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The present review examines retrospective analyses of training intensity distribution (TID), i.e., the proportion of training at moderate (Zone 1, Z1), heavy (Z2) and severe (Z3) intensity by elite-to-world-class endurance athletes during different phases of the season. In addition, we discuss potential implications of our findings for research in this field, as well as for training by these athletes. Altogether, we included 175 TIDs, of which 120 quantified exercise intensity on the basis of heart rate and measured time-in-zone or employed variations of the session goal approach, with demarcation of zones of exercise intensity based on physiological parameters. Notably, 49% of the TIDs were single-case studies, predominantly concerning cross-country skiing and/or the biathlon. Eighty-nine TIDs were pyramidal (Z1 > Z2 > Z3), 65 polarized (Z1 > Z3 > Z2) and 8 “threshold” (Z2 > Z1 = Z3). However, these relative numbers varied between sports and the particular phases of the season. In 91% (n = 160) of the TIDs >60% of the endurance exercise was of low intensity. Regardless of the approach to quantification or phase of the season, cyclists and swimmers were found to perform a lower proportion of exercise in Z1 (<72%) and higher proportion in Z2 (>16%) than athletes involved in the triathlon, speed skating, rowing, running, cross-country skiing or biathlon (>80% in Z1 and <12% in Z2 in all these cases). For most of the athletes their proportion of heavy-to-severe exercise was higher during the period of competition than during the preparatory phase, although with considerable variability between sports. In conclusion, the existing literature in this area does not allow general conclusions to be drawn. The methods utilized for quantification vary widely and, moreover, contextual information concerning the mode of exercise, environmental conditions, and biomechanical aspects of the exercise is often lacking. Therefore, we recommend a more comprehensive approach in connection with future investigations on the TIDs of athletes involved in different endurance sports.
Here, we performed a non-systematic analysis of the strength, weaknesses, opportunities, and threats (SWOT) associated with the application of artificial intelligence to sports research, coaching and optimization of athletic performance. The strength of AI with regards to applied sports research, coaching and athletic performance involve the automation of time-consuming tasks, processing and analysis of large amounts of data, and recognition of complex patterns and relationships. However, it is also essential to be aware of the weaknesses associated with the integration of AI into this field. For instance, it is imperative that the data employed to train the AI system be both diverse and complete, in addition to as unbiased as possible with respect to factors such as the gender, level of performance, and experience of an athlete. Other challenges include e.g., limited adaptability to novel situations and the cost and other resources required. Opportunities include the possibility to monitor athletes both long-term and in real-time, the potential discovery of novel indicators of performance, and prediction of risk for future injury. Leveraging these opportunities can transform athletic development and the practice of sports science in general. Threats include over-dependence on technology, less involvement of human expertise, risks with respect to data privacy, breaching of the integrity and manipulation of data, and resistance to adopting such new technology. Understanding and addressing these SWOT factors is essential for maximizing the benefits of AI while mitigating its risks, thereby paving the way for its successful integration into sport science research, coaching, and optimization of athletic performance.
Universal prevention for non-suicidal self-injury in adolescents is scarce - A systematic review
(2023)
Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI.
In Burkitt lymphoma (BL), a tumor of germinal center B cells, the pro-apoptotic properties of MYC are controlled by tonic B cell receptor (BCR) signals. Since BL cells do not exhibit constitutive NF-κB activity, we hypothesized that anti-apoptotic NFATc1 proteins provide a major transcriptional survival signal in BL. Here we show that post-transcriptional mechanisms are responsible for the calcineurin (CN) independent constitutive nuclear over-expression of NFATc1 in BL and Eµ-MYC – induced B cell lymphomas (BCL). Conditional inactivation of the Nfatc1 gene in B cells of Eµ-MYC mice leads to apoptosis of BCL cells in vivo and ex vivo. Inhibition of BCR/SYK/BTK/PI3K signals in BL cells results in cytosolic re-location of NFATc1 and apoptosis. Therefore, NFATc1 activity is an integrated part of tonic BCR signaling and an alternative target for therapeutic intervention in BL.
