Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells.

Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology.

Sociodemographic profiles and organ damage accural in the Black Women's Experience Living with Lupus study.

OBJECTIVE: Black/African American women with systemic lupus erythematosus (SLE) experience greater organ damage and at younger ages than white women. The objective of this study was to advance research on SLE inequities by identifying sociodemographic risk profiles associated with organ damage accrual specifically among Black/African American women. METHODS: Latent profile analysis was conducted among 438 Black/African American women with SLE living in Atlanta, GA and enrolled in the Black Women's Experiences Living with Lupus (BeWELL) Study (May 2015 to April 2017). Proportional hazard and Poisson regression models examined prospective associations between sociodemographic profiles and the timing and degree of organ damage accrual over 2 years. RESULTS: Four profiles emerged: (1) "Younger/Lower SES with Uncontrolled SLE" (44.8%), (2) "Older/Lower SES with Uncontrolled SLE" (23.3%), (3) "Mid-SES with Controlled SLE" (19.6%), and (4) "Higher SES with Controlled SLE" (11.2%). Approximately 42% of participants experienced new organ damage during the follow-up period. Proportional hazard models indicated that "Older/Lower SES with Uncontrolled SLE" participants were at greatest risk of new organ damage (HR = 2.41; 95% CI = 1.39, 4.19), followed by "Younger/Lower SES with Uncontrolled SLE" participants (HR = 1.56; 95% CI = 0.92, 2.67), compared to those in the "Higher SES with Controlled SLE" profile. Poisson regression models revealed that these two groups also exhibited greater organ damage accrual (b = 0.98, SE = 0.24, 95% CI = 0.52, 1.44 and b = 0.72, SE = 0.23, 95% CI = 0.27, 1.17, respectively). CONCLUSIONS: Black/African American women with fewer socioeconomic resources and uncontrolled SLE are at greatest risk for increasing disease severity over time. Social inequities likely contribute to racial inequities in SLE progression.

Nationwide Analysis of Firearm Injury Versus Other Penetrating Trauma: It's Not All the Same Caliber.

INTRODUCTION: Ballistic injuries cause both a temporary and permanent cavitation event, making them far more destructive and complex than other penetrating trauma. We hypothesized that global injury scoring and physiologic parameters would fail to capture the lethality of gunshot wounds (GSW) compared to other penetrating mechanisms. METHODS: The 2019 American College of Surgeons Trauma Quality Programs participant use file was queried for the mortality rate for GSW and other penetrating mechanisms. A binomial logistic regression model ascertained the effects of sex, age, hypotension, tachycardia, mechanism, Glasgow Coma Scale, ISS, and volume of blood transfusion on the likelihood of mortality. Subgroup analyses examined isolated injuries by body regions. RESULTS: Among 95,458 cases (82% male), GSW comprised 46.4% of penetrating traumas. GSW was associated with longer hospital length of stay (4 [2-9] versus 3 [2-5] days), longer intensive care unit length of stay (3 [2-6] versus 2 [2-4] days), and more ventilator days (2 [1-4] versus 2 [1-3]) compared to stab wounds, all P < 0.001. The model determined that GSW was linked to increased odds of mortality compared to stab wounds (odds ratio 4.19, 95% confidence interval 3.55-4.93). GSW was an independent risk factor for acute kidney injury, acute respiratory distress syndrome, venous thromboembolism, sepsis, and surgical site infection. CONCLUSIONS: Injury scoring systems based on anatomical or physiological derangements fail to capture the lethality of GSW compared to other mechanisms of penetrating injury. Adjustments in risk stratification and reporting are necessary to reflect the proportion of GSW seen at each trauma center. Improved classification may help providers develop quality processes of care. This information may also help shape public discourse on this highly lethal mechanism.

Highly public anti-Black violence is associated with poor mental health days for Black Americans.

