Risk factors for anemia of prematurity among 30-35-week preterm infants

Background: The risk factors for anemia of prematurity (AOP) among late preterm infants are unelucidated. We identified risk factors for declining hemoglobin (Hb) concentration and triggering factors for AOP treatment in infants born at 30-35 gestational weeks. Methods: From 2012 to 2020, we conducted a single-center retrospective study of infants born at 30-35 weeks of gestation without congenital anomalies or severe hemorrhage. The primary outcome was AOP development, defined by initiation of treatments including red blood cell transfusion, subcutaneous injections of erythropoietin, and iron supplementation. A multivariable logistic regression model was used to investigate potential risk factors for AOP. Results: A total of 358 infants were included. Lower gestational age (odds ratio, 0.19; 95% confidence interval 0.11-0.32), small for gestational age (SGA; 7.17, 2.15-23.9), low maternal Hb level before birth (0.66, 0.49-0.87), low Hb at birth (0.71, 0.57-0.89), and multiple large blood samplings (1.79; 1.40-2.29) showed significantly higher odds for AOP development. Conclusions: Gestational age, SGA, low maternal Hb before birth, Hb at birth, and high number of large blood samplings were positively associated with AOP development in infants born at 30-35 gestational weeks

Identification of a Novel Quinvirus in the Family Betaflexiviridae That Infects Winter Wheat

Yellow mosaic disease in winter wheat is usually attributed to the infection by bymoviruses or furoviruses; however, there is still limited information on whether other viral agents are also associated with this disease. To investigate the wheat viromes associated with yellow mosaic disease, we carried out de novo RNA sequencing (RNA-seq) analyses of symptomatic and asymptomatic wheat-leaf samples obtained from a field in Hokkaido, Japan, in 2018 and 2019. The analyses revealed the infection by a novel betaflexivirus, which tentatively named wheat virus Q (WVQ), together with wheat yellow mosaic virus (WYMV, a bymovirus) and northern cereal mosaic virus (a cytorhabdovirus). Basic local alignment search tool (BLAST) analyses showed that the WVQ strains (of which there are at least three) were related to the members of the genus Foveavirus in the subfamily Quinvirinae (family Betaflexiviridae). In the phylogenetic tree, they form a clade distant from that of the foveaviruses, suggesting that WVQ is a member of a novel genus in the Quinvirinae. Laboratory tests confirmed that WVQ, like WYMV, is potentially transmitted through the soil to wheat plants. WVQ was also found to infect rye plants grown in the same field. Moreover, WVQ-derived small interfering RNAs accumulated in the infected wheat plants, indicating that WVQ infection induces antiviral RNA silencing responses. Given its common coexistence with WYMV, the impact of WVQ infection on yellow mosaic disease in the field warrants detailed investigation

The Lifetime of Protoplanetary Disks in a Low-Metallicity Environment

The extreme outer Galaxy (EOG), the region with a Galactic radius of more than 18 kpc, is known to have very low metallicity, about one-tenth that of the solar neighborhood. We obtained deep near-infrared (NIR) images of two very young ($\sim$0.5 Myr) star-forming clusters that are one of the most distant embedded clusters in the EOG. We find that in both clusters the fraction of stars with NIR excess, which originates from the circumstellar dust disk at radii of $\leq$0.1 AU, is significantly lower than those in the solar neighborhood. Our results suggest that most stars forming in the low-metallicity environment experience disk dispersal at an earlier stage ($<$1 Myr) than those forming in the solar metallicity environment (as much as $\sim$5--6 Myr). Such rapid disk dispersal may make the formation of planets difficult, and the shorter disk lifetime with lower metallicity could contribute to the strong metallicity dependence of the well-known "planet-metallicity correlation", which states the probability of a star hosting a planet increases steeply with stellar metallicity. The reason for the rapid disk dispersal could be increase of the mass accretion rate and/or the effective far-ultraviolet photoevaporation due to the low extinction; however, another unknown mechanism for the EOG environment could be contributing significantly.Comment: 27 pages, 7 figures, Accepted for publication in The Astrophysical Journa

ATP Competitive Protein Kinase C Inhibitors Demonstrate Distinct State-Dependent Inhibition

We previously reported that some ATP competitive protein kinase C (PKC) inhibitors are either competitive or uncompetitive inhibitors with respect to substrate peptides. In this report, we demonstrate how the interactions between PKC and inhibitors change PKC activation kinetics. A substrate competitive inhibitor, bisindolylmaleimide I, targets activated PKC and stabilizes PKC in the activated conformation. This leads to transient activation and prolonged deactivation of PKC in the presence of bisindolylmaleimide I. In contrast, an uncompetitive substrate inhibitor, bisindolylmaleimide IV, targets quiescent PKC and stabilizes PKC in the quiescent conformation, which generates slower activation and suppressed translocation upon activation of PKC

