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Objective: It is known that fracture risk is increased in patients with psoriatic arthritis (PsA); however, there is no consensus on the association with osteoporosis. The purpose of this study was to elicit the rate of osteoporosis and the risk factors of osteoporosis in patients with PsA at our institution. Methods: The data in this study were extracted from 163 patients with PsA. Osteoporosis and osteopenia were defined based on the WHO definition. Osteoporosis was also diagnosed when a fragility vertebral compression fracture was observed. Results: The osteoporosis and osteopenia rates for PsA patients were 11.7% and 33.1%, respectively. The rates of osteoporosis and osteopenia in males were particularly high compared to previous reports, at 9.3% and 34.3%, respectively. Trabecular bone score was considered age-appropriate for both males and females. Body mass index and Trabecular bone score were significantly lower in patients with osteoporosis. Conclusions: In patients with PsA, males are at elevated risk of osteoporosis and associated fragility fractures even if they are under 50 years. Body mass index was significantly lower in osteoporotic cases, suggesting the importance of bone mineral density testing and treatment in such cases. [ABSTRACT FROM AUTHOR]

The gut–skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage (CSD) on mouse intestines. Following the CSD model, 4% sodium dodecyl sulfate was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated-dextran. The role of interleukin-13 (IL-13) in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, or innate lymph cell-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut. Gut and skin have been found to affect each other through a bidirectional connection (gut–skin axis), though the precise mechanisms remain to be elucidated. In this study, surfactant-mediated mechanical chronic skin damage caused morphological changes in the small intestine of mice, accompanied by increased intestinal permeability, possibly through the interleukin-13-induced apoptosis of mast cells in the epithelium. Graphical Abstract [ABSTRACT FROM AUTHOR]

Objective: While biologics have been used for the patients with psoriatic arthritis, there remains to be unknown concerning long-term retention rates. This study aims to present real-world data about long-term retention rates of biologics for the patients with psoriatic arthritis, and to undertake an analysis of the contributing factors. Methods: We examined retention rates and the reasons for discontinuation for biologics (adalimumab, certolizumab pegol, secukinumab, and ixekizumab) in 146 prescriptions (of which, 109 prescriptions were as naive) at our hospital since March 2010. Results: Throughout the entire course of the study, the 10-year retention rates were approximately 70% for adalimumab, 50% for ixekizumab, and 40% for secukinumab. When evaluating retention rates in the biologic-naïve subgroups, the 10-year retention rates were all approximately 70%. Regarding certolizumab pegol, the 3-year retention rate was approximately 75%. For adalimumab, a higher degree of arthritis at the initiation of treatment was found to correlate with an increased likelihood of secondary inefficacy. The main reason for discontinuation was secondary inefficacy, except for ixekizumab. Conclusions: Each biologic exhibited a favourable long-term retention rate. The main reason for discontinuation was secondary inefficacy. Regarding adalimumab, secondary inefficacy was linked to the extent of arthritis upon treatment initiation. [ABSTRACT FROM AUTHOR]

The centromere is an essential chromosome region where the kinetochore is formed to control equal chromosome distribution during cell division. The centromere-specific histone H3 variant CENH3 (also called CENP-A) is a prerequisite for the kinetochore formation. Since CENH3 evolves rapidly, associated factors, including histone chaperones mediating the deposition of CENH3 on the centromere, are thought to act through species-specific amino acid sequences. The functions and interaction networks of CENH3 and histone chaperons have been well-characterized in animals and yeasts. However, molecular mechanisms involved in recognition and deposition of CENH3 are still unclear in plants. Here, we used a swapping strategy between domains of CENH3 of Arabidopsis thaliana and the liverwort Marchantia polymorpha to identify specific regions of CENH3 involved in targeting the centromeres and interacting with the general histone H3 chaperone, nuclear autoantigenic sperm protein (NASP). CENH3's LoopN-α1 region was necessary and sufficient for the centromere targeting in cooperation with the α2 region and was involved in interaction with NASP in cooperation with αN, suggesting a species-specific CENH3 recognition. In addition, by generating an Arabidopsis nasp knock-out mutant in the background of a fully fertile GFP-CENH3 / cenh3-1 line, we found that NASP was implicated for de novo CENH3 deposition after fertilization and thus for early embryo development. Our results imply that the NASP mediates the supply of CENH3 in the context of the rapidly evolving centromere identity in land plants. [ABSTRACT FROM AUTHOR]

