Erretrobirus endogenoak: birusen aztarnak gure genometan

Erretrobirus endogenoak hainbat animalien genometan agertzen diren elementu genomikoak dira. Euren jatorria birikoa da eta, behin ostalariaren genoman txertatu direla, belaunaldiz belaunaldi transmititzen dira. DNA zaborra bezala sailkatzen badira ere, elementu hauek ostalariarekin elkarrekintzan egon daitezkela ikusi da. Artikulu honetan elementu genomiko hauei buruz ezagutzen diren punturik garrantzitsuenak birpasatuko ditugu

Novel CircRNA Discovery in Sheep Shows Evidence of High Backsplice Junction Conservation

Circular RNAs (circRNAs) are covalently closed circular non-coding RNAs. Due to their structure, circRNAs are more stable and have longer half-lives than linear RNAs making them good candidates for disease biomarkers. Despite the scientific relevance of these molecules, the study of circRNAs in non-model organisms is still in its infancy. Here, we analyse total RNA-seq data to identify circRNAs in sheep from peripheral blood mononuclear cells (PBMCs) and parietal lobe cortex. Out of 2510 and 3403 circRNAs detected in parietal lobe cortex and in PBMCs, a total of 1379 novel circRNAs were discovered. Remarkably, around 63% of all detected circRNAs were found to be completely homologous to a circRNA annotated in human. Functional enrichment analysis was conducted for both tissues based on GO terms and KEGG pathways. The enriched terms suggest an important role of circRNAs from encephalon in synaptic functions and the involvement of circRNAs from PBMCs in basic immune system functions. In addition to this, we investigated the role of circRNAs in repetitive vaccination experiments via differential expression analysis and did not detect any significant relationship. At last, our results support both the miRNA sponge and the miRNA shuttle functions of CDR1-AS in sheep brain. To our knowledge, this is the first study on circRNA annotation in sheep PBMCs or parietal lobe cortex samples.This work was supported by a Spanish Ministry of Economy grant AGL2013-49137-C3 to BMJ; EV-M is a predoctoral fellow from the University of the Basque Country (UPV/EHU) [PIF15/361] and received a grant for a short-term scientific mission (STSM) from the Functional Annotation of Animal Genomes—European network (FAANG-Europe) [COST Action CA15112

Aluminiodun txerto-laguntzaileen eraginaren azterketa sistemen biologiaren bidez

Hamarkadak dira aluminio konposatuak txertoen laguntzaile gisa erabiltzen direla albaitaritzan eta giza txertoetan. Laguntzaile horien erabilera oso hedatua egon arren, ez da ongi ezagutzen zein mekanismoren bidez eragiten dituzten ondorio onuragarriak eta, aldizka, kontrako erreakzioak eragin ditzakete. Sistemen biologiako tekniken bidez laguntzaile hauen sinadura molekularra ikertu da, gizakietan zein etxabereetan. Hainbat eragin-mekanismo proposatu dira aluminioaren sistema immunea pizteko ahalmena azaltzeko eta analisi transkriptomikoetan erlazionatutako geneak aurkitu dira. Batzuetan emaitzak kontraesanezkoak dira, aktibatzen den erantzun immunea desberdina izan daitekeelako egoeraren arabera. Aluminiogatzen tamainak, formak, propietate fisiko-kimikoek eta antigenoen absortzioak eragina dutela ematen du era berean. Laguntzaile hauek ez dira antigeno-garraiatzaile soilak, sistema immunea kitzikatzen duten arriskuseinale endogenoak pizten baitituzte. Argitzeke dago oraindik haien eragin-mekanismo zehatza eta epe luzeko aktibazio immunitarioak sistema immunitarioaren gainestimulazioa eragin dezakeen.; Aluminium compounds have been used as adjuvants for years in veterinary and human vaccines, but, despite their widespread use, the mechanism of how aluminium-based adjuvants exert their beneficial effects is still not fully understood and they occasionally can cause adverse reactions. The molecular signature of these adjuvants has been studied by system biology techniques in human and livestock. Transcriptomic analyses have found dysregulated genes linked to some of the proposed mechanisms of action of aluminium. Sometimes the results are contradictory because the immune reaction that is activated may be different depending on the situation. The shape, size, physicochemical properties or antigen absorption of aluminium salts can also have an effect. It seems that aluminium-containing adjuvants are not simple delivery vehicles for antigens, but also induce endogenous danger signals that stimulate the immune system. Whether this contributes to long-lasting immune activation or to the overstimulation of the immune system remains to be elucidated

