A few genera of diatoms are widespread and thrive in low-nutrient waters of the open ocean due to their close association with N2-fixing, filamentous heterocyst-forming cyanobacteria. In one of these symbioses, the symbiont, Richelia euintracellularis, has penetrated the cell envelope of the host, Hemiaulus hauckii, and lives inside the host cytoplasm. How the partners interact, including how the symbiont sustains high rates of N2 fixation, is unstudied. Since R. euintracellularis has evaded isolation, heterologous expression of genes in model laboratory organisms was performed to identify the function of proteins from the endosymbiont. Gene complementation of a cyanobacterial invertase mutant and expression of the protein in Escherichia coli showed that R. euintracellularis HH01 possesses a neutral invertase that splits sucrose producing glucose and fructose. Several solute-binding proteins (SBPs) of ABC transporters encoded in the genome of R. euintracellularis HH01 were expressed in E. coli, and their substrates were characterized. The selected SBPs directly linked the host as the source of several substrates, e.g. sugars (sucrose and galactose), amino acids (glutamate and phenylalanine), and a polyamine (spermidine), to support the cyanobacterial symbiont. Finally, transcripts of genes encoding the invertase and SBPs were consistently detected in wild populations of H. hauckii collected from multiple stations and depths in the western tropical North Atlantic. Our results support the idea that the diatom host provides the endosymbiotic cyanobacterium with organic carbon to fuel N2 fixation. This knowledge is key to understanding the physiology of the globally significant H. hauckii-R. euintracellularis symbiosis.

Economically progressive candidates-candidates who champion redistributive policies designed to reduce inequality-rarely win elections in the United States. Here, we propose that progressive candidates achieve greater support by framing their policy platforms in terms of values that resonate beyond their progressive base. In two experiments (total N = 4,138), including one preregistered experiment conducted on a nationally representative probability sample, we found that a presidential candidate who framed his progressive economic platform using values consistent with the "binding" moral foundations-e.g. patriotism, family, and respect for tradition-as opposed to values consistent with the "individualizing" foundations, e.g. equality and social justice, received significantly stronger support. This effect was driven by increased support among conservatives and, unexpectedly, moderates as well. By comparison, a manipulation of how progressive the candidate's platform was had small and inconsistent effects. Despite the potential gains associated with binding framing, analyses using presidential candidates' debate speeches reveal that appeals to binding values are least common among progressive candidates. These findings show, however, that the alignment between values and candidate support is malleable, suggesting economically progressive candidates can build broader coalitions by reframing the values they associate with their platforms.

Executive functions are a set of cognitive control processes required for optimizing goal-directed behavior. Despite more than two centuries of research on executive functions, mostly in humans and nonhuman primates, there is still a knowledge gap in what constitutes the mechanistic basis of evolutionary variation in executive function abilities. Here, we show experimentally that size changes in a forebrain structure (i.e. telencephalon) underlie individual variation in executive function capacities in a fish. For this, we used male guppies (Poecilia reticulata) issued from artificial selection lines with substantial differences in telencephalon size relative to the rest of the brain. We tested fish from the up- and down-selected lines not only in three tasks for the main core executive functions: cognitive flexibility, inhibitory control, and working memory, but also in a basic conditioning test that does not require executive functions. Individuals with relatively larger telencephalons outperformed individuals with smaller telencephalons in all three executive function assays but not in the conditioning assay. Based on our findings, we propose that the telencephalon is the executive brain in teleost fish. Together, it suggests that selective enlargement of key brain structures with distinct functions, like the fish telencephalon, is a potent evolutionary pathway toward evolutionary enhancement of advanced cognitive abilities in vertebrates.