Introduction Heated tobacco products (HTPs) have been advertised as "reduced-harm" tobacco products compared to conventional cigarettes (CC); however, no direct evidence supporting HTPs being desirable for human health exists. A previous systematic review reported that evidence on HTPs published in 2017 or earlier was primarily drawn from industry-related papers. We aimed to investigate whether tobacco industry-affiliated studies are more likely to conclude that HTPs are more desirable than CC. Methods PubMed and Ichushi -Web were searched up to March 15, 2022, for studies on HTPs published in 2017 or after. We selected studies that assessed any measures of HTPs and CC, including secondary analyses using gray literature in English or Japanese. We excluded review articles except for a meta-analysis that met the aforementioned criteria. Data on the authors' affiliations, grant, conflict of interest, category of research subjects, and interpretation were extracted. Research members in two groups independently assessed the papers; discrepancies were solved by discussion between the groups. Results Overall, 134 studies met the criteria. Eighty-seven (64.9%) of them were affiliated with the tobacco industry. Of the 134 studies, 56.3% (49/87) of the industry-affiliated studies versus 19.1% (9/47) of nonindustry-affiliated studies concluded that HTPs were more desirable than CC (p  < .01). No study investigated clinically relevant outcomes, such as disease occurrence. Conclusions Publications on HTPs in the biomedical literature from January 2017 to March 2022 were dominated by tobacco industry-affiliated studies. More than half of them concluded that HTPs were more desirable than CC compared to independent studies. Implications Tobacco industry advertises HTPs as "reduced-harm" tobacco products compared to CC. HTP users tend to consider HTPs as alternative tobacco products less harmful than CC (ie, products for "harm reduction"). Our results demonstrated that papers written by tobacco industry-affiliated authors concluded that HTPs were more desirable than CC compared to papers by independent authors. However, all their judgments were based on surrogate outcomes. Surrogate outcomes are not necessarily linked to clinically relevant outcomes such as disease occurrence. Further studies on HTPs using clinically relevant outcomes are warranted by independent authors from tobacco industry. [ABSTRACT FROM AUTHOR]

Many terrestrial plants produce large quantities of alkanes for use in epicuticular wax and the pollen coat. However, their carbon chains must be long to be useful as fuel or as a petrochemical feedstock. Here, we focus on Nymphaea odorata , which produces relatively short alkanes in its anthers. We identified orthologs of the Arabidopsis alkane biosynthesis genes AtCER1 and AtCER3 in N. odorata and designated them NoCER1A, NoCER3A and NoCER3B. Expression analysis of NoCER1A and NoCER3A/B in Arabidopsis cer mutants revealed that the N. odorata enzymes cooperated with the Arabidopsis enzymes and that the NoCER1A produced shorter alkanes than AtCER1, regardless of which CER3 protein it interacted with. These results indicate that AtCER1 frequently uses a C30 substrate, whereas NoCER1A, NoCER3A/B and AtCER3 react with a broad range of substrate chain lengths. The incorporation of shorter alkanes disturbed the formation of wax crystals required for water-repellent activity in stems, suggesting that chain-length specificity is important for surface cleaning. Moreover, cultured tobacco cells expressing NoCER1A and NoCER3A/B effectively produced C19–C23 alkanes, indicating that the introduction of the two enzymes is sufficient to produce alkanes. Taken together, our findings suggest that these N. odorata enzymes may be useful for the biological production of alkanes of specific lengths. 3D modeling revealed that CER1s and CER3s share a similar structure that consists of N- and C-terminal domains, in which their predicted active sites are respectively located. We predicted the complex structure of both enzymes and found a cavity that connects their active sites. [ABSTRACT FROM AUTHOR]

Immunoglobulin A (IgA) is the most abundant isotype of antibodies and provides a first line of defense at the mucosa against pathogens invading the host. It has been widely accepted that the mucosal IgA response provided by vaccination requires mucosal inoculation, and intranasal inoculation has been proposed for vaccines against influenza virus. Considering the difficulty of intranasal vaccination in infants or elderly people, however, parenteral vaccination that provides the mucosal IgA response is desirable. Here, we demonstrate that subcutaneous immunisation with zymosan, a yeast cell wall constituent known to be recognised by Dectin-1 and TLR2, potentiates the production of antigen-specific IgA antibodies in the sera and airway mucosa upon intranasal antigen challenge. We confirmed that the antigen-specific IgA-secreting cells accumulated in the lung and nasal-associated lymphoid tissues after the antigen challenge. Such an adjuvant effect of zymosan in the primary immunisation for the IgA response depended on Dectin-1 signalling, but not on TLR2. The IgA response to the antigen challenge required both antigen-specific memory B and T cells, and the generation of memory T cells, but not memory B cells, depended on zymosan as an adjuvant. Finally, we demonstrated that subcutaneous inoculation of inactivated influenza virus with zymosan, but not with alum, mostly protected the mice from infection with a lethal dose of a heterologous virus strain. These data suggest that zymosan is a possible adjuvant for parenteral immunisation that generates memory IgA responses to respiratory viruses such as influenza virus. [ABSTRACT FROM AUTHOR]

Objective Simultanagnosia is a rare neuropsychological symptom characterized by difficulty recognizing global structures while preserving perception of local detail. The condition is classified into ventral and dorsal types. Clinical presentation of ventral simultanagnosia includes a reduced ability to recognize multiple visual stimuli rapidly, that is, part-by-part recognition. Here, we report a case of ventral simultanagnosia with a unique presentation; when short-duration visual stimuli were presented, the patient could perform global recognition by improving his part-by-part approach. To investigate the relationship between local and global perception bias and the duration of the present stimulus, we conducted a visual perception test using hierarchically organized Navon figures. Methods/Results The patient was a 62-year-old right-handed man who suffered from cerebral infarction in the right occipitotemporal lobe. He had no language dysfunction but exhibited left unilateral neglect, prosopagnosia, and ventral-type simultanagnosia. We conducted a visual perception test using the Navon figures and control figures as a visual stimulus. We randomly presented the figures for intervals of 0.2 or 20 s and let the patient report all the letters (global and/or local element) that he recognized. Global elements of the Navon letter were recognized a rate of 0% and 78.3% at intervals of 20 and 0.2 s, respectively, indicating that shorter presentation made the part-by-part approach less likely to manifest. Conclusions We assumed that the simultanagnosia in this case was caused by failure to maintain the initially perceived global information for a long period of time during visual presentation, due to right occipitotemporal damage. [ABSTRACT FROM AUTHOR]

