Transcriptomic and ChIP-sequence interrogation of EGFR signaling in HER2+ breast cancer cells reveals a dynamic chromatin landscape and S100 genes as targets.

BACKGROUND:The Human Epidermal Growth Factor Receptor (EGFR/HER1) can be activated by several ligands including Transforming Growth Factor alpha (TGF-α) and Epidermal Growth Factor (EGF). Following ligand binding, EGFR heterodimerizes with other HER family members, such as HER2 (human epidermal growth factor receptor-2). Previously, we showed that the EGFR is upregulated in trastuzumab resistant HER2 positive (HER2+) breast cancer cells. This study is aimed to determine the downstream effects on transcription following EGFR upregulation in HER2+ breast cancer cells. METHODS:RNA-sequence and ChIP-sequence for H3K18ac and H3K27ac (Histone H3 lysine K18 and K27 acetylation) were conducted following an Epidermal Growth Factor (EGF) treatment time course in HER2+ breast cancer cells, SKBR3. The levels of several proteins of interest were confirmed by western blot analysis. The cellular localization of proteins of interest was examined using biochemically fractionated lysates followed by western blot analysis. RESULTS:Over the course of 24 h, EGFR stimulation resulted in the modulation of over 4000 transcripts. Moreover, our data demonstrates that EGFR/HER2 signaling regulates the epigenome, with global H3K18ac and H3K27ac oscillating as a function of time following EGF treatment. RNA-sequence data demonstrates the activation of immediate early genes (IEGs) and delayed early genes (DEGs) within 1 h of EGF treatment. More importantly, we have identified members of the S100 (S100 Calcium Binding Protein) gene family as likely direct targets of EGFR signaling as H3K18ac, H3K27ac and pol2 (RNA polymerase II) increase near the transcription start sites of some of these genes. CONCLUSIONS:Our data suggests that S100 proteins, which act as Ca2+ sensors, could play a role in EGF induced tumor cell growth and metastasis, contribute to trastuzumab resistance and cell migration and that they are likely drug targets in HER2+ breast cancer

Interferometric Observations of V838 Monocerotis

We have used long-baseline near-IR interferometry to resolve the peculiar eruptive variable V838 Mon and to provide the first direct measurement of its angular size. Assuming a uniform disk model for the emission we derive an apparent angular diameter at the time of observations (November-December 2004) of $1.83 \pm 0.06$ milli-arcseconds. For a nominal distance of $8\pm2$ kpc, this implies a linear radius of $1570 \pm 400 R_{\odot}$. However, the data are somewhat better fit by elliptical disk or binary component models, and we suggest that the emission may be strongly affected by ejecta from the outburst.Comment: 12 pages, 1 two-part encapsulated postscript figure. Accepted by ApJL. Added a table of observation

Nonlinear acoustic waves in channels with variable cross sections

The point symmetry group is studied for the generalized Webster-type equation describing non-linear acoustic waves in lossy channels with variable cross sections. It is shown that, for certain types of cross section profiles, the admitted symmetry group is extended and the invariant solutions corresponding to these profiles are obtained. Approximate analytic solutions to the generalized Webster equation are derived for channels with smoothly varying cross sections and arbitrary initial conditions.Comment: Revtex4, 10 pages, 2 figure. This is an enlarged contribution to Acoustical Physics, 2012, v.58, No.3, p.269-276 with modest stylistic corrections introduced mainly in the Introduction and References. Several typos were also correcte

The GEOS-3 orbit determination investigation

The nature and improvement in satellite orbit determination when precise altimetric height data are used in combination with conventional tracking data was determined. A digital orbit determination program was developed that could singly or jointly use laser ranging, C-band ranging, Doppler range difference, and altimetric height data. Two intervals were selected and used in a preliminary evaluation of the altimeter data. With the data available, it was possible to determine the semimajor axis and eccentricity to within several kilometers, in addition to determining an altimeter height bias. When used jointly with a limited amount of either C-band or laser range data, it was shown that altimeter data can improve the orbit solution

