DBTGR: a database of tunicate promoters and their regulatory elements

The high similarity of tunicates and vertebrates during their development coupled with the transparency of tunicate larvae, their well-studied cell lineages and the availability of simple and efficient transgenesis methods makes of this subphylum an ideal system for the investigation of vertebrate physiological and developmental processes. Recently, the sequencing of two different Ciona genomes has lead to the identification of numerous genes. In order to better understand the regulation of these genes, a database was created containing information on regulation of tunicate genes collected from literature. It includes for instance information regarding the minimal promoter length, the transcription factors involved and their binding sites, as well as the localization of the gene expression. Additionally, binding sites for characterized transcription factors were predicted based on published in vitro recognition sites. Comparison of the promoters of homologous genes in different species is also provided to allow identification of conserved cis elements. At the time of writing, information about 184 promoters, containing 73 identified binding sites and >2000 newly predicted binding sites is available. This database is accessible at

Profiling ascidian promoters as the primordial type of vertebrate promoter

<p>Abstract</p> <p>Background</p> <p>CpG islands are observed in mammals and other vertebrates, generally escape DNA methylation, and tend to occur in the promoters of widely expressed genes. Another class of promoter has lower G+C and CpG contents, and is thought to be involved in the spatiotemporal regulation of gene expression. Non-vertebrate deuterostomes are reported to have a single class of promoter with high-frequency CpG dinucleotides, suggesting that this is the original type of promoter. However, the limited annotation of these genes has impeded the large-scale analysis of their promoters.</p> <p>Results</p> <p>To determine the origins of the two classes of vertebrate promoters, we chose <it>Ciona intestinalis</it>, an invertebrate that is evolutionarily close to the vertebrates, and identified its transcription start sites genome-wide using a next-generation sequencer. We indeed observed a high CpG content around the transcription start sites, but their levels in the promoters and background sequences differed much less than in mammals. The CpG-rich stretches were also fairly restricted, so they appeared more similar to mammalian CpG-poor promoters.</p> <p>Conclusions</p> <p>From these data, we infer that CpG islands are not sufficiently ancient to be found in invertebrates. They probably appeared early in vertebrate evolution via some active mechanism and have since been maintained as part of vertebrate promoters.</p

Drilling Research of a high-latiude coral reef in Mage Island, Stsunan Islands, Japan

Four drilling cores are observed from a high-latitude coral reef at the northwestern Mage Island (N30゜45' 40"). The thickness of the Holocene reef is around 2.5m in the reef edge and 4m in back reef. The Holocene thickness is relatively thin comparing to the modern reefs in the middle or the southern Ryukyu Islands. The reef structure Acropora facies, reworked coral rubble facies. This zonal structure conforms to the ecological coral-zonation corresponding to the wave-energy gradient

Risk factors for incisional hernia according to different wound sites after open hepatectomy using combinations of vertical and horizontal incisions: A multicenter cohort study.

Background:Although several risk factors for incisional hernia after hepatectomy have been reported, their relationship to different wound sites has not been investigated. Therefore, this study aimed to examine the risk factors for incisional hernia according to various wound sites after hepatectomy.Methods:Patients from the Osaka Liver Surgery Study Group who underwent open hepatectomy using combinations of vertical and horizontal incisions (J-shaped incision, reversed L-shaped incision, reversed T-shaped incision, Mercedes incision) between January 2012 and December 2015 were included. Incisional hernia was defined as a hernia occurring within 3 y after surgery. Abdominal incisional hernia was classified into midline incisional hernia and transverse incisional hernia. The risk factors for each posthepatectomy incisional hernia type were identified.Results:A total of 1057 patients met the inclusion criteria. The overall posthepatectomy incisional hernia incidence rate was 5.9% (62 patients). In the multivariate analysis, the presence of diabetes mellitus and albumin levels <3.5 g/dL were identified as independent risk factors. Moreover, incidence rates of midline and transverse incisional hernias were 2.4% (25 patients), and 2.3% (24 patients), respectively. In multivariate analysis, the independent risk factor for transverse incisional hernia was the occurrence of superficial or deep incisional surgical site infection, and interrupted suturing for midline incisional hernia.Conclusions:Risk factors for incisional hernia after hepatectomy depend on the wound site. To prevent incisional hernia, running suture use might be better for midline wound closure. The prevention of postoperative wound infection is important for transverse wounds, under the presumption of preoperative nutrition and normoglycemia

New Hepatic Resection Criteria for Intermediate-Stage Hepatocellular Carcinoma Can Improve Long-Term Survival: A Retrospective, Multicenter Collaborative Study.

