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Nipah virus receptor Nipah virus, first recognized in 1999, is an emerging disease that causes fatal encephalitis in humans. Its natural host is thought to be the fruit bat but it is also found in pigs and other animals. It could pose a serious threat to the pig-farming industry and there is recent evidence of human-to-human transmission. A crucial receptor that the virus relies on to infect human cells has now been identified, suggesting ways that the infection might be countered by vaccines or drugs. The virus's attachment protein binds to the ephrinB2 receptor. This receptor is critical for normal vascular developmental processes and is present in tissues targeted by Nipah virus. The enzyme EphB4 can block the entry of the virus into the cell. Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70 per cent of infected patients 1 , and there is evidence of human–to–human transmission 2 . Endothelial syncytia, comprised of multinucleated giant-endothelial cells, are frequently found in NiV infections, and are mediated by the fusion (F) and attachment (G) envelope glycoproteins. Identification of the receptor for this virus will shed light on the pathobiology of NiV infection, and spur the rational development of effective therapeutics. Here we report that ephrinB2, the membrane-bound ligand for the EphB class of receptor tyrosine kinases (RTKs) 3 , specifically binds to the attachment (G) glycoprotein of NiV. Soluble Fc-fusion proteins of ephrinB2, but not ephrinB1, effectively block NiV fusion and entry into permissive cell types. Moreover, transfection of ephrinB2 into non-permissive cells renders them permissive for NiV fusion and entry. EphrinB2 is expressed on endothelial cells and neurons 3 , 4 , which is consistent with the known cellular tropism for NiV 5 . Significantly, we find that NiV-envelope-mediated infection of microvascular endothelial cells and primary cortical rat neurons is inhibited by soluble ephrinB2, but not by the related ephrinB1 protein. Cumulatively, our data show that ephrinB2 is a functional receptor for NiV.

Forkhead box protein P3 (FOXP3) expression in tumor infiltrating CD4(+)T cells is generally associated with an intrinsic capacity to suppress tumor immunity. Based on this notion, different studies have evaluated the prognostic value of this maker in cancer but contradictory results have been found. Indeed, even within the same cancer population, the presence of CD4(+)FOXP3(+)T cells has been associated,with either a poor or a good prognosis, or no correlation has beenfound. Here, we demonstrate,in patients with oral squamous cell carcinoma (OSCC), that what really represents a prognostic parameter is not the overall expression of FOXP3 but its intracellular localization.While overallFOXP3 expression in tumor infiltrating CD4(+)T cells does not correlate with tumor recurrence, its intracellular localization within the CD4 cells does: nuclear FOXP3 (nFOXP3) is associated with tumor recurrence within 3 years, while cytoplasmicFOXP3 (cFOXP3) is associated with a lower likelihood of recurrence. Thus, we propose elevated levels of the cFOXP3/nFOXP3 ratio within tumor infiltrating CD4(+) T cells as a predictor of OSCC recurrence.

Forkhead box protein P3 (FOXP3) expression in tumor infiltrating CD4+T cells is generally associated with an intrinsic capacity to suppress tumor immunity. Based on this notion, different studies have evaluated the prognostic value of this maker in cancer but contradictory results have been found. Indeed, even within the same cancer population, the presence of CD4+FOXP3+T cells has been associated,with either a poor or a good prognosis, or no correlation has beenfound. Here, we demonstrate,in patients with oral squamous cell carcinoma (OSCC), that what really represents a prognostic parameter is not the overall expression of FOXP3 but its intracellular localization.While overallFOXP3 expression in tumor infiltrating CD4+T cells does not correlate with tumor recurrence, its intracellular localization within the CD4 cells does: nuclear FOXP3 (nFOXP3) is associated with tumor recurrence within 3 years, while cytoplasmicFOXP3 (cFOXP3) is associated with a lower likelihood of recurrence. Thus, we propose elevated levels of the cFOXP3/nFOXP3 ratio within tumor infiltrating CD4+ T cells as a predictor of OSCC recurrence.

Objectives We assessed the effect of furosemide administration on noise-induced hearing loss. This drug reversibly elevates the auditory threshold by inducing a temporary reduction of the endocochlear potential and thereby suppresses the cochlear amplifier and active cochlear mechanics. Methods Mice were given a single injection of furosemide 30 minutes before exposure to 113 dB sound pressure level broadband noise. Control animals received saline solution. Furosemide was administered in other mice after the noise exposure. Auditory threshold shifts were assessed by recording auditory nerve brain stem evoked response (ABR) thresholds to broadband clicks. Results The mean ABR threshold in the group injected with furosemide and exposed to temporary threshold shift (TTS)-producing noise was elevated by 20.4 ± 12.3 dB, and that in the saline control group was elevated by 35.4 ± 18.3 dB (p < 0.02). The mean threshold elevations in the group injected with furosemide and exposed to permanent threshold shift (PTS)-producing noise and in the PTS saline control group were 15.0 ± 10.3 dB and 27.0 ± 12.7 dB, respectively (p < 0.01). Similar results were obtained when the PTS was assessed with an 8-kHz tone burst ABR. There was no significant difference in the PTS between mice given a single injection of furosemide and those given saline solution after the noise; this finding shows that furosemide is not acting as an antioxidant. Conclusions It appears that reversible hearing threshold elevation as a result of furosemide administration before noise exposure can reduce the TTS and PTS. This finding provides insight into the mechanism of noise-induced hearing loss.