Mating systems of haploid species such as fungi, algae, and bryophytes are either heterothallic (self‐incompatible) with two sex phenotypes (male and female, or mating type minus and plus in isogamous species) or homothallic (self‐compatible) with only a bisexual phenotype producing zygotes within a clone. The anisogamous volvocine green alga Pleodorina starrii is a haploid species previously reported to have a heterothallic mating system. Here, we found that two additional culture strains originating from the same water system of P. starrii were taxonomically identified as P. starrii and produced male and female gametes and zygotes within a clone (bisexual). Sequences of rapidly evolving plastid genome regions were identical between the bisexual and unisexual (male or female) P. starrii strains. Intercrossings between the bisexual and unisexual strains demonstrated normal thick‐walled zygotes and high survivability of F1 strains. Thus, these strains belong to the same biological species. Pleodorina starrii has a new haploid mating system that is unique in having three sex phenotypes, namely, male, female, and bisexual. Genetic analyses suggested the existence of autosomal "bisexual factor" locus independent of volvocine male and female determining regions. The present findings increase our understanding of the initial evolutionary step of transition from heterothallism to homothallism. [ABSTRACT FROM AUTHOR]

Shoot regeneration involves reprogramming of somatic cells and de novo organization of shoot apical meristems (SAMs). In the best-studied model system of shoot regeneration using Arabidopsis, regeneration is mediated by the auxin-responsive pluripotent callus formation from pericycle or pericycle-like tissues according to the lateral root development pathway. In contrast, shoot regeneration can be induced directly from fully differentiated epidermal cells of stem explants of Torenia fournieri (Torenia), without intervening the callus mass formation in culture with cytokinin; yet, its molecular mechanisms remain unaddressed. Here, we characterized this direct shoot regeneration by cytological observation and transcriptome analyses. The results showed that the gene expression profile rapidly changes upon culture to acquire a mixed signature of multiple organs/tissues, possibly associated with epidermal reprogramming. Comparison of transcriptomes between three different callus-inducing cultures (callus induction by auxin, callus induction by wounding and protoplast culture) of Arabidopsis and the Torenia stem culture identified genes upregulated in all the four culture systems as candidates of common factors of cell reprogramming. These initial changes proceeded independently of cytokinin, followed by cytokinin-dependent, transcriptional activations of nucleolar development and cell cycle. Later, SAM regulatory genes became highly expressed, leading to SAM organization in the foci of proliferating cells in the epidermal layer. Our findings revealed three distinct phases with different transcriptomic and regulatory features during direct shoot regeneration from the epidermis in Torenia, which provides a basis for further investigation of shoot regeneration in this unique culture system. [ABSTRACT FROM AUTHOR]

In most flowering plants, the asymmetric cell division of zygotes is the initial step that establishes the apical–basal axis. In the Arabidopsis zygote, vacuolar accumulation at the basal cell end is crucial to ensure zygotic division asymmetry. Despite the importance, it was unclear whether this polar vacuolar distribution was achieved by predominant biogenesis at the basal region or by directional movement after biogenesis. Here, we found that apical and basal vacuolar contents are dynamically exchanged via a tubular vacuolar network and the vacuoles gradually migrate toward the basal end. The mutant of a vacuolar membrane protein, SHOOT GRAVITROPISM2 (SGR2), failed to form tubular vacuoles, and the mutant of a putative vacuolar fusion factor, VESICLE TRANSPORT THROUGH INTERACTION WITH T-SOLUBLE N -ETHYLMALEIMIDE-SENSITIVE FUSION PROTEIN ATTACHMENT PROTEIN RECEPTORS (SNARES) 11 (VTI11), could not flexibly rearrange the vacuolar network. Both mutants failed to exchange the apical and basal vacuolar contents and to polarly migrate the vacuoles, resulting in a more symmetric division of zygotes. Additionally, we observed that in contrast to sgr2 , the zygotic defects of vti11 were rescued by the pharmacological depletion of phosphatidylinositol 3-phosphate (PI3P), a distinct phospholipid in the vacuolar membrane. Thus, SGR2 and VTI11 have individual sites of action in zygotic vacuolar membrane processes. Further, a mutant of YODA (YDA) mitogen-activated protein kinase kinase kinase, a core component of the embryonic axis formation pathway, generated the proper vacuolar network; however, it failed to migrate the vacuoles toward the basal region, which suggests impaired directional cues. Overall, we conclude that SGR2- and VTI11-dependent vacuolar exchange and YDA-mediated directional migration are necessary to achieve polar vacuolar distribution in the zygote. [ABSTRACT FROM AUTHOR]