Highly public anti-Black violence in the United States may cause widely experienced distress for Black Americans. This study identifies 49 publicized incidents of racial violence and quantifies national interest based on Google searches; incidents include police killings of Black individuals, decisions not to indict or convict the officer involved, and hate crime murders. Weekly time series of population mental health are produced for 2012 through 2017 using two sources: 1) Google Trends as national search volume for psychological distress terms and 2) the Behavioral Risk Factor Surveillance System (BRFSS) as average poor mental health days in the past 30 d among Black respondents (mean weekly sample size of 696). Autoregressive moving average (ARMA) models accounted for autocorrelation, monthly unemployment, season and year effects, 52-wk lags, news-related searches for suicide (for Google Trends), and depression prevalence and percent female (for BRFSS). National search interest varied more than 100-fold between racial violence incidents. Black BRFSS respondents reported 0.26 more poor mental health days during weeks with two or more racial incidents relative to none, and 0.13 more days with each log10 increase in national interest. Estimates were robust to sensitivity tests, including controlling for monthly number of Black homicide victims and weekly search interest in riots. As expected, racial incidents did not predict average poor mental health days among White BRFSS respondents. Results with national psychological distress from Google Trends were mixed but generally unsupportive of hypotheses. Reducing anti-Black violence may benefit Black Americans' mental health nationally.

Musculoskeletal injuries during trail sports: Sex- and age-specific analyses over 20 years from a national injury database.

INTRODUCTION: Musculoskeletal (MSK) injuries in US trail sports are understudied as trail sport popularity grows. This study describes MSK injury patterns among hikers, trail runners, and mountain bikers from 2002 through 2021 and investigates MSK injury trends acquired during mountain sports. METHODS: The National Electronic Injury Surveillance System (NEISS) was used to identify US emergency department (ED) patients from 2002-2021 (inclusive) who endured MSK injuries during hiking, trail running, or mountain biking. Injury rates and national estimates were calculated across demographics. RESULTS: 9835 injuries were included (48.4% male, 51.6% female). Injuries increased over time, with 1213 from 2002-2005 versus 2417 from 2018-2021. No sex differences existed before 2010, after which female injury rates exceeded those of males. The following findings were statistically significant, with P<0.05: females endured more fractures and strains/sprains; males endured more lacerations; concussions and head injuries were higher among those <18 y; dislocations and strains/sprains were higher for 18 to 65 y; fractures were higher for >65 y; <18 y had high mountain-biking and low running rates; 18 to 65 y had high running rates; and >65 y had low biking and running rates. Although all diagnoses increased in number over time, no significant differences existed in the proportion of any given diagnosis relative to total injuries. CONCLUSIONS: MSK injuries during trail sports have increased since 2002. Males endured more injuries until 2009, after which females endured more. Significant sex and age differences were found regarding injury diagnosis and body parts. Further studies are needed to confirm these trends and their causes.

Peptide Stereocomplexation Orchestrates Supramolecular Assembly of Hydrogel Biomaterials.

Stereocomplexation, or specific interactions among complementary stereoregular macromolecules, is burgeoning as an increasingly impactful design tool, exerting exquisite control of material structure and properties. Since stereocomplexation of polymers produces remarkable transformations in mechanics, morphology, and degradation, we sought to leverage stereocomplexation to tune these properties in peptide-based biomaterials. We found that blending the pentapeptides l- and d-KYFIL triggers dual mechanical and morphological transformations from stiff fibrous hydrogels into less stiff networks of plates, starkly contrasting prior reports that blending l- and d-peptides produces stiffer fibrous hydrogels than the individual constituents. The morphological transformation of KYFIL in phosphate-buffered saline from fibers that entangle into hydrogels to plates that cannot entangle explains the accompanying mechanical transformation. Moreover, the blends shield l-KYFIL from proteolytic degradation, producing materials with comparable proteolytic stability to d-KYFIL but with distinct 2D plate morphologies that in biomaterials may promote unique therapeutic release profiles and cell behavior. To confirm that these morphological, mechanical, and stability changes arise from differences in molecular packing as in polymer stereocomplexation, we acquired X-ray diffraction patterns, which showed l- and d-KYFIL to be amorphous and their blends to be crystalline. Stereocomplexation is particularly apparent in pure water, where l- and d-KYFIL are soluble random coils, and their blends form ß-sheets and gel within minutes. Our results highlight the role of molecular details, such as peptide sequence, in determining the material properties resulting from stereocomplexation. Looking forward, the ability of stereocomplexation to orchestrate supramolecular assembly and tune application-critical properties champions stereochemistry as a compelling design consideration.