The Extended Methanol Maser Emission in W51

The European VLBI Network (EVN) has been used to make phase referenced, wide-field (several arcminute) spectral line observations of the 6.7-GHz methanol maser emission towards W51. In the W51main region, the bulk of the methanol is offset from an UCHII region. This probably indicates the methanol emission arises at the interface of the expanding UCHII region and not from an edge-on circumstellar disc, as previously suggested. Near the W51 IRS2 region, the methanol emission is associated with a very compact, extremely embedded source supporting the hypothesis that methanol masers trace the earliest stages of massive star formation. As well as these two previously well studied sites of star formation, many previously unknown regions star formation are detected, demonstrating that methanol masers are powerful means of detection young massive stars.Comment: 5 pages, 3 figure

The Effects of Microbial Inoculation on Short-to-Long Fermentation and Aerobic Stability of Grass-Legume Silage Ensiled in Big Bales

Wilted (35.9 % DM and 2.6% WSC) moderately difficult to ensile grass-legume mixture (red clover, alfalfa and timothy 50:20:30) was ensiled in cylindrical big bales (1.2 m hight and 1.2 m diameter) with a weight about 700 kg. The crop was ensiled for 8, 32 and 120 days with or without a microbial inoculation (SiloSolve® FC containing Lactococcus lactis DSM 11037/1k2081 and Lactobacillus buchneri DSM 22501/1k20738 applied at 1.5×105 CFU g-1 forage). Ten bales per treatment were prepared for each fermentation period. After each period of ensiling the big bales were opened, sampled, and tested for fermentation parameters, yeast and mould counts and aerobic stability. Weight loss during fermentation and aerobic exposure were recorded and DM losses were calculated. After 8 days of fermentation, the addition of SiloSolve® FC showed only significant positive effects on pH, acetic and butyric acid, while after 32 and 120 days of fermentation periods, significant improvements of adding SiloSolve® FC were observed across all parameters investigated. The results show that SiloSolve® FC is an effective treatment to reduce ammonia, ethanol, and butyric acid production, to control yeast and mould growth, and to improve acetic acid levels with a resulting improved aerobic stability of grass-legume mixture fermented in big bales. Total lactic acid bacteria increased significantly and an appreciable decrease number of yeasts were detected in the inoculated silage at all fermentation time points and after aerobic exposure if compared with untreated silage. Reduction in yeast and mould population during anaerobic phase of silage fermentation and during silage aerobic exposure period appears to be the main reason for the improvement aerobic stability of the inoculated silage. Improved fermentation, reduced DM loss during fermentation and during aerobic exposure periods lead to increase nutritive value of the inoculated silage

A low optical depth region in the inner disk of the HerbigAe star HR5999

Circumstellar disks surrounding young stars are known to be the birthplaces of planets, and the innermost astronomical unit is of particular interest. We present new long-baseline spectro-interferometric observations of the HerbigAe star, HR5999, obtained in the H and K bands with the AMBER instrument at the VLTI, and aim to produce near-infrared images at the sub-AU spatial scale. We spatially resolve the circumstellar material and reconstruct images using the MiRA algorithm. In addition, we interpret the interferometric observations using models that assume that the near-infrared excess is dominated by the emission of a circumstellar disk. We compare the images reconstructed from the VLTI measurements to images obtained using simulated model data. The K-band image reveals three main elements: a ring-like feature located at ~0.65 AU, a low surface brightness region inside, and a central spot. At the maximum angular resolution of our observations (1.3 mas), the ring is resolved while the central spot is only marginally resolved, preventing us from revealing the exact morphology of the circumstellar environment. We suggest that the ring traces silicate condensation, i.e., an opacity change, in a circumstellar disk around HR 5999. We build a model that includes a ring at the silicate sublimation radius and an inner disk of low surface brightness responsible for a large amount of the near-infrared continuum emission. The model successfully fits the SED, visibilities, and closure phases, and provides evidence of a low surface brightness region inside the silicate sublimation radius. This study provides additional evidence that in HerbigAe stars, there is material in a low surface brightness region, probably a low optical depth region, located inside the silicate sublimation radius and of unknown nature.Comment: 11 pages, 10 figure

