Two modes of microsatellite instability in human cancer: differential connection of defective DNA mismatch repair to dinucleotide repeat instability

Microsatellite instability (MSI) is associated with defective DNA mismatch repair in various human malignancies. Using a unique fluorescent technique, we have observed two distinct modes of dinucleotide microsatellite alterations in human colorectal cancer. Type A alterations are defined as length changes of ≤6 bp. Type B changes are more drastic and involve modifications of ≥8 bp. We show here that defective mismatch repair is necessary and sufficient for Type A changes. These changes were observed in cell lines and in tumours from mismatch repair gene-knockout mice. No Type B instability was seen in these cells or tumours. In a panel of human colorectal tumours, both Type A MSI and Type B instability were observed. Both types of MSI were associated with hMSH2 or hMLH1 mismatch repair gene alterations. Intriguingly, p53 mutations, which are generally regarded as uncommon in human tumours of the MSI⁺ phenotype, were frequently associated with Type A instability, whereas none was found in tumours with Type B instability, reflecting the prevailing viewpoint. Inspection of published data reveals that the microsatellite instability that has been observed in various malignancies, including those associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is predominantly Type B. Our findings indicate that Type B instability is not a simple reflection of a repair defect. We suggest that there are at least two qualitatively distinct modes of dinucleotide MSI in human colorectal cancer, and that different molecular mechanisms may underlie these modes of MSI. The relationship between MSI and defective mismatch repair may be more complex than hitherto suspected.     

Immunohistochemical Studies on the Transneuronal Spread of Virulent Herpes Simplex Virus Type 2 and Its US3 Protein Kinase-Deficient Mutant after Ocular Inoculation

The transneuronal spread of a virulent wild-type herpes simplex virus type 2 (HSV-2) and its US3 protein kinase-deficient (US3 PK^?) mutant was immunohistochemically studied in mice after inoculations into the cornea, anterior chamber, tongue, and masseter muscle. After corneal inoculation, the wild-type virus was demonstrated in various brain stem areas including the trigeminal tract and nucleus, the reticular formation, and cerebellar nucleus group. Viral antigen-positive neurons were strictly confined to the ipsilateral spinal trigeminal nucleus in mice corneally infected with the US3 PK^? mutant. No viral antigens were detected in the central nervous system (CNS) after inoculation with the mutant into the tongue and masseter muscle. However, when mice were immunosuppressed by treatment with cyclophosphamide, both the corneally infected mutant and wild-type virus could invade the CNS. The results suggest that the US3 PK^? mutant principally retains the capacity to spread in the CNS.     

Increase in Cellular Lysophosphatidylserine Content Exacerbates Inflammatory Responses in LPS-Activated Microglia

Neurochemical Research - Mutations in alpha/beta-hydrolase domain containing (ABHD) 12 gene, which encodes lysophosphatidylserine (LysoPS) lipase, cause the neurodegenerative disease PHARC...     

Three-dimensional analysis of horse and human gaits in therapeutic riding

Therapeutic horse riding or hippotherapy is used as an intervention for treating individuals with mental and physical disabilities. Equine-assisted interventions are based on the hypothesis that the movement of the horse's pelvis during horseback riding resembles human ambulation, and thus provides motor and sensory inputs similar to those received during human walking. However, this hypothesis has not been investigated quantitatively and qualitatively. This study aimed to verify the hypothesis by conducting a three-dimensional analysis of the horse's movements while walking and human ambulation. Using four sets of equipments, we analysed the acceleration patterns of walking in 50 healthy humans and 11 horses. In addition, we analysed the exercise intensity by comparing the heart rate, breathing rate, and blood pressure of 127 healthy individuals before and after walking and horse riding. The acceleration data series of the stride phase of horse walking were compared with those of human walking, and the frequencies (in Hz) were analysed by Fast Fourier transform.The acceleration curves of human walking overlapped with those of horse walking, with the frequency band of human walking corresponding with that of horse walking. Exercise intensity, as measured by the heart rate and breathing rate, was not significantly different between horse riding and human walking. The levels of diastolic blood pressure were slightly higher during horse riding than during walking, but were lower during both conditions compared with those in normal conditions (P < 0.01). The present study shows that, although not completely matched, the accelerations of the horse and human walking are comparable quantitatively and qualitatively. Horse riding at a walking gait could generate motor and sensory inputs similar to those produced by human walking, and thus could provide optimum benefits to persons with ambulatory difficulties.     

Reproductive ecology of three ocypodid crabs I. The influence of activity differences on reproductive traits

Reproductive traits of three ocypodid crabs,Scopimera globosa, Ilyoplax pusillus andMacrophthalmus japonicus, were compared.S. globosa andI. pusillus, inhabiting the upper-middle intertidal zone, produced 1–2 large broods per year, whereasM. japonicus, inhabiting the lower intertidal zone, produced 4–5 small broods per year. InS. globosa andI. pusillus, ovigerous females remained in their plugged burrows without feeding until their eggs hatched. On the other hand, femaleM. japonicus fed actively on surface mud while incubating. We concluded that few large broods may be advantageous in crab species that incubate in burrows, whereas continuous small broods may be advantageous in species that feed actively while incubating.     

A novel transesterification catalyzed by phosphotriesterase in an organic solvent

Summary Phosphotriesterase (PTE) from Flavobacterium sp. was utilized for transesterification of the organophosphate insecticide, Paraoxon, using 2-phenylethyl alcohol as a nucleophile and dimethly sulfoxide as an organic solvent forming the converted phosphotriester compound, diethyl 2-phenylethyl phosphate.