Optoα1AR activation in astrocytes modulates basal hippocampal synaptic excitation and inhibition in a stimulation-specific manner.

Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. While there is abundant evidence that astrocytes modulate excitatory transmission in the hippocampus, evidence for astrocytic modulation of hippocampal synaptic inhibition remains more limited. Furthermore, to better investigate roles for astrocytes in modulating synaptic transmission, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we utilized AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), a viral vector that enables activation of Gq signaling in astrocytes via light-sensitive α1-adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) and low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the effect on miniature IPSCs (mIPSCs) was largely reversible within 20 min. However, low-frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, suggesting that astrocytic Gq -dependent modulation of basal synaptic transmission in the hippocampus is stimulation-dependent. By contrast, low-frequency stimulation of astrocytic ChR2 was effective in increasing both synaptic excitation and inhibition. Together, these data demonstrate that Optoα1AR activation in astrocytes changes basal GABAergic and glutamatergic transmission, but only following high-frequency stimulation, highlighting the importance of temporal dynamics when using optical tools to manipulate astrocyte function.

Transcriptomic response and immunological responses to chimpanzee adenovirus- and MVA viral-vectored vaccines for RSV in healthy adults.

Cohorts of healthy younger adults (18-50yrs) and healthy older adults (60-75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.

Insights into the pathological basis of dementia from population-based neuropathology studies.

The epidemiological neuropathology perspective of population and community-based studies allows unbiased assessment of the prevalence of various pathologies and their relationships to late-life dementia. In addition, this approach provides complementary insights to conventional case-control studies, which tend to be more representative of a younger clinical cohort. The Cognitive Function and Ageing Study (CFAS) is a longitudinal study of cognitive impairment and frailty in the general United Kingdom population. In this review, we provide an overview of the major findings from CFAS, alongside other studies, which have demonstrated a high prevalence of pathology in the ageing brain, particularly Alzheimer's disease neuropathological change and vascular pathology. Increasing burdens of these pathologies are the major correlates of dementia, especially neurofibrillary tangles, but there is substantial overlap in pathology between those with and without dementia, particularly at intermediate burdens of pathology and also at the oldest ages. Furthermore, additional pathologies such as limbic-predominant age-related TDP-43 encephalopathy, ageing-related tau astrogliopathy and primary age-related tauopathies contribute to late-life dementia. Findings from ageing population-representative studies have implications for the understanding of dementia pathology in the community. The high prevalence of pathology and variable relationship to dementia status has implications for disease definition and indicate a role for modulating factors on cognitive outcome. The complexity of late-life dementia, with mixed pathologies, indicates a need for a better understanding of these processes across the life-course to direct the best research for reducing risk in later life of avoidable clinical dementia syndromes.

Large-area periodically-poled lithium niobate wafer stacks optimized for high-energy narrowband terahertz generation.

Periodically-poled lithium niobate (PPLN) sources consisting of custom-built stacks of large-area wafers provide a unique opportunity to systematically study the multi-cycle terahertz (THz) generation mechanism as they are assembled layer-by-layer. Here we investigate and optimize the THz emission from PPLN wafer stacks as a function of wafer number, pump fluence, pulse duration and chirp, wafer separation, and pump focusing. Using 135 µm-thick, 2"-diameter wafers we generate high-energy, narrowband THz pulses with central frequencies up to 0.39 THz, directly suitable for THz-driven particle acceleration applications. We explore the multi-cycle pulse build-up with increasing wafer numbers using electro-optic sampling measurements, achieving THz conversion efficiencies up to 0.17%, while demonstrating unique control over the pulse length and bandwidth these sources offer. Guided by simulations, observed frequency-dependence on both stack-mounting and pump focusing conditions have been attributed to inter-wafer etalon and Gouy phase-shifts respectively, revealing subtle features that are critical to the understanding and performance of PPLN wafer-stack sources for optimal narrowband THz generation.

