Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats.

We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.

Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation.

BACKGROUND: We conducted intratracheal instillations of different molecular weights of polyacrylic acid (PAA) into rats in order to examine what kinds of physicochemical characteristics of acrylic acid-based polymer affect responses in the lung. METHODS: F344 rats were intratracheally exposed to a high molecular weight (HMW) of 598 thousand g/mol or a low molecular weight (LMW) of 30.9 thousand g/mol PAA at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months post exposure. RESULTS: HMW PAA caused persistent increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 3 months and 6 months following instillation. On the other hand, LMW PAA caused only transient increases in neutrophil influx, CINC in BALF, and HO-1 in the lung tissue from 3 days to up to 1 week or 1 month following instillation. Histopathological findings of the lungs demonstrated that the extensive inflammation and fibrotic changes caused by the HMW PAA was greater than that in exposure to the LMW PAA during the observation period. CONCLUSION: HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.

The bryophytes Physcomitrium patens and Marchantia polymorpha as model systems for studying evolutionary cell and developmental biology in plants.

Bryophytes are nonvascular spore-forming plants. Unlike in flowering plants, the gametophyte (haploid) generation of bryophytes dominates the sporophyte (diploid) generation. A comparison of bryophytes with flowering plants allows us to answer some fundamental questions raised in evolutionary cell and developmental biology. The moss Physcomitrium patens was the first bryophyte with a sequenced genome. Many cell and developmental studies have been conducted in this species using gene targeting by homologous recombination. The liverwort Marchantia polymorpha has recently emerged as an excellent model system with low genomic redundancy in most of its regulatory pathways. With the development of molecular genetic tools such as efficient genome editing, both P. patens and M. polymorpha have provided many valuable insights. Here, we review these advances with a special focus on polarity formation at the cell and tissue levels. We examine current knowledge regarding the cellular mechanisms of polarized cell elongation and cell division, including symmetric and asymmetric cell division. We also examine the role of polar auxin transport in mosses and liverworts. Finally, we discuss the future of evolutionary cell and developmental biological studies in plants.

Mitophagy reporter mouse analysis reveals increased mitophagy activity in disuse-induced muscle atrophy.

Muscle disuse induces atrophy through increased reactive oxygen species (ROS) released from damaged mitochondria. Mitophagy, the autophagic degradation of mitochondria, is associated with increased ROS production. However, the mitophagy activity status during disuse-induced muscle atrophy has been a subject of debate. Here, we developed a new mitophagy reporter mouse line to examine how disuse affected mitophagy activity in skeletal muscles. Mice expressing tandem mCherry-EGFP proteins on mitochondria were then used to monitor the dynamics of mitophagy activity. The reporter mice demonstrated enhanced mitophagy activity and increased ROS production in atrophic soleus muscles following a 14-day hindlimb immobilization. Results also showed an increased expression of multiple mitophagy genes, including Bnip3, Bnip3l, and Park2. Our findings thus conclude that disuse enhances mitophagy activity and ROS production in atrophic skeletal muscles and suggests that mitophagy is a potential therapeutic target for disuse-induced muscle atrophy.

Fundamental mechanisms of the stem cell regulation in land plants: lesson from shoot apical cells in bryophytes.

KEY MESSAGE: This review compares the molecular mechanisms of stem cell control in the shoot apical meristems of mosses and angiosperms and reveals the conserved features and evolution of plant stem cells. The establishment and maintenance of pluripotent stem cells in the shoot apical meristem (SAM) are key developmental processes in land plants including the most basal, bryophytes. Bryophytes, such as Physcomitrium (Physcomitrella) patens and Marchantia polymorpha, are emerging as attractive model species to study the conserved features and evolutionary processes in the mechanisms controlling stem cells. Recent studies using these model bryophyte species have started to uncover the similarities and differences in stem cell regulation between bryophytes and angiosperms. In this review, we summarize findings on stem cell function and its regulation focusing on different aspects including hormonal, genetic, and epigenetic control. Stem cell regulation through auxin, cytokinin, CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) signaling and chromatin modification by Polycomb Repressive Complex 2 (PRC2) and PRC1 is well conserved. Several transcription factors crucial for SAM regulation in angiosperms are not involved in the regulation of the SAM in mosses, but similarities also exist. These findings provide insights into the evolutionary trajectory of the SAM and the fundamental mechanisms involved in stem cell regulation that are conserved across land plants.

