Poliovirus (PV) is easily transferred to humans orally; however, no rodent model for oral infections has been developed because of the alimentary tract's low sensitivity to the virus. Here we showed that PV is inactivated by the low pH of the gastric contents in mice. The addition of 3% NaHCO 3 to the viral inoculum increased the titer of virus reaching the small intestine through the stomach after intragastric inoculation of PV. Transgenic mice (Tg) carrying the human PV receptor (hPVR/CD155) gene and lacking the alpha/beta interferon receptor (IFNAR) gene (hPVR-Tg/IfnarKO) were sensitive to the oral administration of PV with 3% NaHCO 3 , whereas hPVR-Tg expressing IFNAR were much less sensitive. The virus was detected in the epithelia of the small intestine and proliferated in the alimentary tract of hPVR-Tg/IfnarKO. By the ninth day after the administration of a virulent PV, the mice had died. These results suggest that IFNAR plays an important role in determining permissivity in the alimentary tract as well as the generation of virus-specific immune responses to PV via the oral route. Thus, hPVR-Tg/IfnarKO are considered to be the first oral infection model for PV, although levels of anti-PV antibodies were not elevated dramatically in serum and intestinal secretions of surviving mice when hPVR-Tg/IfnarKO were administered an attenuated PV.Poliomyelitis is an acute disease of the central nervous system (CNS) caused by poliovirus (PV), a human enterovirus that belongs to the family Picornaviridae. In humans, an infection is initiated by oral ingestion of the virus, followed by multiplication in the alimentary mucosa (2, 38), from which the virus spreads through the bloodstream. Viremia is considered essential for leading to paralytic poliomyelitis in humans. By use of a PV-sensitive mouse model, previous studies (9, 44) demonstrated that after intravenous inoculation, circulating PV crosses the blood-brain barrier at a high rate, and a neural dissemination pathway from the skeletal muscle without injury is not the primary route by which the circulating virus disseminates to the CNS. Along with the blood-brain barrier pathway of dissemination, a neural pathway has been reported for humans (30), primates (11), and PV-sensitive transgenic mice (Tg) carrying the human PV receptor (hPVR/CD155) gene (31,34); this pathway appears to be important in causing provocation poliomyelitis (9).It has been proved that Tg carrying the hPVR gene (hPVRTg) are susceptible to all three PV serotypes, 1, 2, and 3 (22, 35), although mice without the hPVR gene are generally not susceptible to PV. This observation indicates that hPVR is the most important determinant of the host range of PV. After inoculation with PV by the intracerebral, intraspinal, intravenous, or intramuscular route (10,(20)(21)(22)(33)(34)(35), hPVR-Tg develop a flaccid paralysis in their limbs, which is clinically similar to human poliomyelitis. However, in contrast to its behavior in humans, PV does not replicate in the alimentary tracts of hPVR-Tg after oral a...

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Poliovirus (PV), when injected intramuscularly into the calf, is incorporated into the sciatic nerve and causes an initial paralysis of the inoculated limb in transgenic (Tg) mice carrying the human PV receptor (hPVR/ CD155) gene. We have previously demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerves of hPVR-Tg mice and that intramuscularly inoculated PV causes paralytic disease in an hPVR-dependent manner. Here we showed that hPVR-independent axonal transport of PV was observed in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Using primary motor neurons (MNs) isolated from these mice or rats, we demonstrated that the axonal transport of PV requires several kinetically different motor machineries and that fast transport relies on a system involving cytoplasmic dynein. Unexpectedly, the hPVR-independent axonal transport of PV was not observed in cultured MNs. Thus, PV transport machineries in cultured MNs and in vivo differ in their hPVR requirements. These results suggest that the axonal trafficking of PV is carried out by several distinct pathways and that MNs in culture and in the sciatic nerve in situ are intrinsically different in the uptake and axonal transport of PV.In humans, paralytic poliomyelitis results from the invasion of the central nervous system by circulating poliovirus (PV), probably via the blood-brain barrier. This conclusion is supported by the finding that circulating PV after intravenous inoculation in mice appears to cross the blood-brain barrier at a high rate in a human PV receptor (hPVR/CD155)-independent manner (44). After the virus enters the central nervous system, it replicates in neurons, especially in motor neurons (MNs), inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, a neuron-specific pathway has been reported in humans (31), monkeys (18), and PV-sensitive transgenic (Tg) mice carrying the hPVR gene (34,37). This neuron-specific pathway appears to be important in causing "provocation poliomyelitis," which is triggered by injuries after PV ingestion (11). Using differentiated PC12 cells and a PV-sensitive Tg mouse line, we have shown that intramuscularly inoculated PV is taken up by endocytosis at synapses.hPVR is a member of the immunoglobulin (Ig) superfamily, with three linked extracellular Ig-like domains, followed by a membrane-spanning domain and a cytoplasmic domain. Two membrane-bound forms (␣ and ␦) and two secreted forms (␤ and ␥) of hPVR derived by alternative splicing are likely to be expressed in human cells (23). Membrane-bound hPVRs are considered to play important roles in the early steps of infection, such as the binding of the virus to the cell surface, its entry into the cell, and the uncoating of the virus. The N-terminal Ig-like domain harbors the sites for PV binding, and antihPVR monoclonal antibodies (MAbs) directed against this region block PV infection (9,24,39).hPVR ...

