Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19.

The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.

A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules.

Halogen-containing molecules are ubiquitous in modern society and present unique chemical possibilities. As a whole, de novo fermentation and synthetic pathway construction for these molecules remain relatively underexplored and could unlock molecules with exciting new applications in industries ranging from textiles to agrochemicals to pharmaceuticals. Here, we report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in Escherichia coli from glucose. First, we engineer E. coli to produce between 300 and 700 mg/L of six different halogenated tryptophan precursors. Second, we harness the native promiscuity of multiple downstream enzymes to access unexplored regions of metabolism. Finally, through modular co-culture fermentations, we demonstrate a plug-and-play bioproduction platform, culminating in the generation of 26 distinct halogenated molecules produced de novo including precursors to prodrugs 4-chloro- and 4-bromo-kynurenine and new-to-nature halogenated beta carbolines.

Multiparametric Single-Vesicle Flow Cytometry Resolves Extracellular Vesicle Heterogeneity and Reveals Selective Regulation of Biogenesis and Cargo Distribution.

Mammalian cells release a heterogeneous array of extracellular vesicles (EVs) that contribute to intercellular communication by means of the cargo that they carry. To resolve EV heterogeneity and determine if cargo is partitioned into select EV populations, we developed a method named "EV Fingerprinting" that discerns distinct vesicle populations using dimensional reduction of multiparametric data collected by quantitative single-EV flow cytometry. EV populations were found to be discernible by a combination of membrane order and EV size, both of which were obtained through multiparametric analysis of fluorescent features from the lipophilic dye Di-8-ANEPPS incorporated into the lipid bilayer. Molecular perturbation of EV secretion and biogenesis through respective ablation of the small GTPase Rab27a and overexpression of the EV-associated tetraspanin CD63 revealed distinct and selective alterations in EV populations, as well as cargo distribution. While Rab27a disproportionately affects all small EV populations with high membrane order, the overexpression of CD63 selectively increased the production of one small EV population of intermediate membrane order. Multiplexing experiments subsequently revealed that EV cargos have a distinct, nonrandom distribution with CD63 and CD81 selectively partitioning into smaller vs larger EVs, respectively. These studies not only present a method to probe EV biogenesis but also reveal how the selective partitioning of cargo contributes to EV heterogeneity.

Nature as Medicine and Classroom: Evaluating an Innovative, Outdoor Course for Medical and Dental Students.

Background: There is a growing, global awareness and recognition of the important, interdependent relationships between our natural world and human health. Several contemporary health organizations have placed calls to action and emphasize an urgent need for collaboration and interdisciplinary research, education, and clinical work to address the increasing degradation of our planetary and human health. With more research dedicated to nature's health impacts, health professions schools would benefit by including such training in their programs while also cultivating a comprehensive mind-body health perspective to support both the health of student practitioners and their future patients. Objective: The present program evaluation investigates a five-day outdoor mini-course covering nature-based health techniques at a medical and dental school in the American Northeast. This unique outdoor course combines nature, creativity, and reflection within the context of modern medicine. Methods: A concurrent mixed-method design using descriptive statistics, quantitative and qualitative data from students' anonymous final course evaluations and final reflection projects are evaluated. Results: Data suggests that students benefitted from their experience during this five-day course. Students provided feedback reinforcing the enjoyment and transformative outcomes gleaned from the course experiences. Students entered the course describing feeling stressed, overwhelmed, and overextended, not uncommon for learners in medical and dental school, and completed the course describing the acquisition of applicable skills, increased attention and mindfulness, creativity, and connection to the natural world. Conclusions: Students described a positive experience of the course. Several areas of personal and professional development were also described, such as improvements within cognitive domains, enhanced connection with nature, others, and themselves, increased mindfulness, and overall improved well-being. Findings have implications for medical and dental programs on how such innovative training may lean into the work of nature-based care to provide for the whole person.

Life satisfaction and job and personal resources among public workers with non-standard work schedules.