The origin and evolution of the ALOG proteins, members of a plant-specific transcription factor family, in land plants.

The Arabidopsis LSH1 and Oryza G1 (ALOG) protein is a family of plant-specific transcription factors that regulate reproductive growth in angiosperms. Despite their importance in plant development, little research has been conducted on ALOG proteins in basal land plants and the processes involved in their evolution remain largely unknown. Here, we studied the molecular evolution of ALOG family proteins. We found that ALOG proteins are absent in green algae but exist in all land plants analyzed as well as in some Charophycean algae, closest relatives of land plants. Multiple sequence alignments identified the high sequence conservation of ALOG domains in divergent plant lineages. Phylogenetic analyses also identified a distinct clade of ALOG protein member of lycophytes and bryophytes, including two of Marchantia polymorpha LATERAL ORGAN SUPPRESOR (MpLOS1 and MpLOS2) with a long branch length in MpLOS2. Consistent with this, the function of MpLOS1 was replaceable by Phycomitrella patens ALOG proteins, whereas MpLOS2 failed to replace the molecular function of MpLOS1. Moreover, the rice ALOG proteins, OsTAW1 and OsG1, were not able to replace the molecular function of MpLOS1 although we previously found that the function of OsG1 was replaceable by MpLOS1. Altogether, these findings suggest that ALOG proteins emerged before the evolution of land plants and that they exhibit functional conservation and diversification during the evolution of land plants. The finding that MpLOS1 is able to complement rice ALOG mutants but not vice versa also suggest the existence of conserved and the partly divergent functions of ALOG proteins in bryophytes and angiosperms.

Highly Selective Rh(III) Recovery from HCl Solutions Using Aromatic Primary Diamines via Formation of Three-Dimensional Ionic Crystals.

A new Rh(III) separation method using metal-containing hydrochloric acid (HCl) solutions has been developed. This method includes Rh(III) precipitation with high selectivity using aromatic primary diamines as precipitants. The compound p-phenylene diamine dihydrochloride (PPDA) successfully precipitates only Rh(III) from HCl solutions containing Pd(II), Pt(IV), and Rh(III). Furthermore, highly selective Rh(III) recovery from the simulated spent catalyst leach solution, comprising Pd, Pt, Rh, Ce, Al, Ba, Zr, La, and Y in 5 M HCl, was achieved using PPDA. Single-crystal X-ray analysis revealed that the Rh(III)-containing precipitate using PPDA forms three-dimensional ionic crystals comprising the [RhCl6]3-/ammonium form of PPDA/chloride anion/H2O at a 1:2:1:2 ratio. Formation of these unique ionic crystals plays a key role in the highly selective Rh(III) recovery. This Rh(III) recovery method will be promising for use in the purification process of Rh as well as the practical Rh recovery from spent catalysts.

BLADE-ON-PETIOLE genes are not involved in the transition from protonema to gametophore in the moss Physcomitrella patens.

The timing of the transition between developmental phases is a critical determinant of plant form. In the moss Physcomitrella patens, the transition from protonema to gametophore is a particularly important step as it results in a change from two-dimensional to three-dimensional growth of the plant body. It is well known that this transition is promoted by cytokinin (CK), however, the underlying mechanisms are poorly understood. Previously, it was reported that P. patens orthologs of BLADE-ON-PETIOLE (BOP) genes (PpBOPs) work downstream of CK to promote the transition to gametophore. To further understand the role of PpBOPs in the control of this transition, we performed functional analyses of PpBOP genes. We simultaneously disrupted the function of all three PpBOP genes in P. patens using CRISPR technology, however, no abnormal phenotypes were observed in the triple mutant during either the gametophytic or the sporophytic growth stages. CK treatment did not alter the phase change in the triple mutant. We conclude that PpBOP genes are unnecessary in the control of P. patens development under normal conditions. We propose that BOP genes are not involved in the control of developmental processes in bryophytes and other basal land plants, but may function in physiological processes such as in the defense response.

