The hydrophilic bile salt ursodeoxycholic acid (UDCA) protects against the membrane-damaging effects associated with hydrophobic bile acids. This study was undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid (DCA), as well as from ethanol, TGF-␤1, Fas ligand, and okadaic acid; and to (b) determine whether mitochondrial membrane perturbation is modulated by UDCA. DCA induced significant hepatocyte apoptosis in vivo and in isolated hepatocytes determined by terminal transferase-mediated dUTP-digoxigenin nick end-labeling assay and nuclear staining, respectively (P Ͻ 0.001). Apoptosis in isolated rat hepatocytes increased 12-fold after incubation with 0.5% ethanol (P Ͻ 0.001). HuH-7 cells exhibited increased apoptosis with 1 nM TGF-␤1 (P Ͻ 0.001) or DCA at Ն 100 M (P Ͻ 0.001), as did Hep G2 cells after incubation with anti-Fas antibody (P Ͻ 0.001). Finally, incubation with okadaic acid induced significant apoptosis in HuH-7, Saos-2, Cos-7, and HeLa cells. Coadministration of UDCA with each of the apoptosis-inducing agents was associated with a 50-100% inhibition of apoptotic changes (P Ͻ 0.001) in all the cell types. Also, UDCA reduced the mitochondrial membrane permeability transition (MPT) in isolated mitochondria associated with both DCA and phenylarsine oxide by Ͼ 40 and 50%, respectively (P Ͻ 0.001). FACS ® analysis revealed that the apoptosis-inducing agents decreased the mitochondrial transmembrane potential and increased reactive oxygen species production (P Ͻ 0.05). Coadministration of UDCA was associated with significant prevention of mitochondrial membrane alterations in all cell types. The results suggest that UDCA plays a central role in modulating the apoptotic threshold in both hepatocytes and nonliver cells, and inhibition of MPT is at least one pathway by which UDCA protects against apoptosis.

The recent discovered antiferromagnetic topological insulators in Mn-Bi-Te family with intrinsic magnetic ordering have rapidly drawn broad interest since its cleaved surface state is believed to be gapped, hosting the unprecedented axion states with half-integer quantum Hall effect. Here, however, we show unambiguously by using high-resolution angle-resolved photoemission spectroscopy that a gapless Dirac cone at the (0001) surface of MnBi2Te4 exists between the bulk band gap. Such unexpected surface state remains unchanged across the bulk Né el temperature, and is even robust against severe surface degradation, indicating additional topological protection. Through symmetry analysis and ab-initio calculations we consider different types of surface reconstruction of the magnetic moments as possible origins giving rise to such linear dispersion. Our results reveal that the intrinsic magnetic topological insulator hosts a rich platform to realize various topological phases such

Human bocavirus (HBoV), a newly cloned human virus of the genus Bocavirus, was detected by PCR from nasopharyngeal swab samples (8 of 318; 5.7%) collected from children with lower respiratory tract infections. HBoV may be one of the causative agents of lower respiratory tract infections in young children.The family Parvoviridae contains two subfamilies: Parvovirinae, which infects vertebrates, and Densovirinae, which infects insects. The subfamily Parvovirinae consists of five genera: Parvovirus, Erythrovirus, Dependovirus, Amdovirus, and Bocavirus (12). Parvovirus B19, which belongs to the genus Erythrovirus, is a well-known human pathogen (3,12). A new human virus of the genus Bocavirus, provisionally named human bocavirus (HBoV), was recently cloned from pooled human respiratory tract samples and is considered to be pathogenic to humans (1). In this study, nasopharyngeal swab samples obtained from children with lower respiratory tract infections were investigated for the presence of HBoV.

The hydrophilic bile salt ursodeoxycholic acid (UDCA) is a potent inhibitor of apoptosis. In this paper, we further characterize the mechanism by which UDCA inhibits apoptosis induced by deoxycholic acid, okadaic acid and transforming growth factor b1 in primary rat hepatocytes. Our data indicate that coincubation of cells with UDCA and each of the apoptosis-inducing agents was associated with an approximately 80% inhibition of nuclear fragmentation (P50.001). Moreover, UDCA prevented mitochondrial release of cytochrome c into the cytoplasm by 70 ± 75% (P50.001), thereby, inhibiting subsequent activation of DEVD-specific caspases and cleavage of poly(ADP-ribose) polymerase. Each of the apoptosis-inducing agents decreased mitochondrial transmembrane potential and increased mitochondrial-associated Bax protein levels. Coincubation with UDCA was associated with significant inhibition of these mitochondrial membrane alterations. The results suggest that the mechanism by which UDCA inhibits apoptosis involves an interplay of events in which both depolarization and channel-forming activity of the mitochondrial membrane are inhibited.

A new human virus, provisionally named human bocavirus (HBoV), was discovered by Swedish researchers in 2005. A new immunofluorescence assay using Trichoplusia ni insect cells infected with a recombinant baculovirus expressing the VP1 protein of HBoV was developed, and the levels of immunoglobulin G antibody to the VP1 protein of HBoV in serum samples were measured. The overall seroprevalence rate of antibodies against the VP1 protein of HBoV in a Japanese population aged from 0 months to 41 years was 71.1% (145 of 204). The seropositive rate was lowest in the age group of 6 to 8 months and gradually increased with age. All of the children had been exposed to HBoV by the age of 6 years. A rise in titers of antibody against the VP1 protein of HBoV during the convalescent phase was observed for four patients with lower respiratory tract infections, and HBoV DNA was detected in nasopharyngeal swab and serum samples from all four patients. These results suggest that HBoV is a ubiquitous virus acquired early in life and that HBoV might play a role in the course of lower respiratory tract infections.