The mega-evolution of life with its three memory systems depends on sender-receiver communication and problem-solving. A narrative review.

It should be the ultimate goal of any theory of evolution to delineate the contours of an integrative system to answer the question: How does life (in all its complexity) evolve (which can be called mega-evolution)? But how to plausibly define 'life'? My answer (1994-2023) is: 'life' sounds like a noun, but denotes an activity, and thus is a verb. Life (L) denotes nothing else than the total sum (∑) of all acts of communication (transfer of information) (C) executed by any type of senders-receivers at all their levels (up to at least 15) of compartmental organization: L = ∑C. The 'communicating compartment' is better suited to serve as the universal unit of structure, function and evolution than the cell, the smallest such unit.

Point-of-care applicable metabotyping using biofluid-specific electrospun MetaSAMPs directly amenable to ambient LA-REIMS.

In recent years, ambient ionization mass spectrometry (AIMS) including laser ablation rapid evaporation IMS, has enabled direct biofluid metabolome analysis. AIMS procedures are, however, still hampered by both analytical, i.e.

The mega-evolution of life depends on sender-receiver communication and problem-solving.

It is logical to define "Life" prior to uncovering the mechanisms that allow changes, e.g. short (development) and long (evolution).

Late Trypsin Biosynthesis Is Translationally Regulated by Trypsin Modulating Oostatic Factor.

Trypsin is a serine protease that is synthesized by the gut epithelial cells of female mosquitoes; it is the enzyme that digests the blood meal. To study its molecular regulation, late trypsin was purified by diethylaminoethyl (DEAE), affinity, and C reverse-phase high performance liquid chromatography (HPLC) steps, and the N-terminal amino acid sequence was determined for molecular cloning. Five overlapping segments of the late trypsin cDNA were amplified by PCR, cloned, and the full sequence (855 bp) was characterized.

Key role of juvenile hormone in controlling reproductive diapause in females of the Asian lady beetle Harmonia axyridis.

Background: The Asian lady beetle Harmonia axyridis is an important predator of several agricultural pests, including aphids and whiteflies, and thus can contribute to pest management. Commercial viability as a pest control method requires that the beetle can be mass-reared, and that workable conditions for extended shelf-life can be guaranteed. One of the features of Harmonia's life cycle is that it enters diapause in the adult stage when the length of the photophase starts shortening in late summer.

Two Undervalued Functions of the Golgi Apparatus: Removal of Excess Ca and Biosynthesis of Farnesol-Like Sesquiterpenoids, Possibly as Ca-Pump Agonists and Membrane "Fluidizers-Plasticizers".

The extensive literature dealing with the Golgi system emphasizes its role in protein secretion and modification, usually without specifying from which evolutionary ancient cell physiological necessity such secretion originated. Neither does it specify which functional requirements the secreted proteins must meet. From a reinterpretation of some classical and recent data gained mainly, but not exclusively, from (insect) endocrinology, the view emerged that the likely primordial function of the rough endoplasmic reticulum (RER)-Golgi complex in all eukaryotes was not the secretion of any type of protein but the removal of toxic excess Ca from the cytoplasm.

Intraluminal Farnesol and Farnesal in the Mealworm's Alimentary Canal: An Unusual Storage Site Uncovering Hidden Eukaryote Ca-Homeostasis-Dependent "Golgicrine" Activities.

Farnesol, the sesquiterpenoid precursor of the six presently known insect juvenile hormones (JHs) was for the first time chemically identified in 1961, not in JH synthesizing glands or whole body extracts, but in excrements of the mealworm . This finding was thought to be irrelevant and remained unexplored. In 1970, it was reported that the fall to zero of the JH titer in both prediapausing adults and in last instar larvae of the Colorado potato beetle causes severe malfunctioning of the Golgi system in the fat body, among various other effects.

Nature, Calcigender, Nurture: Sex-dependent differential Ca homeostasis as the undervalued third pillar.

