals dynamic paracrine control of cellular variation

PubMed Central

Shalek, Alex K.; Satija, Rahul; Shuga, Joe; Trombetta, John J.; Gennert, Dave; Lu, Diana; Chen, Peilin; Gertner, Rona S.; Gaublomme, Jellert T.; Yosef, Nir; Schwartz, Schraga; Fowler, Brian; Weaver, Suzanne; Wang, Jing; Wang, Xiaohui; Ding, Ruihua; Raychowdhury, Raktima; Friedman, Nir; Hacohen, Nir; Park, Hongkun; May, Andrew P.; Regev, Aviv

2014-01-01

High-throughput single-cell transcriptomics offers an unbiased approach for understanding the extent, basis, and function of gene expression variation between seemingly identical cells. Here, we sequence single-cell RNA-Seq libraries prepared from over 1,700 primary mouse bone marrow derived dendritic cells (DCs) spanning several experimental conditions. We find substantial variation between identically stimulated DCs, in both the fraction of cells detectably expressing a given mRNA and the transcript’s level within expressing cells. Distinct gene modules are characterized by different temporal heterogeneity profiles. In particular, a “core” module of antiviral genes is expressed very early by a few “precocious” cells, but is later activated in all cells. By stimulating cells individually in sealed microfluidic chambers, analyzing DCs from knockout mice, and modulating secretion and extracellular signaling, we show that this response is coordinated via interferon-mediated paracrine signaling. Surprisingly, preventing cell-to-cell communication also substantially reduces variability in the expression of an early-induced “peaked” inflammatory module, suggesting that paracrine signaling additionally represses part of the inflammatory program. Our study highlights the importance of cell-to-cell communication in controlling cellular heterogeneity and reveals general strategies that multicellular populations use to establish complex dynamic responses. PMID:24919153

Discriminative segmentation of microscopic cellular images.

PubMed

Cheng, Li; Ye, Ning; Yu, Weimiao; Cheah, Andre

2011-01-01

Microscopic cellular images segmentation has become an important routine procedure in modern biological research, due to the rapid advancement of fluorescence probes and robotic microscopes in recent years. In this paper we advocate a discriminative learning approach for cellular image segmentation. In particular, three new features are proposed to capture the appearance, shape and context information, respectively. Experiments are conducted on three different cellular image datasets. Despite the significant disparity among these datasets, the proposed approach is demonstrated to perform reasonably well. As expected, for a particular dataset, some features turn out to be more suitable than others. Interestingly, we observe that a further gain can often be obtained on top of using the "good" features, by also retaining those features that perform poorly. This might be due to the complementary nature of these features, as well as the capacity of our approach to better integrate and exploit different sources of information.

Driver hand-held cellular phone use: a four-year analysis.

PubMed

Eby, David W; Vivoda, Jonathon M; St Louis, Renée M

2006-01-01

The use of hand-held cellular (mobile) phones while driving has stirred more debate, passion, and research than perhaps any other traffic safety issue in the past several years. There is ample research showing that the use of either hand-held or hands-free cellular phones can lead to unsafe driving patterns. Whether or not these performance deficits increase the risk of crash is difficult to establish, but recent studies are beginning to suggest that cellular phone use elevates crash risk. The purpose of this study was to assess changes in the rate of hand-held cellular phone use by motor-vehicle drivers on a statewide level in Michigan. This study presents the results of 13 statewide surveys of cellular phone use over a 4-year period. Hand-held cellular phone use data were collected through direct observation while vehicles were stopped at intersections and freeway exit ramps. Data were weighted to be representative of all drivers traveling during daylight hours in Michigan. The study found that driver hand-held cellular phone use has more than doubled between 2001 and 2005, from 2.7% to 5.8%. This change represents an average increase of 0.78 percentage points per year. The 5.8% use rate observed in 2005 means that at any given daylight hour, around 36,550 drivers were conversing on cellular phones while driving on Michigan roadways. The trend line fitted to these data predicts that by the year 2010, driver hand-held cellular phone use will be around 8.6%, or 55,000 drivers at any given daylight hour. These results make it clear that cellular phone use while driving will continue to be an important traffic safety issue, and highlight the importance of continued attempts to generate new ways of alleviating this potential hazard.

HPV integration hijacks and multimerizes a cellular enhancer to generate a viral-cellular super-enhancer that drives high viral oncogene expression

PubMed Central

Redmond, Catherine J.; Dooley, Katharine E.; Fu, Haiqing; Gillison, Maura L.; Akagi, Keiko; Symer, David E.; Aladjem, Mirit I.

2018-01-01

Integration of human papillomavirus (HPV) genomes into cellular chromatin is common in HPV-associated cancers. Integration is random, and each site is unique depending on how and where the virus integrates. We recently showed that tandemly integrated HPV16 could result in the formation of a super-enhancer-like element that drives transcription of the viral oncogenes. Here, we characterize the chromatin landscape and genomic architecture of this integration locus to elucidate the mechanisms that promoted de novo super-enhancer formation. Using next-generation sequencing and molecular combing/fiber-FISH, we show that ~26 copies of HPV16 are integrated into an intergenic region of chromosome 2p23.2, interspersed with 25 kb of amplified, flanking cellular DNA. This interspersed, co-amplified viral-host pattern is frequent in HPV-associated cancers and here we designate it as Type III integration. An abundant viral-cellular fusion transcript encoding the viral E6/E7 oncogenes is expressed from the integration locus and the chromatin encompassing both the viral enhancer and a region in the adjacent amplified cellular sequences is strongly enriched in the super-enhancer markers H3K27ac and Brd4. Notably, the peak in the amplified cellular sequence corresponds to an epithelial-cell-type specific enhancer. Thus, HPV16 integration generated a super-enhancer-like element composed of tandem interspersed copies of the viral upstream regulatory region and a cellular enhancer, to drive high levels of oncogene expression. PMID:29364907

Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

PubMed Central

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young

2017-01-01

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation. PMID:28122968

Cellular phone use and brain tumor: a meta-analysis.

PubMed

Kan, Peter; Simonsen, Sara E; Lyon, Joseph L; Kestle, John R W

2008-01-01

The dramatic increase in the use of cellular phones has generated concerns about potential adverse effects, especially the development of brain tumors. We conducted a meta-analysis to examine the effect of cellular phone use on the risk of brain tumor development. We searched the literature using MEDLINE to locate case-control studies on cellular phone use and brain tumors. Odds ratios (ORs) for overall effect and stratified ORs associated with specific brain tumors, long-term use, and analog/digital phones were calculated for each study using its original data. A pooled estimator of each OR was then calculated using a random-effects model. Nine case-control studies containing 5,259 cases of primary brain tumors and 12,074 controls were included. All studies reported ORs according to brain tumor subtypes, and five provided ORs on patients with > or =10 years of follow up. Pooled analysis showed an overall OR of 0.90 (95% confidence interval [CI] 0.81-0.99) for cellular phone use and brain tumor development. The pooled OR for long-term users of > or =10 years (5 studies) was 1.25 (95% CI 1.01-1.54). No increased risk was observed in analog or digital cellular phone users. We found no overall increased risk of brain tumors among cellular phone users. The potential elevated risk of brain tumors after long-term cellular phone use awaits confirmation by future studies.

Humoral and Cellular Immunity Changed after Traumatic Brain Injury in Human Patients.

PubMed

Wang, Jia-Wei; Li, Jin-Ping; Song, Ying-Lun; Zhao, Qi-Huang

2017-01-01

Previous studies have suggested that there is a disproportionally higher risk of infection following traumatic brain injury (TBI). This predisposition to infection may be driven by a poorly understood, brain-specific response in the immune system after TBI. However, there is a lack of studies that have fully characterized TBI patients to understand the relationship between TBI and peripheral immune function. In the present study, markers for humoral immunity and cellular immunity were measured for up to 2 weeks in the peripheral blood of 37 patients with TBI in order to elucidate the time course and the type of the peripheral immune response following TBI. 12 relatively healthy individuals without TBI and other neurological diseases were enrolled into the control group. Our data indicated that TBI could induce significant changes in humoral immunity characterized by a decrease in IgG and IgM levels and an increase in the complements C3 and C4 levels in comparison with the control group. Moreover, compared with the control group, a significant reduction in peripheral blood CD3 + and CD3 + CD4 + lymphocyte counts occurred early (days 1-3) following the onset of trauma. These results provide evidence that TBI is associated with substantial changes in humoral immunity and cellular immunity, which may explain the high incidence of infection encountered in these patients. © 2017 by the Association of Clinical Scientists, Inc.

Evolution of early embryogenesis in rhabditid nematodes

PubMed Central

Brauchle, Michael; Kiontke, Karin; MacMenamin, Philip; Fitch, David H. A.; Piano, Fabio

2009-01-01

The cell biological events that guide early embryonic development occur with great precision within species but can be quite diverse across species. How these cellular processes evolve and which molecular components underlie evolutionary changes is poorly understood. To begin to address these questions, we systematically investigated early embryogenesis, from the one- to the four-cell embryo, in 34 nematode species related to C. elegans. We found 40 cell-biological characters that captured the phenotypic differences between these species. By tracing the evolutionary changes on a molecular phylogeny, we found that these characters evolved multiple times and independently of one another. Strikingly, all these phenotypes are mimicked by single-gene RNAi experiments in C. elegans. We use these comparisons to hypothesize the molecular mechanisms underlying the evolutionary changes. For example, we predict that a cell polarity module was altered during the evolution of the Protorhabditis group and show that PAR-1, a kinase localized asymmetrically in C. elegans early embryos, is symmetrically localized in the one-cell stage of Protorhabditis group species. Our genome-wide approach identifies candidate molecules—and thereby modules—associated with evolutionary changes in cell-biological phenotypes. PMID:19643102

Membrane contact sites, ancient and central hubs of cellular lipid logistics.

PubMed

Jain, Amrita; Holthuis, Joost C M

2017-09-01

Membrane contact sites (MCSs) are regions where two organelles are closely apposed to facilitate molecular communication and promote a functional integration of compartmentalized cellular processes. There is growing evidence that MCSs play key roles in controlling intracellular lipid flows and distributions. Strikingly, even organelles connected by vesicular trafficking exchange lipids en bulk via lipid transfer proteins that operate at MCSs. Herein, we describe how MCSs developed into central hubs of lipid logistics during the evolution of eukaryotic cells. We then focus on how modern eukaryotes exploit MCSs to help solve a major logistical problem, namely to preserve the unique lipid mixtures of their early and late secretory organelles in the face of extensive vesicular trafficking. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann. Copyright © 2017. Published by Elsevier B.V.

The Relationship between Cellular Phone Use, Performance, and Reaction Time among College Students: Implications for Cellular Phone Use while Driving

ERIC Educational Resources Information Center

Szyfman, Adam; Wanner, Gregory; Spencer, Leslie

2003-01-01

Two studies were performed to determine the relationship between cellular phone use and either reaction time or performance among college students. In the first study 60 undergraduates completed a computerized reaction time test. Mean reaction times were significantly higher when participants were talking on a cellular phone, either handheld or on…

Unique Cellular Organization in the Oldest Root Meristem.

