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We present observations of the 3 P 1–3 P 0 fine-structure line of atomic carbon using the ASTE 10m sub-mm telescope towards RCW 38, the youngest super star cluster in the Milky Way. The detected [C  i ] emission is compared with the CO J = 1–0 image cube presented in Fukui et al. (2016 , ApJ, 820, 26) which has an angular resolution of 40″ (∼0.33 pc). The overall distribution of the [C  i ] emission in this cluster is similar to that of the 13CO emission. The optical depth of the [C  i ] emission was found to be τ = 0.1–0.6, suggesting mostly optically thin emission. An empirical conversion factor from the [C  i ] integrated intensity to the H2 column density was estimated as X [C  i ] |$= 6.3 \times 10 ^{20}\:$| cm−2 K−1 km−1 s (for visual extinction: A V ≤ 10 mag) and 1.4 × 1021 cm−2 K−1 km−1 s (for A V of 10–100 mag). The column density ratio of the [C  i ] to CO (N [C  i ] |$/N_{\rm CO}$|⁠) was derived as ∼0.1 for A V of 10–100 mag, which is consistent with that of the Orion cloud presented in Ikeda et al. (2002 , ApJ, 571, 560). However, our results cover an A V regime of up to 100 mag, which is wider than the coverage found in Orion, which reaches up to ∼60 mag. Such a high [C  i ] |$/$| CO ratio in a high- A V region is difficult to explain via the plane-parallel photodissociation region model, which predicts that this ratio is close to 0 due to the heavy shielding of the ultraviolet (UV) radiation. Our results suggest that the molecular gas in this cluster is highly clumpy, allowing deep penetration of UV radiation even at averaged A V values of 100 mag. Recent theoretical works have presented models consistent with such clumped gas distribution with a sub-pc clump size (e.g. Tachihara et al. 2018 , arXiv:1811.02224). [ABSTRACT FROM AUTHOR]

Summary PIWI-interacting RNAs (piRNAs) play a crucial role in transposon silencing in animal germ cells. In piRNA biogenesis, single-stranded piRNA intermediates are loaded into PIWI-clade proteins and cleaved by Zucchini/MitoPLD, yielding precursor piRNAs (pre-piRNAs). Pre-piRNAs that are longer than the mature piRNA length are then trimmed at their 3′ ends. Although recent studies implicated the Tudor domain protein Papi/Tdrkh in pre-piRNA trimming, the identity of Trimmer and its relationship with Papi/Tdrkh remain unknown. Here, we identified PNLDC1, an uncharacterized 3′-5′ exonuclease, as Trimmer in silkworms. Trimmer is enriched in the mitochondrial fraction and binds to Papi/Tdrkh. Depletion of Trimmer and Papi/Tdrkh additively inhibits trimming, causing accumulation of ∼35–40-nt pre-piRNAs that are impaired for target cleavage and prone to degradation. Our results highlight the cooperative action of Trimmer and Papi/Tdrkh in piRNA maturation. [ABSTRACT FROM AUTHOR]

PIWI-interacting RNAs (piRNAs) guide PIWI proteins to target transposons in germline cells, thereby suppressing transposon activity to preserve genome integrity in metazoans' gonadal tissues. Piwi, one of three Drosophila PIWI proteins, is expressed in the nucleus and suppresses transposon activity by forming heterochromatin in an RNA cleavage-independent manner. Recently, Piwi was reported to control cell metabolism in Drosophila fat body, providing an example of piRNAs acting in non-gonadal somatic tissues. However, mutant flies of the other two PIWI proteins, Aubergine (Aub) and Argonaute3 (Ago3), show no apparent phenotype except for infertility, blurring the importance of the piRNA pathway in non-gonadal somatic tissues. The silkworm, Bombyx mori, possesses two PIWI proteins, Siwi (Aub homolog) and BmAgo3 (Ago3 homolog), whereas B. mori does not have a Piwi homolog. Siwi and BmAgo3 are mainly expressed in gonadal tissues and play a role in repressing transposon activity by cleaving transposon RNA in the cytoplasm. Here, we generated Siwi and BmAgo3 loss-of-function mutants of B. mori and found that they both showed delayed larval growth and failed to become adult moths. They also exhibited defects in wing development and sexual differentiation. Transcriptome analysis revealed that loss of somatic piRNA biogenesis pathways results in abnormal expression of not only transposons but also host genes, presumably causing severe growth defects. Our results highlight the roles of non-gonadal somatic piRNAs in B. mori development. Author summary: In animal germ cells, PIWI proteins and piRNAs play an important role in the defense system against selfish elements such as transposons. The fruit fly Drosophila possesses two PIWI proteins, Aub and Ago3, both of which are required for piRNA production and transposon repression in the cytoplasm of germ cells. However, their roles in somatic cells are unclear. Using a lepidopteran model insect, the silkworm Bombyx mori, we established Siwi (Aub homolog) and BmAgo3 (Ago3 homolog) germline knockout mutants and characterized non-gonadal somatic piRNA functions in B. mori development. We found that somatic piRNAs are utilized to suppress transposon activity and maintain normal gene expression in several somatic tissues. Unlike Drosophila, disruption of somatic piRNA pathways severely inhibited normal development in somatic tissues of B. mori: both mutants grew slowly, did not develop to adult moths, and exhibited defects in wing development and sexual differentiation. This study is the first to generate germline knockout insects of PIWI genes in non-Drosophila insects and expands the knowledge on the ancestral or universal functions of piRNAs in arthropods. [ABSTRACT FROM AUTHOR]

Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative "PIKK regulatory chaperone complex" including other PIKK regulators, Hsp90 and the Tel2 complex [ABSTRACT FROM AUTHOR]

Summary: PIWI-interacting RNAs (piRNAs) are 23–30 nucleotides small RNAs that act with PIWI proteins to silence transposon activity in animal gonads. In contrast to microRNAs and small interfering RNAs, the biogenesis of piRNAs, including how 3′ ends are formed, remains largely unknown. Here, by using lysate from BmN4, a silkworm ovary-derived cell line, we have developed a cell-free system that recapitulates key steps of piRNA biogenesis: loading of long single-stranded precursor RNAs into PIWI proteins with 5′-nucleotide bias, followed by Mg2+-dependent 3′ to 5′ exonucleolytic trimming and 2′-O-methylation at 3′ ends. Importantly, 3′ end methylation is tightly coupled with trimming and yet is not a prerequisite for determining the mature piRNA length. Our system provides a biochemical framework for dissecting piRNA biogenesis. [Copyright &y& Elsevier]

Fragmentation during the early stages of high-mass star formation is crucial for understanding the formation of high-mass clusters. We investigated fragmentation within 39 high-mass star-forming clumps as part of the Atacama Large Millimeter/submillimeter Array Survey of 70 μ m Dark High-mass Clumps in Early Stages (ASHES) survey. Considering projection effects, we have estimated core separations for 839 cores identified from the continuum emission and found mean values between 0.08 and 0.32 pc within each clump. We find compatibility of the observed core separations and masses with the thermal Jeans length and mass, respectively. We also present subclump structures revealed by the 7 m array continuum emission. Comparison of the Jeans parameters using clump and subclump densities with the separation and masses of gravitationally bound cores suggests that they can be explained by clump fragmentation, implying the simultaneous formation of subclumps and cores within rather than a step-by-step hierarchical fragmentation. The number of cores in each clump positively correlates with the clump surface density and the number expected from the thermal Jeans fragmentation. We also find that the higher the fraction of protostellar cores, the larger the dynamic range of the core mass, implying that the cores are growing in mass as the clump evolves. The ASHES sample exhibits various fragmentation patterns: aligned, scattered, clustered, and subclustered. Using the Q -parameter, which can help distinguish between centrally condensed and subclustered spatial core distributions, we finally find that in the early evolutionary stages of high-mass star formation, cores tend to follow a subclustered distribution. [ABSTRACT FROM AUTHOR]