Many plant processes occur in the context of and in interaction with a surrounding matrix such as soil (e.g. root growth and root–microbe interactions) or surrounding tissues (e.g. pollen tube growth through the pistil), making it difficult to study them with high-resolution optical microscopy. Over the past decade, microfabrication techniques have been developed to produce experimental systems that allow researchers to examine cell behavior in microstructured environments that mimic geometrical, physical and/or chemical aspects of the natural growth matrices and that cannot be generated using traditional agar plate assays. These microfabricated environments offer considerable design flexibility as well as the transparency required for high-resolution, light-based microscopy. In addition, microfluidic platforms have been used for various types of bioassays, including cellular force assays, chemoattraction assays and electrotropism assays. Here, we review the recent use of microfluidic devices to study plant cells and organs, including plant roots, root hairs, moss protonemata and pollen tubes. The increasing adoption of microfabrication techniques by the plant science community may transform our approaches to investigating how individual plant cells sense and respond to changes in the physical and chemical environment. [ABSTRACT FROM AUTHOR]

To understand how the body of plants is made, it is essential to observe the morphology, structure and arrangement of constituent cells. However, the opaque nature of the plant body makes it difficult to observe the internal structures directly under a microscope. To overcome this problem, we developed a reagent, ClearSee, that makes plants transparent, allowing direct observation of the inside of a plant body without inflicting damage on it, e.g. through physical cutting. However, because ClearSee is not effective in making some plant species and tissues transparent, in this study, we further improved its composition to prevent oxidation, and have developed ClearSeeAlpha, which can be applied to a broader range of plant species and tissues. Sodium sulfite, one of the reductants, prevented brown pigmentation due to oxidation during clearing treatment. Using ClearSeeAlpha, we show that it is possible to obtain clear chrysanthemum leaves, tobacco and Torenia pistils and fertilized Arabidopsis thaliana fruits—tissues that have hitherto been challenging to clear. Moreover, we show that the fluorescence intensity of purified fluorescent proteins emitting light of various colors was unaffected in the ClearSeeAlpha solution; only the fluorescence intensity of TagRFP was reduced by about half. ClearSeeAlpha should be useful in the discovery and analysis of biological phenomena occurring deep inside the plant tissues. [ABSTRACT FROM AUTHOR]

Large-scale nuclear shell-model calculations are performed in the neutron- and proton-deficient Pt, Au, Hg, and Tl isotopes (⁠|$Z < 82$| and |$N \le 126$|⁠) near |$^{208}$| Pb. All the single-particle levels in the one-major shells, six neutron (⁠|$2p_{1/2}$|⁠ , |$1f_{5/2}$|⁠ , |$2p_{3/2}$|⁠ , |$0i_{13/2}$|⁠ , |$1f_{7/2}$|⁠ , and |$0h_{9/2}$|⁠) orbitals and five proton (⁠|$2s_{1/2}$|⁠ , |$1d_{3/2}$|⁠ , |$0h_{11/2}$|⁠ , |$1d_{5/2}$|⁠ , and |$0g_{7/2}$|⁠) orbitals are considered. For an effective two-body interaction, one set of the multipole pairing, quadrupole–quadrupole interactions is employed for all the nuclei considered. These phenomenological interactions are determined to reproduce the experimental energy spectra. Some of the isomeric states are analyzed in terms of the shell-model configurations. Octupole correlated states are discussed in terms of a collective octupole excitation on top of each shell model state. [ABSTRACT FROM AUTHOR]

Development of pollen, the male gametophyte of flowering plants, is tightly controlled by dynamic changes in gene expression. Recent research to clarify the molecular aspects of pollen development has revealed the involvement of several transcription factors in the induction of gene expression. However, limited information is available about the factors involved in the negative regulation of gene expression to eliminate unnecessary transcripts during pollen development. In this study, we revealed that AtNOT1 is an essential protein for proper pollen development and germination capacity. AtNOT1 is a scaffold protein of the AtCCR4–NOT complex, which includes multiple components related to mRNA turnover control in Arabidopsis. Phenotypic analysis using atnot1 heterozygote mutant pollen showed that the mature mutant pollen failed to germinate and also revealed abnormal localization of nuclei and a specific protein at the tricellular pollen stage. Furthermore, transcriptome analysis of atnot1 heterozygote mutant pollen showed that the downregulation of a large number of transcripts, along with the upregulation of specific transcripts required for pollen tube germination by AtNOT1 during late microgametogenesis, is important for proper pollen development and germination. Overall, our findings provide new insights into the negative regulation of gene expression during pollen development, by showing the severely defective phonotype of atnot1 heterozygote mutant pollen. [ABSTRACT FROM AUTHOR]

Angiosperms exhibit double fertilization, a process in which one of the sperm cells released from the pollen tube fertilizes the egg, while the other sperm cell fertilizes the central cell, giving rise to the embryo and endosperm, respectively. We have previously reported two polar nuclear fusion-defective double knockout mutants of Arabidopsis thaliana immunoglobulin binding protein (BiP), a molecular chaperone of the heat shock protein 70 (Hsp70) localized in the endoplasmic reticulum (ER), (bip1 bip2) and its partner ER-resident J-proteins, ERdj3A and P58IPK (erdj3a p58ipk). These mutants are defective in the fusion of outer nuclear membrane and exhibit characteristic seed developmental defects after fertilization with wild-type pollen, which are accompanied by aberrant endosperm nuclear proliferation. In this study, we used time-lapse live-cell imaging analysis to determine the cause of aberrant endosperm nuclear division in these mutant seeds. We found that the central cell of bip1 bip2 or erdj3a p58ipk double mutant female gametophytes was also defective in sperm nuclear fusion at fertilization. Sperm nuclear fusion was achieved after the onset of the first endosperm nuclear division. However, division of the condensed sperm nucleus resulted in aberrant endosperm nuclear divisions and delayed expression of paternally derived genes. By contrast, the other double knockout mutant, erdj3b p58ipk , which is defective in the fusion of inner membrane of polar nuclei but does not show aberrant endosperm nuclear proliferation, was not defective in sperm nuclear fusion at fertilization. We thus propose that premitotic sperm nuclear fusion in the central cell is critical for normal endosperm nuclear proliferation. [ABSTRACT FROM AUTHOR]