DIEP Flap Breast Reconstruction Using 3-dimensional Surface Imaging and a Printed Mold.

Recent advances in 3-dimensional (3D) surface imaging technologies allow for digital quantification of complex breast tissue. We performed 11 unilateral breast reconstructions with deep inferior epigastric artery perforator (DIEP) flaps (5 immediate, 6 delayed) using 3D surface imaging for easier surgery planning and 3D-printed molds for shaping the breast neoparenchyma. A single- or double-pedicle flap was preoperatively planned according to the estimated tissue volume required and estimated total flap volume. The DIEP flap was then intraoperatively shaped with a 3D-printed mold that was based on a horizontally inverted shape of the contralateral breast. Cosmetic outcomes were assessed as satisfactory, as confirmed by the postoperative 3D measurements of bilateral breasts. We believe that DIEP flap reconstruction assisted with 3D surface imaging and a 3D-printed mold is a simple and quick method for rebuilding a symmetric breast.

Topological Analysis for Arteriovenous Malformations via Computed Tomography Angiography: Part 1: Mathematical Concepts.

BACKGROUND: Evaluating the progression of soft-tissue arteriovenous malformation (AVMs) is still problematic. To establish a quantitative method, we took a morphological approach. METHODS: Normal blood vessels in early-phase 3D-computed tomography angiography images are theoretically expected to be tree-like structures without loops, whereas AVM blood vessels are expected to be mesh-like structures with loops. Simplified to the utmost limit, these vascular structures can be symbolized with wire-frame models composed of nodes and connecting edges, in which making an extra loop always needs one more of edges than of nodes. RESULTS: TOTAL AMOUNT OF ABNORMAL VASCULAR STRUCTURES IS ESTIMATED FROM A SIMPLE EQUATION: Number of vascular loops = 1 - ([Number of nodes] - [Number of edges]). CONCLUSION: Abnormalities of AVM vascular structures can be mathematically quantified using computed tomography angiography images.

Topological Analysis for Arteriovenous Malformations via Computed Tomography Angiography: Part 2: Practical Application.

BACKGROUND: In a previous study, the authors outlined a technique for calculating the number of abnormal vascular loop structures described in 3-dimensional computed tomography angiography. To be developed into a quantitative evaluation method for soft-tissue arteriovenous malformations (AVMs), the concept needs assessment of validity. METHODS: Computed tomography angiography results of 19 soft-tissue AVMs and 18 control abdominal vessels are utilized. Enhanced vascular lumen regions over 120 HU were extracted by a region growing method and skeletonized into wire frame graph models. The number of vascular loop structures in graphs is calculated as 1 - [Number of nodes] + [Number of edges], and results are compared between AVM/control groups, pre-/postprogression, and pre-/posttreatment. RESULTS: Average vascular lumen capacity of AVMs was 57.5 ml/lesion, and average number of vascular loops was 548 loops/lesion. Loop density of AVMs (weighted average, 9.5 loops/ml) exhibited statistically significant (P < 0.001) greater value than normal abdominal blood vessels (weighted average, 1.3 loops/ml). In all 4 cases without treatment, number of loops and loop density both increased. Particularly, number of loops increased greatly by 2 times or more in 3 cases. In all 7 cases with treatment, number of loops and vascular lumen capacity significantly (P = 0.0156) decreased. Particularly, number of loops showed clearer decrease in cases with entire lesion treatment than partial treatment. CONCLUSIONS: Total number of described vascular loop structures and their density or volume well reflected the existence, progression, and remission of soft-tissue AVMs. Topological analysis can be expected to be developed into a quantitative evaluation for AVMs.

(+)-Catechin protects dermal fibroblasts against oxidative stress-induced apoptosis.