We examine spatial variations of the C0 |$/$| CO abundance ratio (X C/CO) in the vicinity of the γ-ray supernova remnant W 51 C, based on [C  i ] (3 P 1–3 P 0), 12CO(1–0), and 13CO(1–0) observations with the ASTE and Nobeyama 45 m telescopes. We find that X C/CO varies in a range of 0.02–0.16 (0.05 in median) inside the molecular clouds of A V > 100 mag, where photodissociation of CO by the interstellar UV is negligible. Furthermore, X C/CO is locally enhanced by a factor of up to four near the W 51 C center, depending on the projected distance from the W 51 C center. In high- A V molecular clouds, X C/CO is determined by the ratio of the cosmic-ray (CR) ionization rate to the H2 density, and we find no clear spatial variation of the H2 density against the projected distance. Hence, the high CR ionization rate may locally enhance X C/CO near the W 51 C center. We also find that the observed spatial extent of the enhanced X C/CO (∼17 pc) is consistent with the diffusion distance of CRs with an energy of 100 MeV. This fact suggests that the low-energy CRs accelerated in W 51 C enhance X C/CO. The CR ionization rate in the X C/CO-enhanced cloud is estimated to be 3 × 10−16 s−1 on the basis of time-dependent photodissociation region simulations of X C/CO, the value of which is 30 times higher than that in the standard Galactic environment. These results demonstrate that [C  i ] is a powerful probe to investigate the interaction between CRs and the interstellar medium for a wide area in the vicinity of supernova remnants. [ABSTRACT FROM AUTHOR]

We report the discovery of star formation activity in perhaps the most distant molecular cloud in the extreme outer galaxy. We performed deep near-infrared imaging with the Subaru 8.2 m telescope, and found two young embedded clusters at two CO peaks of “Digel Cloud 1” at the kinematic distance of D = 16 kpc (Galactocentric radius RG = 22 kpc). We identified 18 and 45 cluster members in the two peaks, and the estimated stellar densities are ∼5 and ∼3 pc–2, respectively. The observed K-band luminosity function suggests that the age of the clusters is less than 1 Myr and also that the distance to the clusters is consistent with the kinematic distance. On the sky, Cloud 1 is located very close to the H I peak of high-velocity cloud Complex H, and there are some H I intermediate velocity structures between the Complex H and the Galactic disk, which could indicate an interaction between them. We suggest the possibility that Complex H impacting on the Galactic disk has triggered star formation in Cloud 1 as well as the formation of the Cloud 1 molecular cloud. [ABSTRACT FROM AUTHOR]

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs containing premature translation termination codons (PTCs). SMG-1 and Upf1 transiently form a surveillance complex termed "SURF" that includes eRF1 and eRF3 on post-spliced mRNAs during recognition of PTC. If an exon junction complex (EJC) exists downstream from the SURF complex, SMG-1 phosphorylates Upf1, the step that is a rate-limiting for NMD. We provide evidence of an association between the SURF complex and the ribosome in association with mRNPs, and we suggest that the SURF complex functions as a translation termination complex during NMD. We identified SMG-8 and SMG-9 as novel subunits of the SMG-1 complex. SMG-8 and SMG-9 suppress SMG-1 kinase activity in the isolated SMG-1 complex and are involved in NMD in both mammals and nematodes. SMG-8 recruits SMG-1 to the mRNA surveillance complex, and inactivation of SMG-8 induces accumulation of a ribosome:Upf1:eRF1:eRF3:EJC complex on mRNP, which physically bridges the ribosome and EJC through eRF1, eRF3, and Upf1. These results not only reveal the regulatory mechanism of SMG-1 kinase but also reveal the sequential remodeling of the ribosome:SURF complex to the predicted DECID (DECay InDucing) complex, a ribosome:SURF:EJC complex, as a mechanism of in vivo PTC discrimination. [ABSTRACT FROM AUTHOR]

Studying the physical and chemical properties of cold and dense molecular clouds is crucial for the understanding of how stars form. Under the typical conditions of infrared dark clouds, CO is removed from the gas phase and trapped onto the surface of dust grains by the so-called depletion process. This suggests that the CO-depletion factor (f D) can be a useful chemical indicator for identifying cold and dense regions (i.e., prestellar cores). We have used the 1.3 mm continuum and C18O (2â€"1) data observed at the resolution of ∼5000 au in the ALMA Survey of 70 ÎĽ m Dark High-mass Clumps in Early Stages (ASHES) to construct averaged maps of f D in 12 clumps to characterize the earliest stages of the high-mass star formation process. The average f D determined for 277 of the 294 ASHES cores follows an unexpected increase from the prestellar to the protostellar stage. If we exclude the temperature effect due to the slight variations in the NH3 kinetic temperature among different cores, we explain this result as a dependence primarily on the average gas density, which increases in cores where protostellar conditions prevail. This shows that f D determined in high-mass star-forming regions at the core scale is insufficient to distinguish among prestellar and protostellar conditions for the individual cores and should be complemented by information provided by additional tracers. However, we confirm that the clump-averaged f D values correlate with the luminosity-to-mass ratio of each source, which is known to trace the evolution of the star formation process. [ABSTRACT FROM AUTHOR]

