The Influence of Polyploidy and Genome Composition on Genomic Imprinting in Mice

Genomic imprinting is an epigenetic mechanism that switches the expression of imprinted genes involved in normal embryonic growth and development in a parent-of-origin-specific manner. Changes inDNAmethylation statuses from polyploidization are a well characterized epigenetic modification in plants. However, how changes in ploidy affect both imprinted gene expression and methylation status in mammals remains unclear. To address this, we used quantitative real time PCR to analyze expression levels of imprinted genes in mouse tetraploid fetuses. We used bisulfite sequencing to assess the methylation statuses of differentially methylated regions (DMRs) that regulate imprinted gene expression in triploid and tetraploid fetuses. The nine imprinted genes H19, Gtl2, Dlk1, Igf2r, Grb10, Zim1, Peg3, Ndn, and Ipw were all unregulated; in particular, the expression of Zim1 was more than 10-fold higher, and the expression of Ipw was repressed in tetraploid fetuses. The methylation statuses of four DMRs H19, intergenic (IG), Igf2r, and Snrpn in tetraploid and triploid fetuses were similar to those in diploid fetuses. We also performed allele-specific RT-PCR sequencing to determine the alleles expressing the three imprinted genes Igf2, Gtl2, and Dlk1 in tetraploid fetuses. These three imprinted genes showed monoallelic expression in a parent-of-origin-specific manner. Expression of non-imprinted genes regulating neural cell development significantly decreased in tetraploid fetuses, which might have been associated with unregulated imprinted gene expression. This study provides the first detailed analysis of genomic imprinting in tetraploid fetuses, suggesting that imprinted gene expression is disrupted, but DNA methylation statuses of DMRs are stable following changes in ploidy in mammals

Disclosure of congenital cleft lip and palate to Japanese patients : reported patient experiences and relationship to self-esteem

Background:The present study investigated when and how Japanese people with cleft lip and palate (CL/P) learn that their condition is congenital; the perceived effects of withholding the CL/P diagnosis on patients; and whether the resulting social experience and self-esteem are related. A questionnaire survey was conducted in 71 adults with CL/P recruited through a hospital, a patients’ association, and by snowball sampling.Results:The participants became aware of their physical difference in childhood, but many reported difficulty in understanding their condition. Participants reported that their families avoided the topic of diagnosis. Participants who understood their condition during childhood rather than in adulthood were significantly more likely to consider this scenario as positive (p < 0.001). Although stigmatising experiences were extremely painful, most patients hid their suffering, making it more difficult to obtain social support. Participants with high self-esteem were more likely to feel that they received adequate support.Conclusions:It is important to explain the congenital nature of CL/P sufficiently and early. In addition, openness by the family about the diagnosis, rather than avoidance, may improve patients’ self-esteem. Sufficient support from family, health care providers, and significant others is needed for patients to develop adequate self-esteem

Differentiation and seasonality in suitable microsites of seed dispersal by an assemblage of omnivorous mammals

acceptedVersio

Mapping of the local environmental changes in proteins by cysteine scanning

Protein conformational changes, which regulate the activity of proteins, are induced by the alternation of intramolecular interactions. Therefore, the detection of the local environmental changes around the key amino acid residues is essential to understand the activation mechanisms of functional proteins. Here we developed the methods to scan the local environmental changes using the vibrational band of cysteine S-H group. We validated the sensitivity of this method using bathorhodopsin, a photoproduct of rhodopsin trapped at liquid nitrogen temperature, which undergoes little conformational changes from the dark state as shown by the X-ray crystallography. The cysteine residues were individually introduced into 15 positions of Helix III, which contains several key amino acid residues for the light-induced conformational changes of rhodopsin. The shifts of S-H stretching modes of these cysteine residues and native cysteine residues upon the formation of bathorhodopsin were measured by Fourier transform infrared spectroscopy. While most of cysteine residues demonstrated no shift of S-H stretching mode, cysteine residues introduced at positions 117, 118, and 122, which are in the vicinity of the chromophore, demonstrated the significant changes. The current results are consistent with the crystal structure of bathorhodopsin, implying that the cysteine scanning is sensitive enough to detect the tiny conformational changes

Incidence and Risk Factors of Hypomagnesemia in Head and Neck Cancer Patients Treated with Cetuximab