PubMed

Hetherington, Alexander J; Dubrovsky, Joseph G; Dolan, Liam

2016-06-20

Roots and shoots of plant bodies develop from meristems-cell populations that self-renew and produce cells that undergo differentiation-located at the apices of axes [1].The oldest preserved root apices in which cellular anatomy can be imaged are found in nodules of permineralized fossil soils called coal balls [2], which formed in the Carboniferous coal swamp forests over 300 million years ago [3-9]. However, no fossil root apices described to date were actively growing at the time of preservation [3-10]. Because the cellular organization of meristems changes when root growth stops, it has been impossible to compare cellular dynamics as stem cells transition to differentiated cells in extinct and extant taxa [11]. We predicted that meristems of actively growing roots would be preserved in coal balls. Here we report the discovery of the first fossilized remains of an actively growing root meristem from permineralized Carboniferous soil with detail of the stem cells and differentiating cells preserved. The cellular organization of the meristem is unique. The position of the Körper-Kappe boundary, discrete root cap, and presence of many anticlinal cell divisions within a broad promeristem distinguish it from all other known root meristems. This discovery is important because it demonstrates that the same general cellular dynamics are conserved between the oldest extinct and extant root meristems. However, its unique cellular organization demonstrates that extant root meristem organization and development represents only a subset of the diversity that has existed since roots first evolved. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cellular therapies: Day by day, all the way.

PubMed

Atilla, Erden; Kilic, Pelin; Gurman, Gunhan

2018-04-18

Tremendous effort and knowledge have elucidated a new era of 'cellular therapy,' also called "live" or "living" drugs. There are currently thousands of active clinical trials that are ongoing, seeking hope for incurable conditions thanks to the increased accessibility and reliability of gene editing and cellular reprogramming. Accomplishments in various adoptive T cell immunotherapies and chimeric antigen receptor (CART) T cell therapies oriented researchers to the field. Cellular therapies are believed to be the next generation of curative therapeutics in many ways, the classification and nomenclature for these applications have not yet reached a consensus. Trends in recent years are moving towards making tissues and cell processes only in centers with production permits. It is quite promising that competent authorities have increased licensing activities of tissue and cell establishments in their countries, under good practice (GxP) rules, and preclinical and clinical trials involving cell-based therapies have led to significant investments. Despite the initiatives undertaken and the large budgets that have been allocated, only limited success has been achieved in cellular therapy compared to conventional drug development. Cost, and cost effectiveness, are important issues for these novel therapies to meet unmet clinical needs, and there are still many scientific, translational, commercializational, and ethical questions that do not have answers. The main objectives of this review is to underline the current position of cellular therapies in research, highlight the timely topic of immunotherapy and chimeric antigen receptor (CAR) T-cell treatment, and compile information related to regulations and marketing of cellular therapeutic approaches worldwide. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of cellular origin on differentiation of human induced pluripotent stem cell–derived endothelial cells

PubMed Central

Zhao, Ming-Tao; Jahanbani, Fereshteh; Lee, Won Hee; Snyder, Michael P.

2016-01-01

Human induced pluripotent stem cells (iPSCs) can be derived from various types of somatic cells by transient overexpression of 4 Yamanaka factors (OCT4, SOX2, C-MYC, and KLF4). Patient-specific iPSC derivatives (e.g., neuronal, cardiac, hepatic, muscular, and endothelial cells [ECs]) hold great promise in drug discovery and regenerative medicine. In this study, we aimed to evaluate whether the cellular origin can affect the differentiation, in vivo behavior, and single-cell gene expression signatures of human iPSC–derived ECs. We derived human iPSCs from 3 types of somatic cells of the same individuals: fibroblasts (FB-iPSCs), ECs (EC-iPSCs), and cardiac progenitor cells (CPC-iPSCs). We then differentiated them into ECs by sequential administration of Activin, BMP4, bFGF, and VEGF. EC-iPSCs at early passage (10 < P < 20) showed higher EC differentiation propensity and gene expression of EC-specific markers (PECAM1 and NOS3) than FB-iPSCs and CPC-iPSCs. In vivo transplanted EC-iPSC–ECs were recovered with a higher percentage of CD31+ population and expressed higher EC-specific gene expression markers (PECAM1, KDR, and ICAM) as revealed by microfluidic single-cell quantitative PCR (qPCR). In vitro EC-iPSC–ECs maintained a higher CD31+ population than FB-iPSC–ECs and CPC-iPSC–ECs with long-term culturing and passaging. These results indicate that cellular origin may influence lineage differentiation propensity of human iPSCs; hence, the somatic memory carried by early passage iPSCs should be carefully considered before clinical translation. PMID:27398408

Algorithm for cellular reprogramming.

PubMed

Ronquist, Scott; Patterson, Geoff; Muir, Lindsey A; Lindsly, Stephen; Chen, Haiming; Brown, Markus; Wicha, Max S; Bloch, Anthony; Brockett, Roger; Rajapakse, Indika

2017-11-07

The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. Here we describe an approach for optimizing the use of transcription factors (TFs) in cellular reprogramming, based on a device commonly used in optimal control. We construct an approximate model for the natural evolution of a cell-cycle-synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points during the cell cycle. To arrive at a model of moderate complexity, we cluster gene expression based on division of the genome into topologically associating domains (TADs) and then model the dynamics of TAD expression levels. Based on this dynamical model and additional data, such as known TF binding sites and activity, we develop a methodology for identifying the top TF candidates for a specific cellular reprogramming task. Our data-guided methodology identifies a number of TFs previously validated for reprogramming and/or natural differentiation and predicts some potentially useful combinations of TFs. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes. Copyright © 2017 the Author(s). Published by PNAS.

Cellular studies and interaction mechanisms of extremely low frequency fields

NASA Astrophysics Data System (ADS)

Liburdy, Robert P.

1995-01-01

Worldwide interest in the biological effects of ELF (extremely low frequency, <1 kHz) electromagnetic fields has grown significantly. Health professionals and government administrators and regulators, scientists and engineers, and, importantly, an increasing number of individuals in the general public are interested in this health issue. The goal of research at the cellular level is to identify cellular responses to ELF fields, to develop a dose threshold for such interactions, and with such information to formulate and test appropriate interaction mechanisms. This review is selective and will discuss the most recent cellular studies directed at these goals which relate to power line, sinusoidal ELF fields. In these studies an interaction site at the cell membrane is by consensus a likely candidate, since changes in ion transport, ligand-receptor events such as antibody binding, and G protein activation have been reported. These changes strongly indicate that signal transduction (ST) can be influenced. Also, ELF fields are reported to influence enzyme activation, gene expression, protein synthesis, and cell proliferation, which are triggered by earlier ST events at the cell membrane. The concept of ELF fields altering early cell membrane events and thereby influencing intracellular cell function via the ST cascade is perhaps the most plausible biological framework currently being investigated for understanding ELF effects on cells. For example, the consequence of an increase due to ELF fields in mitogenesis, the final endpoint of the ST cascade, is an overall increase in the probability of mutagenesis and consequently cancer, according to the Ames epigenetic model of carcinogenesis. Consistent with this epigenetic mechanism and the ST pathway to carcinogenesis is recent evidence that ELF fields can alter breast cancer cell proliferation and can act as a copromoter in vitro. The most important dosimetric question being addressed currently is whether the electric (E

47 CFR 22.911 - Cellular geographic service area.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Section 22.911 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.911 Cellular geographic service area. The... Communications Act of 1934, as amended, is applicable. [59 FR 59507, Nov. 17, 1994, as amended at 59 FR 59954...

47 CFR 22.911 - Cellular geographic service area.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Section 22.911 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.911 Cellular geographic service area. The... Communications Act of 1934, as amended, is applicable. [59 FR 59507, Nov. 17, 1994, as amended at 59 FR 59954...

Cellular Senescence, Neurological Function, and Redox State.

PubMed

Maciel-Barón, Luis Ángel; Moreno-Blas, Daniel; Morales-Rosales, Sandra Lizbeth; González-Puertos, Viridiana Yazmín; López-Díazguerrero, Norma Edith; Torres, Claudio; Castro-Obregón, Susana; Königsberg, Mina

2018-06-20

Cellular senescence, characterized by permanent cell cycle arrest, has been extensively studied in mitotic cells such as fibroblasts. However, senescent cells have also been observed in the brain. Even though it is recognized that cellular energetic metabolism and redox homeostasis are perturbed in the aged brain and neurodegenerative diseases (NDDs), it is still unknown which alterations in the overall physiology can stimulate cellular senescence induction and their relationship with the former events. Recent Advances: Recent findings have shown that during prolonged inflammatory and pathologic events, the blood-brain barrier could be compromised and immune cells might enter the brain; this fact along with the brain's high oxygen dependence might result in oxidative damage to macromolecules and therefore senescence induction. Thus, cellular senescence in different brain cell types is revised here. Most information related to cellular senescence in the brain has been obtained from research in glial cells since it has been assumed that the senescent phenotype is a feature exclusive to mitotic cells. Nevertheless, neurons with senescence hallmarks have been observed in old mouse brains. Therefore, although this is a controversial topic in the field, here we summarize and integrate the observations from several studies and propose that neurons indeed senesce. It is still unknown which alterations in the overall metabolism can stimulate senescence induction in the aged brain, what are the mechanisms and signaling pathways, and what is their relationship to NDD development. The understanding of these processes will expose new targets to intervene age-associated pathologies.-Antioxid. Redox Signal. 28, 1704-1723.

Triangles bridge the scales: Quantifying cellular contributions to tissue deformation

NASA Astrophysics Data System (ADS)

Merkel, Matthias; Etournay, Raphaël; Popović, Marko; Salbreux, Guillaume; Eaton, Suzanne; Jülicher, Frank

2017-03-01

In this article, we propose a general framework to study the dynamics and topology of cellular networks that capture the geometry of cell packings in two-dimensional tissues. Such epithelia undergo large-scale deformation during morphogenesis of a multicellular organism. Large-scale deformations emerge from many individual cellular events such as cell shape changes, cell rearrangements, cell divisions, and cell extrusions. Using a triangle-based representation of cellular network geometry, we obtain an exact decomposition of large-scale material deformation. Interestingly, our approach reveals contributions of correlations between cellular rotations and elongation as well as cellular growth and elongation to tissue deformation. Using this triangle method, we discuss tissue remodeling in the developing pupal wing of the fly Drosophila melanogaster.

Characteristics of excessive cellular phone use in Korean adolescents.

PubMed

Ha, Jee Hyun; Chin, Bumsu; Park, Doo-Heum; Ryu, Seung-Ho; Yu, Jaehak

2008-12-01

Abstract The objective of this study was to evaluate the possible psychological problems related to excessive cellular phone use in adolescents. Results from 595 participants showed that the potentially excessive user group had a tendency to identify themselves with their cellular phones and to have difficulties in controlling usage. They expressed more depressive symptoms, higher interpersonal anxiety, and lower self-esteem. A positive correlation was also observed between excessive cellular phone use and Internet addiction.

Effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer.

PubMed

Cai, Yong; Sheng, Zhao-Ying; Chen, Yun; Bai, Chong

2014-01-01

To explore the effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer (NSCLC). NSCNC cell line A549 was selected to explore the effect of Withaferin A on A549 cellular proliferation, apoptosis and the PI3K/Akt signal pathway capable of regulating tumor biological behavior by assessment of cellular proliferation, cellular apoptotic rates and cellular cycling as well as by immuno-blotting. Withaferin A could inhibit A549 cellular proliferation and the control rate was dosage-dependent (P<0.05), which also increased time-dependently with the same dosage of Withaferin A (P<0.05). The apoptotic indexes in A549 cells treated with 0, 2.5, 5.0, 10.0 and 20.0 μmol·L-1 Withaferin A for 48 h were significantly different (P<0.05). In addition, the apoptotic rates of each group in both early and advanced stages were higher than those in 0 μmol·L-1 (P<0.05), which were evidently higher after 48 h than those after 24 h (P<0.05). A549 cells treated by Withaferin A for 48 h were markedly lower in Bcl-2 level and obviously higher in Bax and cleaved caspase-3 levels than those treated by 0 μmol·L-1 Withaferin A (P<0.05), and there were significant differences among 5, 10 and 20 μmol·L-1 Withaferin A (P<0.05). The ratios of A549 cells treated by Withaferin A for 48 h in G0/G1 stage were higher than those in 0 μmol·L-1 , while those in S and G2/M stages were obviously lower than those in G2/M stage, and there were significant differences in 5.0, 10.0 and 20.0 μmol·L-1 Withaferin A (P<0.05). Additionally, p-Akt/Akt values were in reverse association with dosage, and the differences were significant (P<0.05). Withaferin A can inhibit the proliferation and apoptosis of A549 cells by suppressing activation of the PI3K/Akt pathways.

Discriminating cellular heterogeneity using microwell-based RNA cytometry

PubMed Central

Dimov, Ivan K.; Lu, Rong; Lee, Eric P.; Seita, Jun; Sahoo, Debashis; Park, Seung-min; Weissman, Irving L.; Lee, Luke P.

2014-01-01

Discriminating cellular heterogeneity is important for understanding cellular physiology. However, it is limited by the technical difficulties of single-cell measurements. Here, we develop a two-stage system to determine cellular heterogeneity. In the first stage, we perform multiplex single-cell RNA-cytometry in a microwell array containing over 60,000 reaction chambers. In the second stage, we use the RNA-cytometry data to determine cellular heterogeneity by providing a heterogeneity likelihood score. Moreover, we use Monte-Carlo simulation and RNA-cytometry data to calculate the minimum number of cells required for detecting heterogeneity. We applied this system to characterize the RNA distributions of aging related genes in a highly purified mouse hematopoietic stem cell population. We identified genes that reveal novel heterogeneity of these cells. We also show that changes in expression of genes such as Birc6 during aging can be attributed to the shift of relative portions of cells in the high-expressing subgroup versus low-expressing subgroup. PMID:24667995

Inter-Cellular Forces Orchestrate Contact Inhibition of Locomotion

PubMed Central

Davis, John R.; Luchici, Andrei; Mosis, Fuad; Thackery, James; Salazar, Jesus A.; Mao, Yanlan; Dunn, Graham A.; Betz, Timo; Miodownik, Mark; Stramer, Brian M.

2015-01-01

Summary Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors. PMID:25799385

Inter-cellular forces orchestrate contact inhibition of locomotion.

PubMed

Davis, John R; Luchici, Andrei; Mosis, Fuad; Thackery, James; Salazar, Jesus A; Mao, Yanlan; Dunn, Graham A; Betz, Timo; Miodownik, Mark; Stramer, Brian M

2015-04-09

Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Cellular Mechanism Underlying Hypothermia-Induced VT/VF in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol and Milrinone

PubMed Central

Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V.; Antzelevitch, Charles

2014-01-01

Background Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 µM) and verapamil (1µM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3µM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 µM) or the phosphodiesterase III inhibitors cilostazol (10 µM) or milrinone (5 µM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase-2-reentry. Quinidine, cilostazol and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities. PMID:24429494

Determined Initial lead for South Of Isua (SOI) terrain suggests a single homogeneous source for it and possibly other archaean rocks

NASA Astrophysics Data System (ADS)

Tera, F.

2011-12-01

other rocks from Isua Greenstone Belt (1) and Amîtsoq gneiss (4) fall inside the TULIP triangle of SOI, suggesting potential derivation of these Archaean rocks from the same homogeneous source.

Genetic and cellular mechanisms of the formation of Esophageal Atresia and Tracheoesophageal Fistula

PubMed Central

Jacobs, Ian J.; Que, Jianwen

2015-01-01

Foregut separation involves dynamic changes in the activities of signaling pathways and transcription factors. Recent mouse genetic studies demonstrate that some of these pathways interact with each other to form a complex network, leading to a unique dorsal-ventral patterning in the early foregut. In this review we will discuss how this unique dorsal-ventral patterning is set prior to the foregut separation and how disruption of this patterning affects the separation process. We will further discuss the roles of downstream targets of these pathways in regulating separation at cellular and molecular levels. Understanding the mechanism of normal separation process will provide us insights into the pathobiology of a relatively common birth defect Esophageal Atresia (EA) with/without Tracheo-esophageal Fistula (TEF). PMID:23679023

Breast cancer risk accumulation starts early – Prevention must also

PubMed Central

Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S.

2014-01-01

Purpose Nearly 1 in 4 breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. Methods Literature review Results Exposures during childhood and adolescence affect a woman’s long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors are related to breast cancer risk and risk of premalignant proliferative benign lesions. Conclusion Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention. PMID:24820413

Expression profiling of the mouse early embryo: Reflections and Perspectives

PubMed Central

Ko, Minoru S. H.

2008-01-01

Laboratory mouse plays important role in our understanding of early mammalian development and provides invaluable model for human early embryos, which are difficult to study for ethical and technical reasons. Comprehensive collection of cDNA clones, their sequences, and complete genome sequence information, which have been accumulated over last two decades, have provided even more advantages to mouse models. Here the progress in global gene expression profiling in early mouse embryos and, to some extent, stem cells are reviewed and the future directions and challenges are discussed. The discussions include the restatement of global gene expression profiles as snapshot of cellular status, and subsequent distinction between the differentiation state and physiological state of the cells. The discussions then extend to the biological problems that can be addressed only through global expression profiling, which include: bird’s-eye view of global gene expression changes, molecular index for developmental potency, cell lineage trajectory, microarray-guided cell manipulation, and the possibility of delineating gene regulatory cascades and networks. PMID:16739220

The relation between the age of the subconducting slab and the recycling of sediments into the mantle

NASA Technical Reports Server (NTRS)

Abbott, D.; Hoffman, S.

1985-01-01

The recycling of sediments into the mantle has become an important issue because recent papers have suggested that the geochemical inverse models of the evolution of radiogenic isotope abundances over the history of the Earth have nonunique solutions. Both the recycling of continent-derived sediments into the mantle and mixing in the mantle could produce similar geochemical effects in the mean isotopic ratios of new igneous material emplaced in continents. Recent models of Archaean heat flow and of plate tectonics during early Earth history have demonstrated that higher internal heat production of the early Earth was mainly dissipated through a higher creation rate of oceanic lithosphere. If the seafloor creation rate was higher on the early Earth, then the residence time of any one piece of oceanic lithosphere on the surface would have been shorter. It is possible that a higher rate of recycling of oceanic lithosphere into the mantle could have resulted in some transport of sediment into the mantle.

The New Cellular Immunology

ERIC Educational Resources Information Center

Claman, Henry N.

1973-01-01

Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

Genetic Dominance & Cellular Processes

ERIC Educational Resources Information Center

Seager, Robert D.

2014-01-01

In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

A Wireless Communications Laboratory on Cellular Network Planning

ERIC Educational Resources Information Center

Dawy, Z.; Husseini, A.; Yaacoub, E.; Al-Kanj, L.

2010-01-01

The field of radio network planning and optimization (RNPO) is central for wireless cellular network design, deployment, and enhancement. Wireless cellular operators invest huge sums of capital on deploying, launching, and maintaining their networks in order to ensure competitive performance and high user satisfaction. This work presents a lab…

Potency assay development for cellular therapy products: an ISCT review of the requirements and experiences in the industry.

PubMed

Bravery, Christopher A; Carmen, Jessica; Fong, Timothy; Oprea, Wanda; Hoogendoorn, Karin H; Woda, Juliana; Burger, Scott R; Rowley, Jon A; Bonyhadi, Mark L; Van't Hof, Wouter

2013-01-01

The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development. Copyright © 2013. Published by Elsevier Inc.

Cellular preservation of musculoskeletal specializations in the Cretaceous bird Confuciusornis

PubMed Central

Jiang, Baoyu; Zhao, Tao; Regnault, Sophie; Edwards, Nicholas P.; Kohn, Simon C.; Li, Zhiheng; Wogelius, Roy A.; Benton, Michael J.; Hutchinson, John R.

2017-01-01

The hindlimb of theropod dinosaurs changed appreciably in the lineage leading to extant birds, becoming more ‘crouched' in association with changes to body shape and gait dynamics. This postural evolution included anatomical changes of the foot and ankle, altering the moment arms and control of the muscles that manipulated the tarsometatarsus and digits, but the timing of these changes is unknown. Here, we report cellular-level preservation of tendon- and cartilage-like tissues from the lower hindlimb of Early Cretaceous Confuciusornis. The digital flexor tendons passed through cartilages, cartilaginous cristae and ridges on the plantar side of the distal tibiotarsus and proximal tarsometatarsus, as in extant birds. In particular, fibrocartilaginous and cartilaginous structures on the plantar surface of the ankle joint of Confuciusornis may indicate a more crouched hindlimb posture. Recognition of these specialized soft tissues in Confuciusornis is enabled by our combination of imaging and chemical analyses applied to an exceptionally preserved fossil. PMID:28327586

Reprogramming cellular identity for regenerative medicine

PubMed Central

Cherry, Anne B.C.; Daley, George Q.

2012-01-01

The choreographed development of over 200 distinct differentiated cell types from a single zygote is a complex and poorly understood process. Whereas development leads unidirectionally towards more restricted cell fates, recent work in cellular reprogramming has proven that striking conversions of one cellular identity into another can be engineered, promising countless applications in biomedical research and paving the way for modeling disease with patient-derived stem cells. To date, there has been little discussion of which disease models are likely to be most informative. We here review evidence demonstrating that because environmental influences and epigenetic signatures are largely erased during reprogramming, patient-specific models of diseases with strong genetic bases and high penetrance are likely to prove most informative in the near term. However, manipulating in vitro culture conditions may ultimately enable cell-based models to recapitulate gene-environment interactions. Here, we discuss the implications of the new reprogramming paradigm in biomedicine and outline how reprogramming of cell identities is enhancing our understanding of cell differentiation and prospects for cellular therapies and in vivo regeneration. PMID:22424223

Vascular biology: cellular and molecular profiling.

