Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension

Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P_pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P_pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.     

Introduction of chemically labile substructures into Arabidopsis lignin through the use of LigD,the Cα‐dehydrogenase from Sphingobium sp. strain SYK‐6

Bacteria‐derived enzymes that can modify specific lignin substructures are potential targets to engineer plants for better biomass processability. The Gram‐negative bacterium Sphingobium sp. SYK‐6 possesses a Cα‐dehydrogenase (LigD) enzyme that has been shown to oxidize the α‐hydroxy functionalities in β–O–4‐linked dimers into α‐keto analogues that are more chemically labile. Here, we show that recombinant LigD can oxidize an even wider range of β–O–4‐linked dimers and oligomers, including the genuine dilignols, guaiacylglycerol‐β‐coniferyl alcohol ether and syringylglycerol‐β‐sinapyl alcohol ether. We explored the possibility of using LigD for biosynthetically engineering lignin by expressing the codon‐optimized ligD gene in Arabidopsis thaliana. The ligD cDNA, with or without a signal peptide for apoplast targeting, has been successfully expressed, and LigD activity could be detected in the extracts of the transgenic plants. UPLC‐MS/MS‐based metabolite profiling indicated that levels of oxidized guaiacyl (G) β–O–4‐coupled dilignols and analogues were significantly elevated in the LigD transgenic plants regardless of the signal peptide attachment to LigD. In parallel, 2D NMR analysis revealed a 2.1‐ to 2.8‐fold increased level of G‐type α‐keto‐β–O–4 linkages in cellulolytic enzyme lignins isolated from the stem cell walls of the LigD transgenic plants, indicating that the transformation was capable of altering lignin structure in the desired manner.     

Preterm birth is associated with an increased fundamental frequency of spontaneous crying in human infants at term-equivalent age

Human infant crying has been researched as a non-invasive tool for assessing neurophysiological states at an early developmental stage. Little is known about the acoustic features of spontaneous cries in preterm infants, although their pain-induced cries are at a higher fundamental frequency (F₀) before term-equivalent age. In this study, we investigated the effects of gestational age, body size at recording and intrauterine growth retardation (IUGR) on the F₀ of spontaneous cries in healthy preterm and full-term infants at term-equivalent age. We found that shorter gestational age was significantly associated with higher F₀, although neither smaller body size at recording nor IUGR was related to increased F₀ in preterm infants. These findings suggest that the increased F₀ of spontaneous cries is not caused by their smaller body size, but instead might be caused by more complicated neurophysiological states owing to their different intrauterine and extrauterine experiences.     

Spatial Segregation and Aggregation of Ectomycorrhizal and Root-Endophytic Fungi in the Seedlings of Two Quercus Species

Diverse clades of mycorrhizal and endophytic fungi are potentially involved in competitive or facilitative interactions within host-plant roots. We investigated the potential consequences of these ecological interactions on the assembly process of root-associated fungi by examining the co-occurrence of pairs of fungi in host-plant individuals. Based on massively-parallel pyrosequencing, we analyzed the root-associated fungal community composition for each of the 249 Quercus serrata and 188 Quercus glauca seedlings sampled in a warm-temperate secondary forest in Japan. Pairs of fungi that co-occurred more or less often than expected by chance were identified based on randomization tests. The pyrosequencing analysis revealed that not only ectomycorrhizal fungi but also endophytic fungi were common in the root-associated fungal community. Intriguingly, specific pairs of these ectomycorrhizal and endophytic fungi showed spatially aggregated patterns, suggesting the existence of facilitative interactions between fungi in different functional groups. Due to the large number of fungal pairs examined, many of the observed aggregated/segregated patterns with very low P values (e.g., < 0.005) turned non-significant after the application of a multiple comparison method. However, our overall results imply that the community structures of ectomycorrhizal and endophytic fungi could influence each other through interspecific competitive/facilitative interactions in root. To test the potential of host-plants'' control of fungus–fungus ecological interactions in roots, we further examined whether the aggregated/segregated patterns could vary depending on the identity of host plant species. Potentially due to the physiological properties shared between the congeneric host plant species, the sign of hosts'' control was not detected in the present study. The pyrosequencing-based randomization analyses shown in this study provide a platform of the high-throughput investigation of fungus–fungus interactions in plant root systems.     