Background Hypomagnesemia is a common adverse event during cetuximab (Cmab) treatment. However, few reports have investigated the incidence and risk factors of hypomagnesemia in head and neck cancer patients treated with Cmab. Methods We retrospectively reviewed 131 head and neck cancer patients who received Cmab-containing therapy. Main eligibility criteria were ≥3 Cmab administrations, no prior EGFR-directed therapy, and no prophylactic Mg supplementation.Results Median baseline serum Mg level and number of Cmab administrations were 2.2 mg/dl and eight, respectively. Overall incidence of hypomagnesemia was 50.4% (grade 1, 46.6%; grade 2, 3.1%; grade 3, 0%; grade 4, 0.8%) and differed between patients treated with palliative chemotherapy and bioradiation (Cmab and radiation) (63% vs. 24%; p<0.01). Independent risk factors were low baseline serum Mg [Odds ratio (OR) 161.988, 95% confidence interval (CI) 9.436-2780.895], ≥7 Cmab administrations (OR 3.56, 95% CI 1.16-13.98), and concurrent administration of platinum (cisplatin; OR 23.695, 95% CI 5.219-107.574, carboplatin; OR 5.487, 95% CI 1.831-16.439). Respective incidence of hypomagnesemia in patients in high- (concurrent platinum and ≥7 Cmab administrations) and low-risk (no concurrent platinum and <7 Cmab administrations) groups was 66.0% and 6.6% (P<0.001, OR 28.0). Conclusion Cmab is associated with a significant risk of hypomagnesemia in patients with head and neck cancer with longer term administration and concurrent platinum therapy. High-risk patients should be treated with particular care

歯槽骨内における局所麻酔薬の注射位置の差異は麻酔薬の浸潤と作用に影響する

付着歯肉や歯槽粘膜に麻酔薬を注入した際の顎骨への麻酔作用を、ウサギを用いた実験で評価した。30羽の日本白色ウサギを5%セボフルランで全身麻酔して、動脈圧モニタリングのための大腿動脈カニューレ挿入と気管切開術を行い3%セボフルランで維持した。上顎第三大臼歯頬域の右側付着歯肉と左側歯槽粘膜に0.5mLの局所麻酔薬(1/80000アドレナリンを含む2%リドカイン)を注入し、5～30分後に両側歯槽骨を除去すると共に、動脈圧を測定した。局所麻酔薬注入から30分後における平均動脈圧の変化は付着歯肉で14.0mmHg、歯槽粘膜で40.0mmHgであり、その時点での歯槽骨内のHPLCで計測したリドカイン濃度は付着歯肉で131.8μg/g、歯槽粘膜で11.4μg/gであった。また浸潤性麻酔薬の平均注入圧は付着歯肉で450.4mmHg、歯槽粘膜で80.1mmHgであった。動脈圧の大きな変化は低いリドカイン骨内濃度と相関しており、付着歯肉への浸潤性麻酔薬注入は、たとえ注入圧力の観点から困難であっても、顎骨内のリドカインレベルが直ちに上昇して強い鎮痛作用が得られることが分かった

A Study on ""Evaluation"" in British Higher Education : An Argument over Grants to The Hartley Institutions, Southampton in 1889-1911

The aim of this article is to examine ""university evaluation"" in the United Kingdom (especially England), focusing on an argument over grants to The Hartley Institution, Southampton in prehistory of University Grants Committee (1889-1911). The following three are pointed out as conclusions. Firstly, a character of the grants had changed from ""supplement and encouragement of local effort"" into ""support for University work"". Secondly, as an argument was made, concrete content of ""education of a University standard"" was gradually defined. In other words, advisory committees concluded that ""education of a University standard"" should contain ""Arts and Science"". Thirdly, advisory committees regarded ""quality"" as important and did a certain kind of ""quality assurance"". British higher education had maintained a standard by doing two phases of ""pre-evaluation"", UGC and Royal Charter

Difficulties and Coping Strategies Experienced by Employed People with HIV in Japan: A Qualitative Study Comparing High and Low Sense of Coherence Groups

People with HIV experience anxiety about discrimination in the workplace and disclosing their disease. Effective coping ability toward HIV-related challenges may be associated with a person’s sense of coherence (SOC). This study describes the range of difficulties HIV-positive individuals experience and their coping strategies, especially in the workplace. The experiences of those with high and low SOC are compared. Data were collected in Japan from 2007 to 2009 using a qualitative approach. Semistructured interviews were conducted with 40 participants with HIV with work experience. Interviews focused on individual’s perspectives, including self-perceptions of physical and mental functioning, work conditions, and perceived changes in their circumstances. Participants were divided into high and low SOC groups based on SOC-13 scores. A number of categories and subcategories of experiences were extracted, including “acute feeling of the severe social positioning of HIV,” with some categories specific to those with low SOC. Those with high SOC appeared to have a unique perspective that supported more successful coping, for example, “Awareness of death is linked to valuing living in the present,” “Do not be discouraged by uncertainties and difficulties,” and so on. It suggests that development of coping skills may help people with HIV