Investigation of the Role of TNF-α Converting Enzyme (TACE) in the Inhibition of Cell Surface and Soluble TNF-α Production by Acute Ethanol Exposure

Toll-like receptors (TLRs) play a fundamental role in the immune system by detecting pathogen associated molecular patterns (PAMPs) to sense host infection. Ethanol at doses relevant for humans inhibits the pathogen induced cytokine response mediated through TLRs. The current study was designed to investigate the mechanisms of this effect by determining whether ethanol inhibits TLR3 and TLR4 mediated TNF-α secretion through inhibition of transcription factor activation or post-transcriptional effects. In NF-κB reporter mice, activation of NF-κB in vivo by LPS was inhibited by ethanol (LPS alone yielded 170,000±35,300 arbitrary units of light emission; LPS plus ethanol yielded 56,120±16880, p = 0.04). Inhibition of protein synthesis by cycloheximide revealed that poly I:C- or LPS-induced secreted TNF-α is synthesized de novo, not released from cellular stores. Using real time RT-PCR, we found inhibition of LPS and poly I:C induced TNF-α gene transcription by ethanol. Using an inhibitor of tumor necrosis factor alpha converting enzyme (TACE), we found that shedding caused by TACE is a prerequisite for TNF-α release after pathogen challenge. Flow cytometry was used to investigate if ethanol decreases TNF-α secretion by inhibition of TACE. In cells treated with LPS, ethanol decreased both TNF-α cell surface expression and secretion. For example, 4.69±0.60% of untreated cells were positive for cell surface TNF-α, LPS increased this to 25.18±0.85%, which was inhibited by ethanol (86.8 mM) to 14.29±0.39% and increased by a TACE inhibitor to 57.88±0.62%. In contrast, cells treated with poly I:C had decreased secretion of TNF-α but not cell surface expression. There was some evidence for inhibition of TACE by ethanol in the case of LPS, but decreased TNF-α gene expression seems to be the major mechanism of ethanol action in this system

The reproductive capacity of Monk Parakeets Myiopsitta monachus is higher in their invasive range

Breeding parameters for Monk Parakeets Myiopsitta monachus nesting in Barcelona, Spain, were collected for 651 nests over five breeding seasons. This invasive population has a high reproductive capacity compared with the species in the native range: fledging success was double, the percentage of pairs attempting second broods three times higher and 55% of first-year birds bred compared with almost zero in South America

Dichotomy of Tyrosine Hydroxylase and Dopamine Regulation between Somatodendritic and Terminal Field Areas of Nigrostriatal and Mesoaccumbens Pathways

Measures of dopamine-regulating proteins in somatodendritic regions are often used only as static indicators of neuron viability, overlooking the possible impact of somatodendritic dopamine (DA) signaling on behavior and the potential autonomy of DA regulation between somatodendritic and terminal field compartments. DA reuptake capacity is less in somatodendritic regions, possibly placing a greater burden on de novo DA biosynthesis within this compartment to maintain DA signaling. Therefore, regulation of tyrosine hydroxylase (TH) activity may be particularly critical for somatodendritic DA signaling. Phosphorylation of TH at ser31 or ser40 can increase activity, but their impact on L-DOPA biosynthesis in vivo is unknown. Thus, determining their relationship with L-DOPA tissue content could reveal a mechanism by which DA signaling is normally maintained. In Brown-Norway Fischer 344 F1 hybrid rats, we quantified TH phosphorylation versus L-DOPA accumulation. After inhibition of aromatic acid decarboxylase, L-DOPA tissue content per recovered TH protein was greatest in NAc, matched by differences in ser31, but not ser40, phosphorylation. The L-DOPA per catecholamine and DA turnover ratios were significantly greater in SN and VTA, suggesting greater reliance on de novo DA biosynthesis therein. These compartmental differences reflected an overall autonomy of DA regulation, as seen by decreased DA content in SN and VTA, but not in striatum or NAc, following short-term DA biosynthesis inhibition from local infusion of the TH inhibitor α-methyl-p-tyrosine, as well as in the long-term process of aging. Such data suggest ser31 phosphorylation plays a significant role in regulating TH activity in vivo, particularly in somatodendritic regions, which may have a greater reliance on de novo DA biosynthesis. Thus, to the extent that somatodendritic DA release affects behavior, TH regulation in the midbrain may be critical for DA bioavailability to influence behavior

Multiple hypotheses explain variation in extra-pair paternity at different levels in a single bird family

Extra‐pair paternity (EPP), where offspring are sired by a male other than the social male, varies enormously both within and among species. Trying to explain this variation has proved difficult because the majority of the interspecific variation is phylogenetically based. Ideally, variation in EPP should be investigated in closely related species, but clades with sufficient variation are rare. We present a comprehensive multifactorial test to explain variation in EPP among individuals in 20 populations of nine species over 89 years from a single bird family (Maluridae). Females had higher EPP in the presence of more helpers, more neighbours or if paired incestuously. Furthermore, higher EPP occurred in years with many incestuous pairs, populations with many helpers and species with high male density or in which males provide less care. Altogether, these variables accounted for 48% of the total and 89% of the interspecific and interpopulation variation in EPP. These findings indicate why consistent patterns in EPP have been so challenging to detect and suggest that a single predictor is unlikely to account for the enormous variation in EPP across levels of analysis. Nevertheless, it also shows that existing hypotheses can explain the variation in EPP well and that the density of males in particular is a good predictor to explain variation in EPP among species when a large part of the confounding effect of phylogeny is excluded

Bearded Reedlings Adjust Their Pair-Bond Behaviour in Relation to the Sex and Attractiveness of Unpaired Conspecifics

An individual's investment in mating or keeping a pair bond intact may be influenced not only by the attractiveness of its current mate, but also by that of other potential mates. In this study, we investigated the effect of relative attractiveness on pair-bond behaviour in bearded reedlings, Panurus biarmicus. We showed that mate attractiveness, in terms of beard length in males and tail length in females, influenced courtship behaviour when the pair was kept isolated. In the presence of a conspecific, contact initiations within a pair increased. This increment was mainly related to the sex of the unpaired conspecific, however, and less to differences in attractiveness between the current partner and the unpaired conspecific. Female contact initiations towards potential extra mates were independent of male attractiveness, whereas male contact behaviour was significantly influenced by female attractiveness. However, females displayed more contact initiations to their current mate when they were less attractive than the unpaired females. Males decreased their overtures towards other females with increasing attractiveness of their current mates. Overall, our results suggested that, when there was a risk of losing their mate, bearded reedlings adjust their pair-bond investment mainly in response to the presence or absence of a competitor, and fine-tune investment to a lesser extent in response to the attractiveness of that potential competitor