Comparative analysis of anti-osteoporosis medications in preventing vertebral body fractures after balloon kyphoplasty.

This retrospective study compared the efficacy of anabolic agents (romosozumab and teriparatide) with that of alendronate in preventing subsequent vertebral body fractures (SVBFs) after balloon kyphoplasty (BKP). All anabolic agents significantly reduced SVBFs. Romosozumab was most effective in increasing bone mineral density (BMD) and completely suppressed distant vertebral body fractures. INTRODUCTION: To determine optimal anti-osteoporosis medications, we compared romosozumab and teriparatide to alendronate as a control from perioperative BKP to the 1st postoperative year for treatment and secondary fracture prevention in osteoporosis. METHODS: A total of 603 patients who underwent initial BKP for osteoporotic vertebral fractures were evaluated and categorized into five groups based on drug administration: romosozumab (group R, 155 patients), twice-weekly teriparatide (group TW, 48), weekly teriparatide (group W, 151), daily teriparatide (group D, 138), and alendronate (control) (group C, 111). The 1-year incidence of SVBFs, BMD change rate, and probability of requiring BKP were compared among the groups. RESULTS: SVBF incidence was 3.9%, 6.5%, 8.3%, 6.0%, and 14.4% in groups R, D, TW, W, and C, respectively, with all other groups exhibiting significantly lower rates than group C. The groups that administered the anabolic agents had a notably lower incidence of distant fractures than group C. Compared with group C, group R showed significantly higher BMD change rates in lumbar vertebral bodies at 4, 8, and 12 months and group D at 12 months. Anabolic agent groups exhibited significantly higher improvement rates than group C after conservative treatment alone. CONCLUSION: The anabolic agents were found to be more effective at reducing the incidence of SVBF (especially distant vertebral fractures) than alendronate. These agents decreased the rate of repeat BKP even after the occurrence of a fracture. Overall, the use of an anabolic agent for the treatment of osteoporosis after BKP is better than the use of alendronate, even when treatment is initiated in the perioperative stage.

Living donor liver transplantation for myocerebrohepatopathy spectrum due to POLG mutations.

BACKGROUND: POLG is one of several nuclear genes associated with mitochondrial DNA maintenance defects and is a group of diseases caused by mitochondrial DNA deficiency that results in impaired adenosine triphosphate production and organ dysfunction. Myocerebrohepatopathy spectrum (MCHS) is the most severe and earliest presentation of POLG mutations, and liver transplantation (LT) for MCHS has never been reported. CASE PRESENTATION: The patient was a 3-month-old boy with acute liver failure and no neurological manifestations (e.g., seizures). We performed a living donor LT using a left lateral segment graft from his father. The postoperative course was uneventful. Subsequently, a homozygous POLG mutation (c.2890C>T, p. R964C) was identified by multigene analysis of neonatal/infantile intrahepatic cholestasis. Moreover, respiratory chain complex I, II, and III enzyme activities and the ratio of mtDNA to nuclear DNA in the liver were reduced. Therefore, we considered that these clinical manifestations and examination findings met the definition for MCHS. During meticulous follow-up, the patient had shown satisfactory physical growth and mental development until the time of writing this report. CONCLUSION: We presumed that the absence of remarkable neurologic manifestations prior to LT in patients with MCHS is a good indication for LT and contributes to a better prognosis in the present case.

Mechanistic characterization of disulfide bond reduction of an ERAD substrate mediated by cooperation between ERdj5 and BiP.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality control process that eliminates misfolded proteins from the ER. DnaJ homolog subfamily C member 10 (ERdj5) is a protein disulfide isomerase family member that accelerates ERAD by reducing disulfide bonds of aberrant proteins with the help of an ER-resident chaperone BiP. However, the detailed mechanisms by which ERdj5 acts in concert with BiP are poorly understood. In this study, we reconstituted an in vitro system that monitors ERdj5-mediated reduction of disulfide-linked J-chain oligomers, known to be physiological ERAD substrates. Biochemical analyses using purified proteins revealed that J-chain oligomers were reduced to monomers by ERdj5 in a stepwise manner via trimeric and dimeric intermediates, and BiP synergistically enhanced this action in an ATP-dependent manner. Single-molecule observations of ERdj5-catalyzed J-chain disaggregation using high-speed atomic force microscopy, demonstrated the stochastic release of small J-chain oligomers through repeated actions of ERdj5 on peripheral and flexible regions of large J-chain aggregates. Using systematic mutational analyses, ERAD substrate disaggregation mediated by ERdj5 and BiP was dissected at the molecular level.

