mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been ...unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.
Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 ...(HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E<N1<N2). In this series of cells, the expression of HAI-2 but not HAI-1 was significantly decreased throughout the progression and occurred in parallel with increased activation of matriptase. The expression level and activity of matriptase increased whereas the HAI-2 protein level decreased over the course of orthotopic tumor growth in mice, which was consistent with the immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens. Knockdown of matriptase reduced the PCa cell invasion induced by HAI-2 knockdown. HAI-2 overexpression or matriptase silencing in N2 cells downregulated matriptase activity and significantly decreased tumorigenicity and metastatic capability in orthotopically xenografted mice. These results suggest that during the progression of human PCa, matriptase activity is primarily controlled by HAI-2 expression. The imbalance between HAI-2 and matriptase expression led to matriptase activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis.
Most studies of logistics outsourcing have focused on cost reduction, while few studies have reported on service benefits. This study empirically examines if outsourcing different logistics ...activities results in differences in logistics service performance. We identify and analyze the outsourcing of four levels of logistics activities: transportation (level 1), packaging (level 2), transportation management (level 3), and distribution network management (level 4). A research framework was formulated to discuss the effect of the outsourcing decision of different levels on perceived logistics service performance and includes the moderating role that supply chain complexity may play in the proposed relationships. Our findings show that outsourcing has no direct impact on service performance (delivery reliability, flexibility and lead-time) in any of the four levels. However, the performance when outsourcing level 4 activities increases with an increasing degree of demand complexity. Furthermore, chilled foods have higher service performance than non-chilled foods. These findings show the complex relationships between levels of outsourcing, performance and supply chain characteristics.
Abstract
We present our analysis of the Type II supernova DLT16am (SN 2016ija). The object was discovered during the ongoing
(DLT40) one-day cadence supernova search at
in the “edge-on” nearby (
) ...galaxy NGC 1532. The subsequent prompt and high-cadenced spectroscopic and photometric follow-up revealed a highly extinguished transient, with
, consistent with a standard extinction law with
R
V
= 3.1 and a bright (
) absolute peak magnitude. A comparison of the photometric features with those of large samples of SNe II reveals a fast rise for the derived luminosity and a relatively short plateau phase, with a slope of
, consistent with the photometric properties typical of those of fast-declining SNe II. Despite the large uncertainties on the distance and the extinction in the direction of DLT16am, the measured photospheric expansion velocity and the derived absolute
V
-band magnitude at
after the explosion match the existing luminosity–velocity relation for SNe II.
SN 2014J in M82 is the closest detected Type Ia supernova (SN Ia) in at least 28 yr and perhaps in 410 yr. Despite its small distance of 3.3 Mpc, SN 2014J is surprisingly faint, peaking at ...V = 10.6 mag, and assuming a typical SN Ia luminosity, we infer an observed visual extinction of A
V
= 2.0 ± 0.1 mag. But this picture, with R
V
= 1.6 ± 0.2, is too simple to account for all observations. We combine 10 epochs (spanning a month) of HST/Space Telescope Imaging Spectrograph (STIS) ultraviolet through near-infrared spectroscopy with HST/Wide Field Camera 3 (WFC3), Katzman Automatic Imaging Telescope, and FanCam photometry from the optical to the infrared and nine epochs of high-resolution TRES (Tillinghast Reflection Echelle Spectrograph) spectroscopy to investigate the sources of extinction and reddening for SN 2014J. We argue that the wide range of observed properties for SN 2014J is caused by a combination of dust reddening, likely originating in the interstellar medium of M82, and scattering off circumstellar material. For this model, roughly half of the extinction is caused by reddening from typical dust (E(B − V) = 0.45 mag and R
V
= 2.6) and roughly half by scattering off Large Magellanic Cloud-like dust in the circumstellar environment of SN 2014J.
We present nebular phase optical and near-infrared spectroscopy of the Type Ia supernova (SN) 2017cbv. The early light curves of SN 2017cbv showed a prominent blue bump in the U, B, and g bands ...lasting for ∼5 days. One interpretation of the early light curve is that the excess blue light is due to shocking of the SN ejecta against a nondegenerate companion star-a signature of the single degenerate scenario. If this is the correct interpretation, the interaction between the SN ejecta and the companion star could result in significant H (or helium) emission at late times, possibly along with other species, depending on the companion star and its orbital separation. A search for H emission in our +302 d spectrum yields a nondetection, with a LH < 8.0 × 1035 erg s−1 (given an assumed distance of D = 12.3 Mpc), which we verified by implanting simulated H emission into our data. We make a quantitative comparison to models of swept-up material stripped from a nondegenerate companion star and limit the mass of hydrogen that might remain undetected to MH < 1 × 10−4 M . A similar analysis of helium star related lines yields a MHe < 5 × 10−4 M . Taken at face value, these results argue against a nondegenerate H- or He-rich companion in Roche lobe overflow as the progenitor of SN 2017cbv. Alternatively, there could be weaknesses in the envelope-stripping and radiative transfer models necessary to interpret the strong H and He flux limits.
