A spectral line survey of Orion KL in the bands 486-492 and 541-577 GHz with the Odin satellite. I. The observational data

NASA Astrophysics Data System (ADS)

Olofsson, A. O. H.; Persson, C. M.; Koning, N.; Bergman, P.; Bernath, P. F.; Black, J. H.; Frisk, U.; Geppert, W.; Hasegawa, T. I.; Hjalmarson, Å.; Kwok, S.; Larsson, B.; Lecacheux, A.; Nummelin, A.; Olberg, M.; Sandqvist, Aa.; Wirström, E. S.

2007-12-01

Aims:Spectral line surveys are useful since they allow identification of new molecules and new lines in uniformly calibrated data sets. The subsequent multi-transition analysis will provide improved knowledge of molecular abundances, cloud temperatures and densities, and may also reveal previously unsuspected blends of molecular lines, which otherwise may lead to erroneous conclusions. Nonetheless, large portions of the sub-millimetre spectral regime remain unexplored due to severe absorptions by H{2}O and O{2} in the terrestrial atmosphere. The purpose of the measurements presented here is to cover wavelength regions at and around 0.55 mm - regions largely unobservable from the ground. Methods: Using the Odin astronomy/aeronomy satellite, we performed the first spectral survey of the Orion KL molecular cloud core in the bands 486-492 and 541-576 GHz with rather uniform sensitivity (22-25 mK baseline noise). Odin's 1.1 m size telescope, equipped with four cryo-cooled tuneable mixers connected to broad band spectrometers, was used in a satellite position-switching mode. Two mixers simultaneously observed different 1.1 GHz bands using frequency steps of 0.5 GHz (25 h each). An on-source integration time of 20 h was achieved for most bands. The entire campaign consumed 1100 orbits, each containing one hour of serviceable astro-observation. Results: We identified 280 spectral lines from 38 known interstellar molecules (including isotopologues) having intensities in the range 80 to 0.05 K. An additional 64 weak lines remain unidentified. Apart from the ground state rotational 1{1,0}-1{0,1} transitions of ortho-H{2}O, H{2}18O and H{2}17O, the high energy 6{2,4}-7{1,7} line of para-H{2}O (Eu=867 K) and the HDO(2{0,2}-1{1,1}) line have been observed, as well as the 1{0}-0{1} lines from NH{3} and its rare isotopologue 15NH{3}. We suggest assignments for some unidentified features, notably the new interstellar molecules ND and SH-. Severe blends have been detected in the

A Search for Low-Luminosity BL Lacertae Objects

NASA Astrophysics Data System (ADS)

Rector, Travis A.; Stocke, John T.; Perlman, Eric S.

1999-05-01

Many properties of BL Lacs have become explicable in terms of the ``relativistic beaming'' hypothesis, whereby BL Lacs are FR 1 radio galaxies viewed nearly along the jet axis. However, a possible problem with this model is that a transition population between beamed BL Lacs and unbeamed FR 1 galaxies has not been detected. A transition population of ``low-luminosity BL Lacs'' was predicted to exist in abundance in X-ray-selected samples such as the Einstein Extended Medium Sensitivity Survey (EMSS) by Browne & Marcha. However, these BL Lacs may have been misidentified as clusters of galaxies. We have conducted a search for such objects in the EMSS with the ROSAT High-Resolution Imager (HRI) here we present ROSAT HRI images, optical spectra, and VLA radio maps for a small number of BL Lacs that were previously misidentified in the EMSS catalog as clusters of galaxies. While these objects are slightly lower in luminosity than other EMSS BL Lacs, their properties are too similar to the other BL Lacs in the EMSS sample to ``bridge the gap'' between BL Lacs and FR 1 radio galaxies. Also, the number of new BL Lacs found is too low to alter significantly the X-ray luminosity function or value for the X-ray-selected EMSS BL Lac sample. Thus, these observations do not explain fully the discrepancy between the X-ray- and radio-selected BL Lac samples.

Molecular actions of two synthetic brassinosteroids, iso-carbaBL and 6-deoxoBL, which cause altered physiological activities between Arabidopsis and rice.

PubMed

Nakamura, Ayako; Tochio, Naoya; Fujioka, Shozo; Ito, Shinsaku; Kigawa, Takanori; Shimada, Yukihisa; Matsuoka, Makoto; Yoshida, Shigeo; Kinoshita, Toshinori; Asami, Tadao; Seto, Hideharu; Nakano, Takeshi

2017-01-01

Brassinosteroid (BR) is an important plant hormone that is perceived by the BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor. BRI1 is conserved among dicot and monocot species; however, the molecular mechanism underlying BR perception in monocots is not fully understood. We synthesised two BRs, iso-carbabrassinolide (iso-carbaBL) and 6-deoxoBL, which have different BR activities in Arabidopsis thaliana (Arabidopsis) and rice. Our bioassay indicated that iso-carbaBL has relatively strong BR activity in Arabidopsis, but is inactive in rice and competitively inhibits BR activity. The bioactivity of 6-deoxoBL was similar to that of BL in Arabidopsis, but was much lower in rice. Binding experiments using recombinant Arabidopsis and rice BRI1 protein fragments suggested that iso-carbaBL and 6-deoxoBL bind to both receptors. These results showed that iso-carbaBL and 6-deoxoBL act as an antagonist and agonist, respectively, of BRs in rice. A docking simulation analysis suggested that iso-carbaBL fits deeper in the binding pocket to block the binding of active BR to rice BRI1. The simulated binding energy of 6-deoxoBL with rice BRI1 is much lower than that with Arabidopsis BRI1. The possible structural characteristics of rice BRI1 were determined based on the difference in the BR activities of iso-carbaBL and 6-deoxoBL in Arabidopsis and rice.

The Discovery of Low-Luminosity BL Lacs

NASA Astrophysics Data System (ADS)

Rector, Travis A.; Stocke, John T.

1995-12-01

Many of the properties of BL Lacs have become explicable in terms of the ``relativistic beaming'' hypothesis whereby BL Lacs are ``highly beamed'' FR-I radio galaxies (i.e. our line of sight to these objects is nearly along the jet axis). Further, radio-selected BL Lacs (RBLs) are believed to be seen nearly ``on-axis'' (the line-of-sight angle theta ~ 8deg ) while X-ray selected BL Lacs (XBLs) are seen at larger angles (theta ~ 30deg ; the X-ray emitting jet is believed to be less collimated). However, a major problem with this model was that a transition population between beamed BL Lacs and unbeamed FR-Is had not been detected. Low-luminosity BL Lacs may be such a transition population, and were predicted to exist by Browne and Marcha (1993). We present ROSAT HRI images, VLA radio maps and optical spectra which confirm the existence of low-luminosity BL Lacs, objects which were previously mis-identified in the EMSS catalog as clusters of galaxies. Thus our results strengthen the relativistic beaming hypothesis.

Molecular actions of two synthetic brassinosteroids, iso-carbaBL and 6-deoxoBL, which cause altered physiological activities between Arabidopsis and rice

PubMed Central

Fujioka, Shozo; Ito, Shinsaku; Kigawa, Takanori; Shimada, Yukihisa; Matsuoka, Makoto; Yoshida, Shigeo; Kinoshita, Toshinori; Asami, Tadao; Seto, Hideharu; Nakano, Takeshi

2017-01-01

Brassinosteroid (BR) is an important plant hormone that is perceived by the BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor. BRI1 is conserved among dicot and monocot species; however, the molecular mechanism underlying BR perception in monocots is not fully understood. We synthesised two BRs, iso-carbabrassinolide (iso-carbaBL) and 6-deoxoBL, which have different BR activities in Arabidopsis thaliana (Arabidopsis) and rice. Our bioassay indicated that iso-carbaBL has relatively strong BR activity in Arabidopsis, but is inactive in rice and competitively inhibits BR activity. The bioactivity of 6-deoxoBL was similar to that of BL in Arabidopsis, but was much lower in rice. Binding experiments using recombinant Arabidopsis and rice BRI1 protein fragments suggested that iso-carbaBL and 6-deoxoBL bind to both receptors. These results showed that iso-carbaBL and 6-deoxoBL act as an antagonist and agonist, respectively, of BRs in rice. A docking simulation analysis suggested that iso-carbaBL fits deeper in the binding pocket to block the binding of active BR to rice BRI1. The simulated binding energy of 6-deoxoBL with rice BRI1 is much lower than that with Arabidopsis BRI1. The possible structural characteristics of rice BRI1 were determined based on the difference in the BR activities of iso-carbaBL and 6-deoxoBL in Arabidopsis and rice. PMID:28369122

Clustering environments of BL Lac objects

NASA Technical Reports Server (NTRS)

Wurtz, Ronald; Ellingson, Erica; Stocke, John T.; Yee, H. K. C.

1993-01-01

We report measurements of the amplitude of the BL Lac galaxy spatial covariance function, B(gb), for the fields of five BL Lacertae objects. We present evidence for rich clusters around MS 1207+39 and MS 1407+59, and confirm high richness for the cluster containing H0414+009. We discuss the ease of 3C 66 A and find evidence for a poor cluster based on an uncertain redshift of z = 0.444. These data suggest that at least some BL Lac objects are consistent with being FR 1 radio galaxies in rich clusters.

The cosmic evolution of Fermi BL lacertae objects

DOE PAGES

Ajello, M.; Romani, R. W.; Gasparrini, D.; ...

2013-12-13

Fermi has provided the largest sample of γ-ray-selected blazars to date. We use a uniformly selected set of 211 BL Lacertae (BL Lac) objects detected by Fermi during its first year of operation. We obtained redshift constraints for 206 out of the 211 BL Lac objects in our sample, making it the largest and most complete sample of BL Lac objects available in the literature. We use this sample to determine the luminosity function of BL Lac objects and its evolution with cosmic time. Here, we find that for most BL Lac classes the evolution is positive, with a space density peaking at modest redshift (z ≈ 1.2). Low-luminosity, high-synchrotron-peaked (HSP) BL Lac objects are an exception, showing strong negative evolution, with number density increasing for z lesssim 0.5. Since this rise corresponds to a drop-off in the density of flat-spectrum radio quasars (FSRQs), a possible interpretation is that these HSPs represent an accretion-starved end state of an earlier merger-driven gas-rich phase. Additionally, we find that the known BL Lac correlation between luminosity and photon spectral index persists after correction for the substantial observational selection effects with implications for the so-called "blazar sequence." Finally, by estimating the beaming corrections to the luminosity function, we find that BL Lac objects have an average Lorentz factor ofmore » $$\\gamma =6.1^{+1.1}_{-0.8}$$, and that most are seen within 10° of the jet axis.« less

Study on Na layer response to geomagnetic activities based on Odin/OSIRIS Na density data

NASA Astrophysics Data System (ADS)

Tsuda, Takuo; Nakamura, Takuji; Hedin, Jonas; Gumbel, Jorg; Hosokawa, Keisuke; Ejiri, Mitsumu K.; Nishiyama, Takanori; Takahashi, Toru

2016-07-01

The Na layer is normally distributed from 80 to 110 km, and the height range is corresponding to the ionospheric D and E region. In the polar region, the energetic particles precipitating from the magnetosphere can often penetrate into the E region and even into the D region. Thus, the influence of the energetic particles to the Na layer is one of interests in the aspect of the atmospheric composition change accompanied with the auroral activity. There are several previous studies in this issue. For example, recently, we have reported an initial result on a clear relationship between the electron density increase (due to the energetic particles) and the Na density decrease from observational data sets obtained by Na lidar, EISCAT VHF radar, and optical instruments at Tromsoe, Norway on 24-25 January 2012. However, all of the previous studies had been carried out based on case studies by ground-based lidar observations. In this study, we have performed, for the first time, statistical analysis using Na density data from 2004 to 2009 obtained with the Optical Spectrograph and InfraRed Imager System (OSIRIS) onboard Odin satellite. In the presentation, we will show relationship between the Na density and geomagnetic activities, and its latitudinal variation. Based on these results, the Na layer response to the energetic particles will be discussed.

The Cosmic Evolution of Fermi BL Lacertae Objects

NASA Astrophysics Data System (ADS)

Ajello, Marco; Gasparrini, Dario; Romani, Roger W.; Shaw, Michael S.

2014-06-01

It has been notoriously difficult in the past to measure the cosmological evolution of BL Lacs because of the challenges related to measure their redshift. Extensive optical follow-up observations of a sample of ~200 Fermi-detected BL Lac objects have provided much-needed redshift information for many of them. This stands as the largest and most complete sample of BL Lacs available in the literature and was used to determine the cosmological properties of this elusive source class. This talk will review the cosmic evolution of BL Lacs and discuss the link to their siblings flat-spectrum radio quasars (FSRQs). Evidence suggests that BL Lacs of the high-synchrotron peaked class might be an accretion-starved end-state of an earlier merger-driven gas-rich phase.

Are some BL Lacs artefacts of gravitational lensing?

PubMed

Ostriker, J P; Vietri, M

1990-03-01

WE suggested in 1985 that a significant fraction of BL Lacertae objects, a kind of lineless quasar, seen in nearby galaxies are in fact images, gravitationally lensed and substantially amplified by stars in the nearby galaxy, of background objects, optically violent variable (OVV) quasars at redshifts z > 1 (ref. 1). This hypothesis was made on the basis of certain general similarities between BL Lacs and O Ws, but for two recently observed BL Lacs(2,3) a strong case can be made that the accompanying elliptical galaxy is a foreground object. In addition, we argue that the distribution of BL Lac redshifts is hard to understand without gravitational lensing, unless we happen to be at a very local maximum of the spatial cosmic distribution of BL Lacs. Our analysis also indicates that the galaxies whose stars are likely to act as microlenses will be found in two peaks, one nearby, with redshift 0.05-0.10, and the other near the distant quasar.

Revised Correlation between Odin/OSIRIS PMC Properties and Coincident TIMED/SABER Mesospheric Temperatures

NASA Technical Reports Server (NTRS)

Feofilov, A. G.; Petelina, S V.; Kutepov, A. A.; Pesnell, W. D.; Goldberg, R. A.; Llewellyn, E. J.; Russell, J. M.

2006-01-01

The Optical Spectrograph and Infrared Imaging System (OSIRIS) instrument on board the Odin satellite detects Polar Mesospheric Clouds (PMCs) through the enhancement in the limb scattered solar radiance. The Sounding of the Atmosphere using the Broadband Emission Radiometry (SABER) instrument on board the TIMED satellite is a limb scanning infrared radiometer that measures temperature and vertical profiles and energetic parameters for minor constituents in the mesosphere and lower thermosphere. The combination of OSIRIS and SABER data has been previously used to statistically derive thermal conditions for PMC existence [Petelina et al., 2005]. In this work, we employ the simultaneous common volume measurements of PMCs by OSIRIS and temperature profiles measured by SABER for the Northern Hemisphere summers of 2002-2005 and corrected in the polar region by accounting for the vibrational-vibrational energy exchange among the CO2 isotopes [Kutepov et al., 2006]. For each of 20 coincidences identified within plus or minus 1 degree latitude, plus or minus 2 degrees longitude and less than 1 hour time the frost point temperatures were calculated using the corresponding SABER temperature profile and water vapor densities of 1,3, and 10 ppmv. We found that the PMC presence and brightness correlated only with the temperature threshold that corresponds to the frost point. The absolute value of the temperature below the frost point, however, didn't play a significant role in the intensity of PMC signal for the majority of selected coincidences. The presence of several bright clouds at temperatures above the frost point is obviously related to the limitation of the limb geometry when some near- or far-field PMCs located at higher (and warmer) altitudes appear to be at lower altitudes.

Revised Correlation between Odin/OSIRIS PMC Properties and Coincident TIMED/SABER Mesospheric Temperatures

NASA Technical Reports Server (NTRS)

Feofilov, A. G.; Petelina, S. V.; Kutepov, A. A.; Pesnell, W. D.; Goldberg, R. A.; Llewellyn, E. J.; Russell, J. M.

2006-01-01

The Optical Spectrograph and Infrared Imaging System (OSIRIS) instrument on board the Odin satellite detects Polar Mesospheric Clouds (PMCs) through the enhancement in the limb-scattered solar radiance. The Sounding of the Atmosphere using the Broadband Emission Radiometry (SABER) instrument on board the TIMED satellite is a limb scanning infrared radiometer that measures temperature and vertical profiles and energetic parameters for minor constituents in the mesosphere and lower thermosphere. The combination of OSIRIS and SABER data has been previously used to statistically derive thermal conditions for PMC existence [Petelina et al., 2005]. a, A.A. Kutepov, W.D. Pesnell, In this work, we employ the simultaneous common volume measurements of PMCs by OSIRIS and temperature profiles measured by SABER for the Northern Hemisphere summers of 2002-2005 and corrected in the polar region by accounting for the vibrational-vibrational energy exchange among the CO2 isotopes [Kutepov et al., 2006]. For each of 20 coincidences identified within plus or minus 1 degree latitude, plus or minus 2 degrees longitude and less than 1 hour time the frost point temperatures were calculated using the corresponding SABER temperature profile and water vapor densities of 1,3, and 10 ppmv. We found that the PMC presence and brightness correlated only with the temperature threshold that corresponds to the frost point. The absolute value of the temperature below the frost point, however, didn't play a significant role in the intensity of PMC signal for the majority of selected coincidences. The presence of several bright clouds at temperatures above the frost point is obviously related to the limitation of the limb geometry when some near- or far-field PMCs located at higher (and warmer) altitudes appear to be at lower altitudes.

Brain damage resulting from postnatal hypoxic-ischemic brain injury is reduced in C57BL/6J mice as compared to C57BL/6N mice.

PubMed

Wolf, S; Hainz, N; Beckmann, A; Maack, C; Menger, M D; Tschernig, T; Meier, C

2016-11-01

Perinatal hypoxia is a critical complication during delivery and is mostly studied in animal models of postnatal hypoxic-ischemic brain injury. We here studied the effects of postnatal hypoxic-ischemic brain injury in two different sub-strains of C57BL/6 mice, i.e. C57BL/6J and C57BL/6N mice. These two sub-strains show different metabolic properties, for instance an impaired glucose tolerance in C57BL/6J mice. Genetically, this was linked to differences in their nicotinamide nucleotide transhydrogenase (Nnt) genes: In C57BL/6J mice, exons 7-11 of the Nnt gene are deleted, resulting in the absence of functional Nnt protein. The mitochondrial Nnt-protein is one of several enzymes that catalyses the generation of NADPH, which in turn is important for the elimination of reactive oxygen species (ROS). As ROS is thought to contribute to the pathophysiology of hypoxia-ischemia, the lack of Nnt might indirectly increase ROS levels and therefore result in increased brain damage. We therefore hypothesize that lesion score and lesion size will increase in C57BL/6J mice as compared to C57BL/6N mice. Surprisingly, the results showed exactly the opposite: C57BL/6J mice showed a decrease in lesion score and size, associated with a reduced number of apoptotic cells and activated microglia. In contrast, the number of cells with ROS-induced DNA modifications (detected by 8OHdG) was higher in C57BL/6J than C57BL/6N mice. In conclusion, C57BL/6J mice showed reduced ischemic consequences after postnatal hypoxic-ischemic brain injury compared to C57BL/6N mice, with the exception of the amount of ROS-induced DNA-damage. These differences might relate to the lack of Nnt, but also to a modified metabolic setting (cardiovascular parameters, oxygen and glucose metabolism, immune function) in C57BL/6J mice. Copyright © 2016 Elsevier B.V. All rights reserved.

Photometric monitoring of three BL Lacertae objects in 1993-1998

NASA Astrophysics Data System (ADS)

Bai, J. M.; Xie, G. Z.; Li, K. H.; Zhang, X.; Liu, W. W.

1999-05-01

The results of optical photometric (BVRI) monitoring of three BL Lac objects over a time interval of about four years are presented. The sources are three classical radio-selected BL Lac objects, BL Lac, OJ 287 and PKS 0735+178. During our observation OJ 287 was in the stage of a large periodic outburst which consisted of at least two peaks. Almost all the observations obtained over consecutive nights detected intranight variations. In 1995 and 1996 BL Lac kept in faint states, with fewer and smaller rapid flares and fluctuations. On the contrary, in late 1997 BL Lac was at the stage of a large outburst, accompanied with much more large amplitude rapid flares and fluctuations. PKS 0735+178 was almost at its faint end from 1994 to early 1998. Over this time interval, the intraday variations and microvariations in PKS 0735+178 were rare and the amplitude was very small, except a rapid darkening of ~ 0.4 mag on 24 January 1995. Previous work by \\cite[Webb et al. (1988);]{web88} \\cite[Wagner et al. (1996);]{wag96} \\cite[Pian et al. (1997)]{pia97} also showed the same behaviour of variability as BL Lac and PKS 0735+178 in BL Lac, S5 0716+714, PKS 2155-304, respectively. We propose that the motion of orientation of the relativistic jet in a BL Lac object be responsible for these variability behaviours. Table~1 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/Abstract.html

X-Ray Variability of BL Lac Objects

NASA Astrophysics Data System (ADS)

McHardy, Ian

I present an overview of the X-ray temporal and spectral variability of BL Lacs on both short and long timescales. The previously observed behaviour of short (~days) flares superimposed on a relatively steady `quiescent' level is still broadly correct. However, for the brighter BL Lacs, the well sampled lightcurves from the RXTE ASM show that the `quiescent' level also varies considerably on timescales of ~100 days in a manner similar to that seen in Optically Violently Variable Quasars (OVVs) such as 3C279 and 3C273. Possible reasons for this behaviour are discussed. For the large majority of BL Lacs the soft and medium energy X-ray bands are dominated by synchrotron emission and, unlike the case of OVVs, the emission mechanism is not in doubt. Most interest then centres on the structure of the emitting region, and the electron acceleration processes, particularly during outbursts. That structure, and the acceleration processes, can be investigated by consideration of the spectral variability during flares, which is not simple. I review the observations of spectral variability and consider the evidence for and against homogeneous models. I also briefly compare the X-ray spectral variability of BL Lacs with that of OVVs such as 3C273.

Optical and radio properties of X-ray selected BL Lacertae objects

NASA Technical Reports Server (NTRS)

Stocke, J. T.; Liebert, J.; Schmidt, G.; Gioia, I. M.; Maccacaro, T.

1985-01-01

The eight BL Lac objects from the HEAO 1 A-2 all-sky survey and from the Einstein medium-sensitivity survey (MSS) form a flux-limited complete X-ray selected sample. The optical and radio properties of the MSS BL Lac objects are presented and compared with those of the HEAO 1 A-2 sample and with those of radio-selected BL Lac objects. The X-ray selected BL Lac objects possess smaller polarized fractions and less violent optical variability than radio-selected BL Lac objects. These properties are consistent with the substantial starlight fraction seen in the optical spectra of a majority of these objects. This starlight allows a determination of definite redshifts for two of four MSS BL Lac objects and a probable redshift for a third. These redshifts are 0.2, 0.3, and 0.6. Despite the differences in characteristics between the X-ray selected and radio-selected samples, it is concluded that these eight objects possess most of the basic qualities of BL Lac objects and should be considered members of that class. Moreover, as a class, these X-ray selected objects have the largest ratio of X-ray to optical flux of any active galactic nuclei yet discovered.

Polarimetry of optically selected BL Lacertae candidates from the SDSS

NASA Astrophysics Data System (ADS)

Heidt, J.; Nilsson, K.

2011-05-01

We present and discuss polarimetric observations of 182 targets drawn from an optically selected sample of 240 probable BL Lac candidates out of the SDSS compiled by Collinge et al. (2005, AJ, 129, 2542). In contrast to most other BL Lac candidate samples extracted from the SDSS, its radio- and/or X-ray properties have not been taken into account for its derivation. Thus, because its selection is based on optical properties alone, it may be less prone to selection effects inherent in other samples derived at different frequencies, so it offers a unique opportunity to extract the first unbiased BL Lac luminosity function that is suitably large in size. We found 124 out of 182 targets (68%) to be polarized, 95 of the polarized targets (77%) to be highly polarized (>4%). The low-frequency peaked BL Lac candidates in the sample are on average only slightly more polarized than the high-frequency peaked ones. Compared to earlier studies, we found a high duty cycle in high polarization (˜ 66+2-14% to be >4% polarized) in high-frequency peaked BL Lac candidates. This may come from our polarization analysis, which minimizes the contamination by host galaxy light. No evidence of radio-quiet BL Lac objects in the sample was found. Our observations show that the probable sample of BL Lac candidates of Collinge et al. (2005) indeed contains a large number of bona fide BL Lac objects. High S/N spectroscopy and deep X-ray observations are required to construct the first luminosity function of optically selected BL Lac objects and to test more stringently for any radio-quiet BL Lac objects in the sample. Based on observations collected with the NTT on La Silla (Chile) operated by the European Southern Observatory in the course of the observing proposal 082.B-0133.Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA), operated jointly by the Max-Planck-Institut für Astronomie and the Instituto de Astrofisica de Andalucia (CSIC).Based on observations

Water Vapor, Temperature, and Ice Particles in Polar Mesosphere as Measured by SABER/TIMED and OSIRIS/Odin Instruments

NASA Technical Reports Server (NTRS)

Feofilov, A. G.; Petelina, S. V.; Kutepov, A. A.; Pesnell, W. D.; Goldberg, R. A.

2009-01-01

Although many new details on the properties of mesospheric ice particles that farm Polar Mesospheric Clouds (PMCs) and also cause polar mesospheric summer echoes have been recently revealed, certain aspects of mesospheric ice microphysics and dynamics still remain open. The detailed relation between PMC parameters and properties of their environment, as well as interseasonal and interhemispheric differences and trends in PMC properties that are possibly related to global change, are among those open questions. In this work, mesospheric temperature and water vapor concentration measured by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on board the Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) satellite are used to study the properties of PMCs with respect to the surrounding atmosphere. The cloud parameters, namely location, brightness, and altitude, are obtained from the observations made by the Optical Spectrograph and Infrared Imager System (OSIRIS) on the Odin satellite. About a thousand of simultaneous common volume measurements made by SABER and OSIRIS in both hemispheres from 2002 until 2008 are used. The correlation between PMC brightness (and occurrence rate) and temperatures at PMC altitudes and at the mesopause is analysed. The relation between PMC parameters, frost point temperature, and gaseous water vapor content in and below the cloud is also discussed. Interseasonal and interhemispheric differences and trends in the above parameters, as well as in PMC peak altitudes and mesopause altitudes are evaluated.

Evolutionary behaviour of AGN: Investigations on BL Lac objects and Seyfert II galaxies

NASA Astrophysics Data System (ADS)

Beckmann, V.

2000-12-01

The evolution and nature of AGN is still one of the enigmatic questions in astrophysics. While large and complete Quasar samples are available, special classes of AGN, like BL Lac objects and Seyfert II galaxies, are still rare objects. In this work I present two new AGN samples. The first one is the HRX-BL Lac survey, resulting in a sample of X-ray selected BL Lac objects. This sample results from 223 BL Lac candidates based on a correlation of X-ray sources with radio sources. The identification of this sample is 98% complete. 77 objects have been identified as BL Lac objects and form the HRX-BL Lac complete sample, the largest homogeneous sample of BL Lac objects existing today. For this sample, redshifts are now known for 62 objects (81 %). In total I present 101 BL Lac objects in the enlarged HRX-BL Lac survey, for which redshift information is available for 84 objects. During the HRX-BL Lac survey I found several objects of special interest. 1ES 1517+656 turned out to be the brightest known BL Lac object in the universe. 1ES 0927+500 could be the first BL Lac object with a line detected in the X-ray region. RX J1211+2242 is probably the the counterpart of the up to now unidentified gamma-ray source 3EG J1212+2304. Additionally I present seven candidates for ultra high frequency peaked BL Lac objects. RX J1054+3855 and RX J1153+3517 are rare high redshift X-ray bright QSO or accreting binary systems with huge magnetic fields. For the BL Lac objects I suggest an unified scenario in which giant elliptical galaxies, formed by merging events of spiral galaxies at z > 2, start as powerful, radio dominated BL Lacs. As the jet gets less powerful, the BL Lacs start to get more X-ray dominated, showing less total luminosities (for z < 1). This effect is seen in the different evolutionary behavior detected in high and low frequency cut off BL Lac objects (HBL and LBL, respectively). The model of negative evolution is supported by assumptions about the energetic effects

Effect of crossing C57BL/6 and FVB mouse strains on basal cytokine expression.

PubMed

Szade, Agata; Nowak, Witold N; Szade, Krzysztof; Gese, Anna; Czypicki, Ryszard; Waś, Halina; Dulak, Józef; Józkowicz, Alicja

2015-01-01

C57BL/6 is the most often used laboratory mouse strain. However, sometimes it is beneficial to cross the transgenic mice on the C57BL/6 background to the other strain, such as FVB. Although this is a common strategy, the influence of crossing these different strains on homeostatic expression of cytokines is not known. Here we have investigated the differences in the expression of selected cytokines between C57BL/6J and C57BL/6JxFVB mice in serum and skeletal muscle. We have found that only few cytokines were altered by crossing of the strains. Concentrations of IL5, IL7, LIF, MIP-2, and IP-10 were higher in serum of C57BL/6J mice than in C57BL/6JxFVB mice, whereas concentration of G-CSF was lower in C57BL/6J. In the skeletal muscle only the concentration of VEGF was higher in C57BL/6J mice than in C57BL/6JxFVB mice. Concluding, the differences in cytokine expression upon crossing C57BL/6 and FVB strain in basal conditions are not profound.

Optical polarimetry and photometry of X-ray selected BL Lacertae objects

NASA Technical Reports Server (NTRS)

Jannuzi, Buell T.; Smith, Paul S.; Elston, Richard

1993-01-01

We present the data from 3 years of monitoring the optical polarization and apparent brightness of 37 X-ray-selected BL Lacertae objects. The monitored objects include a complete sample drawn from the Einstein Extended Medium Sensitivity Survey. We confirm the BL Lac identifications for 15 of these 22 objects. We include descriptions of the objects and samples in our monitoring program and of the existing complete samples of BL Lac objects, highly polarized quasars, optically violent variable quasars, and blazars.

Probiotic Strain Lactobacillus casei BL23 Prevents Colitis-Associated Colorectal Cancer

PubMed Central

Jacouton, Elsa; Chain, Florian; Sokol, Harry; Langella, Philippe; Bermúdez-Humarán, Luis G.

2017-01-01

The gut microbiota plays a major role in intestinal health, and an imbalance in its composition can lead to chronic gut inflammation and a predisposition to developing colorectal cancer (CRC). Currently, the use of probiotic bacteria represents an emerging alternative to treat and prevent cancer. Moreover, consumption of these beneficial bacteria may also favorably modulate the composition of the gut microbiota, which has been described in several studies to play an important role in CRC carcinogenesis. In this context, the aim of this study was to assess the protective effect of oral treatment with Lactobacillus casei BL23, a probiotic strain well known for its anti-inflammatory and anticancer properties. First, CRC was induced in C57BL6 mice by a single intraperitoneal injection with azoxymethane (8 mg/kg), followed by four courses of dextran sodium sulfate (2.5%) in drinking water that were separated by an adjustable recovery period. At the time of sacrifice (day 46), tumor incidence, histological scores, and epithelial proliferation were determined in colon samples. Our results show that L. casei BL23 significantly protected mice against CRC development; specifically, L. casei BL23 treatment reduced histological scores and proliferative index values. In addition, our analysis revealed that L. casei BL23 had an immunomodulatory effect, mediated through the downregulation of the IL-22 cytokine, and an antiproliferative effect, mediated through the upregulation of caspase-7, caspase-9, and Bik. Finally, L. casei BL23 treatment tended to counterbalance CRC-induced dysbiosis in mice, as demonstrated by an analysis of fecal microbiota. Altogether our results demonstrate the high potential of L. casei BL23 for the development of new, probiotic-based strategies to fight CRC. PMID:29209314

Are some BL Lac objects artefacts of gravitational lensing?

NASA Technical Reports Server (NTRS)

Ostriker, J. P.; Vietri, M.

1985-01-01

It is proposed here that a significant fraction of BL Lac objects are optically violently variable quasars whose continuum emission has been greatly amplified, relative to the line emission, by pointlike gravitational lenses in intervening galaxies. Several anomalous physical and statistical properties of BL Lacs can be understood on the basis of this model, which is immediately testable on the basis of absorption line studies and by direct imaging.

Radio constraints on the nature of BL Lacertae objects and their parent population

NASA Technical Reports Server (NTRS)

Kollgaard, R. I.; Wardle, J. F. C.; Roberts, D. H.; Gabuzda, D. C.

1992-01-01

5 GHz VLA observations of 17 BL Lac objects with bright radio cores at both high and low resolution are reported. Extended emission is detected around most objects. None of the sources observed at low resolution show evidence of giant halos on the scale of tens of arcmin. In general, the sources with the most luminous extended emission exhibit FR II characteristics in both morphology and polarization, and less luminous sources exhibit FR I characteristics. Thus, the parent population of the BL Lac objects contains both FR I and FR II radio sources. No BL Lac objects are found that clearly exhibit quasarlike polarization at milliarcsec resolution. This argues against the view that the more luminous BL Lac objects are simply an extension of the quasar/OVV population, or that most BL Lac objects are gravitationally microlensed images of distant quasars. Other properties are generally consistent with the view the BL Lac objects are normal radio galaxies whose jets make a small angle to the line of sight.

The Radio-optical Spectra of BL Lacs and Possible Relatives

NASA Astrophysics Data System (ADS)

Dennett-Thorpe, J.

I consider the suggestion that, in a complete sample of flat-spectrum radio sources with available optical spectra (Marcha et al 1996), the strong emission line objects, or those with passive elliptical spectra are close relatives of the BL Lacs. New observations at four frequencies from 8 to 43GHz are presented, together with evidence for radio variability. Combined with other radio and optical data from the literature, we are able to construct the non-thermal SEDs and use these to address the questions: are the optically passive objects potentially `unrecognised' BL Lacs (either intrinsically weak and/or hidden by starlight)? What is the relationship between the surprising number of strong emission-line objects and the BL Lacs?

Efficacy of convenience sampling through the internet versus respondent driven sampling among males who have sex with males in Tallinn and Harju County, Estonia: challenges reaching a hidden population.

PubMed

Johnston, Lisa Grazina; Trummal, Aire; Lohmus, Liilia; Ravalepik, Ardi

2009-09-01

This paper examines challenges obtaining representative samples of males who have sex with males (MSM) in Estonia and provides descriptive HIV behavioral data gathered from four cross-sectional surveys; three using the internet, and one using respondent driven sampling (RDS) to recruit MSM in Tallinn and Harju County. Estonian MSM were sampled between March and May in 2004 (n=193), August and November in 2005 (n=146) and September and December in 2007 (n=238) using internet websites. MSM in Tallinn and Harju County were sampled between April and June in 2007 (n=59) using RDS. Recruitment of MSM using RDS did not acquire the calculated sample size. The RDS study reached a less diverse group of MSM than did the internet studies which recruited a larger proportion of MSM who were older, bisexual, having female sexual partners during the last six months, and unlikely to have been tested for HIV. The findings and observations presented in this paper could inform researchers in Estonia, and the region, about the efficacy of and socio-cultural challenges to sampling MSM to collect HIV biological and/or behavioral data.

The REX survey as a Tool to Test the Beaming Model for BL Lacs

NASA Astrophysics Data System (ADS)

Caccianiga, A.; della Ceca, R.; Gioia, I. M.; Maccacaro, T.; Wolter, A.

We present the preliminary properties of the BL Lacs discovered in the REX survey (Caccianiga et al. 1998). In particular, we discuss a few sources with optical spectral properties ``intermediate'' between those of BL Lacs and those of elliptical galaxies. These objects could harbour weak (in the optical band) sources of non-thermal continuum in their nuclei and, if confirmed, they could represent the faint tail of the BL Lac population. The existence of such ``weak'' BL Lacs is matter of discussion in recent literature (e.g. Marcha et al. 1996) and could lead to a revision of the defining criteria of a BL Lac and, consequently, of their cosmological and statistical properties.

On the surface density of X-ray selected BL Lacertae objects

NASA Technical Reports Server (NTRS)

Maccacaro, T.; Gioia, I. M.; Maccagni, D.; Stocke, J. T.

1984-01-01

Only a handful of BL Lac objects have been found as a result of systematic optical identification of serendipitous Einstein X-ray sources. By combining the data from two flux-limited complete X-ray surveys (the HEAO 1 A-2 and the Einstein Observatory Medium Sensitivity Survey) the surface density of X-ray emitting BL Lac objects is evaluated as a function of their X-ray flux. It is found that a single power law is not an acceptable representation of the BL Lac objects' X-ray log N-log S. The number-flux relationship is consistent with the Euclidean slope at 'high' flux levels but shows a drastic flattnring below fluxes of the order of 10 to the -12th ergs per sq cm/s. The implications of this result are briefly discussed with respect to the luminosity function, the cosmological evolution, and the X-ray to optical flux ratio in BL Lac objects.

Making limb and nadir measurements comparable: A common volume study of PMC brightness observed by Odin OSIRIS and AIM CIPS

NASA Astrophysics Data System (ADS)

Benze, Susanne; Gumbel, Jörg; Randall, Cora E.; Karlsson, Bodil; Hultgren, Kristoffer; Lumpe, Jerry D.; Baumgarten, Gerd

2018-01-01

Combining limb and nadir satellite observations of Polar Mesospheric Clouds (PMCs) has long been recognized as problematic due to differences in observation geometry, scattering conditions, and retrieval approaches. This study offers a method of comparing PMC brightness observations from the nadir-viewing Aeronomy of Ice in the Mesosphere (AIM) Cloud Imaging and Particle Size (CIPS) instrument and the limb-viewing Odin Optical Spectrograph and InfraRed Imaging System (OSIRIS). OSIRIS and CIPS measurements are made comparable by defining a common volume for overlapping OSIRIS and CIPS observations for two northern hemisphere (NH) PMC seasons: NH08 and NH09. We define a scattering intensity quantity that is suitable for either nadir or limb observations and for different scattering conditions. A known CIPS bias is applied, differences in instrument sensitivity are analyzed and taken into account, and effects of cloud inhomogeneity and common volume definition on the comparison are discussed. Not accounting for instrument sensitivity differences or inhomogeneities in the PMC field, the mean relative difference in cloud brightness (CIPS - OSIRIS) is -102 ± 55%. The differences are largest for coincidences with very inhomogeneous clouds that are dominated by pixels that CIPS reports as non-cloud points. Removing these coincidences, the mean relative difference in cloud brightness reduces to -6 ± 14%. The correlation coefficient between the CIPS and OSIRIS measurements of PMC brightness variations in space and time is remarkably high, at 0.94. Overall, the comparison shows excellent agreement despite different retrieval approaches and observation geometries.

Radio-weak BL Lac Objects in the Fermi Era

NASA Astrophysics Data System (ADS)

Massaro, F.; Marchesini, E. J.; D'Abrusco, R.; Masetti, N.; Andruchow, I.; Smith, Howard A.

2017-01-01

The existence of “radio-weak BL Lac objects” (RWBLs) has been an open question, and has remained unsolved since the discovery that quasars could be radio-quiet or radio-loud. Recently, several groups identified RWBL candidates, mostly found while searching for low-energy counterparts of the unidentified or unassociated gamma-ray sources listed in the Fermi catalogs. Confirming RWBLs is a challenging task since they could be confused with white dwarfs (WDs) or weak emission line quasars (WELQs) when there are not sufficient data to precisely draw their broadband spectral energy distribution, and their classification is mainly based on a featureless optical spectra. Motivated by the recent discovery that Fermi BL Lacs appear to have very peculiar mid-IR emission, we show that it is possible to distinguish between WDs, WELQs, and BL Lacs using the [3.4]-[4.6]-[12] μm color-color plot built using the WISE magnitudes when the optical spectrum is available. On the basis of this analysis, we identify WISE J064459.38+603131 and WISE J141046.00+740511.2 as the first two genuine RWBLs, both potentially associated with Fermi sources. Finally, to strengthen our identification of these objects as true RWBLs, we present multifrequency observations for these two candidates to show that their spectral behavior is indeed consistent with that of the BL Lac population.

Time-dependent inhomogeneous jet models for BL Lac objects

NASA Technical Reports Server (NTRS)

Marlowe, A. T.; Urry, C. M.; George, I. M.

1992-01-01

Relativistic beaming can explain many of the observed properties of BL Lac objects (e.g., rapid variability, high polarization, etc.). In particular, the broadband radio through X-ray spectra are well modeled by synchrotron-self Compton emission from an inhomogeneous relativistic jet. We have done a uniform analysis on several BL Lac objects using a simple but plausible inhomogeneous jet model. For all objects, we found that the assumed power-law distribution of the magnetic field and the electron density can be adjusted to match the observed BL Lac spectrum. While such models are typically unconstrained, consideration of spectral variability strongly restricts the allowed parameters, although to date the sampling has generally been too sparse to constrain the current models effectively. We investigate the time evolution of the inhomogeneous jet model for a simple perturbation propagating along the jet. The implications of this time evolution model and its relevance to observed data are discussed.

Time-dependent inhomogeneous jet models for BL Lac objects

NASA Astrophysics Data System (ADS)

Marlowe, A. T.; Urry, C. M.; George, I. M.

1992-05-01

Relativistic beaming can explain many of the observed properties of BL Lac objects (e.g., rapid variability, high polarization, etc.). In particular, the broadband radio through X-ray spectra are well modeled by synchrotron-self Compton emission from an inhomogeneous relativistic jet. We have done a uniform analysis on several BL Lac objects using a simple but plausible inhomogeneous jet model. For all objects, we found that the assumed power-law distribution of the magnetic field and the electron density can be adjusted to match the observed BL Lac spectrum. While such models are typically unconstrained, consideration of spectral variability strongly restricts the allowed parameters, although to date the sampling has generally been too sparse to constrain the current models effectively. We investigate the time evolution of the inhomogeneous jet model for a simple perturbation propagating along the jet. The implications of this time evolution model and its relevance to observed data are discussed.

Properties of optically selected BL Lacertae candidates from the SDSS

NASA Astrophysics Data System (ADS)

Kügler, S. D.; Nilsson, K.; Heidt, J.; Esser, J.; Schultz, T.

2014-09-01

Context. Deep optical surveys open the avenue for finding large numbers of BL Lac objects that are hard to identify because they lack the unique properties classifying them as such. While radio or X-ray surveys typically reveal dozens of sources, recent compilations based on optical criteria alone have increased the number of BL Lac candidates considerably. However, these compilations are subject to biases and may contain a substantial number of contaminating sources. Aims: In this paper we extend our analysis of 182 optically selected BL Lac object candidates from the SDSS with respect to an earlier study. The main goal is to determine the number of bona fide BL Lac objects in this sample. Methods: We examine their variability characteristics, determine their broad-band radio-UV spectral energy distributions (SEDs), and search for the presence of a host galaxy. In addition we present new optical spectra for 27 targets with improved signal-to-noise ratio with respect to the SDSS spectra. Results: At least 59% of our targets have shown variability between SDSS DR2 and our observations by more than 0.1-0.27 mag depending on the telescope used. A host galaxy was detected in 36% of our targets. The host galaxy type and luminosities are consistent with earlier studies of BL Lac host galaxies. Simple fits to broad-band SEDs for 104 targets of our sample derived synchrotron peak frequencies between 13.5 ≤ log 10(νpeak) ≤ 16 with a peak at log 10 ~ 14.5. Our new optical spectra do not reveal any new redshift for any of our objects. Thus the sample contains a large number of bona fide BL Lac objects and seems to contain a substantial fraction of intermediate-frequency peaked BL Lacs. Based on observations collected with the NTT on La Silla (Chile) operated by the European Southern Observatory under proposal 082.B-0133.Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA), operated jointly by the Max-Planck-Institut für Astronomie and the

Complete Genome Sequence of the Probiotic Lactobacillus casei Strain BL23▿

PubMed Central

Mazé, Alain; Boël, Grégory; Zúñiga, Manuel; Bourand, Alexa; Loux, Valentin; Yebra, Maria Jesus; Monedero, Vicente; Correia, Karine; Jacques, Noémie; Beaufils, Sophie; Poncet, Sandrine; Joyet, Philippe; Milohanic, Eliane; Casarégola, Serge; Auffray, Yanick; Pérez-Martínez, Gaspar; Gibrat, Jean-François; Zagorec, Monique; Francke, Christof; Hartke, Axel; Deutscher, Josef

2010-01-01

The entire genome of Lactobacillus casei BL23, a strain with probiotic properties, has been sequenced. The genomes of BL23 and the industrially used probiotic strain Shirota YIT 9029 (Yakult) seem to be very similar. PMID:20348264

RADIO-WEAK BL LAC OBJECTS IN THE FERMI ERA

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

Massaro, F.; Marchesini, E. J.; D’Abrusco, R.

2017-01-10

The existence of “radio-weak BL Lac objects” (RWBLs) has been an open question, and has remained unsolved since the discovery that quasars could be radio-quiet or radio-loud. Recently, several groups identified RWBL candidates, mostly found while searching for low-energy counterparts of the unidentified or unassociated gamma-ray sources listed in the Fermi catalogs. Confirming RWBLs is a challenging task since they could be confused with white dwarfs (WDs) or weak emission line quasars (WELQs) when there are not sufficient data to precisely draw their broadband spectral energy distribution, and their classification is mainly based on a featureless optical spectra. Motivated bymore » the recent discovery that Fermi BL Lacs appear to have very peculiar mid-IR emission, we show that it is possible to distinguish between WDs, WELQs, and BL Lacs using the [3.4]–[4.6]–[12] μ m color–color plot built using the WISE magnitudes when the optical spectrum is available. On the basis of this analysis, we identify WISE J064459.38+603131 and WISE J141046.00+740511.2 as the first two genuine RWBLs, both potentially associated with Fermi sources. Finally, to strengthen our identification of these objects as true RWBLs, we present multifrequency observations for these two candidates to show that their spectral behavior is indeed consistent with that of the BL Lac population.« less

The intraday variability in the radio-selected and X-ray-selected BL Lacertae objects

NASA Astrophysics Data System (ADS)

Bai, J. M.; Xie, G. Z.; Li, K. H.; Zhang, X.; Liu, W. W.

1998-10-01

Seven BL Lac objects have been photometrically observed in an effort to study the difference of optical intraday variability between the radio-selected BL Lac objects (RBLs) and X-ray-selected BL Lac objects (XBLs). The objects we observed are selected arbitrarily. They are four RBLs, PKS 0735+178, PKS 0754+101, OJ 287 and BL Lac, and three XBLs, H 0323+022, H 0548-322 and H 2154-304. During the observation all of them exhibited microvariation, and H 0323+022 and H 0548-322 sometimes showed brightness oscillation. PKS 0735+178 and BL Lac were in their faint states and not very active. It seems that RBLs do not show microvariability more frequently than XBLs. Table 2 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5)

Retrieval of stratospheric ozone and nitrogen dioxide profiles from Odin Optical Spectrograph and Infrared Imager System (OSIRIS) limb-scattered sunlight measurements

NASA Astrophysics Data System (ADS)

Haley, Craig Stuart

2009-12-01

Key to understanding and predicting the effects of global environmental problems such as ozone depletion and global warming is a detailed understanding of the atmospheric processes, both dynamical and chemical. Essential to this understanding are accurate global data sets of atmospheric constituents with adequate temporal and spatial (vertical and horizontal) resolutions. For this purpose the Canadian satellite instrument OSIRIS (Optical Spectrograph and Infrared Imager System) was launched on the Odin satellite in 2001. OSIRIS is primarily designed to measure minor stratospheric constituents, including ozone (O3) and nitrogen dioxide (NO2), employing the novel limb-scattered sunlight technique, which can provide both good vertical resolution and near global coverage. This dissertation presents a method to retrieve stratospheric O 3 and NO2 from the OSIRIS limb-scatter observations. The retrieval method incorporates an a posteriori optimal estimator combined with an intermediate spectral analysis, specifically differential optical absorption spectroscopy (DOAS). A detailed description of the retrieval method is presented along with the results of a thorough error analysis and a geophysical validation exercise. It is shown that OSIRIS limb-scatter observations successfully produce accurate stratospheric O3 and NO2 number density profiles throughout the stratosphere, clearly demonstrating the strength of the limb-scatter technique. The OSIRIS observations provide an extremely useful data set that is of particular importance for studies of the chemistry of the middle atmosphere. The long OSIRIS record of stratospheric ozone and nitrogen dioxide may also prove useful for investigating variability and trends.

The Futures of Adult Educator(s): Agency, Identity and Ethos. Joint Conference Proceedings of the 2nd ESREA/ReNAdET Meeting and the 4th TQF Seminar (Tallinn, Estonia, November 9-11, 2011)

ERIC Educational Resources Information Center

Heikkinen, Anja, Ed.; Jogi, Larissa, Ed.; Jutte, Wolfgang, Ed.; Zarifis, Georgios K., Ed.

2012-01-01

This edited volume contains the papers presented in the 2nd ESREA|ReNAdet meeting that was jointly organised with the VET & CULTURE Network in the University of Tallinn (Estonia), 9-11 November 2011. The papers that appear in the volume discuss the future (or the futures) of adult educators in respect to issues of developing their identities…

CNN-BLPred: a Convolutional neural network based predictor for β-Lactamases (BL) and their classes.

PubMed

White, Clarence; Ismail, Hamid D; Saigo, Hiroto; Kc, Dukka B

2017-12-28

The β-Lactamase (BL) enzyme family is an important class of enzymes that plays a key role in bacterial resistance to antibiotics. As the newly identified number of BL enzymes is increasing daily, it is imperative to develop a computational tool to classify the newly identified BL enzymes into one of its classes. There are two types of classification of BL enzymes: Molecular Classification and Functional Classification. Existing computational methods only address Molecular Classification and the performance of these existing methods is unsatisfactory. We addressed the unsatisfactory performance of the existing methods by implementing a Deep Learning approach called Convolutional Neural Network (CNN). We developed CNN-BLPred, an approach for the classification of BL proteins. The CNN-BLPred uses Gradient Boosted Feature Selection (GBFS) in order to select the ideal feature set for each BL classification. Based on the rigorous benchmarking of CCN-BLPred using both leave-one-out cross-validation and independent test sets, CCN-BLPred performed better than the other existing algorithms. Compared with other architectures of CNN, Recurrent Neural Network, and Random Forest, the simple CNN architecture with only one convolutional layer performs the best. After feature extraction, we were able to remove ~95% of the 10,912 features using Gradient Boosted Trees. During 10-fold cross validation, we increased the accuracy of the classic BL predictions by 7%. We also increased the accuracy of Class A, Class B, Class C, and Class D performance by an average of 25.64%. The independent test results followed a similar trend. We implemented a deep learning algorithm known as Convolutional Neural Network (CNN) to develop a classifier for BL classification. Combined with feature selection on an exhaustive feature set and using balancing method such as Random Oversampling (ROS), Random Undersampling (RUS) and Synthetic Minority Oversampling Technique (SMOTE), CNN-BLPred performs

Clinical Chemistry Reference Intervals for C57BL/6J, C57BL/6N, and C3HeB/FeJ Mice (Mus musculus)

PubMed Central

Otto, Gordon P; Rathkolb, Birgit; Oestereicher, Manuela A; Lengger, Christoph J; Moerth, Corinna; Micklich, Kateryna; Fuchs, Helmut; Gailus-Durner, Valérie; Wolf, Eckhard; de Angelis, Martin Hrabě

2016-01-01

Although various mouse inbred strains are widely used to investigate disease mechanisms and to establish new therapeutic strategies, sex-specific reference intervals for laboratory diagnostic analytes that are generated from large numbers of animals have been unavailable. In this retrospective study, we screened data from more than 12,000 mice phenotyped in the German Mouse Clinic from January 2006 through June 2014 and selected animals with the genetic background of C57BL/6J, C57BL/6N, or C3HeB/FeJ. In addition, we distinguished between the C57BL/6NTac substrain and C57BL/6N mice received from other vendors. The corresponding data sets of electrolytes (sodium, potassium, calcium, chloride, inorganic phosphate), lipids (cholesterol, triglyceride), and enzyme activities (ALT, AST, ALP, α-amylase) and urea, albumin, and total protein levels were analyzed. Significant effects of age and sex on these analytes were identified, and strain- or substrain- and sex-specific reference intervals for 90- to 135-d-old mice were calculated. In addition, we include an overview of the literature that reports clinical chemistry values for wild-type mice of different strains. Our results support researchers interpreting clinical chemistry values from various mouse mutants and corresponding wild-type controls based on the examined strains and substrains. PMID:27423143

Clinical Chemistry Reference Intervals for C57BL/6J, C57BL/6N, and C3HeB/FeJ Mice (Mus musculus).

PubMed

Otto, Gordon P; Rathkolb, Birgit; Oestereicher, Manuela A; Lengger, Christoph J; Moerth, Corinna; Micklich, Kateryna; Fuchs, Helmut; Gailus-Durner, Valérie; Wolf, Eckhard; Hrabě de Angelis, Martin

2016-01-01

Although various mouse inbred strains are widely used to investigate disease mechanisms and to establish new therapeutic strategies, sex-specific reference intervals for laboratory diagnostic analytes that are generated from large numbers of animals have been unavailable. In this retrospective study, we screened data from more than 12,000 mice phenotyped in the German Mouse Clinic from January 2006 through June 2014 and selected animals with the genetic background of C57BL/6J, C57BL/6N, or C3HeB/FeJ. In addition, we distinguished between the C57BL/6NTac substrain and C57BL/6N mice received from other vendors. The corresponding data sets of electrolytes (sodium, potassium, calcium, chloride, inorganic phosphate), lipids (cholesterol, triglyceride), and enzyme activities (ALT, AST, ALP, α-amylase) and urea, albumin, and total protein levels were analyzed. Significant effects of age and sex on these analytes were identified, and strain- or substrain- and sex-specific reference intervals for 90- to 135-d-old mice were calculated. In addition, we include an overview of the literature that reports clinical chemistry values for wild-type mice of different strains. Our results support researchers interpreting clinical chemistry values from various mouse mutants and corresponding wild-type controls based on the examined strains and substrains.

Identification of hemolysin BL-producing Bacillus cereus isolates by a discontinuous hemolytic pattern in blood agar.

PubMed Central

Beecher, D J; Wong, A C

1994-01-01

Bacillus cereus causes distinct exotoxin-mediated diarrheal and emetic food poisoning syndromes and a variety of nongastrointestinal infections. Evidence is accumulating that hemolysin BL is a major B. cereus virulence factor. We describe two methods for detection of hemolysin BL in crude samples and on primary culture media. In the first method, the highly unusual discontinuous hemolysis pattern that is characteristic of pure hemolysin BL was produced in sheep and calf blood agar around wells filled with crude culture supernatant from hemolysin BL-producing strains. In the second method, the pattern was formed surrounding colonies of hemolysin BL-producing strains grown on media consisting of nutrient agar, 0.15 M NaCl, 2% calf serum, and sheep or calf blood. Hemolysin BL production was detected with these methods in 41 of 62 (66%) previously identified B. cereus isolates and in 46 of 136 (34%) presumptive B. cereus isolates from soil. All nine isolates tested that were associated with diarrhea or nongastrointestinal illness were positive for hemolysin BL. The methods presented here are specific, simple, inexpensive, and applicable to the screening of large numbers of samples or isolates. Images PMID:8017944

Tuberculosis knowledge among injecting drug users visiting syringe exchange programme in Tallinn, Estonia.

PubMed

Rüütel, Kristi; Parker, R David; Sobolev, Igor; Loit, Helle-Mai

2012-12-01

The purpose of the current study was to describe tuberculosis (TB) knowledge, beliefs, and experience with TB services among injecting drug users. Participants for this anonymous, cross-sectional study were recruited from a community based syringe exchange programme in Tallinn, Estonia. A structured questionnaire was completed and included information on socio-demographics, health history, drug use, and knowledge about TB and HIV. The study included 407 people (79% male, mean age 27.9 years, mean injection drug use 9.4 years). 32.9% of participants reported HIV infection and 1.7% lifetime history of TB. 26.4% participants (n=106) reported symptoms suggestive of TB. 93% of participants recognized correctly that TB is air-borne infection and 91% that HIV is a risk factor for TB. Only 40% of the participants knew that TB diagnostics and treatment in Estonia are free of charge for everybody and 58% reported they knew where to get health care services in case they suspected that they had TB. TB transmission and treatment adherence knowledge was better among those in contact with either health care or harm reduction services, e.g the community based syringe exchange programme. Similar to HIV services, TB prevention and education should be integrated into harm reduction and drug treatment programmes to facilitate early diagnosis and treatment of TB among injecting drug users.

Optical polarization of high-energy BL Lacertae objects

NASA Astrophysics Data System (ADS)

Hovatta, T.; Lindfors, E.; Blinov, D.; Pavlidou, V.; Nilsson, K.; Kiehlmann, S.; Angelakis, E.; Fallah Ramazani, V.; Liodakis, I.; Myserlis, I.; Panopoulou, G. V.; Pursimo, T.

2016-12-01

Context. We investigate the optical polarization properties of high-energy BL Lac objects using data from the RoboPol blazar monitoring program and the Nordic Optical Telescope. Aims: We wish to understand if there are differences between the BL Lac objects that have been detected with the current-generation TeV instruments and those objects that have not yet been detected. Methods: We used a maximum-likelihood method to investigate the optical polarization fraction and its variability in these sources. In order to study the polarization position angle variability, we calculated the time derivative of the electric vector position angle (EVPA) change. We also studied the spread in the Stokes Q/I-U/I plane and rotations in the polarization plane. Results: The mean polarization fraction of the TeV-detected BL Lacs is 5%, while the non-TeV sources show a higher mean polarization fraction of 7%. This difference in polarization fraction disappears when the dilution by the unpolarized light of the host galaxy is accounted for. The TeV sources show somewhat lower fractional polarization variability amplitudes than the non-TeV sources. Also the fraction of sources with a smaller spread in the Q/I-U/I plane and a clumped distribution of points away from the origin, possibly indicating a preferred polarization angle, is larger in the TeV than in the non-TeV sources. These differences between TeV and non-TeV samples seem to arise from differences between intermediate and high spectral peaking sources instead of the TeV detection. When the EVPA variations are studied, the rate of EVPA change is similar in both samples. We detect significant EVPA rotations in both TeV and non-TeV sources, showing that rotations can occur in high spectral peaking BL Lac objects when the monitoring cadence is dense enough. Our simulations show that we cannot exclude a random walk origin for these rotations. Conclusions: These results indicate that there are no intrinsic differences in the

NLO+NLL collider bounds, Dirac fermion and scalar dark matter in the B-L model

NASA Astrophysics Data System (ADS)

Klasen, Michael; Lyonnet, Florian; Queiroz, Farinaldo S.

2017-05-01

Baryon and lepton numbers being accidental global symmetries of the Standard Model (SM), it is natural to promote them to local symmetries. However, to preserve anomaly-freedom, only combinations of B-L are viable. In this spirit, we investigate possible dark matter realizations in the context of the U(1)_B{-L} model: (i) Dirac fermion with unbroken B-L; (ii) Dirac fermion with broken B-L; (iii) scalar dark matter; (iv) two-component dark matter. We compute the relic abundance, direct and indirect detection observables and confront them with recent results from Planck, LUX-2016, and Fermi-LAT and prospects from XENON1T. In addition to the well-known LEP bound M_{Z^' }}/g_BL ≳ 7 TeV, we include often ignored LHC bounds using 13 TeV dilepton (dimuon + dielectron) data at next-to-leading order plus next-to-leading logarithmic accuracy. We show that, for gauge couplings smaller than 0.4, the LHC gives rise to the strongest collider limit. In particular, we find M_{Z^' }}/g_BL > 8.7 TeV for g_BL=0.3. We conclude that the NLO+NLL corrections improve the dilepton bounds on the Z^' } mass and that both dark matter candidates are only viable in the Z^' } resonance region, with the parameter space for scalar dark matter being fully probed by XENON1T. Lastly, we show that one can successfully have a minimal two-component dark matter model.

The environment of x ray selected BL Lacs: Host galaxies and galaxy clustering

NASA Technical Reports Server (NTRS)

Wurtz, Ron; Stocke, John T.; Ellingson, Erica; Yee, Howard K. C.

1993-01-01

Using the Canada-France-Hawaii Telescope, we have imaged a complete, flux-limited sample of Einstein Medium Sensitivity Survey BL Lacertae objects in order to study the properties of BL Lac host galaxies and to use quantitative methods to determine the richness of their galaxy cluster environments.

Gene Transfer in Leptolyngbya sp. Strain BL0902, a Cyanobacterium Suitable for Production of Biomass and Bioproducts

PubMed Central

Taton, Arnaud; Lis, Ewa; Adin, Dawn M.; Dong, Guogang; Cookson, Scott; Kay, Steve A.; Golden, Susan S.; Golden, James W.

2012-01-01

Current cyanobacterial model organisms were not selected for their growth traits or potential for the production of renewable biomass, biofuels, or other products. The cyanobacterium strain BL0902 emerged from a search for strains with superior growth traits. Morphology and 16S rRNA sequence placed strain BL0902 in the genus Leptolyngbya. Leptolyngbya sp. strain BL0902 (hereafter Leptolyngbya BL0902) showed robust growth at temperatures from 22°C to 40°C and tolerated up to 0.5 M NaCl, 32 mM urea, high pH, and high solar irradiance. Its growth rate under outdoor conditions rivaled Arthrospira (“pirulina” strains. Leptolyngbya BL0902 accumulated higher lipid content and a higher proportion of monounsaturated fatty acids than Arthrospira strains. In addition to these desirable qualities, Leptolyngbya BL0902 is amenable to genetic engineering that is reliable, efficient, and stable. We demonstrated conjugal transfer from Escherichia coli of a plasmid based on RSF1010 and expression of spectinomycin/streptomycin resistance and yemGFP reporter transgenes. Conjugation efficiency was investigated in biparental and triparental matings with and without a “elper”plasmid that carries DNA methyltransferase genes, and with two different conjugal plasmids. We also showed that Leptolyngbya BL0902 is amenable to transposon mutagenesis with a Tn5 derivative. To facilitate genetic manipulation of Leptolyngbya BL0902, a conjugal plasmid vector was engineered to carry a trc promoter upstream of a Gateway recombination cassette. These growth properties and genetic tools position Leptolyngbya BL0902 as a model cyanobacterial production strain. PMID:22292073

VizieR Online Data Catalog: The CLASS BL Lac sample (Marcha+, 2013)

NASA Astrophysics Data System (ADS)

Marcha, M. J. M.; Caccianiga, A.

2014-04-01

This paper presents a new sample of BL Lac objects selected from a deep (30mJy) radio survey of flat spectrum radio sources (the CLASS blazar survey). The sample is one of the largest well-defined samples in the low-power regime with a total of 130 sources of which 55 satisfy the 'classical' optical BL Lac selection criteria, and the rest have indistinguishable radio properties. The primary goal of this study is to establish the radio luminosity function (RLF) on firm statistical ground at low radio luminosities where previous samples have not been able to investigate. The gain of taking a peek at lower powers is the possibility to search for the flattening of the luminosity function which is a feature predicted by the beaming model but which has remained elusive to observational confirmation. In this study, we extend for the first time the BL Lac RLF down to very low radio powers ~1022W/Hz, i.e. two orders of magnitude below the RLF currently available in the literature. In the process, we confirm the importance of adopting a broader, and more physically meaningful set of classification criteria to avoid the systematic missing of low-luminosity BL Lacs. Thanks to the good statistics we confirm the existence of weak but significant positive cosmological evolution for the BL Lac population, and we detect, for the first time the flattening of the RLF at L~1025W/Hz in agreement with the predictions of the beaming model. (1 data file).

Is BL Lacertae an ``orphan'' AGN?. Multiband and spectroscopic constraints on the parent population

NASA Astrophysics Data System (ADS)

Capetti, A.; Raiteri, C. M.; Buttiglione, S.

2010-06-01

Aims: We have analysed optical spectra of BL Lacertae, the prototype of its blazar subclass, to verify the broad Hα emission line detected more than a decade ago and its possible flux variation. We used the spectroscopic information to investigate the question of the BL Lacertae parent population. Methods: Low- and high-resolution optical spectra of BL Lacertae were acquired with the DOLORES spectrograph at the 3.58 m telescopio nazionale Galileo (TNG) during four nights in 2007-2008, when the source was in a relatively faint state. In three cases we were able to fit the complex Hα spectral range with multiple line components and to measure both the broad Hα and several narrow emission line fluxes. Results: A critical comparison with previous results suggests that the broad Hα flux has increased by about 50% in ten years. This might be due to an addition of gas in the broad line region (BLR), or to a strengthening of the disc luminosity, but such flux changes are not unusual in Broad Lined active nuclei. We estimated the BL Lacertae black hole mass by means of its relation with the bulge luminosity, finding 4-6 × 108 M⊙. The virial mass estimated from the spectroscopic data gives instead a value 20-30 times lower. An analysis of the disc and BLR properties in different AGNs suggests that this discrepancy is due to an underluminosity of the BL Lacertae BLR. Finally, we addressed the problem of the BL Lacertae parent population, comparing its isotropic quantities with those of other AGN classes. From the point of view of the narrow emission line spectrum, the source is located close to low-excitation radio galaxies. When one also considers its diffuse radio power, an association with FR I radio galaxies is severely questioned due to the lower radio luminosity (at a given line luminosity) of BL Lacertae. The narrow line and radio luminosities of BL Lacertae instead match those of a sample of miniature radio galaxies, which however do not show a BLR. Yet, if

Photometric Redshifts of High-z BL Lacs from 3FGL Catalog

NASA Astrophysics Data System (ADS)

Kaur, A.; Rau, Arne; Ajello, Marco; Paliya, Vaidehi; Hartmann, Dieter; Greiner, Jochen; Bolmer, Jan; Schady, Patricia

2017-08-01

Determining redshifts for BL Lacertae (BL Lac) objects using the traditional spectroscopic method is challenging due to the absence of strong emission lines in their optical spectra. We employ the photometric dropout technique to determine redshifts for this class of blazars using the combined 13 broad-band filters from Swift-UVOT and the multi-channel imager GROND at the MPG 2.2 m telescope at ESO's La Silla Observatory. The wavelength range covered by these 13 filters extends from far ultraviolet to the near-Infrared. We report results on 40 new Fermi detected BL Lacs with the photometric redshifts determinations for 5 sources, with 3FGL J1918.2-4110 being the most distance in our sample at z=2.16. Reliable upper limits are provided for 20 sources in this sample. Using the highest energy photons for these Fermi-LAT sources, we evaluate the consistency with the Gamma-ray horizon due to the extragalactic background light.

Analysis of Microvariable Activity of BL Lacertae

NASA Astrophysics Data System (ADS)

Sadun, Alberto C.; Asadi-Zeydabadi, Masoud; Hindman, Lauren; Moody, J. Ward

2018-06-01

BL Lac is a low-frequency peaked blazar (LBL) which emits synchrotron radiation at near-IR and optical wavelengths. Therefore optical observations are helpful in, among other things, studying the acceleration and cooling timescales of the electrons in the relativistic jets. We have made very high cadence observations of BL Lac over a number of nights with the Remote Observatory for Variable Object Research (ROVOR). Each night shows secular drift as well as a number of microvariable events lasting only a few minutes each. These data were then processed, compiled, and analyzed in order to examine the underlying mechanism that resulted in such activity. A geometric model is introduced that has worked well in the past on other similar sources.Our relativistic jet model consists of a slowly varying beamed source that already appears bright because it lies nearly to our line of sight. From this, individual relativistic components are ejected a few degrees relative to the aforementioned beaming angle. This is what we believe is responsible for the microvariability emission.

New High-z BL Lacs Using the Photometric Method with Swift and SARA

NASA Astrophysics Data System (ADS)

Kaur, A.; Rau, A.; Ajello, M.; Domínguez, A.; Paliya, V. S.; Greiner, J.; Hartmann, D. H.; Schady, P.

2018-06-01

BL Lacertae (BL Lac) objects are prominent members of the third Fermi Large Area Telescope catalog of γ-ray sources. Half of the members of the BL Lac population (∼300) lack redshift measurements, which is due to the absence of lines in their optical spectra, thereby making it difficult to utilize spectroscopic methods. Our photometric dropout technique can be used to establish the redshift for a fraction of these sources. This work employed six filters mounted on the Swift-UVOT and four optical filters on two telescopes, the 0.65 m SARA-CTIO in Chile and 1.0 m SARA-ORM in the Canary Islands, Spain. A sample of 15 sources was extracted from the Swift archival data for which six filter UVOT observations were conducted. By complementing the Swift observations with the SARA ones, we were able to discover two high-redshift sources: 3FGL J1155.4-3417 and 3FGL J1156.7–2250 at z={1.83}-0.13+0.10 and z={1.73}-0.19+0.11, respectively, resulting from the dropouts in the power-law template fits to these data. The discoveries add to the important (26 total) sample of high-redshift BL Lacs. While the sample of high-z BL Lacs is still rather small, these objects do not seem to fit well within known schemes of the blazar population and represent the best probes of the extragalactic background light.

Three new BL Lacertae objects in the Palomar-Green survey

NASA Technical Reports Server (NTRS)

Fleming, Thomas A.; Green, Richard F.; Jannuzi, Buell T.; Liebert, James; Smith, Paul S.; Fink, Henner

1993-01-01

We have identified three BL Lacertae objects in the Palomar-Green Survey which were previously misclassified as DC white dwarfs, namely PG 1246+586, PG 1424+240, and PG 1437+398. Our reclassification is based on the detection of these objects as x-ray sources in the ROSAT all-sky survey and upon our subsequent detection of intrinsic linearly polarized and variable optical emission from these sources. As a result of the ROSAT survey, the number of identified BL Lac objects in the Palomar-Green catalog of UV excess objects has been doubled. Corrected optical positions are presented for PG 1246+586 and PG 1437+398.

Ethanol inhibits B16-BL6 melanoma metastasis and cell phenotypes associated with metastasis.

PubMed

Kushiro, Kyoko; Núñez, Nomelí P

2012-01-01

Every year, approximately 68,000 new cases of malignant melanoma are diagnosed in the US. Ethanol consumption inhibits metastasis of melanoma in mice, but the mechanism is not well understood. C57BL/6J ob/+ mice, given either water or 20% ethanol, were injected intravenously with B16-BL6 melanoma cells to determine pulmonary metastasis. The effects of ethanol on cell phenotypes and markers of the epithelial-to-mesenchymal transition were determined in cell culture. In mice, ethanol consumption inhibited experimental pulmonary metastasis. This inhibition was associated with decreased body weight, and levels of systemic leptin, and insulin. In cell culture, ethanol inhibited B16-BL6 cell motility, invasion, and anchorage-independent growth. Additionally, ethanol reduced Snai1 expression and increased E-cadherin expression. Lastly, ethanol increased the expression of Kiss1 metastasis-suppressor and the metastasis suppressor Nm23/nucleoside diphosphate kinase. In both animal and in cell culture conditions, ethanol inhibited the metastatic ability of B16-BL6 melanoma cells.

Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 mice.

PubMed

Taylor, Peter; Noriega, Raquel; Farah, Carla; Abad, María-Jesús; Arsenak, Miriam; Apitz, Rafael

2006-08-08

Ajoene is an organosulphur compound derived from garlic with important effects on several membrane-associated processes such as platelet aggregation, as well as being cytotoxic for tumor cell lines in vitro. In the present study, we investigated the effect of ajoene on different cell types in vitro, as well as its inhibitory effects on both primary tumors and metastasis in a mouse model. We found ajoene to inhibit tumor cell growth in vitro, but also to inhibit strongly metastasis to lung in the B16/BL6 melanoma tumor model in C57BL/6 mice. As far as we are aware, this is the first report of the anti-metastatic effect of ajoene. Ajoene also inhibited tumor-endothelial cell adhesion, as well as the in vivo TNF-alpha response to lipopolysaccharide. Possible mechanisms of its antitumoral activity are discussed in the light of these results.

Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells.

PubMed

Slovak, M L; Hoeltge, G A; Ganapathi, R

1986-08-01

B16-BL6 murine melanoma cells were selected for cytogenetic evaluation during the stepwise development of increasing resistance in vitro to the antitumor antibiotic, doxorubicin (DOX). Karyotypic studies demonstrated extensive heteroploidy with both numerical and structural abnormalities which were not present in the parental DOX-sensitive B16-BL6 cells. Trypsin-Giemsa banding revealed the presence of several marker chromosomes containing abnormally banding regions (ABRs) in the 44-fold B16-BL6 DOX-resistant subline. These ABRs appeared to be more homogeneously staining at the higher DOX concentrations. Length measurements (ABR index) in seven banded metaphases indicated a direct correlation with increasing DOX concentration. When the DOX-resistant cells were grown in drug-free medium for 1 yr, the drug-resistant phenotype gradually declined in parallel with the level of resistance and the ABR index. DOX-induced cytogenetic damage examined by sister chromatid exchange methodology in parental B16-BL6 cells indicated a linear sister chromatid exchange:DOX dose-response relationship. However, after continuous treatment of parental B16-BL6 cells with DOX (0.01 microgram/ml) for 30 days, sister chromatid exchange scores were found to return to base-line values. The B16-BL6 resistant cells demonstrated a cross-resistant phenotype with N-trifluoroacetyladriamycin-14-valerate, actinomycin D, and the Vinca alkaloids but not with 1-beta-D-arabinofuranosylcytosine. The results suggest that ABR-containing chromosomes in DOX-resistant sublines may represent cytogenetic alterations of specific amplified genes involved in the expression of DOX resistance. Further studies are required to identify and define the possible gene products and to correlate their relationship to the cytotoxic action of doxorubicin.

