Systematic Association Mapping Identifies NELL1 as a Novel IBD Disease Gene

Crohn disease (CD), a sub-entity of inflammatory bowel disease (IBD), is a complex polygenic disorder. Although recent studies have successfully identified CD-associated genetic variants, these susceptibility loci explain only a fraction of the heritability of the disease. Here, we report on a multi-stage genome-wide scan of 393 German CD cases and 399 controls. Among the 116,161 single-nucleotide polymorphisms tested, an association with the known CD susceptibility gene NOD2, the 5q31 haplotype, and the recently reported CD locus at 5p13.1 was confirmed. In addition, SNP rs1793004 in the gene encoding nel-like 1 precursor (NELL1, chromosome 11p15.1) showed a consistent disease-association in independent German population- and family-based samples (942 cases, 1082 controls, 375 trios). Subsequent fine mapping and replication in an independent sample of 454 French/Canadian CD trios supported the authenticity of the NELL1 association. Further confirmation in a large German ulcerative colitis (UC) sample indicated that NELL1 is a ubiquitous IBD susceptibility locus (combined p<10−6; OR = 1.66, 95% CI: 1.30–2.11). The novel 5p13.1 locus was also replicated in the French/Canadian sample and in an independent UK CD patient panel (453 cases, 521 controls, combined p<10−6 for SNP rs1992660). Several associations were replicated in at least one independent sample, point to an involvement of ITGB6 (upstream), GRM8 (downstream), OR5V1 (downstream), PPP3R2 (downstream), NM_152575 (upstream) and HNF4G (intron)

Multipotent glia-like stem cells mediate stress adaptation

The neural crest-derived adrenal medulla is closely related to the sympathetic nervous system; however, unlike neural tissue, it is characterized by high plasticity which suggests the involvement of stem cells. Here, we show that a defined pool of glia-like nestin–expressing progenitor cells in the adult adrenal medulla contributes to this plasticity. These glia-like cells have features of adrenomedullary sustentacular cells, are multipotent, and are able to differentiate into chromaffin cells and neurons. The adrenal is central to the body’s response to stress making its proper adaptation critical to maintaining homeostasis. Our results from stress experiments in vivo show the activation and differentiation of these progenitors into new chromaffin cells. In summary, we demonstrate the involvement of a new glia-like multipotent stem cell population in adrenal tissue adaptation. Our data also suggest the contribution of stem and progenitor cells in the adaptation of neuroendocrine tissue function in general

ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow temporal biodiversity change to be assessed at the community scale, reaching back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century

<scp>ReSurveyEurope</scp>: A database of resurveyed vegetation plots in Europe

AbstractAimsWe introduce ReSurveyEurope — a new data source of resurveyed vegetation plots in Europe, compiled by a collaborative network of vegetation scientists. We describe the scope of this initiative, provide an overview of currently available data, governance, data contribution rules, and accessibility. In addition, we outline further steps, including potential research questions.ResultsReSurveyEurope includes resurveyed vegetation plots from all habitats. Version 1.0 of ReSurveyEurope contains 283,135 observations (i.e., individual surveys of each plot) from 79,190 plots sampled in 449 independent resurvey projects. Of these, 62,139 (78%) are permanent plots, that is, marked in situ, or located with GPS, which allow for high spatial accuracy in resurvey. The remaining 17,051 (22%) plots are from studies in which plots from the initial survey could not be exactly relocated. Four data sets, which together account for 28,470 (36%) plots, provide only presence/absence information on plant species, while the remaining 50,720 (64%) plots contain abundance information (e.g., percentage cover or cover–abundance classes such as variants of the Braun‐Blanquet scale). The oldest plots were sampled in 1911 in the Swiss Alps, while most plots were sampled between 1950 and 2020.ConclusionsReSurveyEurope is a new resource to address a wide range of research questions on fine‐scale changes in European vegetation. The initiative is devoted to an inclusive and transparent governance and data usage approach, based on slightly adapted rules of the well‐established European Vegetation Archive (EVA). ReSurveyEurope data are ready for use, and proposals for analyses of the data set can be submitted at any time to the coordinators. Still, further data contributions are highly welcome.</jats:sec