The enhanced recruitment of leukocytes to the inflamed colon is a key feature of ulcerative colitis (UC). The gut‐specific adhesion molecules involved in leukocyte recruitment have emerged as recent therapeutic targets. Nicotine absorbed from smoking has been reported to work protectively in UC patients. Our hypothesis is that nicotine may suppress the aberrant leukocyte recruitment and colonic inflammation via the suppression of the overexpressed gut‐specific adhesion molecules in the inflamed colon. To test this hypothesis, the severity of colitis and the degree of leukocyte recruitment induced by gut‐specific adhesion molecules were assessed in dextran sulfate sodium (DSS) colitis mice (C57BL/6J mice treated with 3% DSS) with or without nicotine treatment. We also studied the in vitro changes in the expression of adhesion molecules by using a vascular endothelial cell line. DSS‐induced colitis was accompanied by increases in disease activity index (DAI), histological score, recruitment of leukocytes, and the expression of adhesion molecules, mucosal vascular addressin cell adhesion molecule‐1 (MAdCAM‐1) and VCAM‐1. Nicotine treatment significantly attenuated MAdCAM‐1 expression, leukocyte recruitment, DAI, and histological score. The expression of β7‐integrin, the ligand for MAdCAM‐1, on leukocytes was not affected by nicotine treatment. In vitro study, the TNF‐α‐enhanced mRNA expression of MAdCAM‐1 was reduced by the coadministration of nicotine in a dose‐dependent manner, possibly via nicotinic receptor activation. These results supported our hypothesis that nicotine treatment ameliorated colitis through the suppression of MAdCAM‐1 expression on the microvessels in the inflamed colon. Further investigation is warranted on the role of nicotine in the treatment of UC. Nicotine ameliorated the over‐expressed MAdCAM‐1 and inhibited leukocyte recruitment in murine colitis. [ABSTRACT FROM AUTHOR]

GPR120 is a receptor for long chain fatty acids and is expressed in small intestinal endocrine cells, L cells and adipose tissue. Activation of GPR120 promotes the secretion of incretin GLP-1, which is known to have effects on anti-metabolic syndrome. As such, GPR120 is a potential target of pharmaceuticals for type II diabetes. In this study, we performed ligand-screening for GPR120 on glycero- and sphingo-type lipids and their derivatives using a Transforming Growth Factor α-shedding assay. We found that phytosphingosine (PHS) activates GPR120 in a manner comparable to the natural ligand α-linolenic acid (ALA) and superior to that of the synthetic ligand GW9508. The IC50 value of PHS was 33.4 μM, of ALA was 31.0 μM and of GW9508 was 41.7 μM. Additionally, PHS-induced activation of GPR120 was inhibited by the specific antagonist AH7614. Many of the natural or synthetic ligands found thus far are compounds with carboxyl groups. However, PHS does not possess a carboxyl group, suggesting that its manner of interaction with GPR120 may be significantly different from that of other ligands. Since PHS is rich in the plasma membrane of yeast, our results imply that PHS found in fermented food could have effects on anti-diabetes through activation of GPR120. [ABSTRACT FROM AUTHOR]

Plants coordinate the timing of flower opening with pollen and gynoecium maturation to achieve successful pollination. However, little is known about how the coordination is executed. We found that flower bud development was paused immediately before flower opening in a jasmonic acid (JA)-insensitive tomato mutant,jai1-1. Phytohormone measurement and RNA analysis in flower buds revealed that newly synthesised JA peaked at two days before flower opening and the expression of a transcription factor geneSlMYB21delayed injai1-1. Buds of transgenic tomato plants expressing an artificial repressor,AtMYB24-SRDX, which was expected to impede the function ofSlMYB21, aborted flower opening and resembled those ofjai1-1. Furthermore, theAtMYB24-SRDXplants produced abnormal pollen grains deficient in germination and pistils that did not support pollen tube elongation. We concluded that JA facilitates the expression ofSlMYB21, which coordinates flower opening, pollen maturation, and gynoecium function in tomato. Jasmonic acid stimulatesSlMYB21expression, which is required for coordinated flower opening and fertility in male and female organs in tomato. [ABSTRACT FROM PUBLISHER]

Tissue remodelling and regeneration in various pathophysiological conditions (e.g. the processes of development, pregnancy, inflammation, wound healing, tissue regeneration, tumor growth, etc.) require angiogenesis, a dynamically coordinated response to stimuli from the extracellular microenvironment. During angiogenic and angiostatic responses, endothelial cells play a central role in the blood vessel formation and regression. Angiostatic responses, which are evoked by crucial factors such as VEGF and DLL4, have been elucidated. However, it has not been revealed, how endothelial cells process these conflicting signals. The study of VEGFRNotch cross-signalling provided some clues. We discuss here the potential roles of cullin 3-based ubiquitin E3 ligases as key players in the process of various signals in endothelial cell function and angiogenesis. Our recent findings show that they function as units to process conflicting signalling crosstalk, epigenetic regulation of key factors, and functional barrier maintenance. We also expect more divergent roles of cullin 3-based ubiquitin E3 ligases in endothelial cell function and angiogenesis, and for their potential use as therapeutic targets. [ABSTRACT FROM AUTHOR]

