Efim Liberman (1925-2011) introduced in 1972 the idea of natural computation realized internally by living systems. He considered the physical principles employed by living systems as essential constraints that limit the computational process occurring in the course of adaptation, morphogenesis, and neural activity. The most general limits determined by the physical fundamental constants are universal for all nature. However, the more specific constraints are intrinsic to each biological system and can be overcome in the course of the evolutionary process. We discuss the roles of biological macromolecules, particularly the cytoskeleton, in shaping the actualization patterns formed in the internal measurement process occurring in living systems. Cytoskeletal rearrangements determine cellular, morphogenetic, and perceptive transformations in living systems and participate in the combinatorial genetic events that lead to evolutionary transformations. The operation of neurons is based on the transmission of signals via the cytoskeleton, where the digital output is generated that can be decoded through a reflexive action of the perceiving agent. It is concluded that the principles of natural computation formulated by Liberman represent the most fundamental feature of living beings and form the basis for the general theory of biological systems, with essential consequences for understanding metabolic closure, morphogenesis, evolution, and consciousness.

Neural stem cells (NSCs) persist in the adult mammalian brain and are able to give rise to new neurons and glia throughout life. The largest stem cell niche in the adult mouse brain is the ventricular-subventricular zone (V-SVZ) lining the lateral ventricles. Adult NSCs in the V-SVZ coexist in quiescent and actively proliferating states, and they exhibit a regionalized molecular identity. The importance of such spatial diversity is just emerging, as depending on their position within the niche, adult NSCs give rise to distinct subtypes of olfactory bulb interneurons and different types of glia. However, the functional relevance of stem cell heterogeneity in the V-SVZ is still poorly understood. Here, we put into perspective findings highlighting the importance of adult NSC diversity for brain plasticity, and how the body signals to brain stem cells in different physiological states to regulate their behavior.

Cell diversification is at the base of increasing multicellular organism complexity in phylogeny achieved during ontogeny. However, there are also functions common to all cells, such as cell division, cell migration, translation, endocytosis, exocytosis, etc. Here we revisit the organelles involved in such common functions, reviewing recent evidence of unexpected differences of proteins at these organelles. For instance, centrosomes or mitochondria differ significantly in their protein composition in different, sometimes closely related, cell types. This has relevance for development and disease. Particularly striking is the high amount and diversity of RNA-binding proteins at these and other organelles, which brings us to review the evidence for RNA at different organelles and suborganelles. We include a discussion about (sub)organelles involved in translation, such as the nucleolus and ribosomes, for which unexpected cell type-specific diversity has also been reported. We propose here that the heterogeneity of these organelles and compartments represents a novel mechanism for regulating cell diversity. One reason is that protein functions can be multiplied by their different contributions in distinct organelles, as also exemplified by proteins with moonlighting function. The specialized organelles still perform pan-cellular functions but in a cell type-specific mode, as discussed here for centrosomes, mitochondria, vesicles, and other organelles. These can serve as regulatory hubs for the storage and transport of specific and functionally important regulators. In this way, they can control cell differentiation, plasticity, and survival. We further include examples highlighting the relevance for disease and propose to examine organelles in many more cell types for their possible differences with functional relevance.

As microtubule-organizing centers, centrosomes direct assembly of the bipolar mitotic spindle required for chromosome segregation and genome stability. Centrosome activity requires the dynamic assembly of pericentriolar material (PCM), the composition and organization of which changes throughout the cell cycle. Recent studies highlight the conserved localization of several mRNAs encoded from centrosome-associated genes enriched at centrosomes, including Pericentrin-like protein (Plp) mRNA. However, relatively little is known about how RNAs localize to centrosomes and influence centrosome function. Here, we examine mechanisms underlying the subcellular localization of Plp mRNA. We find that Plp mRNA localization is puromycin-sensitive, and the Plp coding sequence is both necessary and sufficient for RNA localization, consistent with a co-translational transport mechanism. We identify regions within the Plp coding sequence that regulate Plp mRNA localization. Finally, we show that protein-protein interactions critical for elaboration of the PCM scaffold permit RNA localization to centrosomes. Taken together, these findings inform the mechanistic basis of Plp mRNA localization and lend insight into the oscillatory enrichment of RNA at centrosomes.

There are many gynecological diseases, among which breast cancer (BC), cervical cancer (CC), endometriosis (EMs), and polycystic ovary syndrome (PCOS) are common and difficult to cure. Stem cells (SCs) are a focus of regenerative medicine. They are commonly used to treat organ damage and difficult diseases because of their potential for self-renewal and multidirectional differentiation. SCs are also commonly used for difficult-to-treat gynecological diseases because of their strong directional differentiation ability with unlimited possibilities, their tendency to adhere to the diseased tissue site, and their use as carriers for drug delivery. SCs can produce exosomes in a paracrine manner. Exosomes can be produced in large quantities and have the advantage of easy storage. Their safety and efficacy are superior to those of SCs, which have considerable potential in gynecological treatment, such as inhibiting endometrial senescence, promoting vascular reconstruction, and improving anti-inflammatory and immune functions. In this paper, we review the mechanisms of the regenerative and anti-inflammatory capacity of SCs and exosomes in incurable gynecological diseases and the current progress in their application in genetic engineering to provide a foundation for further research.

The centrosome governs many pan-cellular processes including cell division, migration, and cilium formation. However, very little is known about its cell type-specific protein composition and the sub-organellar domains where these protein interactions take place. Here, we outline a protocol for the spatial interrogation of the centrosome proteome in human cells, such as those differentiated from induced pluripotent stem cells (iPSCs), through co-immunoprecipitation of protein complexes around selected baits that are known to reside at different structural parts of the centrosome, followed by mass spectrometry. The protocol describes expansion and differentiation of human iPSCs to dorsal forebrain neural progenitors and cortical projection neurons, harvesting and lysis of cells for protein isolation, co-immunoprecipitation with antibodies against selected bait proteins, preparation for mass spectrometry, processing the mass spectrometry output files using MaxQuant software, and statistical analysis using Perseus software to identify the enriched proteins by each bait. Given the large number of cells needed for the isolation of centrosome proteins, this protocol can be scaled up or down by modifying the number of bait proteins and can also be carried out in batches. It can potentially be adapted for other cell types, organelles, and species as well.

Mesoscale characteristics and their interdimensional correlation are the focus of contemporary interdisciplinary research. Mesoscience is a discipline that has the potential to radically update the existing knowledge structure, which differs from the conventional unit-scale and system-scale research models, revealing a previously untouchable area for scientific research. Integrative biology research aims to dissect the complex problems of life systems by conducting comprehensive research and integrating various disciplines from all biological levels of the living organism. However, the mesoscientific issues between different research units are neglected and challenging. Mesoscale research in biology requires the integration of research theories and methods from other disciplines (mathematics, physics, engineering, and even visual imaging) to investigate theoretical and frontier questions of biological processes through experiments, computations, and modeling. We reviewed  integrative paradigms and methods for the biological mesoscale problems (focusing on oncology research) and prospected the potential of their multiple dimensions and upcoming challenges. We expect to establish an interactive and collaborative theoretical platform for further expanding the depth and width of our understanding on the nature of biology.