The role of cardiac troponin T quantity and function in cardiac development and dilated cardiomyopathy

Background: Hypertrophic (HCM) and dilated (DCM) cardiomyopathies results from sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT function or quantity; whether the severity of DCM is related to the ratio of mutant to wildtype cTnT; whether Ca2+ desensitization occurs in DCM; and whether absence of cTnT impairs early embryonic cardiogenesis. Methods and Findings: We ablated Tnnt2 to produce heterozygous Tnnt2+/ mice, and crossbreeding produced homozygous null Tnnt2-/-embryos. We also generated transgenic mice overexpressing wildtype (TGWT) or DCM mutant (TGK210Δ) Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying wildtype (Tnnt2+/-/TGWT) or mutant (Tnnt2+/-/TGK210Δ) transgenes. Tnnt2+/-mice relative to wildtype had significantly reduced transcript (0.82 ± 0.06 [SD] vs. 1.00 ± 0.12 arbitrary units; p = 0.025), but not protein (1.01 ± 0.20 vs. 1.00 ± 0.13 arbitrary units; p = 0.44). Tnnt2+/-mice had normal hearts (histology, mass, left ventricular end diastolic diameter [LVEDD], fractional shortening [FS]). Moreover, whereas Tnnt2+/-/ TGK210Δ mice had severe DCM, TGK210Δ mice had only mild DCM (FS 18 ± 4 vs. 29 ± 7%; p < 0.01). The difference in severity of DCM may be attributable to a greater ratio of mutant to wildtype Tnnt2 transcript in Tnnt2+/-/TGK210Δ relative to TGK210Δ mice (2.42±0.08, p = 0.03). Tnnt2+/-/TGK210Δ muscle showed Ca2+ desensitization (pCa50 = 5.34 ± 0.08 vs. 5.58 ± 0.03 at sarcomere length 1.9 μm. p<0.01), but no difference in maximum force generation. Day 9.5 Tnnt2-/-embryos had normally looped hearts, but thin ventricular walls, large pericardial effusions, noncontractile hearts, and severely disorganized sarcomeres. Conclusions: Absence of one Tnnt2 allele leads to a mild deficit in transcript but not protein, leading to a normal cardiac phenotype. DCM results from abnormal function of a mutant protein, which is associated with myocyte Ca2+ desensitization. The severity of DCM depends on the ratio of mutant to wildtype Tnnt2 transcript. cTnT is essential for sarcomere formation, but normal embryonic heart looping occurs without contractile activity. © 2008 Ahmad et al

Discovery of the peculiar supernova 1998bw in the error box of GRB980425

The discovery of X-ray, optical and radio afterglows of gamma-ray bursts (GRBs) and the measurements of the distances to some of them have established that these events come from Gpc distances and are the most powerful photon emitters known in the Universe, with peak luminosities up to 10^52 erg/s. We here report the discovery of an optical transient, in the BeppoSAX Wide Field Camera error box of GRB980425, which occurred within about a day of the gamma-ray burst. Its optical light curve, spectrum and location in a spiral arm of the galaxy ESO 184-G82, at a redshift z = 0.0085, show that the transient is a very luminous type Ic supernova, SN1998bw. The peculiar nature of SN1998bw is emphasized by its extraordinary radio properties which require that the radio emitter expand at relativistical speed. Since SN1998bw is very different from all previously observed afterglows of GRBs, our discovery raises the possibility that very different mechanisms may give rise to GRBs, which differ little in their gamma-ray properties.Comment: Under press embargo at Nature (submitted June 10, 1998