PubMed

Baird, Alison E; Wright, Violet L

2006-02-01

Our understanding of the mechanisms underlying cerebrovascular atherosclerosis has improved in recent years, but significant gaps remain. New insights into the vascular biological processes that result in ischemic stroke may come from cellular and molecular profiling studies of the peripheral blood. In recent cellular profiling studies, increased levels of a proinflammatory T-cell subset (CD4 (+)CD28 (-)) have been associated with stroke recurrence and death. Expansion of this T-cell subset may occur after ischemic stroke and be a pathogenic mechanism leading to recurrent stroke and death. Increases in certain phenotypes of endothelial cell microparticles have been found in stroke patients relative to controls, possibly indicating a state of increased vascular risk. Molecular profiling approaches include gene expression profiling and proteomic methods that permit large-scale analyses of the transcriptome and the proteome, respectively. Ultimately panels of genes and proteins may be identified that are predictive of stroke risk. Cellular and molecular profiling studies of the peripheral blood and of atherosclerotic plaques may also pave the way for the development of therapeutic agents for primary and secondary stroke prevention.

Evaluation of cellular glasses for solar mirror panel applications

NASA Technical Reports Server (NTRS)

Giovan, M.; Adams, M.

1979-01-01

An analytic technique was developed to compare the structural and environmental performance of various materials considered for backing of second surface glass solar mirrors. Cellular glass was determined to be a prime candidate due to its low cost, high stiffness-to-weight ratio, thermal expansion match to mirror glass, evident minimal environmental impact and chemical and dimensional stability under conditions of use. The current state of the art and anticipated developments in cellular glass technology are discussed; material properties are correlated to design requirements. A mathematical model is presented which suggests a design approach which allows minimization of life cost; and, a mechanical and environmental testing program is outlined, designed to provide a material property basis for development of cellular glass hardware, together with methodology for collecting lifetime predictive data. Preliminary material property data from measurements are given. Microstructure of several cellular materials is shown, and sensitivity of cellular glass to freeze-thaw degradation and to slow crack growth is discussed. The effect of surface coating is addressed.

Inferring the Limit Behavior of Some Elementary Cellular Automata

NASA Astrophysics Data System (ADS)

Ruivo, Eurico L. P.; de Oliveira, Pedro P. B.

Cellular automata locally define dynamical systems, discrete in space, time and in the state variables, capable of displaying arbitrarily complex global emergent behavior. One core question in the study of cellular automata refers to their limit behavior, that is, to the global dynamical features in an infinite time evolution. Previous works have shown that for finite time evolutions, the dynamics of one-dimensional cellular automata can be described by regular languages and, therefore, by finite automata. Such studies have shown the existence of growth patterns in the evolution of such finite automata for some elementary cellular automata rules and also inferred the limit behavior of such rules based upon the growth patterns; however, the results on the limit behavior were obtained manually, by direct inspection of the structures that arise during the time evolution. Here we present the formalization of an automatic method to compute such structures. Based on this, the rules of the elementary cellular automata space were classified according to the existence of a growth pattern in their finite automata. Also, we present a method to infer the limit graph of some elementary cellular automata rules, derived from the analysis of the regular expressions that describe their behavior in finite time. Finally, we analyze some attractors of two rules for which we could not compute the whole limit set.

Cellular phone enabled non-invasive tissue classifier.

PubMed

Laufer, Shlomi; Rubinsky, Boris

2009-01-01

Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro.

Cellular Phone Enabled Non-Invasive Tissue Classifier

PubMed Central

Laufer, Shlomi; Rubinsky, Boris

2009-01-01

Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro. PMID:19365554

Cellular automatons applied to gas dynamic problems

NASA Technical Reports Server (NTRS)

Long, Lyle N.; Coopersmith, Robert M.; Mclachlan, B. G.

1987-01-01

This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

The role of actin networks in cellular mechanosensing

NASA Astrophysics Data System (ADS)

Azatov, Mikheil

Physical processes play an important role in many biological phenomena, such as wound healing, organ development, and tumor metastasis. During these processes, cells constantly interact with and adapt to their environment by exerting forces to mechanically probe the features of their surroundings and generating appropriate biochemical responses. The mechanisms underlying how cells sense the physical properties of their environment are not well understood. In this thesis, I present my studies to investigate cellular responses to the stiffness and topography of the environment. In order to sense the physical properties of their environment, cells dynamically reorganize the structure of their actin cytoskeleton, a dynamic network of biopolymers, altering the shape and spatial distribution of protein assemblies. Several observations suggest that proteins that crosslink actin filaments may play an important role in cellular mechanosensitivity. Palladin is an actin-crosslinking protein that is found in the lamellar actin network, stress fibers and focal adhesions, cellular structures that are critical for mechanosensing of the physical environment. By virtue of its close interactions with these structures in the cell, palladin may play an important role in cell mechanics. However, the role of actin crosslinkers in general, and palladin in particular, in cellular force generation and mechanosensing is not well known. I have investigated the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. I have shown that the expression levels of palladin modulate the forces exerted by cells and their ability to sense substrate stiffness. Perturbation experiments also suggest that palladin levels in cells altered myosin motor activity. These results suggest that the actin crosslinkers, such as palladin, and myosin motors coordinate for optimal cell function and to prevent aberrant

The cellular basis for animal regeneration

PubMed Central

Tanaka, Elly; Reddien, Peter W.

2011-01-01

The ability of animals to regenerate missing parts is a dramatic and poorly understood aspect of biology. The sources of new cells for these regenerative phenomena have been sought for decades. Recent advances involving cell fate tracking in complex tissues have shed new light on the cellular underpinnings of regeneration in Hydra, planarians, zebrafish, Xenopus, and Axolotl. Planarians accomplish regeneration with use of adult pluripotent stem cells, whereas several vertebrates utilize a collection of lineage-restricted progenitors from different tissues. Together, an array of cellular strategies—from pluripotent stem cells to tissue-specific stem cells and dedifferentiation—are utilized for regeneration. PMID:21763617

Cellular Automata Simulation for Wealth Distribution

NASA Astrophysics Data System (ADS)

Lo, Shih-Ching

2009-08-01

Wealth distribution of a country is a complicate system. A model, which is based on the Epstein & Axtell's "Sugars cape" model, is presented in Netlogo. The model considers the income, age, working opportunity and salary as control variables. There are still other variables should be considered while an artificial society is established. In this study, a more complicate cellular automata model for wealth distribution model is proposed. The effects of social welfare, tax, economical investment and inheritance are considered and simulated. According to the cellular automata simulation for wealth distribution, we will have a deep insight of financial policy of the government.

Multi-scale Imaging of Cellular and Sub-cellular Structures using Scanning Probe Recognition Microscopy.

NASA Astrophysics Data System (ADS)

Chen, Q.; Rice, A. F.

2005-03-01

Scanning Probe Recognition Microscopy is a new scanning probe capability under development within our group to reliably return to and directly interact with a specific nanobiological feature of interest. In previous work, we have successfully recognized and classified tubular versus globular biological objects from experimental atomic force microscope images using a method based on normalized central moments [ref. 1]. In this paper we extend this work to include recognition schemes appropriate for cellular and sub-cellular structures. Globular cells containing tubular actin filaments are under investigation. Thus there are differences in external/internal shapes and scales. Continuous Wavelet Transform with a differential Gaussian mother wavelet is employed for multi- scale analysis. [ref. 1] Q. Chen, V. Ayres and L. Udpa, ``Biological Investigation Using Scanning Probe Recognition Microscopy,'' Proceedings 3rd IEEE Conference on Nanotechnology, vol. 2, p 863-865 (2003).

The Potential of Cellular- and Viral-Based Immunotherapies for Malignant Glioma-Dendritic Cell Vaccines, Adoptive Cell Transfer, and Oncolytic Viruses.

PubMed

Maxwell, Russell; Luksik, Andrew S; Garzon-Muvdi, Tomas; Lim, Michael

2017-06-01

Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses. Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma. Due to their successes in the preclinical arena, many of these therapies have undergone phase I and II clinical testing. These early clinical trials have demonstrated the feasibility, safety, and efficacy of these immunotherapies. Dendritic cell vaccines, adoptive cell transfer, and oncolytic viruses may have a potential role in the treatment of malignant glioma. However, these modalities must be investigated in well-designed phase III trials to prove their efficacy.

PSYCHIATRIC DISORDERS AND LEUKOCYTE TELOMERE LENGTH: UNDERLYING MECHANISMS LINKING MENTAL ILLNESS WITH CELLULAR AGING

PubMed Central

Lindqvist, Daniel; Epel, Elissa S.; Mellon, Synthia H.; Penninx, Brenda W.; Révész, Dóra; Verhoeven, Josine E.; Reus, Victor I.; Lin, Jue; Mahan, Laura; Hough, Christina M.; Rosser, Rebecca; Bersani, F. Saverio; Blackburn, Elizabeth H.; Wolkowitz, Owen M.

2015-01-01

Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell’s mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets. PMID:25999120

Cellular mechanics and motility

NASA Astrophysics Data System (ADS)

Hénon, Sylvie; Sykes, Cécile

2015-10-01

The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

Early nutrition programming of long-term health.

PubMed

Koletzko, Berthold; Brands, Brigitte; Poston, Lucilla; Godfrey, Keith; Demmelmair, Hans

2012-08-01

Increasing evidence from the EU Project EARNEST and many other investigators demonstrates that early nutrition and lifestyle have long-term effects on later health and the risk of common non-communicable diseases (known as 'developmental programming'). Because of the increasing public health importance and the transgenerational nature of the problem, obesity and associated disorders are the focus of the new EU funded project 'EarlyNutrition'. Currently, three key hypotheses have been defined: the fuel mediated 'in utero' hypothesis suggests that intrauterine exposure to an excess of fuels, most notably glucose, causes permanent changes of the fetus that lead to obesity in postnatal life; the accelerated postnatal weight gain hypothesis proposes an association between rapid weight gain in infancy and an increased risk of later obesity and adverse outcomes; and the mismatch hypothesis suggests that experiencing a developmental 'mismatch' between a sub-optimal perinatal and an obesogenic childhood environment is related to a particular predisposition to obesity and corresponding co-morbidities. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme to investigate those key hypotheses, project EarlyNutrition will provide the scientific foundations for evidence-based recommendations for optimal nutrition considering long-term health outcomes, with a focus on obesity and related disorders. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level of the relationships between early life nutritional status and the risk of later adiposity. This will help refine strategies for intervention in early life to prevent obesity.

Early development of the circumferential axonal pathway in mouse and chick spinal cord.

PubMed

Holley, J A

1982-03-10

The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

Sub-cellular distribution and translocation of TRP channels.

