Failure of homologous synapsis and sex-specific reproduction problems

The prophase of meiosis I ensures the correct segregation of chromosomes to each daughter cell. This includes the pairing, synapsis, and recombination of homologous chromosomes. A subset of chromosomal abnormalities, including translocation and inversion, disturbs these processes, resulting in the failure to complete synapsis. This activates the meiotic pachytene checkpoint, and the gametes are fated to undergo cell cycle arrest and subsequent apoptosis. Spermatogenic cells appear to be more vulnerable to the pachytene checkpoint, and male carriers of chromosomal abnormalities are more susceptible to infertility. In contrast, oocytes tend to bypass the checkpoint and instead generate other problems, such as chromosome imbalance that often leads to recurrent pregnancy loss in female carriers. Recent advances in genetic manipulation technologies have increased our knowledge about the pachytene checkpoint and surveillance systems that detect chromosomal synapsis. This review focuses on the consequences of synapsis failure in humans and provides an overview of the mechanisms involved. We also discuss the sexual dimorphism of the involved pathways that leads to the differences in reproductive outcomes between males and females

Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats

There is an emerging consensus that secondary structures of DNA have the potential for genomic instability. Palindromic AT-rich repeats (PATRRs) are a characteristic sequence identified at each breakpoint of the recurrent constitutional t(11;22) and t(17;22) translocations in humans, named PATRR22 (∼600 bp), PATRR11 (∼450 bp) and PATRR17 (∼190 bp). The secondary structure-forming propensity in vitro and the instability in vivo have been experimentally evaluated for various PATRRs that differ regarding their size and symmetry. At physiological ionic strength, a cruciform structure is most frequently observed for the symmetric PATRR22, less often for the symmetric PATRR11, but not for the other PATRRs. In wild-type E. coli, only these two PATRRs undergo extensive instability, consistent with the relatively high incidence of the t(11;22) in humans. The resultant deletions are putatively mediated by central cleavage by the structure-specific endonuclease SbcCD, indicating the possibility of a cruciform conformation in vivo. Insertion of a short spacer at the centre of the PATRR22 greatly reduces both its cruciform extrusion in vitro and instability in vivo. Taken together, cruciform extrusion propensity depends on the length and central symmetry of the PATRR, and is likely to determine the instability that leads to recurrent translocations in humans

Experimental observations on the optimal layout of orientation blocks for safe road crossing by the visually impaired

For people with visual impairments who face difficulties when crossing the road, in urban areas of Japan the infrastructure designed to provide an indication of crossing direction and the curbstones at sidewalk-roadway boundaries often varies in reliability from one crossing to another. If anything, this promotes stress for users and is an issue for which improvement is urgently needed. The authors have proposed new orientation blocks to be installed at crosswalk entrances as a means of more accurately indicating to people with visual impairments the trajectory to follow when crossing the road, and in prior research have derived desirable specifications for the profile of these blocks and their position relative to tactile walking surface indicators (TWSI). For this paper, in order to examine in greater detail the desirable position of orientation blocks relative to TWSI, the authors conducted an experiment using totally blind subjects to evaluate conditions on a 10 m walk that simulated an actual crossing. The results, based on observations of the trajectories walked by participants in the experiment and interviews eliciting their subjective evaluations, showed that separating orientation blocks and blister tactile blocks by about 8–12 cm is effective in constraining lateral deviation at a point 5 m from the start of crossing and that an 8 cm separation was desirable in order to maintain an effective reduction of mental stress while crossing