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This article will take Jan Patočka’s concepts of care for the soul and sacrifice for nothing as a starting point to discuss the ontological premises of a renewed epimeleia heautou, or care of the self. I will argue that Patočka understands the ancient Good in terms of Heidegger’s ontological difference. Care for the soul thus ends up with an empty transcendence. In contrast, I will advocate a hyperbolic concept of Being. All that exists is characterized by being beyond beingness, an inner transcendence of itself. This provides new ontocosmological as well as political perspectives.

Epidemiological studies indicate that the consumption of caffeine, the most commonly ingested psychoactive substance found in coffee, tea or soft drinks, reduces the risk of developing Alzheimer’s disease (AD). Previous treatment studies with transgenic AD mouse models reported a reduced amyloid plaque load and an amelioration of behavioral deficits. It has been further shown that moderate doses of caffeine have the potential to attenuate the health burden in preclinical mouse models of a variety of brain disorders (reviewed in Cunha in J Neurochem 139:1019–1055, 2016). In the current study, we assessed whether long-term caffeine consumption affected hippocampal neuron loss and associated behavioral deficits in the Tg4-42 mouse model of AD. Treatment over a 4-month period reduced hippocampal neuron loss, rescued learning and memory deficits, and ameliorated impaired neurogenesis. Neuron-specific RNA sequencing analysis in the hippocampus revealed an altered expression profile distinguished by the up-regulation of genes linked to synaptic function and processes, and to neural progenitor proliferation. Treatment of 5xFAD mice, which develop prominent amyloid pathology, with the same paradigm also rescued behavioral deficits but did not affect extracellular amyloid-β (Aβ) levels or amyloid precursor protein (APP) processing. These findings challenge previous assumptions that caffeine is anti-amyloidogenic and indicate that the promotion of neurogenesis might play a role in its beneficial effects. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-04062-8.

This essay follows the assumption that the first principle of classical metaphysics has its counterpart in political sovereignty as suprema potestas. Therefore, both can be equally described as arché. Their epitome is the God of so-called ontotheology, who thus proves to be what I call the Ur-Arché. In contrast to current post-metaphysical approaches, however, I suggest overcoming ontotheology through a different metaphysics, which emphasizes the self-transcending surplus character of being. I regard early Christian martyrdom as an eminent way in which the surplus of being is manifested. This has two interwoven aspects, one ontological and one political, both arising from the excessive idea of the Christ event, or the notion that there is life beyond life unto death. I will analyse the mechanism allowing early Christian martyrs to counteract Roman imperial sovereignty. Finally, I will relate this to contemporary life systems in which sovereignty has become anonymous biopower.

Brain accumulation and aggregation of amyloid-β (Aβ) peptides is a critical step in the pathogenesis of Alzheimer's disease (AD). Full-length Aβ peptides (mainly Aβ1-40 and Aβ1-42) are produced through sequential proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. However, studies of autopsy brain samples from AD patients have demonstrated that a large fraction of insoluble Aβ peptides are truncated at the N-terminus, with Aβ4-x peptides being particularly abundant. Aβ4-x peptides are highly aggregation prone, but their origin and any proteases involved in their generation are unknown. We have identified a recognition site for the secreted metalloprotease ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) in the Aβ peptide sequence, which facilitates Aβ4-x peptide generation. Inducible overexpression of ADAMTS4 in HEK293 cells resulted in the secretion of Aβ4-40 but unchanged levels of Aβ1-x peptides. In the 5xFAD mouse model of amyloidosis, Aβ4-x peptides were present not only in amyloid plaque cores and vessel walls, but also in white matter structures co-localized with axonal APP. In the ADAMTS4-/- knockout background, Aβ4-40 levels were reduced confirming a pivotal role of ADAMTS4 in vivo. Surprisingly, in the adult murine brain, ADAMTS4 was exclusively expressed in oligodendrocytes. Cultured oligodendrocytes secreted a variety of Aβ species, but Aβ4-40 peptides were absent in cultures derived from ADAMTS4-/- mice indicating that the enzyme was essential for Aβ4-x production in this cell type. These findings establish an enzymatic mechanism for the generation of Aβ4-x peptides. They further identify oligodendrocytes as a source of these highly amyloidogenic Aβ peptides.

Sandra Lehmann continues on the previous discussion of the ontological grounding of truth by comparing Desmond’s metaxology to the revival of metaphysics in the New Realism of Quentin Meillassoux. While noting the superficial similarities between these philosophical projects, Lehmann clarifies that metaxology provides a more robust alternative to the anti-metaphysical philosophies of finitude of the twentieth century. Particularly prominent in her argument is that Meillassoux’s discussion of the ground of being does not allow him to escape the shadow of Heidegger’s critique of metaphysics, which is something more ably accomplished by metaxology.

Apple Malus × domestica Borkh. has a long period of juvenility during which plants are unable to produce flowers and fruits. Flowering is only possible on trees which have passed the transition from juvenility to the adult stage. Several genes have been identified which control this switch and promote or delay flowering in different plant species. FLOWERING LOCUS T (FT) and TERMINAL FLOWER 1 (TFL1) are two flowering genes of Arabidopsis which are similar, but act antagonistically. FT and TFL1 homologous genes are present in the apple genome, but little is known about their function. Therefore we produced transgenic apple lines which over-expressed the MdFT2 gene under the control of the constitutive CaMV 35S promoter. Transgenic shoots expressing the MdFT2 gene driven by the CaMV 35S promoter flowered in vitro. To study the function of MdTFL1 we silenced the gene by expressing an MdTFL1 specific hairpin under the control of the CaMV 35S promoter. Transgenic plants of different apple cultivars flowered in vitro and later in the greenhouse. Transgenic flowers were evaluated for phenotypic differences and tested on their usability for crossbred breeding programs.

