Measles virus infects both polarized epithelial and immune cells by using distinctive receptor-binding sites on its hemagglutinin

Measles is one of the most contagious human infectious diseases and remains a major cause of childhood morbidity and mortality worldwide. The signaling lymphocyte activation molecule (SLAM), also called CD150, is a cellular receptor for measles virus (MV), presumably accounting for its tropism for immune cells and its immunosuppressive properties. On the other hand, pathological studies have shown that MV also infects epithelial cells at a later stage of infection, although its mechanism has so far been unknown. In this study, we show that wild-type MV can infect and produce syncytia in human polarized epithelial cell lines independently of SLAM and CD46 (a receptor for the vaccine strains of MV). Progeny viral particles are released exclusively from the apical surface of these polarized epithelial cell lines. We have also identified amino acid residues on the MV attachment protein that are likely to interact with a putative receptor on epithelial cells. All of these residues have aromatic side chains and may form a receptor-binding pocket located in a different position from the putative SLAM- and CD46-binding sites on the MV attachment protein. Thus, our results indicate that MV has an intrinsic ability to infect both polarized epithelial and immune cells by using distinctive receptor-binding sites on the attachment protein corresponding to each of their respective receptors. The ability of MV to infect polarized epithelial cells and its exclusive release from the apical surface may facilitate its efficient transmission via aerosol droplets, resulting in its highly contagious nature.     

A highly efficient construction of GM1 epitope tetrasaccharide and its conjugation with KLH

GM1 epitope tetrasaccharide was synthesized by a condensation of sialyl-alpha(2-3)-gal acceptor and gal-beta(1-3)-GalN donor in a highly efficient manner. After introduction of mercaptohexanol to the tetrasaccharide, it was coupled to maleimide-activated KLH carrier protein to give the desired GM1 epitope-KLH conjugate.     

Design and synthesis of versatile ganglioside probes for carbohydrate microarrays

A series of ganglioside GM1-, GM2-, and GM3-type probes, in which the ceramide portion is replaced with a glucose residue, were systematically synthesized based on a convergent synthetic method.     

Detection and changes in levels of testosterone during spermatogenesis in the freshwater planarian Bdellocephala brunnea

It was reported recently that vertebrate-type steroids exist and control reproduction in several groups of invertebrates, including molluscs. Sexually reproductive freshwater planarians of the species Bdellocephala brunnea have a limited breeding season in their natural habitat. This phenomenon suggests that some endogenous reproductive hormones might play a role in vivo. However, to date, sex steroids such as androgen, estrogen, and progesterone have not been found in planarians. The goal of the present study was to determine whether androgen is present in sexual planarians such as B. brunnea. The presence of testosterone was detected by high-pressure liquid chromatography and, in sexually reproductive individuals in which no seminal vesicles were visible, the level of testosterone was about twice than that in individuals with visible seminal vesicles. An enzyme-linked immunosorbent assay revealed that the levels of testosterone during terminal spermatogenesis were three times higher than during the spermatocyte-building phase. Our results indicate that sexually reproductive freshwater planarians such as B. brunnea might have vertebrate-type steroids and show variation in testosterone levels during spermatogenesis.     

Phylogenetic position of the endemic large carpenter bee of the Ogasawara Islands, Xylocopa ogasawarensis (Matsumura, 1912) (Hymenoptera: Apidae), inferred from four genes

The Ogasawara (Bonin) Islands are oceanic islands of volcanic origin located in the northwestern Pacific Ocean about 1,000 km south of the Japanese mainland. A large carpenter bee, Xylocopa (Koptortosoma) ogasawarensis, is endemic to the islands but its closest relative is unknown. The Ogasawara Islands are geographically closest to the Japanese Archipelago, but this area is inhabited only by species of a different subgenus, Alloxylocopa. Thus, X. ogasawarensis is commonly thought to have originated from other members of Koptortosoma, which is widely distributed in the Oriental tropical region. In this study, we investigated the origin of X. ogasawarensis using a phylogenetic analysis of Xylocopa based on four genes: mitochondrial cytochrome oxidase subunit I (COI) and cytochrome b (Cyt b), and nuclear elongation factor-1alpha (EF-1alpha) and phosphoenolpyruvate carboxykinase (PEPCK). A combined analysis of the four genes strongly suggests that Koptortosoma is a large, polyphyletic group, within which Alloxylocopa is embedded. Xylocopa ogasawarensis emerged as the species most closely related to Alloxylocopa and not to Oriental species of Koptortosoma. Contrary to previous views of the origin of X. ogasawarensis, our results suggest that X. ogasawarensis and Alloxylocopa share a common origin and diverged after they colonized the island regions of East Asia.     

Human group III secreted phospholipase A2 promotes neuronal outgrowth and survival

Human sPLA2-III [group III secreted PLA2 (phospholipase A2)] is an atypical sPLA2 isoenzyme that consists of a central group III sPLA2 domain flanked by unique N- and C-terminal domains. In the present study, we found that sPLA2-III is expressed in neuronal cells, such as peripheral neuronal fibres, spinal DRG (dorsal root ganglia) neurons and cerebellar Purkinje cells. Adenoviral expression of sPLA2-III in PC12 cells (pheochromocytoma cells) or DRG explants facilitated neurite outgrowth, whereas expression of a catalytically inactive sPLA2-III mutant or use of sPLA2-III-directed siRNA (small interfering RNA) reduced NGF (nerve growth factor)-induced neuritogenesis. sPLA2-III also suppressed neuronal death induced by NGF deprivation. Lipid MS revealed that sPLA2-III overexpression increased the cellular level of lysophosphatidylcholine, a PLA2 reaction product with neuritogenic and neurotropic activities, whereas siRNA knockdown reduced the level of lysophosphatidylcholine. These observations suggest the potential contribution of sPLA2-III to neuronal differentiation and its function under certain conditions.     