BACKGROUND: While the link between non-standard work schedules and poor health outcomes is established, few studies have examined how resources both in and outside of work can support the well-being of workers with non-standard work schedules. METHODS: Using a cross-sectional survey, we assessed the association between one facet of well-being, life satisfaction, and job and personal resources. In 2019, an electronic survey was administered to two unionized, public service populations who work non-standard work schedules: transportation maintainers and correctional supervisors. We assessed life satisfaction with a 10-item scale; a broad set of job resources (reward satisfaction, supervisor support, co-worker support, schedule satisfaction, and working hours fit); and a broad set of personal resources (health status, sleep, physical activity, and finances). We used log-binomial regression models to estimate prevalence ratios and 95% confidence intervals among statistically significant univariate predictors. RESULTS: Of the 316 workers surveyed, the majority were male (86%), White (68%), and reported positive life satisfaction (56%). In multivariate models, the prevalence of positive life satisfaction was higher in workers reporting reward satisfaction (PR:1.35, 95% CI: 1.11, 1.65; p = 0.003), good work schedule fit (PR:1.43, 95% CI: 1.12, 1.83; p = 0.004), good health (PR:2.92, 95% CI: 1.70, 4.99; p < 0.0001), and good finances (PR:1.32, 95% CI: 1.01, 1.72; p = 0.04). CONCLUSION: Employers should consider increasing work recognition, as well as improving schedule fit, financial well-being, and overall good health in support of worker life satisfaction and ultimately well-being.

Adaptive foraging behaviours in the Horn of Africa during Toba supereruption.

Although modern humans left Africa multiple times over 100,000 years ago, those broadly ancestral to non-Africans dispersed less than 100,000 years ago1. Most models hold that these events occurred through green corridors created during humid periods because arid intervals constrained population movements2. Here we report an archaeological site-Shinfa-Metema 1, in the lowlands of northwest Ethiopia, with Youngest Toba Tuff cryptotephra dated to around 74,000 years ago-that provides early and rare evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow. The diet included a wide range of terrestrial and aquatic animals. Stable oxygen isotopes from fossil mammal teeth and ostrich eggshell show that the site was occupied during a period of high seasonal aridity. The unusual abundance of fish suggests that capture occurred in the ever smaller and shallower waterholes of a seasonal river during a long dry season, revealing flexible adaptations to challenging climatic conditions during the Middle Stone Age. Adaptive foraging along dry-season waterholes would have transformed seasonal rivers into 'blue highway' corridors, potentially facilitating an out-of-Africa dispersal and suggesting that the event was not restricted to times of humid climates. The behavioural flexibility required to survive seasonally arid conditions in general, and the apparent short-term effects of the Toba supereruption in particular were probably key to the most recent dispersal and subsequent worldwide expansion of modern humans.

Fluorescence-Based Screens for Engineering Enzymes Linked to Halogenated Tryptophan.

Directed evolution is often limited by the throughput of accurate screening methods. Here we demonstrate the feasibility of utilizing a singular transcription factor (TF)-system that can be refactored in two ways (both as an activator and repressor). Specifically, we showcase the use of previously evolved 5-halo- or 6-halo-tryptophan-specific TF biosensors suitable for the detection of a halogenated tryptophan molecule in vivo. We subsequently validate the biosensor's utility for two halogenase-specific halo-tryptophan accumulation screens. First, we isolated 5-tryptophan-halogenase, XsHal, from a mixed pool of halogenases with 100% efficiency. Thereafter, we generated a targeted library of the catalytic residue of 6-tryptophan halogenase, Th-Hal, and isolated functioning halogenases with 100% efficiency. Lastly, we refactor the TF circuit to respond to the depletion of halogenated tryptophan and prototype a high-throughput biosensor-directed evolution scheme to screen for downstream enzyme variants capable of promiscuously converting halogenated tryptophan. Altogether, this work takes a significant step toward the rapid and higher throughput screening of halogenases and halo-tryptophan converting enzymes to further reinforce efforts to enable high-level bioproduction of halogenated chemicals.

Trust with increasing and decreasing reliability.

