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Abstract Mars is a particularly attractive candidate among known astronomical objects to potentially host life. Results from space exploration missions have provided insights into Martian geochemistry that indicate oxychlorine species, particularly perchlorate, are ubiquitous features of the Martian geochemical landscape. Perchlorate presents potential obstacles for known forms of life due to its toxicity. However, it can also provide potential benefits, such as producing brines by deliquescence, like those thought to exist on present-day Mars. Here we show perchlorate brines support folding and catalysis of functional RNAs, while inactivating representative protein enzymes. Additionally, we show perchlorate and other oxychlorine species enable ribozyme functions, including homeostasis-like regulatory behavior and ribozyme-catalyzed chlorination of organic molecules. We suggest nucleic acids are uniquely well-suited to hypersaline Martian environments. Furthermore, Martian near- or subsurface oxychlorine brines, and brines found in potential lifeforms, could provide a unique niche for biomolecular evolution.

Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

ABSTRACT Members of the Enterobacteriaceae and Enterococcus are associated with persistent gut inflammation due to rapid colonization combined with pathogenic tendencies. Here, we investigated the functions of gut microbial populations resulting in persistent gut inflammation. In this study, we utilized the IL-10 knockout mouse model and induced colitis using dextran sulfate sodium (2%) after development. Dams during gestation were provided cefoperazone to induce vertically transmitted dysbiosis in the pups that were monitored in this study. We characterized the dysbiotic gut microbial community and potential crosstalk of these microbes, and host gene expression changes to identify bacterial populations and potential functions that were involved in gut inflammation. We isolated Enterobacteriaceae populations from mice to validate the utilization of sulfur-containing amino acids. Members of Enterobacteriaceae and Enterococcus were highly detected in inflamed mice. Enterobacteriaceae populations containing L-cysteine dioxygenase were strongly correlated with the upregulation of host gene CSAD, responsible for cysteine breakdown. We observed that bacterial isolates from dysbiotic mice displayed increased growth rates when supplemented with L-cysteine, highlighting the use of sulfur metabolism. Our results show that microbial populations use alternate metabolisms and sequester host nutrients for growth, associated with inflammation in the gut.IMPORTANCEInflammatory bowel disease is associated with an increase in Enterobacteriaceae and Enterococcus species; however, the specific mechanisms are unclear. Previous research has reported the associations between microbiota and inflammation, here we investigate potential pathways that specific bacteria populations use to drive gut inflammation. Richie et al. show that these bacterial populations utilize an alternate sulfur metabolism and are tolerant of host-derived immune-response products. These metabolic pathways drive host gut inflammation and fuel over colonization of these pathobionts in the dysbiotic colon. Cultured isolates from dysbiotic mice indicated faster growth supplemented with L-cysteine, showing these microbes can utilize essential host nutrients.

Structural biology education commonly employs molecular visualization software, such as PyMol, RasMol, and VMD, to allow students to appreciate structure--function relationships in biomolecules. In on-ground, classroom-based education, these programs are commonly used on University-owned devices with software preinstalled. Remote education typically involves the use of student-owned devices, which complicates the use of such software, owing to the fact that (a) student devices have differing configurations (e.g., Windows vs MacOS) and processing power, and (b) not all student devices are suitable for use with such software. Smartphones are near-ubiquitous devices, with smartphone ownership exceeding personal computer ownership, according to a recent survey. Here, we show the use of a smartphone-based augmented reality app, Augment, in a structural biology classroom exercise, which students installed independently without IT support. Post-lab attitudinal survey results indicate positive student experiences with this app. Based on our experiences, we suggest that smartphone-based molecular visualization software, such as that used in this exercise, is a powerful educational tool that is particularly well-suited for use in remote education.

Kinetic modeling has relied on using a tedious number of mathematical equations to describe molecular kinetics in interacting reactions. The long list of differential equations with associated abstract variables and parameters inevitably hinders readers’ easy understanding of the models. However, the mathematical equations describing the kinetics of biochemical reactions can be exactly mapped to the dynamics of voltages and currents in simple electronic circuits wherein voltages represent molecular concentrations and currents represent molecular fluxes. For example, we theoretically derive and experimentally verify accurate circuit models for Michaelis-Menten kinetics. Then, we show that such circuit models can be scaled via simple wiring among circuit motifs to represent more and arbitrarily complex reactions. Hence, we can directly map reaction networks to equivalent circuit schematics in a rapid, quantitatively accurate, and intuitive fashion without needing mathematical equations. We verify experimentally that these circuit models are quantitatively accurate. Examples include 1) different mechanisms of competitive, noncompetitive, uncompetitive, and mixed enzyme inhibition, important for understanding pharmacokinetics; 2) product-feedback inhibition, common in biochemistry; 3) reversible reactions; 4) multi-substrate enzymatic reactions, both important in many metabolic pathways; and 5) translation and transcription dynamics in a cell-free system, which brings insight into the functioning of all gene-protein networks. We envision that circuit modeling and simulation could become a powerful scientific communication language and tool for quantitative studies of kinetics in biology and related fields.

