Especially, the olfactory route, which could be a route

of entry into the CNS, has not been studied in detail. Although the multibasic cleavage site (MBCS) in the hemagglutinin (HA) of HPAI H5N1 viruses is a major determinant of systemic spread in poultry, the association between the MBCS and systemic spread in mammals is less clear. Here we determined the virus distribution of HPAI H5N1 virus in ferrets in time and space-including along the olfactory route-and the role of the MBCS in systemic replication. Intranasal inoculation with wild-type H5N1 virus revealed Selleckchem GW4869 extensive replication in the olfactory mucosa, from which it spread to the olfactory bulb and the rest of the CNS, including the cerebrospinal fluid (CSF). Virus spread to the heart, liver, pancreas, and colon was also detected, indicating hematogenous spread. Ferrets inoculated intranasally with H5N1 virus lacking an MBCS demonstrated respiratory tract infection only. In conclusion, HPAI H5N1 virus can spread systemically via two different routes, olfactory and hematogenous, in ferrets. This systemic spread was dependent on the presence of the MBCS in HA.”
“Background. Several lines of research suggest a disturbance of

reversal learning (reward and punishment processing, and affective switching) in patients with major depressive disorder (MDD). Obsessive-compulsive disorder (OCD) is also characterized by abnormal reversal learning, and is often co-morbid LXH254 cell line with MDD. However, neurobiological distinctions between the disorders are unclear. Functional neuroimaging (activation) studies comparing MDD and OCD directly are lacking.

Method. Twenty non-medicated OCD-free patients with MDD, 20 non-medicated MDD-free patients with OCD, and 27 healthy controls performed a self-paced reversal learning task in an event-related design during functional magnetic resonance imaging (fMRI).

Results.

Compared with healthy controls, both MDD and OCD patients displayed prolonged mean reaction times (RTs) but normal accuracy. In MDD subjects, mean RTs were correlated with disease severity. Imaging results showed MDD-specific hyperactivity in the anterior insula www.selleck.cn/products/torin-1.html during punishment processing and in the putamen during reward processing. Moreover, blood oxygen level-dependent (BOLD) responses in the dorsolateral prefrontal cortex (DLPFC) and the anterior PFC during affective switching showed a linear decrease across controls, MDD and OCD. Finally, the OCD group showed blunted responsiveness of the orbitofrontal (OFC)-striatal loop during reward, and in the OFC and anterior insula during affective switching.

Conclusions. This study shows frontal-striatal and (para)limbic functional abnormalities during reversal learning in MDD, in the context of generic psychomotor slowing.