BACKGROUND: Oxidative stress has been suggested as a mechanism underlying skin aging, as it triggers apoptosis in various cell types, including fibroblasts, which play important roles in the preservation of healthy, youthful skin. Catechins, which are antioxidants contained in green tea, exert various actions such as anti-inflammatory, anti-bacterial, and anti-cancer actions. In this study, we investigated the effect of (+)-catechin on apoptosis induced by oxidative stress in fibroblasts. METHODS: Fibroblasts (NIH3T3) under oxidative stress induced by hydrogen peroxide (0.1 mM) were treated with either vehicle or (+)-catechin (0-100 µM). The effect of (+)-catechin on cell viability, apoptosis, phosphorylation of c-Jun terminal kinases (JNK) and p38, and activation of caspase-3 in fibroblasts under oxidative stress were evaluated. RESULTS: Hydrogen peroxide induced apoptotic cell death in fibroblasts, accompanied by induction of phosphorylation of JNK and p38 and activation of caspase-3. Pretreatment of the fibroblasts with (+)-catechin inhibited hydrogen peroxide-induced apoptosis and reduced phosphorylation of JNK and p38 and activation of caspase-3. CONCLUSION: (+)-Catechin protects against oxidative stress-induced cell death in fibroblasts, possibly by inhibiting phosphorylation of p38 and JNK. These results suggest that (+)-catechin has potential as a therapeutic agent for the prevention of skin aging.

Effect of heat treatment conditions on the mechanical properties of Ti-6Mo-4Sn alloy for orthodontic wires.

ß-titanium alloy is frequently used in nickel-free orthodontic wires for patients with a metal allergy. However, the Young's modulus of ß-titanium alloy wires is lower than that of Co-Cr-Ni alloys, causing loss of anchorage and failure to prevent unwanted tooth movements. To improve its mechanical properties for use in anchorage appliances such as transpalatal arches, Ti-6Mo-4Sn alloy wire was heat-treated at 300, 400, 500 and 600 °C for 5 min, 30 min, and 4 h in this study. Tensile testing revealed that the wire heated at 500 °C/30 min had a Young's modulus of 75 GPa and a tensile strength of 1,650 MPa - the highest among all the heat treatment groups. Therefore, Ti-6Mo-4Sn alloy wire heat-treated at 500 °C/30 min yielded mechanical properties approximating those of wires currently used for retainers and transpalatal arches.

A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population.

Our previous genome-wide association study has demonstrated that single-nucleotide polymorphisms (SNPs) located in intronic and downstream regions of IL1A (interleukin 1α) were associated with the risk of endometriosis. These SNPs on the genome-wide association study platform could be only surrogates for the true causal variant. Thus, we resequenced all the exons of IL1A in 377 patients with endometriosis and 457 healthy controls. We detected seven rare variants (minor allele frequency <0.01) and four common variants. All the rare variants were not associated with endometriosis. The four common variants (rs17561, rs1304037, rs2856836 and rs3783553) in IL1A were significantly associated with endometriosis (P=0.0024, 0.0024, 0.0014 and 0.0061, respectively). All the four SNPs were within a linkage disequilibrium block. Among them, only rs17561 was nonsynonymous (p.A114S), which has been reported to be associated with susceptibility to ovarian cancer. Taken together, we examined association between rs17561 and endometriosis in an independent validation data set (524 patients and 533 healthy controls) replicating significant association (P=4.0 × 10(-5); odds ratio (OR), 1.91; 95% confidence interval (CI), 1.41-2.61). Meta-analysis by combining results from the two stages strengthened the evidence of association (P=2.5 × 10(-7); OR, 1.90; 95% CI, 1.49-2.43). Our findings demonstrated that the nonsynonymous variant of IL1A might confer genetic susceptibility to endometriosis in Japanese population.

Photoexcited singlet and triplet states of a UV absorber ethylhexyl methoxycrylene.