Ions in the Hofmeister series exhibit varied effects on biopolymers. Those classed as kosmotropes generally stabilize secondary structure, and those classed as chaotropes generally destabilize secondary structure. Here, we report that several anionic chaotropes exhibit unique effects on one DNA secondary structure - a G quadruplex. These chaotropes exhibit the expected behaviour (destabilization of secondary structure) in two other structural contexts: a DNA duplex and i-Motifs. Uniquely among secondary structures, we observe that G quadruplexes are comparatively insensitive to the presence of anionic chaotropes, but not other denaturants. Further, the presence of equimolar NaCl provided greater mitigation of the destabilization caused by other non-anionic denaturants. These results are consistent with the presence of monovalent cations providing an especially pronounced stabilizing effect to G quadruplexes when studied in denaturing solution conditions.

Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings. [ABSTRACT FROM AUTHOR]

The bacterial pathogen responsible for causing Lyme disease, Borrelia burgdorferi, is an atypical Gram-negative spirochete that is transmitted to humans via the bite of an infected Ixodes tick. In diderms, peptidoglycan (PG) is sandwiched between the inner and outer membrane of the cell envelope. In many other Gram-negative bacteria, PG is bound by protein(s), which provide both structural integrity and continuity between envelope layers. Here, we present evidence of a peptidoglycan-associated protein (PAP) in B. burgdorferi. Using an unbiased proteomics approach, we identified Neutrophil Attracting Protein A (NapA) as a PAP. Interestingly, NapA is a Dps homologue, which typically functions to bind and protect cellular DNA from damage during times of stress. While B. burgdorferi NapA is known to be involved in the oxidative stress response, it lacks the critical residues necessary for DNA binding. Biochemical and cellular studies demonstrate that NapA is localized to the B. burgdorferi periplasm and is indeed a PAP. Cryo-electron microscopy indicates that mutant bacteria, unable to produce NapA, have structural abnormalities. Defects in cell-wall integrity impact growth rate and cause the napA mutant to be more susceptible to osmotic and PG-specific stresses. NapA-linked PG is secreted in outer membrane vesicles and augments IL-17 production, relative to PG alone. Using microfluidics, we demonstrate that NapA acts as a molecular beacon-exacerbating the pathogenic properties of B. burgdorferi PG. These studies further our understanding of the B. burgdorferi cell envelope, provide critical information that underlies its pathogenesis, and highlight how a highly conserved bacterial protein can evolve mechanistically, while maintaining biological function.

Brucella abortus is a facultative, intracellular, zoonotic pathogen that resides inside macrophages during infection. This is a specialized niche where B. abortus encounters various stresses as it navigates through the macrophage. In order to survive this harsh environment, B. abortus utilizes post‐transcriptional regulation of gene expression through the use of small regulatory RNAs (sRNAs). Here, we characterize a Brucella sRNAs called MavR (for MurF‐ and virulence‐regulating sRNA), and we demonstrate that MavR is required for the full virulence of B. abortus in macrophages and in a mouse model of chronic infection. Transcriptomic and proteomic studies revealed that a major regulatory target of MavR is MurF. MurF is an essential protein that catalyzes the final cytoplasmic step in peptidoglycan (PG) synthesis; however, we did not detect any differences in the amount or chemical composition of PG in the ΔmavR mutant. A 6‐nucleotide regulatory seed region within MavR was identified, and mutation of this seed region resulted in dysregulation of MurF production, as well as significant attenuation of infection in a mouse model. Overall, the present study underscores the importance of sRNA regulation in the physiology and virulence of Brucella. [ABSTRACT FROM AUTHOR]

For layered metamaterial devices, the reflection and transmission coefficients at an interface typically depend on the properties of the coupling between different layers. In this paper, we set out to engineer the reflection/transmission behaviour at boundaries to obtain desirable properties such as achieving total reflection and transmission. Based on the quantum graph formulation for modelling metamaterials developed in Sci. Rep. 12 (1), 18006 (2022), we tailor the interface reflection and transmission coefficients by patterning the boundary with resonant elements at each interface vertex. By tuning the internal lengths of the resonant elements, we demonstrate both minimization and maximization of the reflection coefficient via a scattering formulation. In addition, we present an interface set-up incorporating beyond-nearest-neighbour connections, which yields narrow-band transmission for certain angles only, creating an angular filtering interface. [ABSTRACT FROM AUTHOR]