BL Lacertae: X-ray spectral evolution and a black-hole mass estimate

NASA Astrophysics Data System (ADS)

Titarchuk, Lev; Seifina, Elena

2017-06-01

We present an analysis of the spectral properties observed in X-rays from active galactic nucleus BL Lacertae using RXTE, Suzaku, ASCA, BeppoSAX, and Swift observations. The total time covered by these observations is approximately 20 yr. We show strong observational evidence that this source undergoes X-ray spectral transitions from the low hard state (LHS) through the intermediate state (IS) to the high soft state (HSS) during these observations. During the RXTE observations (1997-2001, 180 ks, for a total 145 datasets), the source was approximately 75%, 20% and only 5% of the time in the IS, LHS, and HSS, respectively. We also used Swift observations (470 datasets, for a total 800 ks), which occurred during 12 yr (2005-2016), the broadband (0.3-200 keV) data of BeppoSAX (1997-2000, 160 ks), and the low X-ray energy (0.3-10 keV) data of ASCA (1995-1999, 160 ks). Two observations of Suzaku (2006, 2013; 50 ks) in combinations with long-term RXTE and Swift data-sets fortunately allow us to describe all spectral states of BL Lac. The spectra of BL Lac are well fitted by the so-called bulk motion Comptonization (BMC) model for all spectral states. We have established the photon index saturation level, Γsat = 2.2 ± 0.1, in the Γ versus mass accretion rate (Ṁ) correlation. This Γ - Ṁ correlation allows us to estimate the black-hole (BH) mass in BL Lac to be MBH 3 × 107M⊙ for a distance of 300 Mpc. For the BH mass estimate, we use the scaling method taking stellar-mass Galactic BHs 4U 1543-47 and GX 339-4 as reference sources. The Γ - Ṁ correlation revealed in BL Lac is similar to those in a number of stellar-mass Galactic BHs and two recently studied intermediate-mass extragalactic BHs. It clearly shows the correlation along with the very extended Γ saturation at 2.2. This is robust observational evidence for the presence of a BH in BL Lac. We also reveal that the seed (disk) photon temperatures are relatively low, of order of 100 eV, which are consistent

STRUCTURED JETS IN BL LAC OBJECTS: EFFICIENT PeV NEUTRINO FACTORIES?

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

Tavecchio, Fabrizio; Ghisellini, Gabriele; Guetta, Dafne

2014-09-20

The origin of high-energy neutrinos (0.1–1 PeV range) detected by IceCube remains a mystery. In this work, we explore the possibility that efficient neutrino production can occur in structured jets of BL Lac objects, characterized by a fast inner spine surrounded by a slower layer. This scenario has been widely discussed in the framework of the high-energy emission models for BL Lac objects and radio galaxies. One of the relevant consequences of a velocity structure is the enhancement of the inverse Compton emission caused by the radiative coupling of the two zones. We show that a similar boosting could occurmore » for the neutrino output of the spine through the photo-meson reaction of high-energy protons scattering off the amplified soft target photon field of the layer. Assuming the local density and the cosmological evolution of γ-ray BL Lac object derived from Fermi Large Area Telescope data, we calculate the expected diffuse neutrino intensity, which can match the IceCube data for a reasonable choice of parameters.« less

Establishment of a C57BL/6N mouse model of giardiasis.

PubMed

Lu, Siqi; Luo, Xiaobing; Chen, Xiaoning; Wang, Fengyun

2002-10-01

To establish a C57BL/6N mouse model infected with Giardia lamblia (G. lamblia) isolates from human origin. Two groups of C57BL/6N mouse were inoculated with purified cysts of two G. lamblia isolates (CD and XZ) by gavage separately. Patterns and curves of cyst excretion of the infected mice were observed and summarized. Histopathological changes of the small intestines of the infected mice were observed. Thirty-six mice receiving 1 x 10(4) cysts each were all infected. The C57BL/6N mouse showed high susceptibility to G. lamblia infection. There was no notable distinction between the two groups of the mice infected by the cysts of CD and XZ isolates. Cyst excretion occurred with intermittence. Of 36 infected mice, 32 (89%) passed cysts intermittently and 4 (11%) others persistently. The latent period of cyst excretion was 0 - 3 days p.i. (post-inoculation). The interruption of cyst excretion ranged from 12 to 20 days p.i. The fastigium of the cyst excretion was on day 6 p.i. The peak count of the cysts passed during a 2 h collection period was 2.3 x 10(7)/g fecal specimen. Edema, inflammation, cell infiltration, small blood vessels congestion, mitotic figures and mucosa necrosis appeared in sections of intestines. C57Bl/6N mouse is a suitable animal model of G. lamblia.

Effect of ketamine on exploratory behaviour in BALB/C and C57BL/6 mice.

PubMed

Akillioglu, Kubra; Melik, Emine Babar; Melik, Enver; Boga, Ayper

2012-01-01

In this study, we evaluated the effect of ketamine on exploratory locomotion behaviours in the Balb/c and C57BL/6 strains of mice, which differ in their locomotion behaviours. Intraperitoneal administration of ketamine at three different doses (1, 5 or 10 mg/kg, 0.1 ml/10 gr body weight) was performed on adult male Balb/c and C57BL/6 mice. The same volume of saline was applied to the control group. The open-field and elevated plus maze apparatus were used to evaluate exploratory locomotion. In the open-field test, Balb/c mice less spend time in the centre of the field and was decreased locomotor activity compared to C57BL/6 mice (p<0.01). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in locomotor activity and an increase in the amount of time spent in the centre in the open-field test, compared to the control group (p<0.05). In C57BL/6 mice, ketamine treatment (1 and 10 mg/kg) decreased locomotor activity (p<0.05). In C57BL/6 mice, the three different doses of ketamine application each caused a decrease in the frequency of centre crossing (p<0.001) and the spent time in the centre (p<0.05). In the elevated plus maze, the number of open-arm entries, the percentage of open-arm time and total arm entries were decreased in Balb/c mice compared to C57BL/6 mice (p<0.001). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in the open-arm activity (p<0.001). Ketamine application (10 mg/kg) decreased the open-arm activity in C57BL/6 mice (p<0.05). A subanaesthetic dose of ketamine increased exploratory locomotion in Balb/c mice. In contrast, a subanaesthetic dose of ketamine decreased exploratory locomotion in C57BL/6 mice. In conclusion, hereditary factors may play an important role in ketamine-induced responses. Copyright © 2011 Elsevier Inc. All rights reserved.

Phenotypic stability of B16-BL6 melanoma exposed to low levels of tyrosine and phenylalanine.

PubMed

Elstad, C A; Meadows, G G

1990-01-01

We previously demonstrated that tyrosine (Tyr) and phenylalanine (Phe) restriction suppresses metastatic heterogeneity of B16-BL6 (BL6) melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigate stability of this Tyr- and Phe-modulated tumor phenotype by sequentially transplanting BL6 in vivo into mice fed Low Tyr and Phe Diet. Metastatic potential of BL6 is suppressed after one subcutaneous passage. Suppression is unlikely to result from inhibition of tumor growth, since growth in vitro is significantly increased. The metastatic potential of the Tyr- and Phe-modulated tumor is unstable after in vivo passage, and lung colonizing ability is regenerated after ten in vivo passages. Conversely, the antimetastatic effect of Tyr and Phe restriction is stable after prolonged in vitro passage. The metastatic potential of tumors from mice fed Normal Diet is unstable after long-term in vitro culture. Sensitivity to adriamycin of BL6 from mice fed Low Tyr and Phe Diet is increased and is not altered by change in metastatic potential.

The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors.

PubMed

Kim, Jieun; Lee, Haeryung; Kim, Yujin; Yoo, Sooyeon; Park, Eunjeong; Park, Soochul

2010-04-01

We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.

C57BL/6N mutation in Cytoplasmic FMR interacting protein 2 regulates cocaine response

PubMed Central

Kumar, Vivek; Kim, Kyungin; Joseph, Chryshanthi; Kourrich, Saïd; Yoo, Seung Hee; Huang, Hung Chung; Vitaterna, Martha H.; de Villena, Fernando Pardo-Manuel; Churchill, Gary; Bonci, Antonello; Takahashi, Joseph S.

2015-01-01

The inbred mouse C57BL/6J is the reference strain for genome sequence and for most behavioral and physiological phenotypes. However the International Knockout Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N substrain. We found that C57BL/6N has lower acute and sensitized response to cocaine and methamphetamine. We mapped a single causative locus and identified a non-synonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMR interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation destabilizes CYFIP2 and deletion of the C57BL/6N mutant allele leads to acute and sensitized cocaine response phenotypes. We propose CYFIP2 is a key regulator of cocaine response in mammals and present a framework to utilize mouse substrains to discover novel genes and alleles regulating behavior. PMID:24357318

Inhibition of B16-BL6 melanoma growth in mice by methionine-enkephalin.

PubMed

Murgo, A J

1985-08-01

The antitumor effect of methionine-enkephalin [( Met]enkephalin) was demonstrated in C57BL/6J mice inoculated with B16-BL6 melanoma cells. Local subcutaneous tumor growth was inhibited with a 50-micrograms dose daily for 7 or 14 days. The antitumor effect of [Met]enkephalin was inhibited by the administration of the opioid receptor antagonist naloxone. Naloxone alone had no significant effect on tumor growth.

Molecular basis for erythromycin-dependent ribosome-stalling during translation of the ErmBL leader peptide

PubMed Central

Arenz, Stefan; Ramu, Haripriya; Gupta, Pulkit; Berninghausen, Otto; Beckmann, Roland; Vázquez-Laslop, Nora; Mankin, Alexander S.; Wilson, Daniel N.

2014-01-01

In bacteria, ribosome-stalling during translation of ErmBL leader peptide occurs in the presence of the antibiotic erythromycin and leads to induction of expression of the downstream macrolide resistance methyltransferase ErmB. The lack of structures of drug-dependent stalled ribosome complexes (SRCs) has limited our mechanistic understanding of this regulatory process. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmBL-SRC. The structure reveals that the antibiotic does not interact directly with ErmBL, but rather redirects the path of the peptide within the tunnel. Furthermore, we identify a key peptide-ribosome interaction that defines an important relay pathway from the ribosomal tunnel to the peptidyltransferase center (PTC). The PTC of the ErmBL-SRC appears to adopt an uninduced state that prevents accommodation of Lys-tRNA at the A-site, thus providing structural bases for understanding how the drug and the nascent peptide cooperate to inhibit peptide-bond formation and induce translation arrest. PMID:24662426

Search for Cross-Correlations of Ultrahigh-Energy Cosmic Rays with BL Lacertae Objects

NASA Astrophysics Data System (ADS)

Abbasi, R. U.; Abu-Zayyad, T.; Amann, J. F.; Archbold, G.; Belov, K.; Belz, J. W.; BenZvi, S.; Bergman, D. R.; Blake, S. A.; Boyer, J. H.; Burt, G. W.; Cao, Z.; Connolly, B. M.; Deng, W.; Fedorova, Y.; Findlay, J.; Finley, C. B.; Hanlon, W. F.; Hoffman, C. M.; Holzscheiter, M. H.; Hughes, G. A.; Hüntemeyer, P.; Jui, C. C. H.; Kim, K.; Kirn, M. A.; Knapp, B. C.; Loh, E. C.; Maestas, M. M.; Manago, N.; Mannel, E. J.; Marek, L. J.; Martens, K.; Matthews, J. A. J.; Matthews, J. N.; O'Neill, A.; Painter, C. A.; Perera, L.; Reil, K.; Riehle, R.; Roberts, M. D.; Rodriguez, D.; Sasaki, M.; Schnetzer, S. R.; Seman, M.; Sinnis, G.; Smith, J. D.; Snow, R.; Sokolsky, P.; Springer, R. W.; Stokes, B. T.; Thomas, J. R.; Thomas, S. B.; Thomson, G. B.; Tupa, D.; Westerhoff, S.; Wiencke, L. R.; Zech, A.; HIRES Collaboration

2006-01-01

Data taken in stereo mode by the High Resolution Fly's Eye (HiRes) air fluorescence experiment are analyzed to search for correlations between the arrival directions of ultrahigh-energy cosmic rays with the positions of BL Lacertae objects. Several previous claims of significant correlations between BL Lac objects and cosmic rays observed by other experiments are tested. These claims are not supported by the HiRes data. However, we verify a recent analysis of correlations between HiRes events and a subset of confirmed BL Lac objects from the 10th Veron Catalog, and we study this correlation in detail. Due to the a posteriori nature of the search, the significance level cannot be reliably estimated and the correlation must be tested independently before any claim can be made. We identify the precise hypotheses that will be tested with statistically independent data.

Finding the rarest objects in the universe: A new, efficient method for discovering BL Lacertae objects

NASA Technical Reports Server (NTRS)

Stocke, John; Perlman, Eric; Granados, Arno; Schachter, Jonathan; Elvis, Martin; Urry, Meg; Impey, Chris; Smith, Paul

1993-01-01

We present a new, efficient method for discovering new BL Lac Objects based upon the results of the Einstein Extended Medium Sensitivity Survey (EMSS). We have found that all x-ray selected BL Lacs are radio emitters, and further, that in a 'color-color' diagram (radio/optical and optical/x-ray) the BL Lac Objects occupy an area distinct from both radio loud quasars and the radio quiet QSOs and Seyferts which dominate x-ray selected samples. After obtaining radio counterparts via VLA 'snapshot' observations of a large sample of unidentified x-ray sources, the list of candidates is reduced. These candidates then can be confirmed with optical spectroscopy and/or polarimetry. Since greater than 70 percent of these sources are expected to be BL Lacs, the optical observations are very efficient. We have tested this method using unidentified sources found in the Einstein Slew Survey. The 162 Slew Survey x-ray source positions were observed with the VLA in a mixed B/C configuration at 6 cm resulting in 60 detections within 1.5 position error circle radii. These x-ray/optical/radio sources were then plotted, and 40 BL Lac candidates were identified. To date, 10 candidates have been spectroscopically observed resulting in 10 new BL Lac objects! Radio flux, optical magnitude, and polarization statistics (obtained in white light with the Steward Observatory 2.3 m CCD polarimeter) for each are given.

SPring-8 BL41XU, a high-flux macromolecular crystallography beamline

PubMed Central

Hasegawa, Kazuya; Shimizu, Nobutaka; Okumura, Hideo; Mizuno, Nobuhiro; Baba, Seiki; Hirata, Kunio; Takeuchi, Tomoyuki; Yamazaki, Hiroshi; Senba, Yasunori; Ohashi, Haruhiko; Yamamoto, Masaki; Kumasaka, Takashi

2013-01-01

SPring-8 BL41XU is a high-flux macromolecular crystallography beamline using an in-vacuum undulator as a light source. The X-rays are monochromated by a liquid-nitrogen-cooling Si double-crystal monochromator, and focused by Kirkpatrick–Baez mirror optics. The focused beam size at the sample is 80 µm (H) × 22 µm (V) with a photon flux of 1.1 × 1013 photons s−1. A pinhole aperture is used to collimate the beam in the range 10–50 µm. This high-flux beam with variable size provides opportunities not only for micro-crystallography but also for data collection effectively making use of crystal volume. The beamline also provides high-energy X-rays covering 20.6–35.4 keV which allows ultra-high-resolution data to be obtained and anomalous diffraction using the K-edge of Xe and I. Upgrade of BL41XU for more rapid and accurate data collection is proceeding. Here, details of BL41XU are given and an outline of the upgrade project is documented. PMID:24121338

Effective sextic superpotential and B-L violation in NMSGUT

NASA Astrophysics Data System (ADS)

Aulakh, C. S.; Awasthi, R. L.; Krishna, Shri

2017-10-01

We list operators of the superpotential of the effective MSSM that emerge from the NMSGUT up to sextic degree. We give illustrative expressions for the coefficients in terms of NMSGUT parameters. We also estimate the impact of GUT scale threshold corrections on these effective operators in view of the demonstration that B violation via quartic superpotential terms can be suppressed to acceptable levels after including such corrections in the NMSGUT. We find a novel B, B-L violating quintic operator that leads to the decay mode n→ e^- K^+. We also remark that the threshold corrections to the Type-I seesaw mechanism make the deviation of right-handed neutrino masses from the GUT scale more natural while Type-II seesaw neutrino masses, which earlier tended to utterly negligible receive threshold enhancement. Our results are of relevance for analysing B-L violating operator-based, sphaleron-safe, baryogenesis.

Comparison of male chimeric mice generated from microinjection of JM8.N4 embryonic stem cells into C57BL/6J and C57BL/6NTac blastocysts.

PubMed

Fielder, Thomas J; Yi, Charles S; Masumi, Juliet; Waymire, Katrina G; Chen, Hsiao-Wen; Wang, Shuling; Shi, Kai-Xuan; Wallace, Douglas C; MacGregor, Grant R

2012-12-01

To identify ways to improve the efficiency of generating chimeric mice via microinjection of blastocysts with ES cells, we compared production and performance of ES-cell derived chimeric mice using blastocysts from two closely related and commonly used sub-strains of C57BL/6. Chimeras were produced by injection of the same JM8.N4 (C57BL/6NTac) derived ES cell line into blastocysts of mixed sex from either C57BL/6J (B6J) or C57BL/6NTac (B6NTac) mice. Similar efficiency of production and sex-conversion of chimeric animals was observed with each strain of blastocyst. However, B6J chimeric males had fewer developmental abnormalities involving urogenital and reproductive tissues (1/12, 8%) compared with B6NTac chimeric males (7/9, 78%). The low sample size did not permit determination of statistical significance for many parameters. However, in each category analyzed the B6J-derived chimeric males performed as well, or better, than their B6NTac counterparts. Twelve of 14 (86%) B6J male chimeras were fertile compared with 6 of 11 (55%) B6NTac male chimeras. Ten of 12 (83%) B6J chimeric males sired more than 1 litter compared with only 3 of 6 (50%) B6NTac chimeras. B6J male chimeras produced more litters per productive mating (3.42 ± 1.73, n = 12) compared to B6NTac chimeras (2.17 ± 1.33, n = 6). Finally, a greater ratio of germline transmitting chimeric males was obtained using B6J blastocysts (9/14; 64%) compared with chimeras produced using B6NTac blastocysts (4/11; 36%). Use of B6J host blastocysts for microinjection of ES cells may offer improvements over blastocysts from B6NTac and possibly other sub-strains of C57BL/6 mice.

Therapeutic efficacy of interleukin-2 activated killer cells against adriamycin resistant mouse B16-BL6 melanoma.

PubMed

Gautam, S C; Chikkala, N F; Lewis, I; Grabowski, D R; Finke, J H; Ganapathi, R

1992-01-01

Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells. Adriamycin (ADM) resistant B16-BL6 melanoma, L1210 and P388 leukemic cell lines were tested for sensitivity to lysis by LAK cells in vitro. While ADM-resistant B16-BL6 and L1210 sublines were found to exhibit at least 2-fold greater susceptibility to lysis by LAK cells, sensitivity of ADM-resistant P388 cell was similar to that of parental cells. Since ADM-resistant B16-BL6 cells were efficiently lysed by LAK cells in vitro, the efficacy of therapy with LAK cells against the ADM-resistant B16-BL6 subline in vivo was evaluated. Compared to mice bearing parental B16-BL6 tumor cells, the adoptive transfer of LAK cells and rIL2 significantly reduced formation of experimental metastases (P less than 0.009) and extended median survival time (P less than 0.001) of mice bearing ADM-resistant B16-BL6 tumor cells. Results suggest that immunotherapy with LAK cells and rIL2 may be a useful modality in the treatment of cancers with the MDR phenotype.

Total alkaloid content in various fractions of Tabernaemonata sphaerocarpa Bl. (Jembirit) leaves

NASA Astrophysics Data System (ADS)

Salamah, N.; Ningsih, D. S.

2017-11-01

Tabernaemontana sphaerocarpa Bl. (Jembirit) is one of the Apocynaceae family plants containing alkaloid compound. Traditionally, it is used as an anti-inflammatory medicine. It is found to have a new bisindole alkaloid compound that shows a potent cytotoxic activity in human cancer. This study aimed to know the total alkaloid content in some fractions of ethanolic extract of T. sphaerocarpa Bl. leaf powder was extracted by maceration method in 70% ethanol solvent. Then, the extract was fractionated in a separatory funnel using water, ethyl acetate, and hexane. The total alkaloid content in each fraction was analyzed with visible spectrophotometric methods based on the reaction with Bromocresol Green (BCG). The total alkaloids in water fraction and ethyl acetate fraction were (0.0312±0.0009)% and (0.0281±0.0014)%, respectively. Meanwhile, the total alkaloid content in hexane was not detected. The statistical analysis, performed in SPSS, resulted in a significant difference between the total alkaloids in water fraction and ethyl acetate fraction. The total alkaloid in water fraction of T. sphaerocarpa Bl. was higher than the one in ethyl acetate fraction.

Comparative physical mapping between wheat chromosome arm 2BL and rice chromosome 4.

PubMed

Lee, Tong Geon; Lee, Yong Jin; Kim, Dae Yeon; Seo, Yong Weon

2010-12-01

Physical maps of chromosomes provide a framework for organizing and integrating diverse genetic information. DNA microarrays are a valuable technique for physical mapping and can also be used to facilitate the discovery of single feature polymorphisms (SFPs). Wheat chromosome arm 2BL was physically mapped using a Wheat Genome Array onto near-isogenic lines (NILs) with the aid of wheat-rice synteny and mapped wheat EST information. Using high variance probe set (HVP) analysis, 314 HVPs constituting genes present on 2BL were identified. The 314 HVPs were grouped into 3 categories: HVPs that match only rice chromosome 4 (298 HVPs), those that match only wheat ESTs mapped on 2BL (1), and those that match both rice chromosome 4 and wheat ESTs mapped on 2BL (15). All HVPs were converted into gene sets, which represented either unique rice gene models or mapped wheat ESTs that matched identified HVPs. Comparative physical maps were constructed for 16 wheat gene sets and 271 rice gene sets. Of the 271 rice gene sets, 257 were mapped to the 18-35 Mb regions on rice chromosome 4. Based on HVP analysis and sequence similarity between the gene models in the rice chromosomes and mapped wheat ESTs, the outermost rice gene model that limits the translocation breakpoint to orthologous regions was identified.

Homoeologous cloning of omega-secalin gene family in a wheat 1BL/1RS translocation.

PubMed

Chai, Jian Fang; Liu, Xu; Jia, Ji Zeng

2005-08-01

Wheat 1BL/1RS translocations are widely planted in China as well as in most of the wheat producing area in the world for their good qualities of disease resistance and high yield. 1BL/1RS translocations are however poor in bread making, partially caused by a family of small monomeric proteins, omega-secalins, which are encoded by genes on 1RS. Based on published sequence of a rye omega-secalin gene we designed a pair of primers to cover the whole mature protein coding sequence. A major band could be amplified from 1BL/1RS translocations but not from euploid wheat. Using this primer set we conducted PCR amplification by using high fidelity Pfu polymerase on the genomic DNAs and cDNAs purified from a 1BL/1RS translocation Lankao 906. Sequencing analysis indicated that this gene family contains several members of 1150 bp, 1076 bp, 1075 bp, 1052 bp and 1004 bp genes, including two pseudogenes and three active genes. The gene transcripts were differentially expressed in developing seeds.

Crystal Structure of Crataeva tapia Bark Protein (CrataBL) and Its Effect in Human Prostate Cancer Cell Lines

PubMed Central

Ferreira, Joana Gasperazzo; Silva, Mariana Cristina Cabral; Silva-Lucca, Rosemeire Aparecida; Mentele, Reinhard; Paredes-Gamero, Edgar Julian; Bertolin, Thiago Carlos; dos Santos Correia, Maria Tereza; Paiva, Patrícia Maria Guedes; Gustchina, Alla; Wlodawer, Alexander; Oliva, Maria Luiza Vilela

2013-01-01

A protein isolated from the bark of Crataeva tapia (CrataBL) is both a Kunitz-type plant protease inhibitor and a lectin. We have determined the amino acid sequence and three-dimensional structure of CrataBL, as well as characterized its selected biochemical and biological properties. We found two different isoforms of CrataBL isolated from the original source, differing in positions 31 (Pro/Leu); 92 (Ser/Leu); 93 (Ile/Thr); 95 (Arg/Gly) and 97 (Leu/Ser). CrataBL showed relatively weak inhibitory activity against trypsin (Kiapp = 43 µM) and was more potent against Factor Xa (Kiapp = 8.6 µM), but was not active against a number of other proteases. We have confirmed that CrataBL contains two glycosylation sites and forms a dimer at high concentration. The high-resolution crystal structures of two different crystal forms of isoform II verified the β-trefoil fold of CrataBL and have shown the presence of dimers consisting of two almost identical molecules making extensive contacts (∼645 Å2). The structure differs from those of the most closely related proteins by the lack of the N-terminal β-hairpin. In experiments aimed at investigating the biological properties of CrataBL, we have shown that addition of 40 µM of the protein for 48 h caused maximum growth inhibition in MTT assay (47% of DU145 cells and 43% of PC3 cells). The apoptosis of DU145 and PC3 cell lines was confirmed by flow cytometry using Annexin V/FITC and propidium iodide staining. Treatment with CrataBL resulted in the release of mitochondrial cytochrome c and in the activation of caspase-3 in DU145 and PC3 cells. PMID:23823708

[Bridge role of Jingming (BL 1) for VDT asthenopia and brainfag based on human instinct].

PubMed

Zhang, Wei; Li, Huanan; Zhao, Na; Hai, Xinghua; Dong, Hua; Wang, Jingui

2017-01-12

To explore the bridge role of Jingming (BL 1) for video display terminal (VDT) asthenopia and brainfag. Ancient literature and modern scientific research on the acupoint have been analyzed and summarized so as to explore pressing the acupoint the instinct feedback of brain after asthenopia. It is demonstrated that Jingming (BL 1) is a key channel between eyes, brain and the outside world, and it is one of major feedback points of brain after asthenopia. In this paper we try to establish a new research thinking and ascertain it, namely Jingming (BL 1) reflecting the relationship between asthenopia and brainfag. We hope that it can provide some references for further research on cognizing brain through eye.

Probing BL Lac and Cluster Evolution via a Wide-angle, Deep X-ray Selected Sample

NASA Astrophysics Data System (ADS)

Perlman, E.; Jones, L.; White, N.; Angelini, L.; Giommi, P.; McHardy, I.; Wegner, G.

1994-12-01

The WARPS survey (Wide-Angle ROSAT Pointed Survey) has been constructed from the archive of all public ROSAT PSPC observations, and is a subset of the WGACAT catalog. WARPS will include a complete sample of >= 100 BL Lacs at F_x >= 10(-13) erg s(-1) cm(-2) . A second selection technique will identify ~ 100 clusters at 0.15BL Lacs are known and the largest complete samples are also small, with 20-50 objects each. Current data shows a discrepancy between XBL (X-ray selected BL Lac) and RBL (Radio-selected BL Lac) evolution, with = 0.304 +/- 0.062 for XBLs but = 0.60 +/- 0.05 for RBLs. Models of the X-ray luminosity function (XLF) are also poorly constrained. WARPS will allow us to compute an accurate XLF, decreasing the error bars above by over a factor of two. We will also test for low-luminosity BL Lacs, whose non-thermal nuclear sources are dim compared to the host galaxy. Browne and Marcha (1993) claim the EMSS missed most of these objects and is incomplete. If their predictions are correct, 20-40% of the BL Lacs we find will fall in this category, enabling us to probe the evolution and internal workings of BL Lacs at lower luminosities than ever before. By removing likely QSOs before optical spectroscopy, WARPS requires only modest amounts of telescope time. It will extend measurement of the cluster XLF both to higher redshifts (z>0.5) and lower luminosities (LX<1x10(44) erg s(-1) ) than previous measurements, confirming or rejecting the 3sigma detection of negative evolution found in the EMSS, and constraining Cold Dark Matter cosmologies. Faint NELGs are a recently discovered major contributor to the X-ray background. They are a mixture of Sy2s, starbursts and galaxies of unknown type. Detailed classification and evolution of their XLF will be determined for the first time.

X-Ray Spectral Variability Signatures of Flares in BL Lac Objects

NASA Technical Reports Server (NTRS)

Boettcher, Markus; Chiang, James; White, Nicholas E. (Technical Monitor)

2002-01-01

We are presenting a detailed parameter study of the time-dependent electron injection and kinematics and the self-consistent radiation transport in jets of intermediate and low-frequency peaked BL Lac objects. Using a time-dependent, combined synchrotron-self-Compton and external-Compton jet model, we study the influence of variations of several essential model parameters, such as the electron injection compactness, the relative contribution of synchrotron to external soft photons to the soft photon compactness, the electron- injection spectral index, and the details of the time profiles of the electron injection episodes giving rise to flaring activity. In the analysis of our results, we focus on the expected X-ray spectral variability signatures in a region of parameter space particularly well suited to reproduce the broadband spectral energy distributions of intermediate and low-frequency peaked BL Lac objects. We demonstrate that SSC- and external-Compton dominated models for the gamma-ray emission from blazars are producing significantly different signatures in the X-ray variability, in particular in the soft X-ray light curves and the spectral hysteresis at soft X-ray energies, which can be used as a powerful diagnostic to unveil the nature of the high-energy emission from BL Lac objects.

77 FR 1090 - Post Office Closing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-09

... POSTAL REGULATORY COMMISSION [Docket No. A2012-93; Order No. 1081] Post Office Closing AGENCY... the closing of the Odin, Minnesota post office has been filed. It identifies preliminary steps and... office in Odin, Minnesota. The first petition for review received November 30, 2011, was filed by Paul S...

DEVELOPMENTAL TOXICITY OF METHANOL: PATHOGENESIS IN CD-1 AND C57BL/6J MICE EXPOSED IN WHOLE EMBRYO CULTURE

EPA Science Inventory

BACKGROUND: Methanol causes axial skeleton and craniofacial defects in both CD-1 and C57BL/6J mice during gastrulation, but C57BL/6J embryos are more severely affected. We evaluated methanol-induced pathogenesis in CD-1 and C57BL/6J embryos exposed during gastrulation in whole em...

Hematopoietic Responses to Lipopolysaccharide in C57BL/10Sn and C57BL/10ScN Strain Mice

DTIC Science & Technology

1982-12-01

Responses of endogenous (E-CFU) stem cells as well as bone marrow and spleen-derived exogenous (CFU-s) stem cells, granulocyte-macrophage (GM;-CFC... endogenous (E-CFU) stem cells as well as bone marrow and spleen-derived exogenous (CFU-s) stem cells, granulocyte-macrophage (GM-CFC) and macrophage (M...IOScN in comparison to the normal C57BL/1OSn strain mice, as measured by endogenous (E-CFU) and exogenous (CFU-s) stem cells and committed granulocyte

New BVR Photometry of BL Camelopardalis

NASA Astrophysics Data System (ADS)

Joner, Michael D.

2015-01-01

New BVR photometry of the SX Phe star BL Camelopardalis has been secured with the 0.9 m reflector at the BYU West Mountain Observatory. The new data have been used to determine times of maximum light, standardize light curves in each of the three filters, and examine the frequencies that are currently detectable in the light curves from a single location.We acknowledge the Brigham Young University College of Physical and Mathematical Sciences as well as the Department of Physics and Astronomy for continued support of this and other research efforts currently being done at the West Mountain Observatory.

Interval Timing Accuracy and Scalar Timing in C57BL/6 Mice

PubMed Central

Buhusi, Catalin V.; Aziz, Dyana; Winslow, David; Carter, Rickey E.; Swearingen, Joshua E.; Buhusi, Mona C.

2010-01-01

In many species, interval timing behavior is accurate—appropriate estimated durations—and scalar—errors vary linearly with estimated durations. While accuracy has been previously examined, scalar timing has not been yet clearly demonstrated in house mice (Mus musculus), raising concerns about mouse models of human disease. We estimated timing accuracy and precision in C57BL/6 mice, the most used background strain for genetic models of human disease, in a peak-interval procedure with multiple intervals. Both when timing two intervals (Experiment 1) or three intervals (Experiment 2), C57BL/6 mice demonstrated varying degrees of timing accuracy. Importantly, both at individual and group level, their precision varied linearly with the subjective estimated duration. Further evidence for scalar timing was obtained using an intraclass correlation statistic. This is the first report of consistent, reliable scalar timing in a sizable sample of house mice, thus validating the PI procedure as a valuable technique, the intraclass correlation statistic as a powerful test of the scalar property, and the C57BL/6 strain as a suitable background for behavioral investigations of genetically engineered mice modeling disorders of interval timing. PMID:19824777

StagBL : A Scalable, Portable, High-Performance Discretization and Solver Layer for Geodynamic Simulation

NASA Astrophysics Data System (ADS)

Sanan, P.; Tackley, P. J.; Gerya, T.; Kaus, B. J. P.; May, D.

2017-12-01

StagBL is an open-source parallel solver and discretization library for geodynamic simulation,encapsulating and optimizing operations essential to staggered-grid finite volume Stokes flow solvers.It provides a parallel staggered-grid abstraction with a high-level interface in C and Fortran.On top of this abstraction, tools are available to define boundary conditions and interact with particle systems.Tools and examples to efficiently solve Stokes systems defined on the grid are provided in small (direct solver), medium (simple preconditioners), and large (block factorization and multigrid) model regimes.By working directly with leading application codes (StagYY, I3ELVIS, and LaMEM) and providing an API and examples to integrate with others, StagBL aims to become a community tool supplying scalable, portable, reproducible performance toward novel science in regional- and planet-scale geodynamics and planetary science.By implementing kernels used by many research groups beneath a uniform abstraction layer, the library will enable optimization for modern hardware, thus reducing community barriers to large- or extreme-scale parallel simulation on modern architectures. In particular, the library will include CPU-, Manycore-, and GPU-optimized variants of matrix-free operators and multigrid components.The common layer provides a framework upon which to introduce innovative new tools.StagBL will leverage p4est to provide distributed adaptive meshes, and incorporate a multigrid convergence analysis tool.These options, in addition to a wealth of solver options provided by an interface to PETSc, will make the most modern solution techniques available from a common interface. StagBL in turn provides a PETSc interface, DMStag, to its central staggered grid abstraction.We present public version 0.5 of StagBL, including preliminary integration with application codes and demonstrations with its own demonstration application, StagBLDemo. Central to StagBL is the notion of an

Junctional Adhesion Molecule (JAM)-C Deficient C57BL/6 Mice Develop a Severe Hydrocephalus

PubMed Central

Liebner, Stefan; Mittelbronn, Michel; Deutsch, Urban; Enzmann, Gaby; Adams, Ralf H.; Aurrand-Lions, Michel; Plate, Karl H.; Imhof, Beat A.; Engelhardt, Britta

2012-01-01

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C. PMID:23029139

Radio outburst of BL Lacertae

NASA Astrophysics Data System (ADS)

Buemi, C. S.; Leto, P.; Trigilio, C.; Umana, G.; Giroletti, M.; Orienti, M.; Raiteri, C. M.; Villata, M.; Bach, U.

2013-04-01

We report on extremely high radio flux of BL Lacertae at 43 and 8 GHz. Observations at 43 GHz with the 32 m radio telescope in Noto (Italy) revealed a flux density of 10.5 +/- 0.2 Jy on 2013 April 10.65, while observations at 8 GHz with the 32 m radio telescope in Medicina (Italy) detected a flux density of 8.2 +/- 0.7 Jy on April 12.22. These extremely high radio fluxes show that the radio activity likely correlated to the strong optical, near-infrared, and gamma-ray activity of 2011-2012 (see ATels #4028, #4031, #4155, #4271, #4277, #4349, #4565, #4600), and X-ray activity of late 2012 (ATels #4557, #4627), is far to be exhausted.

Soft X-Ray Observations of a Complete Sample of X-Ray--selected BL Lacertae Objects

NASA Astrophysics Data System (ADS)

Perlman, Eric S.; Stocke, John T.; Wang, Q. Daniel; Morris, Simon L.

1996-01-01

We present the results of ROSAT PSPC observations of the X-ray selected BL Lacertae objects (XBLs) in the complete Einstein Extended Medium Sensitivity Survey (EM MS) sample. None of the objects is resolved in their respective PSPC images, but all are easily detected. All BL Lac objects in this sample are well-fitted by single power laws. Their X-ray spectra exhibit a variety of spectral slopes, with best-fit energy power-law spectral indices between α = 0.5-2.3. The PSPC spectra of this sample are slightly steeper than those typical of flat ratio-spectrum quasars. Because almost all of the individual PSPC spectral indices are equal to or slightly steeper than the overall optical to X-ray spectral indices for these same objects, we infer that BL Lac soft X-ray continua are dominated by steep-spectrum synchrotron radiation from a broad X-ray jet, rather than flat-spectrum inverse Compton radiation linked to the narrower radio/millimeter jet. The softness of the X-ray spectra of these XBLs revives the possibility proposed by Guilbert, Fabian, & McCray (1983) that BL Lac objects are lineless because the circumnuclear gas cannot be heated sufficiently to permit two stable gas phases, the cooler of which would comprise the broad emission-line clouds. Because unified schemes predict that hard self-Compton radiation is beamed only into a small solid angle in BL Lac objects, the steep-spectrum synchrotron tail controls the temperature of the circumnuclear gas at r ≤ 1018 cm and prevents broad-line cloud formation. We use these new ROSAT data to recalculate the X-ray luminosity function and cosmological evolution of the complete EMSS sample by determining accurate K-corrections for the sample and estimating the effects of variability and the possibility of incompleteness in the sample. Our analysis confirms that XBLs are evolving "negatively," opposite in sense to quasars, with Ve/Va = 0.331±0.060. The statistically significant difference between the values for

Type II Cepheids: evidence for Na-O anticorrelation for BL Her type stars?

NASA Astrophysics Data System (ADS)

Kovtyukh, V.; Yegorova, I.; Andrievsky, S.; Korotin, S.; Saviane, I.; Lemasle, B.; Chekhonadskikh, F.; Belik, S.

2018-06-01

The chemical composition of 28 Population II Cepheids and one RR Lyrae variable has been studied using high-resolution spectra. The chemical composition of W Vir variable stars (with periods longer than 8 d) is typical for the halo and thick disc stars. However, the chemical composition of BL Her variables (with periods of 0.8-4 d) is drastically different, although it does not differ essentially from that of the stars belonging to globular clusters. In particular, the sodium overabundance ([Na/Fe] ≈ 0.4) is reported for most of these stars, and the Na-O anticorrelation is also possible. The evolutionary tracks for BL Her variables (with a progenitor mass value of 0.8 solar masses) indicate that mostly helium-overabundant stars (Y = 0.30-0.35) can fall into the instability strip region. We suppose that it is the helium overabundance that accounts not only for the existence of BL Her variable stars but also for the observed abnormalities in the chemical composition of this small group of pulsating variables.

ULTRAVIOLET SPECTROSCOPY OF BL Hyi AND EF Eri IN HIGH AND INTERMEDIATE STATES

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

Sanad, M. R.; Abdel-Sabour, M. A.

2016-08-01

We present the first phase-resolved ultraviolet spectroscopy of two polar systems, BL Hyi and EF Eri, in high and intermediate states from the International Ultraviolet Explorer ( IUE ) during the periods between 1982–1995 and 1979–1991, respectively. The flux curves for the C iv and He ii emission lines for both systems showing variations in their fluxes at different orbital phases are presented. The emission lines are produced in the accretion stream. The reddening for the two polars is found to be 0.00. Our results show that there are variations of the line fluxes with time, similar to the lightmore » curves found for both BL Hyi and EF Eri in the optical, infrared, ultraviolet, and X-ray bands. IUE observations support a radiative shock model of BL Hyi with the heating of matter by radiation from the accretion shock and cooling by the electrons scattering off ultraviolet photons from the surface of the white dwarf. EF Eri observations support a two-temperature white dwarf model producing sufficient ultraviolet flux for orbital modulations.« less

Functional Analysis of the Lactobacillus casei BL23 Sortases

PubMed Central

Muñoz-Provencio, Diego; Rodríguez-Díaz, Jesús; Collado, María Carmen; Langella, Philippe; Bermúdez-Humarán, Luis G.

2012-01-01

Sortases are a class of enzymes that anchor surface proteins to the cell wall of Gram-positive bacteria. Lactobacillus casei BL23 harbors four sortase genes, two belonging to class A (srtA1 and srtA2) and two belonging to class C (srtC1 and srtC2). Class C sortases were clustered with genes encoding their putative substrates that were homologous to the SpaEFG and SpaCBA proteins that encode mucus adhesive pili in Lactobacillus rhamnosus GG. Twenty-three genes encoding putative sortase substrates were identified in the L. casei BL23 genome with unknown (35%), enzymatic (30%), or adhesion-related (35%) functions. Strains disrupted in srtA1, srtA2, srtC1, and srtC2 and an srtA1 srtA2 double mutant were constructed. The transcription of all four sortase encoding genes was detected, but only the mutation of srtA1 resulted in a decrease in bacterial surface hydrophobicity. The β-N-acetyl-glucosaminidase and cell wall proteinase activities of whole cells diminished in the srtA1 mutant and, to a greater extent, in the srtA1 srtA2 double mutant. Cell wall anchoring of the staphylococcal NucA reporter protein fused to a cell wall sorting sequence was also affected in the srtA mutants, and the percentages of adhesion to Caco-2 and HT-29 intestinal epithelial cells were reduced for the srtA1 srtA2 strain. Mutations in srtC1 or srtC2 result in an undetectable phenotype. Together, these results suggest that SrtA1 is the housekeeping sortase in L. casei BL23 and SrtA2 would carry out redundant or complementary functions that become evident when SrtA1 activity is absent. PMID:23042174

Bl-1020, a new γ-aminobutyric acid-enhanced antipsychotic: results of 6-week, randomized, double-blind, controlled, efficacy and safety study.

PubMed

Geffen, Yona; Keefe, Richard; Rabinowitz, Jonathan; Anand, Ravi; Davidson, Michael

2012-09-01

BL-1020 is a γ-aminobutyric acid (GABA)-enhanced antipsychotic that combines dopamine antagonism with GABA agonist activity. On the basis of animal models, we tested the hypotheses that BL-1020 would be effective in ameliorating both psychotic symptoms and cognitive impairments, with a favorable safety profile in acutely ill schizophrenia patients. 363 hospital-based psychiatric patients in India, Romania, and United States aged 18 to 65 years and meeting criteria for DSM-IV-TR diagnosis of chronic schizophrenia were randomized double-blind to receive BL-1020 10 mg/d, BL-1020 20-30 mg/d, placebo, or risperidone (2-8 mg/d) for 6 weeks. The main outcome measures were the positive and negative syndrome scale (PANSS), brief assessment of cognition in schizophrenia, readiness for discharge questionnaire, clinical global impressions scale (CGI) , and extrapyramidal symptom rating scale. The study ran from July 2008 to June 2009. BL-1020 20-30 mg was significantly better than placebo on PANSS (P = .02) and CGI (P < .001) measurements, with no significant differences noted between BL-1020 20-30 mg and risperidone. There were no significant differences in the maximum change on extrapyramidal symptom rating scale between risperidone and BL-1020 20-30 mg, and both were significantly worse (P < .001) than placebo. BL-1020 20-30 mg was associated with significantly greater improvements on cognitive functioning as measured by the brief assessment of cognition in schizophrenia composite score when compared to placebo (effect size = 0.50, P = .009), risperidone (effect size = 0.43, P = .019), and BL-1020 10 mg (effect size = 0.42, P = .013) after 6 weeks. BL-1020 appears to be an effective antipsychotic with possible procognitive effects that will need to be further tested for short- and long-term effects. A further randomized controlled trial using the U.S. Food and Drug Administration-recommended Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive

Sterile neutrinos and B-L symmetry

NASA Astrophysics Data System (ADS)

Fileviez Pérez, Pavel; Murgui, Clara

2018-02-01

We revisit the relation between the neutrino masses and the spontaneous breaking of the B-L gauge symmetry. We discuss the main scenarios for Dirac and Majorana neutrinos and point out two simple mechanisms for neutrino masses. In this context the neutrino masses can be generated either at tree level or at quantum level and one predicts the existence of very light sterile neutrinos with masses below the eV scale. The predictions for lepton number violating processes such as μ → e and μ → eγ are discussed in detail. The impact from the cosmological constraints on the effective number of relativistic degree of freedom is investigated.

BALB/c and C57BL6 mouse strains vary in their ability to heal corneal epithelial debridement wounds

PubMed Central

Pal-Ghosh, Sonali; Tadvalkar, Gauri; Jurjus, Rosalyn A.; Zieske, James D.; Stepp, Mary Ann

2008-01-01

Genetically engineered mice are usually produced on a mixed genetic background and can be derived from several mouse strains including 129SvJ, C57BL6, and BALB/c. To determine whether differences in recurrent corneal epithelial erosions (RCEEs), corneal epithelial stem cell deficiency (CESCD), and cell migration rate vary between two different mouse strains (BALB/c and C57BL6), 8 week mice were subjected to 1.5 (small) or 2.8 mm (large) manual debridement wounds and allowed to heal for 4 weeks. Syndecan-1 (sdc-1) null mice backcrossed seven generations onto a BALB/c genetic background were also included in the RCEE and CESCD studies to permit comparisons between genotypes within a single strain. After sacrifice, corneas were assessed for the presence of recurrent erosions; no fewer than 15 corneas were used for each strain or genotype studied. Data show that the frequency of recurrent erosions after small wounds was 81 +/− 9% in the C57BL6 mice, 73 +/− 2% in the BALB/c mice, and 32 +/− 6% in sdc-1 null mice. Neither strain developed CESCD after small wounds. The frequency of erosions after large wounds was greater (88 +/− 8%) in the C57BL6 mice compared to BALB/c (60 +/− 2%), and sdc-1 null mice (32 +/− 5%). 4 weeks after the large wounds, fixed, flat mounted corneas were assessed for evidence of CESCD with antibodies against the conjunctival keratin K8 and the goblet cell marker, the mucin Muc5AC. The frequency of CESCD 4 weeks after the large wounds was significantly greater in the C57BL6 mice than in the BALB/c or sdc-1 null mice. To assess cell migration rates, corneas were subjected to 1.5 mm wounds and allowed to heal for 12, 15, 18, 21, and 24 hours. After sacrifice, corneas were stained with Richardson stain (BALB/c) or propidium iodide (C57BL6) to assess reepithelialization rates. While reepithelialization rates were similar for the early times after wounding, by 24 hours the C57BL6 corneas had healed faster: 16 of 30 corneas from the C57BL6

miR expression in MYC-negative DLBCL/BL with partial trisomy 11 is similar to classical Burkitt lymphoma and different from diffuse large B-cell lymphoma.

PubMed

Zajdel, Michalina; Rymkiewicz, Grzegorz; Chechlinska, Magdalena; Blachnio, Katarzyna; Pienkowska-Grela, Barbara; Grygalewicz, Beata; Goryca, Krzysztof; Cieslikowska, Maria; Bystydzienski, Zbigniew; Swoboda, Pawel; Walewski, Jan; Siwicki, Jan Konrad

2015-07-01

Fast and reliable differential diagnosis of Burkitt lymphoma (BL) vs. diffuse large B cell lymphoma (DLBCL) is of major importance for therapeutic decisions and patient outcome. Aggressive B cell non-Hodgkin lymphomas (B-NHLs) that do not belong to the abovementioned entities were categorized by the current WHO lymphoma classification as "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (DLBCL/BL). We have recently described a DLBCL/BL subgroup with recurrent chromosome 11q aberrations, resembling BL (B-NHLs[11q]). Here, we analyzed 102 prospectively collected fine needle aspirates from patients with aggressive B-NHLs in order to investigate the potential of microRNA (miR)-155, its precursor BIC, as well as miR-21 and miR-26a to differentiate BL from DLBCL, and from DLBCL/BL that include B-NHLs[11q]. Both BL and DLBCL/BL cases, including B-NHLs[11q], demonstrated significantly lower expression levels of miR-155/BIC, miR-21, and miR-26a compared to primary DLBCL. In conclusion, the miRs expression in B-NHLs[11q] provides a new suggestion, in addition to pathomorphological and clinical similarities between classical, i.e., MYC translocation-positive BL, and B-NHLs[11q], to recognize the B-NHLs[11q] subgroup of DLBCL/BL category as a MYC translocation-negative variant of BL in most cases, and points to the potential utility of miR-155/BIC/miR-21/miR-26a for the differential diagnosis of a heterogeneous category of DLBCL/BL.

Stellar Populations in BL Lac type Objects

NASA Astrophysics Data System (ADS)

Serote Roos, Margarida

The relationship between an Active Galactic Nucleus (AGN) and its host galaxy is a crucial question in the study of galaxy evolution. We present an estimate of the stellar contribution in a sample of low luminosity BL Lac type objects. We have performed stellar population synthesis for a sample of 19 objects selected from Marchã et al. (1996, MNRAS 281, 425). The stellar content is quantified using the equivalent widths of all absorption features available throughout the spectrum. The synthesis is done by a variant of the GPG method (Pelat: 1997, MNRAS 284, 365).

BL Lacertae Objects Beyond Redshift 1.3 - UV-to-NIR Photometry and Photometric Redshift for Fermi/LAT Blazars

NASA Technical Reports Server (NTRS)

Rau, A.; Schady, P.; Greiner, J.; Salvato, M.; Ajello, M.; Bottacini, E.; Gehrels, N.; Afonso, P. M. J.; Elliott, J.; Filgas, R.;

Competition in Defense Acquisitions

DTIC Science & Technology

2008-05-14

NASA employees to maintain desktop assets No way to track costs, no standardization, not tracking service quality NASA’s Outsourcing Desktop...assets to the private sector. ODIN Goals Cut desktop computing costs Increase service quality Achieve interoperability and standardization Focus...not tracking service quality NASA’s Outsourcing Desktop Initiative (ODIN) transferred the responsibility for providing and managing the vast

Constraining the red shifts of TeV BL Lac objects

NASA Astrophysics Data System (ADS)

Qin, Longhua; Wang, Jiancheng; Yan, Dahai; Yang, Chuyuan; Yuan, Zunli; Zhou, Ming

2018-01-01

We present a model-dependent method to estimate the red shifts of three TeV BL Lac objects (BL Lacs) through fitting their (quasi-)simultaneous multi-waveband spectral energy distributions (SEDs) with a one-zone leptonic synchrotron self-Compton model. Considering the impact of electron energy distributions (EEDs) on the results, we use three types of EEDs to fit the SEDs: a power-law EED with exponential cut-off (PLC), a log-parabola (PLLP) EED and the broken power-law (BPL) EED. We also use a parameter α to describe the uncertainties of the extragalactic background light models, as in Abdo et al. We then use a Markov chain Monte Carlo method to explore the multi-dimensional parameter space and obtain the uncertainties of the model parameters based on the observational data. We apply our method to obtain the red shifts of three TeV BL Lac objects in the marginalized 68 per cent confidence, and find that the PLC EED does not fit the SEDs. For 3C66A, the red shift is 0.14-0.31 and 0.16-0.32 in the BPL and PLLP EEDs. For PKS1424+240, the red shift is 0.55-0.68 and 0.55-0.67 in the BPL and PLLP EEDs. For PG1553+113, the red shift is 0.22-0.48 and 0.22-0.39 in the BPL and PLLP EEDs. We also estimate the red shift of PKS1424+240 in the high stage to be 0.46-0.67 in the PLLP EED, roughly consistent with that in the low stage.

Inhibition of the metastatic spread and growth of B16-BL6 murine melanoma by a synthetic matrix metalloproteinase inhibitor.

PubMed

Chirivi, R G; Garofalo, A; Crimmin, M J; Bawden, L J; Stoppacciaro, A; Brown, P D; Giavazzi, R

1994-08-01

The synthetic matrix metalloproteinase inhibitor batimastat was tested for its ability to inhibit growth and metastatic spread of the B16-BL6 murine melanoma in syngeneic C57BL/6N mice. Intraperitoneal administration of batimastat resulted in a significant inhibition in the number of lung colonies produced by B16-BL6 cells injected i.v. The effect of batimastat on spontaneous metastases was examined in mice inoculated in the hind footpad with B16-BL6 melanoma. The primary tumor was removed surgically after 26-28 days. Batimastat was administered twice a day from day 14 to day 28 (pre-surgery) or from day 26 to day 44 (post-surgery). With both protocols, the median number of lung metastases was not significantly affected, but there was a significant reduction in the weight of the metastases. Finally, the effect of batimastat was examined on s.c. growth of B16-BL6 melanoma. Batimastat administered daily, starting at day of tumor transplantation, resulted in a significant growth delay, whereas treatment starting at advanced stage tumor only reduced tumor growth marginally. Our results indicate that a matrix metalloproteinase inhibitor can not only prevent the colonization of secondary organs by B16-BL6 cells but also limit the growth of solid tumors.

Temporal characteristics of stress-induced decrease in benzodiazepine reception in C57BL/6 and BALB/c mice.

PubMed

Yarkova, M A; Seredenin, S B

2014-10-01

We studied the duration of the drop of specific (3)H-flunitrazepam binding by synaptosomal membranes from the brain of C57Bl/6 and BALB/c mice after open-field and "contact with predator" tests. It was found that reduced benzodiazepine reception in BALB/c mice after open-field test persisted for 1.5 h, but no changes of this parameter were found in C57Bl/6 mice. After contact with predator, the binding capacity of the benzodiazepine site of GABAA receptor was reduced for 8 h in BALB/c mice and for 24 h in C57Bl/6 mice.

A Novel Halophilic Lipase, LipBL, Showing High Efficiency in the Production of Eicosapentaenoic Acid (EPA)

PubMed Central

Pérez, Dolores; Martín, Sara; Fernández-Lorente, Gloria; Filice, Marco; Guisán, José Manuel; Ventosa, Antonio; García, María Teresa; Mellado, Encarnación

2011-01-01

Background Among extremophiles, halophiles are defined as microorganisms adapted to live and thrive in diverse extreme saline environments. These extremophilic microorganisms constitute the source of a number of hydrolases with great biotechnological applications. The interest to use extremozymes from halophiles in industrial applications is their resistance to organic solvents and extreme temperatures. Marinobacter lipolyticus SM19 is a moderately halophilic bacterium, isolated previously from a saline habitat in South Spain, showing lipolytic activity. Methods and Findings A lipolytic enzyme from the halophilic bacterium Marinobacter lipolyticus SM19 was isolated. This enzyme, designated LipBL, was expressed in Escherichia coli. LipBL is a protein of 404 amino acids with a molecular mass of 45.3 kDa and high identity to class C β-lactamases. LipBL was purified and biochemically characterized. The temperature for its maximal activity was 80°C and the pH optimum determined at 25°C was 7.0, showing optimal activity without sodium chloride, while maintaining 20% activity in a wide range of NaCl concentrations. This enzyme exhibited high activity against short-medium length acyl chain substrates, although it also hydrolyzes olive oil and fish oil. The fish oil hydrolysis using LipBL results in an enrichment of free eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), relative to its levels present in fish oil. For improving the stability and to be used in industrial processes LipBL was immobilized in different supports. The immobilized derivatives CNBr-activated Sepharose were highly selective towards the release of EPA versus DHA. The enzyme is also active towards different chiral and prochiral esters. Exposure of LipBL to buffer-solvent mixtures showed that the enzyme had remarkable activity and stability in all organic solvents tested. Conclusions In this study we isolated, purified, biochemically characterized and immobilized a lipolytic enzyme from

The Lcn972 Bacteriocin-Encoding Plasmid pBL1 Impairs Cellobiose Metabolism in Lactococcus lactis▿

PubMed Central

Campelo, Ana B.; Gaspar, Paula; Roces, Clara; Rodríguez, Ana; Kok, Jan; Kuipers, Oscar P.; Neves, Ana Rute; Martínez, Beatriz

2011-01-01

pBL1 is a Lactococcus lactis theta-replicating 10.9-kbp plasmid that encodes the synthetic machinery of the bacteriocin Lcn972. In this work, the transcriptomes of exponentially growing L. lactis strains with and without pBL1 were compared. A discrete response was observed, with a total of 10 genes showing significantly changed expression. Upregulation of the lactococcal oligopeptide uptake (opp) system was observed, which was likely linked to a higher nitrogen demand required for Lcn972 biosynthesis. Strikingly, celB, coding for the membrane porter IIC of the cellobiose phosphoenolpyruvate-dependent phosphotransferase system (PTS), and the upstream gene llmg0186 were downregulated. Growth profiles for L. lactis strains MG1363, MG1363/pBL1, and MG1363 ΔcelB grown in chemically defined medium (CDM) containing cellobiose confirmed slower growth of MG1363/pBL1 and MG1363 ΔcelB, while no differences were observed with growth on glucose. The presence of pBL1 shifted the fermentation products toward a mixed acid profile and promoted substantial changes in intracellular pool sizes for glycolytic intermediates in cells growing on cellobiose as determined by high-pressure liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Overall, these data support the genetic evidence of a constriction in cellobiose uptake. Notably, several cell wall precursors accumulated, while other UDP-activated sugar pools were lower, which could reflect rerouting of precursors toward the production of structural or storage polysaccharides. Moreover, cells growing slowly on cellobiose and those lacking celB were more tolerant to Lcn972 than cellobiose-adapted cells. Thus, downregulation of celB could help to build up a response against the antimicrobial activity of Lcn972, enhancing self-immunity of the producer cells. PMID:21890668

Radio morphology and parent population of X-ray selected BL Lacertae objects

NASA Technical Reports Server (NTRS)

Laurent-Muehleisen, S. A.; Kollgaard, R. I.; Moellenbrock, G. A.; Feigelson, E. D.

1993-01-01

High-dynamic range (typically 1700:1) radio maps of 15 X-ray BL Lac (XBL) objects from the HEAO-1 Large Area Sky Survey are presented. Morphological characteristics of these sources are compared with Fanaroff-Riley (FR) class I radio galaxies in the context of unified schemes, with reference to one-sided kiloparsec-scale emission. Evidence that cluster membership of XBLs is significantly higher than previously thought is also presented. It is shown that the extended radio powers, X-ray emission, core-to-lobe ratios, and linear sizes of the radio selected BL Lac (RBL) and XBL populations are consistent with an FR I radio galaxy parent population. A source list and VLA observing log and map parameters are provided.

Potential of the Lectin/Inhibitor Isolated from Crataeva tapia Bark (CrataBL) for Controlling Callosobruchus maculatus Larva Development.

PubMed

Nunes, Natalia N S; Ferreira, Rodrigo S; Silva-Lucca, Rosemeire A; de Sá, Leonardo F R; de Oliveira, Antônia Elenir A; Correia, Maria Tereza dos S; Paiva, Patrícia Maria G; Wlodawer, Alexander; Oliva, Maria Luiza V

2015-12-09

Callosobruchus maculatus is an important predator of cowpeas. Due to infestation during storage, this insect affects the quality of seed and crop yield. This study aimed to investigate the effects of CrataBL, a multifunction protein isolated from Crataeva tapia bark, on C. maculatus larva development. The protein, which is stable even in extreme pH conditions, showed toxic activity, reducing the larval mass 45 and 70% at concentrations of 0.25 and 1.0% (w/w), respectively. Acting as an inhibitor, CrataBL decreased by 39% the activity of cysteine proteinases from larval gut. Conversely, the activity of serine proteinases was increased about 8-fold. The toxic properties of CrataBL may also be attributed to its capacity of binding to glycoproteins or glycosaminoglycans. Such binding interferes with larval metabolism, because CrataBL-FITC was found in the fat body, Malpighian tubules, and feces of larvae. These results demonstrate the potential of this protein for controlling larva development.

Ulcerative Dermatitis in C57BL/6 Mice Exhibits an Oxidative Stress Response Consistent with Normal Wound Healing

PubMed Central

Williams, Lisa K; Csaki, Lauren S; Cantor, Rita M; Reue, Karen; Lawson, Greg W

2012-01-01

Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds. PMID:22776048

A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells.

PubMed

Ito, Akihiko; Morita, Nobuyoshi; Miura, Daisaku; Koma, Yu-Ichiro; Kataoka, Tatsuki R; Yamasaki, Hiroshi; Kitamura, Yukihiko; Kita, Yasuyuki; Nojima, Hiroshi

2004-10-01

We reported previously that the abnormally augmented expression of connexin 26 (Cx26) is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells, and that the exogenous expression of a dominant negative form of Cx26 inhibits the spontaneous metastasis of BL6. Here we show that daily intraperitoneal (i.p.) injections of oleamide, a sleep-inducing lipid hormone, weakly inhibited the spontaneous metastasis of BL6 cells. To obtain a more effective reagent, 19 oleamide derivatives were chemically synthesized and tested for their ability to inhibit the gap junction-mediated intercellular communications (GJIC) that are formed between HeLa cells by the ectopic expression of Cx26 or Cx43. One of these, denoted metastasis inhibitor-18 (MI-18), inhibited the GJIC formed by Cx26 as well as oleamide but unlike oleamide, which is a non-selective inhibitor of connexin, it did not inhibit the GJIC formed by Cx43. Daily i.p. injections of MI-18 potently blocked the spontaneous metastasis of BL6 cells down to 15% of that in the untreated control mice. MI-18 was safe because even after >7 weeks of daily injections, the survival rate of the mice was 93%. We propose that MI-18 may serve as a novel and clinically important prototype of a potent inhibitor of spontaneous metastasis.

Surface and interface analysis of nanomaterials at microfocus beamline (BL-16) of Indus-2

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

Das, Gangadhar, E-mail: rnrrsgangadhar@gmail.com; Tiwari, M. K., E-mail: mktiwati@rrcat.gov.in; Homi Bhabha National Institute, RRCAT

2016-05-06

Analysis of chemical nature and electronic structure at the interface of a thin film medium is important in many technological applications as well as to understand overall efficiency of a thin film device. Synchrotron radiation based x-ray spectroscopy is a promising technique to study interface nature of the nanomaterials with atomic resolutions. A combined x-ray reflectivity and grazing incidence x-ray fluorescence measurement facility has been recently constructed at the BL-16 microfocus beamline of Indus-2 synchrotron facility to accomplish surface-interface microstructural characterization of thin layered materials. It is also possible to analyze contaminates or adsorbed ad-atoms on the surface of themore » thin nanostructure materials. The BL-16 beamline also provides an attractive platform to perform a variety of analytical research activities especially in the field of micro x-ray fluorescence and ultra-trace elements analysis using Synchrotron radiation. We describe various salient features of the BL-16 reflectometer experimental station and the detailed description of its capabilities through the measured results, obtained for various thin layered nanomaterials.« less

The mass spectra, hierarchy and cosmology of B-L MSSM heterotic compactifications

DOE PAGES

Ambroso, Michael; Ovrut, Burt A.

2011-04-10

The matter spectrum of the MSSM, including three right-handed neutrino supermultiplets and one pair of Higgs-Higgs conjugate superfields, can be obtained by compactifying the E₈ x E₈ heterotic string and M-theory on Calabi-Yau manifolds with specific SU(4) vector bundles. These theories have the standard model gauge group augmented by an additional gauged U(1) B-L. Their minimal content requires that the B-L gauge symmetry be spontaneously broken by a vacuum expectation value of at least one right-handed neutrino. In previous papers, we presented the results of a quasi-analytic renormalization group analysis showing that B-L gauge symmetry is indeed radiatively broken withmore » an appropriate B-L/electroweak hierarchy. In this paper, we extend these results by 1) enlarging the initial parameter space and 2) explicitly calculating all renormalization group equations numerically. The regions of the initial parameter space leading to realistic vacua are presented and the B-L/electroweak hierarchy computed over these regimes. At representative points, the mass spectrum for all particles and Higgs fields is calculated and shown to be consistent with present experimental bounds. Some fundamental phenomenological signatures of a non-zero right-handed neutrino expectation value are discussed, particularly the cosmology and proton lifetime arising from induced lepton and baryon number violating interactions.« less

Effects of electroacupuncture at BL33 on detrusor smooth muscle activity in a rat model of urinary retention.

PubMed

Liu, Xiaoxu; Liu, Kun; Zhi, Mujun; Mo, Qian; Gao, Xinyan; Liu, Zhishun

2017-12-01

Detrusor smooth muscle (DSM) underactivity may lead to urinary retention (UR). Electroacupuncture (EA) at BL33 may be effective in improving DSM contractions. This study aimed to investigate: (1) the effect of EA at BL33; and (2) the effect of different manipulation methods at BL33 on the modulation of DSM contractions in UR rats. 30 male Sprague-Dawley rats were anaesthetised with urethane and modelled by urethral outlet obstruction. First, 2 Hz EA at BL33, SP6 and LI4 wasrandomly applied to the UR rats for 5 min to observe the immediate effects (n=10); second, manual acupuncture (MA) (n=10) and 100 Hz EA (n=10) were applied with the same programme. DSM electromyography (EMG) and cystometrogram data were evaluated. (1) 2 Hz EA at BL33 and SP6 significantly increased DSM discharging frequency (0.80±0.10 Hz, P<0.001, and 0.22±0.14 Hz, P=0.038), shortened micturation intervals (65.67±20.65 s, P=0.008, and 35.62±15.84 s, P=0.042), prolonged the duration of voiding (2.13±0.61 s, P=0.005, and 0.47±0.16 s, P=0.015), and reduced residual pressure (-0.91±0.31 mmHg, P=0.019, and -0.66±0.27 mmHg, P=0.046). EA at LI4 was not associated with any functional effects (P>0.05). Compared with SP6, EA at BL33 had greater positive effects on DSM discharging frequency, duration of discharging, and duration of voiding (all P<0.05). (2) No statistically significant differences were shown between MA, 2 Hz EA and 100 Hz EA interventions when stimulating at BL33, SP6 or LI4. EA at BL33 improved DSM contractions to a greater degree than EA at SP6 or LI4. There were no differences in effect when stimulating using 2 Hz EA, 100 Hz EA and MA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cat odor exposure induces distinct changes in the exploratory behavior and Wfs1 gene expression in C57Bl/6 and 129Sv mice.

PubMed

Raud, Sirli; Sütt, Silva; Plaas, Mario; Luuk, Hendrik; Innos, Jürgen; Philips, Mari-Anne; Kõks, Sulev; Vasar, Eero

2007-10-16

129Sv and C57Bl/6 (Bl6) strains are two most widely used inbred mice strains for generation of transgenic animals. The present study confirms the existence of substantial differences in the behavior of these two mice strains. The exploratory behavior of Bl6 mice in a novel environment was significantly higher compared to 129Sv mice. The exposure of mice to cat odor-induced an anxiety-like state in Bl6, but not in 129Sv mice. The levels of Wfs1 gene expression did not differ in the prefrontal cortex, mesolimbic area and temporal lobe of experimentally naive Bl6 and 129Sv mice. However, after cat odor exposure the expression of Wfs1 gene was significantly lower in the mesolimbic area and temporal lobe of Bl6 mice compared to 129Sv strain. Dynamics of Wfs1 gene expression and exploratory behavior suggest that the down-regulation of Wfs1 gene in Bl6 mice might be related to the increased anxiety. Further studies are needed to test the robustness and possible causal relationship of this finding.

Optimization and Validation of the TZM-bl Assay for Standardized Assessments of Neutralizing Antibodies Against HIV-1

PubMed Central

Sarzotti-Kelsoe, Marcella; Bailer, Robert T; Turk, Ellen; Lin, Chen-li; Bilska, Miroslawa; Greene, Kelli M.; Gao, Hongmei; Todd, Christopher A.; Ozaki, Daniel A.; Seaman, Michael S.; Mascola, John R.; Montefiori, David C.

2014-01-01

The TZM-bl assay measures antibody-mediated neutralization of HIV-1 as a function of reductions in HIV-1 Tat-regulated firefly luciferase (Luc) reporter gene expression after a single round of infection with Env-pseudotyped viruses. This assay has become the main endpoint neutralization assay used for the assessment of preclinical and clinical trial samples by a growing number of laboratories worldwide. Here we present the results of the formal optimization and validation of the TZM-bl assay, performed in compliance with Good Clinical Laboratory Practice (GCLP) guidelines. The assay was evaluated for specificity, accuracy, precision, limits of detection and quantitation, linearity, range and robustness. The validated manual TZM-bl assay was also adapted, optimized and qualified to an automated 384-well format. PMID:24291345

Advanced Structural Optimization Under Consideration of Cost Tracking

NASA Astrophysics Data System (ADS)

Zell, D.; Link, T.; Bickelmaier, S.; Albinger, J.; Weikert, S.; Cremaschi, F.; Wiegand, A.

2014-06-01

In order to improve the design process of launcher configurations in the early development phase, the software Multidisciplinary Optimization (MDO) was developed. The tool combines different efficient software tools such as Optimal Design Investigations (ODIN) for structural optimizations, Aerospace Trajectory Optimization Software (ASTOS) for trajectory and vehicle design optimization for a defined payload and mission.The present paper focuses to the integration and validation of ODIN. ODIN enables the user to optimize typical axis-symmetric structures by means of sizing the stiffening designs concerning strength and stability while minimizing the structural mass. In addition a fully automatic finite element model (FEM) generator module creates ready-to-run FEM models of a complete stage or launcher assembly.Cost tracking respectively future improvements concerning cost optimization are indicated.

Numerical study of Tallinn storm-water system flooding conditions using CFD simulations of multi-phase flow in a large-scale inverted siphon

NASA Astrophysics Data System (ADS)

Kaur, K.; Laanearu, J.; Annus, I.

2017-10-01

The numerical experiments are carried out for qualitative and quantitative interpretation of a multi-phase flow processes associated with malfunctioning of the Tallinn storm-water system during rain storms. The investigations are focused on the single-line inverted siphon, which is used as under-road connection of pipes of the storm-water system under interest. A multi-phase flow solver of Computational Fluid Dynamics software OpenFOAM is used for simulating the three-phase flow dynamics in the hydraulic system. The CFD simulations are performed with different inflow rates under same initial conditions. The computational results are compared essentially in two cases 1) design flow rate and 2) larger flow rate, for emptying the initially filled inverted siphon from a slurry-fluid. The larger flow-rate situations are under particular interest to detected possible flooding. In this regard, it is anticipated that the CFD solutions provide an important insight to functioning of inverted siphon under a restricted water-flow conditions at simultaneous presence of air and slurry-fluid.

Immunobiologic effects of cytokine gene transfer of the B16-BL6 melanoma.

PubMed

Strome, S E; Krauss, J C; Cameron, M J; Forslund, K; Shu, S; Chang, A E

1993-12-01

The genetic modification of tumors offers an approach to modulate the host immune response to relatively weak native tumor antigens. We examined the immunobiologic effects of various cytokine genes transferred into the poorly immunogenic B16-BL6 murine melanoma. Retroviral expression vectors containing cDNAs for interleukin 2, interleukin 4, interferon gamma, or a neomycin-resistant control were electroporated into a B16-BL6 tumor clone. Selected transfected clones were examined for in vitro cytokine secretion and in vivo tumorigenicity. When cells from individual clones were injected intradermally into syngeneic mice, the interleukin 4-secreting clone grew significantly slower than did the neomycin-resistant transfected control, while the growth of the interleukin 2- and interferon gamma-expressing clones was not affected. Despite minimal cytokine secretion by interferon gamma-transfected cells, these cells expressed upregulated major histocompatibility class I antigen and were more susceptible to lysis by allosensitized cytotoxic T lymphocytes compared with parental or neomycin-resistant transfected tumor targets. We observed diverse immunobiologic effects associated with cytokine gene transfer into the B16-BL6 melanoma. Interleukin 4 transfection of tumor resulted in decreased in vivo tumorigenicity that may be related to a host immune response. Further studies to evaluate the host T-cell response to these gene-modified tumors are being investigated.

Protein crystallography beamline BL2S1 at the Aichi synchrotron

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

Watanabe, Nobuhisa; Nagae, Takayuki; Yamada, Yusuke

The protein crystallography beamline BL2S1, constructed at one of the 5 T superconducting bending-magnet ports of the Aichi synchrotron, is available to users associated with academic and industrial organizations. The beamline is mainly intended for use in X-ray diffraction measurements of single-crystals of macromolecules such as proteins and nucleic acids. Diffraction measurements for crystals of other materials are also possible, such as inorganic and organic compounds. BL2S1 covers the energy range 7–17 keV (1.8–0.7 Å) with an asymmetric-cut curved single-crystal monochromator [Ge(111) or Ge(220)], and a platinum-coated Si mirror is used for vertical focusing and as a higher-order cutoff filter.more » The beamline is equipped with a single-axis goniometer, a CCD detector, and an open-flow cryogenic sample cooler. Lastly, high-pressure protein crystallography with a diamond anvil cell can also be performed using this beamline.« less

Protein crystallography beamline BL2S1 at the Aichi synchrotron.

PubMed

Watanabe, Nobuhisa; Nagae, Takayuki; Yamada, Yusuke; Tomita, Ayana; Matsugaki, Naohiro; Tabuchi, Masao

2017-01-01

The protein crystallography beamline BL2S1, constructed at one of the 5 T superconducting bending-magnet ports of the Aichi synchrotron, is available to users associated with academic and industrial organizations. The beamline is mainly intended for use in X-ray diffraction measurements of single-crystals of macromolecules such as proteins and nucleic acids. Diffraction measurements for crystals of other materials are also possible, such as inorganic and organic compounds. BL2S1 covers the energy range 7-17 keV (1.8-0.7 Å) with an asymmetric-cut curved single-crystal monochromator [Ge(111) or Ge(220)], and a platinum-coated Si mirror is used for vertical focusing and as a higher-order cutoff filter. The beamline is equipped with a single-axis goniometer, a CCD detector, and an open-flow cryogenic sample cooler. High-pressure protein crystallography with a diamond anvil cell can also be performed using this beamline.

Antimetastatic effect of PSK, a protein-bound polysaccharide, against the B16-BL6 mouse melanoma.

PubMed

Matsunaga, K; Ohhara, M; Oguchi, Y; Iijima, H; Kobayashi, H

1996-01-01

We examined the effect of PSK, a protein-bound polysaccharide, upon in vivo metastasis and in vitro invasion of the B16-BL6 mouse melanoma cells. (1) PSK suppressed in vivo artificial and spontaneous lung metastases of B16-BL6 in C57BL/6 mice. (2) PSK in a dose-dependent fashion suppressed in vitro invasion and chemotaxis of the tumor cells using filters coated with a reconstituted basement membrane. (3) PSK had little effect on DNA synthesis in tumor cells in vitro, but suppressed tumor cell adhesion to, degradation of, and haptotaxis to components of the basement membrane. (4) PSK suppressed the binding of tumor cells to components of the basement membrane. These findings suggest that PSK may suppress metastasis through inhibition of tumor cell invasion and that this effect is the result of interactions between PSK and components of the basement membrane.

Very high energy observations of the BL Lac objects 3C 66A and OJ 287

NASA Astrophysics Data System (ADS)

Lindner, T.; Hanna, D. S.; Kildea, J.; Ball, J.; Bramel, D. A.; Carson, J.; Covault, C. E.; Driscoll, D.; Fortin, P.; Gingrich, D. M.; Jarvis, A.; Mueller, C.; Mukherjee, R.; Ong, R. A.; Ragan, K.; Scalzo, R. A.; Williams, D. A.; Zweerink, J.

