Decadal stability in coral cover could mask hidden changes on reefs in the East Asian Seas.

Coral reefs in the Central Indo-Pacific region comprise some of the most diverse and yet threatened marine habitats. While reef monitoring has grown throughout the region in recent years, studies of coral reef benthic cover remain limited in spatial and temporal scales. Here, we analysed 24,365 reef surveys performed over 37 years at 1972 sites throughout East Asia by the Global Coral Reef Monitoring Network using Bayesian approaches. Our results show that overall coral cover at surveyed reefs has not declined as suggested in previous studies and compared to reef regions like the Caribbean. Concurrently, macroalgal cover has not increased, with no indications of phase shifts from coral to macroalgal dominance on reefs. Yet, models incorporating socio-economic and environmental variables reveal negative associations of coral cover with coastal urbanisation and sea surface temperature. The diversity of reef assemblages may have mitigated cover declines thus far, but climate change could threaten reef resilience. We recommend prioritisation of regionally coordinated, locally collaborative long-term studies for better contextualisation of monitoring data and analyses, which are essential for achieving reef conservation goals.

Prognostic nutritional index and early mortality with percutaneous endoscopic gastrostomy.

BACKGROUND: Although percutaneous endoscopic gastrostomy (PEG) is a well-accepted and less invasive method of feeding tube placement in patients with swallowing difficulties, complications and early death after PEG have been reported. AIM: This study aimed to evaluate predictive factors associated with 30-day mortality after PEG, and to assess the utility of nutritional supporting period before PEG in reducing early mortality following PEG. DESIGN: An observational study. METHODS: We retrospectively analyzed 268 patients who underwent PEG at Sapporo Shirakaba-dai Hospital from 2006 to 2010, using clinical and laboratory data to analyze predictive factors associated with early death after PEG. Then, we prospectively assessed 152 consecutive patients assessed for eligibility for PEG from 2011 to 2014. We assessed the patients' nutritional condition using Onodera's prognostic nutritional index (PNI), and supported nutrition for more than 10 days before PEG in patients with a poor nutritional index (PNI < 37). RESULTS: In both univariate and multivariate analyses in the retrospective study, Onodera's PNI of less than 37 was the only predictive factor for early mortality. In the second study, among the 115 patients who finally underwent PEG, early mortality rates improved to 1.7% from 5.2% in the first study. Conversely, 32% of patients with malnutrition who did not undergo PEG died within 30 days. CONCLUSION: Nutritional status might be a predictive factor for early mortality after PEG. In patients with poor nutritional status, nutritional supporting period before PEG might improve the outcomes and reduce unnecessary PEG.

Management of angiogram-negative acute colonic hemorrhage: safety and efficacy of colonoscopy-guided superselective embolization.

BACKGROUND: We evaluated the efficacy and safety of superselective embolization with assistance of colonoscopy for acute colonic hemorrhage. METHODS: Of 92 cases of acute colonic hemorrhage requiring colonoscopic intervention, 11 (12 %) could not be successfully treated. Of these, 10 patients (9 men, mean age 65.5 years, range 39-75 years) underwent superselective embolization. Hemorrhage was caused by diverticular disease (n = 8), polypectomy (n = 1), and vascular malformation (n = 1). In all 10 cases, the radiopaque clips were placed at the bleeding point via colonoscopy. Microcatheters were used in all procedures, and embolization was performed at the level of the vasa recta leading to or near the clips with Gelfoam particles, microcoils, or both. RESULTS: Immediate hemostasis was achieved in all patients. In 6 of 10 patients (60 %), selective angiograms showed no active extravasation at the time of the procedure and the embolization was performed using clips as a landmark. In the remaining four patients, selective angiograms showed active extravasation from the vasa recta leading to the clips. The mean number of embolized vessels with no active extravasation and with active extravasation was 1.83 (range 1-3) and 1.25 (range 1-2), respectively. The mean duration of clinical follow-up was 11.6 months (range 1-29 months). One patient (10 %) bled from a different site than the treated site a month after embolization, but the bleeding ceased after endoscopic intervention. All the patients (100 %) were evaluated for objective evidence of ischemia by colonoscopy. Four of the 10 patients (40 %) were found endoscopically to have small areas of ischemia involving only the mucosa, but they remained asymptomatic. There was no bowel infarction or stricture. CONCLUSIONS: Colonoscopy-assisted superselective embolization may be a safe and useful procedure for acute colonic hemorrhage without active extravasation on angiogram.

delta15N of seagrass leaves for monitoring anthropogenic nutrient increases in coral reef ecosystems.

