Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.

Biosynthesis of gibberellin-related compounds modulates far-red light responses in the liverwort Marchantia polymorpha.

Gibberellins (GAs) are key phytohormones that regulate growth, development, and environmental responses in angiosperms. From an evolutionary perspective, all major steps of GA biosynthesis are conserved among vascular plants, while GA biosynthesis intermediates such as ent-kaurenoic acid (KA) are also produced by bryophytes. Here, we show that in the liverwort Marchantia polymorpha, KA and GA12 are synthesized by evolutionarily conserved enzymes, which are required for developmental responses to far-red light (FR). Under FR-enriched conditions, mutants of various biosynthesis enzymes consistently exhibited altered thallus growth allometry, delayed initiation of gametogenesis, and abnormal morphology of gamete-bearing structures (gametangiophores). By chemical treatments and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses, we confirmed that these phenotypes were caused by the deficiency of some GA-related compounds derived from KA, but not bioactive GAs from vascular plants. Transcriptome analysis showed that FR enrichment induced the up-regulation of genes related to stress responses and secondary metabolism in M. polymorpha, which was largely dependent on the biosynthesis of GA-related compounds. Due to the lack of canonical GA receptors in bryophytes, we hypothesize that GA-related compounds are commonly synthesized in land plants but were co-opted independently to regulate responses to light quality change in different plant lineages during the past 450 million years of evolution.

Major components of the KARRIKIN INSENSITIVE2-dependent signaling pathway are conserved in the liverwort Marchantia polymorpha.

KARRIKIN INSENSITIVE2 (KAI2) was first identified as a receptor of karrikins, smoke-derived germination stimulants. KAI2 is also considered a receptor of an unidentified endogenous molecule called the KAI2 ligand. Upon KAI2 activation, signals are transmitted through the degradation of D53/SMXL proteins via MAX2-dependent ubiquitination. Although components in the KAI2-dependent signaling pathway, namely MpKAI2A and MpKAI2B, MpMAX2, and MpSMXL, exist in the genome of the liverwort Marchantia polymorpha, their functions remain unknown. Here, we show that early thallus growth is retarded and gemma dormancy in the dark is suppressed in Mpkai2a and Mpmax2 loss-of-function mutants. These defects are counteracted in Mpkai2a Mpsmxl and Mpmax2 Mpsmxl double mutants indicating that MpKAI2A, MpMAX2, and MpSMXL act in the same genetic pathway. Introduction of MpSMXLd53, in which a domain required for degradation is mutated, into wild-type plants mimicks Mpkai2a and Mpmax2 plants. In addition, the detection of citrine fluorescence in Nicotiana benthamiana cells transiently expressing a SMXL-Citrine fusion protein requires treatment with MG132, a proteasome inhibitor. These findings imply that MpSMXL is subjected to degradation, and that the degradation of MpSMXL is crucial for MpKAI2A-dependent signaling in M. polymorpha. Therefore, we claim that the basic mechanisms in the KAI2-dependent signaling pathway are conserved in M. polymorpha.

Total syntheses of borolithochromes H1, H2, I1, and I2.

Total syntheses of borolithochromes H1, H2, I1, and I2, the red pigments isolated from fossils of Jurassic putative red alga Solenopora jurassica, have been achieved. The naphthoquinone possessing a chiral sec-butyl side chain has been synthesized from (S)-2-methylbutanol. The Diels-Alder reaction of the chiral naphthoquinone and the previously reported diene was followed by one pot S-methylation/intramolecular Corey-Chaykovsky reaction/epoxide rearrangement to provide the benzo[gh]tetraphene skeleton. Complexation of the resulting ligand with trimethyl borate and the following O-demethylation furnished a 1:1 mixture of borolithochromes I1 and I2, which were separated by HPLC using CHIRALPAK IC® to afford optically pure borolithochromes I1 (6) and I2 (7). On the other hand, borolithochromes H1 and H2 were not separated by HPLC in our laboratory. Fortunately, the mixture of the methyl ethers of borolithochromes H1 and H2 were separated and O-demethylation with magnesium iodide furnished optically pure borolithochromes H1 (4) and H2 (5).

Single measurement of bowel wall thickness using intestinal ultrasonography in children with ulcerative colitis.