Despite fine tuning voluntary movement as the most prominently studied function of the cerebellum, early human studies suggested cerebellar involvement emotion regulation. Since, the cerebellum has been associated with various mood and anxiety-related conditions. Research in animals provided evidence for cerebellar contributions to fear memory formation and extinction. Fear and anxiety can broadly be referred to as defensive states triggered by threat and characterized by multimodal adaptations such as behavioral and cardiac responses integrated into an intricately orchestrated defense reaction. This is mediated by an evolutionary conserved, highly interconnected network of defense-related structures with functional connections to the cerebellum. Projections from the deep cerebellar nucleus interpositus to the central amygdala interfere with retention of fear memory. Several studies uncovered tight functional connections between cerebellar deep nuclei and pyramis and the midbrain periaqueductal grey. Specifically, the fastigial nucleus sends direct projections to the ventrolateral PAG to mediate fear-evoked innate and learned freezing behavior. The cerebellum also regulates cardiovascular responses such as blood pressure and heart rate-effects dependent on connections with medullary cardiac regulatory structures. Because of the integrated, multimodal nature of defensive states, their adaptive regulation has to be highly dynamic to enable responding to a moving threatening stimulus. In this, predicting threat occurrence are crucial functions of calculating adequate responses. Based on its role in prediction error generation, its connectivity to limbic regions, and previous results on a role in fear learning, this review presents the cerebellum as a regulator of integrated cardio-behavioral defensive states.
Glycine receptor (GlyR) autoantibodies are associated with stiff-person syndrome and the life-threatening progressive encephalomyelitis with rigidity and myoclonus in children and adults. Patient histories show variability in symptoms and responses to therapeutic treatments. A better understanding of the autoantibody pathology is required to develop improved therapeutic strategies. So far, the underlying molecular pathomechanisms include enhanced receptor internalization and direct receptor blocking altering GlyR function. A common epitope of autoantibodies against the GlyRα1 has been previously defined to residues 1A-33G at the N-terminus of the mature GlyR extracellular domain. However, if other autoantibody binding sites exist or additional GlyR residues are involved in autoantibody binding is yet unknown. The present study investigates the importance of receptor glycosylation for binding of anti-GlyR autoantibodies. The glycine receptor α1 harbors only one glycosylation site at the amino acid residue asparagine 38 localized in close vicinity to the identified common autoantibody epitope. First, non-glycosylated GlyRs were characterized using protein biochemical approaches as well as electrophysiological recordings and molecular modeling. Molecular modeling of non-glycosylated GlyRα1 did not show major structural alterations. Moreover, non-glycosylation of the GlyRα1N38Q did not prevent the receptor from surface expression. At the functional level, the non-glycosylated GlyR demonstrated reduced glycine potency, but patient GlyR autoantibodies still bound to the surface-expressed non-glycosylated receptor protein in living cells. Efficient adsorption of GlyR autoantibodies from patient samples was possible by binding to native glycosylated and non-glycosylated GlyRα1 expressed in living not fixed transfected HEK293 cells. Binding of patient-derived GlyR autoantibodies to the non-glycosylated GlyRα1 offered the possibility to use purified non-glycosylated GlyR extracellular domain constructs coated on ELISA plates and use them as a fast screening readout for the presence of GlyR autoantibodies in patient serum samples. Following successful adsorption of patient autoantibodies by GlyR ECDs, binding to primary motoneurons and transfected cells was absent. Our results indicate that the glycine receptor autoantibody binding is independent of the receptor’s glycosylation state. Purified non-glycosylated receptor domains harbouring the autoantibody epitope thus provide, an additional reliable experimental tool besides binding to native receptors in cell-based assays for detection of autoantibody presence in patient sera.
The reversible condensation of catechols and boronic acids to boronate esters is a paradigm reaction in dynamic covalent chemistry. However, facile backward hydrolysis is detrimental for stability and has so far prevented applications for boronate-based materials. Here, we introduce cubic boronate ester cages 6 derived from hexahydroxy tribenzotriquinacenes and phenylene diboronic acids with ortho-t-butyl substituents. Due to steric shielding, dynamic exchange at the Lewis acidic boron sites is feasible only under acid or base catalysis but fully prevented at neutral conditions. For the first time, boronate ester cages 6 tolerate substantial amounts of water or alcohols both in solution and solid state. The unprecedented applicability of these materials under ambient and aqueous conditions is showcased by efficient encapsulation and on-demand release of β-carotene dyes and heterogeneous water oxidation catalysis after the encapsulation of ruthenium catalysts.