Clinicopathologic Features, Genetics, Treatment, and Long-Term Outcomes in Japanese Children and Young Adults with Benign Recurrent Intrahepatic Cholestasis: A Multicenter Study.

BACKGROUND: Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients. METHODS: We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four pediatric centers and one adult center between April 2007 and March 2022. Demographics, clinical course, laboratory results, molecular genetic findings concerning ATP8B1 and ABCB11 genes, histopathology, and treatment response were examined retrospectively. RESULTS: Seven Japanese patients with BRIC were enrolled (four male, three female; four BRIC-1 and three BRIC-2). The median age at onset for BRIC-1 was 12 years; for BRIC-2, it was 1 month. Intermittent cholestatic attacks numbered from one to eight during the 11 years of median follow-up. Six patients received a mainstream education; only one patient attended special education. None developed cirrhosis. Three with BRIC-1 showed compound heterozygosity for a variant ATP8B1 gene, while one was heterozygous; two BRIC-2 patients showed compound heterozygosity in ABCB11 and one was heterozygous. Liver biopsy specimens obtained during cholestatic attacks showed fibrosis varying from none to moderate; inflammation was absent or mild. Rifampicin administered to three patients for cholestatic attacks was effective in all, as was cholestyramine in two of three. CONCLUSIONS: To our knowledge, this is the first East Asian multicenter study of BRIC patients. Onset age and number of cholestatic attacks varied. Rifampicin and cholestyramine were effective against attacks. No patient developed cirrhosis; most had normal growth and development. The long-term outcomes were satisfactory.

A Case of Adult-onset Type II Citrullinemia Developed under Dietary Restrictions during Imprisonment.

A 29-year-old man presented with liver damage, and a liver biopsy was performed, but the cause was unclear. Thereafter, he was referred to our hospital. We found that he had been unable to consume carbohydrates in his diet and preferred fried chicken since childhood. In addition, he had shown disturbance of consciousness and abnormal behavior while he had been in prison, where dietary intake had been restricted. A plasma amino acid analysis revealed hypercitrullinemia. Therefore, we suspected adult-onset type II citrullinemia (CTLN2). Genetic testing showed pathologic variations in the SLC25A13 gene, which allowed us to make a definite diagnosis of CTLN2.

A non-cell-autonomous circadian rhythm of bioluminescence reporter activities in individual duckweed cells.

The circadian clock is responsible for the temporal regulation of various physiological processes in plants. Individual cells contain a circadian oscillator consisting of a clock gene circuit that coordinates physiological rhythms within the plant body in an orderly manner. The coordination of time information has been studied from the perspective of cell-cell local coupling and long-distance communication between tissues based on the view that the behavior of circadian oscillators represents physiological rhythms. Here, we report the cellular circadian rhythm of bioluminescence reporters that are not governed by the clock gene circuit in expressing cells. We detected cellular bioluminescence rhythms with different free-running periods in the same cells using a dual-color bioluminescence monitoring system in duckweed (Lemna minor) transfected with Arabidopsis CIRCADIAN CLOCK ASSOCIATED 1::luciferace+ (AtCCA1::LUC+) and Cauliflower mosaic virus 35S::modified click-beetle red-color luciferase (CaMV35S::PtRLUC) reporters. Co-transfection experiments with the two reporters and a clock gene-overexpressing effector revealed that the AtCCA1::LUC+ rhythm, but not the CaMV35S::PtRLUC rhythm, was altered in cells with a dysfunctional clock gene circuit. This indicated that the AtCCA1::LUC+ rhythm is a direct output of the cellular circadian oscillator, whereas the CaMV35S::PtRLUC rhythm is not. After plasmolysis, the CaMV35S::PtRLUC rhythm disappeared, whereas the AtCCA1::LUC+ rhythm persisted. This suggests that the CaMV35S::PtRLUC bioluminescence has a symplast/apoplast-mediated circadian rhythm generated at the organismal level. The CaMV35S::PtRLUC-type bioluminescence rhythm was also observed when other bioluminescence reporters were expressed. These results reveal that the plant circadian system consists of both cell-autonomous and noncell-autonomous rhythms that are unaffected by cellular oscillators.