OBJECTIVE: The primary purpose was to determine how trust changes over time when automation reliability increases or decreases. A secondary purpose was to determine how task-specific self-confidence is associated with trust and reliability level. BACKGROUND: Both overtrust and undertrust can be detrimental to system performance; therefore, the temporal dynamics of trust with changing reliability level need to be explored. METHOD: Two experiments used a dominant-color identification task, where automation provided a recommendation to users, with the reliability of the recommendation changing over 300 trials. In Experiment 1, two groups of participants interacted with the system: one group started with a 50% reliable system which increased to 100%, while the other used a system that decreased from 100% to 50%. Experiment 2 included a group where automation reliability increased from 70% to 100%. RESULTS: Trust was initially high in the decreasing group and then declined as reliability level decreased; however, trust also declined in the 50% increasing reliability group. Furthermore, when user self-confidence increased, automation reliability had a greater influence on trust. In Experiment 2, the 70% increasing reliability group showed increased trust in the system. CONCLUSION: Trust does not always track the reliability of automated systems; in particular, it is difficult for trust to recover once the user has interacted with a low reliability system. APPLICATIONS: This study provides initial evidence into the dynamics of trust for automation that gets better over time suggesting that users should only start interacting with automation when it is sufficiently reliable.

Leveraging a Y. lipolytica naringenin chassis for biosynthesis of apigenin and associated glucoside.

Flavonoids are a diverse set of natural products with promising bioactivities including anti-inflammatory, anti-cancer, and neuroprotective properties. Previously, the oleaginous host Yarrowia lipolytica has been engineered to produce high titers of the base flavonoid naringenin. Here, we leverage this host along with a set of E. coli bioconversion strains to produce the flavone apigenin and its glycosylated derivative isovitexin, two potential nutraceutical and pharmaceutical candidates. Through downstream strain selection, co-culture optimization, media composition, and mutant isolation, we were able to produce168 mg/L of apigenin, representing a 46% conversion rate of 2-(R/S)-naringenin to apigenin. This apigenin platform was modularly extended to produce isovitexin by addition of a second bioconversion strain. Together, these results demonstrate the promise of microbial production and modular bioconversion to access diversified flavonoids.

Volitional Change in Pathological Traits: Can People Change Their Maladaptive Traits?

Research suggests people want to change their normative personality traits-and they can volitionally do so. However, studies have not yet addressed volitional change in pathological personality. Consequently, the current study examined (a) people's desires to change pathological traits, (b) whether these change goals predict subsequent trait change, (c) whether this withstands controlling normative traits, and (d) the extent to which pathological trait change predicts relevant outcomes. College students (N = 463) self-reported their pathological traits weekly for up to 16 weeks. People with elevated pathological traits generally desired to decrease these traits. Furthermore, goals to change negative affectivity and disinhibition predicted corresponding trait change. Thus, people want to reduce their pathological traits-and they may be able to do so for some traits.

Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not?

BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.

Efficient engineering of human and mouse primary cells using peptide-assisted genome editing.

Simple, efficient and well-tolerated delivery of CRISPR genome editing systems into primary cells remains a major challenge. Here we describe an engineered Peptide-Assisted Genome Editing (PAGE) CRISPR-Cas system for rapid and robust editing of primary cells with minimal toxicity. The PAGE system requires only a 30-min incubation with a cell-penetrating Cas9 or Cas12a and a cell-penetrating endosomal escape peptide to achieve robust single and multiplex genome editing. Unlike electroporation-based methods, PAGE gene editing has low cellular toxicity and shows no significant transcriptional perturbation. We demonstrate rapid and efficient editing of primary cells, including human and mouse T cells, as well as human hematopoietic progenitor cells, with editing efficiencies upwards of 98%. PAGE provides a broadly generalizable platform for next-generation genome engineering in primary cells.

Impact of public health policy and mobility change on transmission potential of severe acute respiratory syndrome coronavirus 2 in Rhode Island, March 2020 - November 2021.