Theory of Low-Mass Stars and Substellar Objects

Since the discovery of the first bona-fide brown dwarfs and extra-solar planets in 1995, the field of low mass stars and substellar objects has considerably progressed, both from theoretical and observational viewpoints.Recent developments in the physics entering the modeling of these objects have led to significant improvements in the theory and to a better understanding of their mechanical and thermal properties. This theory can now be confronted with observations directly in various observational diagrams (color-color, color-magnitude, mass-magnitude, mass-spectral type), a stringent and unavoidable constraint which became possible only recently, with the generation of synthetic spectra. In this paper, we present the current state-of-the-art general theory of low-mass stars and sub-stellar objects, from one solar mass to one Jupiter mass, regarding primarily their interior structure and evolution. This review is a natural complement to the previous review on the atmosphere of low-mass stars and brown dwarfs (Allard et al 1997). Special attention is devoted to the comparison of the theory with various available observations. The contribution of low-mass stellar and sub-stellar objects to the Galactic mass budget is also analysed.Comment: 81 pages, Latex file, uses aasms4.sty, review for Annual Review of Astronomy and Astrophysics, vol. 38 (2000

Defensive properties of pyrrolizidine alkaloids against microorganisms

The understanding of the selection factors that drive chemical diversification of secondary metabolites of constitutive defence systems in plants, such as pyrrolizidine alkaloids (PAs), is still incomplete. Historically, plants always have been confronted with microorganisms. Long before herbivores existed on this planet, plants had to cope with microbial pathogens. Therefore, plant pathogenic microorganisms may have played an important role in the early evolution of the secondary metabolite diversity. In this review, we discuss the impact that plant-produced PAs have on plant-associated microorganisms. The objective of the review is to present the current knowledge on PAs with respect to anti-microbial activities, adaptation and detoxification by microorganisms, pathogenic fungi, root protection and PA induction. Many in vitro experiments showed effects of PAs on microorganisms. These results point to the potential of microorganisms to be important for the evolution of PAs. However, only a few in vivo studies have been published and support the results of the in vitro studies. In conclusion, the topics pointed out in this review need further exploration by carrying out ecological experiments and field studies

A sub-Neptune transiting the young field star HD 18599 at 40 pc

Transiting exoplanets orbiting young nearby stars are ideal laboratories for testing theories of planet formation and evolution. However, to date only a handful of stars with age &amp;lt;1 Gyr have been found to host transiting exoplanets. Here we present the discovery and validation of a sub-Neptune around HD 18599 , a young (300 Myr), nearby (d = 40 pc) K star. We validate the transiting planet candidate as a bona fide planet using data from the TESS , Spitzer , and Gaia  missions, ground-based photometry from IRSF , LCO , PEST , and NGTS , speckle imaging from Gemini, and spectroscopy from CHIRON , NRES , FEROS , and Minerva-Australis . The planet has an orbital period of 4.13 d , and a radius of 2.7 R⊕ . The RV data yields a 3-σ mass upper limit of 30.5 M⊕  which is explained by either a massive companion or the large observed jitter typical for a young star. The brightness of the host star (V∼9 mag) makes it conducive to detailed characterization via Doppler mass measurement which will provide a rare view into the interior structure of young planets

THE PAN-PACIFIC PLANET SEARCH. VI. GIANT PLANETS ORBITING HD 86950 and HD 222076

We report the detection of two new planets orbiting the K giants HD 86950 and HD 222076, based on precise radial velocities obtained with three instruments: AAT/UCLES, FEROS, and CHIRON. HD 86950b has a period of 1270 ± 57 days at a = 2.72 ± 0.08 au, and m sin i = 3.6 ± 0.7 Mjup. HD 222076b has P = 871 ± 19 days at a = 1.83 ± 0.03 au, and m sin i = 1.56 ± 0.11 MJup. These two giant planets are typical of the population of planets known to orbit evolved stars. In addition, we find a high-amplitude periodic velocity signal (K ∼ 50 m s-1) in HD 29399 and show that it is due to stellar variability rather than Keplerian reflex motion. We also investigate the relation between planet occurrence and host-star metallicity for the 164-star Pan-Pacific Planet Search (PPPS) sample of evolved stars. In spite of the small sample of PPPS detections, we confirm the trend of increasing planet occurrence as a function of metallicity found by other studies of planets orbiting evolved stars

Про дачника

Волк прибежал к лисе, говорит: / – Ты знаешь, съел какое-то странное животное. Боюсь, как бы не отравиться, вдруг ядовитое. / – А что оно собой представляло? / – Сверху мохнатое, руки грязные, ноги грязные, пахнет навозом. / – А, - говорит, - не переживай: это дачник