Pulmonary Artery Intimal Sarcoma in a Patient with Lynch Syndrome: Response to an Immune Checkpoint Inhibitor.

Intimal sarcoma is an extremely rare mesenchymal tumor arising in the great vessels. To date, intimal sarcoma has not been reported in patients with Lynch syndrome (LS), even though this syndrome lacks DNA mismatch repair ability genetically and is prone to various malignancies. This patient was diagnosed with LS by the Revised Amsterdam Criteria II, and she suffered from intimal sarcoma in the left pulmonary artery. She had a germline missense variant of PMS2 (c.1399G>A, pV467I) which is classified as a variant of unknown significance. In her intimal sarcoma, PMS2 expression was decreased. Additionally, it exhibited microsatellite instability and a high tumor mutational burden (69 mutations/Mb) which are features of mismatch repair deficiency, although PMS2 (c.1399G>A, pV467I) missense is a variant of unknown significance. The metastatic lesions of intimal sarcoma in this patient responded heterogeneously to pembrolizumab, an immune checkpoint inhibitor. Cytotoxic agents and radiation were also effective for some metastatic lesions, but some lesions, including her liver metastases, were resistant. The hypermutable nature of the LS genotype might acquire resistance to an immune checkpoint inhibitor and other cytotoxic agents such as occurred with her liver metastases.

Intraoperative indocyanine green fluorescence cholangiography can rule out biliary atresia: A preliminary report.

Background: The prognosis of BA is known to be poor if definitive surgery is performed too late. Therefore, excluding BA as a diagnosis at an early stage is crucial. Conventional cholangiography requiring cannulation through the gallbladder may be unnecessarily invasive for patients, especially when ruling out BA. Therefore, a less invasive alternative such as indocyanine green (ICG) cholangiography, which does not require cannulation, should be established. In this study, we focused on excluding BA and confirmed the usefulness of intravenous ICG fluorescence cholangiography. To the best of our knowledge, this is the first preliminary study to report the use of intravenous ICG cholangiography for BA exclusion. Methods: The study participants were patients who underwent liver biopsy and intraoperative cholangiography after they were suspected to have BA, between 2013 and 2022. ICG fluorescence cholangiography was performed on all patients who provided informed consent. Results: During the study period, 88 patients underwent a laparoscopic liver biopsy and cholangiography. Among them, 65 (74%) were diagnosed with BA and underwent a subsequent laparoscopic Kasai portoenterostomy. BA was ruled out intraoperatively in 23 patients. Of the 23 patients in whom BA was ruled out, 14 underwent ICG cholangiography, 11 had gallbladder (GB) fluorescence, and 9 had both GB and common bile duct (CBD) fluorescence. Conventional cholangiography was very difficult in 2 of 23 cases: in 1 case, cannulation of the atrophic gallbladder was impossible, and cholecystectomy was indicated after multiple attempts; in 1 case, upstream cholangiography was not possible. In both cases, ICG fluorescence cholangiography successfully imaged the CBD and the GB. Conclusions: In conclusion, intravenous ICG fluorescence cholangiography might be a useful and less invasive diagnostic procedure that can rule out BA in infants.

A Novel Variation of the Lateral Window Approach for Sinus Floor Elevation in a Case of Bony Nodular Prominence.

Introduction: In sinus floor augmentation, bony nodular prominence at the floor of the maxillary sinus is an obstruction to lateral window approach. It is challenging to detach and elevate the sinus membrane without making any perforations around the nodular prominence, because the membrane is very thin. To overcome these difficulties, we developed a novel method. Method: The membrane was not detached from the surface of the nodular prominence except for at the basal point, but the nodular prominence was cut at the base. Nodular prominence and sinus membrane were elevated upward together. A resorbable collagen membrane was placed beneath it to provide mechanical support and cover any partial tear in the sinus membrane. Autogenous bone and/or bone substitute were packed in the vacant compartment depending on the condition. Conclusion: This method is very easy to be carried out without any difficulties and worries. It gives us great benefit on the sinus floor augmentation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-021-01572-7.