BACKGROUND: Endoscopic monitoring of disease activity in patients with ulcerative colitis (UC) is important. However, frequent colonoscopic examinations are difficult to perform because of their invasiveness, especially in children. Bowel wall thickness (BWT) measurement using intestinal ultrasonography and fecal calprotectin (FC) measurement are useful noninvasive evaluation methods. METHODS: We retrospectively analyzed BWT and FC levels and evaluated the Mayo endoscopic subscore (MES) using colonoscopy in pediatric patients with UC during the same period. The BWT was evaluated using the maximum BWT (mBWT), which was the maximum value of each colonic BWT; the sum of BWT (sBWT), which was the sum of each colonic BWT; and the sum of the adjusted BWT (saBWT), which was corrected using sBWT. RESULTS: In 54 procedures from 40 patients, FC, mBWT, sBWT, and saBWT were significantly different between MES 0-1 and MES 2. The agreement between BWT and MES 2 was 193 out of 216 segments (89.4%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FC were 68.8%, 84.2%, 64.7%, 86.5%, and 79.6% respectively, while those of saBWT were 81.2%, 89.5%, 76.5%, 91.9%, 87.0%, respectively. CONCLUSIONS: BWT in each colonic segment, particularly saBWT, was more useful than FC for detecting moderate colonic inflammation (MES 2) in pediatric patients with UC. Therefore, intestinal ultrasonography may be helpful in the less invasive management of pediatric patients with UC.

[Role of peritoneovenous shunt therapy in end-of-life care of refractory malignant ascites cases].

The short- and long-term outcomes of 34 patients with refractory malignant ascites who underwent peritoneovenous shunt (PVS) therapy were retrospectively reviewed. The primary disease was gastrointestinal cancer in 31 patients and gynecologic cancer in 3 patients. Regarding performance status, 21 patients had Eastern Cooperative Oncology Group Performance Status (PS) 2 and 13 patients were PS 3;thus, many were in a poor general condition. After treatment, abdominal distention disappeared in 79.4% of patients, and appetite improved in 60.9%. The median postoperative survival time was 38 days (range, 1-294 days), and 18 patients (52.9%) were discharged. Disseminated intravascular coagulation with clinical symptoms was observed in 3 patients (8.8%), and heart failure was observed in 7 patients (20.6%). PVS therapy was useful in improving the subjective symptoms of patients with refractory malignant ascites and in enabling them to receive care at home. However, serious postoperative complications are a concern, and appropriate preoperative evaluation is necessary.

Usefulness of ultrasonography for small intestinal evaluations in pediatric Crohn's disease.

BACKGROUND: Small bowel capsule endoscopy (SBCE) for Crohn's disease is useful; however, its use has some limitations, such as invasiveness when endoscopic assistance is required in patients who cannot swallow the capsule, and the burden of interpretation on a physician. In contrast, intestinal ultrasonography (IUS) is a non-invasive modality for children. The purpose of this study is to evaluate the accuracy of IUS for pediatric patients with established Crohn's disease. METHODS: Small bowel capsule endoscopy and IUS findings from the same period in pediatric patients with established Crohn's disease were analyzed retrospectively. First, we compared the Lewis score (LS), small bowel endoscopic activity, and IUS findings by small bowel wall thickness (SBWT) and mesenteric lymph node size (MLNS). Second, we compared the performance of IUS findings with those of some biomarkers. RESULTS: In 22 procedures, SBWT and MLNS were correlated with LS (r = 0.52, P < 0.05, and r = 0.45, P < 0.05, respectively). Small bowel wall thickness, erythrocyte sedimentation rate, and fecal calprotectin levels had the highest accuracy (81.8%, 81.8%, and 81.8%, respectively). The combination of SBWT and MLNS had the highest positive predictive value and negative predictive value (100% and 83.3%, respectively). CONCLUSIONS: Intestinal ultrasonography findings, including SBWT and MLNS, are useful for monitoring small bowel lesions in pediatric patients with established Crohn's disease. We suggest first evaluating small bowel inflammation by IUS in pediatric patients with Crohn's disease before SBCE because IUS is less invasive than SBCE.

Death by suicide, other externally caused injuries and cardiovascular diseases within 6 months of cancer diagnosis (J-SUPPORT 1902).