To study the SARS-CoV-2 transmission potential in Rhode Island (RI) and its association with policy changes and mobility changes, the time-varying reproduction number, Rt, was estimated. The daily incident case counts (16 March 2020, through 30 November 2021) were bootstrapped within a 15-day sliding window and multiplied by Poisson-distributed multipliers (λ = 4, sensitivity analysis: 11) to generate 1000 estimated infection counts, to which EpiEstim was applied to generate Rt time series. The median Rt percentage change when policies changed was estimated. The time lag correlations were assessed between the 7-day moving average of the relative changes in Google mobility data in the first 90 days, and Rt and estimated infection count, respectively. There were three major pandemic waves in RI in 2020-2021: spring 2020, winter 2020-2021 and fall-winter 2021. The median Rt fluctuated within the range of 0.5-2 from April 2020 to November 2021. Mask mandate (18 April 2020) was associated with a decrease in Rt (-25.99%, 95% CrI: -37.42%, -14.30%). Termination of mask mandates on 6 July 2021 was associated with an increase in Rt (36.74%, 95% CrI: 27.20%, 49.13%). Positive correlations were found between changes in grocery and pharmacy, Rt retail and recreation, transit, and workplace visits, for both Rt and estimated infection count, respectively. Negative correlations were found between changes in residential area visits for both Rt and estimated infection count, respectively. Public health policies enacted in RI were associated with changes in the pandemic trajectory. This ecological study provides further evidence of how non-pharmaceutical interventions and vaccination slowed COVID-19 transmission in RI.

Toenail zinc and risk of prostate cancer in the MCC-Spain case-control study.

BACKGROUND: Some researchers have suggested that zinc (Zn) could reduce the risk of prostate cancer (PC). However, research from observational studies on the relationship between PC risk and biomarkers of Zn exposure shows conflicting results. OBJECTIVES: To evaluate the association between toenail Zn and PC, considering tumour extension and aggressiveness, along with a gene-environment approach, exploring the interaction of individual genetic susceptibility to PC in the relationship between toenail Zn and PC. METHODS: In MCC-Spain study we invited all incident PC cases diagnosed in the study period (2008-2013) and recruited randomly selected general population controls. In this report we included 913 cases and 1198 controls with toenail Zn determined by inductively coupled plasma mass spectrometry. To measure individual genetic susceptibility, we constructed a polygenic risk score based on known PC-related single nucleotide polymorphisms. The association between toenail Zn and PC was explored with mixed logistic and multinomial regression models. RESULTS: Men with higher toenail Zn had higher risk of PC (OR quartile 4 vs.1: 1.41; 95% CI: 1.07-1.85). This association was slightly higher in high-grade PC [(ISUP≤2 Relative risk ratio (RRR) quartile 4 vs.1: 1.36; 1.01-1.83) vs. (ISUP3-5 RRR quartile 4 vs.1: 1.64; 1.06-2.54)] and in advanced tumours [(cT1-cT2a RRR quartile 4 vs.1: 1.40; 95% CI: 1.05-1.89) vs. (cT2b-cT4 RRR quartile 4 vs.1: 1.59; 1.00-2.53)]. Men with lower genetic susceptibility to PC were those at higher risk of PC associated with high toenail Zn (OR quartile 4 vs.1: 2.18; 95% CI: 1.08-4.40). DISCUSSION: High toenail Zn levels were related to a higher risk for PC, especially for more aggressive or advanced tumours. This effect was stronger among men with a lower genetic susceptibility to PC.

Protocolo de desensibilización para adalimumab en artritis psoriásica / Desensitization protocol for adalimumab in psoriatic arthritis

Adalimumab es una alternativa terapéutica en diversas enfermedades inflamatorias y autoinmunes. Aunque suele ser un fármaco bien tolerado, las reacciones de hipersensibilidad se presentan aproximadamente en un 1% de los pacientes, y si aparecen, el tratamiento debe interrumpirse y considerarse el cambio a otro fármaco. Se describe el caso de una mujer con artropatía psoriásica que presentó episodios de hipersensibilidad a varias líneas de tratamiento: apremilast, secukinumab, adalimumab, etanercept y tofacitinib. Ante el fracaso de las diversas alternativas utilizadas, se realizó una valoración conjunta por los Servicios de Reumatología, Alergología y Farmacia Hospitalaria sobre la posibilidad de reintroducir adalimumab, proponiéndose un protocolo de desensibilización (PD) con el objetivo de inducir tolerancia a dicho fármaco. El PD se diseñó con el objetivo de alcanzar progresivamente la dosis terapéutica de 40 mg. Para ello, se programó la administración de 6 dosis –una cada 15 días– con un aumento progresivo de la concentración en cada dosis. Durante los ciclos de administración no se observaron efectos adversos. Después de las 6 dosis del PD, la paciente continuó con la dosis habitual de adalimumab de 40 mg cada 15 días durante 7 meses. Se alcanzó mejoría clínica y analítica, con la perspectiva de continuar el tratamiento. Este protocolo permitió la reintroducción de adalimumab con éxito. (AU)