Background:Hepatic resection (HR) is not recommended for intermediate-stage hepatocellular carcinoma (HCC) by the Barcelona Clinic Liver Cancer criteria. We examined the prognostic factors of HR for intermediate-stage HCC and developed new HR criteria for intermediate-stage HCC.Methods:A total of 110 patients who underwent HR without any prior treatment for intermediate-stage HCC between January 2007 and December 2012 were enrolled at eight university hospitals. The outcomes and prognostic factors of HR were evaluated to develop new HR criteria.Results:In terms of tumor size and number, the most significant prognostic factors were within the up-to-seven criteria. Furthermore, serum albumin level ≥35 g/L and serum alpha-fetoprotein (AFP) level

Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients

BackgroundAnti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF.Patients and methodsThe study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsThirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p &lt; 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups.ConclusionNivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma

<原著>肝切除術後におけるfructose-1, 6-bisphosphate投与による肝機能改善効果

The clinical effect of fructose-1, 6-bisphosphate (FBP) administered to posthepatectomy patients was examined . FBP at 0. 25 mmol/kg was administered continuously into the hepatic arter y for 60 minutes on the 1st postoperative day in 11 cases . Hepatic arterial infusion of 0. 25 mmol/kg glucose was performed in 7 cases. Furthermore, in 10 cases in which a catheter was not inserted in to the hepatic artery, 0. 25 mmol/kg FBP was administered intravenously over a 60-minute period. Arterial ketone body ratio (AKBR) and serum levels of cyclic adenosine monophosphate, immunoreactive insulin, inorganic phosphorus, glucose, fructose, pyruvate, lactate and pyruvate kinase (PK) in the arterial blood were measured before and after administration. AKBR hardly changed after hepati c arterial infusion of glucose. It rose until 3 hours after intravenous or intrahepatic arterial administration of FBP. Especially, after hepatic arterial infusion of FBP, the AKBR was significantly higher up to 2 hours after administration than that before administration (P < 0. 01). With hepatic arterial infusion of FBP, serum pyruvate tran sientl y increased immediately after infusion (P <0. 01). PK acti vity was significantly elevated after administration of FBP (P<0. 05). Serum lactate levels decreased significantly after hepatic arterial infusion of FBP (P <0. 05). There was no difference in the recovery of protein synthetic ability and the postoperative changes in serum liver function test values among the three groups. Hepatic arterial infusion of FBP was suggested to promote adenosine triphosphate production by acceleration of the glycolytic pathway and lactate uptake in the hepatic cell.肝切除例に対して, 術後にfructose-1, 6-bisphosphate (FBP) を投与し, その臨床効果を検討した. 肝動脈内にカテーテルを留置した肝癌切除18例のうち, 11例に対して FBP 0. 25 mmol/kg を60分間持続肝動脈内投与し, glucose 0. 25 mmol/kg を肝動脈内に投与した7例を対照とした. なお, 肝動脈カテーテル非留置10例に対して, FBP 0. 25 mmol/kg を60分間持続全身投与した. 投与前後における AKBR, c-AMP, IRI, iP, glucose , fructose, pyruvate, lactate, pyruvate kinase (PK) の血中変化を測定し, 術後の肝機能検査値の推移を検討した. Glucose の肝動注ではAKBRはほとんど変化しなかったが, FBPは肝動注でも全身投与でも, 投与3時間後まで上昇した. とくにFBP肝動注では投与前値に比べ, 2時間後まで統計学的に有意に上昇した(P<0. 01). FBP の肝動注では，血清pyruvateはFBP投与直後に一過性に上昇し(P<0. 01), PK活性はFBP投与2時間後に有意に上昇していた(P<0. 05). また, 血清 Lactate はFBPの肝動脈内投与後有意に低下した(P<0. 05). 術後の肝逸脱酵素の推移や蛋白合成能の回復は3群で有意な差はなかった. 以上より, FBPの肝動脈内投与は肝細胞における解糖系亢進や乳酸摂取の亢進によりATP産生を促進する可能性が示唆された