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At least 1,099 records · Page 61

MUSCLE W49: A multi-scale continuum and line exploration of the most luminous star formation region in the Milky Way. I. Data and the mass structure of the giant molecular cloud

The Multi-scale Continuum and Line Exploration of W49 is a comprehensive gas and dust survey of the giant molecular cloud (GMC) of W49A, the most luminous star-formation region in the Milky Way. The project covers, for the first time, the entire GMC at different scales and angular resolutions. In this paper, we present (1) an all-configuration Submillimeter Array mosaic in the 230 GHz (1.3 mm) band covering the central ∼3' × 3' (∼10 pc, known as W49N), where most of the embedded massive stars reside and (2) Purple Mountain Observatory 14 m telescope observations in the 90 GHz band, covering the entire GMC with maps of up to ∼35' × 35' in size, or ∼113 pc. We also make use of archival data from the Very Large Array, JCMT-SCUBA, the IRAM 30 m telescope, and the Caltech Submillimeter Observatory BOLOCAM Galactic Plane Survey. We derive the basic physical parameters of the GMC at all scales. Our main findings are as follows. (1) The W49 GMC is one of the most massive in the Galaxy, with a total mass M {sub gas} ∼ 1.1 × 10{sup 6} M {sub ☉} within a radius of 60 pc. Within a radius of 6 pc, the total gas mass is M {sub gas} ∼ 2 × 10{sup 5} M {sub ☉}. At these scales, only ∼1% of the material is photoionized. The mass reservoir is sufficient to form several young massive clusters (YMCs) as massive as a globular cluster. (2) The mass of the GMC is distributed in a hierarchical network of filaments. At scales <10 pc, a triple, centrally condensed structure peaks toward the ring of HC H II regions in W49N. This structure extends to scales from ∼10 to 100 pc through filaments that radially converge toward W49N and its less-prominent neighbor W49S. The W49A starburst most likely formed from global gravitational contraction with localized collapse in a 'hub-filament' geometry. (3) Currently, feedback from the central YMCs (with a present mass M {sub cl} ≳ 5 × 10{sup 4} M {sub ☉}) is still not enough to entirely disrupt the GMC, but further stellar mass growth could be enough to allow radiation pressure to clear the cloud and halt star formation. (4) The resulting stellar content will probably remain as a gravitationally bound massive star cluster or a small system of bound clusters.

79 ASTRONOMY AND ASTROPHYSICS↗

Super-relaxed myosins contribute to respiratory muscle hibernation in mechanically ventilated patients

Patients receiving mechanical ventilation in the intensive care unit (ICU) frequently develop contractile weakness of the diaphragm. Consequently, they may experience difficulty weaning from mechanical ventilation, which increases mortality and poses a high economic burden. Because of a lack of knowledge regarding the molecular changes in the diaphragm, no treatment is currently available to improve diaphragm contractility. We compared diaphragm biopsies from ventilated ICU patients (N= 54) to those of non-ICU patients undergoing thoracic surgery (N= 27). By integrating data from myofiber force measurements, x-ray diffraction experiments, and biochemical assays with clinical data, we found that in myofibers isolated from the diaphragm of ventilated ICU patients, myosin is trapped in an energy-sparing, super-relaxed state, which impairs the binding of myosin to actin during diaphragm contraction. Studies on quadriceps biopsies of ICU patients and on the diaphragm of previously healthy mechanically ventilated rats suggested that the super-relaxed myosins are specific to the diaphragm and not a result of critical illness. Exposing slow- and fast-twitch myofibers isolated from the diaphragm biopsies to small-molecule compounds activating troponin restored contractile force in vitro. These findings support the continued development of drugs that target sarcomere proteins to increase the calcium sensitivity of myofibers for the treatment of ICU-acquired diaphragm weakness.

Cell Biology↗

Identification of residues involved in allosteric signal transmission from amino acid binding site of pyruvate kinase muscle isoform 2

PKM2 is a rate-limiting enzyme in the glycolytic process and is involved in regulating tumor proliferation. Several amino acids (AAs) such as Asn, Asp, Val, and Cys have been shown to bind to the AA binding pocket of PKM2 and modulate its oligomeric state, substrate binding affinity, and activity. Although previous studies have attributed that the main chain and side chain of bound AAs are responsible for initiating signal to regulate PKM2, the signal transduction pathway remains elusive. To identify the residues involved in signal transfer process, N70 and N75 located at two ends of a β strand connecting the active site and AA binding pocket were altered. Biochemical studies of these variants with various AA ligands (Asn, Asp, Val, and Cys), illustrate that N70 and N75, along with β1 connecting these residues are part of the signal transduction pathway between the AA binding pocket and the active site. The results demonstrate that mutation of N70 to D prevents the transfer of the inhibitory signal mediated by Val and Cys, whereas N75 to L alteration blocks the activating signal initiated by Asn and Asp. Taken together, this study confirms that N70 is one of the residues responsible for transmitting the inhibitory signal and N75 is involved in the activation signal flow.

36 MATERIALS SCIENCE↗