Applications in chemistry, biology, medicine, and engineering require the large-scale manipulation of a wide range of chemicals, samples, and specimens. To achieve maximum efficiency, parallel control of microlitre droplets using automated techniques is essential. Electrowetting-on-dielectric (EWOD), which manipulates droplets using the imbalance of wetting on a substrate, is the most widely employed method. However, EWOD is limited in its capability to make droplets detach from the substrate (jumping), which hinders throughput and device integration. Here, we propose a novel microfluidic system based on focused ultrasound passing through a hydrophobic mesh with droplets resting on top. A phased array dynamically creates foci to manipulate droplets of up to 300 μL. This platform offers a jump height of up to 10 cm, a 27-fold improvement over conventional EWOD systems. In addition, droplets can be merged or split by pushing them against a hydrophobic knife. We demonstrate Suzuki-Miyaura cross-coupling using our platform, showing its potential for a wide range of chemical experiments. Biofouling in our system was lower than in conventional EWOD, demonstrating its high suitability for biological experiments. Focused ultrasound allows the manipulation of both solid and liquid targets. Our platform provides a foundation for the advancement of micro-robotics, additive manufacturing, and laboratory automation.

Changes in growth and height reflect changes in nutritional status and health. The systematic surveillance of growth can suggest areas for interventions. Moreover, phenotypic variation has a strong intergenerational component. There is a lack of historical family data that can be used to track the transmission of height over subsequent generations. Maternal height is a proxy for conditions experienced by one generation that relates to the health/growth of future generations. Cross-sectional/cohort studies have shown that shorter maternal height is closely associated with lower birth weight of offspring. We analyzed the maternal height and offspring weight at birth in the maternity hospital in Basel, Switzerland, from 1896 to 1939 (N = ∼12,000) using generalized additive models (GAMs). We observed that average height of the mothers increased by ∼4 cm across 60 birth years and that average birth weight of their children shows a similarly shaped and upward trend 28 years later. Our final model (adjusted for year, parity, sex of the child, gestational age, and maternal birth year) revealed a significant and almost linear association between maternal height and birth weight. Maternal height was the second most important variable modeling birth weight, after gestational age. In addition, we found a significant association between maternal height and aggregated average height of males from the same birth years at time of conscription, 19 years later. Our results have implications for public health: When (female/maternal) height increases due to improved nutritional status, size at birth-and subsequently also the height in adulthood of the next generation-increases as well. However, the directions of development in this regard may currently differ depending on the world region.

There are more than 900 genetic syndromes associated with oral manifestations. These syndromes can have serious health implications, and left undiagnosed, can hamper treatment and prognosis later in life. About 6.67% of the population will develop a rare disease during their lifetime, some of which are difficult to diagnose. The establishment of a data and tissue bank of rare diseases with oral manifestations in Quebec will help medical professionals identify the genes involved, will improve knowledge on the rare genetic diseases, and will also lead to improved patient management. It will also allow samples and information sharing with other clinicians and investigators. As an example of a condition requiring additional research, dental ankylosis is a condition in which the tooth's cementum fuses to the surrounding alveolar bone. This can be secondary to traumatic injury but is often idiopathic, and the genes involved in the idiopathic cases, if any, are poorly known. To date, patients with both identified and unidentified genetic etiology for their dental anomalies were recruited through dental and genetics clinics for the study. They underwent sequencing of selected genes or exome sequencing depending on the manifestation. We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.

Most people are much less generous toward strangers than close others, a bias termed social discounting. But people who engage in extraordinary real-world altruism, like altruistic kidney donors, show dramatically reduced social discounting. Why they do so is unclear. Some prior research suggests reduced social discounting requires effortfully overcoming selfishness via recruitment of the temporoparietal junction. Alternatively, reduced social discounting may reflect genuinely valuing strangers' welfare more due to how the subjective value of their outcomes is encoded in regions such as rostral anterior cingulate cortex (ACC) and amygdala. We tested both hypotheses in this pre-registered study. We also tested the hypothesis that a loving-kindness meditation (LKM) training intervention would cause typical adults' neural and behavioral patterns to resemble altruists. Altruists and matched controls (N = 77) completed a social discounting task during functional magnetic resonance imaging; 25 controls were randomized to complete LKM training. Neither behavioral nor imaging analyses supported the hypothesis that altruists' reduced social discounting reflects effortfully overcoming selfishness. Instead, group differences emerged in social value encoding regions, including rostral ACC and amygdala. Activation in these regions corresponded to the subjective valuation of others' welfare predicted by the social discounting model. LKM training did not result in more generous behavioral or neural patterns, but only greater perceived difficulty during social discounting. Our results indicate extraordinary altruists' generosity results from the way regions involved in social decision-making encode the subjective value of others' welfare. Interventions aimed at promoting generosity may thus succeed to the degree they can increase the subjective valuation of others' welfare.

