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In this study, the complexities of intracellular processes have been analyzed, including DNA folding, alternative splicing, mitochondrial function, and enzyme transport in lysosomes. Based on a previously proposed hypothesis (Levinthal's generalized paradox), a conclusion is made that all abovementioned processes cannot be realized with sufficient accuracy and in a realistic timeframe within the framework of classical physics. It is unclear why the cell functions at all. For the cell to function, its internal environment must be highly structured. In this regard, the cell shares similarities with computational devices (computers). In this study, quantum models of interactions between biologically important molecules were constructed, taking into account the long-range effects. One significant aspect of these models is the special role of the phase of the wavefunction, which serves as a controlling parameter. Experiments have been proposed that may confirm or refute these models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cells evolved some 4 billion years ago, and since then the integrity of the structural and functional continuity of cellular life has been maintained via highly conserved and ancient processes of cell reproduction and division. The plasma membrane as well as all the cytoplasmic structures are reproduced and inherited uninterruptedly by each of the two daughter cells resulting from every cell division. Although our understanding of the evolutionary emergence of the very first cells is obscured by the extremely long timeline since that revolutionary event, the generally accepted position is that the de novo formation of cells is not possible; all present cells are products of other prior cells. This essential biological principle was first discovered by Robert Remak and then effectively coined as Omnis Cellula e Cellula (every cell of the cell) by Rudolf Virchow: all currently living cells have direct structural and functional connections to the very first cells. Based on our previous theoretical analysis, all cells are endowed with individual sentient cognition that guides their individual agency, behaviour and evolution. There is a vital consequence of this new sentient and cognitive view of cells: when cells assemble as functional tissue ecologies and organs within multicellular organisms, including plants, animals and humans, these cellular aggregates display derivative versions of aggregate tissue- and organ-specific sentience and consciousness. This innovative view of the evolution and physiology of all currently living organisms supports a singular principle: all organismal physiology is based on cellular physiology that extends from unicellular roots., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Heme is an iron-containing prosthetic group necessary for the function of several proteins termed "hemoproteins." Erythrocytes contain most of the body's heme in the form of hemoglobin and contain high concentrations of free heme. In nonerythroid cells, where cytosolic heme concentrations are 2 to 3 orders of magnitude lower, heme plays an essential and often overlooked role in a variety of cellular processes. Indeed, hemoproteins are found in almost every subcellular compartment and are integral in cellular operations such as oxidative phosphorylation, amino acid metabolism, xenobiotic metabolism, and transcriptional regulation. Growing evidence reveals the participation of heme in dynamic processes such as circadian rhythms, NO signaling, and the modulation of enzyme activity. This dynamic view of heme biology uncovers exciting possibilities as to how hemoproteins may participate in a range of physiologic systems. Here, we discuss how heme is regulated at the level of its synthesis, availability, redox state, transport, and degradation and highlight the implications for cellular function and whole organism physiology., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Protein-protein interactions govern most biological processes. New protein assemblies can be introduced through the fusion of selected proteins with di/oligomerization domains, which interact specifically with their partners but not with other cellular proteins. While four-helical bundle proteins (4HB) have typically been assembled from two segments, each comprising two helices, here we show that they can be efficiently segmented in various ways, expanding the number of combinations generated from a single 4HB. We implement a segmentation strategy of 4HB to design two-, three-, or four-chain combinations for the recruitment of multiple protein components. Different segmentations provide new insight into the role of individual helices for 4HB assembly. We evaluate 4HB segmentations for potential use in mammalian cells for the reconstitution of a protein reporter, transcriptional activation, and inducible 4HB assembly. Furthermore, the implementation of trimerization is demonstrated as a modular chimeric antigen receptor for the recognition of multiple cancer antigens., (© 2023. The Author(s).)

"I don't know the question, but sex is definitely the answer!," was a Woody Allen quote cited by Fuller and Insel in an Editorial Comment in 2013 on the importance of cell sex in submissions to AJP-Cell Physiology , and in biomedical research in general. The notion that cell sex is important is axiomatic in studies on prostate cancer (LnCAP) or placental physiology (BeWo). Indeed, most researchers are aware that HeLa cells are female cervical derived, and CHO are female hamster ovary cells, yet beyond those well-known examples, it would be fair to assume that the sex of cells derived from kidney, lung, or liver, for example, is given cursory, if any thought. In the end, what possible impact could the presence or absence of a Y chromosome have on protein trafficking in a nonreproductive tissue, such as a pancreatic β cell? However, this approach to cell, and indeed organismal physiology, seems to be in conflict with accumulating data, that show that far from being irrelevant, genes expressed off sex chromosomes have a broad-ranging impact on cells as diverse as neurons and renal cells. Moreover, it is also the policy of AJP-Cell Physiology that the source of all cells used (species, sex, etc.) should be clearly indicated when submitting an article for publication (https://journals.physiology.org/author-info.manuscript-composition). In 2013, we wrote a review examining how faithfully such requirements were adhered to in submissions to Cell Physiology . Nearly a decade later, it seems fitting to revisit the topic and ask if any improvements have been made in the description of cells and cell lines used in publications submitted to AJP-Cell Physiology .