In a coral reef environment, a slight increase in dissolved inorganic nitrogen (DIN;> or =1.0 micro M) can alter the ecosystem via macroalgal blooms. We collected seagrass leaves from the tropical and subtropical Pacific Ocean in five countries and examined the interactions between nutrient concentrations (C, N, P), molar ratios of nutrients, and delta15N to find a possible indicator of the DIN conditions. Within most sites, the concentrations of nutrients and their molar ratios showed large variations owing to species-specific values. On the other hand, almost identical delta15N values were found in seagrass leaves of several species at each site. The correlations between delta15N and nutrient concentrations and between delta15N and molar ratios of nutrients suggested that nutrient availability did not affect the delta15N value of seagrass leaves by altering the physiological condition of the plants. Increases in delta15N of seagrass leaves mostly matched increases in DIN concentrations in the bottom water. We suggest that delta15N in seagrass leaves can be a good tool to monitor time-integrated decrease/increase of DIN concentrations at a site, both in the water column and the interstitial water.

APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box.

Nek2 is a NIMA-related kinase implicated in regulating centrosome structure at the G(2)/M transition. Two splice variants have been identified that exhibit distinct patterns of expression during cell cycle progression and development. Here we show that Nek2A, but not Nek2B, is destroyed upon entry into mitosis coincident with cyclin A destruction and in the presence of an active spindle assembly checkpoint. Destruction of Nek2A is mediated by the proteasome and is dependent upon the APC/C-Cdc20 ubiquitin ligase. Nek2 activity is not required for APC/C activation. Nek2A destruction in early mitosis is regulated by a motif in its extreme C-terminus which bears a striking resemblance to the extended destruction box (D-box) of cyclin A. Complete stabilization of Nek2A requires deletion of this motif and mutation of a KEN-box. Destruction of Nek2A is not inhibited by the cyclin B-type D-box, but the C-terminal domain of Nek2A inhibits destruction of both cyclins A and B. We propose that recognition of substrates by the APC/C-Cdc20 in early mitosis depends upon possession of an extended D-box motif.

Lymph folliculitis in ulcerative colitis.

Preferential involvement of the appendix has recently been confirmed in ulcerative colitis. Since the appendix is an aggregate of lymph follicles, this new observation implies a critical role of the lymph follicles, of both the large bowel and the appendix, in an etiopathogenesis of ulcerative colitis. This report presents two cases of ulcerative colitis in which lymph folliculitis and lymphoid hyperplasia were observed. Lymph folliculitis was observed endoscopically in a border between an established lesion and an uninvolved area. Case 1, proctitis type, relapsing remitting, mild in severity, showed lymph folliculitis in a proximal border of an established rectal lesion. Case 2, with left-sided colitis, mild in severity, had a skip appendiceal orifice inflammation. Lymph folliculitis was observed in the cecum surrounding established appendiceal orifice inflammation. In both cases, lymphoid hyperplasia was observed in an uninvolved area with clear vascular patterns. These two cases clearly demonstrate the involvement of gut lymph follicles in ulcerative colitis. Lymph folliculitis and/or lymphoid hyperplasia was proposed to be early lesions in ulcerative colitis. In addition, the need for microbiology targeting lymph follicles of the large bowel and appendix is stressed in order to disclose the casual microbial agents in ulcerative colitis.

Endoscopic mucosal resection of the colon: the Japanese technique.

Early colorectal neoplasms, especially flat-type and depressed-type lesions, should be treated with an EMR technique. In general because depressed-type lesions, in contrast to flat-type or protruded-type lesions, tend to invade the submucosa rapidly, they ought to be treated by EMR at an early stage. Histopathologically in the case of lesions that only minimally invade the submucosa without vessel invasion (sm1a and sm1b without vessel invasion), a treatment can be completed with EMR. Massive submucosal invasive cancers ought to be resected by surgical treatment because of the risk of recurrence or metastasis. In addition, pit pattern diagnosis with magnifying colonoscopy is useful to determine a therapeutic method for colonic neoplasms. Lesions with the type VN pit pattern represent malignancy and usually invade the submucosa massively, so it is better to treat them surgically from the outset. Endoscopic mucosal resection should be conducted under fully controlled endoscopy to prevent complications. EMR is a superior therapeutic method and will be performed frequently in the future. It is necessary for colonoscopists to determine a suitable therapy for each colorectal neoplastic lesion. They also need to master the EMR technique in the correct manner.

Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer.