PubMed

Toro, Carlos A; Arias, Luis A; Brauchi, Sebastian

2011-01-01

Cellular electrical activity is the result of a highly complex processes that involve the activation of ion channel proteins. Ion channels make pores on cell membranes that rapidly transit between conductive and non-conductive states, allowing different ions to flow down their electrochemical gradients across cell membranes. In the case of neuronal cells, ion channel activity orchestrates action potentials traveling through axons, enabling electrical communication between cells in distant parts of the body. Somatic sensation -our ability to feel touch, temperature and noxious stimuli- require ion channels able to sense and respond to our peripheral environment. Sensory integration involves the summing of various environmental cues and their conversion into electrical signals. Members of the Transient Receptor Potential (TRP) family of ion channels have emerged as important mediators of both cellular sensing and sensory integration. The regulation of the spatial and temporal distribution of membrane receptors is recognized as an important mechanism for controlling the magnitude of the cellular response and the time scale on which cellular signaling occurs. Several studies have shown that this mechanism is also used by TRP channels to modulate cellular response and ultimately fulfill their physiological function as sensors. However, the inner-working of this mode of control for TRP channels remains poorly understood. The question of whether TRPs intrinsically regulate their own vesicular trafficking or weather the dynamic regulation of TRP channel residence on the cell surface is caused by extrinsic changes in the rates of vesicle insertion or retrieval remain open. This review will examine the evidence that sub-cellular redistribution of TRP channels plays an important role in regulating their activity and explore the mechanisms that control the trafficking of vesicles containing TRP channels.

Calcium ion as intracellular messenger and cellular toxin.

PubMed

Rasmussen, H; Barrett, P; Smallwood, J; Bollag, W; Isales, C

1990-03-01

Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium ion as intracellular messenger and cellular toxin.

PubMed Central

Rasmussen, H; Barrett, P; Smallwood, J; Bollag, W; Isales, C

1990-01-01

Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2190811

Geometric confinement influences cellular mechanical properties I -- adhesion area dependence.

PubMed

Su, Judith; Jiang, Xingyu; Welsch, Roy; Whitesides, George M; So, Peter T C

2007-06-01

Interactions between the cell and the extracellular matrix regulate a variety of cellular properties and functions, including cellular rheology. In the present study of cellular adhesion, area was controlled by confining NIH 3T3 fibroblast cells to circular micropatterned islands of defined size. The shear moduli of cells adhering to islands of well defined geometry, as measured by magnetic microrheometry, was found to have a significantly lower variance than those of cells allowed to spread on unpatterned surfaces. We observe that the area of cellular adhesion influences shear modulus. Rheological measurements further indicate that cellular shear modulus is a biphasic function of cellular adhesion area with stiffness decreasing to a minimum value for intermediate areas of adhesion, and then increasing for cells on larger patterns. We propose a simple hypothesis: that the area of adhesion affects cellular rheological properties by regulating the structure of the actin cytoskeleton. To test this hypothesis, we quantified the volume fraction of polymerized actin in the cytosol by staining with fluorescent phalloidin and imaging using quantitative 3D microscopy. The polymerized actin volume fraction exhibited a similar biphasic dependence on adhesion area. Within the limits of our simplifying hypothesis, our experimental results permit an evaluation of the ability of established, micromechanical models to predict the cellular shear modulus based on polymerized actin volume fraction. We investigated the "tensegrity", "cellular-solids", and "biopolymer physics" models that have, respectively, a linear, quadratic, and 5/2 dependence on polymerized actin volume fraction. All three models predict that a biphasic trend in polymerized actin volume fraction as a function of adhesion area will result in a biphasic behavior in shear modulus. Our data favors a higher-order dependence on polymerized actin volume fraction. Increasingly better experimental agreement is observed for

Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Dong Suk; Choi, Yoorim; Choi, Seong Mi

2015-11-27

Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. Inmore » contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs. - Highlights: • Resveratrol enhances self-renewal potential and multipotency of early passage MSCs. • Resveratrol accelerates the cellular senescence of late passage MSCs. • The effects of resveratrol on MSCs are dependent on the presence of SIRT1. • SIRT1 modulates ERK/GSK-3β/β-catenin signaling. • Sustained resveratrol treatment maintains MSC stemness up to P10.« less

Taming the Sphinx: Mechanisms of Cellular Sphingolipid Homeostasis

PubMed Central

Olson, D. K.; Fröhlich, F.; Farese, R; Walther, T. C.

2016-01-01

Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. PMID:26747648

Using cellular automata to generate image representation for biological sequences.

PubMed

Xiao, X; Shao, S; Ding, Y; Huang, Z; Chen, X; Chou, K-C

2005-02-01

A novel approach to visualize biological sequences is developed based on cellular automata (Wolfram, S. Nature 1984, 311, 419-424), a set of discrete dynamical systems in which space and time are discrete. By transforming the symbolic sequence codes into the digital codes, and using some optimal space-time evolvement rules of cellular automata, a biological sequence can be represented by a unique image, the so-called cellular automata image. Many important features, which are originally hidden in a long and complicated biological sequence, can be clearly revealed thru its cellular automata image. With biological sequences entering into databanks rapidly increasing in the post-genomic era, it is anticipated that the cellular automata image will become a very useful vehicle for investigation into their key features, identification of their function, as well as revelation of their "fingerprint". It is anticipated that by using the concept of the pseudo amino acid composition (Chou, K.C. Proteins: Structure, Function, and Genetics, 2001, 43, 246-255), the cellular automata image approach can also be used to improve the quality of predicting protein attributes, such as structural class and subcellular location.

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

NASA Astrophysics Data System (ADS)

Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Zoica Dinu, Cerasela

2016-02-01

Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

PubMed Central

Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

2016-01-01

Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. PMID:26820775

Surface engineered biosensors for the early detection of cancer

NASA Astrophysics Data System (ADS)

Islam, Muhymin

Cancer commences in the building block of human body which is cells and in most of the cases remains silent at early stage. Diseases are only expressed at molecular and cellular level at primary stages. Recognition of diseases at this micro and nano level might reduce the mortality rate of cancer significantly. This research work aimed to introduce novel electronic biosensors for for identification of cancer at cellular level. The dissertation study focuses on 1) Label-Free Isolation of Metastatic Tumor Cells Using Filter Based Microfluidic device; 2) Nanotextured Polymer Substrates for Enhanced Cancer Cell Isolation and Cell Growth; 3) Nanotextured Microfluidic Channel for Electrical Profiling and Detection of Tumor Cells from Blood; and 4) Single Biochip for the Detection of Tumor Cells by Electrical Profile and Surface Immobilized Aptamer. Standard silicon processing techniques were followed to fabricate all of the biosensors. Nantoextruing and surface functionalizon were also incorporated to elevate the efficiency of the devices. The first approach aimed to detect cancer cells from blood based on their mechanophysical properties. Cancer cells are larger than blood cells but highly elastic in nature. These cells can squeeze through small microchannels much smaller than their size. The cross sectional area of the microchannels was optimized to isolate tumor cells from blood. Nanotextured polymer substrates, a platform inspired from the natural basement membrane was used to enhance the isolation and growth of tumor cells. Micro reactive ion etching was performed to have better control on features of nantoxtured surfaces and did not require any template. Next, electrical measurement of ionic current was performed across single microchannel to detect tumor cells from blood. Later, nanotexturing enhanced the efficiency of the device by selectively altering the translocation profile of cancer cells. Eventually aptamer functionalized nanotextured polymer surface was

In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion

PubMed Central

Zhang, Yong-Tai; Huang, Zhe-Bin; Zhang, Su-Juan; Zhao, Ji-Hui; Wang, Zhi; Liu, Ying; Feng, Nian-Ping

2012-01-01

Objective To investigate the cellular uptake of evodiamine and rutaecarpine in a microemulsion in comparison with aqueous suspensions and tinctures. Materials and methods A microemulsion was prepared using the dropwise addition method. Mouse skin fibroblasts were cultured in vitro to investigate the optimal conditions for evodiamine and rutaecarpine uptake with different drug concentrations and administration times. Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions. Rhodamine B labeling and laser scanning confocal microscopy (LSCM) were used to explore the distribution of fluorochrome transferred with the microemulsion in fibroblasts. Cellular morphology was also investigated, using optical microscopy to evaluate microemulsion-induced cellular toxicity. Results The maximum cellular drug uptake amounts were obtained with a 20% concentration (v/v) of microemulsion and an 8 hour administration time. Drug uptake by mouse skin fibroblasts was lowest when the drugs were loaded in microemulsion. After incubation with rhodamine B-labeled microemulsion for 8 hours, the highest fluorescence intensity was achieved, and the fluorochrome was primarily distributed in the cytochylema. No obvious cellular morphologic changes were observed with the administration of either the microemulsion or the aqueous suspension; for the tincture group, however, massive cellular necrocytosis was observed. Conclusion The lower cellular uptake with microemulsion may be due to the fact that most of the drug loaded in the microemulsion vehicle was transported via the intercellular space, while a small quantity of free drug (released from the vehicle) was ingested through transmembrane transport. Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle. The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity

In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion.

PubMed

Zhang, Yong-Tai; Huang, Zhe-Bin; Zhang, Su-Juan; Zhao, Ji-Hui; Wang, Zhi; Liu, Ying; Feng, Nian-Ping

2012-01-01

To investigate the cellular uptake of evodiamine and rutaecarpine in a microemulsion in comparison with aqueous suspensions and tinctures. A microemulsion was prepared using the dropwise addition method. Mouse skin fibroblasts were cultured in vitro to investigate the optimal conditions for evodiamine and rutaecarpine uptake with different drug concentrations and administration times. Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions. Rhodamine B labeling and laser scanning confocal microscopy (LSCM) were used to explore the distribution of fluorochrome transferred with the microemulsion in fibroblasts. Cellular morphology was also investigated, using optical microscopy to evaluate microemulsion-induced cellular toxicity. The maximum cellular drug uptake amounts were obtained with a 20% concentration (v/v) of microemulsion and an 8 hour administration time. Drug uptake by mouse skin fibroblasts was lowest when the drugs were loaded in microemulsion. After incubation with rhodamine B-labeled microemulsion for 8 hours, the highest fluorescence intensity was achieved, and the fluorochrome was primarily distributed in the cytochylema. No obvious cellular morphologic changes were observed with the administration of either the microemulsion or the aqueous suspension; for the tincture group, however, massive cellular necrocytosis was observed. The lower cellular uptake with microemulsion may be due to the fact that most of the drug loaded in the microemulsion vehicle was transported via the intercellular space, while a small quantity of free drug (released from the vehicle) was ingested through transmembrane transport. Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle. The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on

Alpha-Synuclein: From Early Synaptic Dysfunction to Neurodegeneration.

PubMed

Ghiglieri, Veronica; Calabrese, Valeria; Calabresi, Paolo

2018-01-01

Over the last two decades, many experimental and clinical studies have provided solid evidence that alpha-synuclein (α-syn), a small, natively unfolded protein, is closely related to Parkinson's disease (PD) pathology. To provide an overview on the different roles of this protein, here we propose a synopsis of seminal and recent studies that explored the many aspects of α-syn. Ranging from the physiological functions to its neurodegenerative potential, the relationship with the possible pathogenesis of PD will be discussed. Close attention will be paid on early cellular and molecular alterations associated with the presence of α-syn aggregates.

