Deciphering the spatiotemporal dynamics of intestinal aging in vertebrates using the African turquoise killifish

Aging is the major risk factor for many top-killing diseases and represents a problem for both the individual and the society. How the aging process is influenced and causally connected to microbiota is an emerging research area, with far-reaching findings obtained within the past few years. However, major underlying connections still remain elusive, in part hindered by a lack of suitable experimental model systems. The turquoise killifish is an ideal model to fill this gap and study microbiota in the context of aging, as it uniquely combines a very short lifespan with vertebrate features, such as a complex gut microbiota. However, knowledge about the killifish intestinal characteristics and gut microbiota is largely absent. Important key aspects I address include a detailed definition of aging dynamics, a characterization of gut compartmentalization and sex-specific intestinal traits, as well as the question whether non-invasive stool samples could be experimentally utilized for assessment of gut microbiota features. I thus set out to characterize killifish spatiotemporal aging dynamics and sex-specific intestinal microbial and molecular patterns by performing multi-omics analyses on intestinal sections of young and old, male and female killifish. I found strong evidence for a compartmentalization of the killifish intestine on a molecular and morphological level, with specific functions that can also be found in the mammalian intestine. Surprisingly, I did not observe section-specific microbial communities in contrast to findings from other animals including fish. I detected compelling evidence for extracellular matrix restructuring in the aged killifish intestine, with an accumulation of collagen and an increase in muscle thickness, possibly impeding the intestinal function in old fish. For the first time, I showed that the killifish intestine exhibits sex-specific molecular traits, especially concerning the coagulation process. Moreover, I asked whether non-invasive stool samples can be used as a proxy for gut microbiota by collecting microbiota samples of stool, intestinal and food samples. In addition, I set out to explore whether stool samples can be utilized to build models predicting fish age or remaining life by conducting a longitudinal collection of individual stool samples along killifish life. Excitingly, I discovered shared microbial features between stool and gut microbiota and showed for the first time that a series of stool microbial samples in combination with a machine learning approach allows prediction of both age and lifespan. My studies not only set the ground for future research on killifish gut microbiota, but provide novel promising results highlighting the importance of gut microbiota research in the context of aging

The Gnostic Myth: Protology

L’estudi presenta les característiques essencials de la protologia gnòstica. En fer-ho, es presenten les tendències de la recerca actual, les quals miren d’evitar generalment el terme «Gnosis», i volen entendre la correlació dels fenòmens com indicis del primitiu judaisme o del misticisme del primer cristianisme.The study presents essential characteristics of Gnostic protology. In doing so, it discusses currents of present Gnosis research which generally try to avoid the term “Gnosis” and want to understand correlating phenomena as traces of early Jewish or early Christian mysticism

Evaluation of the effects of behavioral skills training on practitioner play skills

Behavioral skills training (BST) has been demonstrated through research to be an effective method for teaching skill acquisition (Buck, 2014). Oftentimes, BST is used with caregivers to teach them how to implement clinical treatments outside of the clinical setting and in their homes. Another way that BST is used is when training applied behavior analysis (ABA) interventionists for their career. This study evaluated the effects of BST on implementer play skills. Additionally, this study evaluated the conditions under which skill acquisition and generalization occur and if BST was an effective method for increasing the percentage of play skills implemented correctly by a practitioner. The purpose of this study was to evaluate the effectiveness of BST to increase the percentage of play skills implemented correctly by a practitioner. Two female RBTS in their early twenties were used as participants. The study consisted of a baseline condition, BST, post-BST condition, and maintenance condition. The results of this study suggest that BST was effective at teaching play skills to the two participants. It also suggests that BST could be used to teach play skills to autism practitioners.Includes bibliographical references