Nonpolypoid colorectal neoplasms are grossly classified into three groups: slightly elevated (small flat adenomas), laterally spreading, and depressed. Flat adenomas are not invasive until they are rather large, whereas depressed lesions can invade the submucosa even when they are extremely small. Nonpolypoid lesions are difficult to detect and are often overlooked. Keys to detect them are their slight color change, interruption of the capillary network pattern, slight deformation of the colonic wall, spontaneously bleeding spots, shape change of the lesion with insufflation and deflation of air, and interruption of the innominate grooves. Spraying of indigo carmine dye helps to clarify the lesions. A pit pattern analysis with a zoom colonoscope is useful for the diagnosis and staging of early colorectal cancer. Small flat adenomas are thought to be precursors of protruded polyps and lateral spreading tumors, whereas depressed lesions are thought to grow endophytically and become advanced cancers. Small depressed lesions are treated with an endoscopic mucosal resection (EMR) technique; but when they massively invade the submucosa, surgical resection is indicated. Laterally spreading tumors are not as invasive despite their large size and therefore are good indications for the EMR or piecemeal EMR method. Small flat adenomas need not be treated urgently, as almost none is invasive. Accurate diagnosis with dye-spraying and zoom colonoscopy is vital for deciding the treatment strategy.

The spike of S phase cyclin Cig2 expression at the G1-S border in fission yeast requires both APC and SCF ubiquitin ligases.

We describe a novel set of oscillation mechanisms for the fission yeast S phase cyclin Cig2, which contains an authentic destruction box and is destroyed at anaphase via the APC/cyclosome (APC/C). Unlike the mitotic cyclin Cdc13, however, Cig2 mRNA and protein peak at the G1/S boundary and decline to low levels in G2 and M phases. We show here that SCF(Pop1, Pop2) plays a role in transcriptional periodicity, as pop mutations result in constitutive cig2(+) transcripts. The instability of Cig2 during G2 and M is independent of either the APC/C or Pop1/Pop2, but requires Skp1, a core component of SCF. These data indicate that the APC/C and SCF control Cig2 levels differentially at different stages of the cell cycle.

Carrier-mediated transport systems for glucose in mucosal cells of the human oral cavity.

The in vitro uptake study was performed using the isolated cells of human oral mucosa, buccal and the dorsum of the tongue, to investigate the mechanisms of glucose uptake. The uptake of D-glucose was much larger in cells of the dorsum of the tongue than in buccal cells and was inhibited more extensively by 2-deoxy-D-glucose, a substrate of facilitative glucose transporters, than by alpha-methyl-D-glucoside, a specific substrate of SGLT1, suggesting the larger contribution of a facilitative transporter than Na(+)/glucose cotransporter. Furthermore, from the results of inhibition studies by several sugar analogues including maltose and D-mannose, GLUT1 and/or GLUT3 were suggested to take part in the glucose uptake by oral mucosa. Therefore, we have attempted to confirm the expression of glucose transporters on the oral mucosa by employing Western blotting. As a result, it was suggested that SGLT1, GLUT1, GLUT2, and GLUT3 are expressed in the epithelial cells of human oral mucosa.

Hepatitis C virus 1b(II) infection and development of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma: a case-control study in Japan.

This study was performed to determine the distribution of hepatitis C virus (HCV) genotypes among asymptomatic carriers (ASC) and patients with chronic hepatitis without cirrhosis (NC-CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in the Osaka area, and to assess whether infection with HCV genotype 1b (II) is more likely to develop into hepatocellular carcinoma (HCC) than is that with genotype 2a (III) or genotype 2b (IV). Genotypes of all study subjects were determined by Okamoto's method. HCV genotype 1b was detected in 100 of the 143 ASC (69.9%), 551 of the 726 NC-CH patients (75.9%), 86 of the 103 patients with LC (83.5%), and 153 of the 179 HCC (85.5%) patients. Using unconditional logistic regression analysis, the age- and sex- adjusted odds ratios contrasting NC-CH with ASC, LC with ASC and HCC with ASC were 1.38 [95% confidence interval (CI) = 0.93-2.05], 2.28 (95% CI = 1.12-4.63) and 2.27 (95% CI = 1.02-5.06) respectively. HCV genotype 1b is predominant in both healthy carriers and patients with chronic liver diseases in the Osaka area. The findings from the three case-control studies indicate that type 1b infection is more closely associated with the development of LC and HCC than type 2a or 2b through its role in the progression of chronic liver inflammation to a cirrhotic stage.

The role of the destruction box and its neighbouring lysine residues in cyclin B for anaphase ubiquitin-dependent proteolysis in fission yeast: defining the D-box receptor.

