Microquasars as sources of positron annihilation radiation

We consider the production of positrons in microquasars, i.e. X-ray binary systems that exhibit jets frequently, but not continuously. We estimate the production rate of positrons in microquasars, both by simple energy considerations and in the framework of various proposed models. We then evaluate the collective emissivity of the annihilation radiation produced by Galactic microquasars and we find that it might constitute a substantial contribution to the annihilation flux measured by INTEGRAL/SPI. We also discuss the possible spatial distribution of Galactic microquasars, on the basis of the (scarce) available data and the resulting morphology of the flux received on Earth. Finally, we consider nearby 'misaligned' microquasars, with jets occasionally hitting the atmosphere of the companion star; these would represent interesting point sources, for which we determine the annihilation flux and the corresponding light curve, as well as the line's spectral profile. We discuss the possibility of detection of such point sources by future instruments.Comment: 13 pages, 7 figures, accepted in A&

In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-Synuclein within E. coli cells

α-Synuclein is a small protein strongly implicated in the pathogenesis of Parkinson’s disease and related neurodegenerative disorders. We report here the use of in-cell NMR spectroscopy to observe directly the structure and dynamics of this protein within E. coli cells. To improve the accuracy in the measurement of backbone chemical shifts within crowded in-cell NMR spectra, we have developed a deconvolution method to reduce inhomogeneous line broadening within cellular samples. The resulting chemical shift values were then used to evaluate the distribution of secondary structure populations which, in the absence of stable tertiary contacts, are a most effective way to describe the conformational fluctuations of disordered proteins. The results indicate that, at least within the bacterial cytosol, α-synuclein populates a highly dynamic state that, despite the highly crowded environment, has the same characteristics as the disordered monomeric form observed in aqueous solution

Protein loop compaction and the origin of the effect of arginine and glutamic acid mixtures on solubility, stability and transient oligomerization of proteins

Addition of a 50 mM mixture of l-arginine and l-glutamic acid (RE) is extensively used to improve protein solubility and stability, although the origin of the effect is not well understood. We present Small Angle X-ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) results showing that RE induces protein compaction by collapsing flexible loops on the protein core. This is suggested to be a general mechanism preventing aggregation and improving resistance to proteases and to originate from the polyelectrolyte nature of RE. Molecular polyelectrolyte mixtures are expected to display long range correlation effects according to dressed interaction site theory. We hypothesize that perturbation of the RE solution by dissolved proteins is proportional to the volume occupied by the protein. As a consequence, loop collapse, minimizing the effective protein volume, is favored in the presence of RE

Towards a population of HMXB/NS microquasars as counterparts of low-latitude unidentified EGRET sources

The discovery of the microquasar LS 5039 well within the 95% conficence contour of the Unidentified EGRET Source (UES) 3EG J1824-1514 was a major step towards the possible association between microquasars (MQs) and UESs. The recent discovery of precessing relativistic radio jets in LS I +61 303, a source associated for long time with 2CG 135+01 and with the UES 3EG J0241+6103, has given further support to this idea. Finally, the very recently proposed association between the microquasar candidate AX J1639.0-4642 and the UES 3EG J1639-4702 points towards a population of High Mass X-ray Binary (HMXB)/Neutron Star (NS) microquasars as counterparts of low-latitude unidentified EGRET sources.Comment: 12 pages, 7 figures. Proceedings of the Conference "The Multiwavelength Approach to Unidentified Gamma-ray Sources", to appear in the journal Astrophysics and Space Scienc

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

NMRDyn: A Program for NMR Relaxation Studies of Protein Association

Self-association is an important biological phenomenon that is associated with many cellular processes. NMR relaxation measurements provide data about protein molecular dynamics at the atomic level and are sensitive to changes induced by self-association. Thus, measurements and analysis of NMR relaxation data can provide structurally resolved information on self-association that would not be accessible otherwise. Here, we present a computer program, NMRdyn, which analyses relaxation data to provide parameters defining protein self-association. Unlike existing relaxation analysis software, NMRdyn can explicitly model the monomer-oligomer equilibrium while fitting measured relaxation data. Additionally, the program is packaged with a user-friendly interface, which is important because relaxation data can often be large and complex. NMRdyn is available from http://research1t.imb.uq.edu.au/nmr/NMRdyn