Building on big data from Reddit, we generated two computational text models: (i) Predicting the personality of users from the text they have written and (ii) predicting the personality of users based on the text they have consumed. The second model is novel and without precedent in the literature. We recruited active Reddit users (N=1,105) of fiction-writing communities. The participants completed a Big Five personality questionnaire and consented for their Reddit activity to be scraped and used to create a machine learning model. We trained an natural language processing model [Bidirectional Encoder Representations from Transformers (BERT)], predicting personality from produced text (average performance: r=0.33). We then applied this model to a new set of Reddit users (N=10,050), predicted their personality based on their produced text, and trained a second BERT model to predict their predicted-personality scores based on consumed text (average performance: r=0.13). By doing so, we provide the first glimpse into the linguistic markers of personality-congruent consumed content.

The selective targeting of mutated kinases in cancer therapies has the potential to improve therapeutic success and thereby the survival of patients. In the case of melanoma, the constitutively active MAPK pathway is targeted by a combinatorial inhibition of BRAF and MEK activities. These MAPK pathway players may display patient-specific differences in the onco-kinase mutation spectrum, which needs to be considered for the design of more efficient personalized therapies. Here, we extend a bioluminescence-based kinase conformation biosensor (KinCon) to allow for live-cell tracking of interconnected kinase activity states. First, we show that common MEK1 patient mutations promote a structural rearrangement of the kinase to an opened and active conformation. This effect was reversible by the binding of MEK inhibitors to mutated MEK1, as shown in biosensor assays and molecular dynamics simulations. Second, we implement a novel application of the KinCon technology for tracking the simultaneous, vertical targeting of the two functionally linked kinases BRAF and MEK1. Thus, we demonstrate that, in the presence of constitutively active BRAF-V600E, specific inhibitors of both kinases are efficient in driving MEK1 into a closed, inactive conformation state. We compare current melanoma treatments and show that combinations of BRAFi and MEKi display a more pronounced structural change of the drug sensor than the respective single agents, thereby identifying synergistic effects among these drug combinations. In summary, we depict the extension of the KinCon biosensor technology to systematically validate, anticipate, and personalize tailored drug arrangements using a multiplexed setup.

During political campaigns, candidates use rhetoric to advance competing visions and assessments of their country. Research reveals that the moral language used in this rhetoric can significantly influence citizens' political attitudes and behaviors; however, the moral language actually used in the rhetoric of elites during political campaigns remains understudied. Using a data set of every tweet (N=139,412) published by 39 US presidential candidates during the 2016 and 2020 primary elections, we extracted moral language and constructed network models illustrating how candidates' rhetoric is semantically connected. These network models yielded two key discoveries. First, we find that party affiliation clusters can be reconstructed solely based on the moral words used in candidates' rhetoric. Within each party, popular moral values are expressed in highly similar ways, with Democrats emphasizing careful and just treatment of individuals and Republicans emphasizing in-group loyalty and respect for social hierarchies. Second, we illustrate the ways in which outsider candidates like Donald Trump can separate themselves during primaries by using moral rhetoric that differs from their parties' common language. Our findings demonstrate the functional use of strategic moral rhetoric in a campaign context and show that unique methods of text network analysis are broadly applicable to the study of campaigns and social movements.