Adalimumab is a therapeutic alternative for several inflammatory and autoimmune diseases. Although it is generally a well-tolerated drug, hypersensitivity reactions occur in approximately 1% of patients, and if they appear, treatment should be discontinued and a switch to another drug should be considered. We describe the case of a woman with psoriatic arthritis who presented episodes of hypersensitivity to several lines of treatment: apremilast, secukinumab, adalimumab, etanercept and tofacitinib. Given the failure of the various alternatives used, a joint assessment was made by the Rheumatology, Allergology and Hospital Pharmacy Departments on the possibility of reintroducing adalimumab, proposing a desensitization protocol (DP) with the aim of inducing tolerance to this drug. The DP was designed with the objective of progressively reaching the therapeutic dose of 40 mg. For this purpose, the administration of 6 doses was scheduled -one every 15 days- with a progressive increase in concentration at each dose. No adverse events were observed during the administration cycles. After the 6 doses of DP, the patient continued with the usual dose of adalimumab of 40 mg every 15 days for 7 months. Clinical and analytical improvement was achieved, with the prospect of continuing treatment. This protocol allowed the successful reintroduction of adalimumab. (AU)

Engineered Living Material Bioreactors with Tunable Mechanical Properties using Vat Photopolymerization.

3D-printed engineered living materials (ELM) are promising bioproduction platforms for agriculture, biotechnology, sustainable energy, and green technology applications. However, the design of these platforms faces several challenges, such as the processability of these materials into complex form factors and control over their mechanical properties. Herein, ELM are presented as 3D-printed bioreactors with arbitrary shape geometries and tunable mechanical properties (moduli and toughness). Poly(ethylene glycol) diacrylate (PEGDA) is used as the precursor to create polymer networks that encapsulate the microorganisms during the vat photopolymerization process. A major limitation of PEGDA networks is their propensity to swell and fracture when submerged in water. The authors overcame this issue by adding glycerol to the resin formulation to 3D print mechanically tough ELM hydrogels. While polymer concentration affects the modulus and reduces bioproduction, ELM bioreactors still maintain their metabolic activity regardless of polymer concentration. These ELM bioreactors have the potential to be used in different applications for sustainable architecture, food production, and biomedical devices that require different mechanical properties from soft to stiff.

Neoplasia in an assurance population of Puerto Rican crested toads (Peltophryne lemur).

Disease monitoring of amphibian assurance populations is an important buffer against ongoing global extinctions. This study documents a high incidence of neoplasia in a zoo-managed assurance population of Puerto Rican crested toads (Peltophryne lemur; PRCTs). Over 5 years, neoplasia was diagnosed in 17/49 (35%) submitted adult PRCTs and was the cause of death or euthanasia in 13/17 (72%). Most toads were male (16/17; 94%) and 6 to 11-years-old (average 8.1 years). Notably, seven toads (41%) had multiple neoplasms. Of the 29 neoplasms identified, 17 (59%) were cutaneous or subcutaneous. The most common neoplasms included mast cell tumors (MCTs; 8/29; 28%), histiocytic sarcomas (6/29; 21%), lymphoma/leukemia (4/29; 14%), and squamous cell carcinomas (3/29; 10%). Distant metastases were documented in 6/8 (75%) toads with MCTs. Causes for neoplasia in this population were not determined though may include genetic or environmental factors. Continued investigations of managed endangered amphibians will help elucidate mechanisms of carcinogenesis.

Does the Degree of Prematurity Relate to the Bayley-4 Scores Earned by Matched Samples of Infants and Toddlers across the Cognitive, Language, and Motor Domains?

