The formation of neuronal networks is governed by a limited number of guidance molecules, yet it is immensely complex. The complexity of guidance cues is augmented by posttranslational modification of guidance molecules and their receptors. We report here that cleavage of the floor plate guidance molecule F-spondin generates two functionally opposing fragments: a short-range repellent protein deposited in the membrane of floor plate cells and an adhesive protein that accumulates at the basement membrane. Their coordinated activity, acting respectively as a short-range repellant and a permissive short-range attractant, constricts commissural axons to the basement membrane beneath the floor plate cells. We further demonstrate that the repulsive activity of the inhibitory fragment of F-spondin requires its presentation by the lipoprotein receptor–related protein (LRP) receptors apolipoprotein E receptor 2, LRP2/megalin, and LRP4, which are expressed in the floor plate. Thus, proteolysis and membrane interaction coordinate combinatorial guidance signaling originating from a single guidance cue.

Aging is a complex biological process with multifactorial nature underlined by genetic, environmental, and social factors. In the present paper, we review several mechanisms of aging and the pre-clinically and clinically studied anti-aging therapies. Variability characterizes biological processes from the genome to cellular organelles, biochemical processes, and whole organs’ function. Aging is associated with alterations in the degrees of variability and complexity of systems. The constrained disorder principle defines living organisms based on their inherent disorder within arbitrary boundaries and defines aging as having a lower variability or moving outside the boundaries of variability. We focus on associations between variability and hallmarks of aging and discuss the roles of disorder and variability of systems in the pathogenesis of aging. The paper presents the concept of implementing the constrained disease principle-based second-generation artificial intelligence systems for improving anti-aging modalities. The platform uses constrained noise to enhance systems’ efficiency and slow the aging process. Described is the potential use of second-generation artificial intelligence systems in patients with chronic disease and its implications for the aged population.

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Objective: One of the tools to assess depression severity is the Patient Health Questionnaire (PHQ-9). Our aim was to investigate the correlation between PHQ-9 scores and fitness for work (FFW) in major depressive disorder (MDD). Methods: A cross-sectional study in patients who were evaluated for their FFW and later compared with PHQ-9. Results: Questionnaires were collected for 125 patients. A negative correlation between depression severity and absolute working ability (WA) was found for both women (β = –0.4, P < 0.001) and men (β = –0.4, P = 0.05). Multivariate linear regression revealed a negative correlation between WA and depression severity based on PHQ-9 scores (β = –0.4, P < 0.05). Conclusions: A negative correlation exists between absolute and relative WA and depression severity, meaning, with the higher severity of depression the lower the WA.