The Relationship between Structurally Different Pyrrolizidine Alkaloids and Western Flower Thrips Resistance in F2 Hybrids of Jacobaea vulgaros and Jacobaea aquatica

Segregating plant hybrids often have more ecological and molecular variability compared to parental species, and are therefore useful for studying relationships between different traits, and the adaptive significance of trait variation. Hybrid systems have been used to study the relationship between the expression of plant defense compounds and herbivore susceptibility. We conducted a western flower thrips (WFT) bioassay using a hybrid family and investigated the relationship between WFT resistance and pyrrolizidine alkaloid (PA) variation. The hybrid family consisted of two parental (Jacobaea vulgaris and Jacobaea aquatica) genotypes, two F1 genotypes, and 94 F2 hybrid lines. The J. aquatica genotype was more susceptible to thrips attack than the J. vulgaris genotype, the two F1 hybrids were as susceptible as J. aquatica, and susceptibility to WFT differed among F2 hybrid lines: 69 F2 lines were equally susceptible compared to J. aquatica, 10 F2 lines were more susceptible than J. aquatica and 15 F2 lines were as resistant as J. vulgaris or were intermediate to the two parental genotypes. Among 37 individual PAs that were derived from four structural groups (senecionine-, jacobine-, erucifoline- and otosenine-like PAs), the N-oxides of jacobine, jaconine, and jacoline were negatively correlated with feeding damage caused by WFT, and the tertiary amines of jacobine, jaconine, jacoline, and other PAs did not relate to feeding damage. Total PA concentration was negatively correlated with feeding damage. Among the four PA groups, only the total concentration of the jacobine-like PAs was negatively correlated with feeding damage. Multiple regression tests suggested that jacobine-like PAs play a greater role in WFT resistance than PAs from other structural groups. We found no evidence for synergistic effects of different PAs on WFT resistance. The relationship between PA variation and WFT feeding damage in the Jacobaea hybrids suggests a role for PAs in resistance to generalist insects

Development of nanoparticulate adjuvants based on aluminium salts

The aim of this thesis was to develop aluminium salt-based nanoparticles that may ultimately be used as adjuvant in human vaccines. Compared to traditional aluminium salt-based adjuvants, nanoparticles may improve vaccine efficacy and reduce encountered side effects. Nanoparticles were synthesised and their physicochemical properties were investigated. Their immunostimulating properties were investigated in vitro and in vivo and compared to traditional aluminium salt-based adjuvants. Drug Delivery Technolog

Preparing for an interdisciplinary future: A perspective from early-career researchers

Increasingly, research is moving towards more interdisciplinary endeavours. Effective collaboration between people from different disciplines is necessary to maximise the potential benefits of interdisciplinarity for future research activity. This paper analyses an approach to fostering the skills required for successful cross-disciplinary collaboration from the perspective of an interdisciplinary group of early-career researchers. Our reflection on how specially-designed encounters can help to shape future interdisciplinary research initiatives draws on the discussion of a four-day workshop, a post-event survey, and a review of other experiences. We conclude that interdisciplinary encounters are an effective means to support the development of future interdisciplinary researchers, with a major advantage of this approach being the opportunity for open communication. Depending on the organiser's aim, we distinguish between “cultivation” and “development” encounters. Among the multiple factors that produce successful interdisciplinary encounters, we found that selection of a theme, participants and location need to be tailored to the encounter's particular objectives. We recommend that funding bodies and other members of the research community should take note of the effectiveness of encounters to foster interdisciplinarity and generate space to develop more innovative and high-impact research that delivers solutions to the challenges facing humanity in the future

Camera traps enable the estimation of herbaceous aboveground net primary production (ANPP) in an African savanna at high temporal resolution

Determining the drivers of aboveground net primary production (ANPP), a key ecosystem process, is an important goal of ecosystem ecology. However, accurate estimation of ANPP across larger areas remains challenging, especially for savanna ecosystems that are characterized by large spatiotemporal heterogeneity in ANPP. Satellite remote sensing methods are frequently used to estimate productivity at the landscape scale but generally lack the spatial and temporal resolution to capture the determinants of productivity variation. Here, we developed and tested methods for estimating herbaceous productivity as an alternative to labour-intensive repeated biomass clipping and caging of small plots. We compared measures of three spectral greenness indices, normalized difference vegetation index derived from Sentinel-2 (NDVIs) and a handheld radiometer (NDVIg), and green chromatic coordinate derived from digital repeat cameras (GCC) and tested their relationship to biweekly field-measured herbaceous ANPP using movable exclosures. We found that a satellite-based model including average NDVIs and its rate of change (ΔNDVIs) over the biweekly productivity measurement interval predicted herbaceous ANPP reasonably well (Jackknife R2 = 0.26). However, the predictive accuracy doubled (Jackknife R2 = 0.52) when including the sum of day to day increases in camera trap-derived vegetation greenness (tGCC). This result can be considered promising, given the current lack of productivity estimation methods at comparable spatiotemporal resolution. We furthermore found that the fine (daily) temporal resolution of GCC time series captured fast vegetation responses to rainfall events that were missed when using a coarser temporal resolution (>2 days). These findings demonstrate the importance of measuring at a fine temporal resolution for predicting herbaceous ANPP in savanna ecosystems. We conclude that camera traps are promising in offering a reliable and cost-effective method to estimate productivity in savannas and contribute to a better understanding of ecosystem functioning and its drivers