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Flipper rubbing" behavior was quantitatively analyzed in wild Indo-Pacific bottlenose dolphins (Tursiops aduncus) around Mikura Island, Tokyo, Japan. We observed two types of flipper rubbing: (1) F-B rubbing; one dolphin (Rubber) rubbed its flipper over various parts of a partner's (Rubbee) body, and (2) F-F rubbing; both dolphins rubbed each other's anterior flipper edge in alternating shifts. F-B rubbings tended to be initiated by the Rubbee and were terminated by the Rubber. The Rubbee often moved actively its body part that was in contact with the Rubber's flipper, and assumed side-up, upside-down, or other postures while the Rubber remained horizontal in most cases. These facts suggest that the Rubbee engaged in F-B rubbing more actively than the Rubber, and might receive some benefit from the frictional contact during F-B rubbing. Dolphins often switched their roles as Rubber and Rubbee between episodes of flipper rubbing bout. Adults and subadults exchanged F-B rubbing and F-F rubbing most often with individuals of the same sex in the same age class. F-B rubbing was frequent in mother-and-calf dyads. Our results suggest that flipper rubbing is an affiliative behavior which could be a quantitative measure of social relationships among individuals of this species in future studies. 966 SAKAI ET AL.: FLIPPER RUBBING BEHAVIORS IN WILD BOTTLENOSE DOLPHINS 967

BackgroundAn n-6 essential fatty acid, arachidonic acid (ARA) is converted into prostaglandin E2, which is involved in tumour extension. However, it is unclear whether dietary ARA intake leads to cancer in humans. We thus systematically evaluated available observational studies on the relationship between ARA exposure and the risk of colorectal, skin, breast, prostate, lung, and stomach cancers.MethodsWe searched the PubMed database for articles published up to May 17, 2010. 126 potentially relevant articles from the initial search and 49,670 bibliographies were scrutinised to identify eligible publications by using predefined inclusion criteria. A comprehensive literature search yielded 52 eligible articles, and their reporting quality and methodological quality was assessed. Information on the strength of the association between ARA exposure and cancer risk, the dose-response relationship, and methodological limitations was collected and evaluated with respect to consistency and study design.ResultsFor colorectal, skin, breast, and prostate cancer, 17, 3, 18, and 16 studies, respectively, were identified. We could not obtain eligible reports for lung and stomach cancer. Studies used cohort (n = 4), nested case-control (n = 12), case-control (n = 26), and cross-sectional (n = 12) designs. The number of subjects (n = 15 - 88,795), ARA exposure assessment method (dietary intake or biomarker), cancer diagnosis and patient recruitment procedure (histological diagnosis, cancer registries, or self-reported information) varied among studies. The relationship between ARA exposure and colorectal cancer was inconsistent based on ARA exposure assessment methodology (dietary intake or biomarker). Conversely, there was no strong positive association or dose-response relationship for breast or prostate cancer. There were limited numbers of studies on skin cancer to draw any conclusions from the results.ConclusionsThe available epidemiologic evidence is weak because of the limited number of studies and their methodological limitations, but nonetheless, the results suggest that ARA exposure is not associated with increased breast and prostate cancer risk. Further evidence from well-designed observational studies is required to confirm or refute the association between ARA exposure and risk of cancer.

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Field recordings of echolocation signals produced by Heaviside's dolphins (Cephalorhynchus heavisidii) were made off the coast of South Africa using a hydrophone array system. The system consisted of three hydrophones and an A-tag (miniature stereo acoustic data-logger). The mean centroid frequency was 125 kHz, with a -3 dB bandwidth of 15 kHz and -10 dB duration of 74 μs. The mean back-calculated apparent source level was 173 dB re 1 μPa(p.-p.). These characteristics are very similar to those found in other Cephalorhynchus species, and such narrow-band high-frequency echolocation clicks appear to be a defining characteristic of the Cephalorhynchus genus. Click bursts with very short inter-click intervals (up to 2 ms) were also recorded, which produced the "cry" sound reported in other Cephalorhynchus species. Since inter-click intervals correlated positively to click duration and negatively to bandwidth, Heaviside's dolphins may adjust their click duration and bandwidth based on detection range. The bimodal distribution of the peak frequency and stable bimodal peaks in spectra of individual click suggest a slight asymmetry in the click production mechanism.