Quantifying Catalysis at the Origin of Life.

The construction of hypothetical environments to produce organic molecules such as metabolic intermediates or amino acids is the subject of ongoing research into the emergence of life. Experiments specifically focused on an anabolic approach typically rely on a mineral catalyst to facilitate the supply of organics that may have produced prebiotic building blocks for life. Alternatively to a true catalytic system, a mineral could be sacrificially oxidized in the production of organics, necessitating the emergent 'life' to turn to virgin materials for each iteration of metabolic processes. The aim of this perspective is to view the current 'metabolism-first' literature through the lens of materials chemistry to evaluate the need for higher catalytic activity and materials analyses. While many elegant studies have detailed the production of chemical building blocks under geologically plausible and biologically relevant conditions, few appear to do so with sub-stoichiometric amounts of metals or minerals. Moving toward sub-stoichiometric metals with rigorous materials analyses is necessary to demonstrate the viability of an elusive cornerstone of the 'metabolism-first' hypotheses: catalysis. We emphasize that future work should aim to demonstrate decreased catalyst loading, increased productivity, and/or rigorous materials analyses for evidence of true catalysis.

CO2 reduction driven by a pH gradient.

All life on Earth is built of organic molecules, so the primordial sources of reduced carbon remain a major open question in studies of the origin of life. A variant of the alkaline-hydrothermal-vent theory for life's emergence suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog-and proposed evolutionary predecessor-of the Wood-Ljungdahl acetyl-CoA pathway of modern archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2 with H2 to formate (HCOO-), which has proven elusive in mild abiotic settings. Here we show the reduction of CO2 with H2 at room temperature under moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labeling with 13C confirmed formate production. Separately, deuterium (2H) labeling indicated that electron transfer to CO2 does not occur via direct hydrogenation with H2 but instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, removing H2, or eliminating the precipitate yielded no detectable product. Our work demonstrates the feasibility of spatially separated yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches.

Exploring the impacts of the COVID-19 crisis for the employment prospects of refugees and people seeking asylum in Australia.

As recent research indicates, refugees and people seeking asylum are suffering disproportionately from the COVID-19 pandemic and have become more and more "shut out" and marginalised. An important pathway to integration and self-reliance is sustainable employment. To explore the impacts of COVID-19 on the employment prospects of refugees and people seeking asylum, we conducted 35 interviews with managers from Australian organisations that employ or assist refugees and asylum seekers in finding employment and 20 interviews with refugees and people seeking asylum. Our interviews indicate that the labour market has become more difficult for these groups in the COVID-19 era due to (1) declines in job availabilities, (2) loss of jobs, (3) increased competition in the labour market and (4) increased discrimination and an "Australian first" mentality. Our interviews further suggest four strategies to improve employment prospects in the current situation: (1) pathways to permanent residency and citizenship for people seeking asylum; (2) access to healthcare and a financial safety net; (3) online training and education; and (4) social procurement.

Why the Lipid Divide? Membrane Proteins as Drivers of the Split between the Lipids of the Three Domains of Life.

Recent results from engineered and natural samples show that the starkly different lipids of archaea and bacteria can form stable hybrid membranes. But if the two types can mix, why don't they? That is, why do most bacteria and all eukaryotes have only typically bacterial lipids, and archaea archaeal lipids? It is suggested here that the reason may lie on the other main component of cellular membranes: membrane proteins, and their close adaptation to the lipids. Archaeal lipids in modern bacteria could suggest that the last universal common ancestor (LUCA) had both lipid types. However, this would imply a rather elaborate evolutionary scenario, while negating simpler alternatives. In light of widespread horizontal gene transfer across the prokaryotic domains, hybrid membranes reveal that the lipid divide did not just occur once at the divergence of archaea and bacteria from LUCA. Instead, it continues to occur actively to this day.

Expressions of masculinity and associations with suicidal ideation among young males.

