Systems Biology in ELIXIR: modelling in the spotlight

info:eu-repo/semantics/publishedVersio

Decreased Numbers of Blood Dendritic Cells and Defective Function of Regulatory T Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

BACKGROUND: Dendritic cells (DC) and regulatory cells (Treg) play pivotal roles in controlling both normal and autoimmune adaptive immune responses. DC are the main antigen-presenting cells to T cells, and they also control Treg functions. In this study, we examined the frequency and phenotype of DC subsets, and the frequency and function of Treg from patients with ANCA-associated vasculitis (AAV). METHODOLOGY/PRINCIPAL FINDINGS: Blood samples from 19 untreated patients with AAV during flares and before any immunosuppressive treatment were analyzed, along with 15 AAV patients in remission and 18 age-matched healthy controls. DC and Treg numbers, and phenotypes were assessed by flow cytometry, and in vitro suppressive function of Treg was determined by co-culture assay. When compared to healthy volunteers, absolute numbers of conventional and plasmacytoid DC were decreased in AAV patients. During the acute phase this decrease was significantly more pronounced and was associated with an increased DC expression of CD62L. Absolute numbers of Treg (CD4(+)CD25(high)CD127(low/-) Tcells) were moderately decreased in patients. FOXP3 and CD39 were expressed at similar levels on Treg from patients as compared to controls. The suppressive function of Treg from AAV patients was dramatically decreased as compared to controls, and this defect was more pronounced during flares than remission. This Treg functional deficiency occurred in the absence of obvious Th17 deviation. CONCLUSION: In conclusion, these data show that AAV flares are associated with both a decrease number and altered phenotype of circulating DC and point to a role for Treg functional deficiency in the pathogenesis of AAV

Modern venomics – Current insights, novel methods and future perspectives in biological and applied animal venom research

Venoms have evolved >100 times in all major animal groups, and their components, known as toxins, have been fine-tuned over millions of years into highly effective biochemical weapons. There are many outstanding questions on the evolution of toxin arsenals, such as how venom genes originate, how venom contributes to the fitness of venomous species, and which modifications at the genomic, transcriptomic, and protein level drive their evolution. These questions have received particularly little attention outside of snakes, cone snails, spiders, and scorpions. Venom compounds have further become a source of inspiration for translational research using their diverse bioactivities for various applications. We highlight here recent advances and new strategies in modern venomics and discuss how recent technological innovations and multi-omic methods dramatically improve research on venomous animals. The study of genomes and their modifications through CRISPR and knockdown technologies will increase our understanding of how toxins evolve and which functions they have in the different ontogenetic stages during the development of venomous animals. Mass spectrometry imaging combined with spatial transcriptomics, in situ hybridization techniques, and modern computer tomography gives us further insights into the spatial distribution of toxins in the venom system and the function of the venom apparatus. All these evolutionary and biological insights contribute to more efficiently identify venom compounds, which can then be synthesized or produced in adapted expression systems to test their bioactivity. Finally, we critically discuss recent agrochemical, pharmaceutical, therapeutic, and diagnostic (so-called translational) aspects of venoms from which humans benefit

Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives

Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- A nd older-onset patients are still incompletely understood. Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results: A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion: Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients

Needs and effects of irrigation in corn cultivated for grain in the Kujawsko-Pomorski region