Autotaxin, a synthetic enzyme of lysophosphatidic acid (LPA), mediates the induction of nerve-injured neuropathic pain

The extracellular signal-regulated kinase (ERK) cascade has been shown to be a key modulator of pain processing in the central nucleus of the amygdala (CeA) in mice. ERK is activated in the CeA during persistent inflammatory pain and this activation is both necessary and sufficient to induce peripheral tactile hypersensitivity. Interestingly, biochemical studies show that inflammation-induced ERK activation in the CeA only occurs in the right, but not the left hemisphere. This inflammation-induced ERK activation in the right CeA is independent of the side of peripheral inflammation, suggesting that there is a dominant role of the right hemisphere in the modulation of pain by ERK activation in the CeA. However, the functional significance of this biochemical lateralization has yet to be determined. In the present study, we tested the hypothesis that modulation of pain by ERK signaling in the CeA is functionally lateralized. We acutely blocked ERK activation in the CeA by infusing the MEK inhibitor U0126 into the right or the left hemisphere and then measured the behavioral effects on inflammation-induced mechanical hypersensitivity in mice. Our results show that blockade of ERK activation in the right, but not the left CeA, decreases inflammation-induced peripheral hypersensitivity independent of the side of peripheral injury. These findings demonstrate that modulation of pain by ERK signaling in the CeA is functionally lateralized to the right hemisphere, suggesting a dominant role of the right amygdala in pain processing.     

Correspondence between food consistency and suprahyoid muscle activity, tongue pressure, and bolus transit times during the oropharyngeal phase of swallowing.

This study aimed to evaluate the effects of food texture and viscosity on the swallowing function by measuring tongue pressure and performing a videofluorographic (VF) examination. Eleven normal adults were recruited for this study. Test foods with different consistencies and liquid contents, i.e., a half-solid nutrient made of 0.8 and 1.5% agar powder, syrup, and a liquid containing 40 wt/vol% barium sulfate, were swallowed, and the anterior (AT) and posterior tongue pressures (PT) and electromyographic (EMG) activity of the suprahyoid muscles were recorded, together with VF images. The timing of each event obtained from EMG, tongue pressure, and VF recordings was measured and then compared. We found that the AT and PT activity patterns were similar and showed a single peak. The peak, area, and time duration of all of the variables for AT and PT and EMG burst increased with increasing hardness of the bolus. The onset of the EMG burst always preceded those of the AT and PT activities, while there were no significant differences in peak and offset times among EMG burst, AT, and PT. Total swallowing time and oral ejection time were significantly longer during the swallowing of 1.5% agar than any other boluses, while pharyngeal transit time and clearance time were significantly longer during the swallowing of syrup, which was as hard as the liquid, but showed a higher viscosity than the liquid. The results suggested that the major effects of food hardness were to delay oral ejection time, which strongly delays total swallowing time. In addition, pharyngeal bolus transit is not dependent on the hardness of food but on its viscosity.     

Human T-cell leukemia virus type 1 HBZ protein bypasses the targeting function of ubiquitination

Human T-cell leukemia virus type 1 (HTLV-1) encodes an antisense viral gene product termed HTLV-1 basic leucine-zipper factor (HBZ). HBZ forms heterodimers with c-Jun, a member of the AP-1 family, and promotes its proteasomal degradation. Although most proteasomal substrates are targeted for degradation via conjugation of polyubiquitin chains, we show that ubiquitination is not required for HBZ-mediated proteasomal degradation of c-Jun. We demonstrate that HBZ directly interacts with both the 26 S proteasome and c-Jun and facilitates the delivery of c-Jun to the proteasome without ubiquitination. HBZ acts as a tethering factor between the 26 S proteasome and its substrate, thereby bypassing the targeting function of ubiquitination. These findings disclose a novel viral strategy to utilize the cellular proteolytic system for viral propagation.     

Porcine dentin sialophosphoprotein: length polymorphisms, glycosylation, phosphorylation, and stability

Dentin sialophosphoprotein (DSPP) is critical for proper mineralization of tooth dentin, and mutations in DSPP cause inherited dentin defects. Dentin phosphoprotein (DPP) is the C-terminal cleavage product of DSPP that binds collagen and induces intrafibrillar mineralization. We isolated DPP from individual pigs and determined that its N-terminal and C-terminal domains are glycosylated and that DPP averages 155 phosphates per molecule. Porcine DPP is unstable at low pH and high temperatures, and complexing with collagen improves its stability. Surprisingly, we observed DPP size variations on SDS-PAGE for DPP isolated from individual pigs. These variations are not caused by differences in proteolytic processing or degrees of phosphorylation or glycosylation, but rather to allelic variations in Dspp. Characterization of the DPP coding region identified 4 allelic variants. Among the 4 alleles, 27 sequence variations were identified, including 16 length polymorphisms ranging from 3 to 63 nucleotides. None of the length variations shifted the reading frame, and all localized to the highly redundant region of the DPP code. The 4 alleles encode DPP domains having 551, 575, 589, or 594 amino acids and completely explain the DPP size variations. DPP length variations are polymorphic and are not associated with dentin defects.