Twenty years of "Lipid World": a fertile partnership with David Deamer

"The Lipid World" was published in 2001, stemming from a highly effective collaboration with David Deamer during a sabbatical year 20 years ago at the Weizmann Institute of Science in Israel. The present review paper highlights the benefits of this scientific interaction and assesses the impact of the lipid world paper on the present understanding of the possible roles of amphiphiles and their assemblies in the origin of life. The lipid world is defined as a putative stage in the progression towards life's origin, during which diverse amphiphiles or other spontaneously aggregating small molecules could have concurrently played multiple key roles, including compartment formation, the appearance of mutually catalytic networks, molecular information processing, and the rise of collective self-reproduction and compositional inheritance. This review brings back into a broader perspective some key points originally made in the lipid world paper, stressing the distinction between the widely accepted role of lipids in forming compartments and their expanded capacities as delineated above. In the light of recent advancements, we discussed the topical relevance of the lipid worldview as an alternative to broadly accepted scenarios, and the need for further experimental and computer-based validation of the feasibility and implications of the individual attributes of this point of view. Finally, we point to possible avenues for exploring transition paths from small molecule-based noncovalent structures to more complex biopolymer-containing proto-cellular systems.711473 - Minerva Foundation; 80NSSC17K0295, 80NSSC17K0296, 1724150 - National Science FoundationPublished versio

Short-term memory for pictures seen once or twice

The present study is concerned with the effects of exposure time, repetition, spacing and lag on old/new recognition memory for generic visual scenes presented in a RSVP paradigm. Early memory studies with verbal material found that knowledge of total exposure time at study is sufficient to accurately predict memory performance at test (the Total Time Hypothesis), irrespective of number of repetitions, spacing or lag. However, other studies have disputed such simple dependence of memory strength on total study time, demonstrating super-additive facilitatory effects of spacing and lag, as well as inhibitory effects, such as the Ranschburg effect, Repetition Blindness and the Attentional Blink. In the experimental conditions of the present study we find no evidence of either facilitatory or inhibitory effects: recognition memory for pictures in RSVP supports the Total Time Hypothesis. The data are consistent with an Unequal-Variance Signal Detection Theory model of memory that assumes the average strength and the variance of the familiarity of pictures both increase with total study time. The main conclusion is that the growth of visual scene familiarity with temporal exposure and repetition is a stochastically independent process

Spike-Based Bayesian-Hebbian Learning of Temporal Sequences

Many cognitive and motor functions are enabled by the temporal representation and processing of stimuli, but it remains an open issue how neocortical microcircuits can reliably encode and replay such sequences of information. To better understand this, a modular attractor memory network is proposed in which meta-stable sequential attractor transitions are learned through changes to synaptic weights and intrinsic excitabilities via the spike-based Bayesian Confidence Propagation Neural Network (BCPNN) learning rule. We find that the formation of distributed memories, embodied by increased periods of firing in pools of excitatory neurons, together with asymmetrical associations between these distinct network states, can be acquired through plasticity. The model's feasibility is demonstrated using simulations of adaptive exponential integrate-and-fire model neurons (AdEx). We show that the learning and speed of sequence replay depends on a confluence of biophysically relevant parameters including stimulus duration, level of background noise, ratio of synaptic currents, and strengths of short-term depression and adaptation. Moreover, sequence elements are shown to flexibly participate multiple times in the sequence, suggesting that spiking attractor networks of this type can support an efficient combinatorial code. The model provides a principled approach towards understanding how multiple interacting plasticity mechanisms can coordinate hetero-associative learning in unison