Drosophila melanogaster has two Dicer proteins with specialized functions. Dicer-1 liberates miRNA-miRNA* duplexes from precursor miRNAs (pre-miRNAs), whereas Dicer-2 processes long double-stranded RNAs into small interfering RNA duplexes. It was recently demonstrated that Dicer-2 is rendered highly specific for long double-stranded RNA substrates by inorganic phosphate and a partner protein R2D2. However, it remains unclear how Dicer-1 exclusively recognize pre-miRNAs. Here we show that fly Dicer-1 recognizes the single-stranded terminal loop structure of pre-miRNAs through its N-terminal helicase domain, checks the loop size and measures the distance between the 3? overhang and the terminal loop. This unique mechanism allows fly Dicer-1 to strictly inspect the authenticity of pre-miRNA structures. [ABSTRACT FROM AUTHOR]

With a mass of ∼1000 M ⊙ and a surface density of ∼0.5 g cmâˆ'2, G023.477+0.114, also known as IRDC 18310-4, is an infrared dark cloud (IRDC) that has the potential to form high-mass stars and has been recognized as a promising prestellar clump candidate. To characterize the early stages of high-mass star formation, we have observed G023.477+0.114 as part of the Atacama Large Millimeter/submillimeter Array (ALMA) Survey of 70 ÎĽ m Dark High-mass Clumps in Early Stages. We have conducted ∼1.″2 resolution observations with ALMA at 1.3 mm in dust continuum and molecular line emission. We have identified 11 cores, whose masses range from 1.1 to 19.0 M ⊙. Ignoring magnetic fields, the virial parameters of the cores are below unity, implying that the cores are gravitationally bound. However, when magnetic fields are included, the prestellar cores are close to virial equilibrium, while the protostellar cores remain sub-virialized. Star formation activity has already started in this clump. Four collimated outflows are detected in CO and SiO. H2CO and CH3OH emission coincide with the high-velocity components seen in the CO and SiO emission. The outflows are randomly oriented for the natal filament and the magnetic field. The position-velocity diagrams suggest that episodic mass ejection has already begun even in this very early phase of protostellar formation. The masses of the identified cores are comparable to the expected maximum stellar mass that this IRDC could form (8â€"19 M ⊙). We explore two possibilities on how IRDC G023.477+0.114 could eventually form high-mass stars in the context of theoretical scenarios. [ABSTRACT FROM AUTHOR]

We present a spatio-kinematical analysis of the CO (J = 2 → 1) line emission, observed with the Atacama Large Millimeter/submillimeter Array (ALMA), of the outflow associated with the most massive core, ALMA1, in the 70 μm dark clump G010.991–00.082. The position–velocity (PV) diagram of the molecular outflow exhibits a peculiar S-shaped morphology that has not been seen in any other star-forming region. We propose a spatio-kinematical model for the bipolar molecular outflow that consists of a decelerating high-velocity component surrounded by a slower component whose velocity increases with distance from the central source. The physical interpretation of the model is in terms of a jet that decelerates as it entrains material from the ambient medium, which has been predicted by calculations and numerical simulations of molecular outflows in the past. One side of the outflow is shorter and shows a stronger deceleration, suggesting that the medium through which the jet moves is significantly inhomogeneous. The age of the outflow is estimated to be τ ≈ 1300 yr, after correction for a mean inclination of the system of ≈57°. [ABSTRACT FROM AUTHOR]

We present a study of outflows at extremely early stages of high-mass star formation obtained from the ALMA Survey of 70 μm dark High-mass clumps in Early Stages (ASHES). Twelve massive 3.6−70 μm dark prestellar clump candidates were observed with the Atacama Large Millimeter/submillimeter Array (ALMA) in Band 6. Forty-three outflows are identified toward 41 out of 301 dense cores using the CO and SiO emission lines, yielding a detection rate of 14%. We discover six episodic molecular outflows associated with low- to high-mass cores, indicating that episodic outflows (and therefore episodic accretion) begin at extremely early stages of protostellar evolution for a range of core masses. The time span between consecutive ejection events is much smaller than those found in more evolved stages, which indicates that the ejection episodicity timescale is likely not constant over time. The estimated outflow dynamical timescale appears to increase with core masses, which likely indicates that more massive cores have longer accretion timescales than less massive cores. The lower accretion rates in these 70 μm dark objects compared to the more evolved protostars indicate that the accretion rates increase with time. The total outflow energy rate is smaller than the turbulent energy dissipation rate, which suggests that outflow-induced turbulence cannot sustain the internal clump turbulence at the current epoch. We often detect thermal SiO emission within these 70 μm dark clumps that is unrelated to CO outflows. This SiO emission could be produced by collisions, intersection flows, undetected protostars, or other motions. [ABSTRACT FROM AUTHOR]