Lipid monolayers are ubiquitous in biological systems and have multiple roles in biotechnological applications, such as lipid coatings that enhance colloidal stability or prevent surface fouling. Despite the great technological importance of surface-adsorbed lipid monolayers, the connection between their formation and the chemical characteristics of the underlying surfaces has remained poorly understood. Here, we elucidate the conditions required for stable lipid monolayers nonspecifically adsorbed on solid surfaces in aqueous solutions and water/alcohol mixtures. We use a framework that combines the general thermodynamic principles of monolayer adsorption with fully atomistic molecular dynamics simulations. We find that, very universally, the chief descriptor of adsorption free energy is the wetting contact angle of the solvent on the surface. It turns out that monolayers can form and remain thermodynamically stable only on substrates with contact angles above the adsorption contact angle, θads. Our analysis establishes that θads falls into a narrow range of around 60∘-70∘ in aqueous media and is only weakly dependent on the surface chemistry. Moreover, to a good approximation, θads is roughly determined by the ratio between the surface tensions of hydrocarbons and the solvent. Adding small amounts of alcohol to the aqueous medium lowers θads and thereby facilitates monolayer formation on hydrophilic solid surfaces. At the same time, alcohol addition weakens the adsorption strength on hydrophobic surfaces and results in a slowdown of the adsorption kinetics, which can be useful for the preparation of defect-free monolayers.

Process defects currently limit the use of metal additive manufacturing (AM) components in industries due to shorter fatigue life, potential for catastrophic failure, and lower strength. Conditions under which these defects form, and their mechanisms, are starting to be analyzed to improve reliability and structural integrity of these highly customized parts. We use in situ, high-speed X-ray imaging in conjunction with a high throughput laser, powder-blown directed energy deposition setup to observe powder particle impact behavior within the melt pool. Through fundamental observations of the stochastic, violent powder delivery in powder-blown DED, we uncover a unique pore formation mechanism. We find that a pore can form due to air-cushioning, where vapor from the carrier gas or environment is entrapped between the solid powder particle surface and liquid melt pool surface. A critical time constant is established for the mechanism, and X-ray computed tomography is used to further analyze and categorize the new type of "air-cushioning" pores. It is shown that the air-cushioning mechanism can occur under multiple laser processing conditions, and we show that air-cushioning pores are more likely to be formed when powder particles are larger than 70 μm. By quantifying the effect of powder particle impact, we identify new avenues for development of high-quality laser, powder-blown DED products. Furthermore, we deepen knowledge on defect formation in metal additive manufacturing, which is being increasingly utilized in high performance situations such as aerospace, automotive, and biomedical industries.

Records of element ratios obtained from the Maldives Inner Sea sediments provide a detailed view on how the Indian Monsoon System has varied at high-resolution time scales. Here, we present records from International Ocean Discovery Program (IODP) Site U1471 based on a refined chronology through the past 550,000 years. The record's high resolution and a proper approach to set the chronology allowed us to reconstruct changes in the Indian Monsoon System on a scale of anomalies and to verify their relationships with established records from the East Asian Monsoon System. On the basis of Fe/sum and Fe/Si records, it can be demonstrated that the Asia continental aridity tracks sea-level changes, while the intensity of winter monsoon winds responds to changes in Northern Hemisphere summer insolation. Furthermore, the anomalies of continental aridity and intensity of winter monsoon winds at millennial-scale events exhibit power in the precession band, nearly in antiphase with Northern Hemisphere summer insolation. These observations indicate that the insolation drove the anomalies in the Indian Summer Monsoon. The good correspondence between our record and the East Asian monsoon anomaly records suggests the occurrence of anomalous widespread arid events in Asia.