2007-11-01

Using the Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE), we have observed the BL Lac objects 3C 66A and OJ 287. These are members of the class of low-frequency-peaked BL Lac objects (LBLs) and are two of the three LBLs predicted by Costamante and Ghisellini [L. Costamante, G. Ghisellini, Astron. Astrophys. 384 (2002) 56] to be potential sources of very high energy (>100 GeV) gamma-ray emission. The third candidate, BL Lacertae, has recently been detected by the MAGIC collaboration [J. Albert et al., arXiv:astro-ph/0703084v1 (2007)]. Our observations have not produced detections; we calculate a 99% CL upper limit of flux from 3C 66A of 0.15 Crab flux units and from OJ 287 our limit is 0.52 Crab. These limits assume a Crab-like energy spectrum with an effective energy threshold of 185 GeV.

Host galaxy and environment of the BL Lacertae object PKS 0548-322: Observations with subarcsecond resolution

NASA Technical Reports Server (NTRS)

Falomo, Renato; Pesce, Joseph E.; Treves, Aldo

1995-01-01

We report on direct, subarcsecond resolution imaging of the nebulosity and spectroscopy of galaxies in the field of the BL Lacertae object PKS 0548-322. Surface photometry of the nebulosity is used to derive the properties of the host galaxy (M(sub V) = -23.4), which exhibits signs of interaction with a close companion galaxy at approximately 25 kpc. The radial brightness profile of the nebulosity is well fitted by the contribution of a bulge (r(exp 1/4)) plus a point source and a small internal disk. An analysis of the galaxies in the field shows that the source is located in a rich cluster of galaxies. Spectra of five galaxies in the field indicate that they are at the same redshift as the BL Lac object, thus supporting the imaging result of a surrounding cluster associated with the BL Lac. This cluster is most likely Abell S0549.

Efficient gene-driven germ-line point mutagenesis of C57BL/6J mice

PubMed Central

Michaud, Edward J; Culiat, Cymbeline T; Klebig, Mitchell L; Barker, Paul E; Cain, KT; Carpenter, Debra J; Easter, Lori L; Foster, Carmen M; Gardner, Alysyn W; Guo, ZY; Houser, Kay J; Hughes, Lori A; Kerley, Marilyn K; Liu, Zhaowei; Olszewski, Robert E; Pinn, Irina; Shaw, Ginger D; Shinpock, Sarah G; Wymore, Ann M; Rinchik, Eugene M; Johnson, Dabney K

2005-01-01

Background Analysis of an allelic series of point mutations in a gene, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, is a valuable method for discovering the full scope of its biological function. Here we present an efficient gene-driven approach for identifying ENU-induced point mutations in any gene in C57BL/6J mice. The advantage of such an approach is that it allows one to select any gene of interest in the mouse genome and to go directly from DNA sequence to mutant mice. Results We produced the Cryopreserved Mutant Mouse Bank (CMMB), which is an archive of DNA, cDNA, tissues, and sperm from 4,000 G1 male offspring of ENU-treated C57BL/6J males mated to untreated C57BL/6J females. Each mouse in the CMMB carries a large number of random heterozygous point mutations throughout the genome. High-throughput Temperature Gradient Capillary Electrophoresis (TGCE) was employed to perform a 32-Mbp sequence-driven screen for mutations in 38 PCR amplicons from 11 genes in DNA and/or cDNA from the CMMB mice. DNA sequence analysis of heteroduplex-forming amplicons identified by TGCE revealed 22 mutations in 10 genes for an overall mutation frequency of 1 in 1.45 Mbp. All 22 mutations are single base pair substitutions, and nine of them (41%) result in nonconservative amino acid substitutions. Intracytoplasmic sperm injection (ICSI) of cryopreserved spermatozoa into B6D2F1 or C57BL/6J ova was used to recover mutant mice for nine of the mutations to date. Conclusions The inbred C57BL/6J CMMB, together with TGCE mutation screening and ICSI for the recovery of mutant mice, represents a valuable gene-driven approach for the functional annotation of the mammalian genome and for the generation of mouse models of human genetic diseases. The ability of ENU to induce mutations that cause various types of changes in proteins will provide additional insights into the functions of mammalian proteins that may not be detectable by knockout mutations. PMID:16300676

Empirical multi-wavelength prediction method for very high energy gamma-ray emitting BL Lacertae objects

NASA Astrophysics Data System (ADS)

Fallah Ramazani, V.; Lindfors, E.; Nilsson, K.

2017-12-01

Aim: We have collected the most complete multi-wavelength (6.0-6.0 × 10-18 cm) dataset of very high energy (VHE) γ-ray emitting (TeV) BL Lacs, which are the most numerous extragalactic VHE sources. Using significant correlations between different bands, we aim to identify the best TeV BL Lac candidates that can be discovered by the current and next generation of imaging air Cherenkov telescopes. Methods: We formed five datasets from lower energy data, i.e. radio, mid-infrared, optical, X-rays, and GeV γ-ray, and five VHE γ-ray datasets to perform a correlation study between different bands and to construct the prediction method. The low energy datasets were averaged for individual sources, while the VHE γ-ray data were divided into subsets according to the flux state of the source. We then looked for significant correlations and determined their best-fit parameters. Using the best-fit parameters we predicted the level of VHE γ-ray flux for a sample of 182 BL Lacs, which have not been detected at TeV energies. We identified the most promising TeV BL Lac candidates based on the predicted VHE γ-ray flux for each source. Results: We found 14 significant correlations between radio, mid-infrared, optical, γ-ray, and VHE γ-ray bands. The correlation between optical and VHE γ-ray luminosity is established for the first time. We attribute this to the more complete sample and more accurate handling of host galaxy flux in our work. We found nine BL Lac candidates whose predicted VHE γ-ray flux is high enough for detection in less than 25 h with current imaging air Cherenkov telescopes. Full Tables A.1 and A.2 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/608/A68

Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection.

PubMed

Takahashi, Yuki; Nishikawa, Makiya; Shinotsuka, Haruka; Matsui, Yuriko; Ohara, Saori; Imai, Takafumi; Takakura, Yoshinobu

2013-05-20

The development of exosomes as delivery vehicles requires understanding how and where exogenously administered exosomes are distributed in vivo. In the present study, we designed a fusion protein consisting of Gaussia luciferase and a truncated lactadherin, gLuc-lactadherin, and constructed a plasmid expressing the fusion protein. B16-BL6 murine melanoma cells were transfected with the plasmid, and exosomes released from the cells were collected by ultracentrifugation. Strong luciferase activity was detected in the fraction containing exosomes, indicating their efficient labeling with gLuc-lactadherin. Then, the labeled B16-BL6 exosomes were intravenously injected into mice, and their tissue distribution was evaluated. Pharmacokinetic analysis of the exosome blood concentration-time profile revealed that B16-BL6 exosomes disappeared very quickly from the blood circulation with a half-life of approximately 2min. Little luciferase activity was detected in the serum at 4h after exosome injection, suggesting rapid clearance of B16-BL6 exosomes in vivo. Moreover, sequential in vivo imaging revealed that the B16-BL6 exosome-derived signals distributed first to the liver and then to the lungs. These results indicate that gLuc-lactadherin labeling is useful for tracing exosomes in vivo and that B16-BL6 exosomes are rapidly cleared from the blood circulation after systemic administration. Copyright © 2013 Elsevier B.V. All rights reserved.

Induction of cell-mediated immunity against B16-BL6 melanoma in mice vaccinated with cells modified by hydrostatic pressure and chemical crosslinking.

PubMed

Eisenthal, A; Ramakrishna, V; Skornick, Y; Shinitzky, M

1993-05-01

In the preceding paper we have demonstrated an increase in presentation of both major histocompatibility complex antigens (MHC) and a tumor-associated antigen of the weakly immunogenic B16 melanoma by a straight-forward technique. The method consists in modulating the tumor cell membrane by hydrostatic pressure and simultaneous chemical crosslinking of the cell-surface proteins. In B16-BL6 melanoma, the induced antigenic modulation was found to persist for over 48 h, which permitted the evaluation of the ability of modified B16-BL6 cells to induce immunity against unmodified B16-BL6 cells. In the present study, we have shown that a significant systemic immunity was induced only in mice that were immunized with modified B16-BL6 melanoma cells, whereas immunization with unmodified B16-BL6 cells had only a marginal effect when compared to the results in control sham-immunized mice. The induced immunity was specific since a single immunization affected the growth of B16-BL6 tumors but had no effect on MCA 106, an antigenically unrelated tumor. The addition of interleukin-2 to the immunization regimen had no effect on the antitumor responses induced by the modified B16-BL6 cells. The cell-mediated immunity conferred by immunization with treated B16-BL6 cells was confirmed in experiments in vitro where splenocytes from immunized mice could be sensitized to proliferate by the presence of B16-BL6 cells. In addition, the altered antigenicity of these melanoma cells appeared to correlate with their increased susceptibility to specific effectors. Thus, 51Cr-labeled B16-BL6 target cells, modified by pressure and crosslinking, in comparison to control labeled target cells, were lysed in much greater numbers by effectors such as lymphokine-activated killer cells and allogeneic cytotoxic lymphocytes (anti-H-2b), while such cells remained resistant to lysis by natural killer cells. Our findings indicate that the physical and chemical modifications of the tumor cells that are

A KPC-scale X-ray jet in the BL LAC Source S5 2007+777

NASA Technical Reports Server (NTRS)

Sambruna, Rita; Maraschi, Laura; Tavecchio, Fabrizio

2008-01-01

The BL Lac S3 2007++777, a classical radio-selected BL Lac from the sample of Stirkel et al. exhibiting an extended (19") radio jet. was observed with Chandra revealing an X-ray jet with simi1ar morphology. The hard X-ray spectrum and broad band SED is consistent with an IC/CMB origin for the X-ray emission, implying a highly relativistic flow at small angle to the line of sight with an unusually large deprojected length, 300 kpc. A structured jet consisting of a fast spine and slow wall is consistent with the observations.

New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL/6 Mouse Strain.

PubMed

Takeuchi, Kazuhiro; Naito, Shokichi; Kawashima, Nagako; Ishigaki, Naoko; Sano, Takashi; Kamata, Kouju; Takeuchi, Yasuo

2018-01-01

Focal segmental glomerulosclerosis (FSGS) is considered a subset of the podocytopathies. The molecular pathogenesis of podocytopathy is still unknown. There has not been an experimental animal model of isolated podocytopathy induced by antibody in C57BL/6 strain, which is widely used as the genetic background. Nephrin is closely associated with the slit diaphragm of the glomerular podocyte, and has recently received attention as a potential therapeutic target. The function of nephrin, especially its role in FSGS development via podocytopathy, is being elucidated. We report our experience with a C57BL/6 FSGS model induced by polyclonal rabbit anti-mouse nephrin antibody (α-mNep Ab). α-mNep Ab, which was generated by genetic immunization, was administered into C57BL/6 mice at once, intravenously. Urinary protein excretion, the development of glomerulosclerosis and the number of podocyte in mouse kidney were evaluated. The α-mNep Ab-induced FSGS was associated with massive proteinuria and nephrotic syndrome. In periodic acid-Schiff staining, FSGS was observed from day 7 after antibody injection. Podocyte numbers and podocyte marker (anti-Wilms tumor 1 and anti-synaptopodin)-positive areas were clearly decreased. These results suggest that this FSGS mouse model reliably reproduces the human nephrotic syndrome and FSGS. We succeeded in making the nephrotic syndrome model mice induced by α-mNep Ab using C57BL/6. This model may be useful for studying the mechanisms of podocytopathy. © 2017 S. Karger AG, Basel.

Inflammation has a role in urethane‑induced lung cancer in C57BL/6J mice.

PubMed

Xu, Cai; Zhou, Lingyu; Lu, Lei; Chen, Ting; Wei, Siyu; Lin, Xiaojing; Lian, Xuemei

2016-10-01

Lung cancer is a common and highly frequent cause of cancer‑associated mortality worldwide. Several studies have indicated that chronic inflammation is associated with an increased risk of several types of human cancer. The lung is vulnerable to various chemical and biological insults, and persistent exposure to these factors may result in the release of several inflammatory cytokines from inflammatory cells, thus leading to chronic inflammation and a risk of lung cancer. Due to the extensive application of C57BL/6J mice in lipid metabolism‑related research, it appears important to establish a lung cancer model based on C57BL/6J mice. Therefore, the present study designed an experimental model, in which C57BL/6J mice received several injections of urethane. The study aimed to explore whether inflammation has a role in this model of lung cancer. The results demonstrated that 10 weekly intraperitoneal injections of urethane induced a 100% lung tumor incidence, and urethane‑treated mice possessed higher numbers of immune cells. In addition, the expression levels of cytokines and chemokines in bronchoalveolar lavage fluid were significantly different between the two groups. Activation of the transcription factor nuclear factor‑κB was increased in the lung tissues of urethane‑treated mice, and its expression was upregulated in a time‑dependent manner. These results suggested that the accumulation of lung inflammation may be associated with the occurrence of lung cancer in C57BL/6J mice.

Project Based Learning (PjBL) Practices at Politeknik Kota Bharu, Malaysia

ERIC Educational Resources Information Center

Rahman, Md. Baharuddin Haji Abdul; Daud, Khairul Azhar Mat; Jusoff, Kamaruzaman; Ghani, Nik Azida Abd

2009-01-01

This study explores the utilization of Project-based Learning module in the subject of project development for the Mechanical Engineering students at Politeknik Kota Bharu. This study focuses on the development of the PjBL module based on socio-constructivist approach. The objective of this study is to explore the influence of the utilization of…

DEVELOPMENT OF HOME CAGE SOCIAL BEHAVIORS IN BALB/cJ vs. C57BL/6J MICE

PubMed Central

Fairless, Andrew H.; Katz, Julia M.; Vijayvargiya, Neha; Dow, Holly C.; Kreibich, Arati Sadalge; Berrettini, Wade H.; Abel, Ted; Brodkin, Edward S.

2012-01-01

BALB/cJ and C57BL/6J inbred mouse strains have been proposed as useful models of low and high levels of sociability (tendency to seek social interaction), respectively, based primarily on behaviors of ~30-day-old mice in the Social Approach Test (SAT). In the SAT, approach and sniffing behaviors of a test mouse toward an unfamiliar stimulus mouse are measured in a novel environment. However, it is unclear whether such results generalize to a familiar environment with a familiar social partner, such as with a littermate in a home cage environment. We hypothesized that C57BL/6J mice would show higher levels of social behaviors than BALB/cJ mice in the home cage environment, particularly at 30 days-of-age. We measured active and passive social behaviors in home cages by pairs of BALB/cJ or C57BL/6J littermates at ages 30, 41, and 69 days. The strains did not differ robustly in their active social behaviors. C57BL/6J mice were more passively social than BALB/cJ mice at 30 days, and C57BL/6J levels of passive social behaviors declined to BALB/cJ levels by 69 days. The differences in passive social behaviors at 30 days-of-age were primarily attributable to differences in huddling. These results indicate that different test conditions (SAT conditions vs. home cage conditions) elicit strain differences in distinct types of behaviors (approach/sniffing vs. huddling behaviors, respectively). Assessment of the more naturalistic social interactions in the familiar home cage environment with a familiar littermate will provide a useful component of a comprehensive assessment of social behaviors in mouse models relevant to autism. PMID:22982070

Development of home cage social behaviors in BALB/cJ vs. C57BL/6J mice.

PubMed

Fairless, Andrew H; Katz, Julia M; Vijayvargiya, Neha; Dow, Holly C; Kreibich, Arati Sadalge; Berrettini, Wade H; Abel, Ted; Brodkin, Edward S

2013-01-15

BALB/cJ and C57BL/6J inbred mouse strains have been proposed as useful models of low and high levels of sociability (tendency to seek social interaction), respectively, based primarily on behaviors of ∼30-day-old mice in the Social Approach Test (SAT). In the SAT, approach and sniffing behaviors of a test mouse toward an unfamiliar stimulus mouse are measured in a novel environment. However, it is unclear whether such results generalize to a familiar environment with a familiar social partner, such as with a littermate in a home cage environment. We hypothesized that C57BL/6J mice would show higher levels of social behaviors than BALB/cJ mice in the home cage environment, particularly at 30 days-of-age. We measured active and passive social behaviors in home cages by pairs of BALB/cJ or C57BL/6J littermates at ages 30, 41, and 69 days. The strains did not differ robustly in their active social behaviors. C57BL/6J mice were more passively social than BALB/cJ mice at 30 days, and C57BL/6J levels of passive social behaviors declined to BALB/cJ levels by 69 days. The differences in passive social behaviors at 30 days-of-age were primarily attributable to differences in huddling. These results indicate that different test conditions (SAT conditions vs. home cage conditions) elicit strain differences in distinct types of behaviors (approach/sniffing vs. huddling behaviors, respectively). Assessment of the more naturalistic social interactions in the familiar home cage environment with a familiar littermate will provide a useful component of a comprehensive assessment of social behaviors in mouse models relevant to autism. Copyright © 2012 Elsevier B.V. All rights reserved.

The new NCPSS BL19U2 beamline at the SSRF for small-angle X-ray scattering from biological macromolecules in solution.

PubMed

Li, Na; Li, Xiuhong; Wang, Yuzhu; Liu, Guangfeng; Zhou, Ping; Wu, Hongjin; Hong, Chunxia; Bian, Fenggang; Zhang, Rongguang

2016-10-01

The beamline BL19U2 is located in the Shanghai Synchrotron Radiation Facility (SSRF) and is its first beamline dedicated to biological material small-angle X-ray scattering (BioSAXS). The electrons come from an undulator which can provide high brilliance for the BL19U2 end stations. A double flat silicon crystal (111) monochromator is used in BL19U2, with a tunable monochromatic photon energy ranging from 7 to 15 keV. To meet the rapidly growing demands of crystallographers, biochemists and structural biologists, the BioSAXS beamline allows manual and automatic sample loading/unloading. A Pilatus 1M detector (Dectris) is employed for data collection, characterized by a high dynamic range and a short readout time. The highly automated data processing pipeline SASFLOW was integrated into BL19U2, with help from the BioSAXS group of the European Molecular Biology Laboratory (EMBL, Hamburg), which provides a user-friendly interface for data processing. The BL19U2 beamline was officially opened to users in March 2015. To date, feedback from users has been positive and the number of experimental proposals at BL19U2 is increasing. A description of the new BioSAXS beamline and the setup characteristics is given, together with examples of data obtained.

Optical Variability of BL Lacertae During the Major Outburst of 1997

NASA Technical Reports Server (NTRS)

Ghosh, K. K.; Ramsey, B. D.; Sadun, A. C.; Soundararajaperumal, S.; Wang, J.

2000-01-01

We have undertaken an investigation of recent flux variability in BL Lac. We present optical observations taken over 22 nights documenting major as well as minor outbursts. This has been combined, for purposes of multifrequency analysis, with published X-ray and T-ray data taken for an additional single night, On two nights in particular, including the night of the X-ray observations, a major outburst of about a full magnitude of variation was recorded. All the data have been analyzed with theoretical models. Attempts were made to use synchrotron self-Compton and external Comptonization models to explain the data; however, both classes of models were found lacking. More satisfactory results were obtained using an analytical model proposed by Wang et al. that involves the evolution of synchrotron spectra in a homogeneous jet due to the injection of relativistic electrons, taking into account radiation losses during the outbursts. It is hoped that the results of this study of BL Lac, an archetype for the class of blazars in general, represent a more generic phenomenon applicable to the entire class.

Optical Variability of BL Lacertae During the Major Outburst of 1997

NASA Technical Reports Server (NTRS)

Ghosh, K. K.; Ramsey, B. D.; Sadun, A. C.; Soundarajaperumal, S.; Wang, J.

1999-01-01

We have undertaken an investigation of recent flux variability in BL Lac. We present optical observations taken over 12 nights documenting major as well as minor outbursts. This has been combined, for purposes of multifrequency analysis, with published X-ray and gamma ray data taken for an additional single night. On two nights in particular, which includes the night of the X-ray observations, a major outburst of about a full magnitude of variation was recorded. All the data have been analyzed with theoretical models. Attempts were made to use synchrotron self-Compton and external Comptonization models to explain the data; however both classes of models were found lacking. More satisfactory results were obtained using an analytical model proposed by Wang et al. that involves the evolution of synchrotron spectra in a homogeneous jet due to the injection of relativistic electrons, taking into account radiation losses during the outbursts. It is hoped that the results of this study of BL Lac, an archetype for the class of blazars in general, represent a more generic phenomenon applicable to the entire class.

Sociability and brain development in BALB/cJ and C57BL/6J mice

PubMed Central

Fairless, Andrew H.; Dow, Holly C.; Kreibich, Arati Sadalge; Torre, Matthew; Kuruvilla, Mariyam; Gordon, Elliot; Morton, Elizabeth A.; Tan, Junhao; Berrettini, Wade H.; Li, Hongzhe; Abel, Ted; Brodkin, Edward S.

2012-01-01

Sociability—the tendency to seek social interaction–propels the development of social cognition and social skills, but is disrupted in autism spectrum disorders (ASD). BALB/cJ and C57BL/6J inbred mouse strains are useful models of low and high levels of juvenile sociability, respectively, but the neurobiological and developmental factors that account for the strains’ contrasting sociability levels are largely unknown. We hypothesized that BALB/cJ mice would show increasing sociability with age but that C57BL/6J mice would show high sociability throughout development. We also hypothesized that littermates would resemble one another in sociability more than non-littermates. Finally, we hypothesized that low sociability would be associated with low corpus callosum size and increased brain size in BALB/cJ mice. Separate cohorts of C57BL/6J and BALB/cJ mice were tested for sociability at 19-, 23-, 31-, 42-, or 70-days-of-age, and brain weights and mid-sagittal corpus callosum area were measured. BALB/cJ sociability increased with age, and a strain by age interaction in sociability between 31 and 42 days of age suggested strong effects of puberty on sociability development. Sociability scores clustered according to litter membership in both strains, and perinatal litter size and sex ratio were identified as factors that contributed to this clustering in C57BL/6J, but not BALB/cJ, litters. There was no association between corpus callosum size and sociability, but smaller brains were associated with lower sociability in BALB/cJ mice. The associations reported here will provide directions for future mechanistic studies of sociability development. PMID:22178318

Neuronal Tryptophan Hydroxylase Expression in BALB/cJ and C57Bl/6J Mice

PubMed Central

Bach, Helene; Arango, Victoria; Huang, Yung-Yu; Leong, Sharlene; Mann, J. John; Underwood, Mark D.

2014-01-01

BALB/c is an inbred stress-sensitive mouse strain exhibiting low brain serotonin (5-HT) content and a 5-HT biosynthetic enzyme tryptophan hydroxylase (Tph2) variant reported to have lower catalytic activity compared to other inbred base strains. To evaluate other mechanisms that may explain low 5-HT, we compared BALB/cJ mice and a control inbred strain C57Bl/6J mice, for expression of Tph2 mRNA, TPH2 protein and regional levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). Tph2 mRNA and TPH2 protein in brainstem dorsal raphe nuclei (DRN) was assayed by in situ hybridization and immunocytochemistry respectively. 5-HT and 5-HIAA were determined by high pressure liquid chromatography (HPLC). BALB/cJ mice had 20% less Tph2 mRNA and 28% fewer TPH2 immunolabeled neurons than C57Bl/6J mice (t = -2.59, p = 0.02). The largest difference in Tph2 transcript expression was in rostral DRN (t = 2.731, p = 0.008). 5-HT was 15% lower in the midbrain of BALB/cJ compared to C57Bl/6J mice (p < 0.05). The behavioral differences in BALB/cJ mice relative to the C57Bl/6J strain may be due in part, to fewer 5-HT neurons and lower Tph2 gene expression resulting in less 5-HT neurotransmission. Future studies quantifying expression per neuron are needed to determine whether less expression is explained by fewer neurons or also less expression per neuron, or both. PMID:21740442

Neuronal tryptophan hydroxylase expression in BALB/cJ and C57Bl/6J mice.

PubMed

Bach, Helene; Arango, Victoria; Huang, Yung-Yu; Leong, Sharlene; Mann, J John; Underwood, Mark D

2011-09-01

BALB/c is an inbred stress-sensitive mouse strain exhibiting low brain serotonin (5-HT) content and a 5-HT biosynthetic enzyme tryptophan hydroxylase (Tph2) variant reported to have lower catalytic activity compared with other inbred base strains. To evaluate other mechanisms that may explain low 5-HT, we compared BALB/cJ mice and a control inbred strain C57Bl/6J mice, for expression of Tph2 mRNA, TPH2 protein and regional levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid. Tph2 mRNA and TPH2 protein in brainstem dorsal raphe nuclei was assayed by in situ hybridization and immunocytochemistry respectively. 5-HT and 5-hydroxyindoleacetic acid were determined by HPLC. BALB/cJ mice had 20% less Tph2 mRNA and 28% fewer TPH2 immunolabeled neurons than C57Bl/6J mice (t = -2.59, p = 0.02). The largest difference in Tph2 transcript expression was in rostral dorsal raphe nuclei (t = 2.731, p = 0.008). 5-HT was 15% lower in the midbrain and 18% lower in the cerebral cortex of BALB/cJ compared with C57Bl/6J mice (p < 0.05). The behavioral differences in BALB/cJ mice relative to the C57Bl/6J strain may be due in part, to fewer 5-HT neurons and lower Tph2 gene expression resulting in less 5-HT neurotransmission. Future studies quantifying expression per neuron are needed to determine whether less expression is explained by fewer neurons or also less expression per neuron, or both. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

BL-038, a Benzofuran Derivative, Induces Cell Apoptosis in Human Chondrosarcoma Cells through Reactive Oxygen Species/Mitochondrial Dysfunction and the Caspases Dependent Pathway.

PubMed

Liu, Ju-Fang; Chen, Chien-Yu; Chen, Hsien-Te; Chang, Chih-Shiang; Tang, Chih-Hsin

2016-09-07

Chondrosarcoma is a highly malignant cartilage-forming bone tumor that has the capacity to invade locally and cause distant metastasis. Moreover, chondrosarcoma is intrinsically resistant to conventional chemotherapy or radiotherapy. The novel benzofuran derivative, BL-038 (2-amino-3-(2,6-dichlorophenyl)-6-(4-methoxyphenyl)benzofuran-4-yl acetate), has been evaluated for its anticancer effects in human chondrosarcoma cells. BL-038 caused cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353, but not in primary chondrocytes. Treatment of chondrosarcoma with BL-038 also induced reactive oxygen species (ROS) production. Furthermore, BL-038 decreased mitochondrial membrane potential (MMP) and changed mitochondrial-related apoptosis, by downregulating the anti-apoptotic activity members (Bcl-2, Bcl-xL) and upregulating pro-apoptotic members (Bax, Bak) of the B-cell lymphoma 2 (Bcl-2) family of proteins, key regulators of the apoptotic machinery in cells. These results demonstrate that in human chondrosarcoma cells, the apoptotic and cytotoxic effects of BL-038 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the release of cytochrome c, the activation of caspase-9 and caspase-3, and the cleavage of poly (ADP-ribose) polymerase (PARP), to elicit apoptosis response. Our results show that the benzofuran derivative BL-038 induces apoptosis in chondrosarcoma cells.

Effects of phenazepam on the behavior of C57BL/6 and BALB/c mice in the open field test after naloxone pretreatment.

PubMed

Seredenin, S B; Nadorova, A V; Kolik, L G; Yarkova, M A

2013-07-01

We studied the effects of phenazepam (0.075 mg/kg) after pretreatment (5 minutes before) with naloxone (10 mg/kg) on open-field behavior of C57Bl/6 and BALB/c mice. In ex vivo experiments, we studied the effects of naloxone (1 and 10 mg/kg) on receptor binding of [(3)H]-flunitrazepam by membranes of brain fraction (P1+P2) of C57Bl/6 and BALB/c mice. It was shown that naloxone increased motor activity in the open field in BALB/c mice and decreased this parameter in C57Bl/6 mice. During combined treatment, naloxone potentiated the activating effects of phenazepam on the open-field behavior of BALB/c mice and slightly increased the sedative effect of this drug in C57Bl/6 mice. Naloxone stimulated reception of [(3)H]-flunitrazepam in BALB/c mice and slightly increased radioligand binding in C57Bl/6 mice. These data attest to enhanced reception in benzodiazepine site of GABAA-receptor under conditions of opioid receptor blockade, the presence of anxiolytic or sedative (depending on the phenotype of the response to emotional stress) effect of naloxone, and co-directed effects of naloxone and benzodiazepine tranquilizer on open-field behavior of C57Bl/6 and BALB/c mice.

Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

PubMed

Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

1999-03-15

We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

Strain and sex differences in anxiety-like and social behaviors in C57BL/6J and BALB/cJ mice.

PubMed

An, Xiao-Lei; Zou, Jun-Xian; Wu, Rui-Yong; Yang, Ying; Tai, Fa-Dao; Zeng, Shuang-Yan; Jia, Rui; Zhang, Xia; Liu, En-Qi; Broders, Hugh

2011-01-01

Mood disorders are more frequent in women than men, however, the majority of research has focused on male rodents as animal models. We used a variety of common behavioral tests to look for differences in anxiety-like and social behaviors between and within C57BL/6J and BALB/cJ mice. Our results show that female C57BL/6J mice exhibited lower levels of anxiety-like behavior and higher levels of activity than female BALB/cJ during the open field and elevated plus maze tests. Principal component analysis generated more factors in the behavioral variables of males than females. In the open field, a sex difference was also found and factor 1 emerged as anxiety in males, and motor activity in females. While C57BL/6J mice were found to have higher levels of social exploration and social contacts, differences were found between the sexes (females were more social) in both strains for this measure and also for anxiety-like behaviors. When interacting with animals of the same sex, levels of sniffing body and huddling in both male and female C57BL/6J mice were higher than those in male and female BALB/cJ mice. However, in the between-sex interactions, male C57BL/6J mice sniffed the stimulus mouse less, and female C57BL/6J mice sniffed the stimulus more compared to BALB/cJ mice. This study provides important behavioral phenotypes and confirms the multidimensional behavioral structure of two widely used mice strains.

Lycopene pretreatment improves hepatotoxicity induced by acetaminophen in C57BL/6 mice.

PubMed

Bandeira, Ana Carla Balthar; da Silva, Rafaella Cecília; Rossoni, Joamyr Victor; Figueiredo, Vivian Paulino; Talvani, André; Cangussú, Silvia Dantas; Bezerra, Frank Silva; Costa, Daniela Caldeira

2017-02-01

Acetaminophen (APAP) is an antipyretic and analgesic drug that, in high doses, leads to severe liver injury and potentially death. Oxidative stress is an important event in APAP overdose. Researchers are looking for natural antioxidants with the potential to mitigate the harmful effects of reactive oxygen species in different models. Lycopene has been widely studied for its antioxidant properties. The aim of this study was to evaluate the antioxidant potential of lycopene pretreatment in APAP-induced liver injury in C57BL/6 mice. C57BL/6 male mice were divided into the following groups: control (C); sunflower oil (CO); acetaminophen 500mg/kg (APAP); acetaminophen 500mg/kg+lycopene 10mg/kg (APAP+L10), and acetaminophen 500mg/kg+lycopene 100mg/kg (APAP+L100). Mice were pretreated with lycopene for 14 consecutive days prior to APAP overdose. Analyses of blood serum and livers were performed. Lycopene was able to improve redox imbalance, decrease thiobarbituric acid reactive species level, and increase CAT and GSH levels. In addition, it decreased the IL-1β expression and the activity of MMP-2. This study revealed that preventive lycopene consumption in C57BL/6 mice can attenuate the effects of APAP-induced liver injury. Furthermore, by improving the redox state, and thus indicating its potential antioxidant effect, lycopene was also shown to have an influence on inflammatory events. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long term monitoring of Gamma-Ray emission from the BL Lacertae object (1ES 2200+420)

NASA Astrophysics Data System (ADS)

Gunawardhana, Isuru; VERITAS Collaboration

2016-03-01

Blazars are a class of Active Galactic Nuclei (AGN) that have relativistic jets pointing along the observer line of sight. Blazars exhibit variable emission extending from radio to TeV energies. The variability timescale of the TeV flux is a key component of understanding the location of the very high energy emission zones. Deep observations of the quiescent state measurements are also required to disentangle the flaring state emission from quiescent state emission, a prerequisite for understanding the origin of blazar spectral variability. BL Lacertae (also known as 1ES 2200+420), as the namesake for all BL Lac objects, is a prime example of one such blazar. The VERITAS Observatory, an Imaging Atmospheric Cherenkov Telescope (IACT) array sensitive to gamma rays in the range from 85 GeV to 30 TeV, dedicates approximately 110 hours per year on deep observations of known gamma-ray blazars. In this talk, I will describe the TeV photon flux variability of BL Lacertae measured by VERITAS from 2013 to 2015.

PATHOGENESIS OF METHANOL-INDUCED CRANIOFACIAL DEFECTS IN C57BL/6J MICE

EPA Science Inventory

BACKGROUND: Methanol administered to C57BL/6J mice during gastrulation causes severe craniofacial dysmorphology. We describe dysmorphogenesis, cell death, cell cycle assessment, and effects on development of cranial ganglia and nerves observed following administration of methanol...

Prediction of sonic boom from experimental near-field overpressure data. Volume 1: Method and results

NASA Technical Reports Server (NTRS)

Glatt, C. R.; Hague, D. S.; Reiners, S. J.

1975-01-01

A computerized procedure for predicting sonic boom from experimental near-field overpressure data has been developed. The procedure extrapolates near-field pressure signatures for a specified flight condition to the ground by the Thomas method. Near-field pressure signatures are interpolated from a data base of experimental pressure signatures. The program is an independently operated ODIN (Optimal Design Integration) program which obtains flight path information from other ODIN programs or from input.

Thermoneutral housing is a critical factor for immune function and diet-induced obesity in C57BL/6 nude mice.

PubMed

Stemmer, K; Kotzbeck, P; Zani, F; Bauer, M; Neff, C; Müller, T D; Pfluger, P T; Seeley, R J; Divanovic, S

2015-05-01

Obesity-related cancers represent public health burdens of the first order. Nevertheless, suitable mouse models to unravel molecular mechanisms linking obesity to human cancer are still not available. One translational model is the immunocompromised Foxn1 (winged-helix/forkead transcription factor) nude mouse transplanted with human tumor xenografts. However, most xenograft studies are conducted in nude mice on an in-bred BALB/c background that entails protection from diet-induced obesity. To overcome such resistance to obesity and its sequelae, we here propose the dual strategy of utilizing Foxn1 nude mice on a C57BL/6 background and housing them at their thermoneutral zone. C57BL/6 nude and corresponding wild-type mice, housed at 23 or 33 °C, were subjected to either low-fat diet or high-fat diet (HFD). Energy expenditure, locomotor activity, body core temperature, respiratory quotient as well as food and water intake were analyzed using indirect calorimetry. Immune function at different housing temperatures was assessed by using an in vivo cytokine capture assay. Our data clearly demonstrate that conventional housing protects C57BL/6 nude mice from HFD-induced obesity, potentially via increased energy expenditure. In contrast, HFD-fed C57BL/6 nude mice housed at thermoneutral conditions develop adiposity, increased hepatic triglyceride accumulation, adipose tissue inflammation and glucose intolerance. Moreover, increased circulating levels of lipopolysaccharide-driven cytokines suggest a greatly enhanced immune response in C57BL/6 nude mice housed at thermoneutrality. Our data reveals mild cold stress as a major modulator for energy and body weight homeostasis as well as immune function in C57BL/6 nude mice. Adjusting housing temperatures to the thermoneutral zone may ultimately be key to successfully study growth and progression of human tumors in a diet-induced obese environment.

Thermoneutral housing is a critical factor for immune function and diet-induced obesity in C57BL/6 nude mice

PubMed Central

Stemmer, K; Kotzbeck, P; Zani, F; Bauer, M; Neff, C; Müller, TD; Pfluger, PT; Seeley, RJ; Divanovic, S

2014-01-01

OBJECTIVES Obesity-related cancers represent public health burdens of the first order. Nevertheless, suitable mouse models to unravel molecular mechanisms linking obesity to human cancer are still not available. One translational model is the immunocompromised Foxn1 (winged-helix/forkead transcription factor) nude mouse transplanted with human tumor xenografts. However, most xenograft studies are conducted in nude mice on an in-bred BALB/c background that entails protection from diet-induced obesity. To overcome such resistance to obesity and its sequelae, we here propose the dual strategy of utilizing Foxn1 nude mice on a C57BL/6 background and housing them at their thermoneutral zone. METHODS C57BL/6 nude and corresponding wild-type mice, housed at 23 or 33 °C, were subjected to either low-fat diet or high-fat diet (HFD). Energy expenditure, locomotor activity, body core temperature, respiratory quotient as well as food and water intake were analyzed using indirect calorimetry. Immune function at different housing temperatures was assessed by using an in vivo cytokine capture assay. RESULTS Our data clearly demonstrate that conventional housing protects C57BL/6 nude mice from HFD-induced obesity, potentially via increased energy expenditure. In contrast, HFD-fed C57BL/6 nude mice housed at thermoneutral conditions develop adiposity, increased hepatic triglyceride accumulation, adipose tissue inflammation and glucose intolerance. Moreover, increased circulating levels of lipopolysaccharide-driven cytokines suggest a greatly enhanced immune response in C57BL/6 nude mice housed at thermoneutrality. CONCLUSION Our data reveals mild cold stress as a major modulator for energy and body weight homeostasis as well as immune function in C57BL/6 nude mice. Adjusting housing temperatures to the thermoneutral zone may ultimately be key to successfully study growth and progression of human tumors in a diet-induced obese environment. PMID:25349057

Indomethacin treatment prevents diet-induced obesity and insulin resistance, but not glucose intolerance in C57BL/6J mice

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: We performed experiments to examine the metabolic consequences of inhibition of cyclooxygenase (COX) activity in obesity-prone C57BL/6J mice fed a high fat/high sucrose (HF/HS) diet. RESEARCH DESIGN AND METHODS: C57BL/6J mice were fed a HF/HS diet for 7 weeks under thermoneutral conditio...

Fermi LAT detection of a GeV flare from the BL Lac object PKS 2233-148

NASA Astrophysics Data System (ADS)

Ciprini, Stefano

2012-06-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed gamma-ray flaring activity from a source positionally consistent with the BL Lac object PKS 2233-148 (also known as 2FGL J2236.5-1431, Nolan et al. 2012, ApJS, 199, 31, and OY -156) placed at R.A.: 339.1420296 deg, Dec.: -14.5561633 (J2000, Petrov et al. 2008, AJ, 136, 580). No redshift for the source has been measured up to now, demonstrating the BL Lac object character type of this source.

BL-038, a Benzofuran Derivative, Induces Cell Apoptosis in Human Chondrosarcoma Cells through Reactive Oxygen Species/Mitochondrial Dysfunction and the Caspases Dependent Pathway

PubMed Central

Liu, Ju-Fang; Chen, Chien-Yu; Chen, Hsien-Te; Chang, Chih-Shiang; Tang, Chih-Hsin

2016-01-01

Chondrosarcoma is a highly malignant cartilage-forming bone tumor that has the capacity to invade locally and cause distant metastasis. Moreover, chondrosarcoma is intrinsically resistant to conventional chemotherapy or radiotherapy. The novel benzofuran derivative, BL-038 (2-amino-3-(2,6-dichlorophenyl)-6-(4-methoxyphenyl)benzofuran-4-yl acetate), has been evaluated for its anticancer effects in human chondrosarcoma cells. BL-038 caused cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353, but not in primary chondrocytes. Treatment of chondrosarcoma with BL-038 also induced reactive oxygen species (ROS) production. Furthermore, BL-038 decreased mitochondrial membrane potential (MMP) and changed mitochondrial-related apoptosis, by downregulating the anti-apoptotic activity members (Bcl-2, Bcl-xL) and upregulating pro-apoptotic members (Bax, Bak) of the B-cell lymphoma 2 (Bcl-2) family of proteins, key regulators of the apoptotic machinery in cells. These results demonstrate that in human chondrosarcoma cells, the apoptotic and cytotoxic effects of BL-038 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the release of cytochrome c, the activation of caspase-9 and caspase-3, and the cleavage of poly (ADP-ribose) polymerase (PARP), to elicit apoptosis response. Our results show that the benzofuran derivative BL-038 induces apoptosis in chondrosarcoma cells. PMID:27618007

Gauged $B-L$ number and neutron–antineutron oscillation: long-range forces mediated by baryophotons

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

Addazi, Andrea; Berezhiani, Zurab; Kamyshkov, Yuri

Transformation of a neutron to an antineutron n→n~ has not yet been experimentally observed. In principle, it can occur with free neutrons in the vacuum or with neutrons bound inside the nuclei. In a nuclear medium the neutron and the antineutron have different potentials and for that reason n–n~ conversion in nuclei is heavily suppressed. This transformation can also be suppressed for free neutrons in the presence of an environmental vector field that distinguishes the neutron from the antineutron. We consider the case of a gauge field coupled to the $B-L$ charge of the particles ($B-L$ photon), and we showmore » that discovery of n–n~ oscillation in experiment will lead to few order of magnitudes stronger limits on its coupling constant than present limits from the tests of the equivalence principle. If n–n~ oscillation will be discovered via nuclear instability, but not in free neutron oscillations at a corresponding level, this would indicate the presence of such environmental fifth forces. In the latter case the $B-L$ potential can be measurable by varying the external magnetic field for achieving the resonance conditions for n–n~ conversion. As for neutron–mirror neutron oscillation, such potentials should have no effect once the fifth forces are associated to a common quantum number $(B - L) - (B' - L')$ shared by the ordinary and mirror particles.« less

Gauged $B-L$ number and neutron–antineutron oscillation: long-range forces mediated by baryophotons

DOE PAGES

Addazi, Andrea; Berezhiani, Zurab; Kamyshkov, Yuri

2017-05-11

Transformation of a neutron to an antineutron n→n~ has not yet been experimentally observed. In principle, it can occur with free neutrons in the vacuum or with neutrons bound inside the nuclei. In a nuclear medium the neutron and the antineutron have different potentials and for that reason n–n~ conversion in nuclei is heavily suppressed. This transformation can also be suppressed for free neutrons in the presence of an environmental vector field that distinguishes the neutron from the antineutron. We consider the case of a gauge field coupled to the $B-L$ charge of the particles ($B-L$ photon), and we showmore » that discovery of n–n~ oscillation in experiment will lead to few order of magnitudes stronger limits on its coupling constant than present limits from the tests of the equivalence principle. If n–n~ oscillation will be discovered via nuclear instability, but not in free neutron oscillations at a corresponding level, this would indicate the presence of such environmental fifth forces. In the latter case the $B-L$ potential can be measurable by varying the external magnetic field for achieving the resonance conditions for n–n~ conversion. As for neutron–mirror neutron oscillation, such potentials should have no effect once the fifth forces are associated to a common quantum number $(B - L) - (B' - L')$ shared by the ordinary and mirror particles.« less

Utilization of d-Ribitol by Lactobacillus casei BL23 Requires a Mannose-Type Phosphotransferase System and Three Catabolic Enzymes

PubMed Central

Bourand, A.; Yebra, M. J.; Boël, G.; Mazé, A.

2013-01-01

Lactobacillus casei strains 64H and BL23, but not ATCC 334, are able to ferment d-ribitol (also called d-adonitol). However, a BL23-derived ptsI mutant lacking enzyme I of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) was not able to utilize this pentitol, suggesting that strain BL23 transports and phosphorylates d-ribitol via a PTS. We identified an 11-kb region in the genome sequence of L. casei strain BL23 (LCABL_29160 to LCABL_29270) which is absent from strain ATCC 334 and which contains the genes for a GlpR/IolR-like repressor, the four components of a mannose-type PTS, and six metabolic enzymes potentially involved in d-ribitol metabolism. Deletion of the gene encoding the EIIB component of the presumed ribitol PTS indeed prevented d-ribitol fermentation. In addition, we overexpressed the six catabolic genes, purified the encoded enzymes, and determined the activities of four of them. They encode a d-ribitol-5-phosphate (d-ribitol-5-P) 2-dehydrogenase, a d-ribulose-5-P 3-epimerase, a d-ribose-5-P isomerase, and a d-xylulose-5-P phosphoketolase. In the first catabolic step, the protein d-ribitol-5-P 2-dehydrogenase uses NAD+ to oxidize d-ribitol-5-P formed during PTS-catalyzed transport to d-ribulose-5-P, which, in turn, is converted to d-xylulose-5-P by the enzyme d-ribulose-5-P 3-epimerase. Finally, the resulting d-xylulose-5-P is split by d-xylulose-5-P phosphoketolase in an inorganic phosphate-requiring reaction into acetylphosphate and the glycolytic intermediate d-glyceraldehyde-3-P. The three remaining enzymes, one of which was identified as d-ribose-5-P-isomerase, probably catalyze an alternative ribitol degradation pathway, which might be functional in L. casei strain 64H but not in BL23, because one of the BL23 genes carries a frameshift mutation. PMID:23564164

Sociability and brain development in BALB/cJ and C57BL/6J mice.

PubMed

Fairless, Andrew H; Dow, Holly C; Kreibich, Arati Sadalge; Torre, Matthew; Kuruvilla, Mariyam; Gordon, Elliot; Morton, Elizabeth A; Tan, Junhao; Berrettini, Wade H; Li, Hongzhe; Abel, Ted; Brodkin, Edward S

2012-03-17

Sociability--the tendency to seek social interaction--propels the development of social cognition and social skills, but is disrupted in autism spectrum disorders (ASD). BALB/cJ and C57BL/6J inbred mouse strains are useful models of low and high levels of juvenile sociability, respectively, but the neurobiological and developmental factors that account for the strains' contrasting sociability levels are largely unknown. We hypothesized that BALB/cJ mice would show increasing sociability with age but that C57BL/6J mice would show high sociability throughout development. We also hypothesized that littermates would resemble one another in sociability more than non-littermates. Finally, we hypothesized that low sociability would be associated with low corpus callosum size and increased brain size in BALB/cJ mice. Separate cohorts of C57BL/6J and BALB/cJ mice were tested for sociability at 19-, 23-, 31-, 42-, or 70-days-of-age, and brain weights and mid-sagittal corpus callosum area were measured. BALB/cJ sociability increased with age, and a strain by age interaction in sociability between 31 and 42 days of age suggested strong effects of puberty on sociability development. Sociability scores clustered according to litter membership in both strains, and perinatal litter size and sex ratio were identified as factors that contributed to this clustering in C57BL/6J, but not BALB/cJ, litters. There was no association between corpus callosum size and sociability, but smaller brains were associated with lower sociability in BALB/cJ mice. The associations reported here will provide directions for future mechanistic studies of sociability development. Copyright © 2011 Elsevier B.V. All rights reserved.

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

PubMed Central

Yang, Qian; Zhang, Yafang; Liu, Xiuping; Wang, Nan; Song, Zhenyu; Wu, Kaili

2017-01-01

Models of benzalkonium chloride (BAC)-induced ocular disruption have been created and are widely used in various animals. This study aimed to compare the effects of BAC on the ocular surfaces of C57BL/6 and BALB/c mice. C57BL/6 and BALB/c mice were treated separately with BAC eye-drops at different concentrations. Eyes were evaluated by scoring epithelial disruption, corneal opacity and neovascularization in vivo, and by histological assays with hematoxylin/eosin (H/E) and periodic acid-Schiff stainings and by determining the expression of inflammatory factors in vitro on Days 7 and 14. The in vivo corneal epithelial disruption, corneal edema/opacity and neovascularization, which were in accordance with the results of the H/E staining and peaked at Day 7, were observed in a dose-dependent manner in the BAC-treated mice, with more severe signs in the C57BL/6 mice than the BALB/c mice. The loss of conjunctival goblet cells in the conjunctivas and the increasing expression of monocyte chemoattractant protein 1 (MCP-1), growth-regulated protein alpha (GROa) and macrophage inflammatory protein-1 alpha (MIP-1a) in the corneas were found in a dose-dependent manner in both strains of mice. Topical application of BAC can dramatically disrupt the ocular surfaces of C57BL/6 and BALB/c mice, and the disruptions were much more severe in the C57BL/6 mice that received high doses of BAC. PMID:28245636

Prescription of cardiovascular drugs in the French ODIN cohort of heart failure patients according to age and type of chronic heart failure.

PubMed

Juillière, Yves; Suty-Selton, Christine; Riant, Elisabeth; Darracq, Jean-Pierre; Dellinger, Arnaud; Labarre, Jean-Philippe; Druelle, Justine; Mulak, Geneviève; Danchin, Nicolas; Jourdain, Patrick

2014-01-01

Chronic heart failure (CHF) is a frequent severe disease. Disease-management programmes, which contain a therapeutic patient education component, will play a central role in improving delivery of care and reducing mortality and hospitalizations for CHF. In order to have an up-to-date overview of medical treatment of CHF in France implemented by hospital and clinic cardiologists especially interested in CHF and therapeutic patient education, we described the prescription of cardiovascular drugs in the large ODIN cohort of CHF patients, according to age and type of CHF. From 2007 to 2010 (median follow-up 27.2 months), CHF patients were prospectively enrolled in a multicentre 'real-world' French cohort by centres previously trained in therapeutic patient education. Patients were grouped according to age (< 60 years, 60 to<70 years, 70 to<80 years and ≥ 80 years) and type of CHF (characterized by level of LVEF: reduced, borderline or preserved). Medical prescription was described and mortality was assessed at long-term follow-up. The cohort consisted of 3237 patients (67.6 years; 69.4% men). The oldest age group had the highest LVEF. Blockers of the angiotensin-aldosterone system were prescribed progressively and significantly less frequently as the population advanced in age or as LVEF was more preserved. The mean dosages of the main prescribed CHF drugs remained ≥ 50% lower than those recommended for most drugs in all age and LVEF groups. Drug prescriptions were related to aetiology of reduced or preserved CHF. A global decrease in CHF drug prescription was observed for all medication classes except calcium blockers, according to maintenance of relatively or totally preserved LVEF. Survival was related to age but not to type of CHF. In CHF, and despite management by cardiologists particularly interested in CHF and specifically trained to deliver therapeutic patient education, medical prescription differed substantially from guidelines. Age and type of CHF

A new model of diabetic nephropathy in C57BL/6 mice challenged with advanced oxidation protein products.

PubMed

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Xu, Liting; Wan, Jiao; Liu, Youhua

2018-04-01

There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired phenotypic characteristics. Most genetically modified mice are on the C57BL/6 background; however, they are notorious for resistance to develop DN. To overcome these conundrums, this study reports a novel DN model by challenging with advanced oxidation protein products (AOPPs) in streptozotocin-induced diabetic C57BL/6 mice. AOPPs-challenged diabetic C57BL/6 mice were more sensitive to develop progressive proteinuria, causing a 5.59-fold increase in urine albumin to creatinine ratio as compared to diabetic controls by 24 weeks. Typical lesions were present as demonstrated by significant diffuse mesangial expansion, diffuse podocyte foot process effacement, increased glomerular basement membrane thickness, focal arteriolar hyalinosis, mesangiolysis, and mild interstitial fibrosis. These changes were alleviated by losartan treatment. Collectively, these results suggest that AOPPs can accelerate the progression of DN in the resistant C57BL/6 mouse strain. Our studies offer a novel model for studying the pathogenesis of DN that resembles human diabetic kidney disease. It also makes it possible to interrogate the role of specific genetic modifications and to evaluate novel therapeutics to treat DN in preclinical setting. Copyright © 2018. Published by Elsevier Inc.

Characterization in vitro and in vivo of progressively adriamycin-resistant B16-BL6 mouse melanoma cells.

PubMed

Ganapathi, R; Grabowski, D; Schmidt, H; Bell, D; Melia, M

1987-07-01

Adriamycin (ADR)-resistant sublines of B16-BL6 mouse melanoma selected by exposure to increasing concentrations of ADR were characterized in vitro for growth properties and in vivo for tumorigenicity and pulmonary metastases. The progressively resistant sublines adapted to grow in the presence of 0.025, 0.05, 0.1, and 0.25 microgram/ml ADR in monolayer culture were found to be 5-, 10-, 20-, and 40-fold ADR-resistant, respectively, compared to the parental sensitive cells, using a soft-agar colony assay and continuous ADR treatment for 7 days. The doubling time in monolayer culture of the parent sensitive and progressively ADR-resistant sublines of B16-BL6 melanoma cells was approximately 16-18 h. Although the colony-forming efficiency in soft agar of parental sensitive cells was only 0.5-4%, the 5-, 10-, 20-, and 40-fold ADR-resistant sublines had colony-forming efficiencies of 15, 20, 30, and 77%, respectively. Tumorigenicity in C57BL/6 mice of progressively ADR-resistant sublines was similar to parental sensitive cells following s.c. and i.p. implantation of 10(5)-10(6) tumor cells. Experimental pulmonary metastases were significantly lower in ADR-resistant sublines with progressive resistance. Additionally, unlike the parental sensitive and 5-fold ADR-resistant B16-BL6 cells, the 10-, 20-, and 40-fold ADR-resistant sublines were spontaneously nonmetastatic. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical detection of P-glycoprotein revealed the presence of a Mr 170,000 plasma membrane glycoprotein in the 40-fold ADR-resistant subline and its counterpart maintained for 1 year in ADR-free medium. Results from this study suggest that progressively ADR-resistant B16-BL6 mouse melanoma cells selected in vitro demonstrate a marked increase in colony formation in soft agar and a decrease in the ability to produce pulmonary metastases, without alterations in tumorigenicity.

EGRET observations of the BL Lacertae objects 0716+714 and 0521-365

NASA Technical Reports Server (NTRS)

Lin, Y. C.; Bertsch, D. L.; Dingus, B. L.; Esposito, J. A.; Fichtel, C. E.; Hartman, R. C.; Hunter, S. D.; Kanbach, G.; Kniffen, D. A.; Mayer-Hasselwander, H. A.

1995-01-01

During the Compton Observatory's viewing programs Phase 1 (1991 April to 1992 November, also known as the All-Sky Survey) and Phase 2 (1992 November to 1993 September), the BL Lac object 0716+714 was in the field of view of the EGRET telescope a total of six times, three times in Phase 1 and three more times in Phase 2, while the BL Lac object 0521-365 was in the field of view of EGRET only once in Phase 1. The source 0716+714 was detected in high-energy gamma rays by EGRET at a flux level of (2.0 +/- 0.4) x 10(exp -7) photons/sq cm/s for E greater than 100 MeV with a 6 sigma significance when it was first observed by EGRET in 1992 January 10 to 23. The corresponding spectral slope of the photon number distribution is determined to be -2.04 +/- 0.33. The gamma-ray flux of 0716+714 showed considerable time variability in subsequent EGRET observations. But the spectral slope stayed about the same within the statistical uncertainties of the EGRET data. The average spectral slope of the four viewing periods during which the photon flux of 0716+714 stayed above the EGRET detection threshold is found to be -1.85 +/- 0.20 from the combined data. The source 0521+365 was detected by EGRET in 1992 May 14 to June 4 at a flux level of (1.8 +/- 0.5) x 10(exp -7) photons/sq cm/s for E greater than 100 MeV with a 4 sigma significance. The corresponding spectral slope of the photon number distribution is found to be 2.16 +/- 0.36. Details of the observations of these two BL Lac objects with the EGRET telescope are presented.

The influence of H-2 genetic factors on the development of benign monoclonal gammopathy in ageing H-2 congenic C57BL and BALB mice.

PubMed Central

van den Akker, T W; Tio-Gillen, A P; Benner, R; Zurcher, C; Radl, J

1987-01-01

The role of H-2 genetic factors in the development of benign monoclonal gammopathy (BMG) was investigated in six H-2 congenic C57BL and BALB strains (C57BL/10.ScSn and BALB.B: H-2b; B10.D2 and BALB/c: H-2d; B10.BR and BALB.K: H-2k) during ageing. The frequencies of homogeneous immunoglobulins (H-Ig), both single and multiple, in the three C57BL strains were higher than those in the corresponding three BALB strains. No relationship was found with a particular H-2 haplotype. The most frequent H-Ig isotype within the C57BL strains was IgG2a, within BALB.B and BALB.K mice IgG3 and in BALB/c mice IgG1. Categorization of the monoclonal gammopathies (MG) on the basis of their origin showed a single transient monoclonal B-cell proliferation in 2-5% and 3-9% of the C57BL and BALB mice positive for H-Ig, respectively. Multiple myeloma or B-cell lymphoma were found to be responsible for about 1% of the paraproteinaemias in all strains. Persistent, non-progressive MG, most likely BMG, was detected in 70-81% and 39-46% of the C57BL and BALB mice positive for H-Ig, respectively. The remaining 14-24% and 50-58% of the, respectively, C57BL and BALB mice positive for H-Ig could not be evaluated in time. The H-2 haplotypes under investigation were not associated with the onset, occurrence, multiplicity, persistence or isotype of the MG developing in these H-2 congenic C57BL and BALB strains during ageing. PMID:3443448

Characterization of age-associated changes in peripheral organ and brain region weights in C57BL/6 mice.

PubMed

Lessard-Beaudoin, Mélissa; Laroche, Mélissa; Demers, Marie-Josée; Grenier, Guillaume; Graham, Rona K

2015-03-01

In order to further understand age-related physiological changes and to have in depth reference values for C57BL/6 mice, we undertook a study to assess the effects of aging on peripheral organ weights, and brain region weights in wild type C57BL/6 male mice. Peripheral organs, body and brain region weights were collected from young (3-4 months), mid (12 months), old (23-28 months) and very old (>30 months) mice. Significant increases are observed with aging in body, liver, heart, kidney and spleen organ weights. A decrease in organ weight is observed with aging in liver and kidney only in the very old mice. In contrast, testes weight decreases with age. Within the brain, hippocampi, striata and olfactory bulbs weight decreases with age. These data further our knowledge of the anatomical and biological changes that occur with aging and provide reference values for physiological-based pharmacokinetic studies in C57BL/6 mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Generation of T-cells reactive to the poorly immunogenic B16-BL6 melanoma with efficacy in the treatment of spontaneous metastases.

PubMed

Geiger, J D; Wagner, P D; Cameron, M J; Shu, S; Chang, A E

1993-04-01

The B16-BL6 (BL6) melanoma is a poorly immunogenic murine tumor that is highly invasive and spontaneously metastasizes from the primary site. Utilizing an established anti-CD3/interleukin-2 (IL-2) culture procedure, we have previously reported that lymph nodes (LNs) draining immunogenic murine sarcomas contained preeffector cells that could be activated to differentiate into therapeutic effector cells for adoptive immunotherapy. By contrast, LNs draining the poorly immunogenic BL6 melanoma were found not to be a reliable source of preeffector cells. Instead, sensitization of preeffector cells reactive to BL6 required the subcutaneous inoculation of tumor admixed with Corynebacterium parvum. LN cells draining these vaccination sites demonstrated therapeutic efficacy only after subsequent anti-CD3/IL-2 activation. The sensitization of preeffector cells was dependent on the presence of tumor antigen and an optimal dose of C. parvum (< or = 50 micrograms). Furthermore, kinetic analysis revealed that the preeffector response was transient after tumor vaccination. The therapeutic efficacy of anti-CD3/IL-2 activated LN cells was further evaluated in the treatment of spontaneous macroscopic BL6 visceral metastases. Spontaneous visceral metastases were induced in animals by inoculation with BL6 tumor in the footpad followed by amputation of the primary tumor 3 weeks later. The systemic transfer of 10(8) anti-CD3/IL-2 activated T-cells and the concomitant intraperitoneal administration of subtherapeutic doses of IL-2 1 week after amputation cured 50% of the animals and prolonged median survival time (MST) to > 140 days. All mice except one that received no treatment or was treated with IL-2 alone succumbed to visceral metastases with an MST of approximately 23 days. This study characterizes a model whereby the weak immune response to the BL6 melanoma can be positively or negatively modulated for the generation of antitumor reactive T-cells useful in adoptive immunotherapy.

Identification of immunodominant Leishmania major antigenic markers of the early C57BL/6 and BALB/c mice infection stages.

PubMed

Sassi, Atfa; Kaak, Olfa; Elgaaied, Amel Benammar

2015-08-24

The C57BL/6 mouse strain is resistant to Leishmania (L.) major infection and, unlike susceptible BALB/c, develops small self healing cutaneous lesions. The specific antibody responses of C57BL/6 and BALB/c mice were previously characterized by the predominance of IgG2a ("resistant" isotype associated with Th1) and IgG1 ("pathogenic" isotype associated with Th2) antibodies, respectively. In this study, we looked for the presence of antigens able to elicit an exclusive or predominant IgG1 production during the early stages of C57BL/6 lesion development and checked whether they are recognized or not by BALB/c mice. We demonstrate first that IgG2a predominance in C57BL/6 sera occurs only late after infection whereas in BALB/c, IgG1 antibodies dominate mostly in the early stages. Interestingly, soon after inoculation of live amastigotes, C57BL/6 displayed an exclusive IgG1 reactivity against particular L. major antigens but with MWs different from those identified in BALB/c. Furthermore, mice immunized with killed amastigotes displayed striking differences in their immunodetection profiles, particularly for the IgG1 isotype. Taken together, the observed differences in the specific antibody repertoires between infected mice resulted, at least in part, from immunological events independent from those triggered by the replicating parasite, and bring new insights into the selection of future vaccine candidates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Variation in Airway Responsiveness of Male C57BL/6 Mice from 5 Vendors

PubMed Central

Chang, Herng-Yu Sucie; Mitzner, Wayne; Watson, Julie

2012-01-01

Mice are now the most commonly used animal model for the study of asthma. The mouse asthma model has many characteristics of the human pathology, including allergic sensitization and airway hyperresponsiveness. Inbred strains are commonly used to avoid variations due to genetic background, but variations due to rearing environment are not as well recognized. After a change in mouse vendors and a switch from C57BL/6J mice to C57BL/6N mice, we noted significant differences in airway responsiveness between the substrains. To further investigate the effect of vendor, we tested C57BL/6N mice from 3 other vendors and found significant differences between several of the substrains. To test whether this difference was due to genetic drift or rearing environment, we purchased new groups of mice from all 5 vendors, bred them in separate vendor-specific groups under uniform environmental conditions, and tested male first generation (F1) offspring at 8 to 10 wk of age. These F1 mice showed no significant differences in airway responsiveness, indicating that the rearing environment rather than genetic differences was responsible for the initial variation in pulmonary phenotype. The environmental factors that caused the phenotypic variation are unknown. However, differences between vendor in feed components, bedding type, or microbiome could have contributed. Whatever the basis, investigators using mouse models of asthma should be cautious in comparing data from mice obtained from different vendors. PMID:23043804

Pirbenicillin: Comparison with Carbenicillin and BL-P1654, Alone and with Gentamicin, Against Pseudomonas aeruginosa

PubMed Central

Lopez, Carlos E.; Standiford, Harold C.; Tatem, Beverly A.; Calia, Frank M.; Schimpff, Stephen C.; Snyder, Merrill J.; Hornick, Richard B.

1977-01-01

Minimum inhibitory concentrations (MIC) of pirbenicillin against 135 clinical isolates of Pseudomonas aeruginosa were one-fourth of those required for carbenicillin but two times higher than those for BL-P1654. Increasing the inoculum size produced an adverse effect on the bactericidal activity for all three antibiotics. This was more apparent for pirbenicillin than for carbenicillin, but less than the effect on BL-P1654. When concentrations of antibiotics likely to be achieved clinically were used, gentamicin increased the inhibitory and bactericidal effects of all three semisynthetic penicillins for the majority of isolates. Strains highly resistant to the aminoglycoside antibiotic, however, were inhibited no more by the penicillin-gentamicin combinations than by the most effective of the antibiotics alone. PMID:404963

Computer program BL2D for solving two-dimensional and axisymmetric boundary layers

NASA Technical Reports Server (NTRS)

Iyer, Venkit

1995-01-01

This report presents the formulation, validation, and user's manual for the computer program BL2D. The program is a fourth-order-accurate solution scheme for solving two-dimensional or axisymmetric boundary layers in speed regimes that range from low subsonic to hypersonic Mach numbers. A basic implementation of the transition zone and turbulence modeling is also included. The code is a result of many improvements made to the program VGBLP, which is described in NASA TM-83207 (February 1982), and can effectively supersede it. The code BL2D is designed to be modular, user-friendly, and portable to any machine with a standard fortran77 compiler. The report contains the new formulation adopted and the details of its implementation. Five validation cases are presented. A detailed user's manual with the input format description and instructions for running the code is included. Adequate information is presented in the report to enable the user to modify or customize the code for specific applications.

Upper limits from hard X-ray observations of five BL Lacertae objects

NASA Technical Reports Server (NTRS)

Bezler, M.; Gruber, D. E.; Rothschild, R. E.

1988-01-01

Results are presented from hard X-ray observations of the five brightest X-ray BL Lacertae objects: PKS 0548-322, Mrk 421 (=1101+384), 2A 1219+305, Mrk 501 (=1652+398), and PKS 2155-304. The observations covered the energy range 15-165 keV from August 1977 to December 1978. The results are compared with previous studies.

Increased water temperature renders single-housed C57BL/6J mice susceptible to antidepressant treatment in the forced swim test.

PubMed

Bächli, Heidi; Steiner, Michel A; Habersetzer, Ursula; Wotjak, Carsten T

2008-02-11

To investigate genotype x environment interactions in the forced swim test, we tested the influence of water temperature (20 degrees C, 25 degrees C, 30 degrees C) on floating behaviour in single-housed male C57BL/6J and BALB/c mice. We observed a contrasting relationship between floating and water temperature between the two strains, with C57BL/6J floating more and BALB/c floating less with increasing water temperature, independent of the lightening conditions and the time point of testing during the animals' circadian rhythm. Both strains showed an inverse relationship between plasma corticosterone concentration and water temperature, indicating that the differences in stress coping are unrelated to different perception of the aversive encounter. Treatment with desipramine (20mg/kg, i.p.) caused a reduction in immobility time in C57BL/6J mice if the animals were tested at 30 degrees C water temperature, with no effect at 25 degrees C and no effects on forced swim stress-induced corticosterone secretion. The same treatment failed to affect floating behaviour in BALB/c at any temperature, but caused a decrease in plasma corticosterone levels. Taken together we demonstrate that an increase in water temperature in the forced swim test exerts opposite effects on floating behaviour in C57BL/6J and BALB/c and renders single-housed C57BL/6J mice, but not BALB/c mice, susceptible to antidepressant-like behavioral effects of desipramine.

B16-BL6 melanoma cells release inhibitory factor(s) of active pump activity in isolated lymph vessels.

PubMed

Nakaya, K; Mizuno, R; Ohhashi, T

2001-12-01

We investigated whether supernatant cultured with melanoma cell lines B16-BL6 and K1735 or the Lewis lung carcinoma cell line (LLC) can regulate lymphatic pump activity with bioassay preparations isolated from murine iliac lymph vessels. B16-BL6 and LLC supernatants caused significant dilation of lymph microvessels with cessation of pump activity. B16-BL6 supernatant produced dose-related cessation of lymphatic pump activity. There was no significant tachyphylaxis in the supernatant-mediated inhibitory response of lymphatic pump activity. Pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME) or 10(-7) M or 10(-6) M glibenclamide and 5 x 10(-4) M 5-hydroxydecanoic acid caused significant reduction of supernatant-mediated inhibitory responses. Simultaneous treatment with 10(-3) M L-arginine and 3 x 10(-5) M L-NAME significantly lessened L-NAME-induced inhibition of the supernatant-mediated response, suggesting that endogenous nitric oxide (NO) plays important roles in supernatant-mediated inhibitory responses. Chemical treatment dialyzed substances of <1,000 molecular weight (MW), producing complete reduction of the supernatant-mediated response. In contrast, pretreatment with heating or digestion with protease had no significant effect on supernatant-mediated response. These findings suggest that B16-BL6 cells may release nonpeptide substance(s) of <1,000 MW, resulting in significant cessation of lymphatic pump activity via production and release of endogenous NO and activation of mitochondrial ATP-sensitive K(+) channels.

Differences in extinction of conditioned fear in C57BL/6 substrains are unrelated to expression of alpha-synuclein.

PubMed

Siegmund, Anja; Langnaese, Kristina; Wotjak, Carsten T

2005-02-28

C57BL/6 mice are commonly used as background strains for genetically modified mice, and little attention is usually paid to the notification of the specific substrain. However, it is known that C57BL/6NCrl (B6N) and C57BL/6JOlaHsd (B6JOla) mice differ in the course of extinction of conditioned fear (Stiedl O, Radulovic J, Lohmann R, Birkenfeld K, Palve M, Kammermeier J, et al. Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice. Behav Brain Res 1999;104:1-12), as well as in the expression of alpha-synuclein (Specht CG, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci 2001;2:11). We tested for a causal relationship between the two findings by employing B6N (expressing alpha-synuclein), B6JOla (not expressing alpha-syn) and the third strain C57BL/6JCrl (B6Jax, expressing alpha-syn). We show that alpha-syn does not account for differences in extinction in a fear conditioning task, as its expression did not covary with the decrease of freezing on repeated non-reinforced tone and context exposure in the three strains: B6Jax exhibited fastest extinction followed by B6JOla. In contrast, B6N showed persistent fear over the course of extinction training. The differences in extinction between B6JOla and B6N were unrelated to sensorimotor processing (pain threshold and basal tone reaction) and innate fear (light-dark test). However, B6Jax displayed less innate fear than B6JOla and B6N. Our results of marked differences in innate and conditioned fear in three B6 substrains illustrate the necessity of a strict adherence to an exact mouse strain nomenclature.

EXPERIMENTAL SUBCUTANEOUS CYSTICERCOSIS BY Taenia crassiceps IN BALB/c AND C57BL/6 MICE

PubMed Central

PEREIRA, Íria Márcia; LIMA, Sarah Buzaim; FREITAS, Aline de Araújo; VINAUD, Marina Clare; JUNIOR, Ruy de Souza LINO

2016-01-01

SUMMARY Human cysticercosis is one of the most severe parasitic infections affecting tissues. Experimental models are needed to understand the host-parasite dynamics involved throughout the course of the infection. The subcutaneous experimental model is the closest to what is observed in human cysticercosis that does not affect the central nervous system. The aim of this study was to evaluate macroscopically and microscopically the experimental subcutaneous cysticercosis caused by Taenia crassiceps cysticerci in BALB/c and C57BL/6 mice. Animals were inoculated in the dorsal subcutaneous region and macroscopic and microscopic aspects of the inflammatory process in the host-parasite interface were evaluated until 90 days after the inoculation (DAI). All the infected animals presented vesicles containing cysticerci in the inoculation site, which was translucent at 7 DAI and then remained opaque throughout the experimental days. The microscopic analysis showed granulation tissue in BALB/c mice since the acute phase of infection evolving to chronicity without cure, presenting 80% of larval stage cysticerci at 90 DAI. While C57BL/6 mice presented 67% of final stage cysticerci at 90 DAI, the parasites were surrounded by neutrophils evolving to the infection control. It is possible to conclude that the genetic features of susceptibility (BALB/c) or resistance (C57BL/6) were confirmed in an experimental subcutaneous model of cysticercosis. PMID:27410915

EXPERIMENTAL SUBCUTANEOUS CYSTICERCOSIS BY Taenia crassiceps IN BALB/c AND C57BL/6 MICE.

PubMed

Pereira, Íria Márcia; Lima, Sarah Buzaim; Freitas, Aline de Araújo; Vinaud, Marina Clare; Junior, Ruy de Souza Lino

2016-07-11

Human cysticercosis is one of the most severe parasitic infections affecting tissues. Experimental models are needed to understand the host-parasite dynamics involved throughout the course of the infection. The subcutaneous experimental model is the closest to what is observed in human cysticercosis that does not affect the central nervous system. The aim of this study was to evaluate macroscopically and microscopically the experimental subcutaneous cysticercosis caused by Taenia crassiceps cysticerci in BALB/c and C57BL/6 mice. Animals were inoculated in the dorsal subcutaneous region and macroscopic and microscopic aspects of the inflammatory process in the host-parasite interface were evaluated until 90 days after the inoculation (DAI). All the infected animals presented vesicles containing cysticerci in the inoculation site, which was translucent at 7 DAI and then remained opaque throughout the experimental days. The microscopic analysis showed granulation tissue in BALB/c mice since the acute phase of infection evolving to chronicity without cure, presenting 80% of larval stage cysticerci at 90 DAI. While C57BL/6 mice presented 67% of final stage cysticerci at 90 DAI, the parasites were surrounded by neutrophils evolving to the infection control. It is possible to conclude that the genetic features of susceptibility (BALB/c) or resistance (C57BL/6) were confirmed in an experimental subcutaneous model of cysticercosis.

Genistein suppresses adhesion-induced protein tyrosine phosphorylation and invasion of B16-BL6 melanoma cells.

PubMed

Yan, C; Han, R

1998-07-03

Protein tyrosine phosphorylation occurs as one of the earlier events in cancer cell-extracellular matrix (ECM) interaction. With immunoblot analysis and immunofluorescence microscopy, genistein was found to suppress the tyrosine phosphorylation of proteins located at the cell periphery, including a 125 kDa protein, when B16-BL6 melanoma cells attached to and interacted with ECM. When accompanied by the suppression of adhesion-induced protein tyrosine phosphorylation, the invasive potential of B16-BL6 cells through reconstituted basement membrane was decreased significantly. However, neither adhesive capability nor cell growth was significantly affected by genistein. Therefore, the interruption of cancer cell-ECM interaction by suppression of protein tyrosine phosphorylation may contribute to invasion prevention of genistein.

Effectiveness of a patient education programme in heart failure with preserved ejection fraction: Results from the ODIN cohort study using propensity score matching.