Mitochondrial fusion is frequent in skeletal muscle and supports excitation-contraction coupling

Genetic targeting experiments indicate a fundamental role for mitochondrial fusion proteins in mammalian physiology. However, owing to the multiple functions of fusion proteins, their related phenotypes are not necessarily caused by altered mitochondrial fusion. Perhaps the biggest mystery is presented by skeletal muscle, where mostly globular-shaped mitochondria are densely packed into the narrow intermyofilamental space, limiting the interorganellar interactions. We show here that mitochondria form local networks and regularly undergo fusion events to share matrix content in skeletal muscle fibers. However, fusion events are less frequent and more stable in the fibers than in nondifferentiated myoblasts. Complementation among muscle mitochondria was suppressed by both in vivo genetic perturbations and chronic alcohol consumption that cause myopathy. An Mfn1-dependent pathway is revealed whereby fusion inhibition weakens the metabolic reserve of mitochondria to cause dysregulation of calcium oscillations during prolonged stimulation. Thus, fusion dynamically connects skeletal muscle mitochondria and its prolonged loss jeopardizes bioenergetics and excitation-contraction coupling, providing a potential pathomechanism contributing to myopathies.

Two Late Quaternary Pollen Records from South-Central Alaska

Pollen records from Wonder and Ten Mile lakes, located at aititudinal treeline to the north and south of the Alaska Range respectively, document the vegetation history of a portion of the southern Alaskan boreal forest. The new pollen diagrams indicate a Betula shrub tundra, preceded at Wonder Lake by a sparse herb tundra, which characterized these two areas during latest Wisconsinan times. Populus was in the vicinity of Ten Mile Lake ca. 10,000 BP, but was apparently absent from Wonder Lake. Picea glauca grew at or near Ten Mile Lake by 9100 BP, with P. mariana becoming important ca. 7000 BP. The first forests at Wonder Lake were also dominated by P. glauca and followed by increased numbers of P. mariana. The timing of forest establishment at Wonder Lake is uncertain due to problematic radiocarbon dates. Alnus appears to be common in both regions by ca. 7000 BP. These records suggest that paleo-vegetational reconstructions are more difficult for the southern than northern boreal forests in Alaska because of greater topographic diversity, difficulties with over-representation of some pollen taxa, and problems with radiocarbon dating. Despite these concerns, available data from south-central Alaska suggest that southern and northern forests differ in their vegetational histories. Such differences, when related to temperature fluctuations that have been postulated for the Holocene, imply that the Alaskan boreal forest may not respond uniformly to future global warming.Les inventaires polliniques de Wonder Lake et de Ten Mile Lake, situés à la limite altitudinale des arbres au nord et au sud de la chaîne de l'Alaska permettent de reconstituer l'histoire de la végétation d'une portion de la forêt boréale du sud de l'Alaska. Les nouveaux diagrammes polliniques montrent une toundra arbustive à Betula, précédée au Wonder Lake par une toundra herbacée clairsemée, à la fin du Wisconsinien. Vers 10 000 BP, Populus était dans les environs du Ten Mile Lake, mais était apparamment absent du Wonder Lake. Picea glauca croissait autour du Ten Mile Lake à 9100 BP et P. mariana prenait de l'importance vers 7000 