OBJECTIVE: To conduct the first national population-based study in Japan to characterize risks of death by suicide, other externally caused injuries and cardiovascular diseases within 6 months of cancer diagnosis. METHODS: Cancer patients diagnosed between 1 January and 30 June 2016 and registered in the National Cancer Registry in Japan were followed up until death or 6 months after diagnosis. We calculated standardized mortality ratios and excess absolute risks per 10 000 person-years for death by suicide, other externally caused injuries and cardiovascular diseases compared with the Japanese general population. RESULTS: Of 546 148 patients with cancer (249 116 person-years at risk), we observed 145 suicides, 298 deaths due to other externally caused injuries and 2366 cardiovascular deaths during the follow-up period. Standardized mortality ratios within 6 months were 2.68 for suicide (95% confidence interval, 2.26-3.16; excess absolute risk, 3.65), 1.49 for other externally caused injuries (95% confidence interval, 1.32-1.67; excess absolute risk, 3.92) and 1.38 for cardiovascular diseases (95% confidence interval, 1.33-1.44; excess absolute risk, 26.85). Risks were highest during the first month after cancer diagnosis (standardized mortality ratios: suicide, 4.06 [95% confidence interval, 2.90-5.53]; other externally caused injuries, 2.66 [95% confidence interval, 2.17-3.12] and cardiovascular diseases, 2.34 [95% confidence interval, 2.18-2.51]). CONCLUSIONS: The first 6 months, and especially the first month, after cancer diagnosis were found to be a critical period for risks of death by suicide, other externally caused injuries and cardiovascular diseases. Our findings suggest that oncologists need to evaluate suicidal and cardiovascular risks of patients immediately after cancer diagnosis and provide preventive interventions.

Oscillator networks with tissue-specific circadian clocks in plants.

Many organisms rely on circadian clocks to synchronize their biological processes with the 24-h rotation of the earth. In mammals, the circadian clock consists of a central clock in the suprachiasmatic nucleus and peripheral clocks in other tissues. The central clock is tightly coupled to synchronize rhythmicity and can organize peripheral clocks through neural and hormonal signals. In contrast to mammals, it has long been assumed that the circadian clocks in each plant cell is able to be entrained by external light, and they are only weakly coupled to each other. Recently, however, several reports have demonstrated that plants have unique oscillator networks with tissue-specific circadian clocks. Here, we introduce our current view regarding tissue-specific properties and oscillator networks of plant circadian clocks. Accumulating evidence suggests that plants have multiple oscillators, which show distinct properties and reside in different tissues. A direct tissue-isolation technique and micrografting have clearly demonstrated that plants have hierarchical oscillator networks consisting of multiple tissue-specific clocks.

Reproductive Induction is a Far-Red High Irradiance Response that is Mediated by Phytochrome and PHYTOCHROME INTERACTING FACTOR in Marchantia polymorpha.

Land plants have evolved a series of photoreceptors to precisely perceive environmental information. Among these, phytochromes are the sole photoreceptors for red light (R) and far-red light (FR), and play pivotal roles in modulating various developmental processes. Most extant land plants possess multiple phytochromes that probably evolved from a single phytochrome in the common ancestor of land plants. However, the ancestral phytochrome signaling mechanism remains unknown due to a paucity of knowledge regarding phytochrome functions in basal land plants. It has recently been reported that Mpphy, a single phytochrome in the liverwort Marchantia polymorpha, regulates typical photoreversible responses collectively classified as low fluence response (LFR). Here, we show that Mpphy also regulates the gametangiophore formation analogous to the mode of action of the far-red high irradiance response (FR-HIR) in angiosperms. Our phenotypic analyses using mutant plants obtained by CRISPR/Cas9-based genome editing revealed that MpFHY1, an ortholog of FAR-RED ELONGATED HYPOCOTYL1, as well as Mpphy is critical for the FR-HIR signaling in M. polymorpha. In addition, knockout of MpPIF, a single PHYTOCHROME INTERACTING FACTOR gene in M. polymorpha, completely abolished the FR-HIR-dependent gametangiophore formation, while overexpression of MpPIF accelerated the response. FR-HIR-dependent transcriptional regulation was also disrupted in the Mppif mutant. Our findings suggest that plants had already acquired the FR-HIR signaling mediated by phytochrome and PIF at a very early stage during the course of land plant evolution, and that a single phytochrome in the common ancestor of land plants could mediate both LFR and FR-HIR.

Phytochrome Signaling Is Mediated by PHYTOCHROME INTERACTING FACTOR in the Liverwort Marchantia polymorpha.