The excited states of UV absorber, ethylhexyl methoxycrylene (EHMCR) have been studied through measurements of UV absorption, fluorescence, phosphorescence and electron paramagnetic resonance (EPR) spectra in ethanol. The energy levels of the lowest excited singlet (S1) and triplet (T1) states of EHMCR were determined. The energy levels of the S1 and T1 states of EHMCR are much lower than those of photolabile 4-tert-butyl-4'-methoxydibenzoylmethane. The energy levels of the S1 and T1 states of EHMCR are lower than those of octyl methoxycinnamate. The weak phosphorescence and EPR B(min) signals were observed and the lifetime was estimated to be 93 ms. These facts suggest that the significant proportion of the S1 molecules undergoes intersystem crossing to the T1 state, and the deactivation process from the T1 state is predominantly radiationless. The photostability of EHMCR arises from the (3)ππ* character in the T1 state. The zero-field splitting (ZFS) parameter in the T1 state is D** = 0.113 cm(-1).

Development of an orthodontic elastic material using EMA-based resin combined with 1-butanol.

For the development of new orthodontic elastic material, 1-butanol was added to PEMA-TA/HX resin. In the present study, basic experiments to reveal the mechanical properties of the materials were conducted. FT-IR spectroscopy showed that addition of 1-butanol did not cause any chemical changes to the PEMA-TA/HX resin. After addition of 1-butanol to PEMA-TA/HX resin, the modulus of elasticity, instantaneous modulus elasticity, retarded elasticity and viscosity were lowered in a concentration-dependent manner, whereas the elastic strain was increased in a concentration-dependent manner. Moreover, on the application of heat a shape-memory effect was observed. These results suggest that the modulus of elasticity of this material can be adjusted. Additionally, this material has the ability to restore force as a function of its shape-memory effect in cases of plastic deformation at the insertion of appliances. This new orthodontic elastic material has the potential to be clinically effective in orthodontic treatment.

[Orally administered polaprezinc significantly improves taste disorders in ovarian cancer patient undergoing chemotherapy].

The subject was a 75-year-old female who was receiving paclitaxel and carboplatin(TC)chemotherapy every other week after surgery for ovarian cancer. She greatly complained of taste disorders after four cycles(of every other week administration) of TC chemotherapy. To understand how the taste disorder was caused by chemotherapy objectively, taste examinations were conducted for the patient in our department. These examinations were conducted after receiving the informed consent from the patient. The authors conducted taste examinations for the patient using serum zinc measurement, tongue cell culture, electrogustometry, and filter paper disc tests(before and after starting chemotherapy), and found that her serum zinc level fell significantly after four cycles of chemotherapy. Orally disintegrating tablets of polaprezinc were then administered to the patient, after which the subjective symptom of taste disorder improved. Her serum zinc level increased, and the electrogustometric threshold rapidly fell(an improvement). The filter paper disc test showed some improvement, particularly in the glossopharyngeal nerve and the greater petrosal nerve field.

Clinicopathological assessment of locally recurrent rectal cancer and relation to local re-recurrence.

BACKGROUND: Local re-recurrence after R0 resection of local recurrence of rectal cancer (LRRC) is not rare. The purpose of this study was to examine the pathological features of LRRC and determine the prognostic factors. METHODS: Twenty-one patients underwent R0 resection of LRRC without preoperative therapy from 2000 to 2008. Tumor progression patterns were classified into three types: A, expanding type; B, infiltrating type; and C, intermediate type. Distant isolated cancer cells (DICCs) were defined as cancer cells present in isolation and at a distance (>1 mm) from the tumor edge. RESULTS: Venous invasion was identified in all but one patient (95%). DICCs were observed in 11 of 21 cases. Type A patients had a significantly lower local re-recurrence rate (0/5) compared with type B and/or C patients (11/16, P = 0.012) and a significantly lower incidence of distant metastasis compared with type B and C patients (0/5 vs. 13/16, respectively; P = 0.0028). Multivariate regression analysis identified venous invasion of the primary lesion (P = 0.027) and tumor progression patterns (P = 0.039) as independent predictors of local re-recurrence. CONCLUSIONS: The main features of LRRC were infiltrating growth, venous invasion, and DICCs. Tumor progression patterns correlated with local re-recurrence and distant metastasis. Preoperative adjuvant therapy to terminate peri-tumor cancer cells may be required for better tumor control.