Novel insights into the regulation of nucleolar function and longevity by ncl-1

The nucleolus is primarily described as the control center for ribonuclear protein assembly and rRNA synthesis. However, there is increasing evidence that the nucleolus also plays a role in protein quality, genome stability and cell cycle progression. Previous studies demonstrated that the B-box type zinc finger protein ncl- 1 is tightly linked to nucleolar function, and that its loss leads to increased levels of the nucleolar marker fibrillarin (fib-1) and to an increased nucleolar area. These nucleolar phenotypes are accompanied by the abolishment of lifespan extension in the major longevity pathways. However, the molecular connection between ncl-1, nucleolar function and longevity remains elusive. To identify molecular players and pathways that mediate the function of ncl-1 on longevity, I performed transcriptomic and proteomic analysis, comparing wild-type worms to ncl-1 worms in normal as well as the long-lived glp-1 background. This analysis revealed some shared and some background-specific regulation of distinct biological pathways upon loss of ncl-1: While nuclear outputs such as ribosome biogenesis and rRNA production are increased in multiple tested genotypes, proteasomal components are decreased in ncl-1 single mutants, while lysosomal components show lower abundance in glp-1;ncl-1. Interestingly, NCL-1 seems to affect at least a portion of regulated genes through direct binding of respective mRNAs. Based on transcriptomic and proteomic data, I conducted a follow-up RNA interference screen of potential mediators and uncovered nucleolar downstream processes of ncl- 1 including the RNase P/MRP complex and mitochondrial translation. Knockdown of the shared RNase P/MRP component POPL-1 as well as other RNase P/MRP factors extended lifespan in glp-1;ncl-1 mutants. The same was observed for other rRNA processing and ribosome assembly factors as well as proteins involved in mitochondrial translation such as MRPS-16. Reduction of popl-1 and mrps-16 extended lifespan independent of nucleolar size, fib-1 mRNA levels or steady state rRNA levels, thereby uncoupling nucleolar size from lifespan for the first time. Also, overall translation rate seems unaffected. Thus, the effect of NCL-1 on lifespan may be mediated through altered ribosome assembly in glp-1 worms, while being unaffected in the N2 background. To further investigate the molecular mechanism of NCL-1 action, I conducted a Yeast- 2-Hybrid assay and pulldown experiments to identify NCL-1 protein interactors. In a mini RNAi screen, I found that a reduction of the potential NCL-1 interactor and proteasomal factor RPN-11 affects nucleolar size in glp-1 mutants, indicating a direct connection of NCL-1 to the proteasome. In line with this, ncl-1 affects cellular proteostasis with the proteasome as a presumable key player, as ncl-1 mutants are short-lived under modest thermal stress and are less motile. In addition, I observed that overall ubiquitinylation levels are increased, and that proteasome substrates accumulate in ncl-1 mutants. In the pulldown experiments with NCL-1, I identified several mitochondrial factors in the co-enriched fraction of NCL-1. I also found that NCL-1 forms round network-like structures and strong foci resembling mitochondria within the hypodermis and muscle, further supporting a mitochondrial connection. Further on I established a connection between the RNAi machinery, nucleolar size and lifespan with a central focus on the argonaut protein NRDE-3 being required for longevity and affecting nucleolar size. Using a range of genetic and biochemical approaches, I found that ncl-1 is a multifaceted gene that connects multiple important cellular pathways with a focus on nucleolar outputs, but also proteolytic processes. I identified the RNase P/MRP complex and mitochondrial translation as potential key processes for mediating the function of ncl-1 in longevity

Analysis Of The Relevance Of Models, Influencing Factors And The Point In Time Of The Forecast On The Prediction Quality In Order-Related Delivery Time Determination Using Machine Learning

One of the main objectives of manufacturing companies that structure their manufacturing system according to the workshop principle is to meet the delivery dates communicated to the customer. One approach to avoid large delivery time buffers to stabilize liability of communicated delivery dates is to improve the forecasting quality of the initially determined planned delivery dates. In this context, machine learning methods are a promising approach for the dynamic, order-related forecasting of delivery times. In the development process of machine learning based applications for delivery time forecasting companies are challenged by the following questions: which influencing factors must be considered? Which machine learning models generate the best forecast quality? At what point in the production process does the application of machine learning methods for delivery time forecasting make sense from an economic perspective? Existing approaches do not adequately address these questions. In most cases, only few process steps are considered and only throughput times are forecasted instead of delivery times. The information available at the point in time when the delivery time is forecasted is not discussed. The considered input factors influencing the delivery time are reduced to the company's internal supply chain and therefore do not allow for a satisfactory forecast quality of the delivery time. External influencing factors are often not included. Therefore, this paper describes the influence of different machine learning models, different points in time for the forecasting itself and included influencing factors on the achievable forecast quality. The influence is determined by applying machine learning methods on delivery time forecasting to five real-world use cases

