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Different experimental multiple trauma models induce comparable inflammation and organ injury
(2020)
Multiple injuries appear to be a decisive factor for experimental polytrauma. Therefore, our aim was to compare the inflammatory response and organ damage of five different monotrauma with three multiple trauma models. For this, mice were randomly assigned to 10 groups: Healthy control (Ctrl), Sham, hemorrhagic shock (HS), thoracic trauma (TxT), osteotomy with external fixation (Fx), bilateral soft tissue trauma (bsTT) or laparotomy (Lap); polytrauma I (PT I, TxT + HS + Fx), PT II (TxT + HS + Fx + Lap) and one multi-trauma group (MT, TxT + HS + bsTT + Lap). The inflammatory response and organ damage were quantified at 6 h by analyses of IL-6, IL-1β, IL-10, CXCL1, SAA1, HMGB1 and organ injury. Systemic IL-6 increased in all mono and multiple trauma groups, while CXCL1 increased only in HS, PT I, PT II and MT vs. control. Local inflammatory response was most prominent in HS, PT I, PT II and MT in the liver. Infiltration of inflammatory cells into lung and liver was significant in all multiple trauma groups vs. controls. Hepatic and pulmonary injury was prominent in HS, PT I, PT II and MT groups. These experimental multiple trauma models closely mimic the early post-traumatic inflammatory response in human. Though, the choice of read-out parameters is very important for therapeutic immune modulatory approaches.
Background: The gut microbiome can influence life history traits associated with host fitness such as fecundity and longevity. In most organisms, these two life history traits are traded-off, while they are positively linked in social insects. In ants, highly fecund queens can live for decades, while their non-reproducing workers exhibit much shorter lifespans. Yet, when fertility is induced in workers by death or removal of the queen, worker lifespan can increase. It is unclear how this positive link between fecundity and longevity is achieved and what role the gut microbiome and the immune system play in this. To gain insights into the molecular regulation of lifespan in social insects, we investigated fat body gene expression and gut microbiome composition in workers of the ant Temnothorax rugatulus in response to an experimental induction of fertility and an immune challenge.
Results: Fertile workers upregulated several molecular repair mechanisms, which could explain their extended lifespan. The immune challenge altered the expression of several thousand genes in the fat body, including many immune genes, and, interestingly, this transcriptomic response depended on worker fertility. For example, only fertile, immune-challenged workers upregulated genes involved in the synthesis of alpha-ketoglutarate, an immune system regulator, which extends the lifespan in Caenorhabditis elegans by down-regulating the TOR pathway and reducing oxidant production. Additionally, we observed a dramatic loss in bacterial diversity in the guts of the ants within a day of the immune challenge. Yet, bacterial density did not change, so that the gut microbiomes of many immune challenged workers consisted of only a single or a few bacterial strains. Moreover, the expression of immune genes was linked to the gut microbiome composition, suggesting that the ant host can regulate the microbiome in its gut.
Conclusions: Immune system flare-ups can have negative consequence on gut microbiome diversity, pointing to a previously underrated cost of immunity. Moreover, our results provide important insights into shifts in the molecular regulation of fertility and longevity associated with insect sociality.
A tale of two seasons: The link between seasonal migration and climatic niches in passerine birds
(2020)
The question of whether migratory birds track a specific climatic niche by seasonal movements has important implications for understanding the evolution of migration, the factors affecting species' distributions, and the responses of migrants to climate change. Despite much research, previous studies of bird migration have produced mixed results. However, whether migrants track climate is only one half of the question, the other being why residents remain in the same geographic range year-round. We provide a literature overview and test the hypothesis of seasonal niche tracking by evaluating seasonal climatic niche overlap across 437 migratory and resident species from eight clades of passerine birds. Seasonal climatic niches were based on a new global dataset of breeding and nonbreeding ranges. Overlap between climatic niches was quantified using ordination methods. We compared niche overlap of migratory species to two null expectations, (a) a scenario in which they do not migrate and (b) in comparison with the overlap experienced by closely related resident species, while controlling for breeding location and range size. Partly in accordance with the hypothesis of niche tracking, we found that the overlap of breeding versus nonbreeding climatic conditions in migratory species was greater than the overlap they would experience if they did not migrate. However, this was only true for migrants breeding outside the tropics and only relative to the overlap species would experience if they stayed in the breeding range year-round. In contrast to the hypothesis of niche tracking, migratory species experienced lower seasonal climatic niche overlap than resident species, with significant differences between tropical and nontropical species. Our study suggests that in seasonal nontropical environments migration away from the breeding range may serve to avoid seasonally harsh climate; however, different factors may drive seasonal movements in the climatically more stable tropical regions.
Introduction: From the beginning of the corona pandemic until August 19, 2020, more than 21,989,366 cases have been reported worldwide – 228,495 in Germany alone, including 12,648 children aged 0–14. In many countries, the proportion of infected children in the total population is comparatively low; in addition, children often have no or milder symptoms and are less likely to transmit the pathogen to adults than the other way round. Based on the registration data in Frankfurt am Main, Germany, the symptoms of children in comparison with adults and the likely routes of transmission are presented below.
Materials and methods: The documentation of the mandatory reports includes personal data (name, date of birth, gender, place of residence), disease characteristics (date of report, date of onset of the disease, symptoms), possible contact persons (family, others) and i.a. possible activity or care in children’s community facilities. All reports were viewed, especially with regard to likely transmission routes.