Programmed proteolysis of proteins such as mitotic cyclins and Cut2/Pds1p requires a 9-residue conserved motif known as the destruction box (D-box). Strong expression of protein fragments containing destruction boxes, such as the first 70 residues of Cdc13 (N70), inhibits the growth of Schizosaccharomyces pombe at metaphase. This inhibition can be overcome either by removal of all lysine residues from N70 using site-directed mutagenesis (K0-N70) or by raising the concentration of intracellular ubiquitin. Consistent with the idea that competition for ubiquitin accounts for some of its inhibitory effects, wild-type N70 not only stabilized D-box proteins, but also Rum1 and Cdc18, which are degraded by a different pathway. The K0-N70 construct was neither polyubiquitinated nor degraded in vitro, but it blocked the growth of strains of yeast in which anaphase-promoting complex/cyclosome (APC/C) function was compromised by mutation, and specifically inhibited proteolysis of APC/C substrates in vivo. Both K0-N70 and 20-residue D-box peptides blocked polyubiquitination of other D-box-containing substrates in a cell-free ubiquitination assay system. These data suggest the existence of a D-box receptor protein that recognizes D-boxes prior to ubiquitination.

The risk of hepatitis C virus infection among blood donors in Osaka, Japan.

To estimate the risk of hepatitis C virus (HCV) infection among blood donors, we conducted a retrospective cohort study with 448,020 HCV-seronegative donors who donated blood more than once between February 1992 and July 1997 in Osaka (a total of 2,676,738 allogeneic blood donations). The donors were divided into four age groups according to the age at the initial donation: Group A (16-24 years), Group B (25-34 years), Group C (35-49 years) and Group D (50-64 years). Fifty-nine donors became infected with HCV among the 448,020 HCV-seronegative donors who donated blood more than once within a period of approximately five years. In a total of 1,095,668 person-years of observation (PYO), the incidence rate was 5.38 per 105 PYO, with the 95% confidence interval (95% C.I.) being 4.10 to 6.95. There was no significant difference in the incidence rate between males and females. Young donors between the ages of 16 and 24 (8.89; 95% C.I., 6.04 to 12.61) had a significantly higher incidence rate of HCV infection than donors between the ages of 35 and 49 (1.81; 0.67 to 3.95). The cumulative risk of HCV infection among donors between the ages of 16 and 64 was estimated to be 0.27% (95% C.I., 0.16 to 0.39) for males and 0.27% (95% C.I., 0.15 to 0.38) for females. Based on the recent age-specific incidence rate, the cumulative risk of HCV infection among blood donors was estimated to be about 0.3% in the Osaka district of Japan. The incidence rate differed among age groups, indicating that HCV infection is associated with age-related behaviors and the need for further epidemiological research towards the eradication of community-acquired HCV infection.

Fission yeast Cut2 required for anaphase has two destruction boxes.

The fission yeast Schizosaccharomyces pombe cut2(+) gene is essential for sister chromatid separation. Cut2 protein, which locates in the interphase nucleus and along the metaphase spindle, disappears in anaphase with the same timing as mitotic cyclin destruction. This proteolysis depends on the APC (Anaphase-Promoting Complex)-cyclosome which contains ubiquitin ligase activity. The N-terminus of Cut2 contains two stretches similar to the mitotic cyclin destruction box. We show that both sequences (33RAPLGSTKQ and 52RTVLGGKST) serve as destruction boxes and are required for in vitro polyubiquitination and proteolysis. Cut2 with doubly mutated destruction boxes inhibits anaphase, whereas Cut2 with singly mutated boxes can suppress cut2 mutations. Strong expression of the N-terminal 73 residues containing the destruction boxes leads to the accumulation of endogenous cyclin and Cut2, and arrests cells in metaphase, whereas the same fragment with the mutated boxes does not. Cut2 proteolysis occurs in vitro using Xenopus mitotic extracts in the presence of functional destruction boxes. Furthermore, Cut2 is polyubiquitinated in an in vitro system using HeLa extracts, and this polyubiquitination requires the destruction boxes.

The role of proteolysis in cell cycle progression in Schizosaccharomyces pombe.

A cell-free system derived from Xenopus eggs was used to identify the 'destruction box' of the Schizosaccharomyces pombe B-type cyclin, Cdc13, as residues 59-67: RHALDDVSN. Expression of indestructible Cdc13 from a regulated promoter in S.pombe blocked cells in anaphase and inhibited septation, showing that destruction of Cdc13 is necessary for exit from mitosis, but not for sister chromatid separation. In contrast, strong expression of a polypeptide comprising the N-terminal 70 residues of Cdc13, which acts as a competitive inhibitor of destruction box-mediated proteolysis, inhibited both sister chromatid separation and the destruction of Cdc13, whereas an equivalent construct with a mutated destruction box did not. Appropriately timed expression of this N-terminal fragment of Cdc13 overcame the G1 arrest seen in cdc10 mutant strains, suggesting that proteins required for the initiation of S phase are subject to destruction by the same proteolytic machinery as cyclin.