Growth and development are tightly co-ordinated events in the lifetime of living organisms. In temperate bamboo plants, spring is the season when environmental conditions are suitable for the emergence of new shoots. Previous studies demonstrated that bamboo plants undergo an energyconsuming 'fast stem growth' phase. However, the events during the initiation of stem elongation in bamboo are poorly understood. To understand the onset of bamboo stem growth, we performed hormone and transcriptome profiling of tissue regions in newly elongating shoots of the Moso bamboo Phyllostachys edulis. The growth hormones auxins, cytokinins and gibberellins accumulated in the shoot apex, while the stress hormones ABA, salicylic acid (SA) and jasmonic acid (JA) are predominantly found in the lower part of the stem. The mature basal part of the stem showed enrichment of transcripts associated with cell wall metabolism and biosynthesis of phenylpropanoid metabolites, such as lignin. In the young upper stem region, expression of cell formation- and DNA synthesis-related genes was enriched. Moreover, the apical region showed enhanced expression of genes involved in meristem maintenance, leaf differentiation and development, abaxial/adaxial polarity and flowering. Our findings integrate the spatial regulation of hormones and transcriptome programs during the initiation of bamboo stem growth. [ABSTRACT FROM AUTHOR]

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) system is widely used as a tool for genome engineering in various organisms. A complex consisting of Cas9 and single guide RNA (sgRNA) induces a DNA double-strand break in a sequence-specific manner, resulting in knockout. Some binary vectors for CRISPR/Cas9 in plants have been reported, but there is a problem with low efficiency. Here, we present a newly developed, highly efficient CRISPR/Cas9 vector for Arabidopsis thaliana, pKAMA-ITACHI Red (pKIR), harboring the RIBOSOMAL PROTEIN S5 A (RPS5A) promoter to drive Cas9. The RPS5A promoter maintains high constitutive expression at all developmental stages starting from the egg cell and including meristematic cells. Even in the T1 generation, pKIR induced null phenotypes in some genes: PHYTOENE DESATURASE 3 (PDS3), AGAMOUS (AG) and DUO POLLEN 1 (DUO1). Mutations induced by pKIR were carried in the germ cell line of the T1 generation. Surprisingly, in some lines, 100% of the T2 plants had the adh1 (ALCOHOL DEHYDROGENASE 1) null phenotype, indicating that pKIR strongly induced heritable mutations. Cas9-free T2 mutant plants were obtained by removing T2 seeds expressing a fluorescent marker in pKIR. Our results suggest that the pKIR system is a powerful molecular tool for genome engineering in Arabidopsis. [ABSTRACT FROM AUTHOR]

Pollen tube guidance in flowering plants is a unique and critical process for successful sexual reproduction. The pollen tube that grows from pollen, which is the male gametophyte, precisely navigates to the embryo sac, which is the female gametophyte, within the pistil. Recent advances have clarified the molecular framework of gametophytic pollen tube guidance. Multiple species-specific attractant peptides are secreted from synergid cells, the proper development and function of which are regulated by female gametes. Multiple receptor-like kinases on the pollen tube tip are involved in sensing species-specific attractant peptides. In this Update article, recent progress in our understanding of the mechanism of gametophytic pollen tube guidance is reviewed, including attraction by synergid cells, control of pollen tube guidance by female gametes, and directional growth of the pollen tube by directional cue sensing. Future directions in the study of pollen tube guidance also are discussed. [ABSTRACT FROM AUTHOR]

The phosphorylation of proteins by protein kinases controls many cellular and physiological processes, which include intracellular signal transduction. However, the underlying molecular mechanisms of such controls and numerous substrates of protein kinases remain to be characterized. The mitogen-activated protein kinase (MAPK) cascade is of particular importance in a variety of extracellular and intracellular signaling processes. In plant cells, the progression of cytokinesis is an excellent example of an intracellular phenomenon that requires the MAPK cascade. However, the way in which MAPKs control downstream processes during cytokinesis in plant cells remains to be fully determined. We show here that comparisons, by two-dimensional difference gel electrophoresis, of phosphorylated proteins from wildtype Arabidopsis thaliana and mutant plants defective in a MAPK cascade allow identification of substrates of a specific MAPK. Using this method, we identified the PATELLIN2 (PATL2) protein, which has a SEC14 domain, as a substrate of MPK4 MAP kinase. PATL2 was concentrated at the cell division plane, as is MPK4, and had binding affinity for phosphoinositides. This binding affinity was altered after phosphorylation of PATL2 by MPK4, suggesting a role for the MAPK cascade in the formation of cell plates via regeneration of membranes during cytokinesis. [ABSTRACT FROM AUTHOR]

We analyzed DNA replication in early zebrafish embryos. The replicating DNA of whole embryos was labeled with the thymidine analog 5-ethynyl-2ʹ-deoxyuridine (EdU), and spatial regulation of replication sites was visualized in single embryo-derived cells. The results unveiled uncharacterized replication dynamics during zebrafish early embryogenesis. [ABSTRACT FROM PUBLISHER]