After many years of sometimes heated discussions, the problem regarding the relative importance of two classical dogmas of the Nature (genes and sex-steroid hormones) versus Nurture (education, teaching-learning etc.) debate, is still awaiting a conclusive solution. Males and females differ in only a few (primordial) genes as is well documented by genomic analyses.

Flip-Flopping Retinal in Microbial Rhodopsins as a Template for a Farnesyl/Prenyl Flip-Flop Model in Eukaryote GPCRs.

Thirty years after the first description and modeling of G protein coupled receptors (GPCRs), information about their mode of action is still limited. One of the questions that is hard to answer is: how do the allosteric changes in the GPCR induced by, e.g.

Mode of Action of Farnesol, the "Noble Unknown" in Particular in Ca Homeostasis, and Its Juvenile Hormone-Esters in Evolutionary Retrospect.

Farnesol, the sesquiterpenoid precursor of insect juvenile hormones (JH) that itself has JH activity, existed already long before animals and their hormones came into being. Although it is omnipresent in all eukaryotes, this molecule remains a "noble unknown" in cell physiology. It is neither documented as a hormone nor as another type of signaling molecule.

Only two sex forms but multiple gender variants: How to explain?

Are and r interchangeable terms? In classical biology, both are sometimes but not always used on an equal basis for some groups of animals. However, for our own species the they are not. A major question is why are there only two types of gametes (sperm- and egg cells), two types of sex steroids, (androgens and estrogens in vertebrates, and two types of ecdysteroids in insects), while the reproduction-related behaviour of the gamete producers displays a much greater variability than just two prominent forms, namely heterosexual males and heterosexual females? It indicates that in addition to a few sex-determining genes ( = the first pillar), other factors play a role.

Calcitox-aging counterbalanced by endogenous farnesol-like sesquiterpenoids: An undervalued evolutionarily ancient key signaling pathway.

Cells are powerful miniature electrophoresis chambers, at least during part of their life cycle. They die at the moment the voltage gradient over their plasma membrane, and their ability to drive a self-generated electric current carried by inorganic ions through themselves irreversibly collapses. Senescence is likely due to the progressive, multifactorial damage to the cell's electrical system.

The evolution of "Life": A Metadarwinian integrative approach.

It is undeniably very logical to first formulate an unambiguous definition of "Life" before engaging in defining the parameters instrumental to Life's evolution. Because nearly everybody assumes, erroneously in my opinion, that catching Life's essence in a single sentence is impossible, this way of thinking remained largely unexplored in evolutionary theory. Upon analyzing what exactly happens at the transition from "still alive" to "just dead," the following definition emerged.

The cell's self-generated "electrome": The biophysical essence of the immaterial dimension of Life?

In the classical "mind-body" wording, "body" is usually associated with the "mass aspect" of living entities and "mind" with the "immaterial" one. Thoughts, consciousness and soul are classified as immaterial. A most challenging question emerges: Can something that is truly immaterial, thus that in the wording of physics has no mass, exist at all? Many will answer: "No, impossible.

Neuropeptides as Regulators of Behavior in Insects.

Neuropeptides are by far the largest and most diverse group of signaling molecules in multicellular organisms. They are ancient molecules important in regulating a multitude of processes. Their small proteinaceous character allowed them to evolve and radiate quickly into numerous different molecules.

How to deduce and teach the logical and unambiguous answer, namely L = ∑C, to "What is Life?" using the principles of communication?

Is it possible to understand the very nature of 'Life' and 'Death' based on contemporary biology? The usual spontaneous reaction is: "No way. Life is far too complicated. It involves both material- and an immaterial dimensions, and this combination exceeds the capacities of the human brain.

The endocrine system controlling sexual reproduction in animals: Part of the evolutionary ancient but well conserved immune system?

Drastic changes in hormone titers, in particular of steroid hormones, are intuitively interpreted as necessary and beneficial for optimal functioning of animals. Peaks in progesterone- and estradiol titers that accompany the estrus cycle in female vertebrates as well as in ecdysteroids at each molt and during metamorphosis of holometabolous insects are prominent examples. A recent analysis of insect metamorphosis yielded the view that, in general, a sharp rise in sex steroid hormone titer signals that somewhere in the body some tissue(s) is undergoing programmed cell death/apoptosis.