PubMed

Agrinier, Nelly; Schockmel, Matthieu; Thilly, Nathalie; Laborde-Castérot, Hervé; Jourdain, Patrick; Alla, François; Leclercq, Christophe; Dany, François; Druelle, Justine; Drouet, Emilie; Mulak, Geneviève; Juillière, Yves

2018-01-01

Patient education programmes (PEP) are recommended for patients with heart failure but have not been specifically assessed in heart failure with preserved ejection fraction (HFpEF). To assess the effectiveness of a structured PEP in reducing all-cause mortality in patients with HFpEF. Patients with HFpEF were selected from the ODIN cohort, designed to assess PEP effectiveness in patients with HF whatever their ejection fraction, included from 2007 to 2010, and followed up until 2013. Baseline sociodemographic, clinical, biological and therapeutic characteristics were collected. At inclusion, patients were invited to participate in the PEP, which consisted of educational diagnosis, education sessions and final evaluation. Education focused on HF pathophysiology and medication, symptoms of worsening HF, dietary recommendations and management of exercise. Propensity score matching and Cox models were performed. Of 849 patients with HFpEF, 572 (67.4%) participated in the PEP and 277 (32.6%) did not. Patients who participated in the PEP were younger (67.0±13.1 vs 76.1±13.2 years; standardized difference [StDiff] =-54.6%), less often women (39.7% vs 48.4%; StDiff =-17.6%) and presented more often with hypercholesterolaemia (55.2% vs 35.2%; StDiff 41.2%), smoking (35.1% vs 28.7%; StDiff 13.8%), alcohol abuse (14.1% vs 8.9%; StDiff 16.5%) and ischaemic HF (38.7% vs 29.2%; StDiff 20.0%) than those who did not; they also presented with better clinical cardiovascular variables. After propensity score matching, baseline characteristics were balanced, except hypertension (postmatch StDiff 19.1%). The PEP was associated with lower all-cause mortality (pooled hazard ratio 0.70, 95% confidence interval 0.49-0.99; P=0.042). This association remained significant after adjustment for hypertension (adjusted pooled hazard ratio 0.68, 95% confidence interval 0.48-0.97; P=0.036). In this investigation, a structured PEP was associated with lower all-cause mortality. Patient education

Construction and Commissioning of BL37XU at SPring-8

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

Terada, Yasuko; Goto, Shunji; Takimoto, Naoki

2004-05-12

Trace element analysis beamline (BL37XU) at SPring-8 was designed for application to various X-ray fluorescence analyses such as XRF imaging, XAFS, TXRF and XRF holography. The beamline has of two branches, one being a SPring-8 standard undulator-beamline optics branch (Branch A) and the other a high-energy branch (Branch B). In the experimental hutches, several kinds of experimental device are equipped. The end-stations have been opened to public use since November 2002, and various experiments have been carried out.

Gastrodia elata Bl. Attenuated learning deficits induced by forced-swimming stress in the inhibitory avoidance task and Morris water maze.

PubMed

Chen, Pei-Ju; Liang, Keng-Chen; Lin, Hui-Chen; Hsieh, Ching-Liang; Su, Kuan-Pin; Hung, Mei-Chu; Sheen, Lee-Yan

2011-06-01

This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.

95 years anniversary of Professor BL Kashcheyev (1920 - 2004) - the well-known Ukrainian researcher of meteors by the radar method

NASA Astrophysics Data System (ADS)

Kolomiyets, Svitlana

2015-08-01

Meteor astronomy is constantly evolving. We can distinguish several stages in the development of meteor astronomy. One of these steps is the period associated with carrying out the global program called "International Geophysical Year 1957" (IGY1957). Thanks to this program in Ukraine in Kharkiv has been studied meteors using radar techniques. One of the organizers of the IGY 1957 meteor program execution in Ukraine (and in the former Soviet Union) was prof. BL Kashcheyev (1920-2004). At the IAU GA in 1958 prof. BL Kashcheyev made the report on the meteor radar studies in Kharkiv. These research were considered by the IAU Commission 22 as the best in the world. The name of Professor BL Kashcheyev related to the creation of the Kharkiv meteor radar system and the long series of meteor observations, creating the database of 250 thousand orbits of faint meteors (12^ M), carrying out the variety of meteor projects (including the GLOBMET). In 2004 the Kharkiv meteor radar complex was given the status of national heritage of Ukraine. In 2007, the organizers of the program "International Heliophisic Year 2007" (IHY2007) remarked the BL Kashcheyev contribution to the IGY 1957 (the certificate and the pin "The IGY1957 Gold ").

Creating reference gene annotation for the mouse C57BL6/J genome assembly.

PubMed

Mudge, Jonathan M; Harrow, Jennifer

2015-10-01

Annotation on the reference genome of the C57BL6/J mouse has been an ongoing project ever since the draft genome was first published. Initially, the principle focus was on the identification of all protein-coding genes, although today the importance of describing long non-coding RNAs, small RNAs, and pseudogenes is recognized. Here, we describe the progress of the GENCODE mouse annotation project, which combines manual annotation from the HAVANA group with Ensembl computational annotation, alongside experimental and in silico validation pipelines from other members of the consortium. We discuss the more recent incorporation of next-generation sequencing datasets into this workflow, including the usage of mass-spectrometry data to potentially identify novel protein-coding genes. Finally, we will outline how the C57BL6/J genebuild can be used to gain insights into the variant sites that distinguish different mouse strains and species.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice.

PubMed

Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

2015-01-01

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

A Librational Model for the Propeller Blériot in the Saturnian Ring System

NASA Astrophysics Data System (ADS)

Seiler, M.; Sremčević, M.; Seiß, M.; Hoffmann, H.; Spahn, F.

2017-05-01

The reconstruction of the orbital evolution of the propeller structure Blériot orbiting in Saturn’s A ring from recurrent observations in Cassini ISS images yielded a considerable offset motion from the expected Keplerian orbit. This offset motion can be composed by three sinusoidal harmonics with amplitudes and periods of 1845, 152, 58 km and 11.1, 3.7, and 2.2 years, respectively. In this paper we present results from N-body simulations, where we integrated the orbital evolution of a moonlet, which is placed at the radial position of Blériot under the gravitational action of the Saturnian satellites. Our simulations yield that, especially the gravitational interactions with Prometheus, Pandora, and Mimas are forcing the moonlet to librate with the right frequencies, but the libration amplitudes are too small to explain the observations. Thus, further mechanisms are needed to explain the amplitudes of the forced librations—e.g., moonlet-ring interactions. Here, we develop a model, where the moonlet is allowed to be slightly displaced with respect to its created gaps breaking the point symmetry and causing a repulsive force in this way. As a result, the evolution of the moonlet’s longitude can be described by a harmonic oscillator. In the presence of external forcing by the outer moons, the libration amplitudes get the more amplified the closer the forcing frequency is to the eigenfrequency of the disturbed propeller oscillator. Applying our model to Blériot, it is possible to reproduce a libration period of 13 years with an amplitude of about 2000 km.

Wallerian degeneration in C57BL/6J and A/J mice: differences in time course of neurofilament and myelin breakdown, macrophage recruitment and iNOS expression

PubMed Central

de la Hoz, Cristiane L R; Oliveira, Alexandre L R; de S Queiroz, Luciano; Langone, Francesco

2003-01-01

The lower regeneration potential reported for C57BL/6J mice strain after peripheral nerve lesion may result from alterations in crucial events during Wallerian degeneration. We analysed neurofilament and myelin breakdown, macrophage recruitment, NADPH-diaphorase reaction and inducible nitric oxide synthase (iNOS) expression in transected sciatic nerves of C57BL/6J and A/J mice. The neurofilament volume density was lower in C57BL/6J strain mice at 1 and 3 days after lesion, and later equalled the density observed in A/J. C57BL/6J mice presented a high number of cells containing myelin debris, 3 and 5 days after the lesion. In both strains iNOS immunoreactivity was intense in macrophages and less evident in Schwann cells. However, a delay in macrophage recruitment and a lower percentage of iNOS-expressing macrophages on the third day were observed in C57BL/6J mice. NADPH-diaphorase reaction disclosed a similar pattern for both strains until the seventh day. However, at 5 days, cells with slender processes involving ellipsoid segments showed a well-defined cytoplasmic labelling in C57BL/6J whereas in A/J most of these cells exhibited a more granular and disperse labelling. We propose that these differences between A/J and C57BL/6J strains during Wallerian degeneration may be implicated in the lower regeneration potential observed in the latter. PMID:14686692

Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models

PubMed Central

Karthivashan, Govindarajan; Park, Shin-Young; Kim, Joon-Soo; Cho, Duk-Yeon

2017-01-01

Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains. PMID:28792471

Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models.

PubMed

Karthivashan, Govindarajan; Park, Shin-Young; Kim, Joon-Soo; Cho, Duk-Yeon; Ganesan, Palanivel; Choi, Dong-Kug

2017-08-09

Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.

XAFS and Protein Crystallography Beamline BL38B1 at SPring-8

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

Tanida, Hajime; Miura, Keiko; Takeshita, Kunikazu

2004-05-12

The SPring-8 bending magnet beamline BL38B1 is designed for R and D of optics, detectors, experiments for XAFS and protein X-ray crystallography (PX). This beamline has a multi-purpose hutch for two experimental stations of XAFS and PX, and removable optical benches used for R and D of detectors and instruments. The design and the performance of the beamline are presented.

Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice

NASA Astrophysics Data System (ADS)

Wu, Ruirui; Wu, Xiafang; Wang, Huihui; Fang, Xin; Li, Yongfang; Gao, Lanyue; Sun, Guifan; Pi, Jingbo; Xu, Yuanyuan

2017-03-01

Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.

Soft X-ray observations of two BL Lacertae objects - Markarian 421 and 501

NASA Technical Reports Server (NTRS)

Singh, K. P.; Garmire, G. P.

1985-01-01

This paper reports on the soft X-ray (0.15-2.8 keV) observations of two BL Lacertae-type objects, viz., Mrk 421 and Mrk 501. The observations were made with the low-energy detectors on the HEAO 1 satellite during the period 1977 August-1978 December. Steep, soft X-ray power-law spectra with photon index Gamma = 3 are found for both Mrk 421 and Mrk 501. The power-law models are found to give a significantly better fit than the thermal models to the observed pulse-height spectra of Mrk 421 and Mrk 501. Day-to-day soft X-ray (0.25 keV band) intensity variations are observed only in Mrk 501. No significant change is found in Gamma from both the BL Lac objects during the period of observations. However, the sum of all the X-ray observations from 1976 until 1980 can be understood in terms of two spectral components of variable intensity to account for the X-ray emission observed between 0.15 and 20 keV from Mrk 421 and Mrk 501.

The Millimeter-Radio Emission of BL Lacertae During Two γ-ray Outbursts

NASA Astrophysics Data System (ADS)

Kim, Dae-Won; Trippe, Sascha; Lee, Sang-Sung; Park, Jong-Ho; Kim, Jae-Young; Algaba, Juan-Carlos; Hodgson, Jeffrey A.; Kino, Motoki; Zhao, Guang-Yao; Wajima, Kiyoaki; Kang, Sincheol; Oh, Junghwan; Lee, Taeseok; Byun, Do-Young; Kim, Soon-Wook; Kim, Jeong-Sook

2017-12-01

We present a study of the inexplicit connection between radio jet activity and γ-ray emission of BL Lacertae (BL Lac; 2200+420). We analyze the long-term millimeter activity of BL Lac via interferometric observations with the Korean VLBI Network (KVN) obtained at 22, 43, 86, and 129 GHz simultaneously over three years (from January 2013 to March 2016); during this time, two γ-ray outbursts (in November 2013 and March 2015) can be seen in γ-ray light curves obtained from Fermi observations. The KVN radio core is optically thick at least up to 86 GHz; there is indication that it might be optically thin at higher frequencies. To first order, the radio light curves decay exponentially over the time span covered by our observations, with decay timescales of 411±85 days, 352±79 days, 310±57 days, and 283±55 days at 22, 43, 86, and 129 GHz, respectively. Assuming synchrotron cooling, a cooling time of around one year is consistent with magnetic field strengths B=2 μT and electron Lorentz factors γ=10,000. Taking into account that our formal measurement errors include intrinsic variability and thus over-estimate the statistical uncertainties, we find that the decay timescale τ scales with frequency ν like τ∝ν^{-0.2}. This relation is much shallower than the one expected from opacity effects (core shift), but in agreement with the (sub-)mm radio core being a standing recollimation shock. We do not find convincing radio flux counterparts to the γ-ray outbursts. The spectral evolution is consistent with the 'generalized shock model' of Valtaoja et al. (1992). A temporary increase in the core opacity and the emergence of a knot around the time of the second γ-ray event indicate that this γ-ray outburst might be an 'orphan' flare powered by the 'ring of fire' mechanism.

Finding the Balance of Autonomy on-Board Versus Man-Triggered Actions from Ground

NASA Astrophysics Data System (ADS)

Lundin, Stefan

Odin is a scientific, 3-axis stabilised, fine-pointing, small satellite with a sensitive payload that provides high quality spectroscopy data in the optical, mm and submm regions. End-users are atmosphere scientists as well as astronomers in Canada, France, Finland and Sweden. The satellite was successfully injected into orbit in February 2001 by a START-1 rocket. Designed, developed and procured by the Swedish Space Corporation, Odin is now operated by our company ten times per day from its dedicated control centre located at Esrange in the northern Sweden. The usage of the same organisation gave us the possibility to find an efficient trade-off between "degree of autonomy on-board" versus "future operational cost".. The necessity of sophisticated, hard-to-develop autonomy was judged against mission objectives, spacecraft safety and additional operational cost. In the paper, the operational philosophy of Odin is presented and based on gathered experience in-orbit, the most essential autonomous functions on-board are identified. Odin is a low cost satellite with very high performance. For comparison, it is capable of unique science with a pointing accuracy better than 15 arcseconds. The procurement and launch of the satellite ended up to a total cost of 45 MUSD using a tight project team of only ten persons truly responsible for their subsystems. The same amount of people now operates the satellite and staffs the Mission Control Centre.

Diverse manifestations of tumorigenicity and immunogenicity displayed by the poorly immunogenic B16-BL6 melanoma transduced with cytokine genes.

PubMed

Arca, M J; Krauss, J C; Strome, S E; Cameron, M J; Chang, A E

1996-05-01

We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete interleukin-2 (IL-2), IL-4, interferon gamma (IFN gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFN gamma and IL-4 partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy. Neither IL-2 nor IFN gamma secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not lead to enhanced induction of immune T cells. GM-CSF secretion was found to upregulate B7-1 expression in TDLN, consistent with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T cell immune reactivity to the poorly immunogenic BL6 tumor.

Using the Markov chain Monte Carlo method to study the physical properties of GeV-TeV BL Lac objects

NASA Astrophysics Data System (ADS)

Qin, Longhua; Wang, Jiancheng; Yang, Chuyuan; Yuan, Zunli; Mao, Jirong; Kang, Shiju

2018-01-01

We fit the spectral energy distributions (SEDs) of 46 GeV-TeV BL Lac objects in the frame of leptonic one-zone synchrotron self-Compton (SSC) model and investigate the physical properties of these objects. We use the Markov chain Monte Carlo (MCMC) method to obtain the basic parameters, such as magnetic field (B), the break energy of the relativistic electron distribution (γ ^' }b), and the electron energy spectral index. Based on the modeling results, we support the following scenarios for GeV-TeV BL Lac objects. (1) Some sources have large Doppler factors, implying other radiation mechanism should be considered. (2) Compared with flat spectrum quasars (FSRQs), GeV-TeV BL Lac objects have weaker magnetic fields and larger Doppler factors, which cause the ineffective cooling and shift the SEDs to higher bands. Their jet powers are around 4.0 × 1045 erg s-1, compared with radiation power, 5.0 × 1042 erg s-1, indicating that only a small fraction of jet power is transformed into the emission power. (3) For some BL Lacs with large Doppler factors, their jet components could have two substructures, e.g., the fast core and the slow sheath. For most GeV-TeV BL Lacs, Kelvin-Helmholtz instabilities are suppressed by their higher magnetic fields, leading to micro-variability or intro-day variability in the optical bands. (4) Combined with a sample of FSRQs, an anti-correlation between the peak luminosity, Lpk, and the peak frequency, νpk, is obtained, favoring the blazar sequence scenario. In addition, an anti-correlation between the jet power, Pjet, and the break Lorentz factor, γb, also supports the blazar sequence.

Reduced glutathione enhances fertility of frozen/thawed C57BL/6 mouse sperm after exposure to methyl-beta-cyclodextrin.

PubMed

Takeo, Toru; Nakagata, Naomi

2011-11-01

Sperm cryopreservation is useful for the effective storage of genomic resources derived from genetically engineered mice. However, freezing the sperm of C57BL/6 mice, the most commonly used genetic background for genetically engineered mice, considerably reduces its fertility. We previously reported that methyl-beta-cyclodextrin dramatically improved the fertility of frozen/thawed C57BL/6 mouse sperm. Recently, it was reported that exposing sperm to reduced glutathione may alleviate oxidative stress in frozen/thawed mouse sperm, thereby enhancing in vitro fertilization (IVF); however, the mechanism underlying this effect is poorly understood. In the present study, we examined the combined effects of methyl-beta-cyclodextrin and reduced glutathione on the fertilization rate of IVF with frozen/thawed C57BL/6 mouse sperm and the characteristic changes in the zona pellucida induced by reduced glutathione. Adding reduced glutathione to the fertilization medium increased the fertilization rate. Methyl-beta-cyclodextrin and reduced glutathione independently increased fertilization rates, and their combination produced the strongest effect. We found that reduced glutathione increased the amount of free thiols in the zona pellucida and promoted zona pellucida enlargement. Finally, 2-cell embryos produced by IVF with the addition of reduced glutathione developed normally and produced live offspring. In summary, we have established a novel IVF method using methyl-beta-cyclodextrin during sperm preincubation and reduced glutathione during the IVF procedure to enhance fertility of frozen/thawed C57BL/6 mouse sperm.

Divergent compensatory responses to high-fat diet between C57BL6/J and C57BLKS/J inbred mouse strains.

PubMed

Sims, Emily K; Hatanaka, Masayuki; Morris, David L; Tersey, Sarah A; Kono, Tatsuyoshi; Chaudry, Zunaira Z; Day, Kathleen H; Moss, Dan R; Stull, Natalie D; Mirmira, Raghavendra G; Evans-Molina, Carmella

2013-12-01

Impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) are polygenic disorders with complex pathophysiologies; recapitulating them with mouse models is challenging. Despite 70% genetic homology, C57BL/6J (BL6) and C57BLKS/J (BLKS) inbred mouse strains differ in response to diet- and genetic-induced obesity. We hypothesized these differences would yield insight into IGT and T2DM susceptibility and response to pharmacological therapies. To this end, male 8-wk-old BL6 and BLKS mice were fed normal chow (18% kcal from fat), high-fat diet (HFD; 42% kcal from fat), or HFD supplemented with the PPARγ agonist pioglitazone (PIO; 140 mg PIO/kg diet) for 16 wk. Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were undertaken. BL6 mice gained weight and adiposity in response to HFD, leading to peripheral insulin resistance that was met with increased β-cell proliferation and insulin production. By contrast, BLKS mice responded to HFD by restricting food intake and increasing activity. These behavioral responses limited weight gain and protected against HFD-induced glucose intolerance, which in this strain was primarily due to β-cell dysfunction. PIO treatment did not affect HFD-induced weight gain in BL6 mice, and decreased visceral fat mass, whereas in BLKS mice PIO increased total fat mass without improving visceral fat mass. Differences in these responses to HFD and effects of PIO reflect divergent human responses to a Western lifestyle and underscore the careful consideration needed when choosing mouse models of diet-induced obesity and diabetes treatment.

Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells through inducing apoptosis via decreasing Bcl-2 expression.

PubMed

Zhang, X; Xu, Q; Saiki, I

2000-01-01

Quercetin has been known to have anti-tumor and anti-oxidation activities. In the present study, we have investigated its in vitro anti-metastatic activity. Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in a dose-dependent manner but did not affect their adhesion to either laminin, fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the proliferation of B16-BL6 cells only in the case of time incubation longer than 48 h. Quercetin dose-dependently decreased the cell rates in S and G2-M phases of cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6 cells was also demonstrated by flow cytometric assay as well as DNA fragmentation with a typical 180-bp ladder band in agarose electrophoresis and a quantitative analysis. Furthermore, quercetin markedly inhibited the expression of anti-apoptotic protein Bcl-2 but hardly influenced Bcl-XL. These results suggest that the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are closely associated with the arrest of cell cycle as well as the induction of apoptosis by decreasing the Bcl-2 expression.

Modulation of B16-BL6 murine melanoma metastatic phenotype by tyrosine and phenylalanine restriction in the absence of host selection pressures.

PubMed

Elstad, C A; Meadows, G G

1993-01-01

We previously showed that restriction of tyrosine (Tyr) and phenylalanine (Phe) in vivo dramatically suppresses the metastatic phenotype of B16-BL6 (BL6) murine melanoma. Present results indicate a direct effect of Tyr and Phe restriction on the tumor in the absence of host selection pressures. Lung colonizing ability of BL6 is dramatically suppressed after one passage in vitro in media containing low levels of Tyr and Phe. This antimetastatic effect is immediate, stable for at least 5 in vitro passages in Tyr and Phe restricted media, and evident event after levels of Tyr and Phe are restored to normal. Heterogeneity for lung colonizing ability is suppressed, as evidence by fewer tumor colonies formed by clones following i.v. inoculation into mice fed normal diet. This suppression of BL6 metastatic phenotype is not due to differential clearance and retention in the lung or to decreased growth, but is specific for these two amino acids. As the mechanism(s) for the antitumor effects of Tyr and Phe restriction are detailed, the relevance of Tyr and Phe restriction as an early adjuvant to effective cancer treatment can be explored.

Differences in cocaine-induced place preference persistence, locomotion and social behaviors between C57BL/6J and BALB/cJ mice

PubMed Central

WANG, Jian-Li; WANG, Bei; CHEN, Wen

2014-01-01

C57BL/6J and BALB/cJ mice display significant differences in sociability and response to drugs, but the phenotypic variability of their susceptibility to cocaine is still not well known. In this study, the differences between these two mice strains in the persistence of cocaine-induced conditioned place preference (CPP), as well as the locomotion and social behaviors after the 24-hour withdrawal from a four-day cocaine (20 mg/kg/day) administration were investigated. The results showed that the cocaine-induced CPP persisted over two weeks in C57BL/6J mice, while it diminished within one week among BALB/cJ mice. After 24-hours of cocaine withdrawal, high levels of locomotion as well as low levels of social interaction and aggressive behavior were found in C57BL/6J mice, but no significant changes were found in BALB/cJ mice, indicating that cocaine-induced CPP persistence, locomotion and social behavior are not consistent between these two strains, and that overall C57BL/6J mice are more susceptible to cocaine than BALB/cJ mice at the tested doses. PMID:25297083

Differences in cocaine-induced place preference persistence, locomotion and social behaviors between C57BL/6J and BALB/cJ mice.

PubMed

Wang, Jian-Li; Wang, Bei; Chen, Wen

2014-09-01

C57BL/6J and BALB/cJ mice display significant differences in sociability and response to drugs, but the phenotypic variability of their susceptibility to cocaine is still not well known. In this study, the differences between these two mice strains in the persistence of cocaine-induced conditioned place preference (CPP), as well as the locomotion and social behaviors after the 24-hour withdrawal from a four-day cocaine (20 mg/kg/day) administration were investigated. The results showed that the cocaine-induced CPP persisted over two weeks in C57BL/6J mice, while it diminished within one week among BALB/cJ mice. After 24-hours of cocaine withdrawal, high levels of locomotion as well as low levels of social interaction and aggressive behavior were found in C57BL/6J mice, but no significant changes were found in BALB/cJ mice, indicating that cocaine-induced CPP persistence, locomotion and social behavior are not consistent between these two strains, and that overall C57BL/6J mice are more susceptible to cocaine than BALB/cJ mice at the tested doses.

How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

PubMed

Combe, Roy; Mudgett, John; El Fertak, Lahcen; Champy, Marie-France; Ayme-Dietrich, Estelle; Petit-Demoulière, Benoit; Sorg, Tania; Herault, Yann; Madwed, Jeffrey B; Monassier, Laurent

2016-01-01

Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies. The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry). In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges. Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are

An emerging population of BL Lacs with extreme properties: towards a class of EBL and cosmic magnetic field probes?

NASA Astrophysics Data System (ADS)

Bonnoli, G.; Tavecchio, F.; Ghisellini, G.; Sbarrato, T.

2015-07-01

High-energy observations of extreme BL Lac objects, such as 1ES 0229+200 or 1ES 0347-121, recently focused interest both for blazar and jet physics and for the implication on the extragalactic background light and intergalactic magnetic field estimate. However, the number of these extreme highly peaked BL Lac objects (EHBL) is still rather small. Aiming at increase their number, we selected a group of EHBL candidates starting from the BL Lac sample of Plotkin et al. (2011), considering those undetected (or only barely detected) by the Large Area Telescope onboard Fermi and characterized by a high X-ray versus radio flux ratio. We assembled the multiwavelength spectral energy distribution of the resulting nine sources, profiting of publicly available archival observations performed by Swift, GALEX, and Fermi satellites, confirming their nature. Through a simple one-zone synchrotron self-Compton model we estimate the expected very high energy flux, finding that in the majority of cases it is within the reach of present generation of Cherenkov arrays or of the forthcoming Cherenkov Telescope Array.

BALB/c mice display more enhanced BCG vaccine induced Th1 and Th17 response than C57BL/6 mice but have equivalent protection.

PubMed

Garcia-Pelayo, M Carmen; Bachy, Véronique S; Kaveh, Daryan A; Hogarth, Philip J

2015-01-01

It is generally assumed that the inbred mouse strains BALB/c (H-2(d)) and C57BL/6 (H-2(b)) respond to mycobacterial infection with distinct polarisation of T helper responses, with C57BL/6 predisposed to Th1 and BALB/c to Th2. We investigated this in a BCG-immunisation, Mycobacterium bovis challenge model. Following immunisation, lung and spleen cell cytokine responses to in vitro re-stimulation with a cocktail of seven secreted, immunogenic, recombinant mycobacterial proteins were determined. In both lung and spleen, BALB/c cells produced at least 2-fold more IFN-γ, and up to 7-fold more IL-2 and IL-17 than C57BL/6 cells, whereas IL-10 production was reciprocally increased in C57BL/6 mice. These data suggest that, contrary to reports in the literature, specific mycobacterial antigens are able to induce strong Th1 and Th17 responses in BALB/c mice following BCG vaccination, whilst in C57BL/6 mice, the Th1 response is partly counterbalanced by IL-10. After subsequent M. bovis low dose challenge, protection, as measured in the lungs and dissemination to the spleen, was equivalent in BALB/c and C57BL/6 mice, indicating that BCG-induced immunity was equivalent in both strains. Thus, the differential immune responses do not appear to have a role in protection, but further, as yet unidentified, specific immune responses play a significant role. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

SPring-8 BL44XU, beamline designed for structure analysis of large biological macromolecular assemblies

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

Higashiura, Akifumi, E-mail: hgsur-a@protein.osaka-u.ac.jp; Yamashita, Eiki; Yoshimura, Masato

2016-07-27

Beamline BL44XU at SPring-8 is operated by the Institute for Protein Research of Osaka University. The beamline is designed for X-ray crystallography of large biological macromolecular assemblies. Here we show its detailed performances, results, and the ongoing upgrade plans.

Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior and Metabolite Levels in 129Sv and Bl6 Mouse Strains.

PubMed

Vanaveski, Taavi; Narvik, Jane; Innos, Jürgen; Philips, Mari-Anne; Ottas, Aigar; Plaas, Mario; Haring, Liina; Zilmer, Mihkel; Vasar, Eero

2018-01-01

The main goal of the study was to characterize the behavioral and metabolomic profiles of repeated administration (for 11 days) of d-amphetamine (AMPH, 3 mg/kg i. p.), indirect agonist of dopamine (DA), in widely used 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6) mouse strains. Acute administration of AMPH (acute AMPH) induced significantly stronger motor stimulation in Bl6. However, repeated administration of AMPH (repeated AMPH) caused stronger motor sensitization in 129Sv compared acute AMPH. Body weight of 129Sv was reduced after repeated saline and AMPH, whereas no change occurred in Bl6. In the metabolomic study, acute AMPH induced an elevation of isoleucine and leucine, branched chain amino acids (BCAA), whereas the level of hexoses was reduced in Bl6. Both BCAAs and hexoses remained on level of acute AMPH after repeated AMPH in Bl6. Three biogenic amines [asymmetric dimethylarginine (ADMA), alpha-aminoadipic acid (alpha-AAA), kynurenine] were significantly reduced after repeated AMPH. Acute AMPH caused in 129Sv a significant reduction of valine, lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:2, lysoPC a C20:4), phosphatidylcholine (PC) diacyls (PC aa C34:2, PC aa C36:2, PC aa C36:3, PC aa C36:4) and alkyl-acyls (PC ae C38:4, PC ae C40:4). However, repeated AMPH increased the levels of valine and isoleucine, long-chain acylcarnitines (C14, C14:1-OH, C16, C18:1), PC diacyls (PC aa C38:4, PC aa C38:6, PC aa C42:6), PC acyl-alkyls (PC ae C38:4, PC ae C40:4, PC ae C40:5, PC ae C40:6, PC ae C42:1, PC ae C42:3) and sphingolipids [SM(OH)C22:1, SM C24:0] compared to acute AMPH in 129Sv. Hexoses and kynurenine were reduced after repeated AMPH compared to saline in 129Sv. The established changes probably reflect a shift in energy metabolism toward lipid molecules in 129Sv because of reduced level of hexoses. Pooled data from both strains showed that the elevation of isoleucine and leucine was a prominent biomarker of AMPH-induced behavioral sensitization

[Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

PubMed

Zhang, Li-quan; Xu, Jia-ni; Wang, Zhen-zhen; Zeng, Li-jun; Ye, Yi-lu; Zhang, Wei-ping; Wei, Er-qing; Zhang, Qi

2014-05-01

To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (Ps<0.05). However, minocycline significantly reduced the central distance and central time and increased the periphery time (Ps<0.05). Neurons were damaged in hippocampus, cortex and striatum after GCI, which manifested by decreased neurons and the most serious damage in hippocampal CA1 region. Minocycline significantly improved the neuron appearance and increased the neuron number in hippocampus and striatum (P<0.001 or P<0.05). Locomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.

Effects of genistein, a soybean-derived isoflavone, on proliferation and differentiation of B16-BL6 mouse melanoma cells.

PubMed

Yan, C H; Chen, X G; Li, Y; Han, R

1999-01-01

Genistein, a soybean-derived isoflavone, may contribute to the lower cancer incidence in South Asian countries. In this study, the effects and molecular mechanisms of genistein on growth and differentiation of B16-BL6 mouse melanoma cells were investigated. Genistein suppressed the growth of these melanoma cells. The IC50 value is 15.5 microM. On the other hand, genistein induced the changes of cell shape and cytoskeletal network. The cytoskeletal filaments were induced to form a bundle along the direction of elongation of the cells. Moreover, tyrosine phosphorylation levels of cytoskeleton-associated proteins decreased after the cells were exposed to 20 or 30 microM of genistein for 3 days. All these morphological and molecular changes were accompanied by appearance of the differentiated phenotypes. Genistein induced the increase of cellular melanin content, enhancement of tyrosinase activity, and decrease of colonization potentials in soft agar in a time-dependent and dose-dependent manner. The effective concentration was no more than 10 microM after 3 days' exposure. The tumorigenic potentials of B16-BL6 cells in C57BL/6 mouse also decreased after exposure to 20 or 30 microM of genistein for 3 days. When expressions of tumor-related genes were investigated in the differentiation-induced cells, the content of P53 dramatically increased while that of c-Myc protein decreased. Therefore, due to its ability to induce cellular and molecular changes, genistein suppressed the growth and induced differentiated phenotypes in B16-BL6 melanoma cells.

THE PHYSICAL CHARACTERIZATION OF THE POTENTIALLY HAZARDOUS ASTEROID 2004 BL86: A FRAGMENT OF A DIFFERENTIATED ASTEROID

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

Reddy, Vishnu; Sanchez, Juan A.; Takir, Driss

The physical characterization of potentially hazardous asteroids (PHAs) is important for impact hazard assessment and evaluating mitigation options. Close flybys of PHAs provide an opportunity to study their surface photometric and spectral properties that enable the identification of their source regions in the main asteroid belt. We observed PHA (357439) 2004 BL86 during a close flyby of the Earth at a distance of 1.2 million km (0.0080 AU) on 2015 January 26, with an array of ground-based telescopes to constrain its photometric and spectral properties. Lightcurve observations showed that the asteroid was a binary and subsequent radar observations confirmed themore » binary nature and gave a primary diameter of 300 m and a secondary diameter of 50–100 m. Our photometric observations were used to derive the phase curve of 2004 BL86 in the V-band. Two different photometric functions were fitted to this phase curve, the IAU H–G model and the Shevchenko model. From the fit of the H–G function we obtained an absolute magnitude of H = 19.51 ± 0.02 and a slope parameter of G = 0.34 ± 0.02. The Shevchenko function yielded an absolute magnitude of H = 19.03 ± 0.07 and a phase coefficient b = 0.0225 ± 0.0006. The phase coefficient was used to calculate the geometric albedo (Ag) using the relationship found by Belskaya and Schevchenko, obtaining a value of Ag = 40% ± 8% in the V-band. With the geometric albedo and the absolute magnitudes derived from the H–G and the Shevchenko functions we calculated the diameter (D) of 2004 BL86, obtaining D = 263 ± 26 and D = 328 ± 35 m, respectively. 2004 BL86 spectral band parameters and pyroxene chemistry are consistent with non-cumulate eucrite meteorites. A majority of these meteorites are derived from Vesta and are analogous with surface lava flows on a differentiated parent body. A non-diagnostic spectral curve match using the Modeling for Asteroids tool yielded a best-match with non-cumulate eucrite Bereba. Three

Effect of LI4 and BL32 acupressure on labor pain and delivery outcome in the first stage of labor in primiparous women: A randomized controlled trial.

PubMed

Ozgoli, Giti; Sedigh Mobarakabadi, Sedigheh; Heshmat, Reza; Alavi Majd, Hamid; Sheikhan, Zohreh

2016-12-01

This study examines and compares the effect of LI4 and BL32 acupressure with each other and control group on labor pain and delivery outcomes. In this randomized controlled trial, 105 primiparous women in active phase of first-stage of labor were equally assigned to two experimental groups [acupressure on LI4 (n=35) or BL32 (n=35)] and a control group (n=35). The experimental groups received routine labor care and acupressure in LI4 or BL32 points in three cervical dilatations (4-5, 6-7, and 8-10cm). The control group only received routine labor care. Pain was assessed by numerical rating scale in three cervical dilatations, before and after intervention. Type of delivery (cesarean, vaginal or operative delivery) and neonatal Apgar score were considered as delivery outcomes, these data collected by a check list. Data were analyzed using Repeated Measurement, ANOVA, Chi-Square, Kruskal-Wallis, and Mann-Whitney tests. Pain reduction was significantly greater in LI4 and BL32 groups compared with control in all periods of study. Also, acupressure on BL32 point was superior to LI4 point in pain relief in the first and second but not third intervention. No statistically significant difference was observed in terms of delivery outcomes. Acupressure on BL32 and LI4 points are effective in reducing labor pain compared to control group with a slight superiority for BL32 points. Acupressure on these points could apply for relief pain in labor as an inexpensive and easy to administered method. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differences in the degree of cerulein-induced chronic pancreatitis in C57BL/6 mouse substrains lead to new insights in identification of potential risk factors in the development of chronic pancreatitis.

PubMed

Ulmasov, Barbara; Oshima, Kiyoko; Rodriguez, Michael G; Cox, Roger D; Neuschwander-Tetri, Brent A

2013-09-01

A frequently used experimental model of chronic pancreatitis (CP) recapitulating human disease is repeated injection of cerulein into mice. C57BL/6 is the most commonly used inbred mouse strain for biomedical research, but widespread demand has led to generation of several substrains with subtly different phenotypes. In this study, two common substrains, C57BL/6J and C57BL/6NHsd, exhibited different degrees of CP, with C57BL/6J being more susceptible to repetitive cerulein-induced CP as assessed by pancreatic atrophy, pancreatic morphological changes, and fibrosis. We hypothesized that the deficiency of nicotinamide nucleotide transhydrogenase (NNT) protein in C57BL/6J is responsible for the more severe C57BL/6J phenotype but the parameters of CP in NNT-expressing transgenic mice generated on a C57BL6/J background do not differ with those of wild-type C57BL/6J. The highly similar genetic backgrounds but different CP phenotypes of these two substrains presents a unique opportunity to discover genes important in pathogenesis of CP. We therefore performed whole mouse genome Affymetrix microarray analysis of pancreatic gene expression of C57BL/6J and C57BL/6NHsd before and after induction of CP. Genes with differentially regulated expression between the two substrains that might be candidates in CP progression included Mmp7, Pcolce2, Itih4, Wdfy1, and Vtn. We also identified several genes associated with development of CP in both substrains, including RIKEN cDNA 1810009J06 gene (trypsinogen 5), Ccl8, and Ccl6. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Corticosterone facilitates extinction of fear memory in BALB/c mice but strengthens cue related fear in C57BL/6 mice.

PubMed

Brinks, V; de Kloet, E R; Oitzl, M S

2009-04-01

Corticosterone, the naturally occurring glucocorticoid of rodents is secreted in response to stressors and is known for its facilitating and detrimental effects on emotional learning and memory. The large variability in the action of corticosterone on processing of emotional memories is postulated to depend on genetic background and the spatio-temporal domain in which the hormone operates. To address this hypothesis, mice of two strains with distinct corticosterone secretory patterns and behavioural phenotype (BALB/c and C57BL/6J) were treated with corticosterone (250 microg/kg, i.p.), either 5 min before or directly after acquisition in a fear conditioning task. As the paradigm allowed assessing in one experimental procedure both context- and cue-related fear behaviour, we were able to detect generalization and specificity of fear. BALB/c showed generalized strong fear memory, while C57BL/6J mice discriminated between freezing during context- and cue episodes. Corticosterone had opposite effects on fear memory depending on the strain and time of injection. Corticosterone after acquisition did not affect C57BL/6J mice, but destabilized consolidation and facilitated extinction in BALB/c. Corticosterone 5 min before acquisition strengthened stress-associated signals: BALB/c no longer showed lower fear memory, while C57BL/6J mice displayed increased fear memory and impaired extinction in cue episodes. We propose that corticosterone-induced facilitation of fear memory in C57BL/6J mice can be used to study the development of fear memories, corticosterone administration in BALB/c mice presents a model to examine treatment. We conclude that genetic background and time of corticosterone action are modifiers of fear memory with interesting translational implications for anxiety-related diseases.

Slow Disease Progression in a C57BL/6 Pten-Deficient Mouse Model of Prostate Cancer

PubMed Central

Svensson, Robert U.; Haverkamp, Jessica M.; Thedens, Daniel R.; Cohen, Michael B.; Ratliff, Timothy L.; Henry, Michael D.

2011-01-01

Prostate-specific deletion of Pten in mice has been reported to recapitulate histological progression of human prostate cancer. To improve on this model, we introduced the conditional ROSA26 luciferase reporter allele to monitor prostate cancer progression via bioluminescence imaging and extensively backcrossed mice onto the albino C57BL/6 genetic background to address variability in tumor kinetics and to enhance imaging sensitivity. Bioluminescence signal increased rapidly in Ptenp−/− mice from 3 to 11 weeks, but was much slower from 11 to 52 weeks. Changes in bioluminescence signal were correlated with epithelial proliferation. Magnetic resonance imaging revealed progressive increases in prostate volume, which were attributed to excessive fluid retention in the anterior prostate and to expansion of the stroma. Development of invasive prostate cancer in 52-week-old Ptenp−/− mice was rare, indicating that disease progression was slowed relative to that in previous reports. Tumors in these mice exhibited a spontaneous inflammatory phenotype and were rapidly infiltrated by myeloid-derived suppressor cells. Although Ptenp−/− tumors responded to androgen withdrawal, they failed to exhibit relapsed growth for up to 1 year. Taken together, these data identify a mild prostate cancer phenotype in C57BL/6 prostate-specific Pten-deficient mice, reflecting effects of the C57BL/6 genetic background on cancer progression. This model provides a platform for noninvasive assessment of how genetic and environmental risk factors may affect disease progression. PMID:21703427

Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice.

PubMed

Pratti, Juliana Elena Silveira; Ramos, Tadeu Diniz; Pereira, Joyce Carvalho; da Fonseca-Martins, Alessandra Marcia; Maciel-Oliveira, Diogo; Oliveira-Silva, Gabriel; de Mello, Mirian França; Chaves, Suzana Passos; Gomes, Daniel Claudio Oliveira; Diaz, Bruno Lourenço; Rossi-Bergmann, Bartira; de Matos Guedes, Herbert Leonel

2016-10-06

We have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as a more representative experimental model of human cutaneous leishmaniasis. C57BL/6 mice from different animal facilities were infected with L. amazonensis (Josefa strain) to establish the profile of infection. Intranasal vaccination was performed before the infection challenge with two doses of 10 μg of LaAg alone or associated with the adjuvant ADDAVAX® by instillation in the nostrils. The lesion progression was measured with a dial caliper and the parasite load by limited dilution assay in the acute and chronic phases of infection. Cytokines were quantified by ELISA in the homogenates of infected footpads. C57BL/6 mice from different animal facilities presented the same L. amazonensis infection profile, displaying a progressive acute phase followed by a controlled chronic phase. Parasites cultured in M199 and Schneider's media were equally infective. Intranasal vaccination with LaAg led to milder acute and chronic phases of the disease. The mechanism of protection was associated with increased production of IFN-gamma in the infected tissue as measured in the acute phase. Association with the ADDAVAX® adjuvant did not improve the efficacy of intranasal LaAg vaccination. Rather, ADDAVAX® reduced vaccination efficacy. This study demonstrates that the efficacy of adjuvant-free intranasal vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of infection with L. amazonensis, and is thus not exclusive to the susceptible BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to peripheral protection irrespective of the genetic background of the host.

Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

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

Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae; Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae; Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae

2014-04-15

We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O{sub 2} consumption) and ATPmore » following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection.« less

Temporal Variation of HCO+ 1_0 Galactic Absorption Lines Toward NRAO 150 and BL Lac

NASA Astrophysics Data System (ADS)

Han, Junghwan; Yun, Youngjoo; Park, Yong-Sun

2017-12-01

We present observations of HCO^+ 1-0 absorption lines toward two extragalactic compact radio sources, NRAO 150 and BL Lac with the Korean VLBI Network in order to investigate their time variation over 20 years by Galactic foreground clouds. It is found that the line shape of -17 km s^{-1} component changed marginally during 1993-1998 period and has remained unaltered thereafter for NRAO 150. Its behavior is different from that of H_2CO 1_{10}-1_{11}, suggesting chemical differentiation on ˜ 20 AU scale, the smallest ever seen. On the other hand, BL Lac exhibits little temporal variation for the HCO^+ and H_2CO lines. Our observation also suggests that Korea VLBI Network performs reliably in the spectrum mode in that the shapes of the new HCO^+ 1-0 spectra are in good agreement with the previous ones to an accuracy of a few percent except the time varying component toward NRAO 150.

Antitumor activities of ginseng polysaccharide in C57BL/6 mice with Lewis lung carcinoma.

PubMed

Zhou, Xiao; Shi, Huaiyin; Jiang, Gening; Zhou, Yongan; Xu, Jianfang

2014-12-01

In the present study, we prepared ginseng polysaccharide (GP) and evaluated its antitumor and immunomodulatory activities in C57BL/6 mice bearing with Lewis lung carcinoma (LLC). Administration of GP (50, 100, and 200 mg/kg) could not only significantly inhibit the growth of transplantable LLC tumor in C57BL/6 mice but also remarkably increase relative weight of spleen and thymus, splenocytes proliferation, and the ratio of CD4(+)/CD8(+) T lymphocyte in peripheral blood in LLC-bearing mice. Furthermore, the serum IL-2 and IFN-γ production and NK cytolytic activity were also prompted in LLC-bearing mice in response to GP treatment at three doses. Additionally, GP showed no side effects such as weight loss in body weight and internal organs (lung, liver, kidney, and heart) as well as inactivity during the experiment. Therefore, GP might be conveniently exploited to be good immune-stimulating modifiers and had the potential value for tumor therapy.

Antihyperglycaemic effect of laser acupuncture treatment at BL20 in diabetic rats.

PubMed

Cornejo-Garrido, Jorge; Becerril-Chávez, Flavia; Carlín-Vargas, Gabriel; Ordoñez-Rodríguez, Juan Manuel; Abrajan-González, María Del Carmen; de la Cruz-Ramírez, Rosario; Ordaz-Pichardo, Cynthia

2014-12-01

To investigate the antihyperglycaemic activity of laser acupuncture stimulation at 650 and 980 nm at BL20 in streptozotocin (STZ)-induced diabetic rats. Seventy healthy adult male albino Wistar rats weighing 250±50 g were divided into seven groups of 10 animals each. Groups I-III comprised healthy control rats which were untreated (I) or stimulated with laser acupuncture at 650 nm (II) and 980 nm (III), respectively. Groups IV-VII underwent induction of diabetes with a single intraperitoneal administration of STZ at 50 mg/kg. Animals with blood glucose levels of ≥200 mg/dL on the fifth day were used for the experiments and were left untreated (group IV), treated with glibenclamide (group V) or stimulated with laser acupuncture at 650 nm (group VI) and 980 nm (group VII), respectively. Laser acupuncture was applied at BL20 on alternate days for a total of 12 sessions over a 28-day period. After 28 days of treatment, STZ-induced diabetic rats stimulated with laser acupuncture at 650 and 980 nm had significantly lower glucose levels compared with untreated diabetic rats (242.0±65.0 and 129.8±33.2 vs 376.5±10.0 mg/dL, both p≤0.05). Treatment at 980 nm also attenuated the increase in glucose between day 1 and day 28 compared with the glibenclamide-treated diabetic group (41.5±19.6 mg/dL vs 164.1±13.7 g/dL, p<0.05). Laser acupuncture treatment did not affect the blood count or biochemical profile and was not associated with any morphological changes in the pancreas, liver, kidney or spleen. Stimulation with laser acupuncture at 650 and 980 nm at BL20 in STZ-induced diabetic rats has antihyperglycaemic activity. The results support further evaluation of laser acupuncture as an alternative or complementary treatment for the control of hyperglycaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The NuSTAR view on Hard-TeV BL Lacs

NASA Astrophysics Data System (ADS)

Costamante, L.; Bonnoli, G.; Tavecchio, F.; Ghisellini, G.; Tagliaferri, G.; Khangulyan, D.

2018-05-01

Hard-TeV BL Lacs are a new type of blazars characterized by a hard intrinsic TeV spectrum, locating the peak of their gamma-ray emission in the spectral energy distribution (SED) above 2-10 TeV. Such high energies are problematic for the Compton emission, using a standard one-zone leptonic model. We study six examples of this new type of BL Lacs in the hard X-ray band with NuSTAR. Together with simultaneous observations with the Neil Gehrels Swift Observatory, we fully constrain the peak of the synchrotron emission in their SED, and test the leptonic synchrotron self-Compton (SSC) model. We confirm the extreme nature of 5 objects also in the synchrotron emission. We do not find evidence of additional emission components in the hard X-ray band. We find that a one-zone SSC model can in principle reproduce the extreme properties of both peaks in the SED, from X-ray up to TeV energies, but at the cost of i) extreme electron energies with very low radiative efficiency, ii) conditions heavily out of equipartition (by 3 to 5 orders of magnitude), and iii) not accounting for the simultaneous UV data, which then should belong to a different emission component, possibly the same as the far-IR (WISE) data. We find evidence of this separation of the UV and X-ray emission in at least two objects. In any case, the TeV electrons must not "see" the UV or lower-energy photons, even if coming from different zones/populations, or the increased radiative cooling would steepen the VHE spectrum.

The NuSTAR view on hard-TeV BL Lacs

NASA Astrophysics Data System (ADS)

Costamante, L.; Bonnoli, G.; Tavecchio, F.; Ghisellini, G.; Tagliaferri, G.; Khangulyan, D.

2018-07-01

Hard-TeV BL Lacs are a new type of blazars characterized by a hard intrinsic TeV spectrum, locating the peak of their gamma-ray emission in the spectral energy distribution (SED) above 2-10 TeV. Such high energies are problematic for the Compton emission, using a standard one-zone leptonic model. We study six examples of this new type of BL Lacs in the hard X-ray band with NuSTAR. Together with simultaneous observations with the Neil Gehrels Swift Observatory, we fully constrain the peak of the synchrotron emission in their SED, and test the leptonic synchrotron self-Compton (SSC) model. We confirm the extreme nature of five objects also in the synchrotron emission. We do not find evidence of additional emission components in the hard X-ray band. We find that a one-zone SSC model can in principle reproduce the extreme properties of both peaks in the SED, from X-ray up to TeV energies, but at the cost of (i) extreme electron energies with very low radiative efficiency, (ii) conditions heavily out of equipartition (by three to five orders of magnitude), and (iii) not accounting for the simultaneous UV data, which then should belong to a different emission component, possibly the same as the far-IR (WISE) data. We find evidence of this separation of the UV and X-ray emission in at least two objects. In any case, the TeV electrons must not `see' the UV or lower energy photons, even if coming from different zones/populations, or the increased radiative cooling would steepen the very high energies spectrum.

Effects of naltrexone on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J mice.

PubMed

Tomie, Arthur; Azogu, Idu; Yu, Lei

2013-07-01

The present experiment evaluated the effects of naltrexone, a non-selective opioid receptor antagonist, on post-abstinence alcohol drinking in C57BL/6NCRL and DBA/2J male mice. Home cage 2-bottle (alcohol vs. water) free-choice procedures were employed. During the pre-abstinence period, alcohol intake was much lower for the DBA/2J mice relative to the C57BL/6NCRL mice, and this strain difference was observed for groups receiving either 3% or 10% alcohol concentrations. The four-day abstinence period effectively reduced alcohol intakes (i.e., a negative alcohol deprivation effect, negative ADE) in both groups of DBA/2J mice, but had no effect on alcohol intakes in either group of C57BL/6NCRL mice. Both groups trained with 3% alcohol received the second four-day abstinence period, where the effects of acute administration of either naltrexone or saline on post-abstinence alcohol drinking were assessed. Naltrexone was more effective in reducing post-abstinence drinking of 3% alcohol in the DBA/2J mice than in the C57BL/6NCRL mice. In the DBA/2J mice, naltrexone further reduced, relative to saline-injected controls, the low levels of post-abstinence alcohol intake. Thus, the low baseline levels of alcohol drinking in DBA/2J mice were further diminished by the four-day abstinence period (negative ADE), and this suppressed post-abstinence level of alcohol drinking was still further reduced by acute administration of naltrexone. The results indicate that naltrexone is effective in reducing further the low levels of alcohol drinking induced by the negative ADE. Copyright © 2013 Elsevier Inc. All rights reserved.

Micro-focusing System of the Taiwan Contract Beamline BL12XU at SPring-8 for IXS Experiments under High Pressure

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

Huang, C.-Y.; Cai, Y.-Q.; Chung, S.-C.

The Taiwan Contract Beamline BL12XU at SPring-8 is designed for inelastic X-ray scattering (IXS) experiments. DCS is a powerful technique capable of probing the dynamic behavior and electronic structure of materials under high pressure. The state-of-the-arts technology to generate static high pressure up to mega-bar range uses diamond anvil cells (DAC). The allowed volume of the sample in DAC scales inversely with the pressure and is limited to the order of 1 x 10-3 mm3. In order to utilize such a device to explore the interesting phenomena under high pressure, we have designed a micro-focusing system using a set ofmore » KB mirrors, which is compatible with the existing optical system of BL12XU. Realistic ray-tracing results indicate that the system can achieve a focus of 10 {mu}m x 5.3 {mu}m(H x V) with a total efficiency of about 86%. The improved focus is expected to substantially enhance the experimental capability of BL12XU for high-pressure research.« less

Whisker dependent responsiveness of C57BL/6J mice to different behavioral test paradigms.

PubMed

Haridas, Seenu; Ganapathi, Ramya; Kumar, Mayank; Manda, Kailash

2018-01-15

Whisker trimming is very common in C57BL/6J mice. Dewhiskering may lead to an alteration in the thalamocortical connectivity and relevant behavioral functions. Since C57BL/6J is a commonly used strain for neurobehavioral studies, it is important to examine how whisker dependent heterogeneity affects the internal validity of behavioral phenotypes. The present study aimed to investigate the responsiveness of mice to different behavioral test paradigms in the presence or absence of whiskers. We employed two models of whisker deprivation: Acute Whisker Desensitization (AWD) and Chronic Habitual Dewhiskering (CHD). The AWD model blocks whisker sensation by lidocaine application. For CHD model, mice at the age of 12 weeks were carefully scrutinized for presence or absence of whiskers and divided into three groups, the whiskered mice, partially dewhiskered mice and completely dewhiskered mice. The whisker-dependent behavioral functions were assessed using open field test, novel object recognition test, marble burying test and forced swim test. Our results showed that habitual dewhiskering significantly altered the short-term memory and basal anxiety-like functions. Such behavioral alteration due to dewhiskering was significantly different in fully and partially dewhiskered mice, which is indicative of behavioral adaptation to the whisker desensitization. Contrary to CHD, the Acute Whisker Desensitization ameliorated behavioral compulsivity and basal anxiety. Our results suggest that vibrissal desensitization in the mice may lead to changes in their affective and cognitive state. Since, heterogeneity in whisker status may affect behavioral functions, careful inspection of the whisker status of C57BL/6J mice is recommended to increase the reproducibility and reliability of results obtained from behavioral assessments. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of a Gene Cluster Enabling Lactobacillus casei BL23 To Utilize myo-Inositol▿ †

PubMed Central

Yebra, María Jesús; Zúñiga, Manuel; Beaufils, Sophie; Pérez-Martínez, Gaspar; Deutscher, Josef; Monedero, Vicente

2007-01-01

Genome analysis of Lactobacillus casei BL23 revealed that, compared to L. casei ATCC 334, it carries a 12.8-kb DNA insertion containing genes involved in the catabolism of the cyclic polyol myo-inositol (MI). Indeed, L. casei ATCC 334 does not ferment MI, whereas strain BL23 is able to utilize this carbon source. The inserted DNA consists of an iolR gene encoding a DeoR family transcriptional repressor and a divergently transcribed iolTABCDG1G2EJK operon, encoding a complete MI catabolic pathway, in which the iolK gene probably codes for a malonate semialdehyde decarboxylase. The presence of iolK suggests that L. casei has two alternative pathways for the metabolism of malonic semialdehyde: (i) the classical MI catabolic pathway in which IolA (malonate semialdehyde dehydrogenase) catalyzes the formation of acetyl-coenzyme A from malonic semialdehyde and (ii) the conversion of malonic semialdehyde to acetaldehyde catalyzed by the product of iolK. The function of the iol genes was verified by the disruption of iolA, iolT, and iolD, which provided MI-negative strains. By contrast, the disruption of iolK resulted in a strain with no obvious defect in MI utilization. Transcriptional analyses conducted with different mutant strains showed that the iolTABCDG1G2EJK cluster is regulated by substrate-specific induction mediated by the inactivation of the transcriptional repressor IolR and by carbon catabolite repression mediated by the catabolite control protein A (CcpA). This is the first example of an operon for MI utilization in lactic acid bacteria and illustrates the versatility of carbohydrate utilization in L. casei BL23. PMID:17449687

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

PubMed

Flores-Montoya, Mayra Gisel; Sobin, Christina

2015-07-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). Copyright © 2014 John Wiley & Sons, Ltd.

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

PubMed Central

Flores-Montoya, Mayra Gisel; Sobin, Christina

2014-01-01

Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1. PMID:25219894

Neonatal C57BL/6J and parkin mice respond differently following developmental manganese exposure: Result of a high dose pilot study.

PubMed

Foster, Melanie L; Bartnikas, Thomas B; Maresca-Fichter, Hailey C; Mercadante, Courtney; Dash, Miriam; Miller, Chelsea; Dorman, David C

2018-01-01

It has been suggested that childhood exposure to neurotoxicants may increase the risk of Parkinson's disease (PD) or other neurodegenerative disease in adults. Some recessive forms of PD have been linked to loss-of-function mutations in the Park2 gene that encodes for parkin. The purpose of this pilot study was to evaluate whether responses to neonatal manganese (Mn) exposure differ in mice with a Park2 gene defect (parkin mice) when compared with a wildtype strain (C57BL/6J). Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND) 1 through PND 28. Motor activity was measured on PND 19-22 and 29-32. Tissue Mn concentrations were measured in liver, femur, olfactory bulb, frontal cortex, and striatum on PND 29. Hepatic and frontal cortex gene expression of Slc11a2, Slc40a1, Slc30a10, Hamp (liver only), and Park2 were also measured on PND 29. Some strain differences were seen. As expected, decreased hepatic and frontal cortex Park2 expression was seen in the parkin mice when compared with C57BL/6J mice. Untreated parkin mice also had higher liver and femur Mn concentrations when compared with the C57BL/6J mice. Exposure to≥11mg Mn/kg-day was associated with increased brain Mn concentrations in all mice, no strain difference was observed. Manganese exposure in C57Bl6, but not parkin mice, was associated with a negative correlation between striatal Mn concentration and motor activity. Manganese exposure was not associated with changes in frontal cortex gene expression. Decreased hepatic Slc30a10, Slc40a1, and Hamp expression were seen in PND 29 C57BL/6J mice given 25mg Mn/kg-day. In contrast, Mn exposure was only associated with decreased Hamp expression in the parkin mice. Our results suggest that the Parkin gene defect did not increase the susceptibility of neonatal mice to adverse health effects associated with high-dose Mn exposure. Copyright © 2017 Elsevier B

The X-ray spectra of the BL Lacertae objects PKS 0548 - 322 and 3C 66A

NASA Technical Reports Server (NTRS)

Maccacaro, T.; Maccagni, D.; Tarenghi, M.

1983-01-01

Einstein Observatory simultaneous imaging proportional counter and monitor proportional counter data are combined in order to derive the energy spectra of the BL Lac objects PKS 0548-322 and 3C 66A between 0.2 and 10 keV. While the latter is found to be variable in both intensity and spectral shape, the former, although constant in the present data, is found to have experienced a spectrum variation in view of results from other experiments. Attention is given to the implications of flux and spectral variability in BL Lac objects for models of X-ray emission mechanisms. It is suggested that the wide spread of the spectral index distribution is due to the detection of the highly variable synchrotron-produced X-rays that are generally undetected in QSOs.

The effect of neonatal N-methyl-D-aspartate receptor blockade on exploratory and anxiety-like behaviors in adult BALB/c and C57BL/6 mice.

PubMed

Akillioglu, Kubra; Binokay, Secil; Kocahan, Sayad

2012-07-15

N-methyl-D-aspartate (NMDA) receptors play an important role in brain maturation and developmental processes. In our study, we evaluated the effects of neonatal NMDA receptor blockade on exploratory locomotion and anxiety-like behaviors of adult BALB/c and C57BL/6 mice. In this study, NMDA receptor hypofunction was induced 7-10 days after birth using MK-801 in BALB/c and C57BL/6 mice (0.25mg/kg twice a day for 4 days via intraperitoneal injection). The open-field (OF) and elevated plus maze (EPM) tests were used to evaluate exploratory locomotion and anxiety-like behaviors. In the OF, BALB/c mice spent less time in the center of the field (p<0.05) and had less vertical locomotor activity (p<0.01) compared to C57BL/6 mice. In BALB/c mice, MK-801 caused a decrease in vertical and horizontal locomotor activity in the OF test, compared to the control group (p<0.05). In C57BL/6 mice, MK-801 treatment increased horizontal locomotor activity and decreased time spent in the center in the OF test (p<0.05). In the EPM, the number of open-arm entries, the percentage of open-arm time (p<0.01) and total arm entries (p<0.05) were lower in BALB/c mice compared to C57BL/6 mice. In BALB/c mice, MK-801 caused an increase in the percentage of open-arm time compared to the control group (p<0.05). In C57BL/6 mice, MK-801 caused a decrease in the percentage of open-arm time compared to the control group (p<0.05). MK-801 decreased exploratory and anxiety-like behaviors in BALB/c mice. In contrast, MK-801 increased exploratory and anxiety-like behaviors in C57BL/6 mice. In conclusion, hereditary factors may play an important role in neonatal NMDA receptor blockade-induced responses. Copyright © 2012 Elsevier B.V. All rights reserved.

Alcohol consumption suppresses metastasis of B16-BL6 melanoma in mice.

PubMed

Meadows, G G; Elstad, C A; Blank, S E; Gallucci, R M; Pfister, L J

1993-03-01

Female C57BL/6 mice were fed a defined, pelleted diet and given 10% w/v or 20% w/v ethanol in their drinking water. Natural killer (NK) cell cytolytic activity was compared between water-drinking and ethanol-consuming mice and in mice that were also treated with polyinosinic-polycytidylic acid (poly I:C) to augment NK cell activity or with anti-NK1.1 antibody to decrease activity. NK cell cytolytic activity was not altered in mice given 10% ethanol, but was decreased in mice given 20% ethanol compared to water-drinking mice. Poly I:C treatment increased and anti-NK1.1 antibody treatment decreased NK cell activity in both water-drinking and 20% ethanol-consuming mice. Experimental and spontaneous metastases of B16-BL6 melanoma were evaluated as a function of the duration of ethanol consumption before tumor inoculation and as a function of altered NK cell activity. Experimental metastasis was inhibited after 4 and also after 6.5 weeks of ethanol exposure. Poly I:C treatment inhibited tumor lung colonization irrespective of ethanol consumption. Anti-NK1.1 antibody treatment increased metastasis, although to a lesser degree in mice consuming 10% ethanol. Spontaneous metastasis was inhibited in mice consuming 10% ethanol for 4 weeks, and in mice consuming 20% ethanol for 1 and 4 weeks before melanoma inoculation.

Quantitative trait locus analysis of plasma cholesterol and triglyceride levels in C57BL/6J x RR F2 mice.

PubMed

Suto, Jun-ichi; Takahashi, Yuji; Sekikawa, Kenji

2004-10-01

A highly significant cholesterol quantitative trait locus (QTL) (Cq6) was identified on chromosome 1 in C57BL/6J x RR F2 mice. The Cq6 was located over the gene for apolipoprotein A-Il (Apoa2), and the RR allele was associated with increased plasma cholesterol. C57BL/6J has Apoa2a alleles and RR has Apoa2b alleles. Three different Apoa2 alleles are known on the basis of amino acid substitutions at four residues. Analysis with partial Apoa2 congenic strains possessing Apoa2a, Apoa2b, and Apoa2C alleles revealed that the Apoa2b allele is unique in the ability to increase cholesterol among the three Apoa2 alleles, and that the Ala-to-Val substitution at residue 61 may be crucial as far as cholesterol metabolism is concerned. We also investigated the question of whether the Apoa1 gene is responsible for the cholesterol QTLs (Cq4 and Cq5) that had been identified previously on chromosome 9 in C57BL/6J x KK-Ay/a F2 and in KK x RR F2, but not in C57BL/6J x RR F2 mice. Similar to Apoa2 alleles, three different Apoal alleles with two successive amino acid substitutions were revealed among the strains. However, we could not correlate Apoal polymorphisms with the occurrence of QTLs in these three sets of F2 mice.

A hadronic origin for ultra-high-frequency-peaked BL Lac objects

NASA Astrophysics Data System (ADS)

Cerruti, M.; Zech, A.; Boisson, C.; Inoue, S.

2015-03-01

Current Cherenkov telescopes have identified a population of ultra-high-frequency peaked BL Lac objects (UHBLs), also known as extreme blazars, that exhibit exceptionally hard TeV spectra, including 1ES 0229+200, 1ES 0347-121, RGB J0710+591, 1ES 1101-232, and 1ES 1218+304. Although one-zone synchrotron-self-Compton (SSC) models have been generally successful in interpreting the high-energy emission observed in other BL Lac objects, they are problematic for UHBLs, necessitating very large Doppler factors and/or extremely high minimum Lorentz factors of the emitting leptonic population. In this context, we have investigated alternative scenarios where hadronic emission processes are important, using a newly developed (lepto-)hadronic numerical code to systematically explore the physical parameters of the emission region that reproduces the observed spectra while avoiding the extreme values encountered in pure SSC models. Assuming a fixed Doppler factor δ = 30, two principal parameter regimes are identified, where the high-energy emission is due to: (1) proton-synchrotron radiation, with magnetic fields B ˜ 1-100 G and maximum proton energies Ep; max ≲ 1019 eV; and (2) synchrotron emission from p-γ-induced cascades as well as SSC emission from primary leptons, with B ˜ 0.1-1 G and Ep; max ≲ 1017 eV. This can be realized with plausible, sub-Eddington values for the total (kinetic plus magnetic) power of the emitting plasma, in contrast to hadronic interpretations for other blazar classes that often warrant highly super-Eddington values.

Systematic comparison of co-expression of multiple recombinant thermophilic enzymes in Escherichia coli BL21(DE3).

PubMed

Chen, Hui; Huang, Rui; Zhang, Y-H Percival

2017-06-01

The precise control of multiple heterologous enzyme expression levels in one Escherichia coli strain is important for cascade biocatalysis, metabolic engineering, synthetic biology, natural product synthesis, and studies of complexed proteins. We systematically investigated the co-expression of up to four thermophilic enzymes (i.e., α-glucan phosphorylase (αGP), phosphoglucomutase (PGM), glucose 6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH)) in E. coli BL21(DE3) by adding T7 promoter or T7 terminator of each gene for multiple genes in tandem, changing gene alignment, and comparing one or two plasmid systems. It was found that the addition of T7 terminator after each gene was useful to decrease the influence of the upstream gene. The co-expression of the four enzymes in E. coli BL21(DE3) was demonstrated to generate two NADPH molecules from one glucose unit of maltodextrin, where NADPH was oxidized to convert xylose to xylitol. The best four-gene co-expression system was based on two plasmids (pET and pACYC) which harbored two genes. As a result, apparent enzymatic activities of the four enzymes were regulated to be at similar levels and the overall four-enzyme activity was the highest based on the formation of xylitol. This study provides useful information for the precise control of multi-enzyme-coordinated expression in E. coli BL21(DE3).

Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice.

PubMed

Lalonde, R; Strazielle, C

2008-06-15

The relations between open-field, elevated plus-maze, and emergence tests were examined in two strains of mice. In the open-field, C57BL/6J mice had more ambulatory movements and rears but not stereotyped movements relative to BALB/c. In addition, C57BL/6J mice entered more often than BALB/c into enclosed and open arms of the elevated plus-maze. When placed inside a large enclosure, C57BL/6J mice emerged more quickly than BALB/c from a small toy object. In the entire series of mice, ambulation and rears in the open-field were linearly correlated with open and enclosed arm visits in the elevated plus-maze. Ambulatory movements and rears were also correlated with emergence latencies. In contrast, stereotyped movements were correlated with emergence latencies, but not with any elevated plus-maze value. These results specify the extent and limits of association between the three tests.

Idiopathic paraproteinaemia. I. Studies in an animal model--the ageing C57BL/KaLwRij mouse.

PubMed Central

Radl, J; Hollander, C F; van den Berg, P; de Glopper, E

1978-01-01

A search for a suitable animal model for studies on idiopathic paraproteinaemia showed that an age-dependent increase in the appearance of homogeneous immunoglobulins in serum was common to all of the seven mouse strains investigated to date. The highest frequency was found in C57Bl/KaLwRij mice. Further investigations in this strain demonstrated that, except for some quantitative differences, most of the features of human and C57BL Mouse idiopathic paraproteinaemia were essentially the same. No clear-cut correlation was found between the idiopathic paraproteinaemia and, in the old C57B1 mice, a rather frequently occurring reticulum cell sarcoma B and amyloidosis. The mouse idiopathic paraproteinaemia can be regarded as an analogue of the human idiopathic paraproteinaemia and therefore as a suitable model for further experimental studies. PMID:367647

Effects of housing density and cage floor space on C57BL/6J mice

USGS Publications Warehouse

Smith, A.L.; Mabus, S.L.; Stockwell, J.D.; Muir, C.

2004-01-01

The Guide for the Care and Use of Laboratory Animals (the Guide) is widely accepted as the housing standard by most Institutional Animal Care and Use Committees. The recommendations are based on best professional judgment rather than experimental data. Current efforts are directed toward replacing these guidelines with data-driven, species-appropriate standards. Our studies were undertaken to determine the optimum housing density for C57BL/6J mice, the most commonly used inbred mouse strain. Four-week-old mice were housed for 8 weeks at four densities (the recommended ???12 in2 [ca. 77.4 cm 2]/mouse down to 5.6 in2 [ca. 36.1 cm2]/mouse) in three cage types with various amounts of floor space. Housing density did not affect a variety of physiologic parameters but did affect certain micro-environmental parameters, although these remained within accepted ranges. A second study was undertaken housing C57BL/6J mice with as little as 3.2 in2/mouse (ca. 20.6 cm2). The major effect was elevated ammonia concentrations that exceeded limits acceptable in the workplace at increased housing densities; however, the nasal passages and eyeballs of the mice remained microscopically normal. On the basis of these results, we conclude that C57BL/6J mice as large as 29 g may be housed with 5.6 in2 of floor space per mouse. This area is approximately half the floor space recommended in the Guide. The role of the Guide is to ensure that laboratory animals are well treated and housed in a species-appropriate manner. Our data suggest that current policies could be altered in order to provide the optimal habitation conditions matched to this species' social needs. Copyright 2004 by the American Association for Laboratory Animal Science.

GLAST answers about high-energy peaked BL Lacs: double-humped {gamma}-ray peak and extreme accelerators?

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

Costamante, L.; Aharonian, F.; Khangulyan, D.

2007-07-12

An often overlooked fact is that the MeV-GeV emission from High-energy peaked BL Lacs (HBL) is basically unknown: there are only 3 objects of this type among all EGRET identified blazars with measured spectra. GLAST will be able to measure the spectrum for many of them, in particular TeV-blazars, and surprises are expected. GLAST will tell if the {gamma}-ray peak in some HBL is actually a ''double peak'', as suggested by the comparison of EGRET and HESS data in PKS 2155-304, We also remind and argue that a new class of BL Lacs could exist, where particles are shock-accelerated nearmore » the maximum possible rate, characterized by the synchrotron emission peaking in the GLAST band (100 MeV - few GeV). Such objects could easily have escaped detection or identification so far, and could now be unveiled by GLAST.« less

Association between Hair-Induced Oronasal Inflammation and Ulcerative Dermatitis in C57BL/6 Mice

PubMed Central

Duarte-Vogel, Sandra M; Lawson, Gregory W

2011-01-01

Ulcerative dermatitis (UD) is a genetically linked syndrome that affects the neck, torso, and facial regions of C57BL/6 mice and strains with C57BL/6 background. In this study, 96 mice with skin ulcerations in 3 different regions of the body and 40 control animals without ulcerated lesions were evaluated histologically for the presence of hair-induced inflammation in the oronasal cavity. We found that 73.5% (100 of 136) of the mice had hair-induced periodontitis, glossitis, or rhinitis regardless of the presence or absence of UD. Of those mice with UD, 93.9% had hair-induced oronasal inflammation. The mandibular incisors were the most commonly affected site (64.6%), followed by the maxillary molars (20.8%), maxillary incisors (16.7%), tongue (16.7%), nasal cavity (10.4%), and mandibular molars (7.3%). In addition, oronasal hair-induced inflammation occurred in 25% (10 of 40) of the control mice. Here we show a significant association between UD and hair-induced inflammatory lesions of the oronasal cavities. PMID:21819677

Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma.

PubMed

Mukai, S; Kato, H; Kimura, S; Asai, K; Kawahito, Y; Inoue, M; Yamamura, Y; Sano, H; Sugino, S; Shu, S; Kondo, M

1996-02-01

We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma. C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad. Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days. These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v. injection of 2-4 x 10(5) viable BL6 cells. The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer. Transfer of IVS cells from mice immunized by s.c. injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003). These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003). Functional IVS cells required in vitro stimulation with tumor cells. However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells. These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells. The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma.

Effects of metabolic pathway precursors and polydimethylsiloxane (PDMS) on poly-(gamma)-glutamic acid production by Bacillus subtilis BL53.

PubMed

de Cesaro, Alessandra; da Silva, Suse Botelho; Ayub, Marco Antônio Záchia

2014-09-01

The aims of this study were to evaluate the effects of the addition of metabolic precursors and polydimethylsiloxane (PDMS) as an oxygen carrier to cultures of Bacillus subtilis BL53 during the production of γ-PGA. Kinetics analyses of cultivations of different media showed that B. subtilis BL53 is an exogenous glutamic acid-dependent strain. When the metabolic pathway precursors of γ-PGA synthesis, L-glutamine and a-ketoglutaric acid, were added to the culture medium, production of the biopolymer was increased by 20 % considering the medium without these precursors. The addition of 10 % of the oxygen carrier PDMS to cultures caused a two-fold increase in the volumetric oxygen mass transfer coefficient (kLa), improving γ-PGA production and productivity. Finally, bioreactor cultures of B. subtilis BL53 adopting the combination of optimized medium E, added of glutamine, α-ketoglutaric acid, and PDMS, showed a productivity of 1 g L(-1) h(-1) of g-PGA after only 24 h of cultivation. Results of this study suggest that the use of metabolic pathway precursors glutamine and a-ketolgutaric acid, combined with the addition of PDMS as an oxygen carrier in bioreactors, can improve γ-PGA production and productivity by Bacillus strains .

Single Dose of the CXCR4 Antagonist BL-8040 Induces Rapid Mobilization for the Collection of Human CD34+ Cells in Healthy Volunteers.