We report on measurements of parallax and proper motion for four 22 GHz water maser sources as part of the VERA Outer Rotation Curve project. All the sources show Galactic latitudes of >2° and Galactocentric distances of >11 kpc at the Galactic longitude range of 95° < l < 126°. The sources trace the Galactic warp reaching to 200–400 pc, and also the signature of the warp to 600 pc toward the north Galactic pole. The new results, along with previous results in the literature, show that the maximum height of the Galactic warp increases with Galactocentric distance. Also, we examined velocities perpendicular to the disk for the sample, and found oscillatory behavior between the vertical velocities and Galactic heights. This behavior suggests the existence of bending (vertical density) waves, possibly induced by a perturbing satellite (e.g. the passage of the Sagittarius dwarf galaxy). [ABSTRACT FROM AUTHOR]

We analyze molecular-gas formation in neutral atomic hydrogen (H  i) clouds using the latest CO data, obtained from the FOREST (four-beam receiver system on the 45 m telescope) unbiased Galactic plane imaging survey with the Nobeyama 45 m telescope, and using H  i data taken from the Very Large Array Galactic plane survey. We applied a dendrogram algorithm to the H  i data cube to identify H  i clouds, and we calculated the H  i mass and molecular-gas mass by summing the CO line intensity within each H  i cloud. On the basis of the results, we created a catalog of 5737 identified H  i clouds with local standard of rest (LSR) velocity of V LSR ≤ −20 km s−1 in galactic longitude and latitude ranges of 20° ≤ l ≤ 50° and −1° ≤ b ≤ 1°, respectively. We found that most of the H  i clouds are distributed within a Galactocentric distance of 16 kpc, and most of them are in the cold neutral medium phase. In addition, we determined that the high-mass end of the H  i mass function is fitted well with a power-law function with an index of 2.3. Although two sequences of self-gravitating and diffuse clouds are expected to appear in the M  tot– |$M_{\,{\rm H}_2}$| diagram according to previous works based on a plane-parallel model, the observational data show only a single sequence with large scattering within these two sequences. This implies that most of the clouds are mixtures of these two types of clouds. Moreover, we suggest the following scenario of molecular-gas formation: an H  i -dominant cloud evolved with increasing H2 mass along a path of |$M_{\,{\rm H}_2} \propto M_{\,\rm tot}^2$| by collecting diffuse gas before reaching and moving along the curves of the two sequences. [ABSTRACT FROM AUTHOR]

We developed and deployed a simple add-on multi-temperature calibrator for our multicolor transition edge sensor (TES) bolometer camera aimed at simultaneous observation with observing wavelengths of 1.1 and 0.85 mm. To cover the power loading level from the atmospheric emission corresponding to precipitable water vapor (PWV) of 0.5-4 mm, the calibrator consists of spherical mirrors to show the low-temperature stages of the cryostat and filters with moderate opacity to mimic the eight-temperature cold blackbodies. The loading powers introduced by each filter were self-calibrated by measuring the load curves of the TES bolometers when a filter was placed in front of the cryostat window. Each science observation was preceded by the calibration process, which measures the response of the TES bolometers to the atmosphere and filters of various opacities. Then, the responsivities of TES bolometers were derived to convert their output signal to the loading power and correct for the nonlinearity inherent in its response. Furthermore, the loading power falling on the TES bolometers from atmospheric emission measured at various PWV was in good correlation with the PWV measured with the radiometer, which enables the atmospheric extinction correction by fast and sensitive bolometers compared to the available radiometers with the modest sampling speeds. [ABSTRACT FROM AUTHOR]

