Update in the methodology of the chronic stress paradigm: internal control matters

To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals

Role of hormone cofactors in the human papillomavirus-induced carcinogenesis of the uterine cervix

peer reviewedIf human papillomavirus (HPV) is necessary for the development of (pre)neoplastic lesions of the uterine cervix, it is not sufficient. Among the cofactors involved in the malignant transformation of cells infected by HPV, sex hormones may facilitate the cervical carcinogenesis by different mechanisms, including the induction of squamous metaplasia in the transformation zone of the cervix, interactions between steroid hormones and HPV gene expression and alterations of the local immune microenvironment

Russian Arctic Vegetation Archive—A new database of plant community composition and environmental conditions

Motivation: The goal of the Russian Arctic Vegetation Archive (AVA-RU) is to unite and harmonize data of plot-based plant species and their abundance, vegetation structure and environmental variables from the Russian Arctic. This database can be used to assess the status of the Russian Arctic vegetation and as a baseline to document biodiversity changes in the future. The archive can be used for scientific studies as well as to inform nature protection and restoration efforts. Main types of variables contained: The archive contains 2873 open-access geobotanical plots. The data include the full species. Most plots include information on the horizontal (cover per species and morphological group) and vertical (average height per morphological group) structure of vegetation, site and soil descriptions and data quality estimations. In addition to the open-access data, the AVA-RU website contains 1912 restricted-access plots. Spatial location and grain: The plots of 1–100 m2 size were sampled in Arctic Russia and Scandinavia. Plots in Russia covered areas from the West to the East, including the European Russian Arctic (Kola Peninsula, Nenets Autonomous district), Western Siberia (Northern Urals, Yamal, Taza and Gydan peninsulas), Central Siberia (Taymyr peninsula, Bolshevik island), Eastern Siberia (Indigirka basin) and the Far East (Wrangel island). About 72% of the samples are georeferenced. Time period and grain: The data were collected once at each location between 1927 and 2022. Major taxa and level of measurement: Plots include observations of >1770 vascular plant and cryptogam species and subspecies. Software format: CSV files (1 file with species list and abundance, 1 file with environmental variables and vegetation structure) are stored at the AVA-RU website (https://avarus.space/), and are continuously updated with new datasets. The open-access data are available on Dryad and all the datasets have a backup on the server of the University of Zurich. The data processing R script is available on Dryad

Identification of endoplasmic reticulum stress response genes in homologous vs. heterologous asf infections in vitro

The endoplasmic reticulum (ER) is crucial for the production, processing and transport of proteins. Infection with pathogens activates Unfolded Protein Response (UPR), which can lead to their survival/replication or elimination from the body. Although little is known about the role of the ER stress response in the pathogenesis of viral infections, the regulation of ER stress may be important in intractable infectious diseases. We conducted a comparative analysis of the expression of genes involved in ER stress response in peripheral blood mononuclear cells (PBMCs) from animals immunized with an attenuated strain of ASFV strain Congo-a (KK262) and then stimulated in vitro by two serologically different virulent strains Congo-v (K49) or Mozambique-v (M78), to expand our understanding of the early determinants of response to homologous and heterologous infection. We found up-regulation of genes of all three sensory molecules (PERK, ATF6 and IRE1) of UPR pathway in cells infected with only a homologous strain. For the first time, a number of up-regulated genes of the ER-associated degradation pathway (ERAD), which destroys misfolded proteins, were also detected. By understanding how viruses modify elements of cellular response to stress, we learn more about the pathogenesis, as well as how we can use it to prevent viral diseases

Growth Kinetics and Protective Efficacy of Attenuated ASFV Strain Congo with Deletion of the EP402 Gene

