Improving the effectiveness of anti-aging modalities by using the constrained disorder principle-based management algorithms

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

Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule

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

Investigating the Relationship Between Sleeping Brain Activity and Neural Differentiation of Competing Memories

To accurately remember information from our past, we must not forget it and we must not confuse it with related information. In other words, we want our memories to be stable in our brain’s long-term storage and to be organized in such a way that we can access them without interference from competing memories. Memory models suggest that memory reactivation, which can occur during either wakefulness or sleep, is the key to stabilizing long-term memories and differentiating them from competing ones. In regards to sleep specifically, there is evidence that non-rapid eye movement (NREM) sleep spindle events and rapid eye movement (REM) sleep are linked to memory reactivation. Here, we used a pre-existing fMRI dataset to measure how much two memory representations move apart from one another, a measure called neural differentiation (study design by Dr. K Norman and Dr. E McDevitt; data collection by Dr. E McDevitt). We investigated if spindles and REM sleep, which occurred during an intervening period of sleep between neural measurements, were correlated with neural differentiation using EEG data and source localization techniques. We contrasted periods of spindle activity with equivalent periods of non-spindle activity to spatially localize brain areas with spindle-related activity during NREM sleep and found that neural differentiation was not significantly correlated with spindle activity. Next, we contrasted periods of phasic REM sleep (the segments of REM sleep containing rapid eye movements) with periods of tonic REM sleep to spatially localize REM-related brain activity. Neural differentiation was most strongly, though not significantly, correlated with REM activity localized to the superior frontal gyrus, though our REM pipeline needs to be re-evaluated. We also investigated if the relationship between NREM spindle activity and neural differentiation required a subsequent period of REM sleep. We examined the correlation of spindles and neural differentiation in two experimental nap groups, a NREM sleep only group and a NREM+REM sleep group. A number of small areas had a significantly higher correlation in the NREM+REM nap group compared to the NREM only group, but further analyses is needed to evaluate if these results are significantly different from chance. Finally, we discussed these results in the context of how understanding basic mechanisms of memory transformation during sleep can inform hypotheses about how sleep might be related to memory impairments in disease states (e.g., Alzheimer’s disease)

The rules for deciding halakha in the Talmud.

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Effect of Nanoparticle Dimensionality on Fluorescence Resonance Energy Transfer in Nanoparticle–Dye Conjugated Systems

Fluorescence resonance energy transfer (FRET) involving a semiconductor nanoparticle (NP) acting as a donor, attached to multiple acceptors, is becoming a common tool for sensing, biolabeling, and energy transfer applications. Such nanosystems, with dimensions that are in the range of FRET interactions, exhibit unique characteristics that are related to the shape and dimensionality of the particles and to the spatial distribution of the acceptors. Understanding the effect of these parameters is of high importance for describing the FRET process in such systems and for utilizing them for different applications. In order to demonstrate these dimensionality effects, the FRET between CdSe/CdS core/shell NPs with different geometries and dimensionalities and Atto 590 dye molecules acting as multiple acceptors covalently linked to the NP surface is examined. Steady-state emission and temporal decay measurements were performed on the NPs, ranging from spherical to rod-like shaped systems, as a function of acceptor concentration. Changes in the NP geometry, and consequently in the distributions of acceptors, lead to distinctively different FRET behaviors. The results are analyzed using a modified restricted geometries model, which captures the dimensionality of the acceptor distribution and allows extracting the concentration of dye molecules on the surface of the NP for both spherical and elongated NPs. The results obtained from the model are in good agreement with the experimental results. The approach may be useful for following the spatial dynamics of self-assembly and for a wide variety of sensing applications

Dimensionality Effects on Fluorescence Resonance Energy Transfer between Single Semiconductor Nanocrystals and Multiple Dye Acceptors

Colloidal semiconductor nanocrystals are outstanding donors in energy transfer processes due to their unique size and shape dependent optical properties, their exceptional photostability, and chemical processability. We examine the dimensionality effect in energy transfer between single heterostructure nanocrystals of spherical and rod shape, serving as donors, and multiple dye molecules attached to their surface acting as acceptors. Förster resonant energy transfer (FRET) to individual dyes attached to the surface of a single nanocrystal is identified via step-like changes in both acceptor and donor emission, enabling to calculate the efficiency of energy transfer and distance of each acceptor individually. This offers a unique tool to study the surface chemistry of various nanocrystals. The dimensionality of the nanocrystals is reflected by the acceptors distribution, which enables to study the inner geometry of these heterostructures, such as the location of the seed and shell thickness. Additionally, the nanocrystals serve as an optical antenna that enhances the excitation and emission of the dye molecules through the FRET interaction. These measurements enable to gain deeper understanding of the energy transfer process between semiconductor nanocrystals of various geometries and dye molecules and promote its utilization for extremely sensitive sensing applications at the single molecule level