Selective elimination of chromosomally unbalanced zygotes at the two-cell stage in the Chinese hamster

The gametic and zygotic selection of genome imbalance was investigated in the Chinese hamster by direct chromosome analyses of spermatocytes and preimplantation embryos from crosses between chromosomally normal females and males heterozygous for a reciprocal translocation, T(2;10)3Idr, abbreviated here as T3. The karyotypes and the frequencies of embryos observed at the first cleavage in the cross +/+female X T3/+male were consistent with those expected from MII scoring in male T3 heterozygotes. Therefore, it was concluded that there was neither gametic selection against genome imbalance nor zygotic selection from fertilization until the first cleavage metaphase. However, 9.1-10.8% of embryos were arrested at the two-cell stage, and karyotypes of these embryos were confirmed as 22(2,10,10,10(2)), 21(2,10,10), and 21(2,10,10(2)). The common abnormality of these embryos was partial monosomy of chromosome 2. Among day 4 embryos, some chromosomally unbalanced embryos, mainly with a deficiency of other segments of chromosomes 2 and 10, had fewer blastomeres than chromosomally balanced embryos. This finding suggests that cleavage of these embryos had been retarded by day 4 of gestation.     

Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features

Mutations in ZFHX1B, encoding Smad-interacting protein 1 (SIP1), have been recently reported to cause a form of Hirschsprung disease (HSCR). Patients with ZFHX1B deficiency typically show mental retardation, delayed motor development, epilepsy, microcephaly, distinct facial features, and/or congenital heart disease, in addition to the cardinal form of HSCR. To investigate the breadth of clinical variation, we studied DNA samples from six patients with clinical profiles quite similar to those described elsewhere for ZFHX1B deficiency, except that they did not have HSCR. The results showed the previously reported R695X mutation to be present in three cases, with three novel mutations-a 2-bp insertion (760insCA resulting in 254fs262X), a single-base deletion (270delG resulting in 91fs107X), and a 2-bp deletion (2178delTT resulting in 727fs754X)-newly identified in the other three. All mutations occurred in one allele and were de novo events. These results demonstrate that ZFHX1B deficiency is an autosomal dominant complex developmental disorder and that individuals with functional null mutations present with mental retardation, delayed motor development, epilepsy, and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels.     

Robertsonian metacentrics of the house musk shrew (Suncus murinus, Insectivora, Soricidae) lose the telomeric sequences in the centromeric area

The house musk shrew, Suncus murinus, is polymorphic for five Robertsonian translocations (Rb8.17, 9.13, 10.12, 11.16, 14.15). Fluorescence in situ hybridisation with a biotin-labelled oligonucleotide, (TTAGGG)7, was performed to localise the telomeric DNA sequences at Rb chromosomes of heterozygous shrews. Hybridisation signals were observed at both ends of all chromosomes, but not at the pericentromeric areas of any of the Robertsonian metacentrics. Our results indicate a complete loss of the telomeric sequences at the fusion points of the Rb metacentrics in S. murinus.     

Postural sway parameters using a triaxial accelerometer: comparing elderly and young healthy adults

The purpose of this study was to evaluate the sensitivity of 16 parameters derived from acceleration to detect changes caused by age and visual conditions during quiet standing and detect and minimise possible sources of unwanted variability that could affect accelerometer measures on the trunk. Twenty-seven healthy subjects, including 16 elderly (age, 69.3 ± 3.6 years) and 11 young (age, 23.6 ± 2.2 years) subjects, were evaluated. The parameters evaluated include root-mean-square values, fractal dimensions, path length, range, frequency dispersion and power spectrum among others derived from these values. These 16 parameters evaluated for each axis of movement and/or derivations resulted in 59 sub-parameters. These 59 sub-parameters were analysed in the elderly and young groups and under the open-eye and closed-eye conditions. The results showed that 30 sub-parameters detected differences for an age effect with open eyes, 18 detected differences with closed eyes, 25 detected differences for the young group standing with closed-open eyes and 37 detected differences for the elderly with closed and open eyes (p < 0.01). We used simple signal processing for the accelerometry signals to minimise the effects of unwanted variability that could affect the results. The results showed better performance compared with those results published previously using force platforms to evaluate postural sway. The results presented here should be useful for researchers who want to use accelerometry to evaluate steady postural balance.     

Protocadherin 2C: a new member of the protocadherin 2 subfamily expressed in a redundant manner with OL-protocadherin in the developing brain.

Using cDNA of human protocadherin 2A (pc2A; originally known as protocadherin 2) as a probe, we cloned a new member of the protocadherin 2 subfamily from mouse brain cDNA libraries and named it protocadherin 2C (pc2C). It was similar to pc2A throughout its entire coding region, and its C-terminal region was highly conserved. The locus of the pc2C gene was on the mouse chromosome 18C where the pc2A gene is located, suggesting that genes of the pc2 subfamily form a gene cluster. The expression of pc2C was restricted to the nervous system, and the expression started in the embryonic stage and increased up to the adult stage. The expression pattern was quite similar to that of OL-protocadherin, a distinct class of protocadherin, although the timing and relative strength of expression were different. These results suggest that pc2C may be involved in neural development along with other classes of protocadherins.     