Whole Transcriptome Approach to Evaluate the Effect of Aluminium Hydroxide in Ovine Encephalon

Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences.This work was supported by the Spanish Ministry of Economy grant [MINECO project AGL2013-49137-C3 to BMJ, LL and DA]; University of the Basque Country (UPV/EHU) predoctoral fellowships [PIF15/361 to EV-M and PIF17/306 to MB-A]; and University of the Basque Country (UPV/EHU) postdoctoral fellowship [ESPDOC16/43 to NA]. Thanks to M. Ortega for technical help

Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing

There have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatment with either commercial vaccines containing aluminum hydroxide or an equivalent dose of this compound only with the aim of identifying the activated molecular signature. Blood samples were taken from each animal at the beginning and at the end of the experiment and PBMCs isolated. Total RNA and miRNA libraries were prepared and sequenced. After alignment to the Oar3.1 reference genome and differential expression with 3 programs, gene enrichment modeling was performed. For miRNAs, miRBase and RNAcentral databases were used for detection and characterization. Three expression comparisons were made: vaccinated animals at the beginning and at the end of the treatment, adjuvanted animals at the same times, and animals of both treatments at the end of the experiment. After exposure to both treatments, a total of 2,473; 2,980 and 429 differentially expressed genes were identified in vaccinated animals, adjuvanted animals and animals at the end of both treatments, respectively. In both adjuvant and vaccine treated animals the NF-kappa B signaling pathway was enriched. On the other hand, it can be observed a downregulation of cytokines and cytokine receptors in the adjuvanted group compared to the vaccinated group at the final time, suggesting a milder induction of the immune response when the adjuvant is alone. As for the miRNA analysis, 95 miRNAs were detected: 64 previously annotated in Ovis aries, 11 annotated in Bos taurus and 20 newly described. Interestingly, 6 miRNAs were differentially expressed in adjuvant treated animals, and 3 and 1 in the other two comparisons. Lastly, an integrated miRNA-mRNA expression profile was developed, in which a miRNA-mediated regulation of genes related to DNA damage stimulus was observed. In brief, it seems that aluminum-containing adjuvants are not simple delivery vehicles for antigens, but also induce endogenous danger signals that can stimulate the immune system. Whether this contributes to long-lasting immune activation or to the overstimulation of the immune system remains to be elucidated.This work was supported by a MINECO project grant (AGL2013-49137-C3-3-R to BJ and AGL2013-49137-C3-2-R to LL and AGL2013-49137-C3-1 to DdA), a predoctoral fellowship from the UPV/EHU to EV-M (PIF15/361) and a postdoctoral fellowship from the UPV/EHU to NA (ESPDOC16/43)

Jarduera fisikoaren, obesitatearen eta ezaugarri soziodemografikoen arteko erlazioa unibertsitateko langileetan

Lan-ingurunean bizimodu osasungarriak sustatzea funtsezkoa da langileen osasuna eta autonomia ahalik eta ondoen mantentzeko. Gero eta interes handiagoa dago gehiegizko pisuaren, obesitatearen eta ohitura osasungarrien arteko erlazioa aztertzeko, bai eta jarduera fisikoa edo loaren iraupena eta kalitatea, lanaldiarekiko elkarreraginetan aztertzeko ere. Hala ere, ikerketa gutxik aztertu dituzte elkarreragin horiek unibertsitateko langileen artean. Helburua: Gainpisuaren prebalentzia tasa eta Jarduera Fisikoaren Nazioarteko Gomendioen betetze-maila estimatzea, eta, aldi berean, parametro horien eta faktore soziodemografikoen arteko loturak aztertzea izan dira helburuak. Metodoak: Unibertsitateko 292 langileren datuak bildu ziren, lan-osasuneko azterketan. Aldagai prediktibo eta emaitza bakoitzaren arteko erlazioak aztertzeko khi karratuaren edo Fisher-en proba zehatzak erabili ziren eta hari lotutako ezaugarrien ebaluaziorako aldagai anitzeko ereduak. Emaitzak: gehiegizko pisuaren prebalentzia % 42koa izan zen. Sexuka, 35 eta 54 urte bitarteko gizonek eta ≥ 55 urteko emakumeek II. mailako gehiegizko pisua edo obesitatea izateko arrisku handiagoa izan zuten. Jarduera Fisikoaren Nazioarteko Gomendioekiko atxikimendua % 89koa izan zen, eta 7 ordu / egun baino gutxiago lo egiteak atxikimendua betetzeko probabilitatea handitu egin zuen. Ondorioak: Gehiegizko pisuaren prebalentzia adin ertaineko langileengan areagotu egiten da, eta gizonetan emakumeetan baino lehenago agertzen da. Gainera, loa eta jarduera fisikoa elkarreraginean egon daitezke.; ABSTRACT:The promotion of healthy lifestyles in the workplace is essential for the best maintenance of the health and autonomy of workers. There is an increasing interest in studying the relationship between overweight and obesity and healthy habits, such as physical activity (PA) or sleep duration and quality, in interactions with the work period. However, few studies have examined these interactions in university workers. Objective: To report the prevalence of overweight and the fulfillment of International Physical Activity Recommendations (PAR). To analyze the associations between PAR, body mass index and sociodemographic factors. Methods: Data from 292 university workers were collected during work health examinations. Chi-square or Fisher's exact tests used to assess relationships between each predictor and each outcome, and multivariate models to associated characteristics. Results: The prevalence of overweight was 42%. Interestingly, men at 35-54 years old and women at ≥55 years old presented greater risk of overweight grade II/obesity. The adherence to the PAR was 89% and sleep '7 hours/day increased the probability of fulfilling them. Conclusions: The prevalence of overweight increases in middle-aged workers, and earlier in men than in women, moreover, sleep-activity may be interacting with it.KEYWORDS: Physical activity, BMI, workers, overweight, obesity, sleep duration