The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure.

Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ventricle predominantly expresses alternative complement pathway-related genes, including Cfd and C3aR1. Complement 3 (C3)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd). Cfd-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure.

Circadian-period variation underlies the local adaptation of photoperiodism in the short-day plant Lemna aequinoctialis.

Phenotypic variation is the basis for trait adaptation via evolutionary selection. However, the driving forces behind quantitative trait variations remain unclear owing to their complexity at the molecular level. This study focused on the natural variation of the free-running period (FRP) of the circadian clock because FRP is a determining factor of the phase phenotype of clock-dependent physiology. Lemna aequinoctialis in Japan is a paddy field duckweed that exhibits a latitudinal cline of critical day length (CDL) for short-day flowering. We collected 72 strains of L. aequinoctialis and found a significant correlation between FRPs and locally adaptive CDLs, confirming that variation in the FRP-dependent phase phenotype underlies photoperiodic adaptation. Diel transcriptome analysis revealed that the induction timing of an FT gene is key to connecting the clock phase to photoperiodism at the molecular level. This study highlights the importance of FRP as a variation resource for evolutionary adaptation.

Case Report: A Rare Case of Benign Recurrent Intrahepatic Cholestasis-Type 1 With a Novel Heterozygous Pathogenic Variant of ATP8B1.

Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is a rare autosomal recessive disorder that is characterized by intermittent episodes of jaundice and intense pruritus and caused by pathogenic variants of adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1). The presence of genetic heterogeneity in the variants of ATP8B1 is suggested. Herein, we describe a unique clinical course in a patient with BRIC1 and a novel heterozygous pathogenic variant of ATP8B1. A 20-year-old Japanese man experienced his first cholestasis attack secondary to elevated transaminase at 17 years of age. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, or inborn or acquired metabolic etiologies. Since the patient also had elevated transaminase and hypoalbuminemia, he was treated with ursodeoxycholic acid and prednisolone. However, these treatments did not relieve his symptoms. Histopathological assessment revealed marked cholestasis in the hepatocytes, Kupffer cells, and bile canaliculi, as well as a well-preserved intralobular bile duct arrangement and strongly expressed bile salt export pump at the canalicular membrane. Targeted next-generation sequencing detected a novel heterozygous pathogenic variant of ATP8B1 (c.1429 + 2T > G). Taken together, the patient was highly suspected of having BRIC1. Ultimately, treatment with 450 mg/day of rifampicin rapidly relieved his symptoms and shortened the symptomatic period.

Iron Deficiency Anemia Improved by Dental Implantation: A Case Report.

Treatments for improving iron deficiency anemia are generally aimed at increasing oral iron intake and/or administration. Such treatments, however, have been unsuccessful in managing nutritional disorders, including anemia, in patients with masticatory dysfunction caused by impaired occlusion. Nevertheless, few studies have assessed the potential benefits of providing optimal occlusion in such cases. Here, we report a case involving a 53-year-old woman with iron deficiency anemia, wherein we attempted to facilitate efficient mastication by establishing functional occlusion with dental implant placement. The patient was diagnosed with iron deficiency anemia and hospitalized for blood transfusion 2 years before she visited our dental clinic. At the first visit, her hemoglobin (Hb) and mean corpuscular volume values were low; sodium ferrous citrate administration and dietary guidance led to slight improvement. However, blood transfusions and iron supplementation had been ineffective over longer duration. After dental implant placement, her Hb and mean corpuscular volume values were restored and maintained for >4 years without medication. Through this report, we highlight an alternative, non-pharmacological treatment strategy for iron deficiency anemia.

Novel gene mutations in three Japanese patients with ARC syndrome associated mild phenotypes: a case series.