Celem pracy było określenie częstotliwości występowania susz w okresie wzmożonych potrzeb wodnych kukurydzy uprawianej na ziarno w regionie kujawsko-pomorskim na podstawie wielkości wskaźnika standaryzowanego opadu SPI. Wykorzystując istotną zależność między zwyżkami plonów ziarna a wysokością opadów atmosferycznych dokonano także oceny potrzeb i przewidywanych efektów produkcyjnych nawadniania tej uprawy. W badaniach wykorzystano wyniki pomiarów opadów atmosferycznych w okresie od 1 lipca do 31 sierpnia w wieloleciu 1981-2010, pochodzące z placówek COBORU w Chrząstowie, Głębokim i Głodowie oraz ze Stacji Badawczej UTP w Mochełku. Na podstawie przeprowadzonych badań stwierdzono, że częstotliwość wystąpienia suszy atmosferycznej w okresie wzmożonego zapotrzebowania na wodę kukurydzy na ziarno wynosiła w regionie 26,7-40,0%, w zależności od miejscowości. Silne susze wystąpiły w latach 1983, 1989, 1992 i 1994, umiarkowana w 2005, a słabe w latach 1982, 1984 i 1999. Duże potrzeby deszczowania kukurydzy na ziarno, odpowiadające okresom suszy silnej i umiarkowanej (SPI ≤ – 1,0) stwierdzono w 5 latach na 30 analizowanych. Prognozowana zwyżka plonu ziarna kukurydzy uprawianej na glebach lekkich pod wpływem nawadniania kształtuje się w tych latach na poziomie wyższym od 3,22 t.ha-1. W kolejnych 9 latach stwierdzono średnie potrzeby deszczowania, odpowiadające wielkościom SPI w okresie lipiec-sierpień od 0 do – 1,0.The study was carried out in order to determine the frequency of droughts in the period of increased water needs of corn cultivated for grain in the region of Kujawsko-Pomorskie based on temporal variation of the standardized precipitation index SPI. Also were assessed the needs and expected productive effects of the plants grown under irrigation by a significant correlation between increases of yields of grain and the amount of rainfall. Rainfall data were derived from standard measurements of atmospheric precipitation during a period from 1 July and 31 August in the multi- annual period 1981-2010. These data were obtained from the branches of the Research Centre for Cultivar Testing (COBORU) in Chrząstowo, Głębokie and Głodowo, and the University of Technology and Life Sciences Research Centre in Mochełek. The results of carried research showed that the frequency of occurrence of dry spell during the period of increased needs for water of corn amounted to 26.7-40.0% in the region depended on the locality. Strong droughts occurred in the year 1983, 1989, 1992 and 1994, moderate drought in 2005 and weak droughts in 1982, 1984 and 1999. Great irrigation needs of corn which corresponded to periods of strong and moderate droughts (SPI ≤ – 1.0) have been identified in 5 years of the 30 examined. The expected increase in the yield of corn grain cultivated on light soils under irrigation during those years exceeds 3.22 t.ha-1. In the 9 years occurred medium-level irrigation needs, which in the period of July-August, correspond to SPI values between 0 and – 1.0

Evaluation of requirements and expected effects of sprinkler irrigation in spring cereals in the Kujawsko-Pomorskie region

Badania przeprowadzono w celu określenia częstotliwości występowania susz w okresie wzmożonych potrzeb wodnych zbóż jarych oraz oceny potrzeb i przewidywanych efektów produkcyjnych deszczowania tych roślin w regionie kujawsko-pomorskim, na podstawie zmienności czasowej wskaźnika standaryzowanego opadu SPI. Materiał stanowiły wyniki standardowych pomiarów opadów atmosferycznych w okresie od 1 maja do 30 czerwca w wieloleciu 1981-2010. Dane opadowe pozyskano z placówek COBORU w Chrząstowie, Głębokim i Głodowie oraz ze Stacji Badawczej UTP w Mochełku. W wyniku przeprowadzonych badań stwierdzono, że częstotliwość wystąpienia warunków posusznych w okresie wzmożonego zapotrzebowania na wodę przez zboża jare wynosiła w regionie 23,3-30,0%, zależnie od miejscowości. Susze ekstremalne wystąpiły w latach 2000 i 2008, silna w 1983, umiarkowana w 1989, a słabe w latach 1992, 2003 i 2006. Bardzo duże i duże potrzeby deszczowania zbóż jarych, odpowiadające okresom suszy ekstremalnej, silnej i umiarkowanej (SPI ≤ -1,0) zidentyfikowano w 4 latach na 30 analizowanych. Przewidywana zwyżka plonu ziarna zbóż jarych uprawianych na glebach lekkich pod wpływem deszczowania kształtuje się na poziomie wyższym od 1,8 t.ha-1. W kolejnych 8 latach stwierdzono średnie potrzeby deszczowania, odpowiadające wielkościom SPI w okresie maj-czerwiec od 0 do -1,0.The work was carried out in order to determine the frequency of droughts in the period of increased water needs of spring cereals. In addition, based on the time variation of the standardized precipitation index SPI assessed the needs and the expected production results of the plants irrigated in the Kujawsko-Pomorskie region. Data consisted of the results of standard measurements of rainfall from 1 May to 30 June in the period 1981-2010. Rainfall data were obtained from the branches COBORU in Chrząstowo, Głębokie and Głodowo and also from the Research Station of University and Technology and Life Science in Mochełek. Based on the results of the study, it was found that, during the period of high demand for water of spring cereals, the frequency of drought conditions in the region accounted of 23,3-30,0%, depending on the locality. Extreme droughts occurred in years 2000 and 2008, strong in 1983, moderate in 1989 and weak in 1992, 2003 and 2006. Among the analyzed 30 years, in 4 years were identified very high- and high-level requirements of irrigation in spring cereals corresponding to periods of extreme, strong and moderate droughts (SPI ≤ -1.0). The expected increase in grain yield of spring cereals cultivated on light soils under irrigation is assessed at the level higher than 1.8 t·ha-1. In the subsequent 8 years, occurred medium-level irrigation needs, which in the period of May-June corresponded to the values of the SPI at the level between 0.0 and -1.0