Meristems in apple have to pass the vegetative and the reproductive phase change before they can produce flowers. In the previous ten years several genes of apple were identified which are homologous/orthologous to flowering genes of Arabidopsis thaliana. In relation to results obtained in Arabidopsis, the apple genes MdCOL1, MdCOL2, MdFT, MdSOC1, AFL1, AFL2, MdMADS2, MdMADS5, MdTFL1-1 and MdTFL1-2 are potential candidates to be involved in the vegetative and/or reproductive phase change. Gene transcript analyses were performed in leaves of juvenile apple seedlings from a ‘Braeburn’ × ‘Pisaxa’ progeny to evaluate the role of these genes in the vegetative phase change. These analyses revealed an increase of MdFT, AFL1, AFL2 and MdTFL1 mRNA expression in leaves related to the ascending node number suggesting a potential function in the vegetative transition terminated between the 70th and 80th node. Furthermore, we studied seasonal changes of gene transcription in adult apple tree meristems and we showed that activation of AFL1/2, MdMADS2, MdFT, MdSOC1 and suppression of MdTFL1-1/1-2 are involved in the reproductive phase change occurring at the end of May. We also over-expressed MdFT, a homologue of the predicted florigen FT from A. thaliana, in order to determine the function of MdFT. Overexpression of MdFT in Arabidopsis accelerated flowering, whereas flowers were not detected in MdFT transgenic apple lines growing in vitro and for the first year in greenhouse.

In this contribution Lehmann argues for a strong concept of political subjectivation. In doing so, she proposes to develop the thesis that for a complete ‘thinking’ of political subjectivation, a metaphysical dimension must be opened up. However, this metaphysics is not a static one of substance, according to which political subjects would find themselves assigned a specific identity. Rather, it is about inner excess, an inner transcendence of being, which implies that in a positive sense beings are not identical with themselves, i.e., that every being transcends its actual appearance in an open, qualitative sense. The metaphysics that Lehmann conceives pursues this inner transcendence, and is thus dynamic: it is metaphysical movement.

The protein encoded by the FLOWERING LOCUS T (FT) gene from Arabidopsis thaliana seems to be the long-searched florigen, and over-expression of FT orthologues resulted in accelerated flower development in annual and perennial plants. In the present study, we isolated two allelic mRNA sequences of an FT-homologous gene from apple, which was designated as MdFT1. Using a SSR motif this gene was mapped on LG 12 of apple. Over-expression of MdFT1 in Arabidopsis and the commercially important tree species poplar and apple itself using the CaMV 35S or the Arabidopsis Suc2 promoter resulted in significant accelerated flowering compared with wild-type plants. Transgenic T(0) plants of Arabidopsis flowered 4-6 days on average earlier than wild-type Arabidopsis under LD conditions. Under short-day conditions Suc2::MdFT1 plants of the T(1)-generation flowered after 66 ± 18 days, while wild-type plants flowered about 22 days later. All transgenic Arabidopsis plants showed a normal habit except for the early flowering phenotype. Early flowering was detected 6-10 months after transformation in transgenic polar clones containing MdFT1 driven by the CaMV 35S, whereas plants of the transgenic apple clone T780 set up its first flowers during in vitro cultivation. Based on our results we conclude that MdFT1 is responsible for inducing flowering and that the function of the apple FT1 gene is conserved in annual herbaceous species as well as perennial woody species. Furthermore, we discuss the role of MdFT1 in flower development with regard to the findings of genetic studies on apple.

Little is known about the initial stages of information processing in amnesia as compared to normal memory. In this study, we used electrical spatiotemporal mapping to compare cortical activation during encoding and recognition in a 56-year-old patient with severe, chronic post-anoxic amnesia and an age-matched control group. Event-related potentials were recorded as the subjects performed a continuous recognition task composed of meaningful designs. Activation in the control group rapidly progressed through eight different electrocortical configurations over 700 ms after onset of new stimuli. In contrast, activation in the amnesic patient was highly monotonous: it showed varying electrocortical patterns only during the first 150 ms but then remained abnormally stable for the remainder of the analysed time window. Electrical source localisation revealed that the patient failed to activate distributed cortical networks and that his processing was confined to visual areas. The present study suggests that the rapid activation of distributed cortical networks is critical for efficient encoding.

Past multisensory experiences can influence current unisensory processing and memory performance. Repeated images are better discriminated if initially presented as auditory-visual pairs, rather than only visually. An experience's context thus plays a role in how well repetitions of certain aspects are later recognized. Here, we investigated factors during the initial multisensory experience that are essential for generating improved memory performance. Subjects discriminated repeated versus initial image presentations intermixed within a continuous recognition task. Half of initial presentations were multisensory, and all repetitions were only visual. Experiment 1 examined whether purely episodic multisensory information suffices for enhancing later discrimination performance by pairing visual objects with either tones or vibrations. We could therefore also assess whether effects can be elicited with different sensory pairings. Experiment 2 examined semantic context by manipulating the congruence between auditory and visual object stimuli within blocks of trials. Relative to images only encountered visually, accuracy in discriminating image repetitions was significantly impaired by auditory-visual, yet unaffected by somatosensory-visual multisensory memory traces. By contrast, this accuracy was selectively enhanced for visual stimuli with semantically congruent multisensory pasts and unchanged for those with semantically incongruent multisensory pasts. The collective results reveal opposing effects of purely episodic versus semantic information from auditory-visual multisensory events. Nonetheless, both types of multisensory memory traces are accessible for processing incoming stimuli and indeed result in distinct visual object processing, leading to either impaired or enhanced performance relative to unisensory memory traces. We discuss these results as supporting a model of object-based multisensory interactions.