Results: From March 1 to July 31, 2020, 1,977 infected people were reported, including 138 children between the ages of 0 and 14 years. Children had fewer and milder symptoms than adults. None of the children experienced severe respiratory symptoms or the need for ventilation. 62% of the children had no symptoms at all (19% adults), 5% of the children were hospitalized (24% adults), and none of the children died (3.8% adults).
After excluding a cluster of 34 children from refugee accommodations and 14 children from a parish, 78% of the remaining 90 children had been infected by an adult within the family, and only 4% were likely to have a reverse transmission route. In 5.5% of cases, transmission in a community facility was likely.
Discussion: The results of the registration data from Frankfurt am Main, Germany confirm the results published in other countries: Children are less likely to become infected, and if infected, their symptoms are less severe than in adults, and they are apparently not the main drivers of virus transmission. Therefore, scientific medical associations strongly recommend reopening schools.
Uni-Highlights Dezember 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2020)
This article documents and classifies instances of transnational intellectual property (IP) enforcement and licensing on the Internet with a particular focus on the territorial reach of the respective regimes. Regarding IP enforcement, I show that the bulk of transnational or even global measures is adopted in the context of “voluntary” self-regulation by various intermediaries, namely domain name registrars, access and host providers, search engines, and advertising and payment services. Global IP licensing is, in contrast, less prevalent than one might expect. It is practically limited to freely accessible Open Content, whereas markets for fee-based services remain territorially fragmented. Overall, three layers of IP governance on the Internet can be distinguished. Based on global licenses, Open Content is freely accessible everywhere. Plain IP infringements are equally combatted on a worldwide scale. Territorial fragmentation persists, instead, in the market segment of fee-based services and in hard cases of conflicts of IP laws/rights. All three universal norms (global accessibility, global illegality, global fragmentation) are supported by a quite solid, “rough” global consensus.
Die Zukunft der Freiheit
(2020)
Im Zentrum des Beitrags steht die Frage, ob und wie sich Freiheit verändert, wenn wir uns in Echo-Räumen bewegen, also in digitalen sozialen Netzwerken und in digitalen Welten, die aus den Vorhersagedaten des eigenen Verhaltens zusammengesetzt sind. Beide Varianten digitaler Welten werden als Bestätigungswelten charakterisiert, in denen der Nutzer sich in relevanten Aspekten seines Selbst nicht nur spiegelt, sondern immer wieder bestätigt und anerkannt sieht und auch andere bestätigt und anerkennt. Der Aufsatz verdeutlicht, dass es für die Frage der Freiheit in solchen Bestätigungswelten nicht nur darauf ankommt, ob wir nach den jeweils eigenen Gründen handeln oder nach Regeln, die wir gemeinsam mit anderen akzeptieren können. Denn solche Ansätze beruhen auf der unausgesprochenen Prämisse eines statischen Selbst, eine so verstandene Freiheit wäre eine statische Freiheit. Dem wird ein Verständnis von Freiheit als dynamischer Prozess gegenübergestellt, zu dem es gehört, die eigenen Gründe zu ändern. Dazu muss sich das Selbst von diesen Gründen aber erst einmal distanzieren und sich zu sich selbst verhalten können, was die Erfahrung von Widerspruch und Widerstand voraussetzt. Komplementär zu diesem Widerspruch ist es zudem auf Vertrauen angewiesen, um die Herausforderungen der Freiheit anzunehmen. Es wird gezeigt, dass sich beide Aspekte, die Freiheit als Risiko des Widerspruchs und das für die Freiheit notwendige komplementäre Vertrauen, in den digitalen Bestätigungswelten verflüchtigen.
Die zunehmende Durchdringung nahezu aller Lebensbereiche der Gesellschaft mit neuen digitalen Technologien, insbesondere mit künstlicher Intelligenz, hat zur Entstehung von smarten Ordnungen geführt. Darunter werden Ordnungen verstanden, die darauf ausgerichtet sind, durch intelligentes Design und mit Hilfe algorithmischer Operationen Abweichungen von ihren Normen zu minimieren oder ganz unmöglich zu machen. Der Beitrag erläutert einige Beispiele smarter Ordnungen und zeigt auf, dass zumindest im Grundsatz zwischen einer algorithmisch optimierten, normadressatenorientierten Prävention und einer adressatensubstituierenden Präemption abweichenden Verhaltens durch digitale Technologien unterschieden werden kann. Den Schwerpunkt des Beitrags bildet sodann die Frage ob und, gegebenenfalls, in welchem Sinne, smarte Ordnungen überhaupt noch normative Ordnungen sind. Im Verlauf der Analyse zeigt sich, dass Rechtsordnungen und andere normative Ordnungen zwar das Ziel einer effektiven Durchsetzung ihrer Normen verfolgen, aber nicht das Ideal vollständiger Nicht-Abweichung. Es wird deutlich, dass es zu den wesentlichen Aspekten normativer Ordnungen gehört, dass sie an Personen adressiert sind, die sie sich als autonome und zugleich fehlbare Personen zu eigen machen müssen und dabei unvermeidlich über die faktische Freiheit zur Normabweichung verfügen. Smarte Ordnungen hingegen erfüllen diese Kriterien nicht oder nur in geringem Maße. Letztlich sind sie nur in einem schwachen Sinne normativ, soweit die in technischen Prozessen implementierte Normativität für die Betroffenen noch präsent ist. In dem Maße jedoch, wie Normativität und ihre technische Realisation sich vermischen, bis ihre erfahrbare Präsenz abnimmt, verlieren sie ihren normativen Charakter.
Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry.
Methods:Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria.
Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive.
Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials.
Trial registration: Clinicaltrials, NCT02338167, Registered 14 January 2015 - retrospectively registered.