Nahtoderfahrungen als Zugänge zum Platonismus und zum frühen Christentum

Jene Erfahrungsmuster, die heute als ›Nahtoderfahrungen‹ (NTE) bezeichnet werden, begegnen in unterschiedlichsten Kulturen und Epochen. In dem vorliegenden Beitrag werden zwei kulturgeschichtlichen Vergleichsgrößen betrachtet, deren Affinität zu NTE seit den Anfängen einer modernen Auseinandersetzung mit diesen Phänomenen diskutiert werden. Einerseits wird erörtert, inwiefern zentrale Aspekte der platonischen Philosophie als eine Verarbeitung von NTE gedeutet werden können, andererseits wird zur Geltung gebracht, in welcher Weise die Lebenswende des Paulus – die sogenannte Damaskuserfahrung – mit solchen Phänomenen verglichen werden kann.Those patterns of experience that are now referred to as ›Near-Death Experiences‹ (NDE) occur in a wide variety of cultures and epochs. In the present article, two cultural-historical parallels are considered, whose affinity to NDE has been discussed since the beginning of a modern examination of these phenomena. On the one hand, the extent to which central aspects of Platonic philosophy can be interpreted as a processing of NDE is discussed, and on the other hand, the way in which Paul's turning point in life – the so-called Damascus experience – can be compared with such phenomena is discussed

Grenzarbeiten auf der Nulllinie: Nahtoderfahrung als Gegenstand, Begriff, Konzept

Nachdem Nahtoderfahrungen (NTE) im Diskurs westlicher Gesellschaften inzwischen kein Nischenthema mehr sind, sondern bereits vielfach medial rezipiert und verbreitet wurden und werden, sind die Potentiale der wissenschaftlichen Erforschung des Themas noch bei Weitem nicht ausgeschöpft. Dies mag nicht zuletzt etwas damit zu tun haben, dass die Auseinandersetzung mit NTE vielleicht mehr als andere Themen etablierte Wissenschaftsverständnisse herausfordert. Der vorliegende Band macht daher drei Vorschläge zur Neuperspektivierung des Themas und zur Fortsetzung der begonnenen Diskussion: Gefragt werden soll nach der Aushandlung von Grenzen, nach ›Nahtoderfahrungen‹ als einem wissenschaftlichen Konzept und nach den Potentialen interdisziplinärer Arbeit. Hierzu werden Beiträge aus unterschiedlichen wissenschaftlichen Disziplinen wie etwa der Religionswissenschaft, der Theologie, der Soziologie und der Medizin versammelt, die sich aus ihrer je fachspezifischen Sicht mit dem Thema auseinandersetzen.Since near-death experiences (NDEs) are no longer a niche topic in the discourse of Western societies, but have already been and are being widely received and disseminated in the media, the potentials of scientific research on the topic are far from being exhausted. This may have something to do, not least, with the fact that dealing with NDEs challenges established understandings of science perhaps more than other topics. The present anthology therefore makes three proposals for a new perspective on the topic and for continuing the discussion that has already begun: It will ask about the negotiation of boundaries, about ›near-death experiences‹ as a scientific concept, and about the potentials of interdisciplinary work. For this purpose, contributions from different scientific disciplines such as religious studies, theology, sociology, and medicine will be gathered, each of them dealing with the topic from their own specific view

›Nahtoderfahrungen‹. Ein wissenschaftliches Mysterienspiel heute: Interview mit Dieter Vaitl vom 11. November 2017

