Structure of the unphosphorylated STAT5a dimer

STAT proteins have the function of signaling from the cell membrane into the nucleus, where they regulate gene transcription. Latent mammalian STAT proteins can form dimers in the cytoplasm even before receptor-mediated activation by specific tyrosine phosphorylation. Here we describe the 3.21-angstrom crystal structure of an unphosphorylated STAT5a homodimer lacking the N-terminal domain as well as the C-terminal transactivation domain. The overall structure of this fragment is very similar to phosphorylated STATs. However, important differences exist in the dimerization mode. Although the interface between phosphorylated STATs is mediated by their Src-homology 2 domains, the unphosphorylated STAT5a fragment dimerizes in a completely different manner via interactions between their beta-barrel and four-helix bundle domains. The STAT4 N-terminal domain dimer can be docked onto this STAT5a core fragment dimer based on shape and charge complementarities. The separation of the dimeric arrangement, taking place upon activation and nuclear translocation of STAT5a, is demonstrated by fluorescence resonance energy transfer experiments in living cells

The Joint Council on Thoracic Surgery Education (JCTSE) “Educate the Educators” Faculty Development Course: Analysis of the First 5 Years

BACKGROUND: Since 2010, the Joint Council on Thoracic Surgery Education, Inc (JCTSE) has sponsored an annual "Educate the Educators" (EtE) course. The goal is to provide United States academic cardiothoracic surgeons (CTS) the fundamentals of teaching skills, educational curriculum development, and using education for academic advancement. This report describes the course development and evaluation along with attendee's self-assessment of skills through the first 5 years of the program. METHODS: The content of this 2½-day course was based on needs assessment surveys of CTS and residents attending annual meetings in 2009. From 2010 to 2014, EtE was offered to all CTS at training programs approved by the Accreditation Council for Graduate Medical Education. Course content was evaluated by using end-of-course evaluation forms. A 5-point Likert scale (1 = poor, 5 = excellent) was used to obtain composite assessment mean scores for the 5 years on course variables, session presentations, and self-assessments. RESULTS: With 963 known academic CTS in the United States, 156 (16.3%) have attended, representing 70 of 72 training programs (97%), and 1 international surgeon attended. There were also 7 program coordinators. Ratings of core course contents ranged from 4.4 to 4.8, accompanied with highly complementary comments. Through self-assessment, skills and knowledge in all content areas statistically improved significantly. The effect of the course was evaluated with a follow-up survey in which responders rated the program 4.3 on the usefulness of the information for their career and 3.9 for educational productivity. CONCLUSIONS: The EtE program offers an excellent opportunity for academic CTS to enhance their teaching skills, develop educational activities, and prepare for academic promotion. With its unique networking and mentorship environment, the EtE program is an important resource in the evolution of cardiothoracic surgical training in the United States

Prehistory of Transit Searches

Nowadays the more powerful method to detect extrasolar planets is the transit method. We review the planet transits which were anticipated, searched, and the first ones which were observed all through history. Indeed transits of planets in front of their star were first investigated and studied in the solar system. The first observations of sunspots were sometimes mistaken for transits of unknown planets. The first scientific observation and study of a transit in the solar system was the observation of Mercury transit by Pierre Gassendi in 1631. Because observations of Venus transits could give a way to determine the distance Sun-Earth, transits of Venus were overwhelmingly observed. Some objects which actually do not exist were searched by their hypothetical transits on the Sun, as some examples a Venus satellite and an infra-mercurial planet. We evoke the possibly first use of the hypothesis of an exoplanet transit to explain some periodic variations of the luminosity of a star, namely the star Algol, during the eighteen century. Then we review the predictions of detection of exoplanets by their transits, those predictions being sometimes ancient, and made by astronomers as well as popular science writers. However, these very interesting predictions were never published in peer-reviewed journals specialized in astronomical discoveries and results. A possible transit of the planet beta Pic b was observed in 1981. Shall we see another transit expected for the same planet during 2018? Today, some studies of transits which are connected to hypothetical extraterrestrial civilisations are published in astronomical refereed journals. Some studies which would be classified not long ago as science fiction are now considered as scientific ones.Comment: Submiited to Handbook of Exoplanets (Springer

Protease-Activated Receptor 2 Deficiency Reduces Cardiac Ischemia/Reperfusion Injury

Protease-activated receptor-2 (PAR-2) signaling enhances inflammation in different diseases. The effect of PAR-2 deficiency in cardiac ischemia/reperfusion (I/R) injury is unknown. We investigated the effect of PAR-2 deficiency on I/R injury-induced infarct size, inflammation, heart remodeling and cardiac function

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Planetary Dynamics and Habitable Planet Formation In Binary Star Systems

Whether binaries can harbor potentially habitable planets depends on several factors including the physical properties and the orbital characteristics of the binary system. While the former determines the location of the habitable zone (HZ), the latter affects the dynamics of the material from which terrestrial planets are formed (i.e., planetesimals and planetary embryos), and drives the final architecture of the planets assembly. In order for a habitable planet to form in a binary star system, these two factors have to work in harmony. That is, the orbital dynamics of the two stars and their interactions with the planet-forming material have to allow terrestrial planet formation in the habitable zone, and ensure that the orbit of a potentially habitable planet will be stable for long times. We have organized this chapter with the same order in mind. We begin by presenting a general discussion on the motion of planets in binary stars and their stability. We then discuss the stability of terrestrial planets, and the formation of potentially habitable planets in a binary-planetary system.Comment: 56 pages, 29 figures, chapter to appear in the book: Planets in Binary Star Systems (Ed. N. Haghighipour, Springer publishing company