African swine fever (ASF) is an emerging disease threat to the swine industry worldwide. There is no vaccine against ASF, and progress is hindered by a lack of knowledge concerning the extent of ASFV strain diversity and the viral antigens conferring type-specific protective immunity in pigs. We have previously demonstrated that homologous ASFV serotype-specific proteins CD2v (EP402R) and/or C-type lectin are required for protection against challenge with the virulent ASFV strain Congo (Genotype I, Serogroup 2), and we have identified T-cell epitopes on CD2v which may be associated with serotype-specific protection. Here, using a cell-culture adapted derivative of the ASFV strain Congo (Congo-a) with specific deletion of the EP402R gene (ΔCongoCD2v) in swine vaccination/challenge experiments, we demonstrated that deletion of the EP402R gene results in the failure of ΔCongoCD2v to induce protection against challenge with the virulent strain Congo (Congo-v). While ΔCongoCD2v growth kinetics in COS-1 cells and primary swine macrophage culture were almost identical to parental Congo-a, replication of ΔCongoCD2v in vivo was significantly reduced compared with parental Congo-a. Our data support the idea that the CD2v protein is important for the ability of homologous live-attenuated vaccines to induce protective immunity against the ASFV strain Congo challenge in vivo

Deletion of the CD2 Gene in the Virulent ASFV Congo Strain Affects Viremia in Domestic Swine, but Not the Virulence

African swine fever (ASF) is an infectious disease that causes the most significant losses to the pig industry. One of the effective methods for combating this disease could be the development of vaccines. To date, experimental vaccines based on the use of live attenuated strains of the ASF virus (ASFV) obtained by the deletion of viral genes responsible for virulence are the most effective. Deletion of the EP402R gene encoding a CD2-like protein led to the attenuation of various strains of the ASFV, although the degree of attenuation varies among different isolates. Here we have shown that the deletion of the EP402R gene from the genome of a high-virulent Congo isolate did not change either the virulence of the virus or its ability to replicate in the swine macrophage cell cultures in vitro. However, in vivo, animals infected with ΔCongo-v_CD2v had a delay in the onset of the disease and viremia compared to animals infected with the parental strain. Thus, deletion of the CD2 gene in different isolates of the ASFV has a different effect on the virulence of the virus, depending on its genetic background

Comparison of Attenuated and Virulent Strains of African Swine Fever Virus Genotype I and Serogroup 2

African swine fever (ASF) is a contagious disease of pigs caused by the ASF virus (ASFV). The main problem in the field of ASF control is the lack of vaccines. Attempts to obtain vaccines by attenuating the ASFV on cultured cell lines led to the production of attenuated viruses, some of which provided protection against infection with a homologous virus. Here we report on the biological and genomic features of the attenuated Congo-a (KK262) virus compared to its virulent homologue Congo-v (K49). Our results showed differences in in vivo replication and virulence of Congo-a. However, the attenuation of the K49 virus did not affect its ability to replicate in vitro in the primary culture of pig macrophages. Complete genome sequencing of the attenuated KK262 strain revealed an 8,8 kb deletion in the left variable region of the genome compared to the virulent homologue K49. This deletion concerned five genes of MGF360 and three genes of MGF505. In addition, three inserts in the B602L gene, genetic changes in intergenic regions and missense mutations in eight genes were detected. The data obtained contribute to a better understanding of ASFV attenuation and identification of potential virulence genes for further development of effective vaccines

Mutant ubiquitin (UBB+1) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)

AbstractMutant ubiquitin (UBB+1) accumulates in the hallmarks of tauopathies and polyglutamine diseases. We show that the deubiquitinating enzyme YUH1 of Saccharomyces cerevisiae and its mouse and human ortholog UCH-L3 are able to hydrolyze the C-terminal extension of UBB+1. This yields another dysfunctional ubiquitin molecule (UBG76Y) with biochemical properties similar to full length UBB+1. UBB+1 may be detected in post-mortem tissue due to impaired C-terminal truncation of UBB+1. Although the level of UCH-L3 protein in several neurodegenerative diseases is unchanged, we show that in vitro oxidation of recombinant UCH-L3 impairs its deubiquitinating activity. We postulate that impaired UCH-L3 function may contribute to the accumulation of full length UBB+1 in various pathologies