In hybrid perovskite solar cells (PSCs), the reaction of hydrogens (H) located in the amino group of the organic A-site cations with their neighboring halides plays a central role in degradation. Inspired by the retarded biological activities of cells in heavy water, we replaced the light H atom with its abundant, twice-as-heavy, nonradioactive isotope, deuterium (D) to hamper the motion of H. This D substitution retarded the formation kinetics of the detrimental H halides in Pb-based PSCs, as well as the H bond-mediated oxidation of Sn2+ in Sn-Pb-based narrow-bandgap PSCs, evidenced by accelerated stability studies. A computational study indicated that the zero point energy of D-based formamidinium (FA) is lower than that of pristine FA. In addition, the smaller increase in entropy in D-based FA than in pristine FA accounts for the increased formation free energy of the Sn2+ vacancies, which leads to the retarded oxidation kinetics of Sn2+. In this study, we show that substituting active H with D in organic cations is an effective way to enhance the stability of PSCs without sacrificing photovoltaic (PV) performance. This approach is also adaptable to other stabilizing methods.

The locations of minerals and mineral-forming environments, despite being of great scientific importance and economic interest, are often difficult to predict due to the complex nature of natural systems. In this work, we embrace the complexity and inherent "messiness" of our planet's intertwined geological, chemical, and biological systems by employing machine learning to characterize patterns embedded in the multidimensionality of mineral occurrence and associations. These patterns are a product of, and therefore offer insight into, the Earth's dynamic evolutionary history. Mineral association analysis quantifies high-dimensional multicorrelations in mineral localities across the globe, enabling the identification of previously unknown mineral occurrences, as well as mineral assemblages and their associated paragenetic modes. In this study, we have predicted (i) the previously unknown mineral inventory of the Mars analogue site, Tecopa Basin, (ii) new locations of uranium minerals, particularly those important to understanding the oxidation-hydration history of uraninite, (iii) new deposits of critical minerals, specifically rare earth element (REE)- and Li-bearing phases, and (iv) changes in mineralization and mineral associations through deep time, including a discussion of possible biases in mineralogical data and sampling; furthermore, we have (v) tested and confirmed several of these mineral occurrence predictions in nature, thereby providing ground truth of the predictive method. Mineral association analysis is a predictive method that will enhance our understanding of mineralization and mineralizing environments on Earth, across our solar system, and through deep time.

The expanding field of precision gene editing using CRISPR/Cas9 has demonstrated its potential as a transformative technology in the treatment of various diseases. However, whether this genome-editing tool could be used to modify neural circuits in the central nervous system (CNS), which are implicated in complex behavioral traits, remains uncertain. In this study, we demonstrate the feasibility of noninvasive, intranasal delivery of adeno-associated virus serotype 9 (AAV9) vectors containing CRISPR/Cas9 cargo within the CNS resulting in modification of the HTR2A receptor gene. In vitro, exposure to primary mouse cortical neurons to AAV9 vectors targeting the HT2RA gene led to a concentration-dependent decrease in spontaneous electrical activity following multielectrode array (MEA) analysis. In vivo, at 5 weeks postintranasal delivery in mice, analysis of brain samples revealed single base pair deletions and nonsense mutations, leading to an 8.46-fold reduction in mRNA expression and a corresponding 68% decrease in the 5HT-2A receptor staining. Our findings also demonstrate a significant decrease in anxiety-like behavior in treated mice. This study constitutes the first successful demonstration of a noninvasive CRISPR/Cas9 delivery platform, capable of bypassing the blood-brain barrier and enabling modulation of neuronal 5HT-2A receptor pathways. The results of this study targeting the HTR2A gene provide a foundation for the development of innovative therapeutic strategies for a broad range of neurological disorders, including anxiety, depression, attentional deficits, and cognitive dysfunction.

All female vertebrates develop a pair of ovaries except for birds, in which only the left gonad develops into an ovary, whereas the right gonad regresses. Previous studies found that the transcription factor Paired-Like Homeodomain 2 (PITX2), a key mediator for left/right morphogenesis in vertebrates, was also implicated in asymmetric gonadal development in chickens. In this study, we systematically screened and validated the signaling pathways that could be targeted by Pitx2 to control unilateral gonad development. Integrated chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analyses indicated that Pitx2 directly binds to the promoters of genes encoding neurotransmitter receptors and leads to left-biased expression of both serotonin and dopamine receptors. Forcibly activating serotonin receptor 5-Hydroxytryptamine Receptor 1B (HTR1B) signaling could induce ovarian gene expression and cell proliferation to partially rescue the degeneration of the right gonad. In contrast, inhibiting serotonin signaling could block the development of the left gonad. These findings reveal a PITX2-HTR1B genetic pathway that guides the left-specific ovarian growth in chickens. We also provided new evidence showing neurotransmitters stimulate the growth of nonneuronal cells during the early development of reproductive organs well before innervation.

