Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity

Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs) differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of interspecies differences in immune response to infection. However, because of the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole-genome transcriptomic responses of ape species (human and chimpanzee) and AAMs (rhesus macaque and baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ~40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, up-regulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage. Copyrigh

Divergence across mitochondrial genomes of sympatric members of the Schistosoma indicum group and clues into the evolution of Schistosoma spindale

Schistosoma spindale and Schistosoma indicum are ruminant-infecting trematodes of the Schistosoma indicum group that are widespread across Southeast Asia. Though neglected, these parasites can cause major pathology and mortality to livestock leading to significant welfare and socio-economic issues, predominantly amongst poor subsistence farmers and their families. Here we used mitogenomic analysis to determine the relationships between these two sympatric species of schistosome and to characterise S. spindale diversity in order to identify possible cryptic speciation. The mitochondrial genomes of S. spindale and S. indicum were assembled and genetic analyses revealed high levels of diversity within the S. indicum group. Evidence of functional changes in mitochondrial genes indicated adaptation to environmental change associated with speciation events in S. spindale around 2.5 million years ago. We discuss our results in terms of their theoretical and applied implications

Enhancing Productivity of Sweet Marjoram in Substrate Culture

Sweet Marjoram is considered as one of the important herbal plants, grown in many countries for medical and nutritional purposes and is an abundant source of valuable biologically active substances and mineral components. An experiment has been carried out on sweet marjoram at the experimental site of Central Laboratory for Agricultural Climate (CLAC), Agriculture Research Center,  Ministry of Agriculutre and land reclamation, Egypt under a net duble span house, during seasons of 2019and 2020. The experiment was carried out to study the effect of different nutrient solution sources and verimicompost rates on production of Sweet Marjoram grown in sand culture. In this experiment, Three sources of nutrient solution were under investigation (chemical nutrient solution “CN. S.” as a control treatment, vermi-liquid “V. L.” and mixture of chemical nutrient solution andvermi-liquid (50%:50%) “CN.S.+V.L.”), also, five rates of vermicompost have been added to sand culture(zero% of vermicompost "V.C. 0%"as a control treatment, 10% Vermicompost "V.C. 10%", 20% Vermicompost "V.C. 20%", 30% Vermicompost "V.C. 30%"and 40% Vermicompost "V.C. 40%").Regarding the effect of nutrient solution source; results illustrated that chemical nutrient solution recorded the highest values for  vegetative growth, yield and chemical measurments. also data clearfied that the mixture of chemical nutrient solution and vermi-liquid (50%:50%) “CN.S.+V.L.” recorded a promising results very close to the chemical nutrient solution and more healther; because the amount of chemicals used in this nutrient solution have been reduced into the half amount only comparison with chemical nutrient solution. For that, the mixture of chemical nutrient solution and vermi-liquid (50%:50%) could be considered as the most suitable nutrient solution for sweet marjoram. Concerning the effect of different vermicompost rates, results showed that adding vermicompost rate by 30% to sand culture recorded the highest values for plant height,  number of branches /plant, Fresh and dry weights of the aerial parts /plant, yields of the fresh and dry herb/ m2, yield of aromatic oil/ m2 (V.C. 40% recorded higher values for yield of the aromatic oil/m2 than V.C. 30% but the difference between both of them was not significant), and N,P,K% in leaves.  </jats:p

P723 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: Results from the GO-LEVEL study

Abstract Background The exposure–response relationship associated with the use of golimumab for UC has been previously demonstrated in the PURSUIT trial programme. A significant association between serum golimumab concentrations (SGC) and favourable outcomes was observed during both induction and maintenance therapy. However, data regarding the optimal therapeutic SGC threshold is limited. Methods GO-LEVEL was an open-label, phase IV, investigator initiated study (NCT03124121) which included a prospective cohort of UC patients commencing golimumab induction therapy, as well as a cross-sectional cohort receiving maintenance treatment (&amp;gt;18 weeks from initiation). Patients commencing induction therapy all had disease activity objectively confirmed and were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare, or during stable remission. Clinical disease activity was evaluated using SCCAI and PRO2, and biochemical activity using FC and CRP. Combined clinical-biochemical remission was defined as SCCAI&amp;lt;3 as well as FC&amp;lt;250ug/g. SGC and anti-golimumab antibodies (AGA) were measured using a drug-sensitive ELISA (LISATRACKER, Theradiag). Fishers exact or Mann–Whitney U were used to compare groups, ROC analysis to identify therapeutic thresholds and Spearman’s rank coefficient (rs) for correlations. Results Thirty-nine patients were included in the induction cohort, of whom 15 (38%) achieved combined remission at week 6. The median SGC of those in combined remission was significantly higher than those who were not (5.0 vs. 3.1 μg/ml, respectively, p = 0.03). ROC curve analysis demonstrates 3.8 μg/ml as the optimal therapeutic threshold to achieve combined remission at week 6 (sensitivity 0.71, specificity 0.65, AUC 0.72). Significant, inverse correlations were also observed between week 6 SGC and PRO2, CRP and FC (rs −0.41 (p = 0.01), −0.47 (p = 0.004) and −0.40 (p = 0.02), respectively). However, week 6 SGC did not predict outcomes at week 10 or 14. Sixty-four patients were included in the maintenance cohort; 32 (50%) were in combined remission, 32 were not. The median SGC of those in combined remission was significantly higher (3.0 vs. 2.1 μg/ml, respectively, p = 0.003). ROC curve analysis demonstrates 2.4 μg/ml as the optimal therapeutic threshold to achieve combined remission (sensitivity 0.73, specificity 0.66, AUC 0.71). No AGA were detected in either cohort. Conclusion GO-LEVEL offers further evidence of the exposure-response relationship with golimumab. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested SGC therapeutic thresholds of 3.8 μg/ml at week 6 and 2.4 μg/ml during maintenance. </jats:sec