Phytochromes are red light (R) and far-red light (FR) receptors that play important roles in many aspects of plant growth and development. Phytochromes mainly function in the nucleus and regulate sets of genes by inhibiting negatively acting basic helix-loop-helix transcription factors named PHYTOCHROME INTERACTING FACTORs (PIFs) in Arabidopsis thaliana Although R/FR photoreversible responses and phytochrome genes are well documented in diverse lineages of plants, the extent to which phytochrome signaling is mediated by gene regulation beyond angiosperms remains largely unclear. Here, we show that the liverwort Marchantia polymorpha, an emerging model basal land plant, has only one phytochrome gene, Mp-PHY, and only one PIF gene, Mp-PIF These genes mediate typical low fluence responses, which are reversibly elicited by R and FR, and regulate gene expression. Mp-phy is light-stable and translocates into the nucleus upon irradiation with either R or FR, demonstrating that the single phytochrome Mp-phy exhibits combined biochemical and cell-biological characteristics of type I and type II phytochromes. Mp-phy photoreversibly regulates gemma germination and downstream gene expression by interacting with Mp-PIF and targeting it for degradation in an R-dependent manner. Our findings suggest that the molecular mechanisms for light-dependent transcriptional regulation mediated by PIF transcription factors were established early in land plant evolution.

Photooxidation Reactions of Cyclometalated Palladium(II) and Platinum(II) Complexes.

New C,N,S-cyclometalated palladium(II) and platinum(II) complexes have been synthesized and their structural, electrochemical, and photochemical properties examined. The blue color of these complexes in solution changed to yellow under visible-light irradiation. By measurement of the absorption spectra for quantifying changes in color, isosbestic points for each complex clearly indicated the presence of only two species responsible for the change of color. X-ray analysis revealed that the visible-light-induced yellow species were S-oxygenated sulfinato complexes. Photosensitized generation of singlet oxygen (1O2) was confirmed by the direct detection of singlet oxygen luminescence at 1275 nm. The present cyclometalated palladium(II) and platinum(II) complexes are efficient photosensitizers of singlet oxygen, which rapidly reacts with coordinating sulfur atoms.

Correlation of the endoscopic findings for small and large bowels in pediatric patients with established Crohn's disease.

Small bowel capsule endoscopy can detect subtle mucosal lesions in pediatric patients with Crohn's disease, and our aim was to evaluate its application in established ileocolonic Crohn's disease. Colonic inflammation was evaluated with the colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (excluding the score of the terminal ileum). Small bowel inflammation was evaluated with the Lewis score and/or Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). A Lewis score <135 was defined as small bowel inactive. A colonic SES-CD of 0 (colonic inactive group) was observed in 22/42 procedures (52.4%), and active small bowel lesions were observed in 11/22 procedures (50.0%). The Lewis score was lower in the colonic inactive group compared to the colonic active group. Correlations between the colonic SES-CD, the Lewis score and CECDAI were weak. The Lewis score and CECDAI in the colonic inactive group had significant correlation with fecal calprotectin levels. We suggest that Crohn's disease patients without both colonic active lesions and elevation of fecal calprotectin levels may not need to receive small bowel capsule endoscopy due to low incidence of lesions in small bowel.

TMEM207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma.

The WW domain-containing oxidoreductase (WWOX) functions as a tumour suppressor in oral carcinogenesis. As aberrant TMEM207 expression may lead to tumour progression by hampering the tumour suppressor function of WWOX in various cancers, we explored the expression and pathobiological properties of TMEM207, focusing on the WWOX-mediated regulation of the HIF-1α pathway in oral squamous cell carcinoma (OSCC). TMEM207 immunoreactivity was detected in 40 of 90 OSCC samples but not in neighbouring non-tumorous epithelial tissues. Moreover, TMEM207 expression was significantly correlated with lymph node metastasis and poor prognosis. An in situ proximal ligation assay demonstrated the colocalization of TMEM207 and WWOX in invasive OSCC cells, especially glycogen-rich ones. Enforced expression of TMEM207 abrogated the binding of WWOX to HIF-1α, increased HIF-1α and GLUT-1 expression, even under normoxic conditions, and promoted tumour growth in a xenoplant assay using SAS tongue squamous cancer cells. In contrast, TMEM207 knockdown decreased GLUT-1 expression in two OSCC cell lines. As a whole, our findings indicate that the aberrant expression of TMEM207 contributes to tumour progression in OSCC, possibly via promoting aerobic glycolysis.

Circadian clock during plant development.