PubMed

Abraham, Michal; Pereg, Yaron; Bulvik, Baruch; Klein, Shiri; Mishalian, Inbal; Wald, Hana; Eizenberg, Orly; Beider, Katia; Nagler, Arnon; Golan, Rottem; Vainstein, Abi; Aharon, Arnon; Galun, Eithan; Caraco, Yoseph; Or, Reuven; Peled, Amnon

2017-11-15

Purpose: The potential of the high-affinity CXCR4 antagonist BL-8040 as a monotherapy-mobilizing agent and its derived graft composition and quality were evaluated in a phase I clinical study in healthy volunteers (NCT02073019). Experimental Design: The first part of the study was a randomized, double-blind, placebo-controlled dose escalation phase. The second part of the study was an open-label phase, in which 8 subjects received a single injection of BL-8040 (1 mg/kg) and approximately 4 hours later underwent a standard leukapheresis procedure. The engraftment potential of the purified mobilized CD34 + cells was further evaluated by transplanting the cells into NSG immunodeficient mice. Results: BL-8040 was found safe and well tolerated at all doses tested (0.5-1 mg/kg). The main treatment-related adverse events were mild to moderate. Transient injection site and systemic reactions were mitigated by methylprednisolone, paracetamol, and promethazine pretreatment. In the first part of the study, BL-8040 triggered rapid and substantial mobilization of WBCs and CD34 + cells in all tested doses. Four hours postdose, the count rose to a mean of 8, 37, 31, and 35 cells/μL (placebo, 0.5, 0.75, and 1 mg/kg, respectively). FACS analysis revealed substantial mobilization of immature dendritic, T, B, and NK cells. In the second part, the mean CD34 + cells/kg collected were 11.6 × 10 6 cells/kg. The graft composition was rich in immune cells. Conclusions: The current data demonstrate that BL-8040 is a safe and effective monotherapy strategy for the collection of large amounts of CD34 + cells and immune cells in a one-day procedure for allogeneic HSPC transplantation. Clin Cancer Res; 23(22); 6790-801. ©2017 AACR . ©2017 American Association for Cancer Research.

Inhibition of B16-BL6 melanoma lung colonies by semisynthetic sulfaminoheparosan sulfates from E. coli K5 polysaccharide.

PubMed

Poggi, Andreina; Rossi, Cosmo; Casella, Nicola; Bruno, Cristiana; Sturiale, Luisella; Dossi, Carla; Naggi, Annamaria

2002-08-01

Heparin (H), heparan sulfate (HS), and related glycosaminoglycans can inhibit cancer cell invasion, possibly due to their ability to interact with vascular growth factors, adhesion molecules, endoglycosidases, and signaling proteins, in addition to the well-known effects on the clotting system. We evaluated the antitumor activity of a series of semisynthetic sulfaminoheparosan sulfates (SAHSs) with different degree and distribution of sulfates, obtained by chemical modifications of the E. coli K5 polysaccharide, namely type A, B, and C compounds. B16-BL6 melanoma cells (10 5 cells/mouse) were injected intravenously (i.v.) in a lateral tail vein of C57BL6 mice at a dose of 0.5 mg/ mouse together with test compounds. Tumor lung nodules were significantly reduced as compared with controls only by H (95.5 +/- 1.0% inhibition), SAHS-2 (84.2 +/- 5.0% inhibition), and SAHS-4 (91.1 +/- 4.2% inhibition), among compounds tested. SAHS-2 and SAHS-4 are type B compounds, with a sulfate/carboxylate ratio similar to that of H. A typical mammalian HS showed only 54.8% inhibition. Supersulfated low-molecular-weight heparin and heparan sulfate (ssLMWH and ssLMWHS) showed an activity similar to that of unfractionated compounds. H and SAHS-4 inhibited dose dependently B16-BL6 lung colonies, with IC-50 values of 0.05 and 0.1 mg/mouse, respectively. The relationship with ex vivo anticoagulant potency was evaluated by activated partial thromboplastin time (aPTT) on mouse plasma at different time intervals after i.v. injection (0.1 to 0.5 mg/mouse) of the compound. H showed a dose-dependent anticoagulant activity lasting up to 2 hours, whereas SAHS-4 showed a potent anticoagulant effect only at a dose of 0.5 mg/mouse. Accordingly, H but not SAHS-4 consistently inhibited B16-BL6 lung colonies when given 1 hour before tumor cells. SAHS-4 derivatives, with different size and/or affinity depleted of AT binding sites, showed an inhibitory effect on B16-BL6 melanoma similar to that of SAHS-4

Attitudes towards Science, Technology, Engineering and Mathematics (STEM) in a Project-Based Learning (PjBL) Environment

ERIC Educational Resources Information Center

Tseng, Kuo-Hung; Chang, Chi-Cheng; Lou, Shi-Jer; Chen, Wen-Ping

2013-01-01

Many scholars claimed the integration of science, technology, engineering and mathematics (STEM) education is beneficial to the national economy and teachers and institutes have been working to develop integrated education programs. This study examined a project-based learning (PjBL) activity that integrated STEM using survey and interview…

CHRONIC EXPOSURE TO ARSENITE IN DRINKING WATER IMPAIRS GLUCOSE TOLERANCE IN C57BL/6 MICE

EPA Science Inventory

Chronic exposures to inorganic arsenic (iAs) have been associated with increased prevalence of type 2 diabetes mellitus. This study examines in vivo diabetogenic effects of iAs in an animal model. Here, weanling male C57BL/6 mice received deionized water containing iAs(III) (25 ...

Commissioning of BL 7.2, the new diagnostic beam line at the ALS

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

Sannibale, Fernando; Baum, Dennis; Biocca, Alan

2004-06-29

BL 7.2 is a new beamline at the Advanced Light Source (ALS) of the Lawrence Berkeley National Laboratory (LBNL) dedicated to electron beam diagnostics. The system, which is basically a hard x-ray pinhole camera, was installed in the storage ring in August 2003 and commissioning with the ALS electron beam followed immediately after. In this paper the commissioning results are presented together with the description of the relevant measurements performed for the beamline characterization.

[Effects of electroacupuncture at "Weizhong" (BL 40) on regeneration and morphology in rats with bupivacaine-induced multifidus muscle injury].

PubMed

Peng, Yuanyuan; Liu, Tong; Chen, Yupei; Zou, Dehui; Zhang, Li

2016-03-01

To observe the intervention effect of electroacupuncture (EA) at "Weizhong" (BL 40) on rats with bupivacaine-induced multifidus muscle injury, so as to explore the action mechanism. A total of 72 rats were randomly divided into a control group, a model group, a Weizhong group and a Shenshu group, 18 rats in each group. Each group was again randomly divided into a 4-day subgroup, a 7-day subgroup and a 14-day subgroup, 6 rats in each subgroup. Rats in the model group, Weizhong group and Shenshu group were treated with intramuscular injection of 0.5% bupivacaine (BPVC) to establish the model of multifidus muscle injury. Rats in the Weizhong group and Shenshu group were treated with EA at "Weizhong" (BL 40) and "Shenshu" (BL 23), 20 min per treatment, once a day. Each subgroup was treated for 4 days, 7 days and 14 days respectively. Rats in the control group and model group were treated with immobilization. The morphology and cross sectional area (CSA) changes of multifidus with HE and Masson staining at different time points were observed; the expression of insulin like growth factor 1 (IGF-1) and myogenic differentiation antigen (MyoD) was measured by immunohistochemical method. After the modeling, there were significant morphology changes of multifidus at different time points, which was not fully recovered after 14 days. The morphological observation in the Weizhong group and Shenshu group was superior to that in the model group. At 7th day, the CSA in the Weizhong group was higher than that in the model group (P < 0.05); at 14th day, the CSA in the Weizhong group and Shenshu group was higher than that in the model group (P < 0.01, P < 0.05). At 4th day and 7th day, the expression of IGF-1 in the model group was higher than that in the control group (both P < 0.01); at 4th day, that in the Weizhong group was higher than that in the model group (P < 0.01), and that in the Weizhong group was higher than that in the Shenshu group (P < 0.05), and that in the Shenshu

Superovulation Using the Combined Administration of Inhibin Antiserum and Equine Chorionic Gonadotropin Increases the Number of Ovulated Oocytes in C57BL/6 Female Mice

PubMed Central

Takeo, Toru; Nakagata, Naomi

2015-01-01

Superovulation is a reproductive technique generally used to produce genetically engineered mice. Superovulation in mice involves the administration of equine chorionic gonadotropin (eCG) to promote follicle growth and then that of human chorionic gonadotropin (hCG) to induce ovulation. Previously, some published studies reported that inhibin antiserum (IAS) increased the number of ovulated oocytes in ddY and wild-derived strains of mice. However, the effect of IAS on the C57BL/6 strain, which is the most widely used inbred strain for the production of genetically engineered mice, has not been investigated. In addition, the combined effect of IAS and eCG (IASe) on the number of ovulated oocytes in superovulation treatment has not been examined. In this study, we examined the effect of IAS and eCG on the number of ovulated oocytes in immature female mice of the C57BL/6 strain in superovulation treatment. Furthermore, we evaluated the quality of obtained oocytes produced by superovulation using IASe by in vitro fertilization (IVF) with sperm from C57BL/6 or genetically engineered mice. The developmental ability of fresh or cryopreserved embryos was examined by embryo transfer. The administration of IAS or eCG had a similar effect on the number of ovulated oocytes in C57BL/6 female mice. The number of ovulated oocytes increased to about 3-fold by the administration of IASe than by the administration of IAS or eCG alone. Oocytes derived from superovulation using IASe normally developed into 2-cell embryos by IVF using sperm from C57BL/6 mice. Fresh or cryopreserved 2-cell embryos produced by IVF between oocytes of C57BL/6 mice and sperm from genetically engineered mice normally developed into live pups following embryo transfer. In summary, a novel technique of superovulation using IASe is extremely useful for producing a great number of oocytes and offspring from genetically engineered mice. PMID:26024317

T cell cytokine synthesis at the single-cell level in BALB/c and C57BL/6 mice infected with ectromelia virus.

PubMed

Szulc, Lidia; Gieryńska, Małgorzata; Winnicka, Anna; Martyniszyn, Lech; Boratyńska-Jasińska, Anna; Niemiałtowski, Marek

2012-04-20

The purpose of the study was to evaluate synthesis of IFN-γ, IL-2, TNF-α (Th1/Tc1) and IL-4 (Th2/Tc2) at CD4+ T and CD8+ T cell level in BALB/c and C57BL/6 mice in the course of infection with ectromelia virus Moscow strain (ECTV-MOS). Synthesis of IFN-γ, IL-2, TNF-α and IL-4 in CD4+ T and CD8+ T cells in draining lymph nodes (DLNs) and spleens of BALB/c and C57BL/6 mice was detected by intracellular staining and flow cytometry analysis. Our results showed an increase in percentage of IFN-γ -synthesizing CD8+ T cells only in DLNs and spleens of C57BL/6 mice at the early stages of infection. Moreover, synthesis of IL-2 by CD4+ and CD8+ T cells occurred earlier and was stronger in C57BL/6 mice compared to BALB/c mice. The increase in TNF-α synthesis by CD4+ T and CD8+ T cells was detected mainly in DLNs of infected animals. We did not observe any changes in the percentage of IL-4-synthesizing T cells (Th2 and Tc2) during ECTV-MOS infection in both strains of mice. Results presented in this study confirmed that during the early phase of infection, C57BL/6 mice mounted a strong Th1 and Tc1 immune response against ECTV-MOS. BALB/c mice that survived the acute stage of mousepox, were able to mount an adequate cellular response to ECTV-MOS, however successful elimination of the virus in susceptible mice may occur more slowly compared to resistant strains of mice. Intracellular detection of IL-4 by flow cytometry was not sensitive enough to distinguish the differences in IL-4-synthesizing Th2 and Tc2 cells between susceptible and resistant strains of mice during ECTV-MOS infection.

THE VOLATILE COMPOSITION OF COMET C/2003 K4 (LINEAR) AT NEAR-IR WAVELENGTHS—COMPARISONS WITH RESULTS FROM THE NANÇAY RADIO TELESCOPE AND FROM THE ODIN, SPITZER, AND SOHO SPACE OBSERVATORIES

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

Paganini, L.; Mumma, M. J.; Villanueva, G. L.

2015-07-20

We observed comet C/2003 K4 (LINEAR) using NIRSPEC at the Keck Observatory on UT 2004 November 28, when the comet was at 1.28 AU from the Sun (post-perihelion) and 1.38 AU from Earth. We detected six gaseous species (H{sub 2}O, OH*, C{sub 2}H{sub 6}, CH{sub 3}OH, CH{sub 4}, and HCN) and obtained upper limits for three others (H{sub 2}CO, C{sub 2}H{sub 2}, and NH{sub 3}). Our results indicate a water production rate of (1.72 ± 0.18) × 10{sup 29} molecules s{sup −1}, in reasonable agreement with production rates from SOHO (on the same day), Odin (one day earlier), and Nançaymore » (about two weeks earlier). We also report abundances (relative to water) for seven trace species: CH{sub 3}OH (∼1.8%), CH{sub 4} (∼0.9%), and C{sub 2}H{sub 6} (∼0.4%) that were consistent with mean values among Oort cloud (OC) comets, while NH{sub 3} (<0.55%), HCN (∼0.07%), H{sub 2}CO (<0.07%), and C{sub 2}H{sub 2} (<0.04%) were “lower” than the mean values in other OC comets. We extracted inner-coma rotational temperatures for four species (H{sub 2}O, C{sub 2}H{sub 6}, CH{sub 3}OH, and CH{sub 4}), all of which are consistent with 70 K (within 1σ). The extracted ortho-para ratio for water was 3.0 ± 0.15, corresponding to spin temperatures larger than 39 K (at the 1σ level) and agreeing with those obtained with the Spitzer Space Telescope at the 2σ level.« less

Radix Stellariae extract prevents high-fat-diet-induced obesity in C57BL/6 mice by accelerating energy metabolism

PubMed Central

Li, Yin; Liu, Xin; Fan, Yu

2017-01-01

Stellaria dichotoma L. is widely distributed in Ningxia and surrounding areas in northwestern China. Its root, Radix Stellariae (RS), has been used in herbal formulae for treating asthenic-fever, infection, malaria, dyspepsia in children and several other symptoms. This study investigated whether the RS extract (RSE) alleviates metabolic disorders. The results indicated that RSE significantly inhibited body weight gain in high-fat (HF)-diet-fed C57BL/6 mice, reduced fasting glucose levels, and improved insulin tolerance. Moreover, RSE increased the body temperature of the mice and the expression of uncoupling proteins and peroxisome proliferator-activated receptors in the white adipose tissue. Thus, RSE alleviated metabolic disorders in HF-diet-fed C57BL/6 mice by potentially activating UCP and PPAR signaling. PMID:28507819

Extraordinary Activity in the BL Lac Object OJ 287

NASA Astrophysics Data System (ADS)

Hughes, P. A.; Aller, H. D.; Aller, M. F.

We present the results of a wavelet transform analysis of data for the BL Lac object OJ 287 acquired as part of the UMRAO variability program. We find clear evidence for a persistent modulation of the total flux and polarization with period 1.66 years, and for another signal that dominates activity in the 1980s with period 1.12 years. It appears that the longer time scale periodicity is associated with an otherwise quiescent jet, and the shorter time scale activity is associated with the passage of a shock, or shocks. The periodic behavior in polarization exhibits excursions in U which correspond to a direction 45circ from the VLBI jet axis. This behavior suggests a small amplitude, cyclic variation in the flow direction in that part of the flow that dominates cm-wavelength emission.

Methamphetamine protects against MPTP neurotoxicity in C57BL mice.

PubMed

Sziráki, I; Kardos, V; Patthy, M; Pátfalusi, M; Budai, G

1994-01-14

Methamphetamine (5 mg/kg) administered 30 min prior to each injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (3 x 30 mg/kg, at 24 h intervals) prevents the reduction of striatal levels of dopamine and its metabolites in C57BL mice. Methamphetamine and amphetamine inhibit the uptake of 1-methyl-4-phenylpyridinium (MPP+) by striatal synaptosomes of rats. A 30-min post-treatment with methamphetamine or amphetamine also prevents the MPTP-induced dopamine depletion, suggesting that their protective effect is related to the blockade of MPP+ uptake into dopaminergic neurons. Since amphetamine and methamphetamine are themselves neurotoxins at higher doses, this work demonstrated the protection against the actions of one neurotoxin by the administration of another.

Comparison of refractive development and retinal dopamine in OFF pathway mutant and C57BL/6J wild-type mice

PubMed Central

Chakraborty, Ranjay; Park, Han na; Aung, Moe H.; Tan, Christopher C.; Sidhu, Curran S.; Iuvone, P. Michael

2014-01-01

Purpose Proper visual transmission depends on the retinal ON and OFF pathways. We used Vsx1−/− mice with a retinal OFF visual pathway defect to determine the role of OFF pathway signaling in refractive development (RD) of the eye. Methods Refractive development was measured every 2 weeks in Vsx1−/−, Vsx1+/+ (both on 129S1/Sv background), and commonly used C57BL/6J mice from 4 to 12 weeks of age. Form deprivation (FD) was induced monocularly from 4 weeks of age using head-mounted diffuser goggles. Refractive state, corneal curvature, and ocular biometry were obtained weekly using photorefraction, keratometry, and 1310 nm spectral-domain optical coherence tomography. Retinal dopamine and its metabolite, 3,4-dihydroxyphenylacetate (DOPAC), were measured using high-performance liquid chromatography (HPLC). Results During normal development, the Vsx1−/− and Vsx1+/+ mice showed similar myopic refractions at younger ages (4 weeks, Vsx1−/−: −5.28±0.75 diopter (D); WT: −4.73±0.98 D) and became significantly hyperopic by 12 weeks of age (Vsx1−/−: 3.28±0.82 D; WT: 5.33±0.81 D). However, the C57BL/6J mice were relatively hyperopic at younger ages (mean refraction at 4 weeks, 3.40±0.43 D), and developed more hyperopic refractions until about 7 weeks of age (8.07±0.55 D) before stabilizing. Eight weeks of FD did not induce a myopic shift in the 129S1/Sv animals (0.16±0.85 D), as opposed to a significant shift of −4.29±0.42 D in the C57BL/6J mice. At 4 weeks of visual development, dopamine turnover (the DOPAC/dopamine ratio) was significantly greater in the 129S1/Sv mice compared to the C57BL/6J mice. FD did not alter the levels of dopamine between the goggled and opposite eyes for any genotype or strain. Conclusions OFF pathway signaling may not be critically important for normal refractive development in mice. Elevated retinal dopamine turnover in early refractive development may prevent FD myopia in 129S1/Sv mice compared to C57BL/6J mice

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

NASA Astrophysics Data System (ADS)

Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

2016-07-01

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

REINSTATEMENT OF ETHANOL AND SUCROSE SEEKING BY THE NEUROSTEROID ALLOPREGNANOLONE IN C57BL/6 MICE

PubMed Central

Finn, Deborah A.; Mark, Gregory P.; Fretwell, Andrea M.; Gililland, Katherine R.; Strong, Moriah N.; Ford, Matthew M.

2016-01-01

Rationale Recent work in our laboratory documented that the “sipper” method of operant ethanol self-administration produced high ethanol intake and blood ethanol concentrations as well as the typical extinction “burst” in responding under non-reinforced conditions in male C57BL/6 mice. However, the neurochemical basis for reinstatement of responding following extinction has not been examined in mice with this model. Objectives Based on findings that the GABAergic neurosteroid allopregnanolone (ALLO) significantly increased the consummatory phase of ethanol self-administration, the present study determined the effect of ALLO on reinstatement of extinguished ethanol-seeking behavior and compared this effect to reinstatement of responding for sucrose reward. Methods Separate groups of male C57BL/6 mice were trained to lever press for access to a 10% ethanol (10E) or a 5% sucrose (5S) solution. A single response requirement of 16 presses (RR16) on an active lever resulted in 30 min of continuous access to the 10E or 5S solution. After the animals responded on the RR16 schedule for 14 weeks, mice were exposed to 30 min extinction sessions where responding had no scheduled consequence. Once responding stabilized below the pre-extinction baseline, mice received an IP injection of ALLO (0, 3.2, 5.6, 10 or 17 mg/kg) 15 min prior to the extinction session in a within-subjects design. Results ALLO produced a dose-dependent increase in responding under non-reinforced conditions in both the 10E and 5S groups. Additional work documented the ability of a conditioned cue light or a compound cue (light+lever retraction) to reinstate non-reinforced responding on the previously active lever. Conclusions These findings definitively show that conditioned cues and priming with ALLO are potent stimuli for reinstating both ethanol and sucrose seeking behavior in C57BL/6 mice. PMID:18758755

Double crystal monochromator controlled by integrated computing on BL07A in New SUBARU, Japan

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

Okui, Masato, E-mail: okui@kohzu.co.jp; Laboratory of Advanced Science and Technology for Industry, University of Hyogo; Yato, Naoki

2016-07-27

The BL07A beamline in New SUBARU, University of Hyogo, has been used for many studies of new materials. A new double crystal monochromator controlled by integrated computing was designed and installed in the beamline in 2014. In this report we will discuss the unique features of this new monochromator, MKZ-7NS. This monochromator was not designed exclusively for use in BL07A; on the contrary, it was designed to be installed at low cost in various beamlines to facilitate the industrial applications of medium-scale synchrotron radiation facilities. Thus, the design of the monochromator utilized common packages that can satisfy the wide varietymore » of specifications required at different synchrotron radiation facilities. This monochromator can be easily optimized for any beamline due to the fact that a few control parameters can be suitably customized. The beam offset can be fixed precisely even if one of the two slave axes is omitted. This design reduces the convolution of mechanical errors. Moreover, the monochromator’s control mechanism is very compact, making it possible to reduce the size of the vacuum chamber can be made smaller.« less

Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice.

PubMed

Vogt, M A; Mallien, A S; Pfeiffer, N; Inta, I; Gass, P; Inta, D

2016-03-15

Minocycline is a broad-spectrum tetracycline antibiotic with multiple actions, including anti-inflammatory and neuroprotective effects, that was proposed as novel treatment for several psychiatric disorders including schizophrenia and depression. However, there are contradictory results regarding antidepressant effects of minocycline in rodent models. Additionally, the possible anxiolytic effect of minocycline is still poorly investigated. Therefore, we aimed to clarify in the present study the influence of minocycline on behavioral correlates of mood disorders in standard tests for depression and anxiety, the Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark-Light Box Test and Openfield Test in adult C57BL/6 mice. We found, unexpectedly, that mice treated with minocycline (20-40mg/kg, i.p.) did not display antidepressant- or anxiolytic-like behavioral changes in contrast to mice treated with diazepam (0.5mg/kg, anxiety tests) or imipramine (20mg/kg, depressive-like behavior). These results are relevant for future studies, considering that C57BL/6 mice, the most widely used strain in pharmacological and genetic animal models, did not react as expected to the treatment regime applied. Copyright © 2015 Elsevier B.V. All rights reserved.

An Analysis of Periodic Components in BL Lac Object S5 0716 +714 with MUSIC Method

NASA Astrophysics Data System (ADS)

Tang, J.

2012-01-01

Multiple signal classification (MUSIC) algorithms are introduced to the estimation of the period of variation of BL Lac objects.The principle of MUSIC spectral analysis method and theoretical analysis of the resolution of frequency spectrum using analog signals are included. From a lot of literatures, we have collected a lot of effective observation data of BL Lac object S5 0716 + 714 in V, R, I bands from 1994 to 2008. The light variation periods of S5 0716 +714 are obtained by means of the MUSIC spectral analysis method and periodogram spectral analysis method. There exist two major periods: (3.33±0.08) years and (1.24±0.01) years for all bands. The estimation of the period of variation of the algorithm based on the MUSIC spectral analysis method is compared with that of the algorithm based on the periodogram spectral analysis method. It is a super-resolution algorithm with small data length, and could be used to detect the period of variation of weak signals.

QUANTITATIVE EVALUATION OF THE HYPOTHESIS THAT BL LACERTAE OBJECTS ARE QSO REMNANTS

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

Borra, E. F.

2014-11-20

We evaluate with numerical simulations the hypothesis that BL Lacertae objects (BLLs) are the remnants of quasi-stellar objects. This hypothesis is based on their highly peculiar redshift evolution. They have a comoving space density that increases with decreasing redshift, contrary to all other active galactic nuclei. We assume that relativistic jets are below detection in young radio-quiet quasars and increase in strength with cosmic time so that they eventually are detected as BLLs. Our numerical simulations fit very well the observed redshift distributions of BLLs. There are strong indications that only the high-synchrotron-peaked BLLs could be QSO remnants.

The first Fermi multifrequency campaign on BL Lacertae: Characterizing the low-activity state of the eponymous blazar

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2011-03-10

Here, we report on observations of BL Lacertae during the first 18 months of Fermi LAT science operations and present results from a 48 day multifrequency coordinated campaign from 2008 August 19 to 2008 October 7. The radio to gamma-ray behavior of BL Lac is unveiled during a low-activity state thanks to the coordinated observations of radio-band (Metsähovi and VLBA), near-IR/optical (Tuorla, Steward, OAGH, and MDM), and X-ray ( RXTE and Swift) observatories. No variability was resolved in gamma rays during the campaign, and the brightness level was 15 times lower than the level of the 1997 EGRET outburst. Moderatemore » and uncorrelated variability has been detected in UV and X-rays. The X-ray spectrum is found to be concave, indicating the transition region between the low- and high-energy components of the spectral energy distribution (SED). VLBA observation detected a synchrotron spectrum self-absorption turnover in the innermost part of the radio jet appearing to be elongated and inhomogeneous, and constrained the average magnetic field there to be less than 3 G. Over the following months, BL Lac appeared variable in gamma rays, showing flares (in 2009 April and 2010 January). There is no evidence for the correlation of gamma rays with the optical flux monitored from the ground in 18 months. The SED may be described by a single-zone or a two-zone synchrotron self-Compton (SSC) model, but a hybrid SSC plus external radiation Compton model seems to be preferred based on the observed variability and the fact that it provides a fit closest to equipartition.« less

Genetic basis of HDL variation in 129/SvImJ and C57BL/6J mice: importance of testing candidate genes in targeted mutant mice.

PubMed

Su, Zhiguang; Wang, Xiaosong; Tsaih, Shirng-Wern; Zhang, Aihong; Cox, Allison; Sheehan, Susan; Paigen, Beverly

2009-01-01

To evaluate the effect of genetic background on high-density lipoprotein cholesterol (HDL) levels in Soat1(-/-) mice, we backcrossed sterol O-acyltransferase 1 (Soat1)(-/-) mice, originally reported to have elevated HDL levels, to C57BL/6 mice and constructed a congenic strain with only a small region (3.3Mb) of 129 alleles, specifically excluding the nearby apolipoprotein A-II (Apoa2) gene from 129. HDL levels in these Soat1(-/-) mice were no different from C57BL/6, indicating that the passenger gene Apoa2 caused the previously reported elevation of HDL in these Soat1(-/-) mice. Because many knockouts are made in strain 129 and then subsequently backcrossed into C57BL/6, it is important to identify quantitative trait loci (QTL) that differ between 129 and C57BL/6 so that one can guard against effects ascribed to a knockout but really caused by a passenger gene from 129. To provide such data, we generated 528 F(2) progeny from an intercross of 129S1/SvImJ and C57BL/6 and measured HDL concentrations in F(2) animals first fed chow and then atherogenic diet. A genome wide scan using 508 single-nucleotide polymorphisms (SNPs) identified 19 QTL, 2 of which were male specific and 2 were female specific. Using comparative genomics and haplotype analysis, we narrowed QTL on chromosomes 3, 5, 8, 17, and 18 to 0.5, 6.3, 2.6, 1.1, and 0.6 Mb, respectively. These data will serve as a reference for any effort to test the impact of candidate genes on HDL using a knockout strategy.

Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to resolve visceral Leishmania donovani infection.

PubMed Central

Murray, H W; Hariprashad, J; McDermott, D F; Stoeckle, M Y

1996-01-01

Euthymic C57BL/L ep/ep (pale ear [PE]) mice halt the visceral replication of intracellular Leishmania donovani but fail to properly resolve infection. A previous study identified an isolated defect in tissue granuloma formation in these mice; CD4+ and CD8+ cell number, gamma interferon (IFN-gamma) production, and macrophage antimicrobial activity in vitro were all intact. New in vivo results reported here suggest a considerably more complex immune defect, with evidence indicating (i) enhanced control over L. donovani after transfer of normal C57BL/6 spleen cells, (ii) a partially suppressive Th2 cell-associated response mediated by interleukin-4 (IL-4) but not reversed by CD4+ cell depletion, (iii) absent responses to endogenous Th1 cell lymphokines (IFN-gamma and IL-2) but preserved responsiveness to endogenous tumor necrosis factor alpha, (iv) absent responses to exogenous treatment with recognized antileishmanial cytokines (IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) not corrected by transfer of C57BL/6 spleen cells, and (v) a deficient response to antimony chemotherapy. Defective hepatic granuloma formation was not corrected by transfer of C57BL/6 spleen cells or by anti-IL-4 administration. While treatment with IL-2 and GM-CSF modified the tissue reaction and induced selected effector cells to encase tissue macrophages, no antileishmanial activity resulted. Together, these observations suggest that the failure of PE mice to resolve visceral L. donovani infection likely represents expression of multiple suboptimal immune responses and/or partial defects, probably involving a combination of T-cell dysfunction, a Th2 cell response, and target cell (macrophage) hyporesponsiveness. PMID:8557335

Ulcerative Dermatitis in C57BL/6NCrl Mice on a Low-Fat or High-Fat Diet With or Without a Mineralized Red-Algae Supplement

PubMed Central

Hampton, Anna L; Aslam, Muhammad N; Naik, Madhav K; Bergin, Ingrid L; Allen, Ron M; Craig, Ronald A; Kunkel, Steve L; Veerapaneni, Indiradevi; Paruchuri, Tejaswi; Patterson, Kathleen A; Rothman, Edward D; Hish, Gerald A; Varani, James; Rush, Howard G

2015-01-01

Ulcerative dermatitis (UD) is a spontaneous idiopathic disease that often affects C57BL/6 mice or mice on a C57BL/6 background. UD is characterized by intense pruritus and lesion formation, most commonly on the head or dorsal thorax. Self-trauma likely contributes to wound severity and delayed wound healing. Histologically, changes are nonspecific, consisting of ulceration with neutrophilic and mastocytic infiltration and epithelial hyperplasia and hyperkeratosis. Diet appears to have a profound effect on the development and progression of UD lesions. We investigated the incidence and severity of UD in C57BL/6NCrl mice on a high-fat western-style diet (HFWD) compared with a standard rodent chow. In addition, we examined the protective effects of dietary supplementation with a multimineral-rich product derived from marine red algae on UD in these 2 diet groups. HFWD-fed mice had an increased incidence of UD. In addition, mice on a HFWD had significantly more severe clinical and histologic lesions. Dietary mineral supplementation in mice on a HFWD decreased the histologic severity of lesions and reduced the incidence of UD in female mice in both diets. In conclusion, a high-fat western-style diet may potentiate UD in C57BL/6NCrl mice. Insufficient mineral supply and mineral imbalance may contribute to disease development. Mineral supplementation may be beneficial in the treatment of UD. PMID:26424246

POWERFUL HIGH-ENERGY EMISSION OF THE REMARKABLE BL Lac OBJECT S5 0716+714

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

Vittorini, V.; Chen, A. W.; Ferrari, A.

BL Lac objects of the intermediate subclass (IBLs) are known to emit a substantial fraction of their power in the energy range 0.1-10 GeV. Detecting gamma-ray emission from such sources provides therefore a direct probe of the emission mechanisms and of the underlying powerhouse. The gamma-ray satellite, AGILE, detected the remarkable IBL S5 0716+714 (z approx = 0.3) during a high state in the period from 2007 September-October, marked by two very intense flares reaching peak fluxes of 200 x 10{sup -8} photons cm{sup -2} s{sup -1} above 100 MeV, with simultaneous optical and X-ray observations. We present here amore » theoretical model for the two major flares and discuss the overall energetics of the source. We conclude that 0716+714 is among the brightest BL Lac's ever detected at gamma-ray energies. Because of its high power and lack of signs for ongoing accretion or surrounding gas, the source is an ideal candidate to test the maximal power extractable from a rotating supermassive black hole via the pure Blandford-Znajek (BZ) mechanism. We find that during the 2007 gamma-ray flares 0716+714 approached or just exceeded the upper limit set by BZ for a black hole of mass 10{sup 9} M{sub sun}.« less

Effects of Fortunella margarita fruit extract on metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

PubMed

Tan, Si; Li, Mingxia; Ding, Xiaobo; Fan, Shengjie; Guo, Lu; Gu, Ming; Zhang, Yu; Feng, Li; Jiang, Dong; Li, Yiming; Xi, Wanpeng; Huang, Cheng; Zhou, Zhiqin

2014-01-01

Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice. The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.

A new leaf rust resistance gene Lr79 mapped in chromosome 3BL from the durum wheat landrace Aus26582.

PubMed

Qureshi, Naeela; Bariana, Harbans; Kumran, Vikas Venu; Muruga, Sivasamy; Forrest, Kerrie L; Hayden, Mathew J; Bansal, Urmil

2018-05-01

A new leaf rust resistance gene Lr79 has been mapped in the long arm of chromosome 3B and a linked marker was identified for marker-assisted selection. Aus26582, a durum wheat landrace from the A. E. Watkins Collection, showed seedling resistance against durum-specific and common wheat-specific Puccinia triticina (Pt) pathotypes. Genetic analysis using a recombinant inbred line (RIL) population developed from a cross between Aus26582 and the susceptible parent Bansi with Australian Pt pathotype showed digenic inheritance and the underlying loci were temporarily named LrAW2 and LrAW3. LrAW2 was located in chromosome 6BS and this study focused on characterisation of LrAW3 using RILs lacking LrAW2. LrAW3 was incorporated into the DArTseq map of Aus26582/Bansi and was located in chromosome 3BL. Markers linked with LrAW3 were developed from the chromosome survey sequence contig 3B_10474240 in which closely-linked DArTseq markers 1128708 and 3948563 were located. Although bulk segregant analysis (BSA) with the 90 K Infinium array identified 51 SNPs associated with LrAW3, only one SNP-derived KASP marker mapped close to the locus. Deletion bin mapping of LrAW3-linked markers located LrAW3 between bins 3BL11-0.85-0.90 and 3BL7-0.63. Since no other all stage leaf rust resistance gene is located in chromosome 3BL, LrAW3 represented a new locus and was designated Lr79. Marker sun786 mapped 1.8 cM distal to Lr79 and Aus26582 was null for this locus. However, the marker can be reliably scored as it also amplifies a monomorphic fragment that serves as an internal control to differentiate the null status of Aus26582 from reaction failure. This marker was validated among a set of durum and common wheat cultivars and was shown to be useful for marker-assisted selection of Lr79 at both ploidy levels.

An open-label tolerability study of BL-1020 antipsychotic: a novel gamma aminobutyric acid ester of perphenazine.

PubMed

Anand, Ravi; Geffen, Yona; Vasile, Daniel; Dan, Irina

2010-01-01

BL-1020, a novel gamma aminobutyric acid (GABA) ester of perphenazine, is a new oral antipsychotic with a strong affinity for dopamine and serotonin receptors. Unlike first- and second-generation antipsychotics, it has agonist activity at GABA(A). This is the first study to examine tolerability and safety of BL-1020 in schizophrenia. This was a phase-II, open-label, multicenter, 6-week study treating patients (n = 36) with chronic schizophrenia. Dosing started at 20 mg/d and increased over 7 days to 40 mg/d. Weekly assessments were conducted. All but 1 patient was titrated to 30 mg/d at day 4; on day 7, 30 were titrated to 40 mg/d. Four patients discontinued the study prematurely. There was no clinically relevant increase in vital signs, sedation, dizziness, or other central nervous system effects or electrocardiogram or laboratory abnormalities and a small increase in weight. Ten patients experienced extrapyramidal symptoms (EPS) requiring treatment with an anticholinergic; 4 patients were unable to reach maximum dose because of EPS. Extrapyramidal Symptom Rating Scale did not indicate clinically significant changes in EPS. The most common adverse event was insomnia (6 patients); other frequent adverse effects (all n = 3) were extrapyramidal disorder, headache, parkinsonism, tremor, and hyperprolactinemia. There was improvement on Positive and Negative Syndrome Scale and Clinical Global Impression of Change with 22 patients showing at least 20% decrease by end point on Positive and Negative Syndrome Scale and 31 patients showing at least minimal improvement on Clinical Global Impression of Change. These data suggest that 20 to 40 mg/d of BL-1020 is associated with clinically relevant improvement of psychosis with no worsening of EPS and support further testing in randomized controlled trials.

An Analysis of Light Periods of BL Lac Object S5 0716+714 with the MUSIC Algorithm

NASA Astrophysics Data System (ADS)

Tang, Jie

2012-07-01

The multiple signal classification (MUSIC) algorithm is introduced to the estimation of light periods of BL Lac objects. The principle of the MUSIC algorithm is given, together with a testing on its spectral resolution by using a simulative signal. From a lot of literature, we have collected a large number of effective observational data of the BL Lac object S5 0716+714 in the three optical wavebands V, R, and I from 1994 to 2008. The light periods of S5 0716+714 are obtained by means of the MUSIC algorithm and average periodogram algorithm, respectively. It is found that there exist two major periodic components, one is the period of (3.33±0.08) yr, another is the period of (1.24±0.01) yr. The comparison of the performances of periodicity analysis of two algorithms indicates that the MUSIC algorithm has a smaller requirement on the sample length, as well as a good spectral resolution and anti-noise ability, to improve the accuracy of periodicity analysis in the case of short sample length.

Blended Learning (BL) as Pedagogical Alternative to Teach Business Communication Course: Case Study of UUM Executive Diploma Program

ERIC Educational Resources Information Center

Dzakiria, Hisham; Don @ A. Wahab, Mohd Sobri; Abdul Rahman, Hamzah Dato'

2012-01-01

Globally, blended learning (BL) technologies have been increasingly applied in a variety of fields, both public and private sectors. In recent years, universities, public and private businesses and organizations are among those employing blended learning methods and technologies in training and re-training of professionals in the workforce. In…

Beam line BL11 for LIGA process at the NewSUBARU

NASA Astrophysics Data System (ADS)

Mekaru, Harutaka; Utsumi, Yuichi; Hattori, Tadashi

2001-07-01

A beam line BL11 is constructed for exposure Hard X-ray Lithography (HXL) in the LIGA (German acronym for Lithographite Galvanoformung and Abformung) process at the synchrotron radiation (SR) facility NewSUBARU of the Laboratory of Advanced Science and Technology for Industry (LASTI) in Himeji Institute of Technology (HIT). This beam line was designed by the criteria; photon energy range 4-6 keV, a beam spot size on the exposure stage ⩾60×5 mm 2, a density of total irradiated photons ⩾10 11 photons/cm 2. The PMMA sheet etching was successfully demonstrated by using the output beam. We conclude that this beam line performs sufficiently well to study the exposure of HXL in the LIGA process.

Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trial.

PubMed

Wayne, Alan S; Kreitman, Robert J; Findley, Harry W; Lew, Glen; Delbrook, Cynthia; Steinberg, Seth M; Stetler-Stevenson, Maryalice; Fitzgerald, David J; Pastan, Ira

2010-03-15

Although most children with B-lineage acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma are cured, new agents are needed to overcome drug resistance and reduce toxicities of chemotherapy. We hypothesized that the novel anti-CD22 immunotoxin, RFB4(dsFv)-PE38 (BL22, CAT-3888), would be active and have limited nonspecific side effects in children with CD22-expressing hematologic malignancies. We conducted the first preclinical and phase I clinical studies of BL22 in that setting. Lymphoblasts from children with B-lineage ALL were assessed for CD22 expression by flow cytometry and for BL22 sensitivity by in vitro cytotoxicity assay. BL22 was evaluated in a human ALL murine xenograft model. A phase I clinical trial was conducted for pediatric subjects with CD22+ ALL and non-Hodgkin lymphoma. All samples screened were CD22+. BL22 was cytotoxic to blasts in vitro (median IC(50), 9.8 ng/mL) and prolonged the leukemia-free survival of murine xenografts. Phase I trial cohorts were treated at escalating doses and schedules ranging from 10 to 40 microg/kg every other day for three or six doses repeated every 21 or 28 days. Treatment was associated with an acceptable safety profile, adverse events were rapidly reversible, and no maximum tolerated dose was defined. Pharmacokinetics were influenced by disease burden consistent with rapid drug binding by CD22+ blasts. Although no responses were observed, transient clinical activity was seen in most subjects. CD22 represents an excellent target and anti-CD22 immunotoxins offer therapeutic promise in B-lineage hematologic malignancies of childhood.

Effects of Differing Response-Force Requirements on Food-Maintained Responding in C57BL/6J Mice

ERIC Educational Resources Information Center

Zarcone, Troy J.; Chen, Rong; Fowler, Stephen C.

2009-01-01

The effect of force requirements on response effort was examined using inbred C57BL/6J mice trained to press a disk with their snout. Lateral peak forces greater than 2 g were defined as responses (i.e., all responses above the measurement threshold). Different, higher force requirements were used to define criterion responses (a subclass of all…

Developing and validating trace fear conditioning protocols in C57BL/6 mice.

PubMed

Burman, Michael A; Simmons, Cassandra A; Hughes, Miles; Lei, Lei

2014-01-30

Classical fear conditioning is commonly used to study the biology of fear, anxiety and memory. Previous research demonstrated that delay conditioning requires a neural circuit involving the amygdala, but not usually the hippocampus. Trace and contextual fear conditioning require the amygdala and hippocampus. While these paradigms were developed primarily using rat models, they are increasingly being used in mice. The current studies develop trace fear conditioning and control paradigms to allow for the assessment of trace and delay fear conditioning in C57BL/6N mice. Our initial protocol yielded clear delay and contextual conditioning. However, trace conditioning failed to differentiate from an unpaired group and was not hippocampus-dependent. These results suggested that the protocol needed to be modified to specifically accommodate trace conditioning the mice. In order to reduce unconditioned freezing and increase learning, the final protocol was developed by decreasing the intensity of the tone and by increasing the inter-trial interval. Our final protocol produced trace conditioned freezing that was significantly greater than that followed unpaired stimulus exposure and was disrupted by hippocampus lesions. A review of the literature produced 90 articles using trace conditioning in mice. Few of those articles used any kind of behavioral control group, which is required to rule out non-associative factors causing fearful behavior. Fewer used unpaired groups involving tones and shocks within a session, which is the optimal control group. Our final trace conditioning protocol can be used in future studies examining genetically modified C57BL/6N mice. Copyright © 2013 Elsevier B.V. All rights reserved.

Developing and Validating Trace Fear Conditioning Protocols in C57BL/6 Mice

PubMed Central

Burman, Michael A; Simmons, Cassandra A; Hughes, Miles; Lei, Lei

2013-01-01

Background Classical fear conditioning is commonly used to study the biology of fear, anxiety and memory. Previous research demonstrated that delay conditioning requires a neural circuit involving the amygdala, but not usually the hippocampus. Trace and contextual fear conditioning require the amygdala and hippocampus. While these paradigms were developed primarily using rat models, they are increasingly being used in mice. New Method The current studies develop trace fear conditioning and control paradigms to allow for the assessment of trace and delay fear conditioning in C57BL/6N mice. Our initial protocol yielded clear delay and contextual conditioning. However, trace conditioning failed to differentiate from an unpaired group and was not hippocampus-dependent. These results suggested that the protocol needed to be modified to specifically accommodate trace conditioning the mice. In order to reduce unconditioned freezing and increase learning, the final protocol was developed by decreasing the intensity of the tone and by increasing the inter-trial interval. Results Our final protocol produced trace conditioned freezing that was significantly greater than that followed unpaired stimulus exposure and was disrupted by hippocampus lesions. Comparison with Existing Methods A review of the literature produced 90 articles using trace conditioning in mice. Few of those articles used any kind of behavioral control group, which is required to rule out non-associative factors causing fearful behavior. Fewer used unpaired groups involving tones and shocks within a session, which is the optimal control group. Conclusions Our final trace conditioning protocol can be used in future studies examining genetically modified C57BL/6N mice. PMID:24269252

A high density physical map of chromosome 1BL supports evolutionary studies, map-based cloning and sequencing in wheat

PubMed Central

2013-01-01

Background As for other major crops, achieving a complete wheat genome sequence is essential for the application of genomics to breeding new and improved varieties. To overcome the complexities of the large, highly repetitive and hexaploid wheat genome, the International Wheat Genome Sequencing Consortium established a chromosome-based strategy that was validated by the construction of the physical map of chromosome 3B. Here, we present improved strategies for the construction of highly integrated and ordered wheat physical maps, using chromosome 1BL as a template, and illustrate their potential for evolutionary studies and map-based cloning. Results Using a combination of novel high throughput marker assays and an assembly program, we developed a high quality physical map representing 93% of wheat chromosome 1BL, anchored and ordered with 5,489 markers including 1,161 genes. Analysis of the gene space organization and evolution revealed that gene distribution and conservation along the chromosome results from the superimposition of the ancestral grass and recent wheat evolutionary patterns, leading to a peak of synteny in the central part of the chromosome arm and an increased density of non-collinear genes towards the telomere. With a density of about 11 markers per Mb, the 1BL physical map provides 916 markers, including 193 genes, for fine mapping the 40 QTLs mapped on this chromosome. Conclusions Here, we demonstrate that high marker density physical maps can be developed in complex genomes such as wheat to accelerate map-based cloning, gain new insights into genome evolution, and provide a foundation for reference sequencing. PMID:23800011

X-Ray and TeV Gamma-Ray Emission from Parallel Electron-Positron or Electron-Proton Beams in BL Lacertae Objects

NASA Astrophysics Data System (ADS)

Krawczynski, H.

2007-04-01

In this paper we discuss models of the X-ray and TeV γ-ray emission from BL Lac objects based on parallel electron-positron or electron-proton beams that form close to the central black hole, due to the strong electric fields generated by the accretion disk and possibly also by the black hole itself. Fitting the energy spectrum of the BL Lac object Mrk 501, we obtain tight constraints on the beam properties. Launching a sufficiently energetic beam requires rather strong magnetic fields close to the black hole (~100-1000 G). However, the model fits imply that the magnetic field in the emission region is only ~0.02 G. Thus, the particles are accelerated close to the black hole and propagate a considerable distance before instabilities trigger the dissipation of energy through synchrotron and self-Compton emission. We discuss various approaches to generate enough power to drive the jet and, at the same time, to accelerate particles to ~20 TeV energies. Although the parallel beam model has its own problems, it explains some of the long-standing problems that plague models based on Fermi-type particle acceleration, such as the presence of a very high minimum Lorentz factor of accelerated particles. We conclude with a brief discussion of the implications of the model for the difference between the processes of jet formation in BL Lac-type objects and those in quasars.

X-ray and TeV Gamma-Ray Emission from Parallel Electron-Positron or Electron-Proton Beams in BL Lac Objects

NASA Astrophysics Data System (ADS)

Krawczynski, Henric

2007-04-01

In this contribution we discuss models of the X-rays and TeV gamma-ray emission from BL Lac objects based on parallel electron-positron or electron-proton beams that form close to the central black hole owing to the strong electric fields generated by the accretion disk and possibly also by the black hole itself. Fitting the energy spectrum of the BL Lac object Mrk 501, we obtain tight constrains on the beam properties. Launching a sufficiently energetic beam requires rather strong magnetic fields close to the black hole 100-1000 G. However, the model fits imply that the magnetic field in the emission region is only 0.02 G. Thus, the particles are accelerated close to the black hole and propagate a considerable distance before instabilities trigger the dissipation of energy through synchrotron and self-Compton emission. We discuss various approaches to generate enough power to drive the jet and, at the same time, to accelerate particles to 20 TeV energies. Although the parallel beam model has its own problems, it explains some of the long-standing problems that plague models based on Fermi type particle acceleration, like the presence of a very high minimum Lorentz factor of accelerated particles. We conclude with a brief discussion of the implications of the model for the difference between the processes of jet formation in BL Lac type objects and in quasars.

Quercetin inhibits the invasion of murine melanoma B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

PubMed

Zhang, Xian-Ming; Huang, Shao-Peng; Xu, Qiang

2004-01-01

On the basis of the inhibitory effect of quercetin on the invasion of melanoma B16-BL6 cells previously reported by us, the mechanisms of quercetin-mediated inhibition of invasion were further investigated in the present study. The ability of B16-BL6 cells to invade and migrate was evaluated in terms of the numbers of cells penetrating a reconstituted basement membrane in the Transwell coculture system. The relative levels and activities of matrix metalloproteinase-9 (MMP-9) and MMP-2 were determined by gelatin zymography and quantified using LabWorks 4.0 software. The quercetin-mediated inhibition of invasion was partially blocked by phorbol-12,13-dibutyrate (PDB), a PKC (protein kinase C) activator, and by doxorubicin, a PKC inhibitor. Only the proforms of MMP-9 (92 kDa) and MMP-2 (72 kDa) were detected by gelatin zymography. Quercetin dose-dependently decreased the gelatinolytic activity of pro-MMP-9. Doxorubicin also markedly reversed the quercetin-induced decrease. Quercetin showed a dose-dependent antagonism of increases in gelatinolytic activity of pro-MMP-9 induced by PDB and free fatty acid (another PKC activator). Together with the report that quercetin directly reduces PKC activity, the results reported here suggest that quercetin may inhibit the invasion of B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

NASA Astrophysics Data System (ADS)

Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul

2012-07-01

Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8

Growth inhibition and differentiation of murine melanoma B16-BL6 cells caused by the combination of cisplatin and caffeine.

PubMed

Tsuchiya, H; Tomita, K; Yasutake, H; Ueda, Y; Tanaka, M; Sasaki, T

1989-12-01

We preliminarily investigated the combined effects of cisplatin and caffeine on murine melanoma B16-BL6 cells in vitro. When caffeine was added before or simultaneously with cisplatin, there was little growth inhibition. The addition of 2.0 mM caffeine after 1 h of exposure to cisplatin inhibited growth and induced cell differentiation. This treatment resulted in fewer cells, and the numbers of melanosomes and mitochondria and the amount of Golgi's complex and endoplasmic reticulum were increased. DNA histograms obtained by flow cytometry showed that cells treated with cisplatin alone accumulated in the G2/M phase, with a partial G2 block. The addition of 2.0 mM caffeine after 1 h of treatment with cisplatin reduced this block. Caffeine caused murine melanoma B16-BL6 cells treated with cisplatin to differentiate, and this inhibited growth.

Spectroscopic monitoring of the BL Lac object AO 0235+164

NASA Astrophysics Data System (ADS)

Raiteri, C. M.; Villata, M.; Capetti, A.; Heidt, J.; Arnaboldi, M.; Magazzù, A.

2007-03-01

Aims:Spectroscopic monitoring of BL Lac objects is a difficult task that nonetheless can provide important information on the different components of the active galactic nucleus. Methods: We performed optical spectroscopic monitoring of the BL Lac object AO 0235+164 (z=0.94) with the VLT and TNG telescopes from Aug. 2003 to Dec. 2004, during an extended WEBT campaign. The flux of this source is both contaminated and absorbed by a foreground galactic system at z=0.524, the stars of which can act as gravitational micro-lenses. Results: In this period the object was in an optically faint, though variable state, and a broad Mg II emission line was visible at all epochs. The spectroscopic analysis reveals an overall variation in the Mg II line flux of a factor 1.9, while the corresponding continuum flux density changed by a factor 4.3. Most likely, the photoionising radiation can be identified with the emission component that was earlier recognised to be present as a UV-soft-X-ray bump in the source spectral energy distribution and that is visible in the optical domain only in very faint optical states. We estimate an upper limit to the broad line region (BLR) size of a few light months from the historical minimum brightness level; from this we infer the maximum amplification of the Mg II line predicted by the microlensing scenario. Conclusions: .Unless we have strongly overestimated the size of the BLR, only very massive stars could significantly magnify the broad Mg II emission line, but the time scale of variations due to these (rare) events would be of several years. In contrast, the continuum flux, coming from much smaller emission regions in the jet, could be affected by microlensing from the more plausible MACHO deflectors, with variability time scales of the order of some months. Based on observations collected at the European Southern Observatory, Chile (ESO Programme 71.A-0174), and on observations made with the Italian Telescopio Nazionale Galileo (TNG

Genetic basis of HDL variation in 129/SvImJ and C57BL/6J mice: importance of testing candidate genes in targeted mutant mice*s⃞

PubMed Central

Su, Zhiguang; Wang, Xiaosong; Tsaih, Shirng-Wern; Zhang, Aihong; Cox, Allison; Sheehan, Susan; Paigen, Beverly

2009-01-01

To evaluate the effect of genetic background on high-density lipoprotein cholesterol (HDL) levels in Soat1−/− mice, we backcrossed sterol O-acyltransferase 1 (Soat1)−/− mice, originally reported to have elevated HDL levels, to C57BL/6 mice and constructed a congenic strain with only a small region (3.3Mb) of 129 alleles, specifically excluding the nearby apolipoprotein A-II (Apoa2) gene from 129. HDL levels in these Soat1−/− mice were no different from C57BL/6, indicating that the passenger gene Apoa2 caused the previously reported elevation of HDL in these Soat1−/− mice. Because many knockouts are made in strain 129 and then subsequently backcrossed into C57BL/6, it is important to identify quantitative trait loci (QTL) that differ between 129 and C57BL/6 so that one can guard against effects ascribed to a knockout but really caused by a passenger gene from 129. To provide such data, we generated 528 F2 progeny from an intercross of 129S1/SvImJ and C57BL/6 and measured HDL concentrations in F2 animals first fed chow and then atherogenic diet. A genome wide scan using 508 single-nucleotide polymorphisms (SNPs) identified 19 QTL, 2 of which were male specific and 2 were female specific. Using comparative genomics and haplotype analysis, we narrowed QTL on chromosomes 3, 5, 8, 17, and 18 to 0.5, 6.3, 2.6, 1.1, and 0.6 Mb, respectively. These data will serve as a reference for any effort to test the impact of candidate genes on HDL using a knockout strategy. PMID:18772481

METHANOL EXPOSURE DURING GASTRULATION CAUSES HOLOPROSENCEPHALY, FACIAL DYSGENESIS AND CERVICAL VERTEBRAL MALFORMATIONS IN C57BL/6J MICE

EPA Science Inventory

Exposure of pregnant CD-1 mice to methanol during the period of gastrulation results in exencephaly, cleft palate, and cervical vertebra malformations (Rogers and Mole, 1997, Teratology 55, 364). C57BL/6J mice are sensitive to the teratogenicity of ethanol; fetuses of this strai...

SEVEN-YEAR MULTI-COLOR OPTICAL MONITORING OF BL LACERTAE OBJECT S5 0716+714

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

Dai Yan; Wu Jianghua; Zhu Zonghong

We have monitored the BL Lacertae object S5 0716+714 in five intermediate optical wavebands from 2004 September to 2011 April. Here, we present data that include 8661 measurements representing one of the largest databases obtained for an object in the optical domain. A simple analysis of the data indicates that the object was active most of the time, and intraday variability was frequently observed. In total, the object varied by 2.614 mag in the i band. Strong bluer-when-brighter chromatism was observed on long, intermediate, and short timescales.

Effect of blocking TNF on IL-6 levels and metastasis in a B16-BL6 melanoma/mouse model.

PubMed

Cubillos, S; Scallon, B; Feldmann, M; Taylor, P

1997-01-01

We studied the relationship between tumour necrosis factor (TNF) and interleukin 6 (IL-6) levels, and the metastatic process in C57BL/6 mice after intravenous inoculation of B16-BL6 melanoma cells. Bioactive TNF was not detectable in the sera of inoculated mice, but these animals did show higher TNF levels following intraperitoneal challenge with lipopolysaccharide (LPS) compared to control animals. Serum IL-6 levels were increased in inoculated animals. Injection of a hybrid molecule (p55-sf2) composed of the human p55 TNF receptor extracellular domain coupled to a human constant region backbone, decreased serum TNF (after LPS challenge) and IL-6 levels in inoculated animals. Lung metastases at 7-14 days were reduced, compared to human IgG-injected control animals, but this effect was lost at day 21 postinoculation. The results suggest that the reduction in the number of metastases may be related to the effect of blocking TNF activity.

Characterization of the CD8{sup +} T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

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

Lukens, Michael V.; Claassen, Erwin A.W.; Graaff, Patricia M.A. de

2006-08-15

The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4{sup +} and CD8{sup +} T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8{sup +} T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes weremore » recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8{sup +} T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice.« less

Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice.

PubMed

Stragier, E; Martin, V; Davenas, E; Poilbout, C; Mongeau, R; Corradetti, R; Lanfumey, L

2015-12-15

Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol.

Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice.

PubMed

Sun, Quancai; Xiao, Xiao; Kim, Yoo; Kim, Daeyoung; Yoon, Kyoon Sup; Clark, John M; Park, Yeonhwa

2016-12-14

Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice.

Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice

PubMed Central

2016-01-01

Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice. PMID:27960282

Efficient generation of Rosa26 knock-in mice using CRISPR/Cas9 in C57BL/6 zygotes.

PubMed

Chu, Van Trung; Weber, Timm; Graf, Robin; Sommermann, Thomas; Petsch, Kerstin; Sack, Ulrike; Volchkov, Pavel; Rajewsky, Klaus; Kühn, Ralf

2016-01-16

The CRISPR/Cas9 system is increasingly used for gene inactivation in mouse zygotes, but homology-directed mutagenesis and use of inbred embryos are less established. In particular, Rosa26 knock-in alleles for the insertion of transgenes in a genomic 'safe harbor' site, have not been produced. Here we applied CRISPR/Cas9 for the knock-in of 8-11 kb inserts into Rosa26 of C57BL/6 zygotes. We found that 10-20 % of live pups derived from microinjected zygotes were founder mutants, without apparent off-target effects, and up to 50 % knock-in embryos were recovered upon coinjection of Cas9 mRNA and protein. Using this approach, we established a new mouse line for the Cre/loxP-dependent expression of Cas9. Altogether, our protocols and resources support the fast and direct generation of new Rosa26 knock-in alleles and of Cas9-mediated in vivo gene editing in the widely used C57BL/6 inbred strain.

The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage has impaired glucose tolerance independent of body weight.

PubMed

Jelinek, David; Castillo, Joseph J; Garver, William S

2013-09-15

The human Niemann-Pick C1 (NPC1) gene has been found to be associated with extreme (early-onset and morbid-adult) obesity and type 2 diabetes independent of body weight. We previously performed growth studies using BALB/cJ Npc1 normal (Npc1+/+) and Npc1 heterozygous (Npc1+/-) mice and determined that decreased Npc1 gene dosage interacts with a high-fat diet to promote weight gain and adiposity. The present study was performed using both BALB/cJ and C57BL/6J Npc1+/+ and Npc1+/- mice to determine if decreased Npc1 gene dosage predisposes to metabolic features associated with type 2 diabetes. The results indicated that C57BL/6J Npc1+/- mice, but not BALB/cJ Npc1+/- mice, have impaired glucose tolerance when fed a low-fat diet and independent of body weight. The results also suggest that an accumulation of liver free fatty acids and hepatic lipotoxicity marked by an elevation in the amount of plasma alanine aminotransferase (ALT) may be responsible for hepatic insulin resistance and impaired glucose tolerance. Finally, the peroxisome-proliferator activated receptor α (PPARα) and sterol regulatory element-binding protein-1 (SREBP-1) pathways known to have a central role in regulating free fatty acid metabolism were downregulated in the livers, but not in the adipose or muscle, of C57BL/6J Npc1+/- mice compared to C57BL/6J Npc1+/+ mice. Therefore, decreased Npc1 gene dosage among two different mouse strains interacts with undefined modifying genes to manifest disparate yet often related metabolic diseases. Published by Elsevier B.V.

HESS J1943+213: A Non-classical High-frequency-peaked BL Lac Object

NASA Astrophysics Data System (ADS)

Straal, S. M.; Gabányi, K. É.; van Leeuwen, J.; Clarke, T. E.; Dubner, G.; Frey, S.; Giacani, E.; Paragi, Z.

2016-05-01

HESS J1943+213 is an unidentified TeV source that is likely a high-frequency-peaked BL Lac (HBL) object, but that is also compatible with a pulsar wind nebula (PWN) nature. Each of these enormously different astronomical interpretations is supported by some of the observed unusual characteristics. In order to finally classify and understand this object, we took a three-pronged approach, through time-domain, high angular resolution, and multi-frequency radio studies. First, our deep time-domain observations with the Arecibo telescope failed to uncover the putative pulsar powering the proposed PWN. We conclude with ˜70% certainty that HESS J1943+213 does not host a pulsar. Second, long-baseline interferometry of the source with e-MERLIN at 1.5 and 5 GHz shows only a core, that is, a point source at ˜ 1-100 mas resolution. Its 2013 flux density is about one-third lower than that detected in the 2011 observations with similar resolution. This radio variability of the core strengthens the HBL object hypothesis. Third, additional evidence against the PWN scenario comes from the radio spectrum we compiled. The extended structure follows a power-law behavior with spectral index α \\=\\-0.54+/- 0.04 while the core component displays a flat spectrum (α \\=\\-0.03+/- 0.03). In contrast, the radio synchrotron emission of PWNe predicts a single power-law distribution. Overall, we rule out the PWN hypothesis and conclude that the source is a BL Lac object. The consistently high fraction (70%) of the flux density from the extended structure then leads us to conclude that HESS J1943+213 must be a non-classical HBL object.

Histocompatibility assessment in the chicken colonies of the RIR-Y8/NU, YL, WL-G, and BL-E closed for 28-48 years.

PubMed

Valdez, Marcos B; Kinoshita, Keiji; Mizutani, Makoto; Fujiwara, Akira; Yazawa, Hajime; Yamagata, Takahiro; Shimada, Kiyoshi; Namikawa, Takao

2009-04-01

Histocompatibility was assessed in the RIR-Y8/NU, BL-E, YL, and WL-G chicken closed colonies by hemagglutination test using anti-red blood cell (RBC) antibodies (HT), skin transplantation test (STT), and formation of isohemagglutinins (FIHs) during STT. The YL individuals all showed the survival of skingrafts for more than 17 days with no FIHs in STT and no RBC antigenic variations in HT, indicating a histocompatible nature together with high homogeneity at serological loci. The BL-E as well as WL-G closed colonies were also found to be histocompatible in the STT with no FIHs, although the HT showed heterogeneities at serological locus/loci other than the B and C blood group loci which have significant effects on histocompatibility or FIHs in chicken. In the RIR-Y8/NU closed colonies, one individual in 6 reciprocal combinations of the STT showed early skingraft rejection with positive FIHs caused by different B locus alleles, and the HT suggested relatively high heterogeneities at the other serological loci too. The closed colonies of YL, BL-E, and WL-G will be useful avian materials for transplantation or related experiments, but RIR-Y8/NU needs further pedigree selection for serological homogeneity.

Chronic Intermittent Ethanol Inhalation Increases Ethanol Self-administration in both C57BL/6J and DBA/2J Mice

PubMed Central

McCool, Brian A.; Chappell, Ann M.

2015-01-01

Inbred mouse strains provide significant opportunities to understand the genetic mechanisms controlling ethanol-directed behaviors and neurobiology. They have been specifically employed to understand cellular mechanisms contributing to ethanol consumption, acute intoxication, and sensitivities to chronic effects. However, limited ethanol consumption by some strains has restricted our understanding of clinically relevant endpoints such as dependence-related ethanol intake. Previous work with a novel tastant-substitution procedure using monosodium glutamate (MSG or umami flavor) has shown that the procedure greatly enhances ethanol consumption by mouse strains that express limited drinking phenotypes using other methods. In the current study, we employ this MSG-substitution procedure to examine how ethanol dependence, induced with passive vapor inhalation, modifies ethanol drinking in C57BL/6J and DBA/2J mice. These strains represent ‘high’ and ‘low’ drinking phenotypes, respectively. We found that the MSG substitution greatly facilitates ethanol drinking in both strains, and likewise, ethanol dependence increased ethanol consumption regardless of strain. However, DBA/2J mice exhibited greater sensitivity dependence-enhanced drinking, as represented by consumption behaviors directed at lower ethanol concentrations and relative to baseline intake levels. DBA/2J mice also exhibited significant withdrawal-associated anxiety-like behavior while C57BL/6J mice did not. These findings suggest that the MSG-substitution procedure can be employed to examine dependence-enhanced ethanol consumption across a range of drinking phenotypes, and that C57BL/6J and DBA/2J mice may represent unique neurobehavioral pathways for developing dependence-enhanced ethanol consumption. PMID:25659650

The adaptation of limb kinematics to increasing walking speeds in freely moving mice 129/Sv and C57BL/6.

PubMed

Serradj, Nadjet; Jamon, Marc

2009-07-19

The kinematics of locomotion was analyzed in two strains of great importance for the creation of mutated mice (C56BL/6 and 129/Sv). Different behavioral situations were used to trigger sequences of movement covering the whole range of velocities in the mice, and the variations of kinematic parameters were analyzed in relation with velocity. Both stride frequency and stride length contributed to the moving speed, but stride frequency was found to be the main contributor to the speed increase. A trot-gallop transition was detected at speed about 70 cm/s, in relation with a sharp shift in limb coordination. The results of this study were consistent with pieces of information previously published concerning the gait analyses of other strains, and provided an integrative view of the basic motor pattern of mice. On the other hand some qualitative differences were found in the movement characteristics of the two strains. The stride frequency showed a higher contribution to speed in 129/Sv than in C57BL/6. In addition, 129/Sv showed a phase shift in the forelimb and hindlimb, and a different position of the foot during the stance time that revealed a different gait and body position during walking. Overall, 129/Sv moved at a slower speed than C57BL/6 in any behavioral situation. This difference was related to a basal lower level of motor activity. The possibility that an alteration in the dopamine circuit was responsible for the different movement pattern in 129/Sv is discussed.

Chronic intermittent ethanol inhalation increases ethanol self-administration in both C57BL/6J and DBA/2J mice.

PubMed

McCool, Brian A; Chappell, Ann M

2015-03-01

Inbred mouse strains provide significant opportunities to understand the genetic mechanisms controlling ethanol-directed behaviors and neurobiology. They have been specifically employed to understand cellular mechanisms contributing to ethanol consumption, acute intoxication, and sensitivities to chronic effects. However, limited ethanol consumption by some strains has restricted our understanding of clinically relevant endpoints such as dependence-related ethanol intake. Previous work with a novel tastant-substitution procedure using monosodium glutamate (MSG or umami flavor) has shown that the procedure greatly enhances ethanol consumption by mouse strains that express limited drinking phenotypes using other methods. In the current study, we employ this MSG-substitution procedure to examine how ethanol dependence, induced with passive vapor inhalation, modifies ethanol drinking in C57BL/6J and DBA/2J mice. These strains represent 'high' and 'low' drinking phenotypes, respectively. We found that the MSG substitution greatly facilitates ethanol drinking in both strains, and likewise, ethanol dependence increased ethanol consumption regardless of strain. However, DBA/2J mice exhibited greater sensitivity dependence-enhanced drinking, as represented by consumption behaviors directed at lower ethanol concentrations and relative to baseline intake levels. DBA/2J mice also exhibited significant withdrawal-associated anxiety-like behavior while C57BL/6J mice did not. These findings suggest that the MSG-substitution procedure can be employed to examine dependence-enhanced ethanol consumption across a range of drinking phenotypes, and that C57BL/6J and DBA/2J mice may represent unique neurobehavioral pathways for developing dependence-enhanced ethanol consumption. Copyright © 2015 Elsevier Inc. All rights reserved.

The Luminosity Function of the Host Galaxies of QSOs and BL Lac Objects

NASA Astrophysics Data System (ADS)

Carangelo, Nicoletta; Falomo, Renato; Treves, Aldo

A clear insight of the galaxies hosting active galactic nuclei is of fundamental importance for understanding the processes of galaxies and nuclei formation and their cosmic evolution. A good characterization of the host galaxies properties requires images of excellent quality in order to disentangle the light of the galaxy from that of the bright nucleus. To this aim HST has provided a major improvement of data on QSOs (Disney et al. 1995; Bahcall et al. 1996,1997; Boyce et al. 1998; McLure et al. 1999; Hamilton et al. 2000; Kukula et al. 2001) and BL Lacs (Scarpa et al. 2000, Urry et al. 2000).

Comparison of the Effects of Manual Acupuncture, Laser Acupuncture, and Electromagnetic Field Stimulation at Acupuncture Point BL15 on Heart Rate Variability.

PubMed

Lee, Na Ra; Kim, Soo Byeong; Heo, Hyun; Lee, Yong Heum

2016-10-01

The aim of this study was to compare the influences of manual acupuncture, laser acupuncture, and electromagnetic field stimulation on the autonomic nervous system. We monitored the heart rate variability before and after stimulation to check the influence on the autonomic nervous system. The heart rate variabilities at low frequency (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15-0.4 Hz) were analyzed to acquire LF/HF ratio. Xinshu (BL15) was selected as the stimulation point. Methods included manual acupuncture with a 1-cm depth and laser acupuncture at a wavelength of 660 nm and output power of 50 mW. An electromagnetic field of 2 Hz and 460 gauss (46 mT) was chosen. The LF and the LF/HF ratio were found to be lower in the manual acupuncture and the electromagnetic field groups, but to be higher in the laser acupuncture group. The HF was found to be lower in the laser acupuncture group, but higher in the manual acupuncture and the electromagnetic field groups. In conclusion, we found that manual acupuncture and electromagnetic field stimulation at BL15 activated the parasympathetic nervous system, whereas laser acupuncture at BL15 activated the sympathetic nervous system. Copyright © 2016. Published by Elsevier B.V.

(Re)Counting Meaningful Learning Experiences: Using Student-Created Reflective Videos to Make Invisible Learning Visible during PjBL Experiences

ERIC Educational Resources Information Center

Smith, Shaunna

2016-01-01

This ethnographic case study investigated how the process of learning during a yearlong after-school, project-based learning (PjBL) experience could be documented by student-created reflective videos. Guided by social constructivism, constant comparative analysis was used to explore the meaningful learning that took place in addition to the…

Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice.

PubMed

Rhodes, Justin S; Best, Karyn; Belknap, John K; Finn, Deborah A; Crabbe, John C

2005-01-31

Because of intrinsic differences between humans and mice, no single mouse model can represent all features of a complex human trait such as alcoholism. It is therefore necessary to develop partial models. One important feature is drinking to the point where blood ethanol concentration (BEC) reaches levels that have measurable affects on physiology and/or behavior (>1.0 mg ethanol/ml blood). Most models currently in use examine relative oral self-administration from a bottle containing alcohol versus one containing water (two-bottle preference drinking), or oral operant self-administration. In these procedures, it is not clear when or if the animals drink to pharmacologically significant levels because the drinking is episodic and often occurs over a 24-h period. The aim of this study was to identify the optimal parameters and evaluate the reliability of a very simple procedure, taking advantage of a mouse genotype (C57BL/6J) that is known to drink large quantities of ethanol. We exchanged for the water bottle a solution containing ethanol in tap water for a limited period, early in the dark cycle, in the home cage. Mice regularly drank sufficient ethanol to achieve BEC>1.0 mg ethanol/ml blood. The concentration of ethanol offered (10%, 20% or 30%) did not affect consumption in g ethanol/kg body weight. The highest average BEC ( approximately 1.6 mg/ml) occurred when the water-to-ethanol switch occurred 3 h into the dark cycle, and when the ethanol was offered for 4 rather than 2 h. Ethanol consumption was consistent within individual mice, and reliably predicted BEC after the period of ethanol access. C57BL/6J mice from three sources provided equivalent data, while DBA/2J mice drank much less than C57BL/6J in this test. We discuss advantages of the model for high-throughput screening assays where the goal is to find other genotypes of mice that drink excessively, or to screen drugs for their efficacy in blocking excessive drinking.

Biopsy of embryos produced by in vitro fertilization affects development in C57BL/6 mouse strain

PubMed Central

Sugawara, Atsushi; Ward, Monika A.

2012-01-01

Preimplantation genetic diagnosis (PGD) is considered highly successful in respect to its accuracy in detecting genetic anomalies but the effects of embryo biopsy on embryonic/fetal growth and development are less known, particularly in conjunction with in vitro fertilization (IVF). Here, we compared biopsied (B) and non-biopsied (NB) mouse embryos for their developmental competence. Embryos C57BL/6 (B6) and B6D2F2 (F2) generated by IVF were subjected to single blastomere biopsy at the 4-cell stage, and were either cultured for 120 h and subjected to differential inner cell mass (ICM) and trophoblast (T) staining, or were transferred into the uterine tubes of surrogate mothers after 72 h of culture, to examine their pre- and post-implantation development, respectively. Non-biopsied embryos from the same IVF cohorts served as controls. Embryo biopsy negatively affected preimplantation development to blastocyst in C57BL/6 (69 vs 79%, P<0.01) but not in B6D2F1 mice (89 vs 91%, P=NS). Although B6 embryos had lower total cell number than F2 (B6: 47 and 61 vs. F1: 53 and 70; B and NB, respectively, P<0.05) there were no differences between B and NB blastocysts in %ICM (B6: 19.8 vs 19.8; F2: 20.9 vs 20.4, P=NS) and ICM:T ratio (B6: 4.7 vs 4.7; F2: 4.4 vs. 4.7) in both mouse strains. Post-implantation development to live fetuses of B embryos as compared to NB counterparts was impaired in C57BL/6 (6 vs 18%, P<0.001) but not in B6D2F1 mice (26 vs 35%, P=NS). We conclude that blastomere biopsy impairs embryonic/fetal development in mice known to be sensitive to in vitro culture and manipulations. Such mice model infertile couples with poor quality gametes seeking help in assisted reproduction technologies (ART) clinics. PMID:23174776

Foxp3+ Regulatory T Cells Delay Expulsion of Intestinal Nematodes by Suppression of IL-9-Driven Mast Cell Activation in BALB/c but Not in C57BL/6 Mice

PubMed Central

Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Breloer, Minka

2014-01-01

Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3+ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3+ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6

Restraint stress differentially regulates inflammation and glutamate receptor gene expression in the hippocampus of C57BL/6 and BALB/c mice.