BACKGROUND: Adolescent boys and young men are at particular risk of suicide. Suicidal ideation is an important risk factor for suicide, but is poorly understood among adolescent males. Some masculine behaviors have been associated with deleterious effects on health, yet there has been little quantitative examination of associations between masculinity and suicide or suicidal ideation, particularly among boys/young men. This study aimed to examine associations between conformity to masculine norms and suicidal ideation in a sample of adolescents. METHODS: A prospective cohort design, this study drew on a sample of 829 Australian boys/young men from the Australian Longitudinal Study on Male Health. Boys were 15-18 years at baseline, and 17-20 years at follow-up. Masculine norms (Wave 1), were measured using the Conformity to Masculine Norms Inventory (CMNI-22). Suicidal ideation (Wave 2) was a single-item from the Youth Risk Behavior Survey. Logistic regression analysis was conducted, adjusting for available confounders including parental education, Indigenous Australian identity and area disadvantage. RESULTS: In adjusted models, greater conformity to violent norms (OR = 1.23, 95% Confidence Interval [CI]: 1.03-1.47) and self-reliance norms (OR = 1.40, 95% CI: 1.15-1.70) was associated with higher odds of reporting suicidal ideation. Greater conformity to norms regarding heterosexuality was associated with reduced odds of reporting suicidal ideation (OR = 0.80, 95% CI: 0.68-0.91). CONCLUSIONS: These results suggest that conforming to some masculine norms may be deleterious to the mental health of young males, placing them at greater risk of suicidal ideation. The results highlight the importance of presenting young males with alternative and multiple ways of being a male. Facilitating a relaxation of norms regarding self-reliance, and encouraging help-seeking, is vital. Furthermore, dismantling norms that rigidly enforce masculine norms, particularly in relation to heteronormativity, is likely to benefit the broad population of males, not only those who do not conform to heterosexual and other masculine norms.

Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins across the Tree of Life.

Membrane proteins are crucial in transport, signaling, bioenergetics, catalysis, and as drug targets. Here, we show that membrane proteins have dramatically fewer detectable orthologs than water-soluble proteins, less than half in most species analyzed. This sparse distribution could reflect rapid divergence or gene loss. We find that both mechanisms operate. First, membrane proteins evolve faster than water-soluble proteins, particularly in their exterior-facing portions. Second, we demonstrate that predicted ancestral membrane proteins are preferentially lost compared with water-soluble proteins in closely related species of archaea and bacteria. These patterns are consistent across the whole tree of life, and in each of the three domains of archaea, bacteria, and eukaryotes. Our findings point to a fundamental evolutionary principle: membrane proteins evolve faster due to stronger adaptive selection in changing environments, whereas cytosolic proteins are under more stringent purifying selection in the homeostatic interior of the cell. This effect should be strongest in prokaryotes, weaker in unicellular eukaryotes (with intracellular membranes), and weakest in multicellular eukaryotes (with extracellular homeostasis). We demonstrate that this is indeed the case. Similarly, we show that extracellular water-soluble proteins exhibit an even stronger pattern of low homology than membrane proteins. These striking differences in conservation of membrane proteins versus water-soluble proteins have important implications for evolution and medicine.

A bioenergetic basis for membrane divergence in archaea and bacteria.

Membrane bioenergetics are universal, yet the phospholipid membranes of archaea and bacteria-the deepest branches in the tree of life-are fundamentally different. This deep divergence in membrane chemistry is reflected in other stark differences between the two domains, including ion pumping and DNA replication. We resolve this paradox by considering the energy requirements of the last universal common ancestor (LUCA). We develop a mathematical model based on the premise that LUCA depended on natural proton gradients. Our analysis shows that such gradients can power carbon and energy metabolism, but only in leaky cells with a proton permeability equivalent to fatty acid vesicles. Membranes with lower permeability (equivalent to modern phospholipids) collapse free-energy availability, precluding exploitation of natural gradients. Pumping protons across leaky membranes offers no advantage, even when permeability is decreased 1,000-fold. We hypothesize that a sodium-proton antiporter (SPAP) provided the first step towards modern membranes. SPAP increases the free energy available from natural proton gradients by ∼60%, enabling survival in 50-fold lower gradients, thereby facilitating ecological spread and divergence. Critically, SPAP also provides a steadily amplifying advantage to proton pumping as membrane permeability falls, for the first time favoring the evolution of ion-tight phospholipid membranes. The phospholipids of archaea and bacteria incorporate different stereoisomers of glycerol phosphate. We conclude that the enzymes involved took these alternatives by chance in independent populations that had already evolved distinct ion pumps. Our model offers a quantitatively robust explanation for why membrane bioenergetics are universal, yet ion pumps and phospholipid membranes arose later and independently in separate populations. Our findings elucidate the paradox that archaea and bacteria share DNA transcription, ribosomal translation, and ATP synthase, yet differ in equally fundamental traits that depend on the membrane, including DNA replication.

Steep pH Gradients and Directed Colloid Transport in a Microfluidic Alkaline Hydrothermal Pore.

All life on earth depends on the generation and exploitation of ionic and pH gradients across membranes. One theory for the origin of life proposes that geological pH gradients were the prebiotic ancestors of these cellular disequilibria. With an alkaline interior and acidic exterior, alkaline vents match the topology of modern cells, but it remains unknown whether the steep pH gradients persist at the microscopic scale. Herein, we demonstrate the existence of 6 pH-unit gradients across micrometer scales in a microfluidic vent replicate. Precipitation of metal sulfides at the interface strengthens the gradients, but even in the absence of precipitates laminar flow sustains the disequilibria. The gradients drive directed transport at the fluid interface, leading to colloid accumulation or depletion. Our results confirm that alkaline vents can provide an exploitable pH gradient, supporting their potential role at the emergence of chemiosmosis and the origin of life.

