Chirality and the Origin of Life

The origin of life, based on the homochirality of biomolecules, is a persistent mystery. Did life begin by using both forms of chirality, and then one of the forms disappeared? Or did the choice of homochirality precede the formation of biomolecules that could ensure replication and information transfer? Is the natural choice of L-amino acids and D-sugars on which life is based deterministic or random? Is the handedness present in/of the Universe from its beginning? The whole biosystem on the Earth, all living creatures are chiral. Many theories try to explain the origin of life and chirality on the Earth: e.g., the panspermia hypothesis, the primordial soup hypothesis, theory of parity violation in weak interactions. Additionally, heavy neutrinos and the impact of the fact that only left-handed particles decay, and even dark matter, all have to be considered.

The Primordial Soup: Exploring the Emotional Microfoundations of Cluster Genesis

Previous research on the genesis of industrial clusters has focused on macrolevel (e.g., agglomeration economies and institutions) or mesolevel explanatory factors (e.g., serial entrepreneurship, spin-offs). Less studied are the microfoundations of cluster genesis, intended as the individual- and group-level processes underlying such macrolevel outcomes. Yet, microfoundations are key to understanding the “primordial soup” of cluster genesis—that is, the processes unfolding in the early moments of cluster formation, before the first emergence of commercial activity. Through a historical case study of the British Motorsport Valley (1911–1970s), we trace back the primordial origins of this cluster to the casual leisure activities of groups of amateur motorsport enthusiasts who then prompted the professionalization of motorsport racing and its transformation into the business at the core of the industrial cluster. We theorize that clusters emerge through the layering of different domains (casual leisure, serious leisure, and business), each made of three elements (actors, activities, and artifacts), which interact via two microlevel mechanisms: (1) localizing passion, a shared emotional energy by which people become affectively attached to the spaces where they carry out activities that they enjoy; (2) domain repurposing, the shift of a configuration of actors, activities, and artifacts toward a new purpose, originating a new domain. Whereas domain repurposing induces the transformation of activities from leisure to business (thus originating the industry at the core of a cluster), localizing passion anchors the activities to the same geographical area (clustering the industry). Our key contribution is to explore the emotional microfoundations of cluster genesis.

Precambrian Paleobiology: Precedents, Progress, and Prospects

In 1859, C. R. Darwin highlighted the “inexplicable” absence of evidence of life prior to the beginning of the Cambrian. Given this lack of evidence and the natural rather than theological unfolding of life’s development Darwin espoused, over the following 50 years his newly minted theory was disputed. At the turn of the 19th century, beginning with the discoveries of C. D. Walcott, glimmerings of the previously “unknown and unknowable” early fossil record came to light – but Walcott’s Precambrian finds were also discounted. It was not until the breakthrough advances of the 1950’s and the identification of modern stromatolites (1956), Precambrian phytoplankton in shales (1950’s), stromatolitic microbes in cherts (1953), and terminal-Precambrian soft-bodied animal fossils (1950’s) that the field was placed on firm footing. Over the following half-century, the development and application of new analytical techniques coupled with the groundbreaking contributions of the Precambrian Paleobiology Research Group spurred the field to its international and distinctly interdisciplinary status. Significant progress has been made worldwide. Among these advances, the known fossil record has been extended sevenfold (from ∼0.5 to ∼3.5 Ga); the fossil record has been shown consistent with rRNA phylogenies (adding credence to both); and the timing and evolutionary significance of an increase of environmental oxygen (∼2.3 Ga), of eukaryotic organisms (∼2.0 Ga), and of evolution-speeding and biota-diversifying eukaryotic sexual reproduction (∼1.2 Ga) have been identified. Nevertheless, much remains to be learned. Such major unsolved problems include the absence of definitive evidence of the widely assumed life-generating “primordial soup”; the timing of the origin of oxygenic photosynthesis; the veracity of postulated changes in global photic-zone temperature from 3.5 Ga to the present; the bases of the advent of eukaryotic sexuality-requiring gametogenesis and syngamy; and the timing of origin and affinities of the small soft-bodied precursors of the Ediacaran Fauna.

Ancient Evolutionary Origin and Properties of Universally Produced Natural Exosomes Contribute to Their Therapeutic Superiority Compared to Artificial Nanoparticles

Extracellular vesicles (EVs), such as exosomes, are newly recognized fundamental, universally produced natural nanoparticles of life that are seemingly involved in all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and also the potential therapeutic uses of these nanovesicles requires innovative experimental approaches in virtually every field. Of the EV group, exosome nanovesicles and larger companion micro vesicles can mediate completely new biologic and clinical processes dependent on the intercellular transfer of proteins and most importantly selected RNAs, particularly miRNAs between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern-day exosomes to withstand unusually harsh conditions, perhaps due to unique membrane lipid compositions. This is exemplified by ability of the maternal milk exosomes to survive passing the neonatal acid/enzyme rich stomach. It is postulated that this resistance also applies to their durable presence in phagolysosomes, thus suggesting a unique intracellular release of their contained miRNAs. A major discussed issue is the generally poorly realized superiority of these naturally evolved nanovesicles for therapies when compared to human-engineered artificial nanoparticles, e.g., for the treatment of diseases like cancers.

Ancient Origin Properties of Natural Exosomes Contribute to Their Therapeutic Superiority Compared to Artificial Nanoparticles

Extracellular vesicles (EV) such as exosomes, are newly recognized fundamental, natural and physiologic particles of life that seemingly are involved all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and the potential therapeutic uses of these nano-vesicles requires innovative experimental approaches, in virtually every field. Of the EV group, exosome nano-vesicles and larger companion extracellular micro vesicles (MV) can mediate completely new phenomena dependent on intercellular transfer of proteins and selected RNAs; particularly miRNAs, between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern day exosomes to withstand unusually harsh conditions; perhaps due to unusual membrane lipid compositions. This is exemplified by maternal milk exosome survival of the neonatal acid/enzyme rich stomach. It is postulated that this also applies to their durable presence in phagolysosomes; suggesting unique intracellular release of contents. A major issue discussed is the generally poorly realized superiority of these naturally evolved nano vesicles to therapies compared human engineered artificial nanoparticles; say for treatment of cancers.

Chemoselectivity Switching through Coupled Equilibria

Complex mixtures are found in biological and petrochemical feedstocks, and in the primordial soup implicated in the origins of life. Reacting individual compounds within these mixtures is challenging because of the difficulty in controlling the chemoselectivity of such reactions. We show that the selectivity of imine oxidation can be controlled within doubly dynamic combinatorial libraries, wherein two coupled equilibria determine whether the most oxidizable aldehyde precursor is made available to the oxidant or sequestered away from it. Under the slow oxidation conditions, the most electron-rich precursor can traverse the shallow energy landscape and its oxidation product dominates the final mixture. Faster oxidation captures the imine mixture composition, favoring the products derived from electron poorer push-pull imines. <br>

Chemoselectivity Switching through Coupled Equilibria

Complex mixtures are found in biological and petrochemical feedstocks, and in the primordial soup implicated in the origins of life. Reacting individual compounds within these mixtures is challenging because of the difficulty in controlling the chemoselectivity of such reactions. We show that the selectivity of imine oxidation can be controlled within doubly dynamic combinatorial libraries, wherein two coupled equilibria determine whether the most oxidizable aldehyde precursor is made available to the oxidant or sequestered away from it. Under the slow oxidation conditions, the most electron-rich precursor can traverse the shallow energy landscape and its oxidation product dominates the final mixture. Faster oxidation captures the imine mixture composition, favoring the products derived from electron poorer push-pull imines. <br>