Progression of cell division is controlled by various mitotic kinases. In animal cells, phosphorylation of histone H3 at Thr3 by the kinase Haspin (haploid germ cell-specific nuclear protein kinase) promotes centromeric Aurora B localization to regulate chromosome segregation. However, less is known about the function of Haspin in regulatory networks in plant cells. Here, we show that inhibition of Haspin with 5-iodotubercidin (5-ITu) in Bright Yellow-2 (BY-2) cells delayed chromosome alignment. Haspin inhibition also prevented the centromeric localization of Aurora3 kinase (AUR3) and disrupted its function. This suggested that Haspin plays a role in the specific positioning of AUR3 on chromosomes in plant cells, a function conserved in animals. The results also indicated that Haspin and AUR3 are involved in the same pathway, which regulates chromosome alignment during prometaphase/metaphase. Remarkably, Haspin inhibition by 5-ITu also led to a severe cytokinesis defect, resulting in binuclear cells with a partially formed cell plate. The 5-ITu treatment did not affect microtubules, AUR1/2 or the NACK-PQR pathway; however, it did alter the distribution of actin filaments on the cell plate. Together, these results suggested that Haspin has several functions in regulating cell division in plant cells: in the localization of AUR3 on centromeres and in regulating late cell plate expansion during cytokinesis. [ABSTRACT FROM AUTHOR]

The circadian clock is a biological timekeeping system that provides organisms with the ability to adapt to day-night cycles. Timing of the expression of four members of the Arabidopsis thaliana PSEUDO-RESPONSE REGULATOR (PRR) family is crucial for proper clock function, and transcriptional control of PRRs remains incompletely defined. Here, we demonstrate that direct regulation of PRR5 by CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) determines the repression state of PRR5 in the morning. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) analyses indicated that CCA1 associates with three separate regions upstream of PRR5. CCA1 and its homolog LATE ELONGATED HYPOCOTYL (LHY) suppressed PRR5 promoter activity in a transient assay. The regions bound by CCA1 in the PRR5 promoter gave rhythmic patterns with troughs in the morning, when CCA1 and LHY are at high levels. Furthermore, ChIP-seq revealed that CCA1 associates with at least 449 loci with 863 adjacent genes. Importantly, this gene set contains genes that are repressed but upregulated in cca1 lhy double mutants in the morning. This study shows that direct binding by CCA1 in the morning provides strong repression of PRR5 , and repression by CCA1 also temporally regulates an evening-expressed gene set that includes PRR5. [ABSTRACT FROM AUTHOR]

There had been no reports of investigations into biofilms in chronic respiratory infection in vivo. Recently, we established a new murine model of chronic respiratory infection with Pseudomonas aeruginosa. In the present study, we examined the bacteriological effect of combined clarithromycin and levofloxacin against chronic respiratory infection with P. aeruginosa. Scanning electron micrograph of the surface of the catheter intubated in mouse bronchus for 7 days demonstrated in vivo formation of a biofilm containing blood cells, complex fibrous structures and bacteria. Treatment with either clarithromycin alone or levofloxacin alone had no statistical effect on the number of viable bacteria in lung. The combined use of both drugs resulted in a significant decrease in the number of viable bacteria. The present experiment demonstrates that the newly established murine model was useful to investigate the treatment of biofilm-associated chronic respiratory infection with P. aeruginosa, and combination therapy with clarithromycin and levofloxacin was effective in biofilm-associated chronic respiratory infection. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE To prevent stroke, strategies for atrial fibrillation (AF) prevention and an early detection of AF by electrocardiogram are essential. However, only a limited prospective studies have examined the risk factors for AF, even in blood pressure (BP) and body mass index (BMI), which are not clear among general populations. We investigated the impacts of BP and BMI on the risk of incident AF in a general population. METHODS A total of 6,906 participants (30–84 years) in the Suita Study were prospectively followed up for incident AF. Participants were diagnosed with AF if AF or atrial flutter was present on an electrocardiogram from a routine health examination (every 2 years) or if AF was indicated as a present illness from health examinations and/or medical records during follow-up. Adjusted Cox proportional hazard ratios (HRs) were calculated. RESULTS During the 12.8-year follow-up, 253 incident AF events occurred. Compared with the systolic BP (SBP) < 120 mm Hg and normal-weight, the adjusted HRs (95% confidence intervals; CIs) of incident AF in the systolic hypertension and the overweight (BMI ≥ 25 kg/m2) groups were 1.74 (1.22–2.49) and 1.35 (1.01–1.80), respectively. Compared with SBP < 120 mm Hg and normal weight, the adjusted HRs (95% CIs) of incident AF in the SBP = 120–139 mm Hg with overweight and the systolic hypertension with normal or overweight were 1.72 (1.01–2.91), 1.66 (1.10–2.50), and 2.31 (1.47–3.65), respectively (P for interaction = 0.04). CONCLUSIONS Systolic prehypertension and overweight are associated with incident AF in Japanese population. The association between SBP and AF may be evident by overweight. [ABSTRACT FROM AUTHOR]