Protobiotic Systems Chemistry Analyzed by Molecular Dynamics

Systems chemistry has been a key component of origin of life research, invoking models of life’s inception based on evolving molecular networks. One such model is the graded autocatalysis replication domain (GARD) formalism embodied in a lipid world scenario, which offers rigorous computer simulation based on defined chemical kinetics equations. GARD suggests that the first pre-RNA life-like entities could have been homeostatically-growing assemblies of amphiphiles, undergoing compositional replication and mutations, as well as rudimentary selection and evolution. Recent progress in molecular dynamics has provided an experimental tool to study complex biological phenomena such as protein folding, ligand-receptor interactions, and micellar formation, growth, and fission. The detailed molecular definition of GARD and its inter-molecular catalytic interactions make it highly compatible with molecular dynamics analyses. We present a roadmap for simulating GARD’s kinetic and thermodynamic behavior using various molecular dynamics methodologies. We review different approaches for testing the validity of the GARD model by following micellar accretion and fission events and examining compositional changes over time. Near-future computational advances could provide empirical delineation for further system complexification, from simple compositional non-covalent assemblies towards more life-like protocellular entities with covalent chemistry that underlies metabolism and genetic encoding

Micellar Composition Affects Lipid Accretion Kinetics in Molecular Dynamics Simulations

Mixed lipid micelles were proposed to facilitate the emergence of life through their documented growth dynamics and catalytic properties. Our research predicted that micellar self-reproduction is possible through composition-driven catalyzed accretion of lipid molecules in heterogeneous systems, reaching states that allow micellar growth and split while maintaining compositional homeostasis. However, experimentally studying catalyzed accretion in mixed micelles is technically challenging. Here, we employ atomistic Molecular Dynamics simulations to examine the self-assembly of variegated lipid assemblies allowing us to derive entry and exit rates of monomeric lipids into pre-micelles with different compositions. We observe considerable selective rate-modifications that are compositionally-driven, and illustrate their underlying mechanisms as well as the energy contributions that facilitate these kinetic effects. Lastly, we describe the measured potential for compositional homeostasis in our simulated mixed micelles, the basis for micellar self-reproduction, with implications for the study of the origin of life

Micellar Composition Affects Lipid Accretion Kinetics in Molecular Dynamics Simulations: Support for Lipid Network Reproduction

Mixed lipid micelles were proposed to facilitate life through their documented growth dynamics and catalytic properties. Our previous research predicted that micellar self-reproduction involves catalyzed accretion of lipid molecules by the residing lipids, leading to compositional homeostasis. Here, we employ atomistic Molecular Dynamics simulations, beginning with 54 lipid monomers, tracking an entire course of micellar accretion. This was done to examine the self-assembly of variegated lipid clusters, allowing us to measure entry and exit rates of monomeric lipids into pre-micelles with different compositions and sizes. We observe considerable rate-modifications that depend on the assembly composition and scrutinize the underlying mechanisms as well as the energy contributions. Lastly, we describe the measured potential for compositional homeostasis in our simulated mixed micelles. This affirms the basis for micellar self-reproduction, with implications for the study of the origin of life

Pliocene-Pleistocene waterbodies and associated deposits in southern Israel and southern Jordan

This paper provides an in-depth review of evidence for the presence of twelve waterbodies spanning the Late Pliocene through Late Pleistocene in southern Israel and southern Jordan. A comprehensive description of these waterbodies is presented, combined with new field, paleontological and numerical age data, along with a discussion of their implications for paleohydrology and paleoclimate. The region is currently hyper-arid and there are no permanent rivers, wetlands or lakes in the area. Nevertheless, during the time-frame examined, continuous layers of limestones and mudstones were deposited in wetlands and shallow lakes. According to their location, the waterbodies were classified into either resulting from local tectonic depressions or in wide natural depressions at base levels. Following the types of sediments and fauna associated with these waterbodies, it is suggested that four wetter periods occurred: Late Pliocene/Early Pleistocene, Middle Pleistocene, Middle Late Pleistocene and terminal Late Pleistocene. This resulted in the deposition of limestone, chalk, travertine, calcrete, mudstone, marl, clay, silt and sandstone. For several waterbodies, vertical and lateral transitions between white limestone and fine clastic sediments rich in carbonate, indicate changes in depositional conditions from a shallow lake to a wetland, both associated with wetter hydrological settings compared to current climatic conditions. (C) 2017 Elsevier Ltd. All rights reserved