On the biogenic origins of homochirality.

Homochirality, the single-handedness of optically asymmetric chemical structures, is present in all major biological macromolecules. Terrestrial life's preference for one isomer over its mirror image in D-sugars and L-amino acids has both fascinated and puzzled biochemists for over a century. But the contrasting case of the equally fundamental phospholipids has received less attention. Although the phospholipid glycerol headgroups of archaea and bacteria are both exclusively homochiral, the stereochemistries between the two domains are opposite. Here I argue that the reason for this "dual homochirality" was a simple evolutionary choice at the independent origin of the two synthesizing enzymes. More broadly, this points to a trivial biogenic cause for the evolution of homochirality: the enzymatic processes that produce chiral biomolecules are stereospecific in nature. Once an orientation has been favored, shifting to the opposite is both difficult and unnecessary. Homochirality is thus the simplest and most parsimonious evolutionary case.

Economic inequality is linked to biased self-perception.

People's self-perception biases often lead them to see themselves as better than the average person (a phenomenon known as self-enhancement). This bias varies across cultures, and variations are typically explained using cultural variables, such as individualism versus collectivism. We propose that socioeconomic differences among societies--specifically, relative levels of economic inequality--play an important but unrecognized role in how people evaluate themselves. Evidence for self-enhancement was found in 15 diverse nations, but the magnitude of the bias varied. Greater self-enhancement was found in societies with more income inequality, and income inequality predicted cross-cultural differences in self-enhancement better than did individualism/collectivism. These results indicate that macrosocial differences in the distribution of economic goods are linked to microsocial processes of perceiving the self.

Mediated moderation or moderated mediation: relationship between length of unemployment, resilience, coping and health.

The aim of the present research was to evaluate a model of mediated moderation vs. moderated mediation that could explain the relationship between length of unemployment, dispositional resilience, coping styles and depression and social functioning of Venezuelan unemployed individuals. Self-report measures were administered to a sample of 328 unemployed residents in Caracas, Venezuela. Results indicated that emotional coping acted as a mediator in the relationship between resilience and depression. Individuals with greater resilience used more detachment coping when unemployment was longer, while individuals with poorer resilience in the same situation used less avoidance coping. Resilience acted as a protective moderating factor between longer periods of unemployment and social functioning, a process mediated by detachment coping. Overall, results supported a mediated moderation model, with resilience as the moderating factor and coping as the mediator in the relation between stress due to the length of unemployment and well-being.

Employment Precarity Strengthens the Relationships Between the Dark Triad and Professional Commitment.

The Dark Triad traits of Machiavellianism, narcissism, and psychopathy have been found to negatively impact work behaviors including information sharing, reporting of unethical conduct, and mistreatment of colleagues and subordinates. However, research has found the Dark Triad can also be related to forms of organizational commitment which underpin positive work behaviors, including engaging in tasks and duties beyond those required (i.e., "going above and beyond"). Professional commitment is a broader form of commitment that has been found to be significantly related to organizational commitment, sharing antecedents, and having similar outcomes. Professional commitment, the affective, normative, and continuance commitment toward one's profession or occupation, has the benefit of applying to individuals employed by organizations as well as those working for themselves or between jobs. In this research, we explore relationships between professional commitment, using previous research on the relationship between the dark triad traits of Machiavellianism, psychopathy, and narcissism and organizational commitment, as a basis for predictions. We also explored two forms of precarious employment (career interruptions and part-time or casual work) as possible moderators of the dark triad-professional commitment relationship. Participants were 184 Australian professionals (52.2% men), a slight majority of whom had experienced a career interruption (69.6%) or a year or more of part-time or casual employment (70.7%). The results showed that psychopathy had a negative association with affective commitment, whereas Machiavellianism was positively related to normative commitment, and narcissism was positively related to normative and continuance commitment. Using regression analysis, we found that among individuals who have worked in part-time/casual employment longer, Machiavellianism and psychopathy had significantly stronger negative associations with affective commitment. In contrast, among individuals who have had a significant career interruption, Machiavellianism had significantly stronger positive association with continuance commitment. These findings help expand our understanding of both the dark triad and its contingent impact on workers' attachment to their profession.

A new model for silicification of cyanobacteria in Proterozoic tidal flats.

Microbial fossils preserved by early diagenetic chert provide a window into the Proterozoic biosphere, but seawater chemistry, microbial processes, and the interactions between microbes and the environment that contributed to this preservation are not well constrained. Here, we use fossilization experiments to explore the processes that preserve marine cyanobacterial biofilms by the precipitation of amorphous silica in a seawater medium that is analogous to Proterozoic seawater. These experiments demonstrate that the exceptional silicification of benthic marine cyanobacteria analogous to the oldest diagnostic cyanobacterial fossils requires interactions among extracellular polymeric substances (EPS), photosynthetically induced pH changes, magnesium cations (Mg2+ ), and >70 ppm silica.