Phosphoproteomics sample preparation impacts biological interpretation of phosphorylation signaling outcomes

The influence of phosphoproteomics sample preparation methods on the biological interpretation of signaling outcome is unclear. Here, we demonstrate a strong bias in phosphorylation signaling targets uncovered by comparing the phosphoproteomes generated by two commonly used methods-strong cation exchange chromatography-based phosphoproteomics (SCXPhos) and single-run high-throughput phosphoproteomics (HighPhos). Phosphoproteomes of embryonic stem cells exposed to ionizing radiation (IR) profiled by both methods achieved equivalent coverage (around 20,000 phosphosites), whereas a combined dataset significantly increased the depth (>30,000 phosphosites). While both methods reproducibly quantified a subset of shared IR-responsive phosphosites that represent DNA damage and cell-cycle-related signaling events, most IR-responsive phosphoproteins (>82%) and phosphosites (>96%) were method-specific. Both methods uncovered unique insights into phospho-signaling mediated by single (SCXPhos) versus double/multi-site (HighPhos) phosphorylation events; particularly, each method identified a distinct set of previously unreported IR-responsive kinome/phosphatome (95% disparate) directly impacting the uncovered biology.Genome Instability and Cance

Uphill and downhill walking in unilateral lower limb amputees

Objective: To study adjustment strategies in unilateral amputees in uphill and downhill walking. Design: observational cohort study. Subjects: Seven transfemoral, 12 transtibial unilateral amputees and 10 able-bodied subjects. Methods: In a motion analysis laboratory the subjects walked over a level surface and an uphill and downhill slope. Gait velocity and lower limb joint angles were measured. Results: In uphill walking hip and knee flexion at initial contact and hip flexion in swing were increased in the prosthetic limb of transtibial amputees. In downhill walking transtibial amputees showed more knee flexion on the prosthetic side in late stance and swing. Transfemoral amputees were not able to increase prosthetic knee flexion in uphill and downhill walking. An important adjustment strategy in both amputee Groups was a smaller hip extension in late stance in uphill and downhill walking, probably related with a shorter step length. In addition, amputees increased knee flexion in early stance in the non-affected limb in uphill walking to compensate for the shorter prosthetic limb length. In downhill walking fewer adjustments were necessary, since the shorter prosthetic limb already resulted in lowering of the body. Conclusion: Uphill and downhill walking can be trained in rehabilitation, which may improve safety and confidence of amputees. Prosthetic design should focus on better control of prosthetic knee flexion abilities without reducing stability. (c) 2007 Elsevier B.V. All fights reserved

Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity

Drug-induced liver injury (DILI) is an important problem both in the clinic and in the development of new safer medicines. Two pivotal adaptation and survival responses to adverse drug reactions are oxidative stress and cytokine signaling based on the activation of the transcription factors Nrf2 and NF-κB, respectively. Here, we systematically investigated Nrf2 and NF-κB signaling upon DILI-related drug exposure. Transcriptomics analyses of 90 DILI compounds in primary human hepatocytes revealed that a strong Nrf2 activation is associated with a suppression of endogenous NF-κB activity. These responses were translated into quantitative high-content live-cell imaging of induction of a selective Nrf2 target, GFP-tagged Srxn1, and the altered nuclear translocation dynamics of a subunit of NF-κB, GFP-tagged p65, upon TNFR signaling induced by TNFα using HepG2 cells. Strong activation of GFP-Srxn1 expression by DILI compounds typically correlated with suppression of NF-κB nuclear translocation, yet reversely, activation of NF-κB by TNFα did not affect the Nrf2 response. DILI compounds that provided strong Nrf2 activation, including diclofenac, carbamazepine and ketoconazole, sensitized toward TNFα-mediated cytotoxicity. This was related to an adaptive primary protective response of Nrf2, since loss of Nrf2 enhanced this cytotoxic synergy with TNFα, while KEAP1 downregulation was cytoprotective. These data indicate that both Nrf2 and NF-κB signaling may be pivotal in the regulation of DILI. We propose that the NF-κB-inhibiting effects that coincide with a strong Nrf2 stress response likely sensitize liver cells to pro-apoptotic signaling cascades induced by intrinsic cytotoxic pro-inflammatory cytokines

One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

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