PubMed

Sathyanesan, Monica; Haiar, Jacob M; Watt, Michael J; Newton, Samuel S

2017-03-01

The inbred mouse strains, C57BL/6 and BALB/c have been used widely in preclinical psychiatric research. The differences in stress susceptibility of available strains has provided a useful platform to test pharmacological agents and behavioral responses. Previous brain gene profiling efforts have indicated that the inflammation and immune response gene pathway is the predominant gene network in the differential stress response of BALB/c and C57BL/6 mice. The implication is that a composite stress paradigm that includes a sequence of extended, varied and unpredictable stressors induces inflammation-related genes in the hippocampus. We hypothesized that the regulation of inflammation genes in the brain could constitute a primary stress response and tested this by employing a simple stress protocol, repeated exposure to the same stressor for 10 days, 2 h of restraint per day. We examined stress-induced regulation of 13 proinflammatory cytokine genes in male BALB/c and C57BL/6 mice using quantitative PCR. Elevated cytokine genes included tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), interleukin 10 (IL10), tumor necrosis factor (TNF) super family members and interleukin 1 receptor 1 (IL1R1). In addition, we examined restraint stress-induced regulation of 12 glutamate receptor genes in both strains. Our results show that restraint stress is sufficient to elevate the expression of inflammation-related genes in the hippocampus of both BABLB/c and C57BL/6 mice, but they differ in the genes that are induced and the magnitude of change. Cell types that are involved in this response include endothelial cells and astrocytes. Lay summary Repeated exposure to a simple restraint stress altered the activities of genes involved in inflammation and the functions of the excitatory neurotransmitter, glutamate. These changes in the hippocampus of the mouse brain showed differences that were dependent on the strain of mice and the length of the stress exposure. The effects

Sex differences in novelty- and psychostimulant-induced behaviors of C57BL/6 mice

PubMed Central

Van Swearingen, Amanda E. D.; Walker, Q. David; Kuhn, Cynthia M.

2012-01-01

Rationale Women are more sensitive than men to psychostimulants and progress from initial use to drug addiction more quickly. The mouse has been an under-utilized model to study sex differences in psychostimulant action. Mice could serve as an ideal genetically-tractable model for mechanistic studies into sex and hormone effects on psychostimulant behavior. Objectives To characterize psychostimulant effects in male and female mice with a combination of automated data collection and behavioral observation. Methods Male and female C57BL/6 mice (Charles River) were given a single dose or sequential ascending binge doses of d-amphetamine (AMPH) or cocaine (COC). Behavior was assessed in open field chambers using both automated photobeam interruptions and behavioral observations. Brain psychostimulant concentrations were determined at the time of maximum behavioral stimulation. Results Psychostimulants induced behavioral activation in mice including both increased locomotion as detected with an automated system and a sequence of behaviors progressing from stereotyped sniffing at low doses to patterned locomotion and rearing at high doses. Females exhibited more patterned locomotion and a shift towards higher behavior scores after either psychostimulant despite having lower AMPH and equivalent COC brain levels as males. Conclusions Female C57BL/6 mice exhibit enhanced psychostimulant-induced behavior compared to males, similar to reports in rats. The combination of automated behavioral measures and behavioral observation was essential for verifying the existence of these differences. These results indicate the importance of testing both sexes when characterizing genetically manipulated mice to control for potential sex-specific effects. PMID:22975726

REPRODUCTIVE EFFECTS OF THE WATER DISINFECTANT BYPRODUCT BROMOCHLOROACETIC ACID (BCA) IN ADULT AND JUVENILE MALE C57BL/6 MICE

EPA Science Inventory

REPRODUCTIVE EFFECTS OF THE WATER DISINFECTANT BYPRODUCT BROMOCHLOROACETIC ACID (BCA) IN ADULT AND JUVENILE MALE C57BL/6 MICE.
JC Rockett, JC Luft, JB Garges and DJ Dix. Reproductive Toxicology Division, USEPA, RTP, NC, USA.
Sponsor: G Klinefelter
The development of wate...

Supersymmetric U(1)Y‧⊗ U(1)B-L extension of the Standard Model

NASA Astrophysics Data System (ADS)

Montero, J. C.; Pleitez, V.; Sánchez-Vega, B. L.; Rodriguez, M. C.

2017-06-01

We build a supersymmetric version with SU(3)C ⊗ SU(2)L ⊗ U(1)Y‧⊗ U(1)B-L gauge symmetry, where Y‧ is a new charge and B and L are the usual baryonic and leptonic numbers. The model has three right-handed neutrinos with identical B - L charges, and can accommodate all fermion masses at the tree level. In particular, the type I seesaw mechanism is implemented for the generation of the active neutrino masses. We obtain the mass spectra of all sectors and for the scalar one we also give the flat directions allowed by the model.

5-HT(2C) receptor RNA editing in the amygdala of C57BL/6J, DBA/2J, and BALB/cJ mice.

PubMed

Hackler, Elizabeth A; Airey, David C; Shannon, Caitlin C; Sodhi, Monsheel S; Sanders-Bush, Elaine

2006-05-01

Post-transcriptional RNA editing of the G-protein coupled 5-hydroxytryptamine-2C (5-HT(2C)) receptor predicts an array of 24 receptor isoforms, some of which are characterized by reduced constitutive activity and potency to initiate intracellular signaling. The amygdala is integral to anxiety, fear, and related psychiatric diseases. Activation of 5-HT(2C) receptors within the amygdala is anxiogenic. Here, we describe the RNA editing profiles from amygdala of two inbred mouse strains (BALB/cJ and DBA/2J) known to be more anxious than a third (C57BL/6J). We confirmed the strain anxiety differences using light<-->dark exploration, and we discovered that BALB/cJ and DBA/2J are each characterized by a higher functioning RNA editing profile than C57BL/6J. BALB/cJ and DBA/2J exhibit a roughly two-fold reduction in C site editing, and a corresponding two-fold reduction in the edited isoform VSV. C57BL/6J is characterized by a relative decrease in the unedited highly functional isoform INI. We estimated the heritability of editing at the C site to be approximately 40%. By sequencing genomic DNA, we found complete conservation between C57BL/6J, BALB/cJ, DBA/2J and 37 other inbred strains for the RNA edited region of Htr2c, suggesting Htr2c DNA sequence does not influence variation in Htr2c RNA editing between inbred strains of mice. We did, however, discover that serotonin turnover is reduced in BALB/cJ and DBA/2J, consistent with emerging evidence that synaptic serotonin levels regulate RNA editing. These results encourage further study of the causes and consequences of 5-HT(2C) receptor RNA editing in the amygdala of mice.

AI-BL1.0: a program for automatic on-line beamline optimization using the evolutionary algorithm.

PubMed

Xi, Shibo; Borgna, Lucas Santiago; Zheng, Lirong; Du, Yonghua; Hu, Tiandou

2017-01-01

In this report, AI-BL1.0, an open-source Labview-based program for automatic on-line beamline optimization, is presented. The optimization algorithms used in the program are Genetic Algorithm and Differential Evolution. Efficiency was improved by use of a strategy known as Observer Mode for Evolutionary Algorithm. The program was constructed and validated at the XAFCA beamline of the Singapore Synchrotron Light Source and 1W1B beamline of the Beijing Synchrotron Radiation Facility.

Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16-BL6 melanoma cells orthotopically implanted into syngeneic mice.

PubMed

Aozuka, Yasushi; Koizumi, Keiichi; Saitoh, Yurika; Ueda, Yasuji; Sakurai, Hiroaki; Saiki, Ikuo

2004-12-08

We investigated the effect of bestatin, an inhibitor of aminopeptidase N (APN)/CD13 and aminopeptidase B, on the angiogenesis induced by B16-BL6 melanoma cells. Oral administration of bestatin (100-200 mg/kg/day) was found to significantly inhibit the melanoma cell-induced angiogenesis in a mouse dorsal air sac assay. Additionally, anti-APN/CD13 mAb (WM15), which neutralizes the aminopeptidase activity in tumor cells, as well as bestatin inhibited the tube-like formation of human umbilical vein endothelial cells (HUVECs) in vitro. Furthermore, the intraperitoneal administration of bestatin (50-100 mg/kg/day) after the orthotopic implantation of B16-BL6 melanoma cells into mice reduced the number of vessels oriented towards the established primary tumor mass on the dorsal side of mice. These findings suggest that bestatin is an active anti-angiogenic agent that may inhibit tumor angiogenesis in vivo and tube-like formation of endothelial cells in vitro through its inhibition of APN/CD13 activity.

Evaluating the dose effects of a longitudinal micro-CT study on pulmonary tissue in C57BL/6 mice

NASA Astrophysics Data System (ADS)

Detombe, Sarah A.; Dunmore-Buyze, Joy; Petrov, Ivailo E.; Drangova, Maria

2012-03-01

Background: Micro-computed tomography offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of x-ray dose accumulated over the course of the experiment. In this study, we scan C57BL/6 mice multiple times per week for six weeks, to determine the effect of the cumulative dose on pulmonary tissue at the end of the study. Methods/Results: C57BL/6 male mice were split into two groups (irradiated group=10, control group=10). The irradiated group was scanned (80kVp/50mA) each week for 6 weeks; the weekly scan session had three scans. This resulted in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from weeks 1 and 6 were reconstructed and analyzed: overall, there was no significant difference in lung volume or lung density between the control group and the irradiated group. Similarly, there were no significant differences between the week 1 and week 6 scans in the irradiated group. Histological samples taken from excised lung tissue also showed no evidence of inflammation or fibrosis in the irradiated group. Conclusion: This study demonstrates that a 5 Gy x-ray dose accumulated over six weeks during a longitudinal micro-CT study has no significant effects on the pulmonary tissue of C57BL/6 mice. As a result, the many advantages of micro- CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.

Cordycepin (3'-deoxyadenosine) inhibits the growth of B16-BL6 mouse melanoma cells through the stimulation of adenosine A3 receptor followed by glycogen synthase kinase-3beta activation and cyclin D1 suppression.

PubMed

Yoshikawa, Noriko; Yamada, Shizuo; Takeuchi, Chihiro; Kagota, Satomi; Shinozuka, Kazumasa; Kunitomo, Masaru; Nakamura, Kazuki

2008-06-01

Cordyceps sinensis, a parasitic fungus on the larvae of Lepidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells was inhibited by cordycepin (3'-deoxyadenosine), an active ingredient of C. sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor antagonist. In this study, the radioligand binding assay using [125I]-AB-MECA (a selective adenosine A3 receptor agonist) has shown that B16-BL6 cells express adenosine A3 receptors and that cordycepin binds to these receptors. We also confirmed the involvement of adenosine A3 receptors in the action of cordycepin using MRS1523 and MRS1220, specific adenosine A3 receptor antagonists. Next, indirubin, a glycogen synthase kinase-3beta (GSK-3beta) inhibitor, antagonized the growth suppression induced by cordycepin. Furthermore, the level of cyclin D1 protein in B16-BL6 cells was decreased by cordycepin using Western blot analysis. In conclusion, this study demonstrated that cordycepin inhibits the proliferation of B16-BL6 cells by stimulating adenosine A3 receptors followed by the Wnt signaling pathway, including GSK-3beta activation and cyclin D1 inhibition.

In vivo Proton NMR spectroscopy of genetic mouse models BALB/cJ and C57BL/6By: variation in hippocampal glutamate level and the metabotropic glutamate receptor, subtype 7 (Grm7) gene.

PubMed

Guilfoyle, David N; Gerum, Scott; Vadasz, Csaba

2014-05-01

Glutamatergic neurotransmission in the brain is modulated by metabotropic glutamate receptors (mGluR). In recent studies, we identified a cis-regulated variant of a gene (Grm7) which codes for mGluR subtype 7 (mGluR7), a presynaptic inhibitory receptor. The genetic variant derived from the BALB/cJ mouse strain (Grm7 (BALB/cJ)) codes for higher abundance of mGluR7 mRNA in the hippocampus than the C57BL/6By strain-derived variant (Grm7 (C57BL/6By)). Here, we used localized in vivo (1)H NMR spectroscopy to test the hypothesis that Grm7 (BALB/cJ) is also associated with lower glutamate concentration in the same brain region. All data were obtained on a 7.0 T Agilent (Santa Clara, CA, USA) 40-cm bore system using experimentally naive adult male inbred C57BL/6By, BALB/cJ, and congenic mice (B6By.C.6.132.54) constructed in our laboratory carrying Grm7 (BALB/cJ) on C57BL/6By genetic background. The voxel of interest size was 6 μL (1 × 2 × 3 mm(3)) placed in the hippocampal CA1 region. The results showed that the hippocampal level of glutamate in the congenic mouse strain was significantly lower than that in the background C57BL/6By strain which carried the Grm7 (C57BL/6By) allele. Because the two inbred strains are genetically highly similar except at the region of the Grm7 gene, the results raise the possibility that allelic variation at the Grm7 locus contributes to the strain differences in both hippocampal mRNA abundance and glutamate level which may modulate complex behavioral traits, such as learning and memory, addiction, epilepsy, and mood disorders.

Discovery of VHE γ -ray emission from the BL Lacertae object B3 2247+381 with the MAGIC telescopes

DOE PAGES

Aleksić, J.; Alvarez, E. A.; Antonelli, L. A.; ...

2012-03-02

Here, we study the non-thermal jet emission of the BL Lac object B3 2247+381 during a high optical state. The MAGIC telescopes observed the source during 13 nights between September 30th and October 30th 2010, collecting a total of 14.2 h of good quality very high energy (VHE) γ-ray data. Simultaneous multiwavelength data was obtained with X-ray observations by the Swift satellite and optical R-band observations at the KVA-telescope. We also use high energy γ-ray (HE, 0.1-100 GeV) data from the Fermi satellite. We also dedected the BL Lac object B3 2247+381 (z = 0.119) , for the first time,more » at VHE γ-rays at a statistical significance of 5.6σ. A soft VHE spectrum with a photon index of -3.2 ± 0.6 was determined. No significant short term flux variations were found. Finally, we model the spectral energy distribution using a one-zone SSC-model, which can successfully describe our data.« less

Quasi-simultaneous observations of the BL Lac object MK 501 in X-ray, UV, visible, IR and radio frequencies

NASA Technical Reports Server (NTRS)

Kondo, D. M.; Worrall, D. M.; Mushotzky, R. F.; Hackney, R. L.; Hackney, K. H.; Oke, J. B.; Yee, H.; Neugebauer, G.; Matthews, K.; Feldman, P. A.

1980-01-01

Quasi-simultaneous observations of the BL Lacertae (Lac) objects MK 501 were performed for the first time at X-ray, ultraviolet, visible, infrared, and radio frequencies. The observed spectral slope from the X-ray to UV regions is positive and continuous, but that from the mid UV to visible light region becomes gradually flat and possibly turns down toward lower frequencies; the optical radio emission can not be accounted for by a single power law. Several theoretical models were considered for the emission mechanism. A quantitative comparison was performed with the synchrotron-self-Compton model; the total spectrum is found consistent with this model. The spectrum from visible light to X-ray is consistent with synchrotron radiation or with inverse-Compton scattering by a hot thermal cloud of electrons. The continuity of the spectral slope from X-ray to UV implied by the current data suggests that the previous estimates of the total luminosity of this BL Lac object is underestimated by a factor of about three or four.

Growth Inhibition and Differentiation of Murine Melanoma B16‐BL6 Cells Caused by the Combination of Cisplatin and Caffeine

PubMed Central

Tomita, Katsuro; Yasutake, Hidetoshi; Ueda, Yoshimichi; Tanaka, Motohiro; Sasaki, Takuma

1989-01-01

We preliminarily investigated the combined effects of cisplatin and caffeine on murine melanoma B16‐BL6 cells in vitro. When caffeine was added before or simultaneously with cisplatin, there was little growth inhibition. The addition of 2.0 mM caffeine after 1 h of exposure to cisplatin inhibited growth and induced cell differentiation. This treatment resulted in fewer cells, and the numbers of melanosomes and mitochondria and the amount of Golgi's complex and endoplasmic reticulum were increased. DNA histograms obtained by flow cytometry showed that cells treated with cisplatin alone accumulated in the G2/M phase, with a partial G2 block. The addition of 2.0 mM caffeine after 1 h of treatment with cisplatin reduced this block. Caffeine caused murine melanoma B16‐BL6 cells treated with cisplatin to differentiate, and this inhibited growth. PMID:2516852

Fermi LAT detection of a GeV flare from the BL Lac object Mrk 421

NASA Astrophysics Data System (ADS)

D'Ammando, F.; Orienti, M.

2012-07-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed gamma-ray flaring activity from a source positionally consistent with the BL Lac object Mrk 421 (also known as 2FGL J1104.4+3812, Nolan et al. 2012, ApJS, 199, 31; R.A.= 11h04m27.3139s, Dec.= +38d12m31.799s, J2000.0, Fey et al. 2004, AJ, 127, 3587) at redshift z=0.03 (De Vaucouleurs et al.

VLBA Observations of Low Luminosity Flat Spectrum Radio Galaxies and BL Lac Objects: Polarisation Properties

NASA Astrophysics Data System (ADS)

Bondi, M.; Dallacasa, D.; Stanghellini, C.; Marchã, M. J. M.

We obtained two-epoch VLBA observations at 5 GHz of a list of radio galaxies drawn from the 200 mJy sample (Marcha et al. 1996). The objects selected for milli-arcsecond scale observations are classified, on the basis of their optical spectroscopic and polarimetric properties, as BL Lac objects, normal weak line radio galaxies, broad line radio galaxies, and transition objects (those with intermediate properties). We present preliminary results on the radio polarization properties, on the milli-arcsecond scale, of objects with different optical properties and discuss structural variations detected from the two epochs.

A Real-Time Imaging System for Stereo Atomic Microscopy at SPring-8's BL25SU

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

Matsushita, Tomohiro; Guo, Fang Zhun; Muro, Takayuki

2007-01-19

We have developed a real-time photoelectron angular distribution (PEAD) and Auger-electron angular distribution (AEAD) imaging system at SPring-8 BL25SU, Japan. In addition, a real-time imaging system for circular dichroism (CD) studies of PEAD/AEAD has been newly developed. Two PEAD images recorded with left- and right-circularly polarized light can be regarded as a stereo image of the atomic arrangement. A two-dimensional display type mirror analyzer (DIANA) has been installed at the beamline, making it possible to record PEAD/AEAD patterns with an acceptance angle of {+-}60 deg. in real-time. The twin-helical undulators at BL25SU enable helicity switching of the circularly polarized lightmore » at 10Hz, 1Hz or 0.1Hz. In order to realize real-time measurements of the CD of the PEAD/AEAD, the CCD camera must be synchronized to the switching frequency. The VME computer that controls the ID is connected to the measurement computer with two BNC cables, and the helicity information is sent using TTL signals. For maximum flexibility, rather than using a hardware shutter synchronizing with the TTL signal we have developed software to synchronize the CCD shutter with the TTL signal. We have succeeded in synchronizing the CCD camera in both the 1Hz and 0.1Hz modes.« less

Assessing anxiety in C57BL/6J mice: a pharmacological characterization of the open-field and light/dark tests.

PubMed

Heredia, Luis; Torrente, Margarita; Colomina, María T; Domingo, José L

2014-01-01

In order to assess anxiety in mammals various tests and species are currently available. These current assays measure changes in anxiety-like behaviors. The open-field and the light/dark are anxiety tests based on the spontaneous behavior of the animals, with C57BL/6J mice being a frequently used strain in behavioral studies. However, the suitability of this strain as a choice in anxiety studies has been questioned. In this study, we performed two pharmacological characterizations of this strain in both the open-field and the light/dark tests. We examined the changes in the anxiety-like behaviors of C57BL/6J mice exposed to chlordiazepoxide (CDP), an anxiolytic drug, at doses of 5 and 10 mg/kg, picrotoxine (PTX), an anxiogenic drug, at doses of 0.5 and 1 mg/kg, and methylphenidate (MPH), a psychomotor stimulant drug, at doses of 5 and 10 mg/kg, in a first experiment. In a second experiment, we tested CDP at 2.5 mg/kg, PTX at 2 mg/kg and MPH at 2.5 mg/kg. Results showed an absence of anxiolytic-like effects of CDP in open-field and light/dark tests. Light/dark test was more sensitive to the anxiogenic effects of PTX than the open-field test. Finally, a clear anxiogenic effect of MPH was observed in the two tests. Although C57BL/6J mice could not be a sensitive model to study anxiolytic effects in pharmacological or behavioral interventions, it might be a suitable model to test anxiogenic effects. Further studies are necessary to corroborate these results. Copyright © 2013 Elsevier Inc. All rights reserved.

RuvBL2 Is Involved in Histone Deacetylase Inhibitor PCI-24781-Induced Cell Death in SK-N-DZ Neuroblastoma Cells

PubMed Central

Zhan, Qinglei; Tsai, Sauna; Lu, Yonghai; Wang, Chunmei; Kwan, Yiuwa; Ngai, Saiming

2013-01-01

Neuroblastoma is the second most common solid tumor diagnosed during infancy. The survival rate among children with high-risk neuroblastoma is less than 40%, highlighting the urgent needs for new treatment strategies. PCI-24781 is a novel hydroxamic acid-based histone deacetylase (HDAC) inhibitor that has high efficacy and safety for cancer treatment. However, the underlying mechanisms of PCI-24781 are not clearly elucidated in neuroblastoma cells. In the present study, we demonstrated that PCI-24781 treatment significantly inhibited tumor growth at very low doses in neuroblastoma cells SK-N-DZ, not in normal cell line HS-68. However, PCI-24781 caused the accumulation of acetylated histone H3 both in SK-N-DZ and HS-68 cell line. Treatment of SK-N-DZ with PCI-24781 also induced cell cycle arrest in G2/M phase and activated apoptosis signaling pathways via the up-regulation of DR4, p21, p53 and caspase 3. Further proteomic analysis revealed differential protein expression profiles between non-treated and PCI-24781 treated SK-N-DZ cells. Totally 42 differentially expressed proteins were identified by MALDI-TOF MS system. Western blotting confirmed the expression level of five candidate proteins including prohibitin, hHR23a, RuvBL2, TRAP1 and PDCD6IP. Selective knockdown of RuvBL2 rescued cells from PCI-24781-induced cell death, implying that RuvBL2 might play an important role in anti-tumor activity of PCI-24781 in SK-N-DZ cells. The present results provide a new insight into the potential mechanism of PCI-24781 in SK-N-DZ cell line. PMID:23977108

Clinically-Relevant Cutaneous Lesions by Nitrogen Mustard: Useful Biomarkers of Vesicants Skin Injury in SKH-1 Hairless and C57BL/6 Mice

PubMed Central

Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; White, Carl W.; Agarwal, Rajesh

2013-01-01

A paucity of clinically applicable biomarkers to screen therapies in laboratory is a limitation in the development of countermeasures against cutaneous injuries by chemical weapon, sulfur mustard (SM), and its analog nitrogen mustard (NM). Consequently, we assessed NM-caused progression of clinical cutaneous lesions; notably, skin injury with NM is comparable to SM. Exposure of SKH-1 hairless and C57BL/6 (haired) mice to NM (3.2 mg) for 12–120 h caused clinical sequelae of toxicity, including microblister formation, edema, erythema, altered pigmentation, wounding, xerosis and scaly dry skin. These toxic effects of NM were similar in both mouse strains, except that wounding and altered pigmentation at 12–24 h and appearance of dry skin at 24 and 72 h post-NM exposure were more pronounced in C57BL/6 compared to SKH-1 mice. Conversely, edema, erythema and microblister formation were more prominent in SKH-1 than C57BL/6 mice at 24–72 h after NM exposure. In addition, 40–60% mortality was observed following 120 h of NM exposure in the both mouse strains. Overall, these toxic effects of NM are comparable to those reported in humans and other animal species with SM, and thus represent clinically-relevant cutaneous injury endpoints in screening and optimization of therapies for skin injuries by vesicating agents. PMID:23826320

Performance of the Taiwan Contract Beamline BL12B2 at SPring-8

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

Tang, M.-T.; Du, C.-H.; Lee, J.-F.

2004-05-12

The recent status of the SPring-8 Taiwan Contract Beamline BL12B2 is reported. The beamline was designed to provide multiple applications for materials and biological researches. It is equipped with four end stations, including an EXAFS station, a Huber 6-circle diffractometer for X-ray scattering, a curved image plate for the studies of powder diffraction, and a station for the protein crystallography. The beamline construction was completed in 2000 and it has been in full speed operation since September 2001. To enhance the focusing capacity, the beamline optics has been modified in 2002 and a gain of factor of 10 in photonmore » flux was consequently obtained at protein crystallography station.« less

P7C3 Attenuates the Scopolamine-Induced Memory Impairments in C57BL/6J Mice.

PubMed

Jiang, Bo; Song, Lu; Huang, Chao; Zhang, Wei

2016-05-01

Memory impairment is the most common symptom in patients with Alzheimer's disease. The purpose of this study is to evaluate the memory enhancing effects of P7C3, a recently identified compound with robust proneurogenic and neuroprotective effects, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. Different behavior tests including the Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. Scopolamine significantly decreased the spontaneous alternation and step-through latency of C57BL/6J mice in Y-maze test and passive avoidance test, whereas increased the time of mice spent to find the hidden platform in Morris water maze test. Importantly, intraperitoneal administration of P7C3 effectively reversed those Scopolamine-induced cognitive impairments in C57BL/6J mice. Furthermore, P7C3 treatment significantly enhanced the level of brain-derived neurotrophic factor (BDNF) signaling pathway in the cortex and hippocampus, and the usage of selective BDNF signaling inhibitor fully blocked the anti-amnesic effects of P7C3. Therefore, these findings suggest that P7C3 could improve the scopolamine-induced learning and memory impairment possibly through activation of BDNF signaling pathway, thereby exhibiting a cognition-enhancing potential.

Short timescale photometric and polarimetric behavior of two BL Lacertae type objects

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

Covino, S.; Baglio, M. C.; Foschini, L.

Context. Blazars are astrophysical sources whose emission is dominated by non-thermal processes, typically interpreted as synchrotron and inverse Compton emission. Although the general picture is rather robust and consistent with observations, many aspects are still unexplored. Aims. Polarimetric monitoring can offer a wealth of information about the physical processes in blazars. Models with largely different physical ingredients can often provide almost indistinguishable predictions for the total flux, but usually are characterized by markedly different polarization properties. We explore, with a pilot study, the possibility to derive structural information about the emitting regions of blazars by means of a joint analysismore » of rapid variability of the total and polarized flux at optical wavelengths. Methods. Short timescale (from tens of seconds to a couple of minutes) optical linear polarimetry and photometry for two blazars, BL Lacertae and PKS 1424+240, was carried out with the PAOLO polarimeter at the 3.6 m Telescopio Nazionale Galileo. Several hours of almost continuous observations were obtained for both sources. Results. Our intense monitoring allowed us to draw strongly different scenarios for BL Lacertae and PKS 1424+240, with the former characterized by intense variability on time-scales from hours to a few minutes and the latter practically constant in total flux. Essentially the same behavior is observed for the polarized flux and the position angle. The variability time-scales turned out to be as short as a few minutes, although involving only a few percent variation of the flux. The polarization variability time-scale is generally consistent with the total flux variability. Total and polarized flux appear to be essentially uncorrelated. However, even during our relatively short monitoring, different regimes can be singled out. Conclusions. No simple scenario is able to satisfactorily model the very rich phenomenology exhibited in our data. As

Multi-epoch intranight optical monitoring of eight radio-quiet BL Lac candidates

NASA Astrophysics Data System (ADS)

Kumar, P.; Gopal-Krishna; Stalin, C. S.; Chand, H.; Srianand, R.; Petitjean, P.

2017-10-01

For a new sample of eight weak-line quasars (WLQs) we report a sensitive search in 20 intranight monitoring sessions, for blazar-like optical flux variations on hour-like and longer time-scale (day/month/year-like). The sample consists exclusively of the WLQs that are not radio-loud and either have been classified as 'radio-weak probable BL Lac candidates' and/or are known to have exhibited at least one episode of large, blazar-like optical variability. Whereas only a hint of intranight variability is seen for two of these WLQs, J104833.5+620305.0 (z = 0.219) and J133219.6+622715.9 (z = 3.15), statistically significant internight variability at a few per cent level is detected for three of the sources, including the radio-intermediate WLQ J133219.6+622715.9 (z = 3.15) and the well-known bona fide radio-quiet WLQs J121221.5+534128.0 (z = 3.10) and WLQ J153259.9-003944.1 (z = 4.62). In the rest frame, this variability is intraday and in the far-ultraviolet band. On the time-scale of a decade, we find for three of the WLQs large brightness changes, amounting to 1.655 ± 0.009, 0.163 ± 0.010 and 0.144 ± 0.018 mag, for J104833.5+620305.0, J123743.1+630144.9 and J232428.4+144324.4, respectively. Whereas the latter two are confirmed radio-quiet WLQs, the extragalactic nature of J104833.5+620305.0 remains to be well established, thanks to the absence of any feature(s) in its available optical spectra. This study forms a part of our ongoing campaign of intranight optical monitoring of radio-quiet WLQs, in order to improve the understanding of this enigmatic class of active galactic nuclei and to look among them for a possible tiny, elusive population of radio-quiet BL Lacs.

Short timescale photometric and polarimetric behavior of two BL Lacertae type objects

DOE PAGES

Covino, S.; Baglio, M. C.; Foschini, L.; ...

2015-06-05

Context. Blazars are astrophysical sources whose emission is dominated by non-thermal processes, typically interpreted as synchrotron and inverse Compton emission. Although the general picture is rather robust and consistent with observations, many aspects are still unexplored. Aims. Polarimetric monitoring can offer a wealth of information about the physical processes in blazars. Models with largely different physical ingredients can often provide almost indistinguishable predictions for the total flux, but usually are characterized by markedly different polarization properties. We explore, with a pilot study, the possibility to derive structural information about the emitting regions of blazars by means of a joint analysismore » of rapid variability of the total and polarized flux at optical wavelengths. Methods. Short timescale (from tens of seconds to a couple of minutes) optical linear polarimetry and photometry for two blazars, BL Lacertae and PKS 1424+240, was carried out with the PAOLO polarimeter at the 3.6 m Telescopio Nazionale Galileo. Several hours of almost continuous observations were obtained for both sources. Results. Our intense monitoring allowed us to draw strongly different scenarios for BL Lacertae and PKS 1424+240, with the former characterized by intense variability on time-scales from hours to a few minutes and the latter practically constant in total flux. Essentially the same behavior is observed for the polarized flux and the position angle. The variability time-scales turned out to be as short as a few minutes, although involving only a few percent variation of the flux. The polarization variability time-scale is generally consistent with the total flux variability. Total and polarized flux appear to be essentially uncorrelated. However, even during our relatively short monitoring, different regimes can be singled out. Conclusions. No simple scenario is able to satisfactorily model the very rich phenomenology exhibited in our data. As

Effect of environmental temperature on sleep, locomotor activity, core body temperature and immune responses of C57BL/6J mice

PubMed Central

Jhaveri, KA; Trammell, RA; Toth, LA

2007-01-01

Ambient temperature exerts a prominent influence on sleep. In rats and humans, low ambient temperatures generally impair sleep, whereas higher temperatures tend to promote sleep. The purpose of the current study was to evaluate sleep patterns and core body temperatures of C57BL/6J mice at ambient temperatures of 22°C, 26°C and 30°C under baseline conditions, after sleep deprivation (SD), and after infection with influenza virus. C57BL/6J mice were surgically implanted with electrodes for recording electroencephalogram (EEG) and electromyogram (EMG) and with intraperitoneal transmitters for recording core body temperature (Tc) and locomotor activity. The data indicate that higher ambient temperatures (26°C and 30°C) promote spontaneous slow wave sleep (SWS) in association with reduced delta wave amplitude during SWS in C57BL/6J mice. Furthermore, higher ambient temperatures also promote recuperative sleep after SD. Thus, in mice, higher ambient temperatures reduced sleep depth under normal conditions, but augmented the recuperative response to sleep loss. Mice infected with influenza virus while maintained at 22 or 26°C developed more SWS, less rapid eye movement sleep, lower locomotor activity and greater hypothermia than did mice maintained at 30°C during infection. In addition, despite equivalent viral titers, mice infected with influenza virus at 30°C showed less leucopenia and lower cytokine induction as compared with 22 and 26°C, respectively, suggesting that less inflammation develops at the higher ambient temperature. PMID:17467232

Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice

PubMed Central

Burnett, Colin M. L.

2013-01-01

Substantial research efforts have been aimed at identifying novel targets to increase resting metabolic rate (RMR) as an adjunct approach to the treatment of obesity. Respirometry (one form of “indirect calorimetry”) is unquestionably the dominant technique used in the obesity research field to assess RMR in vivo, although this method relies upon a lengthy list of assumptions that are likely to be violated in pharmacologically or genetically manipulated animals. A “total” calorimeter, including a gradient layer direct calorimeter coupled to a conventional respirometer, was used to test the accuracy of respirometric-based estimations of RMR in laboratory mice (Mus musculus Linnaeus) of the C57Bl/6 and FVB background strains. Using this combined calorimeter, we determined that respirometry underestimates RMR of untreated 9- to 12-wk-old male mice by ∼10–12%. Quantitative and qualitative differences resulted between methods for untreated C57Bl/6 and FVB mice, C57Bl/6 mice treated with ketamine-xylazine anesthesia, and FVB mice with genetic deletion of the angiotensin II type 2 receptor. We conclude that respirometric methods underestimate RMR in mice in a magnitude that is similar to or greater than the desired RMR effects of novel therapeutics. Sole reliance upon respirometry to assess RMR in mice may lead to false quantitative and qualitative conclusions regarding the effects of novel interventions. Increased use of direct calorimetry for the assessment of RMR and confirmation of respirometry results and the reexamination of previously discarded potential obesity therapeutics are warranted. PMID:23964071

Widespread bronchogenic dissemination makes DBA/2 mice more susceptible than C57BL/6 mice to experimental aerosol infection with Mycobacterium tuberculosis.

PubMed

Cardona, Pere-Joan; Gordillo, Sergi; Díaz, Jorge; Tapia, Gustavo; Amat, Isabel; Pallarés, Angeles; Vilaplana, Cristina; Ariza, Aurelio; Ausina, Vicenç

2003-10-01

We have used the murine model of aerosol-induced experimental tuberculosis to assess the effects of four clinical isolates and a reference strain of Mycobacterium tuberculosis on resistant C57BL/6 mice and susceptible DBA/2 mice. Histological studies and detection of 25 cytokines potentially involved in the infection were carried out. DBA/2 mice showed higher concentrations of bacilli in bronchoalveolar lavage fluid and lung tissue. Furthermore, these mice evidenced a larger granulomatous infiltration in the parenchyma due to an increased rate of emigration of infected foamy macrophages from the granulomas to the neighboring pulmonary alveolar spaces. The better control of bacillary concentrations and pulmonary infiltration observed in C57BL/6 mice from week 3 postinfection could result from their higher RANTES, ICAM-1, and gamma interferon (IFN-gamma) mRNA levels. On the other hand, the higher MIP-2 and MCP-3 mRNA levels seen in DBA/2 mice would result in stronger lung recruitment of macrophages and neutrophils. Additionally, DBA/2 mice showed increased inducible nitric oxide synthase expression, induced by the larger number of foamy macrophages, at weeks 18 and 22. This increment was a consequence of phagocytosed bacillary debris, was independent of IFN-gamma expression, and could exert only a bacteriostatic effect. The results of the study suggest that DBA/2 mice are more susceptible than C57BL/6 mice to M. tuberculosis infection due to a higher bronchial dissemination of bacilli inside poorly activated foamy macrophages.

Current status of BL-2B at photon factory

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

Nambu, Akira, E-mail: akia.nambu.tw@hitachi.com; Ueda, Kazuhiro; Horiba, Koji

A new soft x-ray beamline BL-2B at Photon Factory of High Energy Accelerator Research Organization (KEK-PF) covers energy range from vacuum ultraviolet (30 eV) to soft x-ray (4000 eV). This wide energy range could be achieved by employing two undulators and two monochromators. Two different energy range undulators were installed tandem to a 9-meter straight section of PF storage ring. The 1{sup st} undulator is for VUV (30 eV) to SX (280 eV), while the other one is for SX (280 eV) to HX (4000 eV). It is also necessary to be equipped with two different monochrometors for energy abovemore » and under 2000 eV; grating monochrometor and double crystal monochrometor. One of the main purposes of this bemaline is spectroscopic study of light elements contained in several functional materials. The beamline is designed for photoemission spectroscopy (PES), X-ray absorption fine structure (XAFS) and other types of experiments. The performance of the new beamline is reported and typical examples of its application to material science are demonstrated.« less

Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is repressed by transforming growth factor-beta via Smad4 binding element in human BL cells.

PubMed

Liang, C L; Tsai, C N; Chung, P J; Chen, J L; Sun, C M; Chen, R H; Hong, J H; Chang, Y S

2000-11-10

In Epstein-Barr virus (EBV)-infected BL cells, the oncogenic EBV-encoded nuclear antigen 1 (EBNA 1) gene is directed from the latent promoter Qp. Yeast one-hybrid screen analysis using the -50 to -37 sequence of Qp as the bait was carried out to identify transcriptional factors that may control Qp activity. Results showed that Smad4 binds the -50 to -37 sequence of Qp, indicating that this promoter is potentially regulated by TGF-beta. The association of Smad4 with Qp was further confirmed by supershift of EMSA complexes using Smad4-specific antibody. The transfection of a Qp reporter construct in two EBV(+) BL cell lines, Rael and WW2, showed that Qp activity is repressed in response to the TGF-beta treatment. This repression involves the interaction of a Smad3/Smad4 complex and the transcriptional repressor TGIF, as determined by cotransfection assay and coimmunoprecipitation analysis. Results suggest that TGF-beta may transcriptionally repress Qp through the Smad4-binding site in human BL cells. Copyright 2000 Academic Press.

Tracing Assessment Policy Discourses in Neoliberalised Higher Education Settings

ERIC Educational Resources Information Center

Raaper, Rille

2017-01-01

This article explores assessment policy in two European universities with different political, historical and social backgrounds: the University of Glasgow and Tallinn University. The University of Glasgow is a well-established Russell Group university in the UK; Tallinn University is a relatively new university in post-Soviet Estonia, shaped by…

Spectroscopy of 10 γ -Ray BL Lac Objects at High Redshift

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

Paiano, Simona; Falomo, Renato; Landoni, Marco

2017-08-01

We present optical spectra with high signal-to-noise ratio of 10 BL Lac objects detected at GeV energies by the Fermi satellite (3FGL catalog), which previous observations suggested are at relatively high redshift. The new observations, obtained at the 10 m Gran Telescopio Canarias, allowed us to find the redshift for J0814.5+2943 ( z = 0.703), and we can set a spectroscopic lower limit for J0008.0+4713 ( z > 1.659) and J1107.7+0222 ( z > 1.0735) on the basis of Mg ii intervening absorption features. In addition we confirm the redshifts for J0505.5+0416 ( z = 0.423) and J1450+5200 ( zmore » > 2.470). Finally we contradict the previous z estimates for five objects (J0049.7+0237, J0243.5+7119, J0802.0+1005, J1109.4+2411, and J2116.1+3339).« less

Implantation of GL261 neurospheres into C57/BL6 mice: a more reliable syngeneic graft model for research on glioma-initiating cells.

PubMed

Yi, Liang; Zhou, Chun; Wang, Bing; Chen, Tunan; Xu, Minhui; Xu, Lunshan; Feng, Hua

2013-08-01

Recent studies have demonstrated that inflammatory cells and inflammatory mediators are indispensable components of the tumor-initiating cell (TIC) niche and regulate the malignant behavior of TICs. However, conventional animal models for glioma-initiating cell (GIC) studies are based on the implantation of GICs from human glioblastoma (GBM) into immunodeficient mice without the regulation of immune system. Whether animal models can mimic the cellular microenvironment of malignancy and evaluate the biological features of GICs accurately is unclear. Here, we detected the biological features of neurosphere-like tumor cells derived from the murine GBM cell line GL261 (GL261-NS) and from primary human GBM (PGBM-NS) in vitro, injected GL261-NS into syngeneic C57/BL6 mouse brain and injected PGBM-NS into NOD/SCID mouse brain, respectively. The tumorigenic characteristics of the two different orthotopic transplantation models were analyzed and the histological discrepancy between grafts and human primary GBM was compared. We found that GICs enriched in GL261-NS, GL261-NS and PGBM-NS exhibited increased GIC potential and enhanced chemoresistance in vitro. GL261-NS was significantly more aggressive compared to GL261 adhesive cells (GL261-AC) in vivo and the enhanced aggression was more significant in syngeneic mice compared to immunodeficient mice. The discrepancy of tumorigenicity between GL261-NS and GL261-AC in C57/BL6 mice was also larger compared to that between PGBM-NS and PGBM-AC in immunodeficient mice. Syngrafts derived from GL261-NS in C57/BL6 mice corresponded to the human GBM histologically better, compared with xenografts derived from PGBM-NS in NOD/SCID mice, which lack inflammatory cells and inflammatory mediators. We conclude that the inflammatory niche is involved in the tumorigenicity of GICs and implantation of GL261-NS into C57/BL6 mice is a more reliable syngeneic graft model for in vivo study on GICs relative to the immunodeficiency model.

77 FR 26772 - Prospective Grant of Exclusive License: Ocular Therapeutics Agent Delivery Devices and Methods...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-07

... Michael R. Robinson et al (NEI, CC, and NIBIB) (E-241-1999/0), to ODIN Biotech having a place of business... United States of America. The exclusive patent license is one which qualifies under the Start-up...

Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice.

PubMed

Grant, Marianne K O; Seelig, Davis M; Sharkey, Leslie C; Zordoky, Beshay N

2017-01-01

There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known. Therefore, in the present study, we determined the effect of acute DOX exposure on the expression of CYP genes in the hearts of both male and female C57Bl/6 mice. Acute DOX cardiotoxicity was induced by a single intraperitoneal injection of 20 mg/kg DOX in male and female adult C57Bl/6 mice. Cardiac function was assessed 5 days after DOX exposure by trans-thoracic echocardiography. Mice were euthanized 1 day or 6 days after DOX or saline injection. Thereafter, the hearts were harvested and weighed. Heart sections were evaluated for pathological lesions. Total RNA was extracted and expression of natriuretic peptides, inflammatory and apoptotic markers, and CYP genes was measured by real-time PCR. Adult female C57Bl/6 mice were protected from acute DOX-induced cardiotoxicity as they show milder pathological lesions, less inflammation, and faster recovery from DOX-induced apoptosis and DOX-mediated inhibition of beta-type natriuretic peptide. Acute DOX exposure altered the gene expression of multiple CYP genes in a sex-dependent manner. In 24 h, DOX exposure caused male-specific induction of Cyp1b1 and female-specific induction of Cyp2c29 and Cyp2e1. Acute DOX exposure causes sex-dependent alteration of cardiac CYP gene expression. Since cardiac CYP enzymes metabolize several endogenous compounds to biologically active metabolites, sex-dependent alteration of CYP genes may play a role in the sexual dimorphism of acute DOX

Foxp3⁺ regulatory T cells delay expulsion of intestinal nematodes by suppression of IL-9-driven mast cell activation in BALB/c but not in C57BL/6 mice.

PubMed

Blankenhaus, Birte; Reitz, Martina; Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Breloer, Minka

2014-02-01

Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3⁺ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3⁺ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6

Increased projection of MHC and tumor antigens in murine B16-BL6 melanoma induced by hydrostatic pressure and chemical crosslinking.

PubMed

Ramakrishna, V; Eisenthal, A; Skornick, Y; Shinitzky, M

1993-05-01

The B16-BL6 melanoma, like most spontaneously arising tumors, is poorly immunogenic and expresses low levels of major histocompatibility complex (MHC) antigens. Treatment of cells of this tumor in vitro by hydrostatic pressure in the presence of adenosine 2',3'-dialdehyde (oxAdo), a membrane-impermeant crosslinker, caused elevated projection of MHC and a specific tumor antigen as demonstrated by flow-cytometric analysis. Maximum projection of both the MHC and the tumor antigens could be reached by application of 1200 atm for 15 min in the presence of 20 mM oxAdo. It is not yet clear whether this passive increase in availability of antigens on the cell surface originated from a dormant pool of antigens in the plasma membrane or from pressure-induced fusion of antigen-rich intracellular organelles (e.g. the endoplasmic reticulum). The immunogenic properties of the antigen-enriched B16-BL6 cells are described in the following paper.

Contemporaneous broadband observations of three high-redshift BL Lac objects

DOE PAGES

Ackerman, M.

2016-03-20

We have collected broadband spectral energy distributions (SEDs) of three BL Lac objects, 3FGL J0022.1-1855 (z=0.689), 3FGL J0630.9-2406 (z > ~1.239), and 3FGL J0811.2-7529 (z=0.774), detected by Fermi with relatively flat GeV spectra. By observing simultaneously in the near-IR to hard X-ray band, we can well characterize the high end of the synchrotron component of the SED. Thus, fitting the SEDs to synchro-Compton models of the dominant emission from the relativistic jet, we can constrain the underlying particle properties and predict the shape of the GeV Compton component. Standard extragalactic background light (EBL) models explain the high-energy absorption well, withmore » poorer fits for high UV models. The fits show clear evidence for EBL absorption in the Fermi spectrum of our highest redshift source 3FGL J0630.9-2406. While synchrotron self-Compton models adequately describe the SEDs, the situation may be complicated by possible external Compton components.« less

Multiwavelength Observations of the Blazar BL Lacertae: A New Fast TeV Gamma-Ray Flare

NASA Astrophysics Data System (ADS)

Abeysekara, A. U.; Benbow, W.; Bird, R.; Brantseg, T.; Brose, R.; Buchovecky, M.; Buckley, J. H.; Bugaev, V.; Connolly, M. P.; Cui, W.; Daniel, M. K.; Falcone, A.; Feng, Q.; Finley, J. P.; Fortson, L.; Furniss, A.; Gillanders, G. H.; Gunawardhana, I.; Hütten, M.; Hanna, D.; Hervet, O.; Holder, J.; Hughes, G.; Humensky, T. B.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kertzman, M.; Krennrich, F.; Lang, M. J.; Lin, T. T. Y.; McArthur, S.; Moriarty, P.; Mukherjee, R.; O’Brien, S.; Ong, R. A.; Otte, A. N.; Park, N.; Petrashyk, A.; Pohl, M.; Pueschel, E.; Quinn, J.; Ragan, K.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rulten, C.; Sadeh, I.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Wakely, S. P.; Weinstein, A.; Wells, R. M.; Wilcox, P.; Williams, D. A.; Zitzer, B.; The VERITAS Collaboration; Jorstad, S. G.; Marscher, A. P.; Lister, M. L.; Kovalev, Y. Y.; Pushkarev, A. B.; Savolainen, T.; Agudo, I.; Molina, S. N.; Gómez, J. L.; Larionov, V. M.; Borman, G. A.; Mokrushina, A. A.; Tornikoski, M.; Lähteenmäki, A.; Chamani, W.; Enestam, S.; Kiehlmann, S.; Hovatta, T.; Smith, P. S.; Pontrelli, P.

2018-04-01

Combined with measurements made by very-long-baseline interferometry, the observations of fast TeV gamma-ray flares probe the structure and emission mechanism of blazar jets. However, only a handful of such flares have been detected to date, and only within the last few years have these flares been observed from lower-frequency-peaked BL Lac objects and flat-spectrum radio quasars. We report on a fast TeV gamma-ray flare from the blazar BL Lacertae observed by the Very Energetic Radiation Imaging Telescope Array System (VERITAS). with a rise time of ∼2.3 hr and a decay time of ∼36 min. The peak flux above 200 GeV is (4.2 ± 0.6) × 10‑6 photon m‑2 s‑1 measured with a 4-minute-binned light curve, corresponding to ∼180% of the flux that is observed from the Crab Nebula above the same energy threshold. Variability contemporaneous with the TeV gamma-ray flare was observed in GeV gamma-ray, X-ray, and optical flux, as well as in optical and radio polarization. Additionally, a possible moving emission feature with superluminal apparent velocity was identified in Very Long Baseline Array observations at 43 GHz, potentially passing the radio core of the jet around the time of the gamma-ray flare. We discuss the constraints on the size, Lorentz factor, and location of the emitting region of the flare, and the interpretations with several theoretical models that invoke relativistic plasma passing stationary shocks.

Effect of fenbendazole on three behavioral tests in male C57BL/6N mice.

PubMed

Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

2010-11-01

Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment.

Effect of Fenbendazole on Three Behavioral Tests in Male C57BL/6N Mice

PubMed Central

Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

2010-01-01

Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment. PMID:21205447

Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice.

PubMed

Ren, Zhihong; Gay, Raina; Thomas, Adam; Pae, Munkyong; Wu, Dayong; Logsdon, Lauren; Mecsas, Joan; Meydani, Simin Nikbin

2009-12-01

Ageing is associated with a decline in immune function, which predisposes the elderly to a higher incidence of infections. Information on the mechanism of the age-related increase in susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) is limited. In particular, little is known regarding the involvement of the immune response in this age-related change. We employed streptomycin (Sm)-pretreated C57BL/6 mice to develop a mouse model that would demonstrate age-related differences in susceptibility and immune response to S. Typhimurium. In this model, old mice inoculated orally with doses of 3 x 10(8) or 1 x 10(6) c.f.u. S. Typhimurium had significantly greater S. Typhimurium colonization in the ileum, colon, Peyer's patches, spleen and liver than young mice. Old mice had significantly higher weight loss than young mice on days 1 and 2 post-infection. In response to S. Typhimurium infection, old mice failed to increase ex vivo production of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph node cells to the same degree as observed in young mice; this was associated with their inability to maintain the presence of neutrophils and macrophages at a 'youthful' level. These results indicate that Sm-pretreated C57BL/6 old mice are more susceptible to S. Typhimurium infection than young mice, which might be due to impaired IFN-gamma and TNF-alpha production as well as a corresponding change in the number of neutrophils and macrophages in response to S. Typhimurium infection compared to young mice.

DefenseLink.mil - Special Report - Travels With Gates

Science.gov Websites

of Estonia Estonia Defense Secretary Robert M. Gates holds a press conference after the Tallinn High . Sgt. Jerry Morrison Defense Secretary Robert M. Gates holds a press conference after the Tallinn High . Sgt. Jerry Morrison Defense Secretary Robert M. Gates walks with the Prime Minister of Estonia Andrus

The Gamma-Ray Bright BL Lac Object RX J1211+2242

NASA Technical Reports Server (NTRS)

Beckmann, V.; Favre, P.; Tavecchio, F.; Bussien, T.; Fliri, J.; Wolter, A.

2004-01-01

RX J1211+2242 is an optically faint (B approximately equal to 19.2mag) but X-ray bright (f2-10kev = 5 x l0(exp -12)erg per square centimeter per second) AGN, which has been shown to be a BL Lac object at redshift z = 0.455. The ROSAT X-ray, Calar Alto optical, and NVSS radio data suggest that the peak of the synchrotron emission of this object is at energies as high as several keV. BeppoSAX observations have been carried out simultaneously with optical observations in order to extend the coverage to higher energies. The new data indeed indicate a turn-over in the 2 - 10keV energy region. We propose that RX J1211+2242 is the counterpart of the unidentified EGRET source 3EG J1212+2304, making it a gamma-ray emitter with properties similar to, for example, Markarian 501 in its bright state, though being at a much larger distance.

Myeloid-derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice.

PubMed

Schmid, Maximilian; Zimara, Nicole; Wege, Anja Kathrin; Ritter, Uwe

2014-11-01

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of CD11b+ cells. According to the surface molecules Ly6G and Ly6C (where Ly6G and Ly6C are lymphocyte antigen 6, locus G and C, respectively), MDSCs are further divided into monocytic (Mo-MDSCs, CD11b+ /Ly6C(high) /Ly6G-) and polymorphonucleated suppressor cells (PMN-MDSCs, CD11b+ /Ly6C(int) /Ly6G+). Most published manuscripts focus on the suppressive role of MDSCs in cancer, whereas their impact on adaptive immunity against obligatory intracellular parasites is not well understood. Furthermore, it is not clear how the genetic background of mice influences MDSC functionality. Therefore, we implemented an experimental model of leishmaniasis, and analyzed MDSC maturation and the impact of MDSCs on the parasite-specific T-cell responses in resistant C57BL/6 and susceptible BALB/c mice. This experimental setup demonstrated the impaired ability of BALB/c mice to produce Mo-MDSCs when compared with C57BL/6 mice. This phenotype is detectable after subcutaneous infection with parasites and is specifically represented by a reduced accumulation of Mo-MDSCs at the site of infection in BALB/c mice. Moreover, infected C57BL/6-derived MDSCs were able to suppress Leishmania-specific CD4+ -cell proliferation, whereas BALB/c-derived MDSCs harboring parasites lost this suppressive function. In conclusion, we demonstrate that (i) genetic background defines MDSC differentiation; and (ii) Leishmania major parasites are able to modulate the suppressive effect of MDSCs in a strain-dependent manner. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tim-3 is differently expressed in genetically susceptible C57BL/6 and resistant BALB/c mice during oral infection with Toxoplasma gondii

PubMed Central

Berrocal Almanza, L. C.; Muñoz, M.; Kühl, A. A.; Kamradt, T.; Heimesaat, M. M.

2013-01-01

Tim-3 has opposing roles in innate and adaptive immunities. It not only dampens CD4+ and CD8+ T cells responses but also enhances the ability of macrophages to eliminate intracellular pathogens. After peroral infection with 100 cysts of Toxoplasma gondii genetically susceptible C57BL/6 mice develop an unchecked Th1 response associated with the development of small intestinal immunopathology. Here we report that upon infection with T. gondii, both susceptible C57BL/6 and resistant BALB/c mice exhibit increased frequencies of Tim-3+ cells in spleens and mesenteric lymph nodes. The number of Tim-3+ cells was significantly higher in C57BL/6 than in BALB/c mice. Tim-3 was expressed by macrophages, dendritic, natural killer, as well as CD4+ and CD8+ T cells. Highest frequencies of Tim-3+ cells were observed at the peak of Th1 responses (day 7 post infection) concurrent with the development of ileal immunopathology. Infected Tim-3-deficient BALB/c mice did not develop ileal immunopathology nor did their parasite loads differ from those in wildtype BALB/c mice. Thus, although Tim-3 is markedly upregulated upon infection and differentially regulated in susceptible and resistant mice upon infection with T. gondii, the absence of Tim-3 is not sufficient to overcome the genetic resistance of BALB/c mice to the development of Th1-driven small intestinal immunopathology. PMID:24265941

Tim-3 is differently expressed in genetically susceptible C57BL/6 and resistant BALB/c mice during oral infection with Toxoplasma gondii.

PubMed

Berrocal Almanza, L C; Muñoz, M; Kühl, A A; Kamradt, T; Heimesaat, M M; Liesenfeld, O

2013-09-01

Tim-3 has opposing roles in innate and adaptive immunities. It not only dampens CD4+ and CD8+ T cells responses but also enhances the ability of macrophages to eliminate intracellular pathogens. After peroral infection with 100 cysts of Toxoplasma gondii genetically susceptible C57BL/6 mice develop an unchecked Th1 response associated with the development of small intestinal immunopathology. Here we report that upon infection with T. gondii, both susceptible C57BL/6 and resistant BALB/c mice exhibit increased frequencies of Tim-3+ cells in spleens and mesenteric lymph nodes. The number of Tim-3+ cells was significantly higher in C57BL/6 than in BALB/c mice. Tim-3 was expressed by macrophages, dendritic, natural killer, as well as CD4+ and CD8+ T cells. Highest frequencies of Tim-3+ cells were observed at the peak of Th1 responses (day 7 post infection) concurrent with the development of ileal immunopathology. Infected Tim-3-deficient BALB/c mice did not develop ileal immunopathology nor did their parasite loads differ from those in wildtype BALB/c mice. Thus, although Tim-3 is markedly upregulated upon infection and differentially regulated in susceptible and resistant mice upon infection with T. gondii, the absence of Tim-3 is not sufficient to overcome the genetic resistance of BALB/c mice to the development of Th1-driven small intestinal immunopathology.

Augmented growth inhibition of B16-BL6 melanoma by combined treatment with a selective matrix metalloproteinase inhibitor, MMI-166, and cytotoxic agents.

PubMed

Hojo, Kanji; Maki, Hideo; Sawada, Takuko Yamada; Maekawa, Ryuji; Yoshioka, Takayuki

2002-01-01

MMI-166 is a selective matrix metalloproteinase (MMP) inhibitor. The purpose of this study was to evaluate the antitumor efficacy of the combined treatment of MMI-166 with paclitaxel or carboplatin. Mice bearing B16-BL6 melanoma were treated p.o. with MMI-166 from 1 day after tumor inoculation. The mice were administered i.v. with either paclitaxel or carboplatin at the maximum tolerated dose (MTD). MMI-166 monotherapy inhibited in vivo growth of the B16-BL6 tumor to an extent similar to that of paclitaxel or carboplatin monotherapy. When MMI-166 was combined with paclitaxel or carboplatin, the antitumor efficacy was significantly (p < 0.01) augmented in comparison with either MMI-166 or each cytotoxic agent alone. The hematotoxicity study demonstrated that daily treatment with MMI-166 did not affect the blood cell number in the mice and more importantly the combination of MMI-166 with paclitaxel did not augment the hematotoxicity caused by paclitaxel. An in vitro cytotoxicity study showed that MMI-166 itself has neither direct cytotoxicity against B16-BL6 tumor cells nor does it augment the cytotoxicity of paclitaxel or carboplatin. These results indicate that augmented antitumor activity of the combination treatment was not simply due to the augmentation of direct cytotoxic activity, but was rather an additive effect of the antitumor activities of different mechanisms. They suggest the effectiveness of a combination therapy of MMI-166 with paclitaxel or carboplatin in clinical therapy.

Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice.

PubMed

Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis

2016-01-01

The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells.

Probing the Innermost Regions of AGN Jets and Their Magnetic Fields with RadioAstron. I. Imaging BL Lacertae at 21 Microarcsecond Resolution

NASA Astrophysics Data System (ADS)

Gómez, José L.; Lobanov, Andrei P.; Bruni, Gabriele; Kovalev, Yuri Y.; Marscher, Alan P.; Jorstad, Svetlana G.; Mizuno, Yosuke; Bach, Uwe; Sokolovsky, Kirill V.; Anderson, James M.; Galindo, Pablo; Kardashev, Nikolay S.; Lisakov, Mikhail M.

2016-02-01

We present the first polarimetric space very long baseline interferometry (VLBI) imaging observations at 22 GHz. BL Lacertae was observed in 2013 November 10 with the RadioAstron space VLBI mission, including a ground array of 15 radio telescopes. The instrumental polarization of the space radio telescope is found to be less than 9%, demonstrating the polarimetric imaging capabilities of RadioAstron at 22 GHz. Ground-space fringes were obtained up to a projected baseline distance of 7.9 Earth diameters in length, allowing us to image the jet in BL Lacertae with a maximum angular resolution of 21 μas, the highest achieved to date. We find evidence for emission upstream of the radio core, which may correspond to a recollimation shock at about 40 μas from the jet apex, in a pattern that includes other recollimation shocks at approximately 100 and 250 μas from the jet apex. Polarized emission is detected in two components within the innermost 0.5 mas from the core, as well as in some knots 3 mas downstream. Faraday rotation analysis, obtained from combining RadioAstron 22 GHz and ground-based 15 and 43 GHz images, shows a gradient in rotation measure and Faraday-corrected polarization vector as a function of position angle with respect to the core, suggesting that the jet in BL Lacertae is threaded by a helical magnetic field. The intrinsic de-boosted brightness temperature in the unresolved core exceeds 3× {10}12 K, suggesting, at the very least, departure from equipartition of energy between the magnetic field and radiating particles.

Maternal Weight Gain as a Predictor of Litter Size in Swiss Webster, C57BL/6J, and BALB/cJ mice.

PubMed

Finlay, James B; Liu, Xueli; Ermel, Richard W; Adamson, Trinka W

2015-11-01

An important task facing both researchers and animal core facilities is producing sufficient mice for a given project. The inherent biologic variability of mouse reproduction and litter size further challenges effective research planning. A lack of precision in project planning contributes to the high cost of animal research, overproduction (thus waste) of animals, and inappropriate allocation of facility resources. To examine the extent daily prepartum maternal weight gain predicts litter size in 2 commonly used mouse strains (BALB/cJ and C57BL/6J) and one mouse stock (Swiss Webster), we weighed ≥ 25 pregnant dams of each strain or stock daily from the morning on which a vaginal plug (day 0) was present. On the morning when dams delivered their pups, we recorded the weight of the dam, the weight of the litter itself, and the number of pups. Litter sizes ranged from 1 to 7 pups for BALB/cJ, 2 to 13 for Swiss Webster, and 5 to 11 for C57BL/6J mice. Linear regression models (based on weight change from day 0) demonstrated that maternal weight gain at day 9 (BALB/cJ), day 11 (Swiss Webster), or day 14 (C57BL/6J) was a significant predictor of litter size. When tested prospectively, the linear regression model for each strain or stock was found to be accurate. These data indicate that the number of pups that will be born can be estimated accurately by using maternal weight gain at specific or stock-specific time points.

Testing the Pairs-Reflection Model with X-Ray Spectral Variability and X-Ray Properties of Complete Samples of Radio-Selected BL Lacertae Objects

NASA Astrophysics Data System (ADS)

Urry, C. Megan

1997-01-01

This grant was awarded to Dr. C. Megan Urry of the Space Telescope Science Institute in response to two successful ADP proposals to use archival Ginga and Rosat X-ray data for 'Testing the Pairs-Reflection model with X-Ray Spectral Variability' (in collaboration with Paola Grandi, now at the University of Rome) and 'X-Ray Properties of Complete Samples of Radio-Selected BL Lacertae Objects' (in collaboration with then-graduate student Rita Sambruna, now a post-doc at Goddard Space Flight Center). In addition, post-docs Joseph Pesce and Elena Pian, and graduate student Matthew O'Dowd, have worked on several aspects of these projects. The grant was originally awarded on 3/01/94; this report covers the full period, through May 1997. We have completed our project on the X-ray properties of radio-selected BL Lacs.

Attachment, invasion, chemotaxis, and proteinase expression of B16-BL6 melanoma cells exhibiting a low metastatic phenotype after exposure to dietary restriction of tyrosine and phenylalanine.

PubMed

Uhlenkott, C E; Huijzer, J C; Cardeiro, D J; Elstad, C A; Meadows, G G

1996-03-01

We previously reported that low levels of tyrosine (Tyr) and phenylalanine (Phe) alter the metastatic phenotype of B16-BL6 (BL6) murine melanoma and select for tumor cell populations with decreased lung colonizing ability. To more specifically characterize the effects of Tyr and Phe restriction on the malignant phenotype of BL6, we investigated in vitro attachment, invasion, proteinase expression, and chemotaxis of high and low metastatic BL6 variants. High metastatic variant cells were isolated from subcutaneous tumors of mice fed a nutritionally complete diet (ND cells) and low metastatic variant cells were isolated from mice fed a diet restricted in Tyr and Phe (LTP cells). Results indicate that attachment to reconstituted basement membrane (Matrigel) was significantly reduced in LTP cells as compared to ND cells. Attachment to collagen IV, laminin, and fibronectin were similar between the two variants. Invasion through Matrigel and growth factor-reduced Matrigel were significantly decreased in LTP cells as compared to ND cells. Zymography revealed the presence of M(r) 92,000 and M(r) 72,000 progelatinases, tissue plasminogen activator, and urokinase plasminogen activator in the conditioned medium of both variants; however, there were no differences in activity of these secreted proteinases between the two variants. Growth of the variants on growth factor-reduced Matrigel similarly induced expression of the M(r) 92,000 progelatinase. The variants exhibited similar chemotactic responses toward laminin. However, the chemotactic response toward fibronectin by LTP cells was significantly increased. MFR5, a monoclonal antibody which selectively blocks function of the alpha 5 chain of the alpha 5 beta 1 integrin, VLA-5, decreased the chemotactic response toward fibronectin of ND cells by 37%; the chemotactic response by LTP cells was reduced by 49%. This effect was specific for fibronectin-mediated chemotaxis since the chemotaxis toward laminin and invasion through

Dyadic social interaction of C57BL/6 mice versus interaction with a toy mouse: conditioned place preference/aversion, substrain differences, and no development of a hierarchy.

PubMed

Pinheiro, Barbara S; Seidl, Simon S; Habazettl, Eva; Gruber, Bernadette E; Bregolin, Tanja; Zernig, Gerald

2016-04-01

Impaired social interaction is a hallmark symptom of many psychiatric diseases, including dependence syndromes (substance use disorders). Helping the addict reorient her/his behavior away from the drug of abuse toward social interaction would be of considerable therapeutic benefit. To study the neural basis of such a reorientation, we have developed several animal models in which the attractiveness of a dyadic (i.e. one-to-one) social interaction (DSI) can be compared directly with that of cocaine as a prototypical drug of abuse. Our models are based on the conditioned place preference (CPP) paradigm. In an ongoing effort to validate our experimental paradigms in C57BL/6 mice to make use of the plethora of transgenic models available in this genus, we found the following: (a) DSI with a live mouse produced CPP, whereas an interaction with an inanimate mouse-like object (i.e. a 'toy mouse'; toy mouse interaction) led to conditioned place aversion - but only in the Jackson substrain (C57BL/6J). (b) In the NIH substrain (C57BL/6N), both DSI and toy mouse interaction produced individual aversion in more than 50% of the tested mice. (c) Four 15 min DSI episodes did not result in the development of an observable hierarchy, that is, dominance/subordination behavior in the overwhelming majority (i.e. 30 of 32) of the tested Jackson mouse pairs. Therefore, dominance/subordination does not seem to be a confounding variable in our paradigm, at least not in C57BL/6J mice. Respective data for NIH mice were too limited to allow any conclusion. The present findings indicate that (a) DSI with a live mouse produces CPP to a greater degree than an interaction with an inanimate object resembling a mouse and that (b) certain substrain differences with respect to CPP/aversion to DSI do exist between the Jax and NIH substrain of C57BL/6 mice. These differences have to be considered when choosing a proper mouse substrain model for investigating the neural basis of DSI reward versus

Dyadic social interaction of C57BL/6 mice versus interaction with a toy mouse: conditioned place preference/aversion, substrain differences, and no development of a hierarchy

PubMed Central

Pinheiro, Barbara S.; Seidl, Simon S.; Habazettl, Eva; Gruber, Bernadette E.; Bregolin, Tanja

2016-01-01

Impaired social interaction is a hallmark symptom of many psychiatric diseases, including dependence syndromes (substance use disorders). Helping the addict reorient her/his behavior away from the drug of abuse toward social interaction would be of considerable therapeutic benefit. To study the neural basis of such a reorientation, we have developed several animal models in which the attractiveness of a dyadic (i.e. one-to-one) social interaction (DSI) can be compared directly with that of cocaine as a prototypical drug of abuse. Our models are based on the conditioned place preference (CPP) paradigm. In an ongoing effort to validate our experimental paradigms in C57BL/6 mice to make use of the plethora of transgenic models available in this genus, we found the following: (a) DSI with a live mouse produced CPP, whereas an interaction with an inanimate mouse-like object (i.e. a ‘toy mouse’; toy mouse interaction) led to conditioned place aversion – but only in the Jackson substrain (C57BL/6J). (b) In the NIH substrain (C57BL/6N), both DSI and toy mouse interaction produced individual aversion in more than 50% of the tested mice. (c) Four 15 min DSI episodes did not result in the development of an observable hierarchy, that is, dominance/subordination behavior in the overwhelming majority (i.e. 30 of 32) of the tested Jackson mouse pairs. Therefore, dominance/subordination does not seem to be a confounding variable in our paradigm, at least not in C57BL/6J mice. Respective data for NIH mice were too limited to allow any conclusion. The present findings indicate that (a) DSI with a live mouse produces CPP to a greater degree than an interaction with an inanimate object resembling a mouse and that (b) certain substrain differences with respect to CPP/aversion to DSI do exist between the Jax and NIH substrain of C57BL/6 mice. These differences have to be considered when choosing a proper mouse substrain model for investigating the neural basis of DSI reward

Optical and X-ray observations of the two BL Lac objects OJ 287 and MS 1458+22

NASA Astrophysics Data System (ADS)

Massaro, E.; Giommi, P.; Perri, M.; Tagliaferri, G.; Nesci, R.; Tosti, G.; Ciprini, S.; Montagni, F.; Ravasio, M.; Ghisellini, G.; Frasca, A.; Marilli, E.; Valentini, G.; Kurtanidze, O. M.; Nikolashvili, M. G.

2003-02-01

We present the results of recent BeppoSAX observations of the two BL Lac objects OJ 287 and MS 1458+22 in bright optical states and of simultaneous photometric measurements in the bandpasses from I to U. OJ 287 was observed in November 2001 and MS 1458+22 in February of the same year. The X-ray flux of OJ 287 was rather low, F(2-10 keV) = (1.35+/-0.15)x 10-12 erg cm-2 s-1 and its spectrum is well described by a single power law with an energy index 0.45+/-0.08, flatter than that measured in the optical, equal to 1.53+/-0.03. The X-ray emission of MS 1458+22 was characterized by a low flux level of F(2-10 keV) = (7.5+/-0.6)x 10-13 erg cm-2 s-1, with a steeper spectral index of 1.71+/-0.15, while in the optical it was 0.99+/-0.06. We show that the broad-band SEDs of these two sources can be well represented by log-parabolic spectral laws and evaluate their parameters. This law, already observed for the synchrotron components of other BL Lac sources, can be explained if the emitting particles are accelerated by some statistical mechanism having a probability of energy gain that is a decreasing function of the energy itself.

Korean Solar Salt Ameliorates Colon Carcinogenesis in an AOM/DSS-Induced C57BL/6 Mouse Model.

PubMed

Ju, Jaehyun; Kim, Yeung-Ju; Park, Eui Seong; Park, Kun-Young

2017-06-01

The effects of Korean solar salt on an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer C57BL/6 mouse model were studied. Korean solar salt samples (SS-S, solar salt from S salt field; SS-Yb, solar salt from Yb salt field), nine-time-baked bamboo salt (BS-9x, made from SS-Yb), purified salt (PS), and SS-G (solar salt from Guérande, France) were orally administered at a concentration of 1% during AOM/DSS colon cancer induction, and compared for their protective effects during colon carcinogenesis in C57BL/6 mice. SS-S and SS-Yb suppressed colon length shortening and tumor counts in mouse colons. Histological evaluation by hematoxylin and eosin staining also revealed suppression of tumorigenesis by SS-S. Conversely, PS and SS-G did not show a similar suppressive efficacy as Korean solar salt. SS-S and SS-Yb promoted colon mRNA expression of an apoptosis-related factor and cell-cycle-related gene and suppressed pro-inflammatory factor. SS-Yb baked into BS-9x further promoted these anti-carcinogenic efficacies. Taken together, the results indicate that Korean solar salt, especially SS-S and SS-Yb, exhibited anti-cancer activity by modulating apoptosis- and inflammation-related gene expression during colon carcinogenesis in mice, and bamboo salt baked from SS-Yb showed enhanced anti-cancer functionality.

Comprehensive Evaluation of the MBT STAR-BL Module for Simultaneous Bacterial Identification and β-Lactamase-Mediated Resistance Detection in Gram-Negative Rods from Cultured Isolates and Positive Blood Cultures.

PubMed

Lee, Annie W T; Lam, Johnson K S; Lam, Ricky K W; Ng, Wan H; Lee, Ella N L; Lee, Vicky T Y; Sze, Po P; Rajwani, Rahim; Fung, Kitty S C; To, Wing K; Lee, Rodney A; Tsang, Dominic N C; Siu, Gilman K H

2018-01-01

Objective: This study evaluated the capability of a MALDI Biotyper system equipped with the newly introduced MBT STAR-BL module to simultaneously perform species identification and β-lactamase-mediated resistance detection in bacteremia -causing bacteria isolated from cultured isolates and patient-derived blood cultures (BCs). Methods: Two hundred retrospective cultured isolates and 153 prospective BCs containing Gram-negative rods (GNR) were collected and subjected to direct bacterial identification, followed by the measurement of β-lactamase activities against ampicillin, piperacillin, cefotaxime, ceftazidime, and meropenem using the MBT STAR-BL module. The results and turnaround times were compared with those of routine microbiological processing. All strains were also characterized by beta-lactamase PCR and sequencing. Results: Using the saponin-based extraction method, MALDI-TOF MS correctly identified bacteria in 116/134 (86.6%) monomicrobial BCs. The detection sensitivities for β-lactamase activities against ampicillin, piperacillin, third-generation cephalosporin and meropenem were 91.3, 100, 97.9, and 100% for cultured isolates, and 80.4, 100, 68.8, and 40% for monomicrobial BCs ( n = 134) respectively. The overall specificities ranged from 91.5 to 100%. Furthermore, the MBT STAR-BL and conventional drug susceptibility test results were concordant in 14/19 (73.7%) polymicrobial cultures. Reducing the logRQ cut-off value from 0.4 to 0.2 increased the direct detection sensitivities for β-lactamase activities against ampicillin, cefotaxime and meropenem in BCs to 85.7, 87.5, and 100% respectively. The MBT STAR-BL test enabled the reporting of β-lactamase-producing GNR at 14.16 and 47.64 h before the interim and final reports of routine BCs processing, respectively, were available. Conclusion: The MALDI Biotyper system equipped with the MBT STAR-BL module enables the simultaneous rapid identification of bacterial species and �

Comprehensive Evaluation of the MBT STAR-BL Module for Simultaneous Bacterial Identification and β-Lactamase-Mediated Resistance Detection in Gram-Negative Rods from Cultured Isolates and Positive Blood Cultures

PubMed Central

Lee, Annie W. T.; Lam, Johnson K. S.; Lam, Ricky K. W.; Ng, Wan H.; Lee, Ella N. L.; Lee, Vicky T. Y.; Sze, Po P.; Rajwani, Rahim; Fung, Kitty S. C.; To, Wing K.; Lee, Rodney A.; Tsang, Dominic N. C.; Siu, Gilman K. H.