BACKGROUND: Arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is a rare autosomal recessive disorder caused by mutations in VPS33B (ARCS1) and VIPAS39 (ARCS2). As per literature, most patients with ARCS died of persistent infections and bleeding by the age of 1 year. We report the first Japanese cases with ARCS1 and ARCS2 who presented with mild phenotypes and were diagnosed via genetic testing. CASE PRESENTATION: Case 1: A 6-year-old boy born to nonconsanguineous Japanese parents presented with jaundice and normal serum gamma-glutamyl transferase (GGT) levels, proteinuria, bilateral nerve deafness, motor delay, failure to thrive, and persistent pruritus. After cochlear implantation for deafness at the age of 2 years, despite a normal platelet count and prothrombin time-international normalized ratio, the patient presented with persistent bleeding that required hematoma removal. Although he did not show any obvious signs of arthrogryposis, he was suspected to have ARCS based on other symptoms. Compound heterozygous mutations in VPS33B were identified using targeted next-generation sequencing (NGS), which resulted in no protein expression. Case 2: A 7-month-old boy, the younger brother of case 1, presented with bilateral deafness, renal tubular dysfunction, failure to thrive, and mild cholestasis. He had the same mutations that were identified in his brother's VPS33B. Case 3: A 24-year-old man born to nonconsanguineous Japanese parents was suspected to have progressive familial intrahepatic cholestasis 1 (PFIC1) in his childhood on the basis of low GGT cholestasis, renal tubular dysfunction, sensory deafness, mental retardation, and persistent itching. A liver biopsy performed at the age of 16 years showed findings that were consistent with PFIC1. He developed anemia owing to intraperitoneal hemorrhage from a peripheral intrahepatic artery the day after the biopsy, and transcatheter arterial embolization was required. ARCS2 was diagnosed using targeted NGS, which identified novel compound heterozygous mutations in VIPAS39. CONCLUSIONS: The first Japanese cases of ARCS1 and ARCS2 diagnosed using genetic tests were reported in this study. These cases are milder than those previously reported. For patients with ARCS, invasive procedures should be performed with meticulous care to prevent bleeding.

Interspecific divergence of circadian properties in duckweed plants.

The circadian clock system is widely conserved in plants; however, divergence in circadian rhythm properties is poorly understood. We conducted a comparative analysis of the circadian properties of closely related duckweed species. Using a particle bombardment method, a circadian bioluminescent reporter was introduced into duckweed plants. We measured bioluminescence circadian rhythms of eight species of the genus Lemna and seven species of the genus Wolffiella at various temperatures (20, 25, and 30°C) and light conditions (constant light or constant dark). Wolffiella species inhabit relatively warm areas and lack some tissues/organs found in Lemna species. Lemna species tended to show robust bioluminescence circadian rhythms under all conditions, while Wolffiella species showed lower rhythm stability, especially at higher temperatures. For Lemna, two species (L. valdiviana and L. minuta) forming a clade showed relatively lower circadian stability. For Wolffiella, two species (W. hyalina and W. repanda) forming a clade showed extremely long period lengths. These analyses reveal that the circadian properties of species primarily reflect their phylogenetic positions. The relationships between geographical and morphological factors and circadian properties are also suggested.

Kinetics of atrial and brain natriuretic peptides during hemodialysis are regulated in association with different cardiac functional changes.

The blood levels of atrial and brain natriuretic peptides (ANP and BNP) are both increased markedly in hemodialysis patients, but the kinetics of the two are not always parallel. The present study investigated the association of changes in ANP and BNP levels before and after dialysis with changes in cardiac function in hemodialysis patients. A total of 57 patients (mean age 64 years, 47 males and 10 females) on maintenance hemodialysis with sinus rhythm were enrolled. Blood samples were taken at the beginning and end of dialysis, and plasma levels of ANP and BNP were measured. Changes in cardiac function during dialysis were examined by echocardiography performed just before and after dialysis. Both plasma ANP and BNP concentrations decreased significantly after hemodialysis, but the rate of decrease in BNP [mean ± SD, 555 ± 503 to 519 ± 477 pg/mL (- 6.4%), P = 0.011] was much smaller than that in ANP [233 ± 123 to 132 ± 83 pg/mL (- 43.4%), P < 0.001]. As for the relation to the changes in echocardiographic parameters before and after dialysis, the decrease in inferior vena cava diameter had a close correlation with the decrease in ANP (r = 0.528, P < 0.001), but not BNP. In contrast, the decrease in left ventricular end-diastolic volume index was correlated only with the decrease in BNP (r = 0.297, P = 0.035). The peak velocity ratio of early diastolic to atrial filling decreased with preload reduction by dialysis, and its decrease was more strongly correlated with the decrease in BNP (r = 0.407, P = 0.002) than that in ANP (r = 0.273, P = 0.040). These results demonstrated that in hemodialysis patients, the decrease in plasma ANP by a single dialysis was essentially caused by blood volume reduction, while BNP decrease was mainly induced by the reduction of left ventricular overload. Our findings indicate that the kinetics of both peptides during dialysis are regulated by different cardiac and hemodynamic factors.

