Not a melting pot: Plant species aggregate in their non-native range

Aim Plant species continue to be moved outside of their native range by human activities. Here, we aim to determine whether, once introduced, plants assimilate into native communities or whether they aggregate, thus forming mosaics of native- and alien-rich communities. Alien species might aggregate in their non-native range owing to shared habitat preferences, such as their tendency to establish in high-biomass, species-poor areas. Location Twenty-two herbaceous grasslands in 14 countries, mainly in the temperate zone. Time period 2012-2016. Major taxa studied Plants. Methods We used a globally coordinated survey. Within this survey, we found 46 plant species, predominantly from Eurasia, for which we had co-occurrence data in their native and non-native ranges. We tested for differences in co-occurrence patterns of 46 species between their native (home) and non-native (away) range. We also tested whether species had similar habitat preferences, by testing for differences in total biomass and species richness of the patches that species occupy in their native and non-native ranges. Results We found the same species to show different patterns of association depending on whether they were in their native or non-native range. Alien species were negatively associated with native species; instead, they aggregated with other alien species in species-poor, high-biomass communities in their non-native range compared with their native range. Main conclusions The strong differences between the native (home) and non-native (away) range in species co-occurrence patterns are evidence that the way in which species associate with resident communities in their non-native range is not species dependent, but is instead a property of being away from their native range. These results thus highlight that species might undergo important ecological changes when introduced away from their native range. Overall, we show origin-dependent associations that result in novel communities, in which alien-rich patches exist within a mosaic of native-dominated communities

Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients

Background: The concept of the involvement of systemic inflammation in cancer progression and metastases has gained attraction within the past decade. C-reactive protein (CRP), a non-specific blood-based marker of the systemic inflammatory response, has been associated with decreased survival in several cancer types. The aim of the present study was to validate the prognostic value of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft-tissue sarcoma (STS) patients. Methods: Three hundred and four STS patients, operated between 1998 and 2010, were retrospectively evaluated. CRP levels and the impact on cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan–Meier curves and univariate as well as multivariate Cox proportional models. Additionally, we developed a nomogram by supplementing the plasma CRP level to the well-established Kattan nomogram and evaluated the improvement of predictive accuracy of this novel nomogram by applying calibration and Harrell’s concordance index (c-index). Results: An elevated plasma CRP level was significantly associated with established prognostic factors, including age, tumour grade, size and depth (P<0.05). In multivariate analysis, increased CRP levels were significantly associated with a poor outcome for CSS (HR=2.05; 95% CI=1.13–3.74; P=0.019) and DFS (HR=1.88; 95% CI=1.07–3.34; P=0.029). The estimated c-index was 0.74 using the original Kattan nomogram and 0.77 when the plasma CRP level was added. Conclusion: An elevated pre-operative CRP level represents an independent prognostic factor that predicts poor prognosis and improves the predictive ability of the Kattan nomogram in STS patients. Our data suggest to further prospectively validate its potential utility for individual risk stratification and clinical management of STS patients

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS

Identification and structural characterization of a mutant KRAS‐G12V specific TCR restricted by HLA‐A3

Mutations in KRAS are some of the most common across multiple cancer types and are thus attractive targets for therapy. Recent studies demonstrated that mutant KRAS generates immunogenic neoantigens that are targetable by adoptive T‐cell therapy in metastatic diseases. To expand mutant KRAS‐specific immunotherapies, it is critical to identify additional HLA‐I allotypes that can present KRAS neoantigens and their cognate T‐cell receptors (TCR). Here, we identified a murine TCR specific to a KRAS‐G12V neoantigen (7VVVGAVGVGK16) using a vaccination approach with transgenic mice expressing HLA‐A*03:01 (HLA‐A3). This TCR demonstrated exquisite specificity for mutant G12V and not WT KRAS peptides. To investigate the molecular basis for neoantigen recognition by this TCR, we determined its structure in complex with HLA‐A3(G12V). G12V‐TCR CDR3β and CDR1β formed a hydrophobic pocket to interact with p6 Val of the G12V but not the WT KRAS peptide. To improve the tumor sensitivity of this TCR, we designed rational substitutions to improve TCR:HLA‐A3 contacts. Two substitutions exhibited modest improvements in TCR binding avidity to HLA‐A3 (G12V) but did not sufficiently improve T‐cell sensitivity for further clinical development. Our study provides mechanistic insight into how TCRs detect neoantigens and reveals the challenges in targeting KRAS‐G12V mutations

Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer

Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Previous findings from small-scale studies revealed conflicting results about its independent prognostic significance with regard to different clinical end points in pancreatic cancer (PC) patients. Therefore, the aim of our study was the external validation of the prognostic significance of NLR in a large cohort of PC patients. Methods: Data from 371 consecutive PC patients, treated between 2004 and 2010 at a single centre, were evaluated retrospectively. The whole cohort was stratified into two groups according to the treatment modality. Group 1 comprised 261 patients with inoperable PC at diagnosis and group 2 comprised 110 patients with surgically resected PC. Cancer-specific survival (CSS) was assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of the NLR, the modified Glasgow prognostic score (mGPS) and the platelet-lymphocyte ratio univariate and multivariate Cox regression models were applied. Results: Multivariate analysis identified increased NLR as an independent prognostic factor for inoperable PC patients (hazard ratio (HR)=2.53, confidence interval (CI)=1.64–3.91, P<0.001) and surgically resected PC patients (HR=1.61, CI=1.02–2.53, P=0.039). In inoperable PC patients, the mGPS was associated with poor CSS only in univariate analysis (HR=1.44, CI=1.04–1.98). Conclusion: Risk prediction for cancer-related end points using NLR does add independent prognostic information to other well-established prognostic factors in patients with PC, regardless of the undergoing therapeutic modality. Thus, the NLR should be considered for future individual risk assessment in patients with PC

Franck-Condon Effect in Central Spin System

We study the quantum transitions of a central spin surrounded by a collective-spin environment. It is found that the influence of the environmental spins on the absorption spectrum of the central spin can be explained with the analog of the Franck-Condon (FC) effect in conventional electron-phonon interaction system. Here, the collective spins of the environment behave as the vibrational mode, which makes the electron to be transitioned mainly with the so-called "vertical transitions" in the conventional FC effect. The "vertical transition" for the central spin in the spin environment manifests as, the certain collective spin states of the environment is favored, which corresponds to the minimal change in the average of the total spin angular momentum.Comment: 8 pages, 8 figure

TGA2 signaling in response to reactive electrophile species is not dependent on cysteine modification of TGA2

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Reactive electrophile species (RES), including prostaglandins, phytoprostanes and 12-oxo phytodienoic acid (OPDA), activate detoxification responses in plants and animals. However, the pathways leading to the activation of defense reactions related to abiotic or biotic stress as a function of RES formation, accumulation or treatment are poorly understood in plants. Here, the thiol-modification of proteins, including the RES-activated basic region/leucine zipper transcription factor TGA2, was studied. TGA2 contains a single cysteine residue (Cys186) that was covalently modified by reactive cyclopentenones but not required for induction of detoxification genes in response to OPDA or prostaglandin A1. Activation of the glutathione-S-transferase 6 (GST6) promoter was responsive to cyclopentenones but not to unreactive cyclopentanones, including jasmonic acid suggesting that thiol reactivity of RES is important to activate the TGA2-dependent signaling pathway resulting in GST6 activation We show that RES modify thiols in numerous proteins in vivo, however, thiol reactivity alone appears not to be sufficient for biological activity as demonstrated by the failure of several membrane permeable thiol reactive reagents to activate the GST6 promoter.Peer reviewedFinal Published versio