We developed a simple add-on, cryogen-free, and low-power consumption calibrator for a new transition-edge sensor (TES) bolometer camera mounted on the ASTE 10-m telescope. To measure the responsivity of the TES bolometers and accurately correct for the nonlinearity and atmospheric extinction, we designed a motor-driven rotating filter wheel system installed in front of the cryostat window. This calibrator is required to cover the loading power under various atmospheric conditions, which corresponds to precipitable water vapor (PWV) of 0.5-4 mm. For this range of PWV, 25-100 K blackbodies are necessary for the observing bands of 1.1 and 0.85 mm. To simulate the temperature range, bolometers in the cryostat are also optically coupled to the low-temperature stage (<4 K) inside the cryostat by spherical mirrors. In addition, we used moderately absorptive polystyrene plates that are placed between a spherical mirror and the cryostat window. Various combinations of filters result in eight different temperatures by the filter wheel system and simulate the atmospheric emission under various weather conditions at the ASTE site. [ABSTRACT FROM AUTHOR]

We present a high-resolution (R  ≃ 20  000) near-infrared (9100–13 500Å) long-slit spectrum of P Cygni obtained with the newly commissioned WINERED spectrograph in Japan. In the obtained spectrum, we have found that the velocity profiles of the [Fe  ii ] emission lines are resolved into two peaks at a velocity of ≃220 km s−1 with a moderate dip in between and with additional sub-peaks at ≃±100 km s−1. The sub-peak component is confirmed with the long-slit echellogram to originate in the known shell with a radius of ≃10 arcsec, which was originally created by the outburst in 1600 ad. On the other hand, the ≃220 km s−1 component, which dominates the [Fe  ii ] flux from P Cygni, is found to be concentrated closer to the central star with an apparent spatial extent of ≃3 arcsec. The extent is much larger than the compact (<0.1 arcsec) regions traced with hydrogen, helium, and metal permitted lines. The velocity, estimated mass, and dynamical time of the extended emission-line region suggest that the region is an outer part of the stellar wind region. We suggest that the newly identified emission-line region may trace a reverse shock due to the stellar wind overtaking the outburst shell. [ABSTRACT FROM AUTHOR]

Summary PIWI-interacting RNAs (piRNAs) silence transposons in animal germ cells. PIWI proteins bind and amplify piRNAs via the “Ping-Pong” pathway. Because PIWI proteins cleave RNAs between target nucleotides t10 and t11—the nucleotides paired to piRNA guide positions g10 and g11—the first ten nucleotides of piRNAs participating in the Ping-Pong amplification cycle are complementary. Drosophila piRNAs bound to the PIWI protein Aubergine typically begin with uridine (1U), while piRNAs bound to Argonaute3, which are produced by Ping-Pong amplification, often have adenine at position 10 (10A). The Ping-Pong model proposes that the 10A is a consequence of 1U. We find that 10A is not caused by 1U. Instead, fly Aubergine as well as its homologs, Siwi in silkmoth and MILI in mice, have an intrinsic preference for adenine at the t1 position of their target RNAs; during Ping-Pong amplification, this t1A subsequently becomes the g10A of a piRNA bound to Argonaute3. [ABSTRACT FROM AUTHOR]

The basolateral tumor suppressor protein Lgl is important for the regulation of epithelial cell polarity and tissue morphology. Recent studies have shown a physical and functional interaction of Lgl with another polarity-regulating protein machinery, the apical PAR-3-aPKC-PAR-6 complex, in epithelial cells. However, the mechanism of Lgl-mediated regulation of epithelial cell polarity remains obscure. By an siRNA method, we here show that endogenous Lgl is required for the disassembly of apical membrane domains in depolarizing MDCK cells induced by Ca2+ depletion. Importantly, this Lgl function is mediated by the suppression of the apical PAR-3-aPKC-PAR-6 complex activity. Analysis using 2D- or 3D-cultured cells in collagen gel suggests the importance of this suppressive regulation of Lgl on the collagen-mediated re-establishment of apical membrane domains and lumen formation. These results indicate that basolateral Lgl plays a crucial role in the disassembly of apical membrane domains to induce the orientation of apical membrane polarity, which is mediated by the suppression of apical PAR3-aPKC-PAR-6 complex activity. [ABSTRACT FROM AUTHOR]

