Note and Comment

Declaratory Judgments - The widespread interest in this ntw form of remedial instrument, which was. somewhat dashed by the recent decision of the Michigan Supreme. Court \u27n Amwmy v. Grand Ropds.Ry. Co. (r920), 211 Mich. 59, holding declaritoty relief to b! non-judicial and -outside the constitutional power of \u27courts (9ig MicH. LAw Rzv. 86), has been revived by the action of\u27the legislature of. Kansas in enacting a derlaratory judgment statute almost identical with the .Michigan act.. This was done with full knowledge of the decision in the .4mmy case, and inasmuch -as it is well known that some of the judges oti\u27the Supreme Court of Kansas have taken an active interest in advocating this reform, it is fair to assume that the act is likely tQ escape the constitutionalguillotine The English judges. have for two geneiations or m9re been the.chief proponents of English procedural. reform, and nothing *ould be more universally welcomed in this country than the generous participation and leadership of our high. judges in the efforts of\u27the public to. make\u27the administration of justice .more respoksive to social needs

Mycosin-1, a subtilisin-like serine protease of Mycobacterium tuberculosis, is cell wall-associated and expressed during infection of macrophages

BACKGROUND: Exported proteases are commonly associated with virulence in bacterial pathogens, yet there is a paucity of information regarding their role in Mycobacterium tuberculosis. There are five genes (mycP1-5) present within the genome of Mycobacterium tuberculosis H37Rv that encode a family of secreted, subtilisin-like serine proteases (the mycosins). The gene mycP1 (encoding mycosin-1) was found to be situated 3700 bp (four ORF's) from the RD1 deletion region in the genome of the attenuated vaccine strain M. bovis BCG (bacille de Calmette et Guérin) and was selected for further analyses due to the absence of expression in this organism. RESULTS: Full-length, 50 kDa mycosin-1 was observed in M. tuberculosis cellular lysates, whereas lower-molecular-weight species were detected in culture filtrates. A similar lower-molecular-weight species was also observed during growth in macrophages. Mycosin-1 was localized to the membrane and cell wall fractions in M. tuberculosis by Western blotting, and to the cell envelope by electron microscopy. Furthermore, M. tuberculosis culture filtrates were shown to contain a proteolytic activity inhibited by mixed serine/cysteine protease inhibitors and activated by Ca(2+), features typical of the subtilisins. CONCLUSIONS: Mycosin-1 is an extracellular protein that is membrane- and cell wall-associated, and is shed into the culture supernatant. The protein is expressed after infection of macrophages and is subjected to proteolytic processing. Although proteolytically active mycosin-1 could not be generated recombinantly, serine protease activity containing features typical of the subtilisins was detected in M. tuberculosis culture filtrates

Communications Biophysics

Contains reports on five research projects

MAP4K3 mediates amino acid-dependent regulation of autophagy via phosphorylation of TFEB

Autophagy is the major cellular pathway by which macromolecules are degraded, and amino acid depletion powerfully activates autophagy. MAP4K3, or germinal-center kinase-like kinase, is required for robust cell growth in response to amino acids, but the basis for MAP4K3 regulation of cellular metabolic disposition remains unknown. Here we identify MAP4K3 as an amino acid-dependent regulator of autophagy through its phosphorylation of transcription factor EB (TFEB), a transcriptional activator of autophagy, and through amino acid starvation-dependent lysosomal localization of MAP4K3. We document that MAP4K3 physically interacts with TFEB and MAP4K3 inhibition is sufficient for TFEB nuclear localization, target gene transactivation, and autophagy, even when mTORC1 is activated. Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration. Our results uncover a role for MAP4K3 in the control of autophagy and reveal MAP4K3 as a central node in nutrient-sensing regulation

A Luminous Be+White Dwarf Supersoft Source in the Wing of the SMC: MAXI J0158-744

We present a multi-wavelength analysis of the very fast X-ray transient MAXI J0158-744, which was detected by MAXI/GSC on 2011 November 11. The subsequent exponential decline of the X-ray flux was followed with Swift observations, all of which revealed spectra with low temperatures (~100eV) indicating that MAXI J0158-744 is a new Supersoft Source (SSS). The Swift X-ray spectra near maximum show features around 0.8 keV that we interpret as possible absorption from OVIII, and emission from O, Fe, and Ne lines. We obtained SAAO and ESO optical spectra of the counterpart early in the outburst and several weeks later. The early spectrum is dominated by strong Balmer and HeI emission, together with weaker HeII emission. The later spectrum reveals absorption features that indicate a B1/2IIIe spectral type, and all spectral features are at velocities consistent with the Small Magellanic Cloud. At this distance, it is a luminous SSS (>10^37 erg/s) but whose brief peak luminosity of >10^39 erg/s in the 2-4 keV band makes it the brightest SSS yet seen at "hard" X-rays. We propose that MAXI J0158-744 is a Be-WD binary, and the first example to possibly enter ULX territory. The brief hard X-ray flash could possibly be a result of the interaction of the ejected nova shell with the B star wind in which the white dwarf (WD) is embedded. This makes MAXI J0158-744 only the third Be/WD system in the Magellanic Clouds, but it is by far the most luminous. The properties of MAXI J0158-744 give weight to previous suggestions that SSS in nearby galaxies are associated with early-type stellar systems.Comment: 15 pages, 8 figures; ApJ accepte

Imaging X-Ray Polarimeter for Solar Flares (IXPS)

We describe the design of a balloon-borne Imaging X-ray Polarimeter for Solar flares (IX PS). This novel instrument, a Time Projection Chamber (TPC) for photoelectric polarimetry, will be capable of measuring polarization at the few percent level in the 20-50 keV energy range during an M- or X class flare, and will provide imaging information at the approx.10 arcsec level. The primary objective of such observations is to determine the directivity of nonthermal high-energy electrons producing solar hard X-rays, and hence to learn about the particle acceleration and energy release processes in solar flares. Secondary objectives include the separation of the thermal and nonthermal components of the flare X-ray emissions and the separation of photospheric albedo fluxes from direct emissions