Cellular complexity captured in durable silica biocomposites

PubMed Central

Kaehr, Bryan; Townson, Jason L.; Kalinich, Robin M.; Awad, Yasmine H.; Swartzentruber, B. S.; Dunphy, Darren R.; Brinker, C. Jeffrey

2012-01-01

Tissue-derived cultured cells exhibit a remarkable range of morphological features in vitro, depending on phenotypic expression and environmental interactions. Translation of these cellular architectures into inorganic materials would provide routes to generate hierarchical nanomaterials with stabilized structures and functions. Here, we describe the fabrication of cell/silica composites (CSCs) and their conversion to silica replicas using mammalian cells as scaffolds to direct complex structure formation. Under mildly acidic solution conditions, silica deposition is restricted to the molecularly crowded cellular template. Inter- and intracellular heterogeneity from the nano- to macroscale is captured and dimensionally preserved in CSCs following drying and subjection to extreme temperatures allowing, for instance, size and shape preserving pyrolysis of cellular architectures to form conductive carbon replicas. The structural and behavioral malleability of the starting material (cultured cells) provides opportunities to develop robust and economical biocomposites with programmed structures and functions. PMID:23045634

Cellular therapy in bone-tendon interface regeneration

PubMed Central

Rothrauff, Benjamin B; Tuan, Rocky S

2014-01-01

The intrasynovial bone-tendon interface is a gradual transition from soft tissue to bone, with two intervening zones of uncalcified and calcified fibrocartilage. Following injury, the native anatomy is not restored, resulting in inferior mechanical properties and an increased risk of re-injury. Recent in vivo studies provide evidence of improved healing when surgical repair of the bone-tendon interface is augmented with cells capable of undergoing chondrogenesis. In particular, cellular therapy in bone-tendon healing can promote fibrocartilage formation and associated improvements in mechanical properties. Despite these promising results in animal models, cellular therapy in human patients remains largely unexplored. This review highlights the development and structure-function relationship of normal bone-tendon insertions. The natural healing response to injury is discussed, with subsequent review of recent research on cellular approaches for improved healing. Finally, opportunities for translating in vivo findings into clinical practice are identified. PMID:24326955

Cellular response of preosteoblasts to nanograined/ultrafine-grained structures.

PubMed

Misra, R D K; Thein-Han, W W; Pesacreta, T C; Hasenstein, K H; Somani, M C; Karjalainen, L P

2009-06-01

Metallic materials with submicron- to nanometer-sized grains provide surfaces that are different from conventional polycrystalline materials because of the large proportion of grain boundaries with high free energy. In the study described here, the combination of cellular and molecular biology, materials science and engineering advances our understanding of cell-substrate interactions, especially the cellular activity between preosteoblasts and nanostructured metallic surfaces. Experiments on the effect of nano-/ultrafine grains have shown that cell attachment, proliferation, viability, morphology and spread are favorably modulated and significantly different from conventional coarse-grained structures. Additionally, immunofluorescence studies demonstrated stronger vinculin signals associated with actin stress fibers in the outer regions of the cells and cellular extensions on nanograined/ultrafine-grained substrate. These observations suggest enhanced cell-substrate interaction and activity. The differences in the cellular response on nanograined/ultrafine-grained and coarse-grained substrates are attributed to grain size and degree of hydrophilicity. The outcomes of the study are expected to reduce challenges to engineer bulk nanostructured materials with specific physical and surface properties for medical devices with improved cellular attachment and response. The data lay the foundation for a new branch of nanostructured materials for biomedical applications.

Multi-Cellular Logistics of Collective Cell Migration

PubMed Central

Yamao, Masataka; Naoki, Honda; Ishii, Shin

2011-01-01

During development, the formation of biological networks (such as organs and neuronal networks) is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic) blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes “collective migration,” whereas strong noise from non-migratory cells causes “dispersive migration.” Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems. PMID:22205934

Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism?

PubMed

Whitaker-Azmitia, Patricia M

2005-02-01

The hypothesis explored in this review is that the high levels of serotonin in the blood seen in some autistic children (the so-called hyperserotonemia of autism) may lead to some of the behavioral and cellular changes also observed in the disorder. At early stages of development, when the blood-brain Barrier is not yet fully formed, the high levels of serotonin in the blood can enter the brain of a developing fetus and cause loss of serotonin terminals through a known negative feedback function of serotonin during development. The loss of serotonin innervation persists throughout subsequent development and the symptoms of autism appear. A review of the basic scientific literature on prenatal treatments affecting serotonin is given, in support of this hypothesis, with an emphasis on studies using the serotonin agonist, 5-methoxytryptamine (5-MT). In work using 5-MT to mimic hyperserotonemia, Sprague-Dawley rats are treated from gestational day 12 until postnatal 20. In published reports, these animals have been found to have a significant loss of serotonin terminals, decreased metabolic activity in cortex, changes in columnar development in cortex, changes in serotonin receptors, and "autistic-like" behaviors. In preliminary cellular findings given in this review, the animals have also been found to have cellular changes in two relevant brain regions: 1. Central nucleus of the amygdala, a brain region involved in fear-responding, where an increase in calcitonin gene related peptide (CGRP) was found 2. Paraventricular nucleus of the hypothalamus, a brain region involved in social memory and bonding, where a decrease in oxytocin was found. Both of these cellular changes could result from loss of serotonin innervation, possibly due to loss of terminal outgrowth from the same cells of the raphe nuclei. Thus, increased serotonergic activity during development could damage neurocircuitry involved in emotional responding to social stressors and may have relevance to the

Correlating two-photon excited fluorescence imaging of breast cancer cellular redox state with seahorse flux analysis of normalized cellular oxygen consumption

NASA Astrophysics Data System (ADS)

Hou, Jue; Wright, Heather J.; Chan, Nicole; Tran, Richard; Razorenova, Olga V.; Potma, Eric O.; Tromberg, Bruce J.

2016-06-01

Two-photon excited fluorescence (TPEF) imaging of the cellular cofactors nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide is widely used to measure cellular metabolism, both in normal and pathological cells and tissues. When dual-wavelength excitation is used, ratiometric TPEF imaging of the intrinsic cofactor fluorescence provides a metabolic index of cells-the "optical redox ratio" (ORR). With increased interest in understanding and controlling cellular metabolism in cancer, there is a need to evaluate the performance of ORR in malignant cells. We compare TPEF metabolic imaging with seahorse flux analysis of cellular oxygen consumption in two different breast cancer cell lines (MCF-7 and MDA-MB-231). We monitor metabolic index in living cells under both normal culture conditions and, for MCF-7, in response to cell respiration inhibitors and uncouplers. We observe a significant correlation between the TPEF-derived ORR and the flux analyzer measurements (R=0.7901, p<0.001). Our results confirm that the ORR is a valid dynamic index of cell metabolism under a range of oxygen consumption conditions relevant for cancer imaging.

Cellular activation in limbic brain systems during social play behaviour in rats.

PubMed

van Kerkhof, Linda W M; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J M J

2014-07-01

Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-Fos as a marker. After a session of social play behaviour, pronounced increases in c-Fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organized in this network, as indicated by play-specific correlations in c-Fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organized neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats.

Cellular activation in limbic brain systems during social play behaviour in rats

PubMed Central

van Kerkhof, Linda W.M.; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J.M.J.

2013-01-01

Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-fos as a marker. After a session of social play behaviour, pronounced increases in c-fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organised in this network, as indicated by play-specific correlations in c-fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organised neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats. PMID:23670540

Antibiotic efficacy is linked to bacterial cellular respiration

PubMed Central

Lobritz, Michael A.; Belenky, Peter; Porter, Caroline B. M.; Gutierrez, Arnaud; Yang, Jason H.; Schwarz, Eric G.; Dwyer, Daniel J.; Khalil, Ahmad S.; Collins, James J.

2015-01-01

Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes—the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy. PMID:26100898

Microfluidics-based in vivo mimetic systems for the study of cellular biology.

PubMed

Kim, Donghyuk; Wu, Xiaojie; Young, Ashlyn T; Haynes, Christy L

2014-04-15

that focus on modeling both biophysical and biochemical interactions in cellular communication, such as flow and cell-cell networks. We also describe more advanced systems that mimic higher level biological networks, such as organ on-a-chip and animal on-a-chip models. Since the first papers in the early 1990s, interest in the bioanalytical use of microfluidics has grown significantly. Advances in micro-/nanofabrication technology have allowed researchers to produce miniaturized, biocompatible assay platforms suitable for microfluidic studies in biochemistry and chemical biology. Well-designed microfluidic platforms can achieve quick, in vitro analyses on pico- and femtoliter volume samples that are temporally, spatially, and chemically resolved. In addition, controlled cell culture techniques using a microfluidic platform have produced biomimetic systems that allow researchers to replicate and monitor physiological interactions. Pioneering work has successfully created cell-fluid, cell-cell, cell-tissue, tissue-tissue, even organ-like level interfaces. Researchers have monitored cellular behaviors in these biomimetic microfluidic environments, producing validated model systems to understand human pathophysiology and to support the development of new therapeutics.

Cell Proliferation, Reactive Oxygen and Cellular Glutathione

PubMed Central

Day, Regina M.; Suzuki, Yuichiro J.

2005-01-01

A variety of cellular activities, including metabolism, growth, and death, are regulated and modulated by the redox status of the environment. A biphasic effect has been demonstrated on cellular proliferation with reactive oxygen species (ROS)—especially hydrogen peroxide and superoxide—in which low levels (usually submicromolar concentrations) induce growth but higher concentrations (usually >10–30 micromolar) induce apoptosis or necrosis. This phenomenon has been demonstrated for primary, immortalized and transformed cell types. However, the mechanism of the proliferative response to low levels of ROS is not well understood. Much of the work examining the signal transduction by ROS, including H2O2, has been performed using doses in the lethal range. Although use of higher ROS doses have allowed the identification of important signal transduction pathways, these pathways may be activated by cells only in association with ROS-induced apoptosis and necrosis, and may not utilize the same pathways activated by lower doses of ROS associated with increased cell growth. Recent data has shown that low levels of exogenous H2O2 up-regulate intracellular glutathione and activate the DNA binding activity toward antioxidant response element. The modulation of the cellular redox environment, through the regulation of cellular glutathione levels, may be a part of the hormetic effect shown by ROS on cell growth. PMID:18648617

Cellular and molecular deviations in bovine in vitro-produced embryos are related to the large offspring syndrome.

