The 5′ Flanking Region and Intron1 of the Bovine Prion Protein Gene (PRNP) Are Responsible for Negative Feedback Regulation of the Prion Protein

Transcription factors regulate gene expression by controlling the transcription rate. Some genes can repress their own expression to prevent over production of the corresponding protein, although the mechanism and significance of this negative feedback regulation remains unclear. In the present study, we describe negative feedback regulation of the bovine prion protein (PrP) gene PRNP in Japanese Black cattle. The PrP-expressing plasmid pEF-boPrP and luciferase-expressing plasmids containing the partial promoter fragment of PRNP incorporating naturally occurring single-nucleotide or insertion/deletion polymorphisms were transfected into N2a cells. Transfection of pEF-boPrP induced PrP overexpression and decreased the promoter activity of PRNP in the wild-type haplotype (23-bp Del, 12-bp Del, and −47C). Reporter gene assays further demonstrated that the 12- and 23-bp Ins/Del polymorphisms, which are thought to be associated with Sp1 (Specific protein 1) and RP58 (Repressor Protein with a predicted molecular mass of 58 kDa), in intron1 and the upstream region, respectively, and an additional polymorphism (−47C→A) in the Sp1-binding site responded differently to PrP overexpression. With the −47C SNP, the presence of the Del in either the 23-bp Ins/Del or the 12-bp Ins/Del allele was essential for the negative feedback caused by PrP overexpression. Furthermore, deletion mutants derived from the wild-type haplotype showed that nucleotides −315 to +2526, which include the 5′-flanking region and exon1, were essential for the response. These results indicate that certain negative feedback response elements are located in these sequences, suggesting that regulation by transcription factors such as Sp1 and RP58 may contribute to the negative feedback mechanism of PRNP

Eosinophils express a functional receptor for interferon alpha: inhibitory role of interferon alpha on the release of mediators.

Recent reports describe the beneficial use of alpha interferon (IFNalpha) for the treatment of idiopathic hypereosinophilic syndrome (HES) unresponsive to conventional therapy. A clinical improvement associated with a rapid decrease of peripheral blood eosinophilia suggested possible direct effects of IFNalpha on eosinophils through the presence of IFNalpha receptors (IFNalphaR). Reverse transcriptase-polymerase chain reaction (RT-PCR) and cytochemistry were used respectively to detect the presence and define the distribution of IFNalphaR on enriched eosinophil preparations purified from blood cells. IFNalphaR was found on eosinophils collected from patients with various eosinophilic disorders. In addition, IFNalpha inhibited the release of eosinophil granule proteins such as eosinophil cationic protein (ECP), neurotoxin (EDN, or interleukin-5 (IL-5). Moreover, antiparasite cytotoxicity was also strongly reduced in a dose-dependent manner by IFNalpha. These results provide the first evidence that human eosinophils express a functional receptor for IFNalpha and represent a potential basis for the beneficial effects of IFNalpha in patients with hypereosinophilic syndromes.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Case study of a newly-developed genotype for dual-purpose rearing of male chicks

Session 62, Theatre 3International audienceThe culling of male layer chicks has been subject to widespread disapproval and led to its ban in Germany and France.One approach to divert from this practice is the use of dual-purpose genotypes (DPG) with a balanced performancein egg and meat production. Practitioners and stakeholders selected males of a DGP with a focus on laying (C) foron-farm evaluation under organic conditions in France and Germany. In Germany, the medium-growing JA757 (D)while in France the naked neck strain S757N (F) were reared as control groups. Data collection included mortality,feed consumption, live weight, welfare indicators, behaviour observations and carcass characteristics. In Germany,C cockerels were slaughtered at 16 while D at 13 weeks (wks) of age. In France there were two slaughter dates for Cand F: 13 and 15 wks of age. In Germany, the carcass weight of C was 1.8 kg and that of D 2.4 kg. Carcass weights(incl. necks) at 13 and 15 wks of age were 2.9 and 3.3 kg for F while C weighed 2.0 and 2.5 kg in France. The FCRof DPG C until wk 13 was 3.7 for both countries, and 2.6 for F and 2.7 for D. In Germany, D showed dirtier breastsand more footpad lesions than C; on behavioural aspects, D spent more time resting than C while C spent more timeforaging. DPGs could be an alternative to end the practice of chick culling, and thus fulfil the societal demand fora shift towards welfare-oriented production. A longer fattening period with higher FCR of DPG cockerels may beeconomically feasible if their meat is sold at higher price than that of usual genotypes. A perspective is to decipherwhether they could valorise side products of the food industry to decrease feeding cost. Furthermore, the productivityof the females should be considered for a complete economical analysis of DPG. This project received funding fromEU’s Horizon 2020 research & innovation program under grant agreement N°816172

A comparison of Sars-Cov-2 vaccine platforms: the CoviCompare project

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