Farnesol-like endogenous sesquiterpenoids in vertebrates: the probable but overlooked functional "inbrome" anti-aging counterpart of juvenile hormone of insects?

Literature on the question whether the juvenile stage of vertebrates is hormonally regulated is scarce. It seems to be intuitively assumed that this stage of development is automated, and does not require any specific hormone(s). Such reasoning mimics the state of affairs in insects until it was shown that surgical removal of a tiny pair of glands in the head, the corpora allata, ended larval life and initiated metamorphosis.

Epigenetics and locust life phase transitions.

Insects are one of the most successful classes on Earth, reflected in an enormous species richness and diversity. Arguably, this success is partly due to the high degree to which polyphenism, where one genotype gives rise to more than one phenotype, is exploited by many of its species. In social insects, for instance, larval diet influences the development into distinct castes; and locust polyphenism has tricked researchers for years into believing that the drastically different solitarious and gregarious phases might be different species.

The essence of female-male physiological dimorphism: differential Ca2+-homeostasis enabled by the interplay between farnesol-like endogenous sesquiterpenoids and sex-steroids? The Calcigender paradigm.

Ca(2+) is the most omnipresent pollutant on earth, in higher concentrations a real threat to all living cells. When [Ca(2+)]i rises above 100 nM (=resting level), excess Ca(2+) needs to be confined in the SER and mitochondria, or extruded by the different Ca(2+)-ATPases. The evolutionary origin of eggs and sperm cells has a crucial, yet often overlooked link with Ca(2+)-homeostasis.

Initiation of metamorphosis and control of ecdysteroid biosynthesis in insects: The interplay of absence of Juvenile hormone, PTTH, and Ca(2+)-homeostasis.

The paradigm saying that release of the brain neuropeptide big prothoracicotropic hormone (PTTH) initiates metamorphosis by activating the Torso-receptor/ERK pathway in larval prothoracic glands (PGs) is widely accepted nowadays. Upon ligand-receptor interaction Ca(2+) enters the PG cells and acts as a secondary messenger. Ecdysteroidogenesis results, later followed by apoptosis.

The essence of insect metamorphosis and aging: electrical rewiring of cells driven by the principles of juvenile hormone-dependent Ca(2+)-homeostasis.

In holometabolous insects the fall to zero of the titer of Juvenile Hormone ends its still poorly understood "status quo" mode of action in larvae. Concurrently it initiates metamorphosis of which the programmed cell death of all internal tissues that actively secrete proteins, such as the fat body, midgut, salivary glands, prothoracic glands, etc. is the most drastic aspect.

The mode of action of juvenile hormone and ecdysone: towards an epi-endocrinological paradigm?

In some insect species, two sites of juvenile hormone (JH) synthesis have been reported: the very well documented corpora allata that secrete JH for "general use", and the reproductive system, in particular the male accessory glands, in which the function of the sometimes huge amounts of JH (e.g. in Hyalophora cecropia) remains to be clarified.

The Fading Electricity Theory of Ageing: the missing biophysical principle?

Since a few years convincing data are accumulating showing that some of the premises of the master integrative theory of ageing, namely Harman's Reactive Oxygen Species or free radical theory, are less well founded than originally assumed. In addition, none of the about another dozen documented ageing mechanisms seems to hold the final answer as to the ultimate cause and evolutionary significance of ageing. This review raises the question whether, perhaps, something important has been overlooked, namely a biophysical principle, electrical in nature.

Endocrine archeology: do insects retain ancestrally inherited counterparts of the vertebrate releasing hormones GnRH, GHRH, TRH, and CRF?

Vertebrate releasing hormones include gonadotropin releasing hormone (GnRH), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRF), and thyrotropin-releasing hormone (TRH). They are synthesized in the hypothalamus and stimulate the release of pituitary hormones. Here we review the knowledge on hormone releasing systems in the protostomian lineage.