PubMed

Lazzari, Giovanna; Wrenzycki, Christine; Herrmann, Doris; Duchi, Roberto; Kruip, Theo; Niemann, Heiner; Galli, Cesare

2002-09-01

The large offspring syndrome (LOS) is observed in bovine and ovine offspring following transfer of in vitro-produced (IVP) or cloned embryos and is characterized by a multitude of pathologic changes, of which extended gestation length and increased birthweight are predominant features. In the present study, we used bovine blastocysts to analyze cellular parameters, i.e., the number of cells in Day 7 blastocysts and the size of Day 12 elongating blastocysts, and molecular parameters, i.e., the relative abundance of developmentally important genes: glucose transporter (Glut) 1, Glut-2, Glut-3, Glut-4, heat shock protein (Hsp) 70.1, Cu/Zn-superoxide dismutase (SOD), histone H4.1, basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) I receptor (R), and IGFII-R. Some blastocysts were produced by in vitro maturation and fertilization followed by in vitro culture in synthetic oviduct fluid medium supplemented with BSA or human serum or by in vivo culture in the sheep oviduct. Other blastocysts were derived in vivo from the uterine horns of superovulated donors. The findings made in the early embryos were related to a representative number of calves obtained from each production system and from artificial insemination (AI). In vitro culture of bovine embryos in the presence of high concentrations of serum or BSA significantly increased the number of cells in Day 7 blastocysts, the size of blastocysts on Day 12, and the relative abundance of the transcripts for Hsp70.1, Cu/Zn-SOD, Glut-3, Glut-4, bFGF, and IGFI-R when compared with embryos from the in vivo production groups. Birthweights of calves derived from IVP embryos were significantly higher than those of calves derived from sheep oviduct culture, superovulation, or AI. The results support the hypothesis that persistence of early deviations in development is causally involved in the incidence of LOS, in particular in increased birthweights. The cellular and molecular parameters analyzed in this

Earliest Life on Earth - New Data Call for Revision

NASA Astrophysics Data System (ADS)

van Zuilen, M.; Lepland, A.; Arrhenius, G.

2001-12-01

The highly metamorphosed 3.8 Ga old Isua Supracrustal Belt (ISB) in southern West Greenland contains the most widely studied example of ancient Archaean water-lain sediments that carry traces of ancient life. Carbonate deposits in the ISB were originally interpreted as primary platform deposits in a shallow marine environment. Graphite occurring in relatively high concentrations and associating with apatite in these rocks has been interpreted as a remnant of ancient biogenic matter, pointing to the existence of a vast microbial ecosystem in the early Archaean (1,2) Recent discoveries, however, cast considerable doubt on this scenario. The ISB metacarbonates are now found to be secondary deposits, resulting from extensive metasomatism (3,4). The apatite-associated occurrence of graphite, forming the basis for earlier biogenic interpretation, is entirely restricted to these metasomatic carbonate deposits, while true sediments like BIF's and metacherts contain virtually no graphite. Furthermore, within these metacarbonates graphite appears to be specifically associated with iron carbonate (siderite) and magnetite. Thermal decomposition of siderite; 6 FeCO3 ' 2Fe3O4 + 5CO2 + C, is the process seemingly responsible for the graphite formation (5,6). The cation composition (Fe, Mg, Mn, and Ca) of the carbonate minerals, carbon isotope analysis of carbonates and associated graphite and petrographic analysis of a suite of metacarbonates support the conclusion that multiple pulses of metasomatism affected the ISB, causing the deposition of siderite and subsequent partial degradation to graphite and magnetite. Equilibrium isotope fractionation between siderite and graphite in these rocks indicates a temperature of metasomatism between 500 and 600C, which coincides with other estimates of metamorphic temperature for the ISB. The siderite-graphite-apatite association in the ISB consequently appears to be an entirely abiogenic metasomatic feature, which does not point to traces

Active Cellular Mechanics and its Consequences for Animal Development

NASA Astrophysics Data System (ADS)

Noll, Nicholas B.

information about the mechanical state of an epithelial tissue. Utilizing the stress-geometry 'duality', we formulate a local "Mechanical Inference" of cellular-level stress using solely cell geometry that dramatically improves over past image-based inference techniques. In Chapter 4, we generalize the ATN model to explore the controlled re-arrangement of cells within epithelial tissues. This requires us to explicitly consider the effects of cadherin mediated adhesion, and its regulation, on tissue morphogenesis. We find that positive feedback between myosin and cortical tension, along with traction-dependent depletion of cytoskeletal cadherin is sufficient to recapitulate the morphogenetic movement of cells observed during convergent extension of the lateral ectoderm during Drosophila embryogenesis. Statistical analyses of live-imaging data supports the fundamentals of the model. Chapter 5 focuses on morphogenesis at a mesoscopic scale by coarse-graining the cellular ATN model. Under this limit, we expect an epithelial tissue should behave as an effective viscous, compressible fluid driven by myosin gradients on intermediate time-scales. Theoretical predictions are empirically tested against in-toto microscopy data obtained during early Drosophila embryogenesis.

Zn2+ at a cellular crossroads

PubMed Central

Liang, Xiaomeng; Dempski, Robert E.; Burdette, Shawn C.

2016-01-01

Zinc is an essential micronutrient for cellular homeostasis. Initially proposed to only contribute to cellular viability through structural roles and non-redox catalysis, advances in quantifying changes in nM and pM quantities of Zn2+ have elucidated increasing functions as an important signaling molecule. This includes Zn2+-mediated regulation of transcription factors and subsequent protein expression, storage and release of intracellular compartments of zinc quanta into the extracellular space which modulates plasma membrane protein function, as well as intracellular signaling pathways which contribute to the immune response. This review highlights some recent advances in our understanding of zinc signaling. PMID:27010344

A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export.

PubMed

Gong, Danyang; Kim, Yong Hoon; Xiao, Yuchen; Du, Yushen; Xie, Yafang; Lee, Kevin K; Feng, Jun; Farhat, Nisar; Zhao, Dawei; Shu, Sara; Dai, Xinghong; Chanda, Sumit K; Rana, Tariq M; Krogan, Nevan J; Sun, Ren; Wu, Ting-Ting

2016-11-09

Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1. Genome-wide analysis reveals a subset of cellular mRNAs whose nuclear export is blocked by ORF10 with the 3' UTRs of ORF10-targeted transcripts conferring sensitivity to export inhibition. The ORF10-Rae1 interaction is important for the virus to express viral genes and produce infectious virions. These results suggest that a nuclear DNA virus can selectively interfere with RNA export to restrict host gene expression for optimal replication. Published by Elsevier Inc.

ORF phage display to identify cellular proteins with different functions.

PubMed

Li, Wei

2012-09-01

Open reading frame (ORF) phage display is a new branch of phage display aimed at improving its efficiency to identify cellular proteins with specific binding or functional activities. Despite the success of phage display with antibody libraries and random peptide libraries, phage display with cDNA libraries of cellular proteins identifies a high percentage of non-ORF clones encoding unnatural short peptides with minimal biological implications. This is mainly because of the uncontrollable reading frames of cellular proteins in conventional cDNA libraries. ORF phage display solves this problem by eliminating non-ORF clones to generate ORF cDNA libraries. Here I summarize the procedures of ORF phage display, discuss the factors influencing its efficiency, present examples of its versatile applications, and highlight evidence of its capability of identifying biologically relevant cellular proteins. ORF phage display coupled with different selection strategies is capable of delineating diverse functions of cellular proteins with unique advantages. Copyright © 2012 Elsevier Inc. All rights reserved.

Cellular-dendritic transition in directionally solidified binary alloys

NASA Technical Reports Server (NTRS)

Tewari, S. N.; Laxmanan, V.

1987-01-01

The microstructural development of binary alloys during directional solidification is studied. Cellular growth data for the Al-Cu and Pb-Sn binary alloy systems are analyzed in order evaluate the criteria of Kurz and Fisher (1981) and Trivedi (1984) for cellular-dendritic transition. It is observed that the experimental growth values do not correlate with the Kurz and Fisher or Trivedi data.

47 CFR 22.901 - Cellular service requirements and limitations.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... 22.901 Section 22.901 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and... radiotelephone, dispatch, one way or two way paging, and personal communications services (as defined in part 24...

47 CFR 22.901 - Cellular service requirements and limitations.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... 22.901 Section 22.901 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and... radiotelephone, dispatch, one way or two way paging, and personal communications services (as defined in part 24...

Pathway towards Programmable Wave Anisotropy in Cellular Metamaterials

NASA Astrophysics Data System (ADS)

Celli, Paolo; Zhang, Weiting; Gonella, Stefano

2018-01-01

In this work, we provide a proof-of-concept experimental demonstration of the wave-control capabilities of cellular metamaterials endowed with populations of tunable electromechanical resonators. Each independently tunable resonator comprises a piezoelectric patch and a resistor-inductor shunt, and its resonant frequency can be seamlessly reprogrammed without interfering with the cellular structure's default properties. We show that, by strategically placing the resonators in the lattice domain and by deliberately activating only selected subsets of them, chosen to conform to the directional features of the beamed wave response, it is possible to override the inherent wave anisotropy of the cellular medium. The outcome is the establishment of tunable spatial patterns of energy distillation resulting in a nonsymmetric correction of the wave fields.

Endoplasmic Reticulum-Plasma Membrane Contacts Regulate Cellular Excitability.

PubMed

Dickson, Eamonn J

2017-01-01

Cells that have intrinsic electrical excitability utilize changes in membrane potential to communicate with neighboring cells and initiate cellular cascades. Excitable cells like neurons and myocytes have evolved highly specialized subcellular architectures to translate these electrical signals into cellular events. One such structural specialization is sarco-/endoplasmic reticulum-plasma membrane contact sites. These membrane contact sites are positioned by specific membrane-membrane tethering proteins and contain an ever-expanding list of additional proteins that organize information transfer across the junctional space (~ 15-25 nm distance) to shape membrane identity and control cellular excitability. In this chapter we discuss how contacts between the sarco-/endoplasmic reticulum and plasma membrane are essential for regulated excitation-contraction coupling in striated muscle and control of lipid-dependent ion channels.

Cellular senescence in the Penna model of aging

NASA Astrophysics Data System (ADS)

Periwal, Avikar

2013-11-01

Cellular senescence is thought to play a major role in age-related diseases, which cause nearly 67% of all human deaths worldwide. Recent research in mice showed that exercising mice had higher levels of telomerase, an enzyme that helps maintain telomere length, than nonexercising mice. A commonly used model for biological aging was proposed by Penna. I propose a modification of the Penna model that incorporates cellular senescence and find an analytical steady-state solution following Coe, Mao, and Cates [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.89.288103 89, 288103 (2002)]. I find that models corresponding to delayed cellular senescence have younger populations that live longer. I fit the model to the United Kingdom's death distribution, which the original Penna model cannot do.

[Cellular phones and public health].

PubMed

Leventhal, Alex; Karsenty, Eric; Sadetzki, Siegal

2004-08-01

The increased use of mobile cellular phone by the public is associated with a wave of contradictory reports about the possible health effects, due to the exposure of the users to electromagnetic non-ionizing radiation. This article reviews the state of the art of the present knowledge concerning the biological and medical effects of exposure to cellular phones, with an emphasis on its possible carcinogenic effect. Health conditions, which have been ascribed to the use of mobile phones mainly include some types of cancer and changes of brain activity. However, the balance of evidence from available studies has not yet supported these claims. Following the recommendation of special international expert committees, the IARC (International Association for Research on Cancer) is conducting a multi-center study to determine the possible effect of cellular phone use on brain and salivary gland tumors. Israel is one of the participants of this study. The only established health effect associated with the use of such technology is an increased risk for road accidents, unrelated to the amount of radiation emitted by phone. The challenge posed by this new technology to health authorities all over the world has lead to the definition of a new principle, the so-called "prudent avoidance", used as guidelines for the definition of an adequate public health policy. The public policy in Israel has used the prudent avoidance principles, while awaiting the results of the multi-national epidemiological studies.