2018-01-01

Objective: This study evaluated the capability of a MALDI Biotyper system equipped with the newly introduced MBT STAR-BL module to simultaneously perform species identification and β-lactamase-mediated resistance detection in bacteremia -causing bacteria isolated from cultured isolates and patient-derived blood cultures (BCs). Methods: Two hundred retrospective cultured isolates and 153 prospective BCs containing Gram-negative rods (GNR) were collected and subjected to direct bacterial identification, followed by the measurement of β-lactamase activities against ampicillin, piperacillin, cefotaxime, ceftazidime, and meropenem using the MBT STAR-BL module. The results and turnaround times were compared with those of routine microbiological processing. All strains were also characterized by beta-lactamase PCR and sequencing. Results: Using the saponin-based extraction method, MALDI-TOF MS correctly identified bacteria in 116/134 (86.6%) monomicrobial BCs. The detection sensitivities for β-lactamase activities against ampicillin, piperacillin, third-generation cephalosporin and meropenem were 91.3, 100, 97.9, and 100% for cultured isolates, and 80.4, 100, 68.8, and 40% for monomicrobial BCs (n = 134) respectively. The overall specificities ranged from 91.5 to 100%. Furthermore, the MBT STAR-BL and conventional drug susceptibility test results were concordant in 14/19 (73.7%) polymicrobial cultures. Reducing the logRQ cut-off value from 0.4 to 0.2 increased the direct detection sensitivities for β-lactamase activities against ampicillin, cefotaxime and meropenem in BCs to 85.7, 87.5, and 100% respectively. The MBT STAR-BL test enabled the reporting of β-lactamase-producing GNR at 14.16 and 47.64 h before the interim and final reports of routine BCs processing, respectively, were available. Conclusion: The MALDI Biotyper system equipped with the MBT STAR-BL module enables the simultaneous rapid identification of bacterial species and �

Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice

PubMed Central

Lee, Seon-Yong; Lee, Dong-Jin; Kwon, Kang; Lee, Chang-Hyun; Shin, Hyun Jong; Kim, Jai Eun; Ha, Ki-Tae; Jeong, Han-Sol

2016-01-01

Objectives: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. Methods: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. Results: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. Conclusion: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia. PMID:27386145

Studies of the jet in BL Lacertae. I. Recollimation shock and moving emission features

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

Cohen, M. H.; Hovatta, T.; Meier, D. L.

2014-06-01

Parsec-scale VLBA images of BL Lac at 15 GHz show that the jet contains a permanent quasi-stationary emission feature 0.26 mas (0.34 pc projected) from the core, along with numerous moving features. In projection, the tracks of the moving features cluster around an axis at a position angle of –166.°6 that connects the core with the standing feature. The moving features appear to emanate from the standing feature in a manner strikingly similar to the results of numerical two-dimensional relativistic magneto-hydrodynamic (RMHD) simulations in which moving shocks are generated at a recollimation shock (RCS). Because of this, and the closemore » analogy to the jet feature HST-1 in M87, we identify the standing feature in BL Lac as an RCS. We assume that the magnetic field dominates the dynamics in the jet, and that the field is predominantly toroidal. From this we suggest that the moving features are compressions established by slow and fast mode magneto-acoustic MHD waves. We illustrate the situation with a simple model in which the slowest moving feature is a slow-mode wave, and the fastest feature is a fast-mode wave. In the model, the beam has Lorentz factor Γ{sub beam}{sup gal}≈3.5 in the frame of the host galaxy and the fast mode wave has Lorentz factor Γ{sub Fwave}{sup beam}≈1.6 in the frame of the beam. This gives a maximum apparent speed for the moving features, β{sub app} = v{sub app}/c = 10. In this model the Lorentz factor of the pattern in the galaxy frame is approximately three times larger than that of the beam itself.« less

A 4-week study of four 3-monochloropropane-1,2-diol diesters on lipid metabolism in C57BL/6J mice.

PubMed

Lu, Jing; Wang, Zhenning; Ren, Mengrou; Feng, Guangxin; Ye, Beining; Wang, Yi; Fang, Baochen; Deng, Xuming; Guan, Shuang

2015-09-01

3-Monochloropropane-1,2-diol (3-MCPD) esters have been detected in many foods, which have become a new safety issue worldwide. In the study, we investigated the effect of four 3-MCPD diesters (palmitate diester: CDP; stearate diester: CDS; oleate diester: CDO; linoleate diester: CDL) on lipid metabolism in C57BL/6J mice. The results showed that CDP, CDS, CDO and CDL significantly increased the serum TC, LDL-C levels and liver TG, TC levels at dose of 16.5μmol/kg/day. These results indicated that 3-MCPD diesters could potentially cause hyperlipidemia in C57BL/6J mice. Moreover, oil red O staining confirmed fat accumulation in liver induced by 3-MCPD diesters. Our work will provide more information for safety evaluation of 3-MCPD diesters. However, whether free 3-MCPD or free fatty acids or combined action compensates for the hyperlipidemia effects should be elucidated in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Optical Spectroscopy of SDSS J004054.65-0915268: Three Possible Scenarios for the Classification. A z ˜ 5 BL Lacertae, a Blue FSRQ, or a Weak Emission Line Quasar

NASA Astrophysics Data System (ADS)

Landoni, M.; Zanutta, A.; Bianco, A.; Tavecchio, F.; Bonnoli, G.; Ghisellini, G.

2016-02-01

The haunt of high-redshift BL Lacerate objects is day by day more compelling to firmly understand their intrinsic nature and evolution. SDSS J004054.65-0915268 is, at the moment, one of the most distant BL Lac candidates, at z ˜ 5. We present a new optical-near-IR spectrum obtained with ALFOSC-NOT with a new, custom designed dispersive grating aimed to detect broad emission lines that could disprove this classification. In the obtained spectra, we do not detect any emission features and we provide an upper limit to the luminosity of the C IV broad emission line. Therefore, the nature of the object is then discussed, building the overall spectral energy distribution (SED) and fitting it with three different models. Our fits, based on SED modeling with different possible scenarios, cannot rule out the possibility that this source is indeed a BL Lac object, though the absence of optical variability and the lack of strong radio flux seem to suggest that the observed optical emission originates from a thermalized accretion disk.

The compression behavior of blödite at low and high temperature up to ~10GPa: Implications for the stability of hydrous sulfates on icy planetary bodies

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

Comodi, Paola; Stagno, Vincenzo; Zucchini, Azzurra

Recent satellite inferences of hydrous sulfates as recurrent minerals on the surface of icy planetary bodies link with the potential mineral composition of their interior. Blödite, a mixed Mg-Na sulfate, is here taken as representative mineral of icy satellites surface to investigate its crystal structure and stability at conditions of the interior of icy bodies. To this aim we performed in situ synchrotron angle-dispersive X-ray powder diffraction experiments on natural blödite at pressures up to ~10.4 GPa and temperatures from ~118.8 K to ~490.0 K using diamond anvil cell technique to investigate the compression behavior and establish a low-to-high temperaturemore » equation of state that can be used as reference when modeling the interior of sulfate-rich icy satellites such as Ganymede. The experimentally determined volume expansivity, α, varies from 7.6 (7) 10 -5 K -1 at 0.0001 GPa (from 118.8 to 413.15 K) to 2.6 (3) 10 -5 K -1 at 10 GPa (from 313.0 to 453.0 K) with a δα/δ P coefficient = -5.6(9)10 -6 GPa -1 K -1. The bulk modulus calculated from the least squares fitting of P-V data on the isotherm at 413 K using a second-order Birch - Murnaghan equation of state is 38(5) GPa, which gives the value of δK/δ T equal to 0.01(5) GPa K -1. The thermo-baric behavior of blödite appears strongly anisotropic with c lattice parameter being more deformed with respect to a and b. Thermogravimetric analyses performed at ambient pressure showed three endotherms at 413 K, 533 K and 973 K with weight losses of approximately 11%, 11% and 43% caused by partial dehydration, full dehydration and sulfate decomposition respectively. Interestingly, no clear evidence of dehydration was observed up to ~453 K and ~10.4 GPa, suggesting that pressure acts to stabilize the crystalline structure of blödite. The data collected allow to write the following equation of state, V(P, T) = V 0[1 + 7.6(7)10 - 5ΔT - 0.026(3)P - 5.6(9)10 - 6PΔT-6.6(9)10 - 6PΔT)] from which the density

A KPC-Scale X-Ray Jet in the BL Lac Source S5 2007+777

NASA Technical Reports Server (NTRS)

Sambruna, Rita M.; Donato, Davide; Cheung, C.C.; Tavecchio, F.; Maraschi, L.

2008-01-01

X-ray jets in AGN are commonly observed in FRII and FRI radiogalaxies, but rarely in BL Lacs, most probably due to their orientation close to the line of sight and the ensuing foreshortening effects. Only three BL Lacs are known so far to contain a kpc-scale X-ray jet. In this paper, we present the evidence for the existence of a fourth extended X-ray jet in the classical radio-selected source S5 2007+777, which for its hybrid FRI/II radio morphology has been classified as a HYMOR (HYbrid MOrphology Radio source). Our Chandra ACISS observations of this source revealed an X-ray counterpart to the 19"-long radio jet. Interestingly, the X-ray properties of the kpc-scale jet in S5 2007+777 are very similar to those observed in FRII jets. First, the X-ray morphology closely mirrors the radio one, with the X-rays being concentrated in the discrete radio knots. Second, the X-ray continuum of the jet/brightest knot is described by a very hard power law, with photon index gamma(sub x) approximately 1. Third, the optical upper limit from archival HST data implies a concave radio-to-X-ray SED. If the X-ray emission is attributed to IC/CMB with equipartition, strong beaming (delta= 13) is required, implying a very large scale (Mpc) jet. The beaming requirement can be somewhat relaxed assuming a magnetic field lower than equipartition. Alternatively, synchrotron emission from a second population of very high-energy electrons is viable. Comparison to other HYMOR jets detected with Chandra is discussed, as well as general implications for the origin of the FRI/II division.

Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice.

PubMed

Tirelli, E; Witkin, J M

1994-10-01

Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations.

Improving the Expression of Recombinant Proteins in E. coli BL21 (DE3) under Acetate Stress: An Alkaline pH Shift Approach

PubMed Central

Wang, Hengwei; Wang, Fengqing; Wang, Wei; Yao, Xueling; Wei, Dongzhi; Cheng, Hairong; Deng, Zixin

2014-01-01

Excess acetate has long been an issue for the production of recombinant proteins in E. coli cells. Recently, improvements in acetate tolerance have been achieved through the use of genetic strategies and medium supplementation with certain amino acids and pyrimidines. The aim of our study was to evaluate an alternative to improve the acetate tolerance of E. coli BL21 (DE3), a popular strain used to express recombinant proteins. In this work we reported the cultivation of BL21 (DE3) in complex media containing acetate at high concentrations. In the presence of 300 mM acetate, compared with pH 6.5, pH 7.5 improved cell growth by approximately 71%, reduced intracellular acetate by approximately 50%, and restored the expression of glutathione S-transferase (GST), green fluorescent protein (GFP) and cytochrome P450 monooxygenase (CYP). Further experiments showed that alkaline pHs up to 8.5 had little inhibition in the expression of GST, GFP and CYP. In addition, the detrimental effect of acetate on the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) by the cell membrane, an index of cellular metabolic capacity, was substantially alleviated by a shift to alkaline pH values of 7.5–8.0. Thus, we suggest an approach of cultivating E. coli BL21 (DE3) at pH 8.0±0.5 to minimize the effects caused by acetate stress. The proposed strategy of an alkaline pH shift is a simple approach to solving similar bioprocessing problems in the production of biofuels and biochemicals from sugars. PMID:25402470

Improving the expression of recombinant proteins in E. coli BL21 (DE3) under acetate stress: an alkaline pH shift approach.

PubMed

Wang, Hengwei; Wang, Fengqing; Wang, Wei; Yao, Xueling; Wei, Dongzhi; Cheng, Hairong; Deng, Zixin

2014-01-01

Excess acetate has long been an issue for the production of recombinant proteins in E. coli cells. Recently, improvements in acetate tolerance have been achieved through the use of genetic strategies and medium supplementation with certain amino acids and pyrimidines. The aim of our study was to evaluate an alternative to improve the acetate tolerance of E. coli BL21 (DE3), a popular strain used to express recombinant proteins. In this work we reported the cultivation of BL21 (DE3) in complex media containing acetate at high concentrations. In the presence of 300 mM acetate, compared with pH 6.5, pH 7.5 improved cell growth by approximately 71%, reduced intracellular acetate by approximately 50%, and restored the expression of glutathione S-transferase (GST), green fluorescent protein (GFP) and cytochrome P450 monooxygenase (CYP). Further experiments showed that alkaline pHs up to 8.5 had little inhibition in the expression of GST, GFP and CYP. In addition, the detrimental effect of acetate on the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) by the cell membrane, an index of cellular metabolic capacity, was substantially alleviated by a shift to alkaline pH values of 7.5-8.0. Thus, we suggest an approach of cultivating E. coli BL21 (DE3) at pH 8.0 ± 0.5 to minimize the effects caused by acetate stress. The proposed strategy of an alkaline pH shift is a simple approach to solving similar bioprocessing problems in the production of biofuels and biochemicals from sugars.

[Effects of nootropic drugs on behavior of BALB/c and C57BL/6 mice in the exploratory cross-maze test].

PubMed

Vasil'eva, E V; Salimov, R M; Kovalev, G I

2012-01-01

Exploratory behavior, locomotor activity, and anxiety in inbred mice of C57BL/6 and BALB/c strains subchronically treated with placebo or various types of nootropic (cognition enhancing) drugs (piracetam, phenotropil, noopept, semax, pantogam, nooglutil) have been evaluated using the exploratory cross-maze test. It was found that BALB/c mice in comparison to C57BL/6 mice are characterized by greater anxiety and lower efficiency of exploratory behavior in the previously unfamiliar environment. All tested drugs clearly improved the exploratory behavior in BALB/c mice only. In BALB/c mice, piracetam, phenotropil, noopept, and semax also reduced anxiety, while phenotropil additionally increased locomotor activity. Thus, the nootropic drugs displayed clear positive modulation of spontaneous orientation in the mice strain with initially low exploratory efficiency (BALB/c) in the cross-maze test. Some drugs (pantogam, nooglutil) exhibited only nootropic properties, while the other drugs exhibited both nootropic effects on the exploratory activity and produced modulation of the anxiety level (piracetam, fenotropil, noopept, semax) and locomotor activity (fenotropil).

Coffee and caffeine improve insulin sensitivity and glucose tolerance in C57BL/6J mice fed a high-fat diet.

PubMed

Matsuda, Yuji; Kobayashi, Misato; Yamauchi, Rie; Ojika, Makoto; Hiramitsu, Masanori; Inoue, Takashi; Katagiri, Takao; Murai, Atsushi; Horio, Fumihiko

2011-01-01

We have previously demonstrated that coffee and caffeine ameliorated hyperglycemia in spontaneously diabetic KK-A(y) mice. This present study evaluates the antidiabetic effects of coffee and caffeine on high-fat-diet-induced impaired glucose tolerance in C57BL/6J mice. C57BL/6J mice fed a high-fat diet were given regular drinking water (control group), or a 2.5-fold-diluted coffee or caffeine solution (200 mg/L) for 17 weeks. The ingestion of coffee or caffeine improved glucose tolerance, insulin sensitivity, and hyperinsulinemia when compared with mice in the control group. The adipose tissue mRNA levels of inflammatory adipocytokines (MCP-1 and IL-6) and the liver mRNA levels of genes related to fatty acid synthesis were lower in the coffee and caffeine groups than those in the control group. These results suggest that coffee and caffeine exerted an ameliorative effect on high-fat-diet-induced impaired glucose tolerance by improving insulin sensitivity. This effect might be attributable in part to the reduction of inflammatory adipocytokine expression.

Neutrinophilic two Higgs doublet model with dark matter under an alternative U(1)_{B-L} gauge symmetry

NASA Astrophysics Data System (ADS)

Nomura, Takaaki; Okada, Hiroshi

2018-03-01

We propose a Dirac type active neutrino with rank two mass matrix and a Majorana fermion dark matter candidate with an alternative local U(1)_{B-L} extension of neutrinophilic two Higgs doublet model. Our dark matter candidate can be stabilized due to charge assignment under the gauge symmetry without imposing extra discrete Z_2 symmetry and the relic density is obtained from an Z' boson exchanging process. Taking into account collider constraints on the Z' boson mass and coupling, we estimate the relic density.

Genetic Analysis of Ligation-Induced Neointima Formation in an F2 Intercross of C57BL/6 and FVB/N Inbred Mouse Strains

PubMed Central

Östergren, Caroline; Shim, Jeong; Larsen, Jens Vinther; Nielsen, Lars Bo; Bentzon, Jacob F.

2015-01-01

Objective Proliferation and migration of vascular smooth muscle cells (SMCs) are central for arterial diseases including atherosclerosis and restenosis. We hypothesized that the underlying mechanisms may be modeled by carotid ligation in mice. In FVB/N inbred mice, ligation leads to abundant neointima formation with proliferating media-derived SMCs, whereas in C57BL/6 mice hardly any neointima is formed. In the present study, we aimed to identify the chromosomal location of the causative gene variants in an F2 intercross between these two mouse strains. Methods and Results The neointimal cross-sectional area was significantly different between FVB/N, C57BL/6 and F1 female mice 4 weeks after ligation. Carotid artery ligation and a genome scan using 800 informative SNP markers were then performed in 157 female F2 mice. Using quantitative trait loci (QTL) analysis, we identified suggestive, but no genome-wide significant, QTLs on chromosomes 7 and 12 for neointimal cross-sectional area and on chromosome 14 for media area. Further analysis of the cross revealed 4 QTLs for plasma cholesterol, which combined explained 69% of the variation among F2 mice. Conclusions We identified suggestive QTLs for neointima and media area after carotid ligation in an intercross of FVB/N and C57BL/6 mice, but none that reached genome-wide significance indicating a complex genetic architecture of the traits. Genome-wide significant QTLs for total cholesterol levels were identified on chromosomes 1, 3, 9, and 12. PMID:25875831

Structure and dating errors in the geologic time scale and periodicity in mass extinctions

NASA Technical Reports Server (NTRS)

Stothers, Richard B.

1989-01-01

Structure in the geologic time scale reflects a partly paleontological origin. As a result, ages of Cenozoic and Mesozoic stage boundaries exhibit a weak 28-Myr periodicity that is similar to the strong 26-Myr periodicity detected in mass extinctions of marine life by Raup and Sepkoski. Radiometric dating errors in the geologic time scale, to which the mass extinctions are stratigraphically tied, do not necessarily lessen the likelihood of a significant periodicity in mass extinctions, but do spread the acceptable values of the period over the range 25-27 Myr for the Harland et al. time scale or 25-30 Myr for the DNAG time scale. If the Odin time scale is adopted, acceptable periods fall between 24 and 33 Myr, but are not robust against dating errors. Some indirect evidence from independently-dated flood-basalt volcanic horizons tends to favor the Odin time scale.

Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α4/δ GABAA Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice

PubMed Central

Sanna, Enrico; Talani, Giuseppe; Obili, Nicola; Mascia, Maria Paola; Mostallino, Maria Cristina; Secci, Pietro Paolo; Pisu, Maria Giuseppina; Biggio, Francesca; Utzeri, Cinzia; Olla, Pierluigi; Biggio, Giovanni; Follesa, Paolo

2011-01-01

Post-weaning social isolation (SI) is a model of prolonged mild stress characterized by behavioral and neurochemical alterations. We used SI in C57BL/6J mice to investigate the effects of ethanol (EtOH) in the free-choice drinking paradigm on gene expression and function of γ-aminobutyric acid type A receptors (GABAARs) and the role of neuroactive steroids in the actions of EtOH in the hippocampus. SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABAAR. The gene expression of the α4 and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ2 subunit was decreased whereas that of the α1 did not change. Patch-clamp recordings in dentate gyrus (DG) granule cells obtained from SI C57BL/6J mice revealed a greater enhancement of tonic currents induced by α-(4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) compared to that in control C57BL/6J mice. These neurochemical, molecular and functional changes observed in SI C57BL/6J mice were associated with an increased EtOH intake and EtOH preference. Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI. EtOH self-administration blocked the changes in gene expression of the α4 subunit but not those of the δ and γ2 subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABAAR-mediated tonic inhibition in hippocampal granule cells but increased the frequency of basal GABAergic sIPSCs in DG granule cells. We conclude that self-administration of EtOH selectively abolishes the increase of α4 subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress. PMID:21347217

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

PubMed

Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

2014-05-01

Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice

PubMed Central

Iñiguez, Sergio D.; Riggs, Lace M.; Nieto, Steven J.; Dayrit, Genesis; Zamora, Norma N.; Shawhan, Kristi L.; Cruz, Bryan; Warren, Brandon L.

2016-01-01

Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35–44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7–12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence. PMID:24689732

Protective effects of grape stem extract against UVB-induced damage in C57BL mice skin.

PubMed

Che, Denis Nchang; Xie, Guang Hua; Cho, Byoung Ok; Shin, Jae Young; Kang, Hyun Ju; Jang, Seon Il

2017-08-01

Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earth's surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm 2 ) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage. Copyright © 2017. Published by Elsevier B.V.

Fatty liver accompanies an increase of Lactobacillus acidophilus in the hind gut of C57/BL mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

High-fat diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease (NAFLD), which also induces changes in the gut microbiome. This study tested the hypothesis that high-fat feeding increases certain predominate hind gut bacteria in a C57BL/6 mouse model o...

Primary Follicular Dystrophy with Scarring Dermatitis in C57BL/6 Mouse Substrains Resembles Central Centrifugal Cicatricial Alopecia in Humans

PubMed Central

Sundberg, John P.; Taylor, Douglas; Lorch, Gwendolen; Miller, Jim; Silva, Kathleen A.; Sundberg, Beth A.; Roopenian, Derry; Sperling, Leonard; Ong, David; King, Lloyd E.; Everts, Helen

2011-01-01

A number of C57BL/6 (B6) substrains are commonly used by scientists for basic biomedical research. One of several B6 strain specific background diseases is focal alopecia that may resolve or progress to severe, ulcerative dermatitis. Clinical and progressive histologic changes of skin disease commonly observed in C57BL/6J and preliminary studies in other closely related substrains are presented. Lesions develop due to a primary follicular dystrophy with rupture of severely affected follicles leading to formation of secondary foreign body granulomas (trichogranulomas) in affected B6 substrains of mice. Histologically these changes resemble the human disease called central centrifugal cicatrical alopecia (CCCA). Four B6 substrains tested have a polymorphism in alcohol dehydrogenase 4 (Adh4) that reduces its activity and potentially affects removal of excess retinol. Using immunohistochemistry, differential expression of epithelial retinol dehydrogenase (DHRS9) was detected which may partially explain anecdotal reports of frequency differences between B6 substrains. The combination of these two defects have the potential to make high dietary vitamin A levels toxic in some B6 substrains while not affecting most other commonly used inbred strains. PMID:20861494

Denervation affects regenerative responses in MRL/MpJ and repair in C57BL/6 ear wounds

PubMed Central

Buckley, Gemma; Wong, Jason; Metcalfe, Anthony D; Ferguson, Mark W J

2012-01-01

The MRL/MpJ mouse displays the rare ability amongst mammals to heal injured ear tissue without scarring. Numerous studies have shown that the formation of a blastema-like structure leads to subsequent tissue regeneration in this model, indicating many parallels with amphibian limb regeneration and mammalian embryogenesis. We have recently shown that the MRL/MpJ mouse also possesses an enhanced capacity for peripheral nerve regeneration within the ear wound. Indeed, nerves are vital for the initial phase of blastema formation in the amphibian limb. In this study we investigated the capacity for wound regeneration in a denervated ear. The left ears of MRL/MpJ mice and C57BL/6 (a control strain known to have a poorer regenerative capacity) were surgically denervated at the base via an incision and nerve transection, immediately followed by a 2-mm ear punch wound. Immunohistochemical analysis showed a lack of neurofilament expression in the denervated ear wound. Histology revealed that denervation prevented blastema formation and chrondrogenesis, and also severely hindered normal healing, with disrupted re-epithelialisation, increasing wound size and progressive necrosis towards the ear tip. Denervation of the ear obliterated the regenerative capacity of the MRL/MpJ mouse, and also had a severe negative effect on the ear wound repair mechanisms of the C57BL/6 strain. These data suggest that innervation may be important not only for regeneration but also for normal wound repair processes. PMID:22066944

Growth of C57BL/6 mice and the material and mechanical properties of cortical bone from the tibia.

PubMed

Somerville, J M; Aspden, R M; Armour, K E; Armour, K J; Reid, D M

2004-05-01

Murine models are becoming increasingly important for studying skeletal growth and regulation because of the relative ease with which their genomes can be manipulated. This study measured the changes in cortical bone of tibiae from one of the more common models, the C57Bl/6, as a function of aging. A total of 97 mice, male and female, were studied at the ages of 1, 2, 3, 6, 9, and 12 months. The body weight of the animals, the length of the tibiae, the composition (in terms of mineral and organic mass fractions), and the density and modulus of the bone were measured. Peripheral quantitative computed tomography was also used to measure bone mineral density (BMD), total and cortical areas, and the cross-sectional moment of inertia. Most parameters measured followed a growth-like curve, which leveled off some time before 6 months of age. Bone composition and modulus were the same at maturity in both sexes, but there were sex-related differences in the modulus with aging. Dimensional measurements and the density of the bone showed significant differences between male and female animals at all ages, with the male mice having larger values. Skeletal maturity for most factors in C57Bl/6 mice has been reached before the age of 6 months.

The compression behavior of blödite at low and high temperature up to ∼10 GPa: Implications for the stability of hydrous sulfates on icy planetary bodies

NASA Astrophysics Data System (ADS)

Comodi, Paola; Stagno, Vincenzo; Zucchini, Azzurra; Fei, Yingwei; Prakapenka, Vitali

2017-03-01

Recent satellite inferences of hydrous sulfates as recurrent minerals on the surface of icy planetary bodies link with the potential mineral composition of their interior. Blödite, a mixed Mg-Na sulfate, is here taken as representative mineral of icy satellites surface to investigate its crystal structure and stability at conditions of the interior of icy bodies. To this aim we performed in situ synchrotron angle-dispersive X-ray powder diffraction experiments on natural blödite at pressures up to ∼10.4 GPa and temperatures from ∼118.8 K to ∼490.0 K using diamond anvil cell technique to investigate the compression behavior and establish a low-to-high temperature equation of state that can be used as reference when modeling the interior of sulfate-rich icy satellites such as Ganymede. The experimentally determined volume expansivity, α, varies from 7.6 (7) 10-5 K-1 at 0.0001 GPa (from 118.8 to 413.15 K) to 2.6 (3) 10-5 K-1 at 10 GPa (from 313.0 to 453.0 K) with a δα/δP coefficient = -5.6(9)10-6 GPa-1 K-1. The bulk modulus calculated from the least squares fitting of P-V data on the isotherm at 413 K using a second-order Birch - Murnaghan equation of state is 38(5) GPa, which gives the value of δK/δT equal to 0.01(5) GPa K-1. The thermo-baric behavior of blödite appears strongly anisotropic with c lattice parameter being more deformed with respect to a and b. Thermogravimetric analyses performed at ambient pressure showed three endotherms at 413 K, 533 K and 973 K with weight losses of approximately 11%, 11% and 43% caused by partial dehydration, full dehydration and sulfate decomposition respectively. Interestingly, no clear evidence of dehydration was observed up to ∼453 K and ∼10.4 GPa, suggesting that pressure acts to stabilize the crystalline structure of blödite. The data collected allow to write the following equation of state, V(P, T) = V0[1 + 7.6(7)10- 5ΔT - 0.026(3)P - 5.6(9)10- 6PΔT-6.6(9)10- 6PΔT)] from which the density of bl

[The dynamics of behavioral and neuroreceptor effects after acute and long-term noopept administration in C57BL/6 and BALB/c mice].

PubMed

Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

2014-01-01

The effect of acute, 7-fold and 14-fold noopept (1 mg/kg/day) administration on the dynamics of anxiolitic and nootropic behavioral effects in cross-maze, as well as their correlations with NMDA- and BDZ-receptor density was studied in inbred mice strains, differing in exploratory and emotional status--C57BL/6 and BALB/c. The dipeptide failed to affect the anxiety and exploration activity in C57BL/6 mice at each of 3 steps of experimental session. In this strain the B(max) values of [3H]-MK-801 and [3H]-Flunitrazepam binding changed only after single administration. In respect to BALB/c mice noopept induced both the anxiolitic and nootropic effects reaching their maximum on 7th day. In BALB/c strain the dynamics of hippocampal NMDA-receptor binding corresponds to the dynamics of exploratory efficacy whereas the dynamics of BDZ-receptors in prefrontal cortex was reciprocally to dynamics of anxiety level.

Fermi LAT detection of a GeV flare from the high redshift BL Lac object PKS 2131-021

NASA Astrophysics Data System (ADS)

Ciprini, Stefano

2012-08-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed gamma-ray flaring activity from a source positionally consistent with the BL Lac object PKS 2131-021 (also known as 2FGL J2133.8-0154, Nolan et al. 2012, ApJS, 199, 31, and 4C -02.81) placed at radio coordinates R.A.: 323.5429567 deg, Dec.: -1.8881217 deg (J2000, Johnston et al. 1995, AJ, 110, 880).

Toward operation of series IDs at BL43LXU of SPring-8

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

Baron, A. Q. R.; Tanaka, T.; Soutome, K.

2016-07-27

This paper discusses two issues relating to using 3 small gap insertion devices in series at BL43LXU of SPring-8 to make a uniquely powerful source in the 15-26 keV region of the x-ray spectrum. The issues discussed are (1) damage to the covers of the downstream IDs by radiation from the upstream IDs and (2) proper steering of the electron beam to get the best photon beam properties. After tests in several configurations, including one where an ID was run without an impedance-reducing cover, the damage issue was solved by installing a distributed absorber in the most downstream ID. Themore » steering issues were mostly resolved by the introduction of appropriate corrector magnets and feedback. The paper is written from the viewpoint of an interested beamline scientist impressed with the cooperation of different groups to make a source for new science possible.« less

Dietary ribonucleic acid suppresses inflammation of adipose tissue and improves glucose intolerance that is mediated by immune cells in C57BL/6 mice fed a high-fat diet.

PubMed

Sakai, Tohru; Taki, Tomoyo; Nakamoto, Akiko; Tazaki, Shiho; Arakawa, Mai; Nakamoto, Mariko; Tsutsumi, Rie; Shuto, Emi

2015-01-01

Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner.

Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

PubMed

Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

2016-10-15

Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid. Copyright © 2016 Elsevier B.V. All rights reserved.

Fear memory for cue and context: opposite and time-dependent effects of a physiological dose of corticosterone in male BALB/c and C57BL/6J mice.

PubMed

Diamantopoulou, Anastasia; Oitzl, Melly S; Grauer, Ettie

2012-07-23

Highly emotional, stress reactive BALB/c mice secrete more corticosterone in response to fear conditioning than the low stress reactive C57BL/6J mice. Fear memory to cue and context differs between the strains. We injected corticosterone at physiological concentrations (250 μg/kg i.p.) 30 min before fear conditioning. Fear memory was tested 48 and 72 h later. Although corticosterone had little effect on acquisition, it differentially affected fear memories in strain dependent manner: while BALB/c mice decreased freezing during cue and context episodes, C57BL/6J mice showed an overall increase in freezing. BALB/c mice showed extinction over days while no such extinction was seen in C57BL/6J mice. Evaluation of these data in the perspective of previous studies using the same fear conditioning paradigm with corticosterone injections 5 min before or immediately after acquisition, revealed the impact of corticosterone during conditioning on the strength of fear memories. In C57BL/6J mice the overall increase in fear memories was higher if corticosterone was injected 30 min pre acquisition than if injected 5 min pre. In contrast, BALB/c mice showed reduced fear memories when injected 30 min pre compared to that seen 5 min pre acquisition. Both strains showed decreased fear memories compared to vehicle if corticosterone was administered immediately after acquisition. We conclude that the timing of physiologically relevant, stress levels increase in corticosterone is essential for the processing of aversive events and the formation of fear memories. However, the quality of the effect depends on the genetic background. These findings contribute to the understanding of the etiology of stress-related disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Acute Stress Facilitates Trace Eyeblink Conditioning in C57BL/6 Male Mice and Increases the Excitability of Their CA1 Pyramidal Neurons

ERIC Educational Resources Information Center

Weiss, Craig; Sametsky, Evgeny; Sasse, Astrid; Spiess, Joachim; Disterhoft, John F.

2005-01-01

The effects of stress (restraint plus tail shock) on hippocampus-dependent trace eyeblink conditioning and hippocampal excitability were examined in C57BL/6 male mice. The results indicate that the stressor significantly increased the concentration of circulating corticosterone, the amount and rate of learning relative to nonstressed conditioned…

Effect of Cage-Induced Stereotypies on Measures of Affective State and Recurrent Perseveration in CD-1 and C57BL/6 Mice

PubMed Central

Novak, Janja; Bailoo, Jeremy D.; Melotti, Luca; Würbel, Hanno

2016-01-01

Stereotypies are abnormal repetitive behaviour patterns that are highly prevalent in laboratory mice and are thought to reflect impaired welfare. Thus, they are associated with impaired behavioural inhibition and may also reflect negative affective states. However, in mice the relationship between stereotypies and behavioural inhibition is inconclusive, and reliable measures of affective valence are lacking. Here we used an exploration based task to assess cognitive bias as a measure of affective valence and a two-choice guessing task to assess recurrent perseveration as a measure of impaired behavioural inhibition to test mice with different forms and expression levels of stereotypic behaviour. We trained 44 CD-1 and 40 C57BL/6 female mice to discriminate between positively and negatively cued arms in a radial maze and tested their responses to previously inaccessible ambiguous arms. In CD-1 mice (i) mice with higher stereotypy levels displayed a negative cognitive bias and this was influenced by the form of stereotypy performed, (ii) negative cognitive bias was evident in back-flipping mice, and (iii) no such effect was found in mice displaying bar-mouthing or cage-top twirling. In C57BL/6 mice neither route-tracing nor bar-mouthing was associated with cognitive bias, indicating that in this strain these stereotypies may not reflect negative affective states. Conversely, while we found no relation of stereotypy to recurrent perseveration in CD-1 mice, C57BL/6 mice with higher levels of route-tracing, but not bar-mouthing, made more repetitive responses in the guessing task. Our findings confirm previous research indicating that the implications of stereotypies for animal welfare may strongly depend on the species and strain of animal as well as on the form and expression level of the stereotypy. Furthermore, they indicate that variation in stereotypic behaviour may represent an important source of variation in many animal experiments. PMID:27145080

Effect of MCM09, an active site-directed inhibitor of factor Xa, on B16-BL6 melanoma lung colonies in mice.

PubMed

Rossi, C; Hess, S; Eckl, R W; di Lena, A; Bruno, A; Thomas, O; Poggi, A

2006-03-01

Treatment with anticoagulant drugs has shown potential inhibitory effect on tumor invasion, although the relationship with clotting inhibition was not clear. The aim of our study was to evaluate the potential antitumor activity of MCM09, a newly developed, active site-directed, small molecule inhibitor of factor Xa (FXa) [WO0216312], and to relate the findings to anticlotting potency. MCM09 (0.1-10 mg kg(-1)) or heparin (H; 10 mg kg(-1)) was injected intravenously (i.v.), with 5 x 10(4) B16-BL6 melanoma cells, in C57BL/6 mice. Mice were killed after 18 days, to count lung colonies. Ex vivo anticoagulant activity was measured by activated partial thromboplastin time (APTT) on mouse plasma. MCM09, a selective inhibitor of FXa (IC-50 = 2.4 nm against human FXa), inhibited in a dose-dependent manner B16-BL6 melanoma lung colonies in mice. Mean lung metastasis number was 20.9 +/- 4.8 in controls (n = 10), 1.2 +/- 0.4 in mice treated with H, 10 mg kg(-1) i.v. (P < 0.01), 0.9 +/- 0.3, 9.2 +/- 2.2 and 15.5 +/- 2.6 in mice treated with MCM09, at 10 (P < 0.01), 1 (P < 0.05) and 0.1 mg kg(-1) i.v. (ns), respectively. MCM09 (10 mg kg(-1) i.v.) significantly prolonged APTT (57.1 +/- 10.2 s) 30 min after i.v. injection when compared with controls (25.3 +/- 1.6 s; P < 0.05). Lung colonies were 74.2-72.6% reduced by MCM09 (10 mg kg(-1)) given 60 or 120 min before cells, but not by MCM09 given 60 min thereafter, suggesting a direct cell interaction as a mechanism underlying antitumor activity.

Soft X-ray spectrum of BL Lacertae object AO 0235+164 as a tracer of elemental abundances at z approximately 0.5

NASA Technical Reports Server (NTRS)

Madejski, Greg

1994-01-01

We report the soft X-ray spectrum of BL Lac object AO 0235+164, observed with the Einstein Observatory Imaging Proportional Counter (IPC). This object (z = 0.94) has an intervening galaxy (or a protogalactic disk) at z = 0.524 present in the line of sight, producing both radio and optical absorption lines in the background BL Lac continuum. The X-ray spectrum exhibits a substantial soft X-ray cutoff, corresponding to several times that expected from our own Galaxy; we interpret that excess cutoff as due to the intervening galaxy. The comparison of the hydrogen column density inferred from the 21 cm radio data and the X-ray absorption allows, in principle, the determination of the elemental abundances in the intervening galaxy. However, the uncertainties in both the H I spin temperature and X-ray spectral parameters only loosely restrict these abundances to be 2 +/- 1 solar, which even at the lower limit appears higher than that inferred from studies of samples of optical absoprtion-line systems.

OPTICAL SPECTROSCOPY OF SDSS J004054.65-0915268: THREE POSSIBLE SCENARIOS FOR THE CLASSIFICATION. A z ∼ 5 BL LACERTAE, A BLUE FSRQ, OR A WEAK EMISSION LINE QUASAR

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

Landoni, M.; Zanutta, A.; Bianco, A.

2016-02-15

The haunt of high-redshift BL Lacerate objects is day by day more compelling to firmly understand their intrinsic nature and evolution. SDSS J004054.65-0915268 is, at the moment, one of the most distant BL Lac candidates, at z ∼ 5. We present a new optical-near-IR spectrum obtained with ALFOSC-NOT with a new, custom designed dispersive grating aimed to detect broad emission lines that could disprove this classification. In the obtained spectra, we do not detect any emission features and we provide an upper limit to the luminosity of the C iv broad emission line. Therefore, the nature of the object is then discussed,more » building the overall spectral energy distribution (SED) and fitting it with three different models. Our fits, based on SED modeling with different possible scenarios, cannot rule out the possibility that this source is indeed a BL Lac object, though the absence of optical variability and the lack of strong radio flux seem to suggest that the observed optical emission originates from a thermalized accretion disk.« less

Ondas de choque em jatos de quasares e objetos BL Lacertae

NASA Astrophysics Data System (ADS)

Melo, F. E.; Botti, L. C. L.

2003-08-01

Este trabalho é parte de um projeto que vem sendo realizado há dois anos no CRAAM, cujos objetivos principais são analisar e aplicar um modelo generalizado de ondas de choque em jatos relativísticos de plasma, presentes em quasares e objetos BL Lacertae, para explicar a variabilidade observada nestes objetos. O método consiste em uma decomposição de curvas de luz em séries de explosões similares, em várias freqüências, baseando-se em uma evolução espectro-temporal média das explosões. A partir da evolução média, um ajuste de cada explosão é feito com base em equações empíricas, modificando-se apenas parâmetros específicos de cada explosão. Inicialmente o modelo foi aplicado ajustando-se as curvas de luz a explosões delineadas por uma evolução do choque em três estágios, segundo a predominância do processo de emissão: síncrotron, Compton e adiabático. Entretanto, nesta nova fase de projeto, visando uma parametrização mais concisa, uma otimização do algoritmo de ajuste e uma convergência mais rápida, a formulação para cada evento foi assumida com uma evolução em apenas dois estágios: subida e descida. Isto possibilitou uma ótima delineação das curvas de luz das fontes OV236, OJ287, 3C273 e BL Lac, entre 1980 e 2000, nas freqüências 4.8, 8.0, 14.5 e 22 GHz, utilizando-se dados do Observatório da Universidade de Michigan, do Observatório do Itapetinga (Atibaia SP) e do Observatório Metsähovi. Como conclusões importantes, verificou-se que: os parâmetros ajustados descrevem o comportamento do jato; os valores do índice que descreve a expansão do jato sugerem que o mesmo se expande de uma forma não-cônica; o campo magnético é turbulento atrás da frente de choque; e as peculiaridades das explosões são devidas à influência de grandezas tais como o coeficiente da distribuição espectral de energia dos elétrons, a intensidade de campo magnético e o fator de feixe Doppler, no início do choque.

Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

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

Zebedeo, Christian Nash; Davis, Chad; Peña, Cecelia

Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposuremore » to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T{sub H}17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were

BLT-humanized C57BL/6 Rag2-/-γc-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection.

PubMed

Lavender, Kerry J; Pang, Wendy W; Messer, Ronald J; Duley, Amanda K; Race, Brent; Phillips, Katie; Scott, Dana; Peterson, Karin E; Chan, Charles K; Dittmer, Ulf; Dudek, Timothy; Allen, Todd M; Weissman, Irving L; Hasenkrug, Kim J

2013-12-12

The use of C57BL/6 Rag2(-/-)γc(-/-) mice as recipients for xenotransplantation with human immune systems (humanization) has been problematic because C57BL/6 SIRPα does not recognize human CD47, and such recognition is required to suppress macrophage-mediated phagocytosis of transplanted human hematopoietic stem cells (HSCs). We show that genetic inactivation of CD47 on the C57BL/6 Rag2(-/-)γc(-/-) background negates the requirement for CD47-signal recognition protein α (SIRPα) signaling and induces tolerance to transplanted human HSCs. These triple-knockout, bone marrow, liver, thymus (TKO-BLT) humanized mice develop organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissue that demonstrate high levels of multilineage hematopoiesis. Importantly, these mice have an intact complement system and showed no signs of graft-versus-host disease (GVHD) out to 29 weeks after transplantation. Sustained, high-level HIV-1 infection was observed via either intrarectal or intraperitoneal inoculation. TKO-BLT mice exhibited hallmarks of human HIV infection including CD4(+) T-cell depletion, immune activation, and development of HIV-specific B- and T-cell responses. The lack of GVHD makes the TKO-BLT mouse a significantly improved model for long-term studies of pathogenesis, immune responses, therapeutics, and vaccines to human pathogens.

Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii

PubMed

Babaie, Jalal; Amiri, Samira; Homayoun, Robab; Azimi, Ebrahim; Mohabati, Reyhaneh; Berizi, Mahboobe; Sadaie, M. Reza; Golkar, Majid

2018-01-01

We have previously reported that immunization with GRA2 antigen of Toxoplasma gondii induces protective immunity in CBA/J (H2k) and BALB/c mice (H2d). We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against T. gondii. C57BL/6 (H2b haplotype) mice were immunized with GRA2, formulated in MPL adjuvant. Strong humoral response, predominantly of IgG1 subclass and cellular response, IFN-γ, was detected at three weeks post immunization. Mice immunized with GRA2 had significantly (p < 0.01) fewer brain cysts than those in the adjuvant group, upon challenge infection. Despite the production of a strong antibody response, IFN-γ production and brain cyst reduction were not significant when the immunized mice were infected four months after the immunization. We can conclude that GRA2 immunization partially protects against T. gondii infection in C57BL/6 mice, though the potency and longevity of this antigen as a standalone vaccine may vary in distinct genetic backgrounds. This observation further emphasizes the utility of GRA2 for incorporation into a multi-antigenic vaccine against T. gondii.

Voluntary running of defined distances reduces body adiposity and its associated inflammation in C57BL/6 mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

A sedentary lifestyle contributes to obesity. This study determined the effects of quantitative voluntary running on body adiposity and its associated inflammation in mice fed a high-fat diet. Male C57BL/6 mice were assigned to six groups and fed an AIN93G (sedentary) or a high-fat diet (sedentary...

Protective effect of Lagerstroemia speciosa against dextran sulfate sodium induced ulcerative colitis in C57BL/6 mice.

PubMed

Chaudhary, Ghanshyam; Mahajan, Umesh B; Goyal, Sameer N; Ojha, Shreesh; Patil, Chandragouda R; Subramanya, Sandeep B

2017-01-01

The protective effect of methanolic extract of Lagerstroemia speciosaleaves (LS) was evaluated against dextran sulfate sodium (DSS) induced ulcerative colitis in C57BL/6 mice. The administration of DSS (2.5% in drinking water ad libitum) in C57BL/6 mice induced ulcerative colitis in 7 days. The LS was orally administered for 7 days at daily doses of 100 and 200 mg/kg. At the end of 7 days of treatment the animals were sacrificed, colonic tissues were removed and processed for further analysis of oxidative stress, and histopathology. In DSS treated mice the oxidative stress markers were elevated compared to controls. There was also significant reduction in the anti-oxidant defense levels marked by reduced cellular glutathione, catalase, and superoxide dismutase. The DSS-induced damage to the colon epithelium was evident from a significant increase in the lipid peroxidation. The histology of colon sections revealed inflammatory changes and marked impairment in the integrity of the mucosal lining with inflammatory changes. Both the doses of LS significantly prevented DSS-induced inflammatory and ulcerative damages of the colon, reduced lipid peroxidation and also restored the levels of innate antioxidants in the colon tissue. These findings indicate the protective effects of LS against the DSS-induced inflammatory and oxidative damage in the mouse colon. Further investigation involving bioactivity guided fractionation of the LS can yield potent constituent which may have a significant role in the treatment of inflammatory bowel disease and ulcerative colitis.

Performance of a Highly Stabilized and High-resolution Beamline BL17SU for Advanced Soft X-ray Spectroscopy at SPring-8

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

Ohashi, Haruhiko; Tanaka, Takashi; Kitamura, Hideo

2007-01-19

A new soft x-ray beamline BL17SU (RIKEN) has been constructed at SPring-8. The beamline consists of two branches with each varied-line-spacing-plane-grating-monochromator. Both monochromators perform high energy resolution (E/{delta}E > 10,000) between 0.2 and 1 keV. One of the monochromator achieves high energy stability of 10 meV over a period of half a day.

C57BL/6 Substrains Exhibit Different Responses to Acute Carbon Tetrachloride Exposure: Implications for Work Involving Transgenic Mice

PubMed Central

McCracken, Jennifer M.; Chalise, Prabhakar; Briley, Shawn M.; Dennis, Katie L.; Jiang, Lu; Duncan, Francesca E.; Pritchard, Michele T.

2017-01-01

Biological differences exist between strains of laboratory mice, and it is becoming increasingly evident that there are differences between substrains. In the C57BL/6 mouse, the primary substrains are called 6J and 6N. Previous studies have demonstrated that 6J and 6N mice differ in response to many experimental models of human disease. The aim of our study was to determine if differences exist between 6J and 6N mice in terms of their response to acute carbon tetrachloride (CCl4) exposure. Mice were given CCl4 once and were euthanized 12 to 96 h later. Relative to 6J mice, we found that 6N mice had increased liver injury but more rapid repair. This was because of the increased speed with which necrotic hepatocytes were removed in 6N mice and was directly related to increased recruitment of macrophages to the liver. In parallel, enhanced liver regeneration was observed in 6N relative to 6J mice. Hepatic stellate cell activation occurred earlier in 6N mice, but there was no difference in matrix metabolism between substrains. Taken together, these data demonstrate specific and significant differences in how the C57BL/6 substrains respond to acute CCl4, which has important implications for all mouse studies utilizing this model. PMID:28234577

Fermi-LAT detection of a GeV flare from the BL Lac object 1ES 2322-409

NASA Astrophysics Data System (ADS)

Ciprini, Stefano

2013-10-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed an increasing gamma-ray flux from a source positionally consistent with the BL Lac object 1ES 2322-409 (also know as 2FGL J2324.7-4042, Nolan et al. 2012, ApJS, 199, 31, and as 1FHL J2324.6-4041, Ackermann et al., ApJS, submitted, arXiv:1306.6772), with 2MASS counterpart coordinates, (J2000.0), R.A.: 351.18612 deg, Dec: -40.68036 deg (Mao 2011, New Ast., 16, 503).

Toyota beamline (BL33XU) at SPring-8

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

Nonaka, T., E-mail: nonaka@mosk.tytlabs.co.jp; Dohmae, K.; Hayashi, Y.

2016-07-27

The Toyota beamline (BL33XU) at SPring-8 is an undulator beamline developed to assist in the study of various automotive-related materials. The light source is a tapered in-vacuum undulator that provides a variable energy band width as well as a high brilliance X-ray beam. Two different optical arrangements are available: Optics 1 and Optics 2. Optics 1 is dedicated to time-resolved X-ray absorption spectroscopy (XAFS), and consists of two channel-cut crystal monochromators and four water-cooled flat Si mirrors. The Si(111) and Si(220) monochromator crystals cover an energy range of 4.0–46.0 keV and are driven by high-speed AC servo motors. These monochromators,more » in conjunction with the tapered undulator, enable high-quality XAFS data acquisition with a temporal resolution of 10 ms. Optics 2 is optimized for X-ray diffraction, scattering and imaging and includes a recently installed double crystal monochromator, two water-cooled flat Si mirrors and Kirkpatrick-Baez (KB) focusing mirrors. The monochromator incorporates parallel mounted Si(111) and Si(311) crystals and covers an energy range of 4.5–70 keV. The beamline provides two experimental stations: Exp. Hutch 2 and Exp. Hutch 3. The gas supply system and mass spectrometers installed in Exp. Hutch 2 allow in-operando measurements under various atmospheres. The scanning three-dimensional X-ray diffraction (scanning 3DXRD) microscopy instrumentation developed and installed in Exp. Hutch 3 enables non-destructive orientation and stress mapping of 1 mm-thick steel specimens using a high energy microbeam.« less

Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity

PubMed Central

Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M.; Park, Jin-Byung

2016-01-01

The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass. PMID:27681369

Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

PubMed

Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

PKS 2155-304 relativistically beamed synchrotron radiation from BL LAC object

NASA Technical Reports Server (NTRS)

Urry, C. M.; Mushotzky, R. F.

1981-01-01

The newly discovered BL Lacertae object, PKS 2155-304, was observed with the medium and high intensity energy detectors of the HEAO-1 A2 experiment. The variability by a factor of two in less than a day reported by Snyder, et al (1979) is confirmed. Two spectra, obtained a year apart, while the satellite was in scanning mode, are well fit by simple power laws with energy spectral index alpha sub 1 equals approximately 1.4. A third spectrum, of higher statistical quality, obtained while the satellite was pointed at its source, has has two components. An acceptable fit was obtained using a two power law model, with indices alpha sub 1 equals 2.0 (+1.2, -0.6) and alpha sub 2 equals -1.5 (+1.5, -2.3). An interpretation of the overall spectrum from radio through X-rays in terms of a synchrotron self-Compton model gives a good description of the data if allowance is made for relativistic beaming. Thus, from a consideration of the spectrum, combined with an estimate of the size of the source, the presence of jets is inferred without their observation.

The effects of intraperitoneal administration of the GABA(B) receptor agonist baclofen on food intake in CFLP and C57BL/6 mice.

PubMed

Ebenezer, Ivor S; Prabhaker, Monika

2007-08-13

The effects of the GABA(B) receptor agonist baclofen were investigated on food intake in non-deprived CFLP and C57BL/6 mice. In Experiment 1, baclofen (1-8 mg /kg) administered i.p. to CFLP mice, produced a dose-related increase in food intake. The 4 and 8 mg/kg doses produced significant increases in cumulative feeding when measure 120 min after administration (at least P < 0.05, in each case). In Experiment 2, baclofen (1-10 mg/kg), administered intraperitoneally (i.p.) to C57BL/6 mice, also produced a dose-related increase in food intake. The 4 mg/kg dose of baclofen significantly increased cumulative food intake at 60 min (P < 0.05), while the 2 and 4 mg/kg doses significantly increased cumulative food intake at 120 min (P < 0.01, in each case). The 10mg/kg dose was without effect. These data show that systemic administration of the GABA(B) agonist baclofen produces an increase in food consumption in two different strains of mice and extend previous observations made in rat to another rodent species.

Autoantibody response and pregnancy-related pathology induced by combined LPS and tetanus toxoid hyperimmunization in BALB/c and C57BL/6 mice.

PubMed

Petrušić, Vladimir; Todorović, Nevena; Živković, Irena; Dimitrijević, Rajna; Muhandes, Lina; Rajnpreht, Irena; Dimitrijević, Ljiljana

2015-03-01

Recent data concerning antiphospholipid syndrome (APS) induction have shown that β2-glycoprotein I (β2GPI) binds lipopolysaccharide (LPS), which results in conformational changes, exposition of a cryptic epitope and possible pathological anti-β2GPI antibody production. In order to investigate the effects of LPS on the induction of APS-related pathology, we performed hyperimmunization of BALB/c and C57BL/6 mice with LPS, alone or in combination with tetanus toxoid (TTd), a protein structurally similar to β2GPI. We report that, although high affinity pathological anti-β2GPI antibodies were produced in all groups of animals, the reproductive pathology was recorded only in mice that received both LPS and TTd, implying on the important roles of both infections and molecular mimicry in APS pathogenesis. Moreover, APS-related reproductive pathology was more pronounced in BALB/c (lowered fertility and fecundity) than C57BL/6 mice (lowered fecundity), which correlated well with the disruption in natural antibody network observed in BALB/c mouse strain.

Vernonia cinerea Less. inhibits tumor cell invasion and pulmonary metastasis in C57BL/6 mice.

PubMed

Pratheeshkumar, Poyil; Kuttan, Girija

2011-06-01

The effect of Vernonia cinerea Less. extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. V cinerea extract significantly (P < .001) inhibited lung tumor formation (78.8%) and significantly increased the life span (72.5%). Moreover, lung collagen hydroxyproline, uronic acid, and hexosamine and also serum sialic acid, γ-glutamyltransferase (GGT), and vascular endothelial growth factor (VEGF) levels were found to be significantly (P < .001) lower in treated animals compared with untreated controls. Histopathological analysis of the lung tissues also correlated with these findings. V cinerea treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix of the Boyden chamber. V cinerea also inhibited the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. It downregulated the production and expression of proinflammatory cytokines such as TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, and GM-CSF (granulocyte monocyte colony-stimulating factor). V cinerea extract administration could suppress or downregulate the expression of matrix metalloproteinase (MMP)-2, MMP-9, lysyl oxidase, prolyl hydroxylase, K-ras, extracellular signal-regulated kinase (ERK)-1, ERK-2, and VEGF and also upregulate the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP-1), and TIMP-2 in the lung tissue of metastasis-induced animals. It also inhibited the protein expression of MMP-2 and MMP-9 in gelatin zymographic analysis of B16F-10 cells. These results indicate that V cinerea could inhibit the metastatic progression of B16F-10 melanoma cells in C57BL/6 mice by regulating MMPs, VEGF, prolyl hydroxylase, lysyl oxidase, ERK-1, ERK-2, TIMPs, nm23, and proinflammatory cytokine gene expression in metastatic lung tissue.

Dietary fiber prevents obesity-related liver lipotoxicity by modulating sterol-regulatory element binding protein pathway in C57BL/6J mice fed a high-fat/cholesterol diet.

PubMed

Han, Shufen; Jiao, Jun; Zhang, Wei; Xu, Jiaying; Wan, Zhongxiao; Zhang, Weiguo; Gao, Xiaoran; Qin, Liqiang

2015-10-29

Adequate intake of dietary fibers has proven metabolic and cardiovascular benefits, molecular mechanisms remain still limited. This study was aimed to investigate the effects of cereal dietary fiber on obesity-related liver lipotoxicity in C57BL/6J mice fed a high-fat/cholesterol (HFC) diet and underlying mechanism. Forty-eight adult male C57BL/6J mice were randomly given a reference chow diet, or a high fat/cholesterol (HFC) diet supplemented with or without oat fiber or wheat bran fiber for 24 weeks. Our results showed mice fed oat or wheat bran fiber exhibited lower weight gain, lipid profiles and insulin resistance, compared with HFC diet. The two cereal dietary fibers potently decreased protein expressions of sterol regulatory element binding protein-1 and key factors involved in lipogenesis, including fatty acid synthase and acetyl-CoA carboxylase in target tissues. At molecular level, the two cereal dietary fibers augmented protein expressions of peroxisome proliferator-activated receptor alpha and gamma, liver X receptor alpha, and ATP-binding cassette transporter A1 in target tissues. Our findings indicated that cereal dietary fiber supplementation abrogated obesity-related liver lipotoxicity and dyslipidemia in C57BL/6J mice fed a HFC diet. In addition, the efficacy of oat fiber is greater than wheat bran fiber in normalizing these metabolic disorders and pathological profiles.

Dietary fiber prevents obesity-related liver lipotoxicity by modulating sterol-regulatory element binding protein pathway in C57BL/6J mice fed a high-fat/cholesterol diet

PubMed Central

Han, Shufen; Jiao, Jun; Zhang, Wei; Xu, Jiaying; Wan, Zhongxiao; Zhang, Weiguo; Gao, Xiaoran; Qin, Liqiang

2015-01-01

Adequate intake of dietary fibers has proven metabolic and cardiovascular benefits, molecular mechanisms remain still limited. This study was aimed to investigate the effects of cereal dietary fiber on obesity-related liver lipotoxicity in C57BL/6J mice fed a high-fat/cholesterol (HFC) diet and underlying mechanism. Forty-eight adult male C57BL/6J mice were randomly given a reference chow diet, or a high fat/choleserol (HFC) diet supplemented with or without oat fiber or wheat bran fiber for 24 weeks. Our results showed mice fed oat or wheat bran fiber exhibtied lower weight gain, lipid profiles and insulin resistance, compared with HFC diet. The two cereal dietary fibers potently decreased protein expressions of sterol regulatory element binding protein-1 and key factors involved in lipogenesis, including fatty acid synthase and acetyl-CoA carboxylase in target tissues. At molecular level, the two cereal dietary fibers augmented protein expressions of peroxisome proliferator-activated receptor alpha and gamma, liver X receptor alpha, and ATP-binding cassette transporter A1 in target tissues. Our findings indicated that cereal dietary fiber supplementation abrogated obesity-related liver lipotoxicity and dyslipidemia in C57BL/6J mice fed a HFC diet. In addition, the efficacy of oat fiber is greater than wheat bran fiber in normalizing these metabolic disorders and pathological profiles. PMID:26510459

ODIN-object-oriented development interface for NMR.

PubMed

Jochimsen, Thies H; von Mengershausen, Michael

2004-09-01

A cross-platform development environment for nuclear magnetic resonance (NMR) experiments is presented. It allows rapid prototyping of new pulse sequences and provides a common programming interface for different system types. With this object-oriented interface implemented in C++, the programmer is capable of writing applications to control an experiment that can be executed on different measurement devices, even from different manufacturers, without the need to modify the source code. Due to the clear design of the software, new pulse sequences can be created, tested, and executed within a short time. To post-process the acquired data, an interface to well-known numerical libraries is part of the framework. This allows a transparent integration of the data processing instructions into the measurement module. The software focuses mainly on NMR imaging, but can also be used with limitations for spectroscopic experiments. To demonstrate the capabilities of the framework, results of the same experiment, carried out on two NMR imaging systems from different manufacturers are shown and compared with the results of a simulation.

Socially dominant mice in C57BL6 background show increased social motivation.

PubMed

Kunkel, Thaddeus; Wang, Hongbing

2018-01-15

A series of behavioral tests measuring social dominance, social motivation, and non-social motivation are examined in adult male C57BL6 mice. By using the well-known tube dominance test to determine social dominance and rank, we find that, in the absence of competition for resource and mating, group-housed mouse cage-mates display stable and mostly linear and transitive social hierarchies. Mice with top and bottom social ranks are subjected to a three-chamber social interaction test to measure social motivation. The top ranked mice spend more time interacting with a stranger mouse than the bottom ranked mice, suggesting that social dominance may positively influence social motivation. When subjected to a novel environment, mice with different social ranks show similar locomotion and exploring activity in the open field test, suggesting no detectable difference in certain aspects of non-social motivation. These results demonstrate a behavioral correlation between social dominance and social motivation. Copyright © 2017 Elsevier B.V. All rights reserved.

CATALOG AND STATISTICAL STUDY OF X-RAY SELECTED BL LACERTAE OBJECTS

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

Kapanadze, Bidzina Z., E-mail: bidzina_kapandaze@iliauni.edu.ge

2013-02-01

This paper presents a catalog of 312 X-ray selected BL Lacerate objects (XBLs), optically identified through the end of 2011. It contains the names from different surveys, equatorial coordinates, redshifts, multifrequency flux values, and luminosities for each source. In addition, the different characteristics of XBLs are statistically investigated (redshift, radio/optical/X-ray luminosities, central black hole (BH) mass, synchrotron peak frequency, broadband spectral indices, optical flux variability). Their values are collected through an extensive bibliographic and database search or calculated by us. The redshifts range from 0.031 to 0.702 with a maximum of the distribution at z = 0.223. The 1.4 GHzmore » luminosities of XBLs log {nu}L{sub {nu}} {approx} 39-42 erg s{sup -1} while optical V and X-ray 0.1-2.4 keV bands show log {nu}L{sub {nu}} {approx} 43-46 erg s{sup -1}. The XBL hosts are elliptical galaxies with effective radii r{sub eff} = 3.2625.40 kpc and ellipticities, in = 0.040.52. Their R-band absolute magnitudes M{sub R} range from -21.11 mag to -24.86 mag with a mean value of -22.83 mag. The V - R indices of the hosts span from 0.61 to 1.52 and reveal a fourth-degree polynomial relationship with z that enables us to evaluate the redshifts of five sources whose V - R indices were determined from the observations but whose irredshifts values are either not found or not confirmed. The XBL nuclei show a wider range of 7.31 mag for M{sub R} with the highest luminosity corresponding to M{sub R} = -27.24 mag. The masses of central BHs are found in the interval log M{sub BH} = 7.39-9.30 solar masses (with distribution maximum at log M{sub BH}/M{sub Sun} = 8.30). The synchrotron peak frequencies are spread over the range log {nu}{sub peak} = 14.56-19.18 Hz with a peak of the distribution at log {nu}{sub peak} = 16.60 Hz. The broadband radio-to-optical ({alpha}{sub ro}), optical-to-X-ray ({alpha}{sub ox}), and radio-to-X-ray ({alpha}{sub rx}) spectral indices

Tributyltin induces distinct effects on cortical and trabecular bone in female C57Bl/6J mice.

PubMed

Watt, James; Baker, Amelia H; Meeks, Brett; Pajevic, Paola D; Morgan, Elise F; Gerstenfeld, Louis C; Schlezinger, Jennifer J

2018-09-01

The retinoid X receptors (RXR), peroxisome proliferator activated receptor gamma (PPARγ), and liver X receptors (LXR) all have been shown to regulate bone homeostasis. Tributyltin (TBT) is an environmental contaminant that is a dual RXRα/β and PPARγ agonist. TBT induces RXR, PPARγ, and LXR-mediated gene transcription and suppresses osteoblast differentiation in vitro. Bone marrow multipotent mesenchymal stromal cells derived from female C57BL/6J mice were more sensitive to suppression of osteogenesis by TBT than those derived from male mice. In vivo, oral gavage of 12 week old female, C57Bl/6J mice with 10 mg/kg TBT for 10 weeks resulted in femurs with a smaller cross-sectional area and thinner cortex. Surprisingly, TBT induced significant increases in trabecular thickness, number, and bone volume fraction. TBT treatment did not change the Rankl:Opg RNA ratio in whole bone, and histological analyses showed that osteoclasts in the trabecular space were minimally reduced. In contrast, expression of cardiotrophin-1, an osteoblastogenic cytokine secreted by osteoclasts, increased. In primary bone marrow macrophage cultures, TBT marginally inhibited the number of osteoclasts that differentiated, in spite of significantly suppressing expression of osteoclast markers Nfatc1, Acp5, and Ctsk and resorptive activity. TBT induced expression of RXR- and LXR-dependent genes in whole bone and in vitro osteoclast cultures. However, only an RXR antagonist, but not an LXR antagonist, significantly inhibited TBTs ability to suppress osteoclast differentiation. These results suggest that TBT has distinct effects on cortical versus trabecular bone, likely resulting from independent effects on osteoblast and osteoclast differentiation that are mediated through RXR. © 2018 Wiley Periodicals, Inc.

Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-alpha and translocating PKC-delta.

PubMed

Zhang, Xian-Ming; Chen, Jia; Xia, Yu-Gui; Xu, Qiang

2005-03-01

In our previous study, quercetin was found to induce apoptosis of murine melanoma B16-BL6 cells. The cellular and molecular mechanism of quercetin-induced apoptosis was investigated in the present study. Nuclear morphology was determined by fluorescence microscopy. DNA fragmentation was analyzed by electrophoresis and quantified by the diphenylamine method. The transmembrane potential of mitochondria was measured by flow cytometry. Bcl-2, Bcl-X(L), PKC-alpha, PKC-beta, and PKC-delta were detected by Western blotting. Caspase activity was determined spectrophotometrically. Quercetin induced the condensation of nuclei of B16-BL6 cells in a dose-dependent pattern as visualized by Hoechst 33258 and propidium iodide dying. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, significantly enhanced apoptosis induced by quercetin, while doxorubicin, a PKC inhibitor, markedly decreased it. Both PMA and doxorubicin showed a consistent effect on the fragmentation of nuclear DNA caused by various dosages of quercetin. Quercetin dose-dependently led to loss of the mitochondrial membrane potential, which was also significantly reinforced or antagonized by PMA and doxorubicin, respectively. Moreover, PMA showed reinforcement, while doxorubicin showed significant antagonization, of the quercetin-mediated decrease in the expression of Bcl-2. Quercetin promoted caspase-3 activity in a dose-dependent manner, which was also regulated by PMA and doxorubicin with a pattern similar to that seen in their effect on apoptosis, mitochondrial membrane potential and Bcl-2 expression, but none of these were directly affected by PMA and doxorubicin. Free fatty acid and chlorpromazine, a PKC activator and inhibitor, respectively, did not interfere with these effects of quercetin. B16-BL6 cells expressed PKC-alpha, PKC-beta, and PKC-delta. Quercetin dose-dependently inhibited the expression of PKC-alpha but not that of PKC-beta and PKC-delta. Doxorubicin almost completely blocked the effect of

The compression behavior of blödite at low and high temperature up to ~10GPa: Implications for the stability of hydrous sulfates on icy planetary bodies

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

Comodi, Paola; Stagno, Vincenzo; Zucchini, Azzurra

Recent satellite inferences of hydrous sulfates as recurrent minerals on the surface of icy planetary bodies link with the potential mineral composition of their interior. Blödite, a mixed Mg-Na sulfate, is here taken as representative mineral of icy satellites surface to investigate its crystal structure and stability at conditions of the interior of icy bodies. To this aim we performed in situ synchrotron angle-dispersive X-ray powder diffraction experiments on natural blödite at pressures up to ~10.4 GPa and temperatures from ~118.8 K to ~490.0 K using diamond anvil cell technique to investigate the compression behavior and establish a low-to-high temperaturemore » equation of state that can be used as reference when modeling the interior of sulfate-rich icy satellites such as Ganymede.« less

Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J mice.

PubMed

Lamming, Dudley W; Baar, Emma L; Arriola Apelo, Sebastian I; Tosti, Valeria; Fontana, Luigi

2017-12-07

Recently, it has become apparent that dietary macronutrient composition has a profound impact on metabolism, health and even lifespan. Work from many laboratories now suggest that dietary protein quality - the precise amino acid composition of the diet, as well as possibly the source of dietary protein - may also be critical in regulating the impact of diet on health. Perhaps in part due to the naturally low methionine content of plants, vegan diets are associated with a decreased risk of diabetes and improved insulin sensitivity, but this association is confounded by the lower overall protein intake of vegans. Here, we test the effect of consuming isocaloric rodent diets with similar amino acid profiles derived from either plant protein or dairy protein. We find that male C57BL/6J mice consuming either diet have similar glycemic control, as assessed by glucose, insulin, and pyruvate tolerance tests, and have similar overall body composition. We conclude that short-term feeding of plant protein has no positive or negative effect on the metabolic health of young male C57BL/6J mice, and suggest that dietary interventions that alter either dietary protein levels or the levels of specific essential amino acids are more likely to improve metabolic health than alterations in dietary protein source.

Absolute Enumeration of Probiotic Strains Lactobacillus acidophilus NCFM® and Bifidobacterium animalis subsp. lactis Bl-04 ® via Chip-Based Digital PCR.

PubMed

Hansen, Sarah J Z; Morovic, Wesley; DeMeules, Martha; Stahl, Buffy; Sindelar, Connie W

2018-01-01

The current standard for enumeration of probiotics to obtain colony forming units by plate counts has several drawbacks: long time to results, high variability and the inability to discern between bacterial strains. Accurate probiotic cell counts are important to confirm the delivery of a clinically documented dose for its associated health benefits. A method is described using chip-based digital PCR (cdPCR) to enumerate Bifidobacterium animalis subsp. lactis Bl-04 and Lactobacillus acidophilus NCFM both as single strains and in combination. Primers and probes were designed to differentiate the target strains against other strains of the same species using known single copy, genetic differences. The assay was optimized to include propidium monoazide pre-treatment to prevent amplification of DNA associated with dead probiotic cells as well as liberation of DNA from cells with intact membranes using bead beating. The resulting assay was able to successfully enumerate each strain whether alone or in multiplex. The cdPCR method had a 4 and 5% relative standard deviation (RSD) for Bl-04 and NCFM, respectively, making it more precise than plate counts with an industry accepted RSD of 15%. cdPCR has the potential to replace traditional plate counts because of its precision, strain specificity and the ability to obtain results in a matter of hours.

Sex differences in response to activity-based anorexia model in C57Bl/6 mice.

PubMed

Achamrah, Najate; Nobis, Séverine; Goichon, Alexis; Breton, Jonathan; Legrand, Romain; do Rego, Jean Luc; do Rego, Jean Claude; Déchelotte, Pierre; Fetissov, Sergueï O; Belmonte, Liliana; Coëffier, Moïse

2017-03-01

Anorexia nervosa is a severe eating disorder often associated with physical hyperactivity and is more frequently observed in female sex. Activity-Based Anorexia (ABA) model combines physical activity (PA) and reduced food intake and thus allows a better understanding of the mechanisms underlying anorexia nervosa. We aimed to assess sex differences in response to ABA model in C57Bl/6 mice. Twenty four male and 16 female C57BL/6 mice were studied. ABA mice were placed in individual cages with a continuously recorded activity wheel. ABA mice had a progressive limited food access from 6h/day (day 6) to 3h/day (day 9) until the end of the protocol (day 17). Body weight and food intake were daily measured. We studied physical activity during 24h, during the dark phase (D-PA) and the light phase (L-PA). We also evaluated the feeding anticipatory physical activity (A-PA), the physical activity during food intake period (FI-PA) and the post-prandial physical activity (PP-PA). We observed 16.7% of mortality in males (4 out of 24 mice) during ABA protocol while no female mice died (p=0.09). At day 17, food intake was significantly higher in females than in males (p<0.05) that was associated with a lower body weight loss than in females (p<0.05). Before limited food access, no gender differences in wheel running activity were observed. From day 9, A-PA significantly increased over time in males (p<0.05 vs females) while females exhibited higher FI-PA and PP-PA (p<0.05 vs males). Correlations between wheel running activities and, respectively, food intake and body weight loss showed gender differences, in particularly for L-PA and A-PA. Our results suggest a greater susceptibility of male mice to develop ABA, males and females exhibit different patterns of physical activity after limitation of food access. Underlying mechanisms should be further investigated. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing effects of BL67 points stimulation on fetal heart rate parameters and fetal movements during nonstress test.

PubMed

Pirhadi, Masume; Valiani, Mahboube

2017-01-01

One of the main goals of antenatal testing is to identify fetuses at the risk of neurologic injury or death so that these adverse outcomes can be prevented. We want to assess the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements during nonstress test (NST). We did a quasi-experimental design in Shahid Beheshti Hospital in Isfahan in 2011. This study aims to assessment of the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements. We did a randomized controlled clinical trial in Shahid Beheshti Hospital in Isfahan in 2011. This study is a quasi-experimental design that was conducted in one group and the two steps (before-after study). Participants were pregnant women (primigravida) who were 35-18 years that refer to Shahid Beheshti Hospital in Isfahan in 2011 to receive routine prenatal care. The 32 pregnant women were selected for acupressure during the second NST. The statistical processing was performed by descriptive, paired t -test through SPSS version 20. There was no significant difference in mean number of accelerations in fetal heart rate and mean number of fetal movement before and after intervention; however, there was a significant difference in mean time to the second acceleration before and after the intervention ( P = 0.04). No difference between parameters of the fetal heart rate before and after stimulation and lack of uterine response by this method is a significant advantage and is probably why stimulating this point could not create a risk to the fetuses.

Sweet and bitter taste of ethanol in C57BL/6J and DBA2/J mouse strains.

PubMed

Blizard, David A

2007-01-01

Studies of inbred strains of rats and mice have suggested a positive association between strain variations in sweet taste and ethanol intake. However, strain associations by themselves are insufficient to support a functional link between taste and ethanol intake. We used conditioned taste aversion (CTA) to explore the sweet and bitter taste of ethanol and ability to detect sucrose, quinine and ethanol in C57BL/6J (B6) and DBA/2J (D2) mouse strains that are frequently used in alcohol research. The present study showed that C57BL/6J mice generalized taste aversions from sucrose and quinine solutions to 10% ethanol and, reciprocally, aversions to 10% ethanol generalized to each of these solutions presented separately. Only conditioned aversions to quinine generalized to ethanol in the DBA/2J strain but an aversion conditioned to ethanol did not generalize reciprocally to quinine. Thus, considering these two gustatory qualities, 10% ethanol tastes both sweet and bitter to B6 mice but only bitter to D2. Both strains were able to generalize taste aversions across different concentrations of the same compound. B6 were able to detect lower concentrations of quinine than D2 but both strains were able to detect sucrose and (in contrast to previous findings) ethanol at similar concentrations. The strain-dependent gustatory profiles for ethanol may make an important contribution to the understanding of the undoubtedly complex mechanisms influencing high ethanol preference of B6 and pronounced ethanol avoidance of D2 mice.

The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice.

PubMed

Ingvorsen, C; Karp, N A; Lelliott, C J

2017-04-10

Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes.

The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice

PubMed Central

Ingvorsen, C; Karp, N A; Lelliott, C J

2017-01-01

Background: Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. Methods: We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. Results: HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. Conclusion: HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes. PMID:28394359

In vivo induction of autophagy in splenocytes of C57BL/6 and BALB/c mice infected with ectromelia orthopoxvirus.