Decoding the Components of Dynamics in Three-Domain Proteins

In this study we examine the feasibility and limitations of describing the motional behavior of three-domain proteins in which the domains are linearly connected. In addition to attempting a determination of both the internal and overall re-orientational correlation times, we investigate the existence of correlations in the motions between the three domains. Since in linearly arranged three-domain proteins there are typically no experimental data that can directly report on motional correlation between the first and third domain, we address this question by dynamics simulations. Two limiting cases occur: 1) for weak repulsive potentials and 2) when strong repulsive potentials are applied between sequential domains. The motions of the first and third domains become correlated in the case of strong inter-domain repulsive potentials when these potentials do not allow the angle between the sequential domains to be smaller than about 60°. Although various modeling approaches are available, we chose to use the model-free and extended model-free formalisms of Lipari and Szabo due to their widespread application in the study of protein dynamics. We find that the motional behavior can be separated into two components; the first component represents the concerted overall motion of the three domains, and the second describes the independent component of the motion of each individual domain. We find that this division of the motional behavior of the protein is maintained only when their timescales are distinct and can be made when the angles between sequential domains remain between 60° and 160°. In this work, we identify and quantify inter-domain motional correlations

Identification and characterization of Cardiac Glycosides as senolytic compounds

Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.We thank Matthias Drosten, Alejo Efeyan and Sean Morrison for plasmids. F.T-M. is a postdoctoral fellow from CONACYT (cvu 268632); P.P. is a predoctoral fellow from Xunta de Galicia; M.C. is a "Miguel Servet II" investigator (CPII16/00015). P.P.-R. receives support from a program by the Deputacion de Coruna (BINV-CS/2019). Work in the laboratory of M.C. is funded by grant RTI2018-095818-B-100 (MCIU/AEI/FEDER, UE). P.J.F.-M. is funded by the IMDEA Food Institute, the Ramon Areces Foundation, (CIVP18A3891), and a Ramon y Cajal Award (MICINN) (RYC-2017-22335). M.P.I. is funded by Talento Modalidad-1 Program Grant, Madrid Regional Government (#2018-T1/BIO-11262). F.P. was funded by a Long Term EMBO Fellowship (ALTF-358-2017) and F.H-G. was funded by the PhD4MD Programme of the IRB, Hospital Clinic and IDIBAPS. Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and "laCaixa" Foundation.S

Unidentified gamma-ray sources off the Galactic plane as low-mass microquasars?

A subset of the unidentified EGRET gamma-ray sources with no active galactic nucleus or other conspicuous counterpart appears to be concentrated at medium latitudes. Their long-term variability and their spatial distribution indicate that they are distinct from the more persistent sources associated with the nearby Gould Belt. They exhibit a large scale height of 1.3 +/- 0.6 kpc above the Galactic plane. Potential counterparts for these sources include microquasars accreting from a low-mass star and spewing a continuous jet. Detailed calculations have been performed of the jet inverse Compton emission in the radiation fields from the star, the accretion disc, and a hot corona. Different jet Lorentz factors, powers, and aspect angles have been explored. The up-scattered emission from the corona predominates below 100 MeV whereas the disc and stellar contributions are preponderant at higher energies for moderate (~15 deg) and small (~1 deg) aspect angles, respectively. Yet, unlike in the high-mass, brighter versions of these systems, the external Compton emission largely fails to produce the luminosities required for 5 to 10 kpc distant EGRET sources. Synchrotron-self-Compton emission appears as a promising alternative.Comment: 11 pages, 5 figures. Contributed paper to the "Multiwavelength Approach to Unidentified Gamma-Ray Sources", Eds. K.S. Cheng & G.E. Romero, to appear in Astrophysics and Space Science journa