Microfluidic Reactors for Carbon Fixation under Ambient-Pressure Alkaline-Hydrothermal-Vent Conditions.

The alkaline-hydrothermal-vent theory for the origin of life predicts the spontaneous reduction of CO2, dissolved in acidic ocean waters, with H2 from the alkaline vent effluent. This reaction would be catalyzed by Fe(Ni)S clusters precipitated at the interface, which effectively separate the two fluids into an electrochemical cell. Using microfluidic reactors, we set out to test this concept. We produced thin, long Fe(Ni)S precipitates of less than 10 µm thickness. Mixing simplified analogs of the acidic-ocean and alkaline-vent fluids, we then tested for the reduction of CO2. We were unable to detect reduced carbon products under a number of conditions. As all of our reactions were performed at atmospheric pressure, the lack of reduced carbon products may simply be attributable to the low concentration of hydrogen in our system, suggesting that high-pressure reactors may be a necessity.

The origin of heredity in protocells.

Here we develop a computational model that examines one of the first major biological innovations-the origin of heredity in simple protocells. The model assumes that the earliest protocells were autotrophic, producing organic matter from CO2 and H2 Carbon fixation was facilitated by geologically sustained proton gradients across fatty acid membranes, via iron-sulfur nanocrystals lodged within the membranes. Thermodynamic models suggest that organics formed this way should include amino acids and fatty acids. We assume that fatty acids partition to the membrane. Some hydrophobic amino acids chelate FeS nanocrystals, producing three positive feedbacks: (i) an increase in catalytic surface area; (ii) partitioning of FeS nanocrystals to the membrane; and (iii) a proton-motive active site for carbon fixing that mimics the enzyme Ech. These positive feedbacks enable the fastest-growing protocells to dominate the early ecosystem through a simple form of heredity. We propose that as new organics are produced inside the protocells, the localized high-energy environment is more likely to form ribonucleotides, linking RNA replication to its ability to drive protocell growth from the beginning. Our novel conceptualization sets out conditions under which protocell heredity and competition could arise, and points to where crucial experimental work is required.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.

The Origin of Life in Alkaline Hydrothermal Vents.

Over the last 70 years, prebiotic chemists have been very successful in synthesizing the molecules of life, from amino acids to nucleotides. Yet there is strikingly little resemblance between much of this chemistry and the metabolic pathways of cells, in terms of substrates, catalysts, and synthetic pathways. In contrast, alkaline hydrothermal vents offer conditions similar to those harnessed by modern autotrophs, but there has been limited experimental evidence that such conditions could drive prebiotic chemistry. In the Hadean, in the absence of oxygen, alkaline vents are proposed to have acted as electrochemical flow reactors, in which alkaline fluids saturated in H2 mixed with relatively acidic ocean waters rich in CO2, through a labyrinth of interconnected micropores with thin inorganic walls containing catalytic Fe(Ni)S minerals. The difference in pH across these thin barriers produced natural proton gradients with equivalent magnitude and polarity to the proton-motive force required for carbon fixation in extant bacteria and archaea. How such gradients could have powered carbon reduction or energy flux before the advent of organic protocells with genes and proteins is unknown. Work over the last decade suggests several possible hypotheses that are currently being tested in laboratory experiments, field observations, and phylogenetic reconstructions of ancestral metabolism. We analyze the perplexing differences in carbon and energy metabolism in methanogenic archaea and acetogenic bacteria to propose a possible ancestral mechanism of CO2 reduction in alkaline hydrothermal vents. Based on this mechanism, we show that the evolution of active ion pumping could have driven the deep divergence of bacteria and archaea.

A beginners guide to estimating the non-synonymous to synonymous rate ratio of all protein-coding genes in a genome.

The ratio of non-synonymous to synonymous substitutions (dN/dS) is a useful measure of the strength and mode of natural selection acting on protein-coding genes. It is widely used to study patterns of selection on protein genes on a genomic scale-from the small genomes of viruses, bacteria, and parasitic eukaryotes to the largest eukaryotic genomes. In this chapter we describe all the steps necessary to calculate the dN/dS of all the genes using at least two genomes. We include a brief discussion on assigning orthologs, and of codon-aware alignment of orthologs. We then describe how to use the CODEML program of the PAML package for phylogenetic analysis to calculate the dN/dS and how to perform some statistical tests for positive selection. We then outline some methods for interpreting output and describe how one may use this data to make discoveries about the biology of your species. Finally, as a worked example we show all the steps we used to calculate dN/dS for 3,261 orthologs from six Plasmodium species, including tests for adaptive evolution (see worked_example.pdf).