Epstein-Barr Virus and Human Papillomavirus Infections and Genotype Distribution in Head and Neck Cancers

ObjectiveTo investigate the prevalence, genotypes, and prognostic values of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infections in Japanese patients with different types of head and neck cancer (HNC).ResultsOf the 209 HNC patients, 63 (30.1%) had HPV infection, and HPV-16 was the most common subtype (86.9%). HPV E6/E7 mRNA expression was found in 23 of 60 (38.3%) HPV DNA-positive cases detected. The site of highest prevalence of HPV was the oropharynx (45.9%). Among 146 (69.9%) HNCs in which EBV DNA was identified, 107 (73.3%) and 27 (18.5%) contained types A and B, respectively, and 124 (84.9%) showed the existence of del-LMP-1. However, only 13 (6.2%) HNCs were positive for EBER, 12 (92.3%) of which derived from the nasopharynx. Co-infection of HPV and EBER was found in only 1.0% of HNCs and 10.0% of NPCs. Kaplan-Meier survival analysis showed significantly better disease-specific and overall survival in the HPV DNA+/mRNA+ oropharyngeal squamous cell carcinoma (OPC) patients than in the other OPC patients (P = 0.027 and 0.017, respectively). Multivariate analysis showed that stage T1–3 (P = 0.002) and HPV mRNA-positive status (P = 0.061) independently predicted better disease-specific survival. No significant difference in disease-specific survival was found between the EBER-positive and -negative NPC patients (P = 0.155).ConclusionsOur findings indicate that co-infection with HPV and EBV is rare in HNC. Oropharyngeal SCC with active HPV infection was related to a highly favorable outcome, while EBV status was not prognostic in the NPC cohort.     

Biophoton Emission Induced by Heat Shock

Ultraweak biophoton emission originates from the generation of reactive oxygen species (ROS) that are produced in mitochondria as by-products of cellular respiration. In healthy cells, the concentration of ROS is minimized by a system of biological antioxidants. However, heat shock changes the equilibrium between oxidative stress and antioxidant activity, that is, a rapid rise in temperature induces biophoton emission from ROS. Although the rate and intensity of biophoton emission was observed to increase in response to elevated temperatures, pretreatment at lower high temperatures inhibited photon emission at higher temperatures. Biophoton measurements are useful for observing and evaluating heat shock.     

Magnetic–Plasmonic FePt@Ag Core–Shell Nanoparticles and Their Magnetic and SERS Properties

Magnetic–plasmonic FePt@Ag core–shell nanoparticles (NPs) with different Ag shell thicknesses were successfully synthesized using a seed-mediated method. They presented not only localized surface plasmon resonance in the visible region, but also superparamagnetic behavior at room temperature. When normalized by the weight of FePt, the saturation magnetization of the FePt@Ag NPs was found to be higher than that of FePt NPs, suggesting that the Ag shell effectively passivated the FePt NP surfaces, avoiding the direct interaction between the FePt core and surface capping ligands that typically forms a magnetically dead layer in FePt NPs. Despite the high colloidal stability and the small size of the FePt@Ag NPs, the NPs were easily separated using a permanent magnet. The surface enhanced Raman scattering (SERS) activity of the FePt@Ag NPs was then examined using thiophenol as a Raman reporter molecule and was found to be equivalent to that of Ag NPs. Moreover, the SERS activity of the FePt@Ag NPs was enhanced when a magnetic field was applied during the preparation of the SERS substrate (FePt@Ag NP film). These FePt@Ag NPs hold promise as dual-functional sensing probes for environmental and diagnostic applications.     

Synthesis and Reactions of Some 3′,4′-Unsaturated 2′,3′-Secouridine Analogues

Abstract

2′,3′-Dibromo-2′,3′-dideoxy-5′-O-trityl-2′,3′-secouridine (8) with sdKF gave the 3′,4′-didehydro-2,2′-anhydro nucleoside 9, which was deprotected to 10. Hydrolysis of 9 gave 3′,4′-didehydro-3′-deoxy-5′-O-trityl-2′,3′-secouridine (11a). Similarly, compound 9 with pyridinium halides gave the corresponding 2′-deoxy-2′-halo nucleosides (11b-d). Compound 11d with azide ion gave 2′-azido analogue 11e. Compound 9 with an excess amount of azide ion gave the 2′-azido triazole (13).