BP. Au Wonder Lake, les premières forêts ont également été dominées par P. glauca, puis par un nombre croissant de P. mariana. La chronologie de !'afforestation est incertaine en raison de datations au radiocarbone douteuses. Alnus semble être une espèce courante dans les deux régions vers 7000 BP. Les inventaires indiquent que la reconstitution de la paléovégétation est plus difficile à faire pour les forêts méridionales que septentrionales de l'Alaska, en raison de la plus grande diversité topographique, la sur-représentation de certains taxons et des problèmes de radio-datation. Les données indiquent tout de même que l'histoire de la végétation des forêts diffèrent au nord et au sud. Ces différences, mises en relation avec les fluctuations de températures présumées de l'Holocène, laissent croire que la forêt de l'Alaska ne répondra pas nécessairement de façon uniforme à un réchauffement climatique éventuel.DbiJibneBbie aiiarpa.viMbi ocaaKOB 03ep Baeae n TeHMaRJi, pacnojioxeHiibix B6JIII3H Bepxiiert rpaiiMUbi Jieca Ha ceBepe H wre A/iflCKiiHCKoro xpeôîa, OTpaacaioT ncropnio pacTHTejibHOCTH KOKIIOH lacr" Sopea/ibHoro jieca AJIBCKH. HoBbie ribiJibuebe anarpaMMbi iiOKaabiBaioT, HTO KycTapmiKOBOfi 6epr30B0fi TyHApe, xapaKTepiioft aJifl 3TMX aByx TeppiiTopufl B Teieime no3iuiero BiicKoiicmia, npemuecTBOBajia B oTaoaceiinnx 03. Banae 6emiaH TpaBHHUCTHa iyHapa. Populus iipopn3parra.n B otcpecruocnix 03. Teii.vianji 10000 /J.H., HO, JlO-BIUHMOMy, OTCyTCTBOBaa B pafione 03. BaHae. 9100 JI.H. B panoHe 03. Tenvianj] H.11I B iienocpeacrBeimoH 6/IH30CTH OT iiero npoH3pacTajia Picea glauca, KOTopan BMepTe c Picea mariana nrpaeT 3Ha'iiiTe/ibnyio pojib B codaBe pacTHTeJibHOCTM OKO/IO 7000 .i.n. B nepBbix Jiecax B paflone 03. BaHae TaKjKe aoMiiiuipoBajia Picea glauca, 110 3aTe,vi pojib Picea mariana iiaHimaeT B03pacacTaTb. Bpe.viH noflB/ieiiHfl jiecoB B panone 03. Banae uoKaiie ycraiiaBJiiiBaeTca iiaaeacHo paaiioyr-jiepoaiibiM McroaoM. Alnus o6pa3yer cooBiuecTBa B06011X pafioiiax OKOJIO 7000 JI.H. nojiyieiuibie aaiiHbie cBiiaeTejibCTByioT 0 TOM, HTO peKoiicTpyKniifl pacTiiTejibiiocTH 6yaer 6ojieecjio>KHon aJin lOîKHbix, ieM aJifl ceaepiibix 6opeajibiibix JiecoB AJIHCKH 1133a SHa'iinejibiioro TonorpafpimecKoro iiecxoacTBa,3aTpyaiieiii!Ji B iiHTepnpeTaumi neKOTopwx nbijibneitbix TaKCOHOB, npoGjieM c paanoyrjiepoaiibiM aaTHpBaiine.M. HeavioTpa tia 3TH npo6jieivibi, nojicpieHHbie aaHiibie noKa3biaiOT, HTO fjopeajibiibie Jieca 11a wre 11 ceBepe ioaciion iacni UetiTajibiion AJIHCKH wweioT pa3Jiiiiyio iiCTopnio. TaKiie pa3Jinmtfl, cBfl3xaiuibie c n3MeiieiijiflMii 3eMJiepaTyp B Teieiuie ro.'ioueiia, cBiiae-Te.TbCTByioT, HTO 6opeajibiibiri Jiec AJIHCKH ,vioxer ne OTBenaTb cienapnio rjio6aJibiioro noTen.ieiina u SyaymeM

Learning to read alters cortico-subcortical crosstalk in the visual system of illiterates

Learning to read is known to result in a reorganization of the developing cerebral cortex. In this longitudinal resting-state functional magnetic resonance imaging study in illiterate adults we show that only 6 months of literacy training can lead to neuroplastic changes in the mature brain. We observed that literacy-induced neuroplasticity is not confined to the cortex but increases the functional connectivity between the occipital lobe and subcortical areas in the midbrain and the thalamus. Individual rates of connectivity increase were significantly related to the individualdecoding skill gains. These findings crucially complement current neurobiological concepts ofnormal and impaired literacy acquisition