Effects of Deregulation on Local Air Passenger Demand

In Japan, supply-demand adjustments for aviation regulation were abolished under the revised Aviation Law of February 2000. This act of deregulation provided airline companies the freedom to set airfares and enter into or withdraw from any route. Competition after deregulation brought many benefits to the consumers of the major routes as well. On the other hand, it inconvenienced the consumers of minor routes by widening the gaps in airfares and services. The purpose of this study is to determine how domestic aviation networks have been affected by airline deregulation. Moreover, the possibility for revitalizing regional airports is suggested.

ATP Competitive Protein Kinase C Inhibitors Demonstrate Distinct State-Dependent Inhibition

We previously reported that some ATP competitive protein kinase C (PKC) inhibitors are either competitive or uncompetitive inhibitors with respect to substrate peptides. In this report, we demonstrate how the interactions between PKC and inhibitors change PKC activation kinetics. A substrate competitive inhibitor, bisindolylmaleimide I, targets activated PKC and stabilizes PKC in the activated conformation. This leads to transient activation and prolonged deactivation of PKC in the presence of bisindolylmaleimide I. In contrast, an uncompetitive substrate inhibitor, bisindolylmaleimide IV, targets quiescent PKC and stabilizes PKC in the quiescent conformation, which generates slower activation and suppressed translocation upon activation of PKC

Models for state-dependent inhibition and its effects on kinase activities.

<p>Schematic diagrams (top), cartoons for relevant states of PKC (middle) and time course of PKC activities (bottom) for two types of state-dependent PKC inhibitor models. The diagram indicates inhibitor (I) and PKC in the quiescent state (Q) and activated state (A). The cartoons show PKC with the pseudosubstrate domain (Psd) and the catalytic domain for the corresponding states described above. Two types of inhibitors are indicated (yellow particle, blue particle). The trace with yellow circles at the bottom shows a conceptual model of slow activation of kinases in the presence of quiescent kinase inhibitors since the inhibitors stabilize PKC in the quiescent state. In contrast, activated PKC inhibitors bind PKC in the activated state and interfere with the deactivation process. The time lag between PKC activation and the inhibitor binding generates the transient activation of PKC (blue circles).</p

Two BIS compounds show distinct time-dependent changes in potency affecting cellular PKC activities.

<p>(<b>A</b>) Molecular structure of bisindolylmaleimide I (BIS I, left) and bisindolylmaleimide IV (BIS IV, right). Lower panels show molecular models for BIS bound PKCβII modified from the PDB file (2I0E). Carbon (yellow), nitrogen (blue) in BIS compounds are shown as spheres. The key residue for the substrate recognition, D470, is highlighted in pink. (<b>B</b>) CHO cells expressing CKAR were stimulated with 3 µM oxotremorine-M (oxo-M) at t = 0. Fluorescent signals from cells from the CFP channel are shown (far left). Oxo-M application induces phosphorylation of CKAR and a change in the CFP/YFP fluorescent ratio of the CKAR probe, shown as pseudocolor images. Images from indicated times are shown. (<b>C</b>) Cellular PKC activities in the presence (blue) or absence (white) of 200 nM BIS I. The black box indicates the presence of oxo-M. (<b>D</b>) Cellular PKC activity in the presence (orange) or absence (white) of 1 µM BIS IV. (<b>E</b>) Relative PKC activity in the presence of BIS I (blue) or BIS IV (orange) normalized to the PKC activity without inhibitors (white) derived from (C) and (D).</p

State-dependent inhibition by staurosporine and K-252c.

<p>(<b>A</b>) The molecular structures for staurosporine (left) and staurosporine aglycone, K-252c (right). (<b>B</b>) Cellular PKC responses with (closed circles) or without (open circles) 100 nM staurosporine (ST). Application of 3 µM oxo-M (black box) is indicated. (<b>C</b>) Cellular PKC responses with (closed circles) or without (open circles) 10 µM K-252c. (<b>D, E</b>) Scaled PKC activities from (B) and (C). (<b>F</b>) Inhibition kinetics measured as oxo-M responses of PKC incubated with 100 nM staurosporine for the indicated times with (closed circles) or without (open circles) 100 nM PDBu. (<b>G</b>) Coimmunoprecipitation of Psd-GFP and (Δ2-31)PKCβII in the control or in the presence of 10 µM staurosporine or 10 µM K-252c.</p