The literature on children born prematurely has consistently shown that full-term babies outperform preterm babies by about 12 IQ points, even when tested as adolescents, and this advantage for full-term infants extends to the language and motor domains as well. The results of comprehensive meta-analyses suggest that the degree of prematurity greatly influences later test performance, but these inferences are based on data from an array of separate studies with no control of potential confounding variables such as age. This study analyzed Bayley-4 data for 66 extremely premature infants and toddlers (<32 weeks), 70 moderately premature children (32-36 weeks), and 133 full-term children. All groups were carefully matched on key background variables by the test publisher during the standardization of the Bayley-4. This investigation analyzed data on the five subtests: cognitive, expressive communication, receptive communication, fine motor, and gross motor. A multivariate analysis of covariance (MANCOVA) assessed for group mean differences across the three subsamples, while controlling for the children's age. Extremely premature children scored significantly lower than moderately premature children on all subtests, and both preterm groups were significantly outscored by the full-term sample across all domains. In each set of comparisons, the cognitive and motor subtests yielded the largest differences, whereas language development, both expressive and receptive, appeared the least impacted by prematurity. A follow-up MANOVA was conducted to examine full-term versus preterm discrepancies on the five subtests for infants (2-17 months) vs. toddlers (18-42 months). For that analysis, the two preterm groups were combined into a single preterm sample, and a significant interaction between the age level and group (full-term vs. preterm) was found. Premature infants scored lower than premature toddlers on receptive communication, fine motor, and cognitive. Neither expressive communication nor gross motor produced significant discrepancies between age groups The findings of this study enrich the preterm literature on the degree of prematurity; the age-based interactions have implications for which abilities are most likely to improve as infants grow into toddlerhood.

Additive Manufacturing of Engineered Living Materials with Bio-augmented Mechanical Properties and Resistance to Degradation.

Engineered living materials (ELMs) combine living cells with polymeric matrices to yield unique materials with programmable functions. While the cellular platform and the polymer network determine the material properties and applications, there are still gaps in our ability to seamlessly integrate the biotic (cellular) and abiotic (polymer) components into singular material, then assemble them into devices and machines. Herein, we demonstrated the additive-manufacturing of ELMs wherein bioproduction of metabolites from the encapsulated cells enhanced the properties of the surrounding matrix. First, we developed aqueous resins comprising bovine serum albumin (BSA) and poly(ethylene glycol diacrylate) (PEGDA) with engineered microbes for vat photopolymerization to create objects with a wide array of 3D form factors. The BSA-PEGDA matrix afforded hydrogels that were mechanically stiff and tough for use in load-bearing applications. Second, we demonstrated the continuous in situ production of L-DOPA, naringenin, and betaxanthins from the engineered cells encapsulated within the BSA-PEGDA matrix. These microbial metabolites bioaugmented the properties of the BSA-PEGDA matrix by enhancing the stiffness (L-DOPA) or resistance to enzymatic degradation (betaxanthin). Finally, we demonstrated the assembly of the 3D printed ELM components into mechanically functional bolts and gears to showcase the potential to create functional ELMs for synthetic living machines.

Humans' (Homo sapiens), capuchin monkeys' (Sapajus [Cebus] apella), and rhesus macaques' (Macaca mulatta) size judgments shift when stimuli change in frequency.

When making decisions, humans often strive to uphold objective, absolute standards, such as about what is small versus large, blue versus purple, or unfair versus fair, suggesting that our judgments should not be swayed by extraneous factors such as the sequence or frequency of events to be judged. Yet in previous research, when some items (e.g., threatening faces) became less frequent, humans responded by expanding their concept (of "threatening") to include more ambiguous stimuli. We assessed the origins of this perceptual frequency bias by testing 25 capuchins, seven rhesus monkeys, and 102 humans on a computer task in which they had to classify one circle at a time (pulled from a continuum of 50 circle sizes) as either small or large. Small and large circles initially appeared with equal probability but over time small circles either became less frequent, more frequent, or did not change in frequency. All three species showed changes in judgment, but contrary to predictions, they contracted, rather than expanded, their size judgments of the less frequent category. In other words, when small circles became rare, participants were more likely to judge ambiguous circles sizes as large (and vice versa). This may have been due to the immediate explicit feedback, as has recently been found in humans, and we consider possible mechanisms driving our participants' responses. These results suggest that humans' difficulties in maintaining absolute standards are shared with other animals. (PsycInfo Database Record (c) 2023 APA, all rights reserved).