PubMed

Martyniszyn, L; Szulc-Dabrowska, L; Boratyńska-Jasińska, A; Badowska-Kozakiewicz, A M; Niemiałtowski, M G

2013-01-01

Autophagy is a self-degradation process of cellular components. It plays both antiviral and pro-viral roles in the life cycle of different viruses and the pathogenesis of different viral diseases. In this study, we evaluated autophagy induction in splenocytes of ectromelia virus (ECTV)-resistant C57BL/6 and ECTV-susceptible BALB/c mice during infection with the Moscow strain of the ectromelia virus (ECTV-MOS). Autophagy was analyzed using the Western blot method by assessing type II microtubule-associated protein 1 (MAP1) light chain 3 (LC3) and Beclin 1 expression levels relative to beta-actin. Results indicated an increased ratio of LC3-II to beta-actin in splenocytes of C57BL/6 mice only at 7 day post infection (d.p.i.) compared to uninfected animals. LC3-II/beta-actin and Beclin 1/beta-actin ratios in splenocytes of BALB/c mice increased at 5 d.p.i. and remained high until day 14 and 7 p.i., respectively. We confirmed the formation of autophagosome structures in the spleen of BALB/c mice by transmission electron microscopy (TEM). Moreover, autophagy accompanied necrosis in the splenocytes of infected animals. Results suggest that ECTV-MOS induced autophagy, especially in the spleen of the susceptible mouse strain, may support viral replication and promote cell necrosis.

Acute Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or Paraquat on Core Temperature in C57BL/6J Mice

PubMed Central

Jiao, Yun; Dou, Yuchen; Lockwood, Georgina; Pani, Amar; Jay Smeyne, Richard

2015-01-01

Abstract Background: MPTP and paraquat are two compounds that have been used to model Parkinson’s disease in mice. Previous studies in two non-traditional strains of mice have shown that a single dose of MPTP can induce changes in body temperature, while the effects of paraquat have not been examined. Examination of body temperature is important since small fluctuations in an animal’s core temperature can significantly affect drug metabolism, and if significant enough can even culminate in an animal’s death. Objective: To determine how external heating can alter the survival of C57BL/6J mice following MPTP administration. Methods: In this study, we examine the effects of MPTP (4×20 mg/kg, 2 hours apart) and paraquat (2×10 mg/kg/week for 3 weeks) on core temperature of C57BL/6J mice. Correlations of purine and catecholamine levels were also done in mice treated with MPTP. Results: We find that MPTP induces a significant hypothermia in C57BL/6J mice that reduces their core temperature below the limit of fatal hypothermia. Unlike MPTP, paraquat did not induce a significant hypothermia. Placement of animals on heating pads significantly abrogates the loss of core temperature. In both heated and non-heated conditions, mice treated with MPTP showed a significant depletion of ATP within 2 hours of administration in both striatum and SN that started to recover 2 hours after MPTP administration was complete. Striatal DA and DOPAC are significantly reduced starting 4–6 hours after MPTP. Conclusions: The fatal hypothermic effects of MPTP can be abrogated through use of external heating. PMID:25633843

Extraordinary Activity in the BL Lacertae Object OJ 287

NASA Astrophysics Data System (ADS)

Hughes, Philip A.; Aller, Hugh D.; Aller, Margo F.

1998-08-01

We use a continuous wavelet transform to analyze more than two decades of data for the BL Lac object OJ 287 acquired as part of the University of Michigan Radio Astronomy Observatory (UMRAO) variability program. We find clear evidence for a persistent modulation of the total flux and polarization with period ~1.66 yr and for another signal that dominates activity in the 1980s with period ~1.12 yr. The relationship between these two variations can be understood in terms of a ``shock-in-jet'' model, in which the longer timescale periodicity is associated with an otherwise quiescent jet and the shorter timescale activity is associated with the passage of a shock. The different periodicities of these two components may reflect different internal conditions of the two flow domains leading to different wave speeds or different contractions of a single underlying periodicity due to the different Doppler factors of the two flow components. We suggest that the modulation arises from a wave driven by some asymmetric disturbance close to the central engine. The periodic behavior in polarization exhibits excursions in U that correspond to a direction ~45° from the VLBI jet axis. This behavior is not explained by the random walk in the Q-U plane that is expected from models in which a pattern of randomly aligned magnetic field elements propagate across the visible portion of the flow and suggests a small amplitude, cyclic variation in the flow direction in that part of the flow that dominates centimeter wavelength emission.

Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice.

PubMed

Varga, Dániel; Herédi, Judit; Kánvási, Zita; Ruszka, Marian; Kis, Zsolt; Ono, Etsuro; Iwamori, Naoki; Iwamori, Tokuko; Takakuwa, Hiroki; Vécsei, László; Toldi, József; Gellért, Levente

2015-01-01

L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice.

Relativistic jet models for the BL Lacertae object Mrk 421 during three epochs of observation

NASA Technical Reports Server (NTRS)

Mufson, S. L.; Hutter, D. J.; Kondo, Y.; Wisniewski, W. Z.

1988-01-01

Coordinated observation of the nearby BL Lacertae object Mrk 421 obtained during May 1980, January 1984, and March 1984 are described. These observations give a time-frozen picture of the continuous spectrum of Mrk 421 at X-ray, ultraviolet, optical, and radio wavelengths. The observed spectra have been fitted to an inhomogeneous relativistic jet model. In general, the models reproduce the data well. Many of the observed differences during the three epochs can be attributed to variations in the opening angle of the jet and in the angle that the jet makes to the line of sight. The jet models obtained here are compared with the homogeneous, spherically symmetric, synchrotron self-Compton models for this source. The models are also compared with the relativistic jet models obtained for other active galactic nuclei.

Functional characteristics of cyclodextrin glucanotransferase from alkalophilic Bacillus sp. BL-31 highly specific for intermolecular transglycosylation of bioflavonoids.

PubMed

Go, Young-Hoon; Kim, Tae-Kwon; Lee, Kwang-Woo; Lee, Yong-Hyun

2007-09-01

The functional characteristics of a beta-cyclodextrin glucanotransferase (CGTase) excreted from alkalophilic Bacillus sp. BL-31 that is highly specific for the intermolecular transglycosylation of bioflavonoids were investigated. The new beta-CGTase showed high specificities for glycosyl acceptor bioflavonoids, including naringin, rutin, and hesperidin, and especially naringin. The transglycosylation of naringin into glycosyl naringin was then carried out under the conditions of 80 units of CGTase per gram of maltodextrin, 5 g/l of naringin, 25 g/l of maltodextrin, and 1 mM Mn2+ ion at 40 degrees C for 6 h, resulting in a high conversion yield of 92.1%.

Oral aniracetam treatment in C57BL/6J mice without pre-existing cognitive dysfunction reveals no changes in learning, memory, anxiety or stereotypy

PubMed Central

Reynolds, Conner D.; Jefferson, Taylor S.; Volquardsen, Meagan; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Lugo, Joaquin N.

2017-01-01

Background: The piracetam analog, aniracetam, has recently received attention for its cognition enhancing potential, with minimal reported side effects.  Previous studies report the drug to be effective in both human and non-human models with pre-existing cognitive dysfunction, but few studies have evaluated its efficacy in healthy subjects. A previous study performed in our laboratory found no cognitive enhancing effects of oral aniracetam administration 1-hour prior to behavioral testing in naïve C57BL/6J mice. Methods: The current study aims to further evaluate this drug by administration of aniracetam 30 minutes prior to testing in order to optimize any cognitive enhancing effects. In this study, all naïve C57BL/6J mice were tested in tasks of delayed fear conditioning, novel object recognition, rotarod, open field, elevated plus maze, and marble burying. Results: Across all tasks, animals in the treatment group failed to show enhanced learning when compared to controls. Conclusions: These results provide further evidence suggesting that aniracetam conveys no therapeutic benefit to subjects without pre-existing cognitive dysfunction. PMID:29946420

Development of sample exchange robot PAM-HC for beamline BL-1A at the photon factory

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

Hiraki, Masahiko, E-mail: masahiko.hiraki@kek.jp; Department of Accelerator Science, SOKENDAI; Matsugaki, Naohiro

A macromolecular crystallography beamline, BL-1A, has been built at the Photon Factory (PF) for low energy experiments and has been operational since 2010. We have installed a sample exchange robot, PAM (PF Automated Mounting system), similar to other macromolecular crystallography beamlines. However, following the installation of a helium chamber to reduce the absorption of the diffraction signal by air, we developed a new sample exchange robot to replace PAM. The new robot, named PAM-HC (Helium Chamber), is designed with the goal of minimizing leakage of helium gas from the chamber. Here, the PAM-HC hardware and the flow of its movementmore » are described. Furthermore, measurements of temperature changes during sample exchange are presented in this paper.« less

Neural mechanism of gastric motility regulation by electroacupuncture at RN12 and BL21: A paraventricular hypothalamic nucleus-dorsal vagal complex-vagus nerve-gastric channel pathway

PubMed Central

Wang, Hao; Liu, Wen-Jian; Shen, Guo-Ming; Zhang, Meng-Ting; Huang, Shun; He, Ying

2015-01-01

AIM: To study the neural mechanism by which electroacupuncture (EA) at RN12 (Zhongwan) and BL21 (Weishu) regulates gastric motility. METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custom-made rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex (DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin (MTL) and gastrin (GAS) in the paraventricular hypothalamic nucleus (PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor (MTL-R) and gastrin receptor (GAS-R) in both the PVN and the gastric antrum were assayed by western blotting. RESULTS: EA at RN12 + BL21 (gastric Shu and Mu points), BL21 (gastric Back-Shu point), RN12 (gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC (2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos (36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL (22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS (24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R (1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R (1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R (1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R (1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure (13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable

The Sam Domain of EphA2 Receptor and its Relevance to Cancer: A Novel Challenge for Drug Discovery?

PubMed

Mercurio, Flavia A; Leone, Marilisa

2016-01-01

Eph receptors play important functions in developmental processes and diseases and among them EphA2 is well known for its controversial role in cancer. Drug discovery strategies are mainly centered on EphA2 extracellular ligand-binding domain however, the receptor also contains a largely unexplored cytosolic Sam (Sterile alpha motif) domain at the C-terminus. EphA2-Sam binds the Sam domain from the lipid phosphatase Ship2 and the first Sam domain of Odin. Sam-Sam interactions may be important to regulate ligand-induced receptor endocytosis and degradation i.e., processes that could be engaged against tumor malignancy. We critically analyzed literature related to a) Eph receptors with particular emphasis on EphA2 and its role in cancer, b) Sam domains, c) heterotypic Sam-Sam interactions involving EphA2-Sam. While literature data indicate that binding of EphA2-Sam to Ship2-Sam should largely generate pro-oncogenic effects in cancer cells, the correlation between EphA2- Sam/Odin-Sam1 complex and the disease is unclear. Recently a few linear peptides encompassing binding interfaces from either Ship2-Sam and Odin-Sam1 have been characterized but failed to efficiently block heterotypic Sam-Sam interactions involving EphA2-Sam due to the lack of a native like fold. Molecule antagonists of heterotypic EphA2-Sam associations could work as potential anticancer agents or be implemented as tools to further clarify receptor functions and eventually validate its role as a novel target in the field of anti-cancer drug discovery. Due to the failure of linear peptides there is a crucial need for novel approaches, based on cyclic or helical molecules, to target Sam-Sam interfaces.

Simultaneous measurements of X-ray reflectivity and grazing incidence fluorescence at BL-16 beamline of Indus-2

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

Das, Gangadhar; Kane, S. R.; Khooha, Ajay

2015-05-15

A new multipurpose x-ray reflectometer station has been developed and augmented at the microfocus beamline (BL-16) of Indus-2 synchrotron radiation source to facilitate synchronous measurements of specular x-ray reflectivity and grazing incidence x-ray fluorescence emission from thin layered structures. The design and various salient features of the x-ray reflectometer are discussed. The performance of the reflectometer has been evaluated by analyzing several thin layered structures having different surface interface properties. The results reveal in-depth information for precise determination of surface and interface properties of thin layered materials demonstrating the immense potential of the combined measurements of x-ray reflectivity and grazingmore » incidence fluorescence on a single reflectometer.« less

A histology-based atlas of the C57BL/6J mouse brain deformably registered to in vivo MRI for localized radiation and surgical targeting

NASA Astrophysics Data System (ADS)

Purger, David; McNutt, Todd; Achanta, Pragathi; Quiñones-Hinojosa, Alfredo; Wong, John; Ford, Eric

2009-12-01

The C57BL/6J laboratory mouse is commonly used in neurobiological research. Digital atlases of the C57BL/6J brain have been used for visualization, genetic phenotyping and morphometry, but currently lack the ability to accurately calculate deviations between individual mice. We developed a fully three-dimensional digital atlas of the C57BL/6J brain based on the histology atlas of Paxinos and Franklin (2001 The Mouse Brain in Stereotaxic Coordinates 2nd edn (San Diego, CA: Academic)). The atlas uses triangular meshes to represent the various structures. The atlas structures can be overlaid and deformed to individual mouse MR images. For this study, we selected 18 structures from the histological atlas. Average atlases can be created for any group of mice of interest by calculating the mean three-dimensional positions of corresponding individual mesh vertices. As a validation of the atlas' accuracy, we performed deformable registration of the lateral ventricles to 13 MR brain scans of mice in three age groups: 5, 8 and 9 weeks old. Lateral ventricle structures from individual mice were compared to the corresponding average structures and the original histology structures. We found that the average structures created using our method more accurately represent individual anatomy than histology-based atlases alone, with mean vertex deviations of 0.044 mm versus 0.082 mm for the left lateral ventricle and 0.045 mm versus 0.068 mm for the right lateral ventricle. Our atlas representation gives direct spatial deviations for structures of interest. Our results indicate that MR-deformable histology-based atlases represent an accurate method to obtain accurate morphometric measurements of a population of mice, and that this method may be applied to phenotyping experiments in the future as well as precision targeting of surgical procedures or radiation treatment.

Age-related morphological changes in the basement membrane in the stria vascularis of C57BL/6 mice.

PubMed

Suzuki, Mitsuya; Sakamoto, Takashi; Kashio, Akinori; Yamasoba, Tatsuya

2016-01-01

Basement membrane anionic sites (BMAS) are involved in the selective transport of electrically charged macromolecules in cochlear capillaries. Using cationic polyethyleneimine (PEI), we examined age-related changes in BMAS in the cochleae of C57BL/6 mice. The mice were grouped according to age as follows: 3 days, 4 weeks, 8 weeks, 6 months, and 12 months. In the right bony labyrinths, widths of the stria vascularis were measured in paraffin-embedded sections using light microscopy. The left bony labyrinths were immersed in a 0.5 % cationic PEI solution and embedded in epoxy resin. Ultrathin sections of the left cochlea were examined using transmission electron microscopy. A significant difference in stria vascularis width was observed between the 4-week-old and 12-month-old mice. The PEI distribution in the capillary and epithelial basement membranes (BMs) of the cochlea was observed. In all animals, PEI particles were evenly distributed in the capillary BM of the spiral ligament and in the subepithelial BM of Reissner's membrane. In the stria vascularis, PEI particles were evenly distributed in the capillary BM in 3-day-old mice. In 4- and 8-week-old mice, PEI particle sizes were markedly lower than those observed in 3-day-old mice. In 6- and 12-month-old mice, PEI particles were hardly detected in the strial capillary BM. In the strial capillary BM in these mice, the laminae rarae externa and interna disappeared, but the lamina densa became larger. We speculated that age-related changes of strial capillary BMAS may affect electrically charged macromolecule transport systems in the stria vascularis of C57BL/6 mice.

Simultaneous assessment of autonomic function and anxiety-related behavior in BALB/c and C57BL/6 mice.

PubMed

Depino, Amaicha Mara; Gross, Cornelius

2007-02-27

In humans, anxiety is accompanied by changes in autonomic nervous system function, including increased heart rate, body temperature, and blood pressure, and decreased heart rate variability. In rodents, anxiety is inferred by examining anxiety-related behavioral responses such as avoidance and freezing, and more infrequently by assessing autonomic responses to anxiogenic stimuli. However, few studies have simultaneously measured behavioral and autonomic responses to aversive stimuli in rodents and it remains unclear whether autonomic measures are reliable correlates of anxiety-related behavior in these animal models. Here we recorded for the first time heart rate and body temperature in freely moving BALB/c and C57BL/6 mice during exposure to an unfamiliar environment. Our data show that upon exposure to a novel open field, BALB/c mice showed increased anxiety-related behavior, reduced heart rate and higher heart rate variability (HRV) when compared with C57BL/6 mice. Regression analysis revealed a significant correlation between both heart rate and long-term HRV measures and locomotor activity and time spent in the center of the open field, but no correlation between body temperature and any behavioral variables. In the free exploration test, in which animals were allowed direct access to a novel environment from a familiar environment without experimenter handling, significant correlations were found only between heart rate and total locomotor activity, but not time spent in the unfamiliar chamber despite increased anxiety-related behavior in BALB/c mice. These findings demonstrate that increased anxiety-related behavior in BALB/c mice is not associated with specific changes in heart rate, HRV, or body temperature.

Asbestos-induced autoimmunity in C57BL/6 mice.

PubMed

Pfau, Jean C; Sentissi, Jami J; Li, Sheng'ai; Calderon-Garciduenas, Lilian; Brown, Jared M; Blake, David J

2008-04-01

Environmental impacts on autoimmunity have significant public health implications. Epidemiological studies have shown associations between exposure to airborne silicates, such as crystalline silica or asbestos, and autoimmunity, but the etiology remains unclear. The purpose of this study was to test the hypothesis that asbestos could lead to a specific pattern of autoantibodies and pathology indicative of systemic autoimmune disease (SAID). Female C57Bl/6 mice were instilled intratracheally with 2 doses x 60 microg/mouse of amphibole asbestos (tremolite), wollastonite (a non-fibrogenic control fiber), or saline alone. Serum samples were collected and urine was checked for protein bi-weekly for 7 months. By 26 weeks, the asbestos-instilled animals had a significantly higher frequency of positive anti-nuclear antibody (ANA) tests compared to wollastonite and saline groups. The majority of positive ANAs showed homogeneous or combined homogeneous/speckled patterns, and tested positive for antibodies to dsDNA and SSA/Ro 52. Serum isotyping showed no significant changes in IgM, IgA, or IgG subclasses. However, there was an overall decrease in the mean IgG serum concentration in asbestos-instilled mice. IgG immune complex deposition was demonstrated in the kidneys of asbestos-instilled mice, with evidence of glomerular and tubule abnormalities suggestive of glomerulonephritis. Flow cytometry demonstrated moderate changes in the percentages of CD25+ T-suppressor cells and B1a B-cells in the superficial cervical lymph nodes of the asbestos-instilled mice. These data demonstrate that asbestos leads to immunologic changes consistent with the development of autoimmunity. This study provides a non-autoimmune prone murine model for use in future elucidation of mechanisms involved in asbestos-induced autoimmune disease.

Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J mice

PubMed Central

Lamming, Dudley W.; Baar, Emma L.; Arriola Apelo, Sebastian I.; Tosti, Valeria; Fontana, Luigi

2017-01-01

Recently, it has become apparent that dietary macronutrient composition has a profound impact on metabolism, health and even lifespan. Work from many laboratories now suggest that dietary protein quality – the precise amino acid composition of the diet, as well as possibly the source of dietary protein – may also be critical in regulating the impact of diet on health. Perhaps in part due to the naturally low methionine content of plants, vegan diets are associated with a decreased risk of diabetes and improved insulin sensitivity, but this association is confounded by the lower overall protein intake of vegans. Here, we test the effect of consuming isocaloric rodent diets with similar amino acid profiles derived from either plant protein or dairy protein. We find that male C57BL/6J mice consuming either diet have similar glycemic control, as assessed by glucose, insulin, and pyruvate tolerance tests, and have similar overall body composition. We conclude that short-term feeding of plant protein has no positive or negative effect on the metabolic health of young male C57BL/6J mice, and suggest that dietary interventions that alter either dietary protein levels or the levels of specific essential amino acids are more likely to improve metabolic health than alterations in dietary protein source. PMID:29276793

The Effect of Oxytocin on Social and Non-Social Behaviour and Striatal Protein Expression in C57BL/6N Mice

PubMed Central

Zhang, Xiaofan; Li, Qi; Zhang, Min; Lam, Sylvia; Sham, Pak Chung; Bu, Bitao; Chua, Siew Eng; Wang, Wei; McAlonan, Grainne Mary

2015-01-01

Oxytocin has been suggested as a promising new treatment for neurodevelopmental disorders. However, important gaps remain in our understanding of its mode of action, in particular, to what extent oxytocin modulates social and non-social behaviours and whether its effects are generalizable across both sexes. Here we investigated the effects of a range of oxytocin doses on social and non-social behaviours in C57BL/6N mice of both sexes. As the striatum modulates social and non-social behaviours, and is implicated in neurodevelopmental disorders, we also conducted a pilot exploration of changes in striatal protein expression elicited by oxytocin. Oxytocin increased prepulse inhibition of startle but attenuated the recognition memory in male C57BL/6N mice. It increased social interaction time and suppressed the amphetamine locomotor response in both sexes. The striatum proteome following oxytocin exposure could be clearly discriminated from saline controls. With the caveat that these results are preliminary, oxytocin appeared to alter individual protein expression in directions similar to conventional anti-psychotics. The proteins affected by oxytocin could be broadly categorized as those that modulate glutamatergic, GABAergic or dopaminergic signalling and those that mediate cytoskeleton dynamics. Our results here encourage further research into the clinical application of this peptide hormone, which may potentially extend treatment options across a spectrum of neurodevelopmental conditions. PMID:26716999

High-fat simple carbohydrate (HFSC) diet impairs hypothalamic and corpus striatal serotonergic metabolic pathway in metabolic syndrome (MetS) induced C57BL/6J mice.

PubMed

Stephen, DSouza Serena; Abraham, Asha

2017-07-26

To study the effect of specially formulated high-fat simple carbohydrate diet (HFSC) on the serotonin metabolic pathway in male C57BL/6J mice. Previous studies from our laboratory have shown that specially formulated HFSC induces metabolic syndrome in C57BL/6J mice. In the present investigation, 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid were analyzed in two brain regions (hypothalamus, corpus striatum), urine and plasma of HFSC-fed mice on a monthly basis up to 5 months using high-performance liquid chromatography fitted with electrochemical detector. The data were analyzed using Graph pad Prism v7.3 by two-way ANOVA and post hoc Tukey's test (to assess the effect of time on the serotonergic metabolic pathway). HFSC feed was observed to lower the hypothalamic serotonergic tone as compared to the age-matched control-fed C57BL/6J mice. Although the hypothalamic serotonergic tone was unaltered over time due to consumption of diet per se, hypothalamic 5-HTP levels were observed to be lower on consumption of HFSC feed over duration of 5 months as compared to 1st month of consumption of HFSC feed. The striatal 5-HTP levels were lowered in the HFSC-fed mice after 4 months of feeding as compared to the age-matched control-fed mice. The striatal 5-HTP levels were also lower in both control and HFSC-fed mice due to consumption of the respective diet over a duration of 5 months. Increased plasma 5-HTP levels were observed due to consumption of HFSC feed over duration of 5 months in the HFSC-fed group. However, higher breakdown of serotonin was observed in both the plasma and urine of HFSC-fed C57BL/6J mice as per the turnover studies. The central and peripheral serotonergic pathway is affected differentially by both the type of diet consumed and the duration for which the diet is consumed. The hypothalamic, striatal and plasma serotonergic pathway were altered both by the type of feed consumed and the duration of feeding. The urine serotonergic pathway was

Hepatoprotective effect of Cirsium arisanense Kitamura in tacrine-treated hepatoma Hep 3B cells and C57BL mice.

PubMed

Ku, Kuo-Lung; Tsai, Chu-Tsai; Chang, Wei-Min; Shen, Mei-Lin; Wu, Chia-Tien; Liao, Hui-Fen

2008-01-01

Cirsium arisanense Kitamura (Compositae) has been used for hundreds of years in Taiwan as a folk medicine for hepatoprotection. However, no scientific research has demonstrated this effect. In the present study, we extracted the phenol-containing aqueous components of C. arisanense roots (CaR) and leaves/stem (CaL), and then assessed their hepatoprotective activities in both human hepatocellular carcinoma Hep 3B cells and C57BL/6 mice strain. High performance liquid chromatography (HPLC) analysis revealed that the components of CaR and CaL differed from those of the positive control silymarin. CaR exhibited a higher phenolic content and antioxidant capacity than CaL. Hep 3B cells treated with silymarin (0-200 microg/ml) demonstrated a concentration-dependent decrease in viability; however, both CaR and CaL did not exhibit any apparent cytotoxicity. Silymarin at 100 microg/ml, as well as CaR and CaL, not only protect Hep 3B cells from tacrine-induced hepatotoxicity but also decrease the expression of hepatitis B surface antigen (HBsAg). Moreover, an animal experiment demonstrated that CaR, CaL, and silymarin have hepatoprotective effects in C57BL/6 mice injected with tacrine, and they significantly decrease the levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These effects of CaR and silymarin, but not of CaL, may occur via an increase in the hepatic glutathione level and the elimination of the nitric oxide production. In conclusion, the phenol-containing aqueous components from C. arisanense have potential in hepatoprotection.

Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis

PubMed Central

Shvedova, A. A.; Kisin, E.; Murray, A. R.; Johnson, V. J.; Gorelik, O.; Arepalli, S.; Hubbs, A. F.; Mercer, R. R.; Keohavong, P.; Sussman, N.; Jin, J.; Yin, J.; Stone, S.; Chen, B. T.; Deye, G.; Maynard, A.; Castranova, V.; Baron, P. A.; Kagan, V. E.

2008-01-01

Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m3, 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5–20 μg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice. PMID:18658273

Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice

PubMed Central

Freet, Christopher S.; Lawrence, Antoneal L.

2015-01-01

Growing evidence implicates glutamate homeostasis in a number of behaviors observed in addiction such as acquisition of drug taking, motivation, and reinstatement. To date, however, the role of glutamate homeostasis in the avoidance of natural rewards due to exposure to drugs of abuse has received little attention. The aim of the current study was to evaluate the beta-lactam antibiotic, ceftriaxone, which has been shown to normalize disrupted glutamate homeostasis associated with exposure to drugs of abuse, in cocaine-induced suppression of saccharin intake in C57BL/6J mice. Briefly, C57BL/6J mice received daily injections of either 200 mg/kg ceftriaxone or saline. Mice were then given access to 0.15% saccharin for 1 hour and immediately injected intraperitoneally with either saline or 30 mg/kg cocaine; taste-drug pairings occurred every 24 hours for 5 trials followed by a final CS only trial. One week following taste-drug pairings, extinction was evaluated in a series of one- and two-bottle saccharin intake tests. Individual differences in cocaine-induced suppression were observed (i.e., low and high suppressors) with differential effects of ceftriaxone. Ceftriaxone delayed suppression of saccharin intake in high suppressors but prevented suppression in low suppressors. In addition, ceftriaxone history facilitated extinction in the high suppressors. These data suggest that changes in glutamate homeostasis may be involved in the formation and expression of cocaine-induced suppression of saccharin intake in mice. PMID:26066719

Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice.

PubMed

Freet, Christopher S; Lawrence, Antoneal L

2015-10-01

Growing evidence implicates glutamate homeostasis in a number of behaviors observed in addiction such as acquisition of drug taking, motivation, and reinstatement. To date, however, the role of glutamate homeostasis in the avoidance of natural rewards due to exposure to drugs of abuse has received little attention. The aim of the current study was to evaluate the beta-lactam antibiotic, ceftriaxone, which has been shown to normalize disrupted glutamate homeostasis associated with exposure to drugs of abuse, in cocaine-induced suppression of saccharin intake in C57BL/6J mice. Briefly, C57BL/6J mice received daily injections of either 200mg/kg ceftriaxone or saline. Mice were then given access to 0.15% saccharin for 1h and immediately injected intraperitoneally with either saline or 30 mg/kg cocaine; taste-drug pairings occurred every 24h for 5 trials followed by a final CS only trial. One week following taste-drug pairings, extinction was evaluated in a series of one- and two-bottle saccharin intake tests. Individual differences in cocaine-induced suppression were observed (i.e., low and high suppressors) with differential effects of ceftriaxone. Ceftriaxone delayed suppression of saccharin intake in high suppressors but prevented suppression in low suppressors. In addition, ceftriaxone history facilitated extinction in the high suppressors. These data suggest that changes in glutamate homeostasis may be involved in the formation and expression of cocaine-induced suppression of saccharin intake in mice. Copyright © 2015. Published by Elsevier Inc.

C57BL/6J mouse apolipoprotein A2 gene is deterministic for apnea.

PubMed

Gillombardo, Carl B; Darrah, Rebecca; Dick, Thomas E; Moore, Michael; Kong, Nathan; Decker, Michael J; Han, Fang; Yamauchi, Motoo; Dutschmann, Mathias; Azzam, Sausan; Strohl, Kingman P

2017-01-01

Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: -/-) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). Apoa2 WT do, but KO and heterozygote (+/-) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo. In the in situ model, pauses and instability in fictive phrenic bursting are substantially reduced in KO vs. WT preparations. In 24 RISs, apnea number in vivo was higher in strains with B6 apoa2 than with DBA apoa2 alleles. The B6 apoa2 polymorphism is directly involved in breath production, and its identification suggests a novel pathway influencing risk for adult sleep apnea. Published by Elsevier B.V.

Optical Design and Performance of the Taiwan Inelastic X-Ray Scattering Beamline (BL12XU) at SPring-8

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

Cai, Y.Q.; Chow, P.; Chen, C.C.

2004-05-12

As part of the Taiwan x-ray facility at SPring-8, we have designed, constructed and commissioned a dedicated Inelastic X-ray Scattering (IXS) beamline (BL12XU) for both resonant and non-resonant experiments on electronic excitations in correlated electron systems with energy resolution from 10-1000 meV. At the Si(555) near-backscattering energy of 9.886 keV, a total energy resolution of 70 meV has been achieved with flux of 1.5x1011 phs/sec/50meV. The optical design and performance of the beamline are presented and discussed with selected results from recent commissioning experiments.

Comparison of Reference Values in Whole Blood of DMDmdx/J and C57BL/6J Mice Using Neutron Activation Analysis

NASA Astrophysics Data System (ADS)

Metairon, S.; Zamboni, C. B.; Suzuki, M. F.; Júnior, C. R. B.; Sant'Anna, O. A.

2011-08-01

The Br, Ca, Cl, K, Na and S concentrations in whole blood of DMDmdx/J and C57BL/6J mice were determined using Neutron Activation Analysis technique. Reference values obtained from twenty one whole blood samples of these strains were analyzed in the IEA-R1 nuclear reactor at IPEN (São Paulo, Brasil). These data contribute for applications in veterinary medicine related to biochemistry analyses using whole blood as well as to evaluate the performance of treatments in muscular dystrophy.

Discovery of Very High Energy Gamma-Ray Emission from BL Lac object H1722+119 by the MAGIC Telescopes

NASA Astrophysics Data System (ADS)

Cortina, Juan

2013-05-01

H1722+119 is a BL Lac object, that was listed as candidate TeV blazar in Costamante & Ghisellini (2002) based on its X-ray and radio properties. Its redshift is uncertain; Sbarufatti et al. 2006 give z>0.17. The source has been detected by Fermi-LAT, in the Second Fermi Catalog with F(>1 GeV) (3.7+-0.3)e-09 cm^-2 s^-1 and with spectral index 1.92+-0.06. H1722+119 was observed for five nights by the MAGIC telescopes starting May 17th 2013 and collecting 11 hours of good quality data.

High quality draft genome sequence of Bacteroides barnesiae type strain BL2T (DSM 18169T) from chicken caecum

DOE PAGES

Sakamoto, Mitsuo; Lapidus, Alla L.; Han, James; ...

2015-08-02

Bacteroides barnesiae Lan et al. 2006 is a species of the genus Bacteroides, which belongs to the family Bacteroidaceae. Strain BL2T is of interest because it was isolated from the gut of a chicken and the growing awareness that the anaerobic microbiota of the caecum is of benefit for the host and may impact poultry farming. We report that the 3,621,509 bp long genome with its 3,059 protein-coding and 97 RNA genes is a part of the Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG) project.

High quality draft genome sequence of Bacteroides barnesiae type strain BL2T (DSM 18169T) from chicken caecum

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

Sakamoto, Mitsuo; Lapidus, Alla L.; Han, James

Bacteroides barnesiae Lan et al. 2006 is a species of the genus Bacteroides, which belongs to the family Bacteroidaceae. Strain BL2T is of interest because it was isolated from the gut of a chicken and the growing awareness that the anaerobic microbiota of the caecum is of benefit for the host and may impact poultry farming. We report that the 3,621,509 bp long genome with its 3,059 protein-coding and 97 RNA genes is a part of the Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG) project.

Differential effects of triacylglycerol positional isomers containing n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/6J mice.

PubMed

Yoshinaga, Kazuaki; Sasaki, Keiichi; Watanabe, Hiroyuki; Nagao, Koji; Inoue, Nao; Shirouchi, Bungo; Yanagita, Teruyoshi; Nagai, Toshiharu; Mizobe, Hoyo; Kojima, Koichi; Beppu, Fumiaki; Gotoh, Naohiro

2015-01-01

The present study investigated the effects of binding position of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to triacylglycerol (TAG) on lipid metabolism in C57BL/6J mice. Mice were treated with pure TAG positional isomers, including 1,2(2,3)-dipalmitoyl-3(1)-eicosapentaenoyl glycerol, 1,3-dipalmitoyl-2-eicosapentaenoyl glycerol, 1,2(2,3)-dipalmitoyl-3(1)-docosahexaenoyl glycerol, and 1,3-dipalmitoyl-2-docosahexaenoyl glycerol. Compared to DHA bound to the α-position of TAG, DHA bound to the β-position more effectively inhibited fatty acid synthetic enzymes and cholesterol-metabolism enzymes and thus reduced TAG and cholesterol concentrations in the serum and liver. EPA bound to the α-position of TAG, but not EPA bound to the β-position of TAG, significantly decreased hepatic cholesterol concentrations. Additionally, EPA bound to the α-position of TAG increased the ratio of PGI2 to TXA2 to a higher degree than EPA bound to the β-position. These results suggested that the binding position of EPA and DHA to TAG affected TAG and cholesterol metabolism as well as eicosanoid production in C57BL/6J mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-diabetic effects of DA-11004, a synthetic IDPc inhibitor in high fat high sucrose diet-fed C57BL/6J mice.

PubMed

Shin, Chang Yell; Jung, Mi Young; Lee, In Ki; Son, Miwon; Kim, Dong Sung; Lim, Joong In; Kim, Soon Hoe; Yoo, Moohi; Huh, Tae Lin; Sohn, Young Taek; Kim, Won Bae

2004-01-01

DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC50 for IDPc is 1.49 microM. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1 hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.

Idiopathic paraproteinaemia V. Expression of Igh1 and Igh5 allotypes within the homogeneous immunoglobulins of ageing (C57BL/LiARij X CBA/BrARij)F1 mouse.

PubMed Central

Radl, J; Vieveen, M H; van den Akker, T W; Benner, R; Haaijman, J J; Zurcher, C

1985-01-01

The role of genetic factors linked to the immunoglobulin loci and the development of idiopathic paraproteinaemia (IP)--a benign B-cell proliferative disorder--was investigated in F1 hybrid mice of low (CBA/BrARij) and high (C57BL/LiARij) IP frequency strains. Igh1 and Igh5 allotypes were used as markers for the (parental type) origin of homogeneous immunoglobulins (H-Ig) which appeared in the sera of the F1 mice with ageing. The frequencies of H-Ig in the F1 mice were intermediate with those of the parental strains. The isotype distribution of the H-Ig was 27%, 24%, 12%, 12%, 11%, 10%, 3% and 1% for IgG2a, IgM, IgG1, IgG3, IgG2b, IgD, IgA and IgE, respectively. H-Ig of the IgG2 subclass carried the Igh1b (C57BL) allotype in 98% and the Igh1a (CBA) allotype in 2% cases. Of the IgD H-Ig, 70% carried the Igh5b and 30% the Igh5a determinant. The Igh1 allotype distribution in the bone marrow and spleen plasma cells showed a large variation in the Igh1a/Igh1b ratio among old individual mice and often also between bone marrow and spleen within a single animal with or without a H-Ig component. The categorization of the paraproteinaemias on the basis of their origin showed that 10% of the H-Ig were the result of a transient monoclonal B-cell proliferation; multiple myeloma or lymphoma was found to be responsible for about 1% of the paraproteinaemias; H-Ig fulfilling the criteria for IP were detected in about 42% of cases. The origin of the remaining old age paraproteinaemias could not be determined. These data indicate that the F1 mice develop monoclonal proliferative disorders in a manner more similar to the C57BL than to the CBA parental strain. The allotype associated genetic material from the parental C57BL strain was shown to be mainly responsible for the development of IP in ageing F1 mice. Images Fig. 4 PMID:3936651

Incubation of cue-induced reinstatement of cocaine, but not sucrose, seeking in C57BL/6J mice.

PubMed

Nugent, Alexandria L; Anderson, Ethan M; Larson, Erin B; Self, David W

2017-08-01

Prior studies have shown that drug-seeking behaviors increase, rather than dissipate, over weeks to months after withdrawal from drug self-administration. This phenomenon - termed incubation - suggests that drug-craving responses elicited by conditioned environmental or discrete cues may intensify over pronged abstinence. While most of this work is conducted in rats with intravenous drug self-administration models, there is less evidence for incubation in mice that have greater utility for molecular genetic analysis and perturbation. We tested whether incubation of cocaine-seeking behavior is evident in C57BL/6J mice following 3weeks (5days/week) of cocaine self-administration in 2h self-administration sessions. We compared cocaine-seeking (drug-paired lever) responses 1, 7, or 28days after withdrawal from cocaine self-administration, and over similar times following sucrose pellet self-administration. We found that the initial re-exposure to the self-administration test chambers elicited increased reward-seeking behavior in both sucrose and cocaine self-administering mice, with maximal responses found at 7days compared to 1 or 28days after self-administration with either reinforcer. However, following extinction training, reinstatement of cocaine seeking reinforced by response-contingent presentation of reward-associated cues (tone/light) was significantly higher after 28days compared to 1 or 7days following cocaine self-administration. In contrast, cue-induced reinstatement of sucrose-paired lever pressing did not increase over this time frame, demonstrating a drug-specific incubation effect not seen with a natural reward. Thus, C57BL/6J mice display incubation of cue-induced reinstatement of cocaine seeking similar to findings with rats, but only show a transient incubation of context-induced cocaine seeking. Copyright © 2017 Elsevier Inc. All rights reserved.

Transcriptome and Allele Specificity Associated with a 3BL Locus for Fusarium Crown Rot Resistance in Bread Wheat

PubMed Central

Ma, Jian; Stiller, Jiri; Zhao, Qiang; Feng, Qi; Cavanagh, Colin; Wang, Penghao; Gardiner, Donald; Choulet, Frédéric; Feuillet, Catherine; Zheng, You-Liang; Wei, Yuming; Yan, Guijun; Han, Bin; Manners, John M.; Liu, Chunji

2014-01-01

Fusarium pathogens cause two major diseases in cereals, Fusarium crown rot (FCR) and head blight (FHB). A large-effect locus conferring resistance to FCR disease was previously located to chromosome arm 3BL (designated as Qcrs-3B) and several independent sets of near isogenic lines (NILs) have been developed for this locus. In this study, five sets of the NILs were used to examine transcriptional changes associated with the Qcrs-3B locus and to identify genes linked to the resistance locus as a step towards the isolation of the causative gene(s). Of the differentially expressed genes (DEGs) detected between the NILs, 12.7% was located on the single chromosome 3B. Of the expressed genes containing SNP (SNP-EGs) detected, 23.5% was mapped to this chromosome. Several of the DEGs and SNP-EGs are known to be involved in host-pathogen interactions, and a large number of the DEGs were among those detected for FHB in previous studies. Of the DEGs detected, 22 were mapped in the Qcrs-3B interval and they included eight which were detected in the resistant isolines only. The enrichment of DEG, and not necessarily those containing SNPs between the resistant and susceptible isolines, around the Qcrs-3B locus is suggestive of local regulation of this region by the resistance allele. Functions for 13 of these DEGs are known. Of the SNP-EGs, 28 were mapped in the Qcrs-3B interval and biological functions for 16 of them are known. These results provide insights into responses regulated by the 3BL locus and identify a tractable number of target genes for fine mapping and functional testing to identify the causative gene(s) at this QTL. PMID:25405461

On the Redshift of TeV BL Lac Objects

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

Paiano, Simona; Falomo, Renato; Landoni, Marco

2017-03-10

We report results of a spectroscopic campaign carried out at the 10 m Gran Telescopio Canarias for a sample of 22 BL Lac objects detected (or candidates) at TeV energies, aiming to determine or constrain their redshift. This is of fundamental importance for the interpretation of their emission models and for population studies and is also mandatory for studying the interaction of high-energy photons with the extragalactic background light using TeV sources. Optical spectra with high signal-to-noise ratios in the range 4250–10000 Å were obtained to search for faint emission or absorption lines from both the host galaxy and themore » nucleus. We determine a new redshift for PKS 1424+240 ( z = 0.604) and a tentative one for 1ES 0033+595 ( z = 0.467). We are able to set new spectroscopic redshift lower limits for three other sources on the basis of Mg ii and Ca ii intervening absorption features: BZB J1243+3627 ( z > 0.483), BZB J1540+8155 ( z > 0.672), and BZB 0J2323+4210 ( z > 0.267). We confirm previous redshift estimates for four blazars: S3 0218+357 ( z = 0.944), 1ES 1215+303 ( z = 0.129), W Comae ( z = 0.102), and MS 1221.8+2452 ( z = 0.218). For the remaining targets, in seven cases (S2 0109+22, 3C 66A, VER J0521+211, S4 0954+65, BZB J1120+4214, S3 1227+25, BZB J2323+4210), we do not validate the proposed redshift. Finally, for all sources of still-unknown redshift, we set a lower limit based on the minimum equivalent width of absorption features expected from the host galaxy.« less

Profound differences in fat versus carbohydrate preferences in CAST/EiJ and C57BL/6J mice: Role of fat taste.

PubMed

Sclafani, Anthony; Vural, Austin S; Ackroff, Karen

2018-06-19

In a nutrient self-selection study, CAST/EiJ mice consumed more carbohydrate than fat while C57BL/6J (B6) mice showed the opposite preference. The present study revealed similar strain differences in preferences for isocaloric fat (Intralipid) and carbohydrate (sucrose, maltodextrin) solutions in chow-fed mice. In initial 2-day choice tests, percent fat intakes of CAST and B6 mice were 4-9% and 71-81% respectively. In subsequent nutrient vs. water tests, CAST mice consumed considerably less fat but not carbohydrate compared to B6 mice. Orosensory rather than postoral factors are implicated in the very low fat preference and intake of CAST mice. This is supported by results of a choice test with Intralipid mixed with non-nutritive sweeteners vs. non-sweet maltodextrin. The preference of CAST mice for sweetened fat exceeded that of B6 mice (94 vs. 74%) and absolute fat intakes were similar in the two strains. When given unsweetened Intralipid vs. water tests at ascending fat concentrations CAST mice displayed reduced fat preferences at 0.1-5% and reduced intakes at 0.5-5% concentrations, compared to B6 mice. The differential fat preferences of CAST and C57BL/6 mice may reflect differences in fat taste sensing or in central neural processes related to fat selection. Copyright © 2017. Published by Elsevier Inc.

Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white

NASA Technical Reports Server (NTRS)

Ponnaiya, B.; Cornforth, M. N.; Ullrich, R. L.

1997-01-01

Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.

Differential learning abilities of 129T2/Sv and C57BL/6J mice as assessed in three water maze protocols.

PubMed

Wolff, Mathieu; Savova, Magdaléna; Malleret, Gaël; Segu, Louis; Buhot, Marie-Christine

2002-11-15

Knockout mice are generated by using ES cells from 129 mouse strains and are frequently backcrossed with other strains, like C57BL/6. It is important to characterise the physiological and, in particular, the behavioural profile of each strain in order to correctly analyse the functional contribution of a single gene mutation on the 'cognitive' phenotype. The present study compared 129T2/Sv (129) and C57BL/6J (C57) mice in three different spatial learning protocols in the water maze, using a hidden platform. In the 'standard' reference memory protocol, 129 and C57 attained an equivalent level of performance as assessed by accuracy in reaching the platform (path length), despite a faster swim speed exhibited by C57 mice. In a stepwise learning task, C57 mice showed poorer performances over all stages of learning. However they performed better than 129 in a massed learning protocol which taxes short-term memory, and in which they exhibited lower levels of perseveration. The results emphasize the importance of using various tasks differing in cognitive demand, but using the same experimental environment and motivation, in order to 1) evaluate strain- or mutation-dependent learning abilities, and 2) dissociate the roles played by cognitive and non-cognitive factors in the behavioural requirements of the tasks. Copyright 2002 Elsevier Science B.V.

[The influence of piracetam on behavior and brain receptors in C57BL/6 and BALB/c mice: nootropic and anxiolytic effects].

PubMed

Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

2013-01-01

The influence of acute and long-term piracetam administration on the dynamics of rapid (non-specific, anxiolytic) and slow (specific, nootropic) behavioral drug effects, as well as on their interrelation with NMDA- and BDZ-receptors was studied in inbred mice strains differing in cognitive and emotional status--C57BL/6 and BALB/c. The BALB/c strain contained 17% less [3H]-flunitrazepam binding sites in frontal cortex and 22% less [3H]-MK801 binding sites in hippocampus as compared to those in C57BL/6 mice. Based on these data, BALB/c strain was used as a model of psychopathology, combining increased anxiety and cognitive deficit. Under the action of single, 7-fold, and 14-fold piracetam i.p. injections (200 mg/kg body weight, daily), a fast increase in NMDA-receptor density and slow escalation of the specific nootropic effect was observed in BALB/c mice. Non-specific anxiolytic effects in these mice increased for the first 1 - 7 days without any changes in BDZ-binding and then decreased to initial values accompanied by decrement of brain receptor concentration. Thus, in BALB/c mice, a slowly manifested specific nootropic action of piracetam develops, following an increase in NMDA receptor density, whereas the non-specific anxiolytic effect precedes the fast-paced changes in BDZ-binding site density.

Hard x-ray photoelectron spectroscopy equipment developed at beamline BL46XU of SPring-8 for industrial researches

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

Yasuno, Satoshi, E-mail: yasuno@spring8.or.jp; Koganezawa, Tomoyuki; Watanabe, Takeshi

Hard X-ray photoelectron spectroscopy (HAXPES) is a powerful tool for investigating the chemical and electronic states of bulk and buried interface in a non-destructive manner due to the large probing depth of this technique. At BL46XU of SPring-8, there are two HAXPES systems equipped with different electron spectrometers, which can be utilized appropriately according to the purpose in various industrial researches. In this article, these systems are outlined, and two typical examples of HAXPES studies performed by them are presented, which focus on the silicidation at Ni/SiC interface and the energy distribution of interface states at SiO{sub 2}/a-InGaZnO.

Z-100, an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B, prevents spontaneous lymphatic metastasis of B16-BL6 melanoma.

PubMed

Horii, Takayuki; Yoshinaga, Koji; Kobayashi, Nobuyoshi; Seto, Koichi; Orikawa, Yuki; Okamoto, Masahiro; Eta, Runa; Ohira, Yuta; Katsunuma, Kokichi; Hori, Yuko; Tanaka, Takao; Takei, Mineo

2014-01-01

Lymphatic metastasis is common in advanced-stage carcinoma and is associated with a poor prognosis. However, few effective treatments to inhibit it are available. Z-100 is an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B that contains polysaccharides such as arabinomannan and mannan. Here, we investigated the inhibitory effect of Z-100 on spontaneous lymphatic metastasis. C57BL/6N mice injected subcutaneously with B16-BL6 melanoma cells in the right hind footpad were administered Z-100 subcutaneously in the right inguinal region on a daily basis. On day twenty-one after the injection, the right inguinal lymph nodes were excised, and the extent of metastasis, the number of immune cells, and the amount of granzyme B protein in the lymph nodes were examined. We also investigated the combined effect of Z-100 and irradiation in this model. Results showed that Z-100 reduced number of animals with metastasis, with respective metastasis rates of 85.7%, 42.9%, 7.1% and 0.0% in saline, 0.1 mg/kg Z-100, 1 mg/kg Z-100 and 10 mg/kg Z-100 group. Further, mice that had been given Z-100 were found to have more immune cells and granzyme B protein in the lymph nodes than control mice. The combination of low dose Z-100 and irradiation also inhibited spontaneous lymph node metastases. These findings suggest that Z-100 may be beneficial in preventing lymphatic metastasis by enhancing the immune response.

Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

PubMed

Kwon, T-R; Oh, C T; Park, H M; Han, H J; Ji, H J; Kim, B J

2015-08-01

Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE + MXD. From our data, we conclude that HPE increases β-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans. © 2015 British Association of Dermatologists.

Lactobacillus plantarum BL011 cultivation in industrial isolated soybean protein acid residue.

PubMed

Coghetto, Chaline Caren; Vasconcelos, Carolina Bettker; Brinques, Graziela Brusch; Ayub, Marco Antônio Záchia

In this study, physiological aspects of Lactobacillus plantarum BL011 growing in a new, all-animal free medium in bioreactors were evaluated aiming at the production of this important lactic acid bacterium. Cultivations were performed in submerged batch bioreactors using the Plackett-Burman methodology to evaluate the influence of temperature, aeration rate and stirring speed as well as the concentrations of liquid acid protein residue of soybean, soy peptone, corn steep liquor, and raw yeast extract. The results showed that all variables, except for corn steep liquor, significantly influenced biomass production. The best condition was applied to bioreactor cultures, which produced a maximal biomass of 17.87gL -1 , whereas lactic acid, the most important lactic acid bacteria metabolite, peaked at 37.59gL -1 , corresponding to a productivity of 1.46gL -1 h -1 . This is the first report on the use of liquid acid protein residue of soybean medium for L. plantarum growth. These results support the industrial use of this system as an alternative to produce probiotics without animal-derived ingredients to obtain high biomass concentrations in batch bioreactors. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

The Neurotropic Properties of AAV-PHP.B Are Limited to C57BL/6J Mice.

PubMed

Hordeaux, Juliette; Wang, Qiang; Katz, Nathan; Buza, Elizabeth L; Bell, Peter; Wilson, James M

2018-03-07

Improved delivery of adeno-associated virus (AAV) vectors to the CNS will greatly enhance their clinical utility. Selection of AAV9 variants in a mouse model led to the isolation of a capsid called PHP.B, which resulted in remarkable transduction of the CNS following intravenous infusion. However, we now show here that this enhanced CNS tropism is restricted to the model in which it was selected, i.e., a Cre transgenic mouse in a C57BL/6J background, and was not found in nonhuman primates or the other commonly used mouse strain BALB/cJ. We also report the potential for serious acute toxicity in NHP after systemic administration of high dose of AAV. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Specific destruction of islet transplants in NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation chimeras irrespective of allelic differences in beta-cell antigens.

PubMed

Leijon, K; Hillörn, V; Bergqvist, I; Holmberg, D

1995-06-01

We have tested the hypothesis that allelic differences in the antigens expressed by the beta-cells of the islets of Langerhans influence the development of insulitis in the non-obese diabetic (NOD) mouse. Islets of Langerhans from NOD, C57BL/6 and C3H/Tif mice were transplanted under the kidney capsule of NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation (EA) chimeras and the infiltration was scored 5-7 weeks later. Mononuclear cell infiltration of pancreatic islets was observed in 60% of the NOD<-->C57BL/6 and in 55% of the NOD<-->C3H/Tif EA chimeras. All transplanted EA chimeras that developed insulitis also displayed mononuclear cell infiltrates in the transplants, irrespective of the origin of the transplanted islets. In contrast, no infiltration of transplants was detected in EA chimeras scoring negative for insulitis. These results demonstrate that the specific destruction of islet transplants does not require the expression of NOD specific antigens by the islets. Moreover, the beta-cell destruction appears not to be restricted to NOD-MHC. The correlation between insulitis and transplant beta-cell destruction suggests the possibility that the development of insulitis is a prerequisite for transplant specific destruction. MHC restricted destruction may, therefore, precede the beta-cell destruction of transplanted islets. The chimerism among the mononuclear cells infiltrating the islet transplants was found to correlate with the overall haematopoetic chimerism in each of the individual EA chimeras. This observation suggests that NOD bone marrow, as well as non-NOD bone marrow, generates cells contributing to the beta-cell destruction process.

Substrain and light regime effects on integrated anxiety-related behavioral z-scores in male C57BL/6 mice-Hypomagnesaemia has only a small effect on avoidance behavior.

PubMed

Labots, M; Zheng, X; Moattari, G; Lozeman-Van't Klooster, J G; Baars, J M; Hesseling, P; Lavrijsen, M; Kirchhoff, S; Ohl, F; van Lith, H A

2016-06-01

Magnesium (Mg) has been described to possess an anxiolytic function, but a number of studies present inconsistent results on this matter. In this study the effect of Mg deficiency on anxiety-related behavior, brain and blood plasma Mg in young adult male C57BL/6JOlaHsd and C57BL/6NCrl mice was studied. The animals were put on a control or Mg deficient diet from day 0 and significant hypomagnesaemia was evident from day 12 onwards in the test animals. Housing and test conditions were under either conventional light regime (white light behavioral test conditions) or reverse light regime (red light behavioral test conditions). The animals were tested in three tests for unconditioned anxiety: the modified Hole Board (day 14), the light-dark test (day 21) and the elevated plus maze (day 28). Overall integrated behavioral z-scores were calculated over these three behavioral tests. Mg showed a structure dependent distribution at the level of the brain, that differed between C57BL/6 substrain and light regime (conventional versus reverse), respectively. Likewise, total brain Mg did differ between substrain and light regime, but was not affected by the diet. Animals on the Mg deficient diet housed under conventional light regime had a higher final (day 28) blood plasma corticosterone level as compared to controls. Animals housed under reverse light regime exhibited no diet effect of plasma corticosterone levels. The significant hypomagnesaemia at blood plasma level resulted in an effect of Mg deficiency on avoidance, but not overall anxiety-related behavior. Significant differences regarding avoidance behavior were found between the two substrains and light regimes, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

[C57BL/6 mice open field behaviour qualitatively depends on arena size].

PubMed

Lebedev, I V; Pleskacheva, M G; Anokhin, K V

2012-01-01

Open field behavior is well known to depend on physical characteristics of the apparatus. However many of such effects are poorly described especially with using of modern methods of behavioral registration and analysis. The previous results of experiments on the effect of arena size on behavior are not numerous and contradictory. We compared the behavioral scores of four groups of C57BL/6 mice in round open field arenas of four different sizes (diameter 35, 75, 150 and 220 cm). The behavior was registered and analyzed using Noldus EthoVision, WinTrack and SegmentAnalyzer software. A significant effect of arena size was found. Traveled distance and velocity increased, but not in proportion to increase of arena size. Moreover a significant effect on segment characteristics of the trajectory was revealed. Detailed behavior analysis revealed drastic differences in trajectory structure and number of rears between smaller (35 and 75 cm) and bigger (150 and 220 cm) arenas. We conclude, that the character of exploration in smaller and bigger arenas depends on relative size of central open zone in arena. Apparently its extension increases the motivational heterogeneity of space, that requires another than in smaller arenas, strategy of exploration.

Sex Differences in the Effect of Finasteride on Acute Ethanol Withdrawal Severity in C57BL/6J and DBA/2J Mice

PubMed Central

Gorin-Meyer, Rebecca E.; Wiren, Kristine M.; Tanchuck, Michelle A.; Long, Season L.; Yoneyama, Naomi; Finn, Deborah A.

2007-01-01

The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of γ-aminobutyric acidA (GABAA) receptors that can modulate ethanol (EtOH) withdrawal. The 5α-reductase inhibitor finasteride can block the formation of ALLO and other GABAergic neurosteroids and also reduce certain effects of EtOH. Treatment with finasteride during chronic EtOH exposure decreased EtOH withdrawal severity and blood EtOH concentrations (BECs), suggesting an additional effect of finasteride on EtOH pharmacokinetics. Thus, the purpose of the present study was to determine the effect of finasteride on acute EtOH withdrawal severity, to minimize the effect of finasteride on EtOH metabolism. Male and female C57BL/6J and DBA/2J mice received a pretreatment of finasteride (50 mg/kg i.p.) or vehicle 24 hours prior to an injection of EtOH (4 g/kg i.p.) or saline. Handling-induced convulsions (HICs) were scored at baseline, and then over a 24 hr period after EtOH or saline injection. In another experiment, plasma estradiol and corticosterone levels were assessed at selected time points (0, 2, 8, and 24 hrs). In a final study, retro-orbital blood samples were collected at 30, 60, 120, and 240 minutes post-EtOH administration to access finasteride’s effects on EtOH clearance parameters. Pretreatment with finasteride increased acute EtOH withdrawal severity in female C57BL/6J and DBA/2J mice but decreased withdrawal severity in male mice of both strains. Finasteride did not alter BECs, EtOH clearance, estradiol, or corticosterone concentrations in a manner that appeared to contribute to the sex difference in finasteride’s effect on acute EtOH withdrawal severity. These findings suggest that male and female C57BL/6J and DBA/2J mice differ in their sensitivity to changes in ALLO or other GABAergic neurosteroid levels during acute EtOH withdrawal. Sex differences in the modulation of GABAergic 5α-reduced steroids may be an important consideration in understanding and developing

Collegiate Cyber Defense Competition Effort

DTIC Science & Technology

2018-03-01

Energy – an electrical utility company. • 2016 : ODIN Security – a small aerospace and defense contracting firm Approved for Public Release...to secure supervisory control and data acquisition (SCADA) networks. Approved for Public Release; Distribution Unlimited 7 During the 2016 NCCDC...COLLEGIATE CYBER DEFENSE COMPETITION EFFORT UNIVERSITY OF TEXAS AT SAN ANTONIO MARCH 2018 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE

Assessing anxiety in C57BL/6J mice: a pharmacological characterization of the zero maze test.

PubMed

Heredia, Luis; Torrente, Margarita; Colomina, María T; Domingo, José L

2013-01-01

Anxiety disorders affect the quality of life and good health of millions of people over the world. Because clinical trials are expensive and frequently show high rates of placebo responses, animal models have become an important tool for drug discovery and brain research. Zero maze is a commonly used test to assess anxiety-like levels in mice, being the C57BL/6J strain one of the most widely used. However, only few studies have focused on the pharmacological characterization of this strain in the various anxiety tests. In this study, we analyzed the changes in the anxiety-like behaviors of mice exposed to chlordiazepoxide (CLZ), as an anxiolytic drug, at doses of 2.5, 5 and 10mg/kg, picrotoxine (PTX), as an anxiogenic drug, at doses of 0.5, 1 and 2mg/kg, and methylphenidate (MPH), as a psychomotor stimulant, at doses of 2.5, 5 and 10mg/kg. Data were hand recorded in situ by an observer and through a camcorder by computer software. Results showed that CLZ and MPH had an anxiogenic effect at the two highest doses. Only CLZ at 2.5mg/kg reduced the anxiety-like levels of mice. Moreover, PTX exerted an anxiogenic effect in mice only at 2mg/kg. The drugs affecting the anxiety-like levels also affected the activity levels. Thus, the differences might have been mediated by changes in activity levels. Globally, these data demonstrate that the results obtained from the zero maze test are difficult to interpret when the C57BL/6J strain is used. On the other hand, high doses of substances that interact with the GABAergic system, as CLZ, can produce sedation in these mice. In contrast, high doses of GABAA antagonists, as PTX, are necessary if anxiogenic effects should be observed. Further investigations with this strain are necessary in order to corroborate the results of the present study. Copyright © 2013 Elsevier Inc. All rights reserved.

Construction and performance of BL28 of the Photon Factory for circularly polarized synchrotron radiation

NASA Astrophysics Data System (ADS)

Kagoshima, Yasushi; Muto, Sadatsugu; Miyahara, Tsuneaki; Koide, Tsuneharu; Yamamoto, Shigeru; Kitamura, Hideo

1992-01-01

A branch beamline, BL28A, has been constructed for the application of circularly polarized vacuum ultraviolet radiation. The radiation can be obtained in the helical undulator operation mode of an insertion device, EMPW♯28, which is also cut for elliptically polarized hard x-ray radiation. T first harmonic of the helical undulator radiation can be tuned from 40 to 350 eV with its corresponding K value from 3 to 0.2. A monochromator working basically with constant deviation optics was installed, and has started its operation. A circularly polarized flux of ˜1010 photons/s has been achieved with energy resolution of around 500-1000 at the first harmonic peak. The circular polarization after the monochromator was estimated to be higher than 70% by comparing theory and experiment on the magnetic circular dichroism of nickel films in the 3p-3d excitation region. The design philosophy of the beamline and recent results on the performance tests are presented.

Antioxidant and free radical scavenging activities of Gastrodia elata Bl. and Uncaria rhynchophylla (Miq.) Jacks.

PubMed

Liu, J; Mori, A

1992-12-01

Gastrodia elata Bl. (GE) and Uncaria rhynchophylla (Miq.) Jacks (UR) are two traditional Chinese medicinal herbal drugs, used for the treatment of convulsions and epilepsy. Their antioxidant effects in vivo and their free radical scavenging effects in vitro were investigated. Epileptogenic foci in the lateral brain of the rat were induced by the injection of ferric chloride into the lateral cortex. Both extracts significantly inhibited the increase in levels of lipid peroxide in the ipsilateral cortex, at all times observed. In addition, the two extracts also induced an early increase of activity of superoxide dismutase in the mitochondrial fraction of the ipsilateral cortex. In in vitro experiments, the two extracts exhibited significant dose-dependent scavenging effects on free radicals, using electron spin resonance spectroscopy. These results suggest that the proposed antiepileptic effects of GE and UR may be attributable to the antioxidant activity of the active components in these two medicinal herbs.

Effect of Modified Alkaline Supplementation on Syngenic Melanoma Growth in CB57/BL Mice.

PubMed

Azzarito, Tommaso; Lugini, Luana; Spugnini, Enrico Pierluigi; Canese, Rossella; Gugliotta, Alessio; Fidanza, Stefano; Fais, Stefano

2016-01-01

Tumor extracellular acidity is a hallmark of malignant cancers. Thus, in this study we evaluated the effects of the oral administration of a commercially available water alkalizer (Basenpulver®) (BP) on tumor growth in a syngenic melanoma mouse model. The alkalizer was administered daily by oral gavage starting one week after tumor implantation in CB57/BL mice. Tumors were calipered and their acidity measured by in vivo MRI guided 31P MRS. Furthermore, urine pH was monitored for potential metabolic alkalosis. BP administration significantly reduced melanoma growth in mice; the optimal dose in terms of tolerability and efficacy was 8 g/l (p< 0.05). The in vivo results were supported by in vitro experiments, wherein BP-treated human and murine melanoma cell cultures exhibited a dose-dependent inhibition of tumor cell growth. This investigation provides the first proof of concept that systemic buffering can improve tumor control by itself and that this approach may represent a new strategy in prevention and/or treatment of cancers.

Effect of Modified Alkaline Supplementation on Syngenic Melanoma Growth in CB57/BL Mice

PubMed Central

Spugnini, Enrico Pierluigi; Canese, Rossella; Gugliotta, Alessio; Fidanza, Stefano; Fais, Stefano

2016-01-01

Tumor extracellular acidity is a hallmark of malignant cancers. Thus, in this study we evaluated the effects of the oral administration of a commercially available water alkalizer (Basenpulver®) (BP) on tumor growth in a syngenic melanoma mouse model. The alkalizer was administered daily by oral gavage starting one week after tumor implantation in CB57/BL mice. Tumors were calipered and their acidity measured by in vivo MRI guided 31P MRS. Furthermore, urine pH was monitored for potential metabolic alkalosis. BP administration significantly reduced melanoma growth in mice; the optimal dose in terms of tolerability and efficacy was 8 g/l (p< 0.05). The in vivo results were supported by in vitro experiments, wherein BP-treated human and murine melanoma cell cultures exhibited a dose-dependent inhibition of tumor cell growth. This investigation provides the first proof of concept that systemic buffering can improve tumor control by itself and that this approach may represent a new strategy in prevention and/or treatment of cancers. PMID:27447181

C57BL/6J Mouse Apolipoprotein A2 Gene is Deterministic for Apnea

PubMed Central

Gillombardo, Carl B.; Darrah, Rebecca; Dick, Thomas E.; Moore, Michael; Kong, Nathan; Decker, Michael J.; Han, Fang; Yamauchi, Motoo; Dutschmann, Mathias; Azzam, Sausan; Strohl, Kingman P.

2016-01-01

Rationale Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. Objectives To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: −/−) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). Measurements and Main Results Apoa2 WT do, but KO and heterozygote (+/−) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo. In the in situ model, pauses and instability in fictive phrenic bursting are substantially reduced in KO vs. WT preparations. In 24 RISs, apnea number in vivo was higher in strains with B6 apoa2 than with DBA apoa2 alleles. Conclusions The B6 apoa2 polymorphism is directly involved in breath production, and its identification suggests a novel pathway influencing risk for adult sleep apnea PMID:27756649

Cannabidiol (CBD) Enhances Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation in C57BL/6 Mice

PubMed Central

Karmaus, Peer W. F.; Wagner, James G.; Harkema, Jack R.; Kaminski, Norbert E.; Kaplan, Barbara L.F.

2012-01-01

Cannabidiol (CBD) is a plant-derived cannabinoid that has been predominantly characterized as anti-inflammatory. However, it is clear that immune effects of cannabinoids can vary with cannabinoid concentration, or type or magnitude of immune stimulus. The present studies demonstrate that oral administration of CBD enhanced lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice. The enhanced inflammatory cell infiltrate as observed in bronchoalveolar lavage fluid (BALF) was comprised mainly of neutrophils, with some monocytes. Concomitantly, CBD enhanced pro-inflammatory cytokine mRNA production, including tumor necrosis factor-α (Tnfa), interleukins (IL) 6 and 23 (Il6, Il23), and granulocyte colony stimulating factor (Gcsf). These results demonstrate that the CBD-mediated enhancement of LPS-induced pulmonary inflammation is mediated at the level of transcription of a variety of pro-inflammatory genes. The significance of these studies is that CBD is part of a therapeutic currently in use for spasticity and pain in multiple sclerosis patients, and therefore it is important to further understand mechanisms by which CBD alters immune function. PMID:23173851

Cannabidiol (CBD) enhances lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice.

PubMed

Karmaus, Peer W F; Wagner, James G; Harkema, Jack R; Kaminski, Norbert E; Kaplan, Barbara L F

2013-01-01

Cannabidiol (CBD) is a plant-derived cannabinoid that has been predominantly characterized as anti-inflammatory. However, it is clear that immune effects of cannabinoids can vary with cannabinoid concentration, or type or magnitude of immune stimulus. The present studies demonstrate that oral administration of CBD enhanced lipopolysaccharide (LPS)-induced pulmonary inflammation in C57BL/6 mice. The enhanced inflammatory cell infiltrate as observed in bronchoalveolar lavage fluid (BALF) was comprised mainly of neutrophils, with some monocytes. Concomitantly, CBD enhanced pro-inflammatory cytokine mRNA production, including tumor necrosis factor-α (Tnfa), interleukins (IL)-5 and -23 (Il6, Il23), and granulocyte colony stimulating factor (Gcsf). These results demonstrate that the CBD-mediated enhancement of LPS-induced pulmonary inflammation is mediated at the level of transcription of a variety of pro-inflammatory genes. The significance of these studies is that CBD is part of a therapeutic currently in use for spasticity and pain in multiple sclerosis patients, and therefore it is important to further understand mechanisms by which CBD alters immune function.

ERRATIC FLARING OF BL LAC IN 2012–2013: MULTIWAVELENGTH OBSERVATIONS

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

Wehrle, Ann E.; Grupe, Dirk; Jorstad, Svetlana G.

2016-01-10

BL Lac, the eponymous blazar, flared to historically high levels at millimeter, infrared, X-ray, and gamma-ray wavelengths in 2012. We present observations made with Herschel, Swift, NuSTAR, Fermi, the Submillimeter Array, CARMA, and the VLBA in 2012–2013, including three months with nearly daily sampling at several wavebands. We have also conducted an intensive campaign of 30 hr with every-orbit observations by Swift and NuSTAR, accompanied by Herschel, and Fermi observations. The source was highly variable at all bands. Time lags, correlations between bands, and the changing shapes of the spectral energy distributions can be explained by synchrotron radiation and inversemore » Compton emission from nonthermal seed photons originating from within the jet. The passage of four new superluminal very long baseline interferometry knots through the core and two stationary knots about 4 pc downstream accompanied the high flaring in 2012–2013. The seed photons for inverse Compton scattering may arise from the stationary knots and from a Mach disk near the core where relatively slow-moving plasma generates intense nonthermal radiation. The 95 spectral energy distributions obtained on consecutive days form the most densely sampled, broad wavelength coverage for any blazar. The observed spectral energy distributions and multi-waveband light curves are similar to simulated spectral energy distributions and light curves generated with a model in which turbulent plasma crosses a conical shock with a Mach disk.« less

High resolution 3D laboratory x-ray tomography data of femora from young, 1-14 day old C57BL/6 mice.

PubMed

Bortel, Emely L; Duda, Georg N; Mundlos, Stefan; Willie, Bettina M; Fratzl, Peter; Zaslansky, Paul

2015-09-01

This data article contains high resolution (1.2 µm effective pixel size) lab-based micro-computed tomography (µCT) reconstructed volume data of the femoral mid-shafts from young C57BL/6 mice. This data formed the basis for the analyses of bone structural development in healthy mice, including closed and open porosity as reported in Bortel et al. [1]. The data reveals changes seen in bone material and porosity distribution observed when mouse bones transform from porous scaffolds into solid structures during normal organogenesis.

Persistent Diet-Induced Obesity in Male C57BL/6 Mice Resulting from Temporary Obesigenic Diets

PubMed Central

Guo, Juen; Jou, William; Gavrilova, Oksana; Hall, Kevin D.

2009-01-01

Background Does diet-induced obesity persist after an obesigenic diet is removed? We investigated this question by providing male C57BL/6 mice with free access to two different obesigenic diets followed by a switch to chow to determine if obesity was reversible. Methodology/Principal Findings Male C57BL/6 mice were randomly assigned to five weight-matched groups: 1) C group that continuously received a chow diet; 2) HF group on a 60% high fat diet; 3) EN group on the high fat diet plus liquid Ensure®; 4) HF-C group switched from high fat to chow after 7 weeks; 5) EN-C group switched from high fat plus Ensure® to chow after 7 weeks. All food intake was ad libitum. Body weight was increased after 7 weeks on both obesigenic diets (44.6±0.65, 39.8±0.63, and 28.6±0.63 g for EN, HF, and C groups, respectively) and resulted in elevated concentrations of serum insulin, glucose, and leptin and lower serum triglycerides. Development of obesity in HF and EN mice was caused by increased energy intake and a relative decrease of average energy output along with decreased ambulatory activity. After the switch to chow, the HF-C and EN-C groups lost weight but subsequently maintained a state of persistent obesity in comparison to the C group (34.8±1.2, 34.1±1.2 vs. 30.8±0.8 g respectively; P<0.05) with a 40–50% increase of body fat. All serum hormones and metabolites returned to control levels with the exception of a trend for increased leptin. The HF-C and EN-C groups had an average energy output in line with the C group and the persistent obesity was maintained despite a non-significant increase of energy intake of less than 1 kcal/d at the end of the study. Conclusion Our results illustrate the importance of considering the history of energy imbalance in determining body weight and that a persistent elevation of body weight after removal of obesigenic diets can result from very small increases of energy intake. PMID:19401758

Ultrastructural study of the effect of cyclophosphamide on the growth area of incisor teeth of DBA/2 and C57BL/6 mice.

PubMed

Anton, E

1996-04-01

The effect of a single dose of 300 mg/kg of cyclophosphamide (CY) on the ultrastructure of the basal area of lower incisor teeth was investigated in two strains of mice (DBA/2 and C57BL/6) which are very differently affected by the delayed toxicity of CY. As in the rat, CY produced necrosis in the primitive mesenchymal cells and preodontoblasts of the pulp. Moreover, important changes were noticed in the associated layers of the enamel organ (presumptive stratum intermedium cells and stellate reticulum); thus, most of the cells displayed degenerative changes including extensive vacuolization, cytoplasm sequestration and variable nuclear alterations ranging from relative integrity to complete disorganization. In contrast, non-dividing columnar odontoblasts and ameloblasts were not affected by the drug. The alterations appeared as early as 21 hours after CY and progressed in the following 2 and 3 days. Normality of the formative tooth end was regained 7 days after CY. These results indicate that in addition to the effect on the pulp, CY produces severe cytopathological changes in the cells of the stratum intermedium and stellate reticulum of the enamel organ. The different sensitivity of DBA/2 and C57BL/6 mice to the delayed toxicity of CY does not seem to be related to its effect on odontogenesis since both strains showed the same response to CY in this respect.

A subchronic feeding safety evaluation of transgenic milk containing human β-defensin 3 on reproductive system of C57BL/6J mouse.

PubMed

Gao, Ming-Qing; Zhang, Ruiqi; Yang, Yange; Luo, Yuru; Jiang, Ming; Zhang, Yingli; Zhang, Yong; Qing, Suzhu

2018-05-01

Bovine mastitis is an infectious disease of the mammary gland which has been generally treated by antibiotic delivery. While the increasing drug-resistant bacteria and the high consumption of the antibiotic had become a noticeable concern. In a previous study, a mammary special vector expressing human β-defensin 3 (hBD3) was transfected into bovine fetal fibroblasts to produce mastitis-resistant bovine. This investigation focused on potential unintended effects of transgenic milk containing hBD3 produced by these mastitis-resistant bovine on the reproductive system of C57BL/6J mice. Mice were fed with diets containing transgenic milk or conventional milk, nutritionally balanced to an AIN93G diet for 90 days, and non-milk diet was selected as the negative group. The reproductive system was given special attention including reproductive organ/body ratios, necropsy and histopathology, serum sex hormone, sperm parameters, estrus cycle and the expression level of some specific genes which could indicate the development and function of reproductive system. No diet-related significant differences were observed among three groups in this 90-day feeding study. The results indicated that hBD3 milk does not appear to exert any effect on the reproductive system in C57BL/6J rats compared with conventional milk or the control diet. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

PubMed

Evangelio, Marian; García-Amado, María; Clascá, Francisco

2018-01-01

A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.