Real-life Progression of the Use of a Genetic Panel in to Diagnose Neonatal Cholestasis.

The study aimed to construct an advanced gene panel to ascertain the genetic etiology of patients with neonatal/infantile intrahepatic cholestasis (NIIC), and test patients with NIIC in a clinical setting. Methods: From the group of NIIC patients, whom we had previously tested with our old 18-gene panel from May 2013 to September 2017 but could not establish a definitive diagnosis, we included 191 in the retrospective reanalysis group for this study. Additionally, we recruited 124 patients with NIIC into a prospective analysis group from October 2017 to October 2019. Cholestasis was defined as a serum direct bilirubin level >1.0 mg/dL. We constructed a 61-gene panel for targeted next-generation sequencing of the patients. Results: In the retrospective reanalysis group, we found mutations in ABCC2, MPV17, NPC1, CFTR, NR1H4, or CYP27A1 in 10 (5.2%) of the 191 patients. In the prospective analysis group, 33 (26.6%) of the 124 patients had a causative mutation in JAG1, NOTCH2, ABCC2, SLC25A13, ABCB11, POLG, NPC1, CFTR, ATP8B1, or ABCB4. The top 3 genetic diagnoses were of Alagille syndrome, neonatal Dubin-Johnson syndrome, and neonatal intrahepatic cholestasis caused by citrin deficiency, which together constitute 78.8% of the genetic causes of cholestasis in Japan. We also identified 3 genotypes associated with Crigler-Najjar syndrome type 2 in the retrospective reanalysis group. Conclusions: The advanced NIIC gene panel successfully uncovered molecular genetic etiologies of NIIC not only in the reanalysis group but also in the prospective cohort. Crigler-Najjar syndrome type 2 patients may be included along with NIIC patients.

An endogenous basis for synchronisation characteristics of the circadian rhythm in proliferating Lemna minor plants.

The circadian clock is a cell-autonomous system that functions through the coordination of time information in the plant body. Synchronisation of cellular clocks is based on coordination mechanisms; the synchronisation characteristics of proliferating plants remain unclear. The bioluminescence circadian rhythms of fronds (leaf-like plant units) of proliferating Lemna minor plants carrying a circadian bioluminescence reporter, AtCCA1:LUC, were spatiotemporally analysed at a cell-level resolution. We focused on spontaneous circadian organisation under constant light conditions for plants with light : dark treatment (LD grown) or without it (LL grown). Fronds developing even from an LL-grown parental frond showed coherent circadian rhythms among them. This allowed the maintenance of circadian rhythmicity in proliferating plants. Inside a frond, a centrifugal phase/period pattern was observed in LD-grown plants, whereas various phase patterns with travelling waves were formed in LL-grown plants. These patterns were model simulated by local coupling of heterogeneous cellular circadian oscillators with different initial synchronous states in fronds. Spatiotemporal analysis of the circadian rhythms in proliferating plants reveals spontaneous synchronisation manners that are associated with local cell-cell coupling, spatial phase patterns and developmental stages.

Role of active site arginine residues in substrate recognition by PPM1A.

Reversible protein phosphorylation is a key mechanism for regulating numerous cellular events. The metal-dependent protein phosphatases (PPM) are a family of Ser/Thr phosphatases, which uniquely recognize their substrate as a monomeric enzyme. In the case of PPM1A, it has the capacity to dephosphorylate a variety of substrates containing different sequences, but it is not yet fully understood how it recognizes its substrates. Here we analyzed the role of Arg33 and Arg186, two residues near the active site, on the dephosphorylation activity of PPM1A. The results showed that both Arg residues were critical for enzymatic activity and docking-model analysis revealed that Arg186 is positioned to interact with the substrate phosphate group. In addition, our results suggest that which Arg residue plays a more significant role in the catalysis depends directly on the substrate.