The female gametophytes of many flowering plants contain one egg cell, one central cell, two synergid cells and three antipodal cells with respective morphological characteristics and functions. These cells are formed by cellularization of a multinuclear female gametophyte. However, the dynamics and mechanisms of female gametophyte development remain largely unknown due to the lack of a system to visualize directly and manipulate female gametophytes in living material. Here, we established an in vitro ovule culture system to examine female gametophyte development in Torenia fournieri, a unique plant species with a protruding female gametophyte. The four-nucleate female gametophyte became eight nucleate by the final (third) mitosis and successively cellularized and matured to attract a pollen tube. The duration of final mitosis was 28 ± 6.5 min, and cellularization was completed in 54 ± 20 min after the end ofthe third mitosis. Fusion of polar nuclei in the central cell occurred in 13.1 ± 1.1 h, and onset of expression of LURE2, a pollen tube attractant gene, was visualized by a green fluorescent protein reporter 10.7 ± 2.3 h after cellularization. Laser disruption analysis demonstrated that the egg and central cells were required for synergid cells to acquire the pollen tube attraction function. Moreover, aberrant nuclear positioning and down-regulation of LURE2 were observed in one of the two synergid cells after disrupting an immature egg cell, suggesting that cell specification was affected. Our system provides insights into the precise dynamics and mechanisms of female gametophyte development in T. fournieri. [ABSTRACT FROM AUTHOR]

Phloem is a conductive tissue that allocates nutrients from mature source leaves to sinks such as young developing tissues. Phloem also delivers proteins and RNA species, such as small RNAs and mRNAs. Intensive studies on plant systemic signaling revealed the essential roles of proteins and RNA species. However, many of their functions are still largely unknown, with the roles of transported mRNAs being particularly poorly understood. A major difficulty is the absence of an accurate and comprehensive list of mobile transcripts. In this study, we used a hetero-graft system with Nicotiana benthamiana as the recipient scion and Arabidopsis as the donor stock, to identify transcripts that moved long distances across the graft union. We identified 138 Arabidopsis transcripts as mobile mRNAs, which we collectively termed the mRNA mobilome. Reverse transcription–PCR, quantitative real-time PCR and droplet digital PCR analyses confirmed the mobility. The transcripts included potential signaling factors and, unexpectedly, more general factors. In our investigations, we found no preferred transcript length, no previously known sequence motifs in promoter or transcript sequences and no similarities between the level of the transcripts and that in the source leaves. Grafting experiments regarding the function of ERECTA, an identified transcript, showed that no function of the transcript mobilized. To our knowledge, this is the first report identifying transcripts that move over long distances using a hetero-graft system between different plant taxa. [ABSTRACT FROM AUTHOR]

BACKGROUND Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are risk factors for coronary artery disease (CAD) and ischemic stroke. However, the hazards of their coexistence are not fully understood in Asian populations. We investigated whether the relationship between BP and cardiovascular disease (CVD) outcomes are modified by LDL-C level in a Japanese population. METHODS Individuals aged 30–79 years (n = 5,151) were classified into 6 groups according to LDL-C levels (<140 and ≥140mg/dL or lipid medication) and BP levels (optimal BP, prehypertension, and hypertension; reference: low LDL-C and optimal BP). Hazard ratios (HRs) were calculated after adjusting for age, high-density lipoprotein cholesterol, diabetes, smoking status, and alcohol consumption. The effect modification of LDL-C on BP–CVD association was assessed using likelihood ratio tests. RESULTS There were 264 CAD and 215 ischemic stroke events during 13 years of follow-up. With low LDL-C, the HRs of prehypertension and hypertension for CAD were 2.01 and 4.71, respectively. Similar trends of HRs were observed with high LDL-C (optimal BP = 2.09, prehypertension = 3.45, hypertension = 5.94). However, the HRs for ischemic stroke did not differ between normal and high LDL-C levels at the same BP level. The apparent effect modification of LDL-C was not observed in the BP–CVD association in either CAD (P = 0.48) or ischemic stroke (P = 0.39). CONCLUSIONS The HRs for CAD in prehypertensive and hypertensive groups were higher than those in the optimal BP group at the same LDL-C levels in a Japanese population; however, there was no statistical effect modification of LDL-C on the BP–CAD association. [ABSTRACT FROM AUTHOR]

The production of the sperm cells in angiosperms requires coordination of cell division and cell differentiation. In Arabidopsis thaliana , the germline-specific MYB protein DUO1 integrates these processes, but the regulatory hierarchy in which DUO1 functions is unknown. Here, we identify an essential role for two germline-specific DUO1 target genes, DAZ1 and DAZ2 , which encode EAR motif–containing C2H2-type zinc finger proteins. We show that DAZ1/DAZ2 are required for germ cell division and for the proper accumulation of mitotic cyclins. Importantly, DAZ1/DAZ2 are sufficient to promote G2- to M-phase transition and germ cell division in the absence of DUO1. DAZ1/DAZ2 are also required for DUO1-dependent cell differentiation and are essential for gamete fusion at fertilization. We demonstrate that the two EAR motifs in DAZ1/DAZ2 mediate their function in the male germline and are required for transcriptional repression and for physical interaction with the corepressor TOPLESS. Our findings uncover an essential module in a regulatory hierarchy that drives mitotic transition in male germ cells and implicates gene repression pathways in sperm cell formation and fertility. [ABSTRACT FROM AUTHOR]