Cellular solidification of transparent monotectics

NASA Technical Reports Server (NTRS)

Kaulker, W. F.

1986-01-01

Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

33 CFR 183.516 - Cellular plastic used to encase fuel tanks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Cellular plastic used to encase....516 Cellular plastic used to encase fuel tanks. (a) Cellular plastic used to encase metallic fuel... water per square foot of cut surface, measure under Military Specification MIL P-21929B. (b) Non...

33 CFR 183.516 - Cellular plastic used to encase fuel tanks.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Cellular plastic used to encase....516 Cellular plastic used to encase fuel tanks. (a) Cellular plastic used to encase metallic fuel... water per square foot of cut surface, measure under Military Specification MIL P-21929B. (b) Non...

33 CFR 183.516 - Cellular plastic used to encase fuel tanks.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Cellular plastic used to encase....516 Cellular plastic used to encase fuel tanks. (a) Cellular plastic used to encase metallic fuel... water per square foot of cut surface, measure under Military Specification MIL P-21929B. (b) Non...

33 CFR 183.516 - Cellular plastic used to encase fuel tanks.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Cellular plastic used to encase....516 Cellular plastic used to encase fuel tanks. (a) Cellular plastic used to encase metallic fuel... water per square foot of cut surface, measure under Military Specification MIL P-21929B. (b) Non...

Adaptive optics optical coherence tomography at 120,000 depth scans/s for non-invasive cellular phenotyping of the living human retina

PubMed Central

Torti, Cristiano; Považay, Boris; Hofer, Bernd; Unterhuber, Angelika; Carroll, Joseph; Ahnelt, Peter Kurt; Drexler, Wolfgang

2012-01-01

This paper presents a successful combination of ultra-high speed (120,000 depth scans/s), ultra-high resolution optical coherence tomography with adaptive optics and an achromatizing lens for compensation of monochromatic and longitudinal chromatic ocular aberrations, respectively, allowing for non-invasive volumetric imaging in normal and pathologic human retinas at cellular resolution. The capability of this imaging system is demonstrated here through preliminary studies by probing cellular intraretinal structures that have not been accessible so far with in vivo, non-invasive, label-free imaging techniques, including pigment epithelial cells, micro-vasculature of the choriocapillaris, single nerve fibre bundles and collagenous plates of the lamina cribrosa in the optic nerve head. In addition, the volumetric extent of cone loss in two colour-blinds could be quantified for the first time. This novel technique provides opportunities to enhance the understanding of retinal pathogenesis and early diagnosis of retinal diseases. PMID:19997159

The cellular and molecular basis of cnidarian neurogenesis.

PubMed

Rentzsch, Fabian; Layden, Michael; Manuel, Michaël

2017-01-01

Neurogenesis initiates during early development and it continues through later developmental stages and in adult animals to enable expansion, remodeling, and homeostasis of the nervous system. The generation of nerve cells has been analyzed in detail in few bilaterian model organisms, leaving open many questions about the evolution of this process. As the sister group to bilaterians, cnidarians occupy an informative phylogenetic position to address the early evolution of cellular and molecular aspects of neurogenesis and to understand common principles of neural development. Here we review studies in several cnidarian model systems that have revealed significant similarities and interesting differences compared to neurogenesis in bilaterian species, and between different cnidarian taxa. Cnidarian neurogenesis is currently best understood in the sea anemone Nematostella vectensis, where it includes epithelial neural progenitor cells that express transcription factors of the soxB and atonal families. Notch signaling regulates the number of these neural progenitor cells, achaete-scute and dmrt genes are required for their further development and Wnt and BMP signaling appear to be involved in the patterning of the nervous system. In contrast to many vertebrates and Drosophila, cnidarians have a high capacity to generate neurons throughout their lifetime and during regeneration. Utilizing this feature of cnidarian biology will likely allow gaining new insights into the similarities and differences of embryonic and regenerative neurogenesis. The use of different cnidarian model systems and their expanding experimental toolkits will thus continue to provide a better understanding of evolutionary and developmental aspects of nervous system formation. WIREs Dev Biol 2017, 6:e257. doi: 10.1002/wdev.257 For further resources related to this article, please visit the WIREs website. © 2016 The Authors. WIREs Developmental Biology published by Wiley Periodicals, Inc.

Cellular compartmentalization of secondary metabolism

USDA-ARS?s Scientific Manuscript database

Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors sh...

Cellular Automata Ideas in Digital Circuits and Switching Theory.

ERIC Educational Resources Information Center

Siwak, Pawel P.

1985-01-01

Presents two examples which illustrate the usefulness of ideas from cellular automata. First, Lee's algorithm is recalled and its cellular nature shown. Then a problem from digraphs, which has arisen from analyzing predecessing configurations in the famous Conway's "game of life," is considered. (Author/JN)

Cellular mechanisms underlying an effect of "early handling" on pCREB and BDNF in the neonatal rat hippocampus.

PubMed

Garoflos, Efstathios; Stamatakis, Antonios; Mantelas, Athanasios; Philippidis, Helen; Stylianopoulou, Fotini

2005-08-09

Early experiences have long-term effects on brain function and behavior. However, the precise mechanisms involved still remain elusive. In an effort to address this issue, we employed the model of "early handling", which is known to affect the ability of the adult organism to respond to stressful stimuli, and determined its effects on hippocampal pCREB and BDNF 2, 4, and 8 h later. 8 h following "handling" on postnatal day 1, there was an increase in pCREB and BDNF positive cells in the hippocampus, a brain area which is a specific target of "handling". On the other hand, vehicle injection resulted in decreased pCREB and BDNF in both handled and non-handled animals 2 and 4 h later. The "handling"-induced increase of pCREB and BDNF was cancelled by inhibition of NMDA, AMPA/kainate, GABA-A, 5-HT1A or 5-HT2A/C receptors, as well as L-type voltage-gated Ca(2+) channels. It thus appears that "early handling" activates these neurotransmitter receptors, leading to increased intracellular Ca(2+), phosphorylation of the transcription factor CREB, and increased BDNF expression. BDNF can then exert its morphogenetic effects and thus "imprint" the effects of "handling" on the brain.

Adenovirus type 5 exerts genome-wide control over cellular programs governing proliferation, quiescence, and survival

PubMed Central

Miller, Daniel L; Myers, Chad L; Rickards, Brenden; Coller, Hilary A; Flint, S Jane

2007-01-01

Background Human adenoviruses, such as serotype 5 (Ad5), encode several proteins that can perturb cellular mechanisms that regulate cell cycle progression and apoptosis, as well as those that mediate mRNA production and translation. However, a global view of the effects of Ad5 infection on such programs in normal human cells is not available, despite widespread efforts to develop adenoviruses for therapeutic applications. Results We used two-color hybridization and oligonucleotide microarrays to monitor changes in cellular RNA concentrations as a function of time after Ad5 infection of quiescent, normal human fibroblasts. We observed that the expression of some 2,000 genes, about 10% of those examined, increased or decreased by a factor of two or greater following Ad5 infection, but were not altered in mock-infected cells. Consensus k-means clustering established that the temporal patterns of these changes were unexpectedly complex. Gene Ontology terms associated with cell proliferation were significantly over-represented in several clusters. The results of comparative analyses demonstrate that Ad5 infection induces reversal of the quiescence program and recapitulation of the core serum response, and that only a small subset of the observed changes in cellular gene expression can be ascribed to well characterized functions of the viral E1A and E1B proteins. Conclusion These findings establish that the impact of adenovirus infection on host cell programs is far greater than appreciated hitherto. Furthermore, they provide a new framework for investigating the molecular functions of viral early proteins and information relevant to the design of conditionally replicating adenoviral vectors. PMID:17430596

ATP-driven and AMPK-independent autophagy in an early branching eukaryotic parasite.

PubMed

Li, Feng-Jun; Xu, Zhi-Shen; Soo, Andy D S; Lun, Zhao-Rong; He, Cynthia Y

2017-04-03

Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) is yet to be identified, deprivation of amino acids, glucose, growth factor and other nutrients can serve as metabolic stimuli to initiate autophagy in higher eukaryotes. In the early-branching unicellular parasite Trypanosoma brucei, which can proliferate as procyclic form (PCF) in the tsetse fly or as bloodstream form (BSF) in animal hosts, autophagy is robustly triggered by amino acid deficiency but not by glucose depletion. Taking advantage of the clearly defined adenosine triphosphate (ATP) production pathways in T. brucei, we have shown that autophagic activity depends on the levels of cellular ATP production, using either glucose or proline as a carbon source. While autophagosome formation positively correlates with cellular ATP levels; perturbation of ATP production by removing carbon sources or genetic silencing of enzymes involved in ATP generation pathways, also inhibited autophagy. This obligate energy dependence and the lack of glucose starvation-induced autophagy in T. brucei may reflect an adaptation to its specialized, parasitic life style.

Flavivirus Infection Impairs Peroxisome Biogenesis and Early Antiviral Signaling

PubMed Central

You, Jaehwan; Hou, Shangmei; Malik-Soni, Natasha; Xu, Zaikun; Kumar, Anil; Rachubinski, Richard A.; Frappier, Lori

2015-01-01

ABSTRACT Flaviviruses are significant human pathogens that have an enormous impact on the global health burden. Currently, there are very few vaccines against or therapeutic treatments for flaviviruses, and our understanding of how these viruses cause disease is limited. Evidence suggests that the capsid proteins of flaviviruses play critical nonstructural roles during infection, and therefore, elucidating how these viral proteins affect cellular signaling pathways could lead to novel targets for antiviral therapy. We used affinity purification to identify host cell proteins that interact with the capsid proteins of West Nile and dengue viruses. One of the cellular proteins that formed a stable complex with flavivirus capsid proteins is the peroxisome biogenesis factor Pex19. Intriguingly, flavivirus infection resulted in a significant loss of peroxisomes, an effect that may be due in part to capsid expression. We posited that capsid protein-mediated sequestration and/or degradation of Pex19 results in loss of peroxisomes, a situation that could result in reduced early antiviral signaling. In support of this hypothesis, we observed that induction of the lambda interferon mRNA in response to a viral RNA mimic was reduced by more than 80%. Together, our findings indicate that inhibition of peroxisome biogenesis may be a novel mechanism by which flaviviruses evade the innate immune system during early stages of infection. IMPORTANCE RNA viruses infect hundreds of millions of people each year, causing significant morbidity and mortality. Chief among these pathogens are the flaviviruses, which include dengue virus and West Nile virus. Despite their medical importance, there are very few prophylactic or therapeutic treatments for these viruses. Moreover, the manner in which they subvert the innate immune response in order to establish infection in mammalian cells is not well understood. Recently, peroxisomes were reported to function in early antiviral signaling, but

Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment

PubMed Central