Diagnosis of colorectal tumorous lesions by magnifying endoscopy.

BACKGROUND: The magnifying colonoscope allows 100-fold magnified viewing of the colonic surface. METHODS: We examined 2050 colorectal tumorous lesions by magnifying endoscopy, stereomicroscopy, and histopathology and classified these lesions according to pit pattern. Based on stereomicroscopy, lesions with a type 1 or 2 pit pattern were nontumors, whereas lesions with types 3s, 3L, 4, and/or 5 pit patterns were neoplastic tumors. RESULTS: The pit patterns observed by magnifying endoscopy were fundamentally similar to those demonstrated in stereomicroscopic images. When the diagnosis by magnifying endoscopy was compared with the stereomicroscopic diagnosis, there was agreement in 1130 of 1387 lesions (81.5%). True neoplasms could be differentiated from non-neoplastic lesions. Of lesions with a type 5 pit pattern with a bounded surface, 11 of 22 (50%) were found to be invasive cancers with involvement of the submucosal layer. If this pit pattern is found to involve a relatively broad area of the mucosal surface, extensive malignant invasion (sm-massive) should be strongly suspected. CONCLUSIONS: The magnifying colonoscope provides an accurate instantaneous assessment of the histology of colorectal tumorous lesions. This may help in decision making during colonoscopy.

Cut2 proteolysis required for sister-chromatid seperation in fission yeast.

Although mitotic cyclins are well-known substrates for ubiquitin-mediated proteolysis at the metaphase-anaphase transition, their degradation is not essential for separation of sister chromatids; several lines of evidence suggest that proteolysis of other protein(s) is required, however. Here we report the anaphase-specific proteolysis of the Schizosaccharomyces pombe Cut2 protein, which is essential for sister-chromatid separation. Cut2 is located in the nucleus, where it is concentrated along the short metaphase spindle. The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction. Expression of non-degradable Cut2 blocks sister-chromatid separation but not cell-cycle progression. This defect can be overcome by grafting the N terminus of cyclin B onto the truncated Cut2, demonstrating that the regulated proteolysis of Cut2 is essential for sister-chromatid separation.

The problem of de novo colorectal carcinoma.

From April 1985 to March 1995, colonoscopy was carried out at our institution in 24,059 patients, 31,800 times in symptomatic and/or asymptomatic average risk persons. 184 submucosal invasive carcinomas were detected. Unlike protruding-type lesion, the depressed-type invades the submucosal layer, even though the size is within 10 mm. The depressed type of invasive carcinoma accounted for 20 lesions, and represented 10.9% (20 of 184) of all the invasive carcinomas. The pit pattern of depressed-type lesions shows a small round pit (type IIIs pit pattern) and that of carcinoma lesions shows the irregular pit and non-structure (type V pit pattern).

Phosphorylation of dis2 protein phosphatase at the C-terminal cdc2 consensus and its potential role in cell cycle regulation.

We show that the fission yeast dis2 protein phosphatase, which is highly similar to mammalian type 1 phosphatase, is a phosphoprotein containing phosphoserine (phospho-S) and threonine (phospho-T). It has several phosphorylation sites, two of which locate in the C-terminus. Phospho-T was abolished in the alanine substitution mutant at the C-terminal T316, which is conserved as a residue in the cdc2 consensus, TPPR, in a number of type 1-like phosphatases. In G2-arrested cdc2-L7 cells, the degree of T316 phosphorylation was reduced, whereas it was enhanced in metaphase-arrested nuc2-663 mutant cells. Phospho-T was produced in dis2 by fission yeast cdc2 kinase, but not in the substitution mutant A316, indicating that the T316 residue was the site for cdc2 kinase in vitro. Phosphatase activity of wild type dis2 was reduced by incubation with cdc2 kinase, but that of mutant dis2-A316 was not. Phosphorylation of T316 hence has a potential significance in cell cycle control in conjunction with cdc2 kinase activation and inactivation. Overexpression phenotypes of wild type dis2+, sds21+ and mutant dis2-A316, sds21-TPPR genes were consistent with negative regulation of dis2 by phosphorylation. This type of regulation would explain why cells harboring the dis2-11 mutation enter mitosis but fail to exit from it.