Plants have endogenous biological clocks that allow organisms to anticipate and prepare for daily and seasonal environmental changes and increase their fitness in changing environments. The circadian clock in plants, as in animals and insects, mainly consists of multiple interlocking transcriptional/translational feedback loops. The circadian clock can be entrained by environmental cues such as light, temperature and nutrient status to synchronize internal biological rhythms with surrounding environments. Output pathways link the circadian oscillator to various physiological, developmental, and reproductive processes for adjusting the timing of these biological processes to an appropriate time of day or a suitable season. Recent genomic studies have demonstrated that polymorphism in circadian clock genes may contribute to local adaptations over a wide range of latitudes in many plant species. In the present review, we summarize the circadian regulation of biological processes throughout the life cycle of plants, and describe the contribution of the circadian clock to local adaptation.

Correction to: Circadian clock during plant development.

The article" Circadian clock during plant development".

Prognostic factors in the early phase of acute encephalopathy.

BACKGROUND: Neurological sequelae occur in 40% of patients with acute encephalopathy (AE). The early prediction of poor outcomes is critical to the initiation of appropriate treatment. The aim of the present study was therefore to elucidate prognostic factors that can be quickly and feasibly evaluated on hospital admission in patients with AE. METHODS: We analyzed data from 51 AE patients admitted to Hirakata City Hospital between January 2005 and December 2014. Age at onset, sex, underlying disease, status epilepticus (SE), presence of benzodiazepine-resistant SE (BZD-resistant SE), and basic blood serum parameters on admission were evaluated in relation to each patient's outcome. RESULTS: On univariate analysis age at onset, BZD-resistant SE, and serum aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and platelet count varied significantly according to outcome. On multivariate analysis age at onset (≤21 months), presence of BZD-resistant SE, and AST (≥46 IU/L) were identified as independent variables associated with poor outcome. CONCLUSION: Age at onset, presence of BZD-resistant SE, and AST are associated with a poor prognosis in AE.

Evolutionary origin of phytochrome responses and signaling in land plants.

Phytochromes comprise one of the major photoreceptor families in plants, and they regulate many aspects of plant growth and development throughout the plant life cycle. A canonical land plant phytochrome originated in the common ancestor of streptophytes. Phytochromes have diversified in seed plants and some basal land plants because of lineage-specific gene duplications that occurred during the course of land plant evolution. Molecular genetic analyses using Arabidopsis thaliana suggested that there are two types of phytochromes in angiosperms, light-labile type I and light-stable type II, which have different signaling mechanisms and which regulate distinct responses. In basal land plants, little is known about molecular mechanisms of phytochrome signaling, although red light/far-red photoreversible physiological responses and the distribution of phytochrome genes are relatively well documented. Recent advances in molecular genetics using the moss Physcomitrella patens and the liverwort Marchantia polymorpha revealed that basal land plants show far-red-induced responses and that the establishment of phytochrome-mediated transcriptional regulation dates back to at least the common ancestor of land plants. In this review, we summarize our knowledge concerning functions of land plant phytochromes, especially in basal land plants, and discuss subfunctionalization/neofunctionalization of phytochrome signaling during the course of land plant evolution.

Supplementation with carnitine reduces the severity of constipation: a retrospective study of patients with severe motor and intellectual disabilities.

Carnitine is an essential nutrient for the mitochondrial transport of fatty acids. Carnitine deficiency causes a variety of symptoms in multiple organs. Patients with severe motor and intellectual disabilities often have carnitine deficiency. This study aimed to determine the correlation between constipation and carnitine deficiency in them. Patients with severe motor and intellectual disabilities at our hospital were retrospectively reviewed. The correlation between level of free carnitine and severity of constipation was examined. Constipation and non-constipation groups were compared for age; sex; body mass index; bed rest period; use of anti-epileptic drugs, valproate sodium, or enteral nutrition; and serum levels of albumin, pre-albumin, totalcholesterol, free carnitine, folic acid, and trace elements. Moreover, severity of constipation before and after carnitine supplementation was assessed. Twenty-seven patients were enrolled. Of these, 14 were assigned to the constipation group and 13 to the non-constipation group. The free carnitine level was significantly correlated with severity of constipation (R = 0.7604, p<0.01). Free carnitine was significantly lower in the constipation compared with the non-constipation group (p<0.01). No other significant differences between the groups were found. The severity of constipation was significantly relieved after carnitine supplementation (p<0.001). In conclusion, carnitine supplementation could reduce the severity of constipation.