Developing an instrument to support oral care in the elderly

Background: The dramatic increase in the number of dependent elderly in developed countries has created a great need for their improved oral care. However, optimal oral care by caregivers is not possible because of time constraints, difficulty involved in brushing other individuals' teeth, lack of co‐operation, and the lack of perceived need. Therefore, the development of an effective instrument simplifying and supporting oral care to relieve the strain on caregivers is a matter of some urgency. Purpose: In order to clean the mouths of elderly dependent patients, we have developed a new oral care support instrument (an electric toothbrush in combination with an antibacterial‐agent supply and suction system). The purpose of the present study was to develop and evaluate a new oral care support instrument. Methods: a) Plaque removal study: The plaque‐ removing ability of this new instrument in 70 outpatients was compared with the Plak Control D9011 (Braun Gillette Japan Inc.) as a control by means of the Turesky modification of the Quigley and Hein plaque index, b) Clinical study: The subjects were 10 dependent elderly who received oral care using the new oral care support instrument for two weeks. The plaque and gingival indices were used for clinical evaluations. Results: a) Plaque removal study: Brushing with the new oral care support instrument removed significantly more plaque than with the Plak Control D9011. b) Clinical study: The new oral care support instrument allows a more effective removal of dental plaque and shows a significant improvement in the gingival indices in dependent elderly. Conclusion: It is concluded that the new oral care support instrument is effective and can be recommended for oral care in the dependent elderly.     

Transmission of chromosomal abnormalities: participation of chromosomally unbalanced gametes in fertilization and early development of unbalanced embryos in the Chinese hamster

Using 14 Chinese hamster stocks with various reciprocal translocations, chromosomally unbalanced gametes were produced and used to investigate the participation of the unbalanced gametes in fertilization and the development of unbalanced embryos. The selection of chromosomally abnormal gametes during fertilization was investigated by the chromosomal analysis of meiotic cells in heterozygotes for the 14 reciprocal translocations and pronuclei of fertilized ova obtained from crossing these heterozygotes. Compared with the expected frequencies from meiotic metaphase II (MII) scoring, the frequencies of male pronuclei having commonly a deficiency of chromosome 1 (q14-->q42) or chromosome 3 (p23-->q31) in one-cell embryos decreased significantly. However, the frequencies of male pronuclei with other abnormalities were all consistent with those expected from MII scoring. In contrast, the frequencies of female pronuclei with any karyotype including the same ones, as those decreased in male pronuclei from the translocation heterozygotes were all consistent with those estimated from MII scoring. These results suggest that gametes with nullisomies as well as disomies for any chromosomal segments may mostly participate in fertilization, whereas some sperm nullisomic for the specific segments of chromosomes 1 and 3 may fail to fertilize. On the other hand, the zygotic selection of chromosomal imbalance was investigated by direct analyses of pre-implantation embryos from crosses between chromosomally normal females and male heterozygotes from the 14 stocks with various reciprocal translocations. The chromosomal and morphological analysis revealed that some embryos were arrested in development at the two-cell stage and their common abnormality was partial monosomy for chromosome 1 or 2. Embryos with partial monosomy including chromosomes 1, 3 and 4 showed arrested development at four-eight-cell stages. Among day 4 embryos, some chromosomally unbalanced embryos, mainly with a deficiency of other segments, such as chromosomes 1p, 2q, 5q and 8, had fewer blastomeres than karyotypically normal and balanced embryos. The homology between the mouse and the Chinese hamster chromosomes relating to the developmental abnormalities at early stages was partially confirmed.     

Genomic organization and chromosomal distribution of rat ID elements.

Identifier (ID) elements are members of a family of short interspersed nuclear elements (SINEs) in rodents. We investigated the genomic organization and chromosomal distribution of the ID elements in the rat, mouse and Chinese hamster. Southern blot hybridization analysis revealed that the ID elements are widespread in the rat genome, but concentrated in the mouse and Chinese hamster genomes, and that the copy of ID elements in the rat is about 5 times and 50 times that in the mouse and Chinese hamster, respectively. FISH analysis showed that the ID elements are predominantly distributed in the R-band regions of rat chromosomes. In mouse and Chinese hamster chromosomes, no specific distribution pattern of the ID elements was found. Furthermore, we found a distinct group of derivative ID elements in the rat, which contain partially repeated ID core domains, by PCR amplification using an ID core sequence. Such derivatives were not found in either the mouse or Chinese hamster. These findings suggest that explosive amplification of the ID elements in the rat has been accompanied by the occurrence of derivative ID elements and a predominant localization to the R-band regions. Similar associations found in the Alu family, one of the human SINEs, allow us to speculate that the rat ID elements and the human Alu family have analogous functions in chromosomal organization.