Dieter Vaitl geht davon aus, dass es sich bei ›Nahtoderfahrungen‹ (NTE) um eine sehr heterogene, begrifflich schwer zu fassende Ansammlung von Phänomenen handelt, die keinesfalls nur in Todesnähe auftreten. Sie sollten deswegen besser innerhalb des wesentlich breiteren Spektrums veränderter Bewusstseinszustände denn als isoliertes Phänomen beschrieben werden. Ihre Komplexität ist vor allem methodologisch eine Herausforderung für die Forschung, die sich dem Thema daher am besten über mehrdimensional angelegte Ansätze widmen sollte. Dieses Potential wurde bislang jedoch noch gar nicht ausgeschöpft. Vaitl sieht daher keinen Grund, aus den bestehenden Erklärungsschwierigkeiten ›Beweisspektakel‹ zugunsten eines Glaubens an jenseitige Wirklichkeiten abzuleiten.In this interview, Dieter Vaitl assumes that ›Near-Death Experience‹ (NDE) is a very heterogeneous collection of phenomena that are difficult to conceptualize and that by no means only occur near death. NDE are therefore better described within the much broader spectrum of altered states of consciousness, rather than as an isolated phenomenon. Their complexity is above all a methodological challenge for research, which should therefore best address the topic using multidimensional approaches. However, this potential has not yet been fully exploited. Vaitl therefore sees no reason to derive from the existing difficulties in explanation an ›evidence spectacle‹ in favor of a belief in otherworldly realities

Medizinische Forschung zu Tod und Bewusstsein: Interview mit Pim van Lommel vom 2. August 2017

Das Herz steht still, die Atmung ist ausgefallen. Die Diagnose lautet: klinisch tot. Kann man in einem solchen Zustand noch etwas wahrnehmen? Ja, sagt der Kardiologe Pim van Lommel. Denn sehr viele Menschen, die aufgrund einer ernsten Erkrankung, eines Herzstillstands oder eines Unfalls an der Schwelle zum Tod standen, berichten nach ihrer Genesung von außergewöhnlichen Bewusstseinserfahrungen: Sie nahmen eine wunderschöne Landschaft und ein heilsames Licht wahr und empfanden unbeschreibbare Glücksgefühle. Sie sahen sich selbst von oben und konnten nachher über Details der Umgebung Auskunft geben – und dass trotz ihrer Bewusstlosigkeit. Das paradoxe Ereignis von erhöhtem Bewusstsein wird heute ›Nahtoderfahrung‹ (NTE) genannt. Aber auf der Basis unserer aktuellen medizinischen Konzepte ist es nicht möglich, Bewusstsein bei Herzstillstand nach Beendigung von Blutkreiskauf und Atmung zu erfahren. Wie ist das trotzdem möglich? Pim van Lommel fand heraus, dass das Bewusstsein nicht an einen funktionierenden Körper gebunden sein muss. Es gibt gute Gründe dafür anzunehmen, dass unser Bewusstsein nicht immer mit dem Funktionieren unseres Gehirns übereinstimmt. Van Lommels These lautet: Das Gehirn fungiert nur als Empfänger eines endlosen Bewusstseins, das nach dem Tod nicht aufhört zu existieren. Denn selbst wenn das Gehirn nachweislich nicht mehr funktioniert, können Menschen über ein klares Bewusstsein verfügen. Seine Erkenntnisse sind spektakulär und zwingen uns, über Leben und Tod und über die bisher üblichen Erklärungsmodelle der Beziehung zwischen Gehirn und Bewusstsein neu nachzudenken.In this interview, Pim van Lommel argues that according to our current medical concepts it is not possible to experience consciousness during a cardiac arrest when circulation and breathing have ceased. But during the period of unconsciousness due to a cardiac arrest or coma, patients may report the paradoxical occurrence of enhanced consciousness, with cognitive functions, with emotions, with self-identity, with memories from early childhood and sometimes with perception out and above their lifeless body. This is called a ›Near-Death Experience‹ (NDE). In a prospective study on NDE by Pim van Lommel, as published in The Lancet, it could not be shown that physiological (anoxia), psychological, pharmacological or demographic factors could explain the cause and content of these experiences. According to this study, the current materialistic view of the relationship between the brain and consciousness held by most physicians, philosophers, and psychologists is too restricted for a proper understanding of this phenomenon. Pim van Lommel argues that there are now good reasons to assume that our consciousness does not always coincide with the functioning of our brain. As he elaborates in this interview, van Lommel has come to the inevitable conclusion that most likely the brain must have a facilitating and not a producing function to experience consciousness. By making a scientific case for consciousness as a nonlocal and thus ubiquitous phenomenon we must question a purely materialist paradigm in science. Moreover, recent research on NDE seems to be a source of new insights into the possibility of a continuity of our consciousness after physical death