The boltzmann-exponential thermodynamic laws govern the noisy molecular flux in chemical reactions as well as the noisy subthreshold electron current flux in transistors. These common mathematical laws enable one to map and simulate arbitrary stochastic biochemical reaction networks in highly efficient cytomorphic systems built on subthreshold analog circuits. Such simulations can accurately and automatically model noisy, nonlinear, asynchronous, stiff, and nonmodular feedback dynamics in interconnected networks in physical circuits. The scaling in simulation time for stochastic networks with the number of reactions or molecules is constant in cytomorphic systems. By contrast, it grows rapidly in digital systems, which are not parallelizable. Therefore, cytomorphic systems enable large-scale supercomputing systems-biology simulations of arbitrary and highly computationally intensive biochemical reaction networks that can nevertheless be compiled via digitally programmable parameters and connectivity. [ABSTRACT FROM AUTHOR]

The bacterial pathogen responsible for causing Lyme disease, Borrelia burgdorferi, is an atypical Gram-negative spirochete that is transmitted to humans via the bite of an infected Ixodes tick. In diderms, peptidoglycan (PG) is sandwiched between the inner and outer membrane of the cell envelope. In many other Gram-negative bacteria, PG is bound by protein(s), which provide both structural integrity and continuity between envelope layers. Here, we present evidence of a peptidoglycan-associated protein (PAP) in B. burgdorferi. Using an unbiased proteomics approach, we identified Neutrophil Attracting Protein A (NapA) as a PAP. Interestingly, NapA is a Dps homologue, which typically functions to bind and protect cellular DNA from damage during times of stress. While B. burgdorferi NapA is known to be involved in the oxidative stress response, it lacks the critical residues necessary for DNA binding. Biochemical and cellular studies demonstrate that NapA is localized to the B. burgdorferi periplasm and is indeed a PAP. Cryo-electron microscopy indicates that mutant bacteria, unable to produce NapA, have structural abnormalities. Defects in cell-wall integrity impact growth rate and cause the napA mutant to be more susceptible to osmotic and PG-specific stresses. NapA-linked PG is secreted in outer membrane vesicles and augments IL-17 production, relative to PG alone. Using microfluidics, we demonstrate that NapA acts as a molecular beacon—exacerbating the pathogenic properties of B. burgdorferi PG. These studies further our understanding of the B. burgdorferi cell envelope, provide critical information that underlies its pathogenesis, and highlight how a highly conserved bacterial protein can evolve mechanistically, while maintaining biological function. Author summary: Diderms typically produce peptidoglycan-associated proteins (PAPs) to enhance structural integrity and continuity within the cell envelope. We have identified a PAP in B. burgdorferi with structural and sequence homology to the near ubiquitous bacterial protein Dps (DNA binding protein from starved bacteria). The B. burgdorferi Dps paralogue is incapable of binding DNA. Instead, it bolsters the protective properties of the PG layer, while playing an important role in host immune modulation. Collectively, our findings highlight the plasticity of bacterial proteins in that they may change how they perform a task despite maintaining the same basic biological function. [ABSTRACT FROM AUTHOR]

The computation of wave-energy distributions in the mid-to-high frequency regime can be reduced to ray-tracing calculations. Solving the ray-tracing problem in terms of an operator equation for the energy density leads to an inhomogeneous equation which involves a Perron–Frobenius operator defined on a suitable Sobolev space. Even for fairly simple geometries, let alone realistic scenarios such as typical boundary value problems in room acoustics or for mechanical vibrations, numerical approximations are necessary. Here we study the convergence of approximation schemes by rigorous methods. For circular billiards we prove that convergence of finite-rank approximations using a Fourier basis follows a power law where the power depends on the smoothness of the source distribution driving the system. The relevance of our studies for more general geometries is illustrated by numerical examples. [ABSTRACT FROM AUTHOR]

Nosema ceranae is a microsporidian parasite that infects the honeybee midgut epithelium. The protein‐coding gene Dicer is lost in most microsporidian genomes but is present in N. ceranae. By feeding infected honeybees with small interfering RNA targeting the N. ceranae gene coding Dicer (siRNA‐Dicer), we found that N. ceranae spore loads were significantly reduced. In addition, over 10% of total parasite protein‐coding genes showed significantly divergent expression profiles after siRNA‐Dicer treatment. Parasite genes for cell proliferation, ABC transporters and hexokinase were downregulated at 3 days postinfection, a key point in the middle of parasite replication cycles. In addition, genes involved in metabolic pathways of honeybees and N. ceranae showed significant co‐expression. Furthermore, the siRNA‐Dicer treatment partly reversed the expression patterns of honeybee genes. The honeybee gene mucin‐2‐like showed significantly upregulation in the siRNA‐Dicer group compared with the infection group continually at 4, 5 and 6 days postinfection, suggesting that the siRNA‐Dicer feeding promoted the strength of the mucus barrier resulted from interrupted parasite proliferation. As the gene Dicer broadly regulates N. ceranae proliferation and honeybee metabolism, our data suggest the RNA interference pathway is an important infection strategy for N. ceranae. [ABSTRACT FROM AUTHOR]