Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

Optimal integration of kinematic and ball-flight information when perceiving the speed of a moving ball

In order to intercept a moving target such as a baseball with high spatio-temporal accuracy, the perception of the target's movement speed is important for estimating when and where the target will arrive. However, it is unclear what sources of information are used by a batter to estimate ball speed and how those sources of information are integrated to facilitate successful interception. In this study, we examined the degree to which kinematic and ball-flight information are integrated when estimating ball speed in baseball batting. Thirteen university level baseball batters performed a ball-speed evaluation task in a virtual environment where they were required to determine which of two comparison baseball pitches (i.e., a reference and comparison stimuli) they perceived to be faster. The reference and comparison stimuli had the same physical ball speed, but with different pitching movement speeds in the comparison stimuli. The task was performed under slow (125 km/h) and fast (145 km/h) ball-speed conditions. Results revealed that the perceived ball-speed was influenced by the movement speed of the pitcher's motion, with the influence of the pitcher's motion more pronounced in the fast ball-speed condition when ball-flight information was presumably less reliable. Moreover, exploratory analyses suggested that the more skilled batters were increasingly likely to integrate the two sources of information according to their relative reliability when making judgements of ball speed. The results provide important insights into how skilled performers may make judgements of speed and time to contact, and further enhance our understanding of how the ability to make those judgements might improve when developing expertise in hitting

Rumen ciliate from wild Japanese sika deer culled in Ohdaigahara, Nara prefecture, Central Japan

Rumen ciliate protozoa composition was analysed on 13 wild Japanese sika deer (Cervus nippon) culled for deer density control during July and September 2013 in Ohdaigahara, Nara prefecture, central Japan. Six species belonging to only genus Entodeminium were detected, namely E. simplex, E. nanellum, E. convexum, E. abruptum, E. dubardi, E. parvum. In these species E. dubardi was dominant, E. simplex and E. nanellum followed, and these three species occupied more than 90% on ciliate protozoa number. Number of ciliate protozoa from fawns estimated 2-3 months old was statistically lesser than that of deer older than 1 year old