Rare occurrence of cryptic 5' splice sites by downstream 3' splice site/exon boundary mutations in a heavy-ion-induced allele of .

Pre-mRNA splicing is a fundamental process in eukaryotic gene expression, and the mechanism of intron definition, involving the recognition of the canonical GU (5'-splice site) and AG (3'-splice site) dinucleotides by splicing factors, has been postulated for most cases of splicing initiation in plants. Splice site mutations have played crucial roles in unraveling the mechanism of pre-mRNA splicing . Typically, splice site mutations abolish splicing events or activate one or more cryptic splice sites surrounding the mutated region.

Efficient oral vaccination program against classical swine fever in wild boar population.

Classical swine fever is a disease that infects wild boars and pigs and had a significant negative economic impact on the swine industry. Oral vaccination is an effective method for controlling classical swine fever. However, information on oral vaccination program has been limited, and its efficiency has not been clarified in Japan.

The potential negative impacts of the classical swine fever virus on wild boar population in Gifu prefecture, Japan.

There is a possibility that classical swine fever (CSF) virus outbreak has negative impacts on wild boar. To adequately manage native wild boar populations, wildlife managers need to gather the field data on wild boar and implement population management practices. We aimed to report the relative abundance index of wild boar before and after this outbreak.

Clonal Spread of Quinolone-Resistant Escherichia coli among Sika Deer (Cervus nippon) Inhabiting an Urban City Park in Japan.

The emergence and dissemination of resistance to clinically important antimicrobials in wild animals is of great concern. The aim of our study was to reveal the prevalence and intraspecies dissemination of quinolone-resistant Escherichia coli (QREC) in sika deer (Cervus nippon) in Nara Park, a famous tourist spot in Japan. Fecal samples were collected from 59 wild deer in Nara Park between July and October 2018.

Application of long-term collected data for conservation: Spatio-temporal patterns of mortality in Japanese serow.

Monitoring the mortality of wildlife provides basic demographic information to support management plan preparation. The utility of mortality records for conservation measures was investigated in the Japanese serow, focusing on temporal trends and spatial distribution. Using the mortality records of Japanese serow from 2006 to 2018 in Gifu prefecture, cause-specific mortality was categorized into five groups (disease, accident, vehicle collision, parapoxvirus infection, and unknown), and the sex ratios were examined.

Antitumor Activity of Eribulin After Fulvestrant Plus CDK4/6 Inhibitor in Breast Cancer Patient-derived Xenograft Models.

Background/aim: There is no established standard chemotherapy after administration of the combination endocrine plus CDK4/6 inhibitor therapy for luminal-type breast cancer. We used patient-derived xenograft (PDX) models to determine the antitumor activity of eribulin and capecitabine after endocrine therapy plus CDK4/6 inhibitor.

Materials And Methods: We examined the antitumor activity of fulvestrant, palbociclib, eribulin, and capecitabine in 4 luminal-type breast cancer PDX models (OD-BRE-0188, -0438, -0450, -0745).

Monitoring relative abundance index and age ratios of wild boar (Sus scrofa) in small scale population in Gifu prefecture, Japan during classical swine fever outbreak.

Although the first cases of classical swine fever were reported in 2018, no studies have explored this impact on wild boar populations in Japan. Comparing the relative abundance indices and age ratios in the wild boar population before and after the outbreak, we investigated the impact of classical swine fever virus on wild boar population dynamics in August 2017-December 2019. Relative abundance indices declined from 2017 to 2019 drastically, while there were no significant differences in age ratios throughout the study period.

Possible transmission of Sarcoptes scabiei between herbivorous Japanese serows and omnivorous Caniformia in Japan: a cryptic transmission and persistence?

Background: Two transmission patterns of Sarcoptes scabiei in host mammal communities have been reported based on microsatellite-level genetic studies in the last two decades. While one involves restrictions among different host taxa, the other is associated with predator-prey interactions between different host taxa. In contrast to these observations, the present study reports a possible irregular case of transmission of S.

A landmark in drug discovery based on complex natural product synthesis.

Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions.

Serological and histological evaluation of species-specific immunocontraceptive vaccine antigens based on zona pellucida 3 in the small Indian mongoose (Herpestes auropunctatus).

The small Indian mongoose (Herpestes auropunctatus) was introduced to Japanese islands and has impacted on the island's biodiversity. Population control has been attempted through capturing but its efficiency has rapidly declined. Therefore, new additional control methods are required.

Broad-spectrum Preclinical Antitumor Activity of Eribulin (Halaven®): Combination with Anticancer Agents of Differing Mechanisms.

Background: Eribulin is used in many countries to treat patients with advanced breast cancer or liposarcoma and exerts in vivo anticancer activity under monotherapy conditions against various human tumor xenograft models. Here, eribulin in combination with mechanistically different anticancer agents was evaluated.

Materials And Methods: Eribulin was combined with cytotoxic agents (capecitabine, carboplatin, cisplatin, doxorubicin, gemcitabine) or targeted agents (bevacizumab, BKM-120, E7449, erlotinib, everolimus, lenvatinib, palbociclib) in tumor xenograft models of breast cancer, melanoma, non-small cell lung cancer (NSCLC), and ovarian cancer.

Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models.

We previously reported that eribulin mesylate (eribulin), a tubulin-binding drug (TBD), could remodel tumor vasculature (i.e. increase tumor vessels and perfusion) in human breast cancer xenograft models.

Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma.