Childhood stress has a deleterious impact on youth behavior and brain development. Resilience factors such as positive parenting (e.g. expressions of warmth and support) may buffer youth against the negative impacts of stress. We sought to determine whether positive parenting buffers against the negative impact of childhood stress on youth behavior and brain structure and to investigate differences between youth-reported parenting and caregiver-reported parenting. Cross-sectional behavioral and neuroimaging data were analyzed from 482 youth (39% female and 61% male, ages 10-17) who participated in an ongoing research initiative, the Healthy Brain Network (HBN). Regression models found that youth-reported positive parenting buffered against the association between childhood stress and youth behavioral problems (β = -0.10, P = 0.04) such that increased childhood stress was associated with increased youth behavior problems only for youth who did not experience high levels of positive parenting. We also found that youth-reported positive parenting buffered against the association between childhood stress and decreased hippocampal volumes (β = 0.07, P = 0.02) such that youth who experienced high levels of childhood stress and who reported increased levels of positive parenting did not exhibit smaller hippocampal volumes. Our work identifies positive parenting as a resilience factor buffering youth against the deleterious impact of stressful childhood experiences on problem behaviors and brain development. These findings underscore the importance of centering youth perspectives of stress and parenting practices to better understand neurobiology, mechanisms of resilience, and psychological well-being.

Nearly 95% of Alzheimer's disease (AD) occurs sporadically without genetic linkage. Aging, hypertension, high cholesterol content, and diabetes are known nongenomic risk factors of AD. Aggregation of Aβ peptides is an initial event of AD pathogenesis. Aβ peptides are catabolic products of a type I membrane protein called amyloid precursor protein (APP). Aβ40 is the major product, whereas the 2-residue-longer version, Aβ42, induces amyloid plaque formation in the AD brain. Since cholesterol content is one risk factor for sporadic AD, we aimed to explore whether cholesterol in the membrane affects the structure of the APP transmembrane region, thereby modulating the γ-secretase cutting behavior. Here, we synthesized several peptides containing the APP transmembrane region (sequence 693-726, corresponding to the Aβ22-55 sequence) with one or two Cys mutations for spin labeling. We performed three electron spin resonance experiments to examine the structural changes of the peptides in liposomes composed of dioleoyl phosphatidylcholine and different cholesterol content. Our results show that cholesterol increases membrane thickness by 10% and peptide length accordingly. We identified that the di-glycine region of Aβ36-40 (sequence VGGVV) exhibits the most profound change in response to cholesterol compared with other segments, explaining how the presence of cholesterol affects the γ-secretase cutting site. This study provides spectroscopic evidence showing how cholesterol modulates the structure of the APP transmembrane region in a lipid bilayer.

Evidence suggests that hippocampal adult neurogenesis is critical for discriminating considerably interfering memories. During adult neurogenesis, synaptic competition modifies the weights of synaptic connections nonlocally across neurons, thus providing a different form of unsupervised learning from Hebb's local plasticity rule. However, how synaptic competition achieves separating similar memories largely remains unknown. Here, we aim to link synaptic competition with such pattern separation. In synaptic competition, adult-born neurons are integrated into the existing neuronal pool by competing with mature neurons for synaptic connections from the entorhinal cortex. We show that synaptic competition and neuronal maturation play distinct roles in separating interfering memory patterns. Furthermore, we demonstrate that a feedforward neural network trained by a competition-based learning rule can outperform a multilayer perceptron trained by the backpropagation algorithm when only a small number of samples are available. Our results unveil the functional implications and potential applications of synaptic competition in neural computation.