Conspectus
Nature has established a sustainable way to maintain aerobic life on earth by inventing one of the most sophisticated biological processes, namely, natural photosynthesis, which delivers us with organic matter and molecular oxygen derived from the two abundant resources sunlight and water. The thermodynamically demanding photosynthetic water splitting is catalyzed by the oxygen-evolving complex in photosystem II (OEC-PSII), which comprises a distorted tetramanganese–calcium cluster (CaMn\(_4\)O\(_5\)) as catalytic core. As an ubiquitous concept for fine-tuning and regulating the reactivity of the active site of metalloenzymes, the surrounding protein domain creates a sophisticated environment that promotes substrate preorganization through secondary, noncovalent interactions such as hydrogen bonding or electrostatic interactions. Based on the high-resolution X-ray structure of PSII, several water channels were identified near the active site, which are filled with extensive hydrogen-bonding networks of preorganized water molecules, connecting the OEC with the protein surface. As an integral part of the outer coordination sphere of natural metalloenzymes, these channels control the substrate and product delivery, carefully regulate the proton flow by promoting pivotal proton-coupled electron transfer processes, and simultaneously stabilize short-lived oxidized intermediates, thus highlighting the importance of an ordered water network for the remarkable efficiency of the natural OEC.
Transferring this concept from nature to the engineering of artificial metal catalysts for fuel production has fostered the fascinating field of metallosupramolecular chemistry by generating defined cavities that conceptually mimic enzymatic pockets. However, the application of supramolecular approaches to generate artificial water oxidation catalysts remained scarce prior to our initial reports, since such molecular design strategies for efficient activation of substrate water molecules in confined nanoenvironments were lacking. In this Account, we describe our research efforts on combining the state-of-the art Ru(bda) catalytic framework with structurally programmed ditopic ligands to guide the water oxidation process in defined metallosupramolecular assemblies in spatial proximity. We will elucidate the governing factors that control the quality of hydrogen-bonding water networks in multinuclear cavities of varying sizes and geometries to obtain high-performance, state-of-the-art water oxidation catalysts. Pushing the boundaries of artificial catalyst design, embedding a single catalytic Ru center into a well-defined molecular pocket enabled sophisticated water preorganization in front of the active site through an encoded basic recognition site, resulting in high catalytic rates comparable to those of the natural counterpart OEC-PSII.
To fully explore their potential for solar fuel devices, the suitability of our metallosupramolecular assemblies was demonstrated under (electro)chemical and photocatalytic water oxidation conditions. In addition, testing the limits of structural diversity allowed the fabrication of self-assembled linear coordination oligomers as novel photocatalytic materials and long-range ordered covalent organic framework (COF) materials as recyclable and long-term stable solid-state materials for future applications.
Wie weit kann ein christlicher Denker Avicenna folgen, wenn er dessen Ontologie zur Erklärung des Verhältnisses von Gott und Welt heranzieht? Dieser zentralen Frage der Avicenna-Rezeption widmet sich die vorliegende Arbeit.
Avicenna (Ibn Sīnā, 980–1037) entwickelt in der Metaphysik (al-Ilāhiyyāt) – dem vierten Teil seiner philosophischen Summe Buch der Heilung (Kitāb al-Šifāʾ) – den Grundgedanken seiner Ontologie: die Distinktion von Sein und Wesen, die zu einem seiner bekanntesten und einflussreichsten Lehrstücke wurde. Nach der lateinischen Übersetzung von Avicennas Metaphysik im zwölften Jahrhundert fand die darin entworfene Ontologie rasche Verbreitung unter den lateinisch-christlichen Gelehrten. Für deren monotheistische Weltanschauung war diese Lehre insofern attraktiv, als sich aus der Sein-Wesen-Distinktion die wichtigsten ontologischen Aspekte der Beziehung von Gott und Welt rein rational ableiten lassen. Vor diesem Hintergrund stellt sich die genannte Frage, wie weit ein christlicher Denker mit Avicenna gehen kann, wenn er dessen Ontologie heranzieht, um das Verhältnis von Gott und Welt zu erklären. Diese Frage untersucht die Autorin für die drei Gelehrten Dominicus Gundisalvi († nach 1190), Wilhelm von Auvergne († 1249) und Heinrich von Gent († 1293). Die Verschränkung von Ontologie, Theologie und Kosmogonie gibt der Autorin die Möglichkeit, für diese drei Bereiche jeweils herauszuarbeiten, an welchen Stellen und aus welchen Motiven Modifikationen an der avicennischen Theorie vorgenommen wurden, um sie eigenen Zwecken oder neuen Kontexten wie der Trinitätstheologie anzupassen. Zugleich zeigt sie auf, an welchen Punkten mit Avicennas Theorie gänzlich gebrochen wurde. Was bedeuten diese Änderungen und Brüche inhaltlich? Und insbesondere: Wie werden sie rational gerechtfertigt?