Background: Eribulin mesilate (eribulin), a first-in-class halichondrin B-based microtubule dynamics inhibitor, has been shown to promote vascular remodeling and reversal of epithelial-mesenchymal transition (EMT) apart from its antimitotic activity in breast cancer models.

Materials And Methods: Anti-proliferative activity of eribulin was examined in vitro and in vivo in several human soft tissue sarcoma (STS) cell lines. To assess tumor blood perfusion and phenotypic changes, eribulin was investigated in a leiomyosarcoma xenograft and in vitro in liposarcoma and leiomyosarcoma cell lines.

Impact of dopamine supersensitivity psychosis in treatment-resistant schizophrenia: An analysis of multi-factors predicting long-term prognosis.

Background: Although a variety of factors are known to be significantly related to poor prognosis in schizophrenia, their interactions remain unclear. Dopamine supersensitivity psychosis (DSP) is a clinical concept related to long-term pharmacotherapy and could be one of the key factors contributing to the development of treatment-resistant schizophrenia (TRS). The present study aims to explore the effect of DSP on progression to TRS.

Radiolabeled liposome imaging determines an indication for liposomal anticancer agent in ovarian cancer mouse xenograft models.

Liposomal anticancer agents can effectively deliver drugs to tumor lesions, but their therapeutic effects are enhanced in only limited number of patients. Appropriate biomarkers to identify responder patients to these liposomal agents will improve their treatment efficacies. We carried out pharmacological and histopathological analyses of mouse xenograft models bearing human ovarian cancers (Caov-3, SK-OV-3, KURAMOCHI, and TOV-112D) to correlate the therapeutic effects of doxorubicin-encapsulated liposome (Doxil(®) ) and histological characteristics linked to the enhanced permeability and retention effect.

Coexistence of two different genotypes of Sarcoptes scabiei derived from companion dogs and wild raccoon dogs in Gifu, Japan: The genetic evidence for transmission between domestic and wild canids.

Sarcoptes scabiei is the causal agent of sarcoptic mange in domestic/companion dogs (Canis lupus familiaris) and raccoon dogs (Nyctereutes procyonoides). Although there have been successful cases of experimental transmission of S. scabiei from mangy wild Canidae hosts to healthy dogs, and suspected cases of transmission between raccoon dogs and companion dogs, no clear-cut evidence has been obtained.

Isolation and antimicrobial susceptibility of Plesiomonas shigelloides from great cormorants (Phalacrocorax carbo hanedae) in Gifu and Shiga Prefectures, Japan.

Plesiomonas shigelloides is a causal agent of gastroenteritis, sepsis and meningitis in humans. We examined the prevalence of P. shigelloides among great cormorants (Phalacrocorax carbo hanedae) in Japan and the antimicrobial susceptibility of isolates.

Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models.

Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor of microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show that eribulin induces remodeling of tumor vasculature through a novel antivascular activity in MX-1 and MDA-MB-231 human breast cancer xenograft models.

Onset Pattern and Long-Term Prognosis in Schizophrenia: 10-Year Longitudinal Follow-Up Study.

Background: Although the duration of untreated psychosis (DUP) plays an important role in the short-term prognosis of patients with schizophrenia, their long-term prognosis generally is not determined by DUP alone. It is important to explore how other clinical factors in the early stage are related to DUP and consequent disease courses.

Methods: A total of 664 patients with untreated psychosis were surveyed for this study.

Development of liposomal anticancer drugs.

Liposomes are drug delivery systems that can alter the pharmacokinetic properties of compounds. The adverse effects of anticancer agents are a limiting factor for cancer chemotherapy, therefore, liposomal formulations have the potential to improve the therapeutic efficacy of anticancer agents by enhancing their accumulation in tumors and reducing non-selective distribution to normal tissues, which is known as the enhanced permeability and retention effect. To develop a liposomal anticancer agent as a drug product, its formulation must be designed to ensure its quality until it is administered to patients and to exert maximum potency in clinical use rather than in animal experiments.

Detection of Rickettsia tamurae DNA in ticks and wild boar (Sus scrofa leucomystax) skins in Shimane Prefecture, Japan.

We used 24 wild boars trapped from December 2009 to January 2010 and a further 65 from July 2010 to August 2010 in Misato Town, Shimane Prefecture, Japan. We collected blood, spleens, skins and ticks from the wild boars, which were examined for rickettsial infections using polymerase chain reaction (PCR) primers for the genes rickettsial 17-kDa antigen and citrate synthase (gltA). We amplified Rickettsia tamurae AT-1 DNA from the tick Amblyomma testudinarium and from wild boar skins where ticks attached.

Broad spectrum preclinical antitumor activity of eribulin (Halaven(R)): optimal effectiveness under intermittent dosing conditions.

Background: Eribulin is a pharmaceutically and structurally optimized analog of the marine sponge natural product halichondrin B. Its salt form, eribulin mesylate (Halaven®) is clinically used in the United States, the European Union, and Japan for the treatment of heavily pretreated patients with metastatic breast cancer, who previously received an anthracycline and a taxane. Early preclinical studies of this new inhibitor of microtubule dynamics showed high antitumor potency towards several human cancer types in vitro and in vivo.

Microregional antitumor activity of a small-molecule hypoxia-inducible factor 1 inhibitor.

Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that play crucial roles in the adaptation of cancer cells to hypoxia. HIF-1α overexpression has been associated with poor prognosis in patients with various types of cancer. Here, we describe ER-400583-00 as a novel HIF-1 inhibitor.