Human Papillomavirus (HPV) genotype 18 variants in patients with clinical manifestations of HPV related infections in Bilbao, Spain

Background:Human papillomavirus (HPV) variants differ in their biological and chemical properties, and therefore, may present differences in pathogenicity. Most authors classified variants based on the phylogenetic analysis of L1 region. Nevertheless, recombination in HPV samples is becoming a usual finding and thus, characterizing genetic variability in other regions should be essential. Objectives:We aimed to characterize the genetic variability of HPV 18 in 5 genomic regions: E6, E7, E4, L1 and the Upstream Regulatory Region (URR), working with both single infection and multiple HPV infection samples. Furthermore, we aimed to assess the prevalence of HPV 18 variants in our region and look for possible existence of recombination as well as analyze the relationship between these variants and the type of lesion. Methods: From 2007 to 2010, Clinical Microbiology and Infection Control Department analyzed 44 samples which were positive for HPV 18. Genetic variability was determined in PCR products and variants were assigned to European, Asian-amerindian or African lineage. Recombination and association of variants with different types of lesion was studied. Results: Genetic analysis of the regions revealed a total of 56 nucleotide variations. European, African and Asian-amerindian variants were found in 25/44 (56.8%), 10/44 (22.7%) and 5/44 (11.4%) samples, respectively. We detected the presence of recombinant variants in 2/44 (4.5%) cases. Samples taken from high-grade squamous intraepithelial lesions (H-SIL) only presented variants with specific-african substitutions. Conclusions: Multiple HPV infection, non-european HPV variants prevalence and existence of recombination are considered risk factors for HPV persistence and progression of intraepithelial abnormalities, and therefore, should be taken into consideration in order to help to design and optimize diagnostics protocols as well as improve epidemiologic studies. Our study is one of the few studies in Spain which analyses the genetic variability of HPV18 and we showed the importance of characterizing more than one genomic region in order to detect recombination and classify HPV variants properl

Retroviral Infections in Sheep and Goats: Small Ruminant Lentiviruses and Host Interaction

Small ruminant lentiviruses (SRLV) are members of the Retrovirus family comprising the closely related Visna/Maedi Virus (VMV) and the Caprine Arthritis-Encephalitis Virus (CAEV), which infect sheep and goats. Both infect cells of the monocyte/macrophage lineage and cause lifelong infections. Infection by VMV and CAEV can lead to Visna/Maedi (VM) and Caprine Arthritis-Encephalitis (CAE) respectively, slow progressive inflammatory diseases primarily affecting the lungs, nervous system, joints and mammary glands. VM and CAE are distributed worldwide and develop over a period of months or years, always leading to the death of the host, with the consequent economic and welfare implications. Currently, the control of VM and CAE relies on the control of transmission and culling of infected animals. However, there is evidence that host genetics play an important role in determining Susceptibility/Resistance to SRLV infection and disease progression, but little work has been performed in small ruminants. More research is necessary to understand the host-SRLV interaction.The research of Genomics and Health group is funded by the Basque Government Industry Dpt. (grant SA-10/00120 to B.M.J.) and UPV/EHU (grants GIU07/62 and GIU10/22 to B.M.J. and UFI 11/20