Lactobacillus kefiranofaciens M1, isolated from and identified in Taiwanese milk kefir grain, has demonstrated immune-modulating activity. In the present study, we further investigated the effects of ...Lb. kefiranofaciens M1 on intestinal epithelial cells in vitro and on dextran sodium sulfate (DSS)-induced colitis in vivo. The possible mechanisms regarding the cytokine products and intestinal epithelial barrier restoration as well as the putative receptor for the protective effects of Lb. kefiranofaciens M1 were investigated. In vitro results indicated that Lb. kefiranofaciens M1 could strengthen the epithelial barrier function in vitro by increasing the transepithelial electrical resistance (TEER) and significantly upregulated the level of the chemokine CCL-20 at both the apical and basolateral sites. The in vivo effects of Lb. kefiranofaciens M1 on the regulation of intestinal physiology indicate that this strain could ameliorate DSS-induced colitis with a significant attenuation of the bleeding score and colon length shortening. Production of proinflammatory cytokines was decreased and that of the antiinflammatory cytokine IL-10 was increased in the DSS-treated mice given Lb. kefiranofaciens M1. The putative receptor for the protective effects of Lb. kefiranofaciens M1 was toll-like receptor 2 (TLR2), which was involved in probiotic-induced cytokine production in vitro and in attenuation of the bleeding score and colon length shortening in vivo. In this study, the kefir lactobacillus Lb. kefiranofaciens M1 clearly demonstrated an anticolitis effect. Based on these results, Lb. kefiranofaciens M1 has the potential to be applied in fermented dairy products as an alternative therapy for intestinal disorders.
Abstract
The Type Ia supernova (SN Ia) LSQ14fmg exhibits exaggerated properties that may help to reveal the origin of the “super-Chandrasekhar” (or 03fg-like) group. The optical spectrum is typical ...of a 03fg-like SN Ia, but the light curves are unlike those of any SNe Ia observed. The light curves of LSQ14fmg rise extremely slowly. At −23 rest-frame days relative to
B
-band maximum, LSQ14fmg is already brighter than
mag before host extinction correction. The observed color curves show a flat evolution from the earliest observation to approximately 1 week after maximum. The near-infrared light curves peak brighter than −20.5 mag in the
J
and
H
bands, far more luminous than any 03fg-like SNe Ia with near-infrared observations. At 1 month past maximum, the optical light curves decline rapidly. The early, slow rise and flat color evolution are interpreted to result from an additional excess flux from a power source other than the radioactive decay of the synthesized
56
Ni. The excess flux matches the interaction with a typical superwind of an asymptotic giant branch (AGB) star in density structure, mass-loss rate, and duration. The rapid decline starting at around 1 month past
B
-band maximum may be an indication of rapid cooling by active carbon monoxide (CO) formation, which requires a low-temperature and high-density environment. These peculiarities point to an AGB progenitor near the end of its evolution and the core degenerate scenario as the likely explosion mechanism for LSQ14fmg.
We present ultraviolet through near-infrared (NIR) broadband photometry, and visual-wavelength and NIR spectroscopy of the Type Iax supernova (SN) 2012Z. The data set consists of both early- and ...late-time observations, including the first late phase NIR spectrum obtained for a spectroscopically classified SN Iax. Simple model calculations of its bolometric light curve suggest SN 2012Z produced ~0.3 M⊙ of 56Ni, ejected about a Chandrasekhar mass of material, and had an explosion energy of ~1051 erg, making it one of the brightest (MB = −18.3 mag) and most energetic SN Iax yet observed. The late phase (+269d) NIRspectrum of SN 2012Z is found to broadly resemble similar epoch spectra of normal SNe Ia; however, like other SNe Iax, corresponding visual-wavelength spectra differ substantially from all supernova types. Constraints from the distribution of intermediate mass elements, e.g., silicon and magnesium, indicate that the outer ejecta did not experience significant mixing during or after burning, and the late phase NIR line profiles suggests most of the 56Ni is produced during high density burning. The various observational properties of SN 2012Z are found to be consistent with the theoretical expectations of a Chandrasekhar mass white dwarf progenitor that experiences a pulsational delayed detonation, which produced several tenths of a solar mass of 56Ni during the deflagration burning phase and little (or no) 56Ni during the detonation phase. Within this scenario only a moderate amount of Rayleigh-Taylor mixing occurs both during the deflagration and fallback phase of the pulsation, and the layered structure of the intermediate mass elements is a product of the subsequent denotation phase. The fact that the SNe Iax population does not follow a tight brightness-decline relation similar to SNe Ia can then be understood in the framework of variable amounts of mixing during pulsational rebound and variable amounts of 56Ni production during the early subsonic phase of expansion.
ABSTRACT
The observed diversity in Type Ia supernovae (SNe Ia) – the thermonuclear explosions of carbon–oxygen white dwarf stars used as cosmological standard candles – is currently met with a ...variety of explosion models and progenitor scenarios. To help improve our understanding of whether and how often different models contribute to the occurrence of SNe Ia and their assorted properties, we present a comprehensive analysis of seven nearby SNe Ia. We obtained one to two epochs of optical spectra with Gemini Observatory during the nebular phase (>200 d past peak) for each of these events, all of which had time series of photometry and spectroscopy at early times (the first ∼8 weeks after explosion). We use the combination of early- and late-time observations to assess the predictions of various models for the explosion (e.g. double-detonation, off-centre detonation, stellar collisions), progenitor star (e.g. ejecta mass, metallicity), and binary companion (e.g. another white dwarf or a non-degenerate star). Overall, we find general consistency in our observations with spherically symmetric models for SN Ia explosions, and with scenarios in which the binary companion is another degenerate star. We also present an in-depth analysis of SN 2017fzw, a member of the subgroup of SNe Ia which appear to be transitional between the subluminous ‘91bg-like’ events and normal SNe Ia, and for which nebular-phase spectra are rare.
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