What is the origin of behaviour? Although typically associated with a nervous system, simple organisms also show complex behaviours. Among them, the slime mold Physarum polycephalum , a giant single cell, is ideally suited to study emergence of behaviour. Here, we show how locomotion and morphological adaptation behaviour emerge from self-organized patterns of rhythmic contractions of the actomyosin lining of the tubes making up the network-shaped organism. We quantify the spatio-temporal contraction dynamics by decomposing experimentally recorded contraction patterns into spatial contraction modes. Notably, we find a continuous spectrum of modes, as opposed to a few dominant modes. Our data suggests that the continuous spectrum of modes allows for dynamic transitions between a plethora of specific behaviours with transitions marked by highly irregular contraction states. By mapping specific behaviours to states of active contractions, we provide the basis to understand behaviour's complexity as a function of biomechanical dynamics., Competing Interests: PF, MK, MW, KA No competing interests declared, (© 2022, Fleig et al.)

Understanding how cells change their identity and behaviour in living systems is an important question in many fields of biology. The problem of inferring cell trajectories from single-cell measurements has been a major topic in the single-cell analysis community, with different methods developed for equilibrium and non-equilibrium systems (e.g. haematopoeisis vs. embryonic development). We show that optimal transport analysis, a technique originally designed for analysing time-courses, may also be applied to infer cellular trajectories from a single snapshot of a population in equilibrium. Therefore, optimal transport provides a unified approach to inferring trajectories that is applicable to both stationary and non-stationary systems. Our method, StationaryOT, is mathematically motivated in a natural way from the hypothesis of a Waddington's epigenetic landscape. We implement StationaryOT as a software package and demonstrate its efficacy in applications to simulated data as well as single-cell data from Arabidopsis thaliana root development., Competing Interests: The authors have declared that no competing interests exist.

The major transmembrane protein of the red blood cell, known as band 3, AE1, and SLC4A1, has two main functions: 1 ) catalysis of Cl - /[Formula: see text] exchange, one of the steps in CO 2 excretion, and 2 ) anchoring the membrane skeleton. This review summarizes the 150-year history of research on red cell anion transport and band 3 as an experimental system for studying membrane protein structure and ion transport mechanisms. Important early findings were that red cell Cl - transport is a tightly coupled 1:1 exchange and band 3 is labeled by stilbenesulfonate derivatives that inhibit anion transport. Biochemical studies showed that the protein is dimeric or tetrameric (paired dimers) and that there is one stilbenedisulfonate binding site per subunit of the dimer. Transport kinetics and inhibitor characteristics supported the idea that the transporter acts by an alternating access mechanism with intrinsic asymmetry. The sequence of band 3 cDNA provided a framework for detailed study of protein topology and amino acid residues important for transport. The identification of genetic variants produced insights into the roles of band 3 in red cell abnormalities and distal renal tubular acidosis. The publication of the membrane domain crystal structure made it possible to propose concrete molecular models of transport. Future research directions include improving our understanding of the transport mechanism at the molecular level and of the integrative relationships among band 3, hemoglobin, carbonic anhydrase, and gradients (both transmembrane and subcellular) of [Formula: see text], Cl - , O 2 , CO 2 , pH, and nitric oxide (NO) metabolites during pulmonary and systemic capillary gas exchange.

The activity of local anesthetics (LAs) has been attributed to the inhibition of ion channels, causing anesthesia. However, there is a growing body of research showing that LAs act on a wide range of receptors and channel proteins far beyond simple analgesia. The current concept of ligand recognition may no longer explain the multitude of protein targets influenced by LAs. We hypothesize that LAs can cause anesthesia without directly binding to the receptor proteins just by changing the physical properties of the lipid bilayer surrounding these proteins and ion channels based on LAs' amphiphilicity. It is possible that LAs act in one of the following ways: They 1) dissolve raft-like membrane microdomains, 2) impede nerve impulse propagation by lowering the lipid phase transition temperature, or 3) modulate the lateral pressure profile of the lipid bilayer. This could also explain the numerous additional effects of LAs besides anesthesia. Furthermore, the concepts of membrane-mediated activity and binding to ion channels do not have to exclude each other. If we were to consider LA as the middle part of a continuum between unspecific membrane-mediated activity on one end and highly specific ligand binding on the other end, we could describe LA as the link between the unspecific action of general anesthetics and toxins with their highly specific receptor binding. This comprehensive membrane-mediated model offers a fresh perspective to clinical and pharmaceutical research and therapeutic applications of local anesthetics. SIGNIFICANCE STATEMENT: Local anesthetics, according to the World Health Organization, belong to the most important drugs available to mankind. Their rediscovery as therapeutics and not only anesthetics marks a milestone in global pain therapy. The membrane-mediated mechanism of action proposed in this review can explain their puzzling variety of target proteins and their thus far inexplicable therapeutic effects. The new concept presented here places LAs on a continuum of structures and molecular mechanisms in between small general anesthetics and the more complex molecular toxins., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Biological information processing is generally assumed to be classical. Measured cellular energy budgets of both prokaryotes and eukaryotes, however, fall orders of magnitude short of the power required to maintain classical states of protein conformation and localization at the Å, fs scales predicted by single-molecule decoherence calculations and assumed by classical molecular dynamics models. We suggest that decoherence is limited to the immediate surroundings of the cell membrane and of intercompartmental boundaries within the cell, and that bulk cellular biochemistry implements quantum information processing. Detection of Bell-inequality violations in responses to perturbation of recently-separated sister cells would provide a sensitive test of this prediction. If it is correct, modeling both intra- and intercellular communication requires quantum theory., (Copyright © 2021 Elsevier B.V. All rights reserved.)