Plant communities on trampled sites in villages of Nordrhein-Westfalen

Eine in den Jahren 2004/05 durchgeführte Bestandsaufnahme der spontanen Vegetation von 200 annähernd gleichmäßig über die Landesfläche verteilten nordrhein-westfälischen Dörfern erbrachte bei den Trittpflanzen den Nachweis von insgesamt acht Vegetationstypen, die in früheren Arbeiten über die Dorfvegetation Nordrhein-Westfalens (Wittig & Wittig 1986, Lohmeyer 1983) nicht erwähnt werden. Hierbei handelt es sich um das Herniarietum glabrae, die Eragrostis minor-Polygonum arenastrum-Gesellschaft, zwei auffällige Formen des Bryo-Saginetum procumbentis (Oxalis corniculata-Fazies, Portulaca oleracea-Ausbildung), das Coronopetum squamanti, die Coronopus didymus-Ausbildung des Lolio-Polygonetum arenastri und eine, zumindest im weiteren Sinne, ebenfalls zum Lolio-Polygonetum arenastri zu zählende Puccinellia distans-Gesellschaft, die durch fließende Übergänge mit einer identische Standorte besiedelnden Spergularia rubra-Gesellschaft verbunden ist. Das Neuauftreten dieser Vegetationstypen kann teilweise als rein zeitliches Phänomen gesehen werden: Die Ausbreitung der Neophyten Coronopus didymus, Eragrostis minor, Oxalis corniculata, Portulaca oleracea und der früher im Binnenland auf wenige Salzstellen beschränkten Puccinella distans war vor 20 Jahren noch nicht so weit fortgeschritten wie heute. Sicher ist es aber zu einem großen Teil auch die Folge einer Verstädterung der Dörfer (Pflasterung der Bürgersteige, Hofeinfahrten und Wege und damit mehr Platz und größere Differenzierungsmöglichkeiten für das Bryo-Saginetum procumbentis) sowie des vor 20 Jahren noch deutlich weniger üblichen Einsatzes chemischer Mittel (Herbizide oder Salz) zur Verhinderung des Aufkommens von spontaner Vegetation. Da einige der bezeichnenden Arten der neu gefundenen Vegetationstypen zumindest leicht Wärme liebend sind (Coronopus-Arten, Eragrostis minor, Oxalis corniculata, Portulaca oleracea), kann nicht ausgeschlossen werden, dass auch die globale Erwärmung eine gewisse Rolle spielt.An evenly distributed vegetation inventory of trampled sites was carried out in the years 2004-05 in 200 villages of Nordrhein-Westfalen. The resulting classification revealed eight plant communities that were not mentioned in previous studies on the village vegetation of the state (WlTTIG & WlTTIG 1986, LOHMEYER 1983). These are the association Herniarietum glabrae, the Eragrostis minor-Polygonum arenastrurn-community, two remarkable facies or types of the Bryo-Saginetum procumbentis {Oxalis corniculata-iacles, Portulaca olerácea-type), the Coronopetum squamati, the Coronopus didymus-type of the Lolio-Polygonetum arenastri, and the Puccinellia distans-community. The latter, in a broader sense, also belongs to the association Lolio-Polygonetum arenastri and has close floristic relationships to the Spergularia rubra-community, which prefers identical habitats. The new occurrence of these communities or facies can partly be regarded as a phenomenon of time: The spreading of neophytes such as Coronopus didymus, Eragrostis minor, Oxalis corniculata, Portulaca olerácea and Puccinellia distans, which was formerly restricted to some small salt meadows in Nordrhein-Westfalen, needs time and therefore was not as advanced twenty years ago as it is nowadays. On the other hand the new occurrence follows the urbanisation of villages (e. g. the paving of pathways and driveways to private areas provides more space and better conditions for the differentiation of the Bryo-Saginetum procumbentis), as well as the use of chemicals (herbicides or salt) to reduce or eliminate the spontaneous occurrence of plants. As some of the species concerned are slightly thermophilous (Coronopus species, Eragrostis minor, Oxalis corniculata, Portulaca oleráceo) global warming can possibly be regarded as an additional factor influencing the new occurrence of these vegetation types

Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer

Background: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients. Methods: Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0–6 weeks prior to and 0–6 weeks after RT using the maintrac® method, and patients were followed over a median period of 8.97 (1.16–19.09) years. Results: Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886). Conclusions: Using the maintrac® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment. Clinical Trial registration: The trial is registered (2 May 2019) at trials.gov under NCT03935802

Low Rates of Antimicrobial-Resistant Enterobacteriaceae in Wildlife in Taï National Park, Côte d’Ivoire, Surrounded by Villages with High Prevalence of Multiresistant ESBL-Producing Escherichia coli in People and Domestic Animals

Antimicrobial resistance genes can be found in all ecosystems, including those where antibiotic selective pressure has never been exerted. We investigated resistance genes in a collection of faecal samples of wildlife (non-human primates, mice), people and domestic animals (dogs, cats) in Côte d’Ivoire; in the chimpanzee research area of Taï National Park (TNP) and adjacent villages. Single bacteria isolates were collected from antibiotic-containing agar plates and subjected to molecular analysis to detect Enterobacteriaceae isolates with plasmid-mediated genes of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR). While the prevalence of ESBL-producing E. coli in the villages was 27% in people (n = 77) and 32% in dogs (n = 38), no ESBL-producer was found in wildlife of TNP (n = 75). PMQR genes, mainly represented by qnrS1, were also present in human- and dog-originating isolates from the villages (36% and 42% in people and dogs, respectively), but no qnrS has been found in the park. In TNP, different variants of qnrB were detected in Citrobacter freundii isolates originating non-human primates and mice. In conclusion, ESBL and PMQR genes frequently found in humans and domestic animals in the villages were rather exceptional in wildlife living in the protected area. Although people enter the park, the strict biosecurity levels they are obliged to follow probably impede transmission of bacteria between them and wildlife

Multipotent glia-like stem cells mediate stress adaptation

The neural crest-derived adrenal medulla is closely related to the sympathetic nervous system; however, unlike neural tissue, it is characterized by high plasticity which suggests the involvement of stem cells. Here, we show that a defined pool of glia-like nestin–expressing progenitor cells in the adult adrenal medulla contributes to this plasticity. These glia-like cells have features of adrenomedullary sustentacular cells, are multipotent, and are able to differentiate into chromaffin cells and neurons. The adrenal is central to the body’s response to stress making its proper adaptation critical to maintaining homeostasis. Our results from stress experiments in vivo show the activation and differentiation of these progenitors into new chromaffin cells. In summary, we demonstrate the involvement of a new glia-like multipotent stem cell population in adrenal tissue adaptation. Our data also suggest the contribution of stem and progenitor cells in the adaptation of neuroendocrine tissue function in general