Background: aPKC and PAR-1 are required for cell polarity in various contexts. In mammalian epithelial cells, aPKC localizes at tight junctions (TJs) and plays an indispensable role in the development of asymmetric intercellular junctions essential for the establishment and maintenance of apicobasal polarity. On the other hand, one of the mammalian PAR-1 kinases, PAR-1b/EMK1/MARK2, localizes to the lateral membrane in a complimentary manner with aPKC, but little is known about its role in apicobasal polarity of epithelial cells as well as its functional relationship with aPKC.Results: We demonstrate that PAR-1b is essential for the asymmetric development of membrane domains of polarized MDCK cells. Nonetheless, it is not required for the junctional localization of aPKC nor the formation of TJs, suggesting that PAR-1b works downstream of aPKC during epithelial cell polarization. On the other hand, aPKC phosphorylates threonine 595 of PAR-1b and enhances its binding with 14-3-3/PAR-5. In polarized MDCK cells, T595 phosphorylation and 14-3-3 binding are observed only in the soluble form of PAR-1b, and okadaic acid treatment induces T595-dependent dissociation of PAR-1b from the lateral membrane. Furthermore, T595A mutation induces not only PAR-1b leakage into the apical membrane, but also abnormal development of membrane domains. These results suggest that in polarized epithelial cells, aPKC phosphorylates PAR-1b at TJs, and in cooperation with 14-3-3, promotes the dissociation of PAR-1b from the lateral membrane to regulate PAR-1b activity for the membrane domain development.Conclusions: These results suggest that mammalian aPKC functions upstream of PAR-1b in both the establishment and maintenance of epithelial cell polarity. [Copyright &y& Elsevier]

We present a comprehensive survey of diffuse interstellar bands (DIBs) in 0.91-1.32 μm with the newly developed near-infrared (NIR) spectrograph WINERED mounted on the Araki 1.3 m telescope in Japan. We obtained high-resolution (R = 28, 300) spectra of 25 early-type stars with color excesses of 0.07 < E(B – V) < 3.4. In addition to the 4 DIBs previously detected in this wavelength range, we identified 15 new DIBs, 7 of which were reported as DIB “candidates” by Cox. We analyze the correlations among NIR DIBs, strong optical DIBs, and the reddening of the stars. Consequently, we found that all NIR DIBs show weaker correlations with the reddening rather than the optical DIBs, suggesting that the equivalent widths of NIR DIBs depend on some physical conditions of the interstellar clouds, such as UV flux. Three NIR DIBs, λλ10780, 10792, and 11797, are found to be classifiable as a “family,” in which the DIBs are well correlated with each other, suggesting that the carriers of these DIBs are connected with some chemical reactions and/or have similar physical properties such as ionization potential. We also found that the three strongest NIR DIBs, λλ10780, 11797, and 13175 are well correlated with the optical DIB λ5780.5, whose carrier is proposed to be a cation molecule with high ionization potential, indicating that the carriers of the NIR DIBs could be cation molecules. [ABSTRACT FROM AUTHOR]

Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance pathway that regulates the degradation of mRNAs harboring premature translation termination codons. NMD also influences the expression of many physiological transcripts. SMG-1 is a large kinase essential to NMD that phosphorylates Upf1, which seems to be the definitive signal triggering mRNA decay. However, the regulation of the kinase activity of SMG-1 remains poorly understood. Here, we reveal the three-dimensional architecture of SMG-1 in complex with SMG-8 and SMG-9, and the structural mechanisms regulating SMG-1 kinase. A bent arm comprising a long region of HEAT (huntington, elongation factor 3, a subunit of PP2A and TOR1) repeats at the N terminus of SMG-1 functions as a scaffold for SMG-8 and SMG-9, and projects from the C-terminal core containing the phosphatidylinositol 3-kinase domain. SMG-9 seems to control the activity of SMG-1 indirectly through the recruitment of SMG-8 to the N-terminal HEAT repeat region of SMG-1. Notably, SMG-8 binding to the SMG-1:SMG-9 complex specifically down-regulates the kinase activity of SMG-1 on Upf1 without contacting the catalytic domain. Assembly of the SMG-1:SMG-8:SMG-9 complex induces a significant motion of the HEAT repeats that is signaled to the kinase domain. Thus, large-scale conformational changes induced by SMG-8 after SMG-9-mediated recruitment tune SMG-1 kinase activity to modulate NMD. [ABSTRACT FROM AUTHOR]