Incident racial discrimination predicts elevated C-Reactive protein in the Black Women's experiences Living with Lupus (BeWELL) study.

INTRODUCTION: Racial discrimination is a distinct health threat that increases disease risk among Black Americans. Psychosocial stress may compromise health through inflammatory mechanisms. This study examines incident experiences of racial discrimination and changes in the inflammatory biomarker C-reactive protein (CRP) over a two-year period among Black women with systemic lupus erythematosus (SLE)-an inflammatory autoimmune disease sensitive to psychosocial stress and characterized by stark racial inequities in outcomes. METHODS: Data are from the Black Women's Experiences Living with Lupus (BeWELL) Study. Participants (n = 380) from metropolitan Atlanta, Georgia were enrolled from April 2015 to May 2017. Incident racial discrimination was assessed bi-annually via self-report using the Experiences of Discrimination measure. CRP was assessed annually over a two-year period. Latent change score analyses modeled longitudinal within-person associations between incident racial discrimination and change in log-transformed CRP from baseline to Year 2. RESULTS: Incident experiences of racial discrimination were associated with elevated log-CRP across the two-year study period (b = 0.039, SE = 0.017, 95% CI: 0.006, 0.071). For each domain of incident racial discrimination experienced, CRP increased 3.98%. CONCLUSION: This study contributes to growing evidence on the biological consequences of racism and is the first to document an association between incident racial discrimination and changes in inflammation among Black women with SLE. Racial inequities in SLE outcomes and other diseases driven by inflammatory pathways may be explained in part through experiences of racial discrimination.

Effects of Cell-Adhesive Ligand Presentation on Pentapeptide Supramolecular Assembly and Gelation: Simulations and Experiments.

The extracellular matrix (ECM) is a complex, hierarchical material containing structural and bioactive components. This complexity makes decoupling the effects of biomechanical properties and cell-matrix interactions difficult, especially when studying cellular processes in a 3D environment. Matrix mechanics and cell adhesion are both known regulators of specific cellular processes such as stem cell proliferation and differentiation. However, more information is required about how such variables impact various neural lineages that could, upon transplantation, therapeutically improve neural function after a central nervous system injury or disease. Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels are one biomaterial approach to meet these goals, consisting of a family of peptide sequences that assemble into physical hydrogels in physiological media. In this study, we studied our previously reported supramolecularly-assembling RAPID hydrogels functionalized with the ECM-derived cell-adhesive peptide ligands RGD, IKVAV, and YIGSR. Using molecular dynamics simulations and experimental rheology, we demonstrated that these integrin-binding ligands at physiological concentrations (3-12 mm) did not impact the assembly of the KYFIL peptide system. In simulations, molecular measures of assembly such as hydrogen bonding and pi-pi interactions appeared unaffected by cell-adhesion sequence or concentration. Visualizations of clustering and analysis of solvent-accessible surface area indicated that the integrin-binding domains remained exposed. KYFIL or AYFIL hydrogels containing 3 mm of integrin-binding domains resulted in mechanical properties consistent with their non-functionalized equivalents. This strategy of doping RAPID gels with cell-adhesion sequences allows for the precise tuning of peptide ligand concentration, independent of the rheological properties. The controllability of the RAPID hydrogel system provides an opportunity to investigate the effect of integrin-binding interactions on encapsulated neural cells to discern how hydrogel microenvironment impacts growth, maturation, or differentiation.

Visual imagery deficits in posterior cortical atrophy.

Visual imagery has a close overlapping relationship with visual perception. Posterior cortical atrophy (PCA) is a neurodegenerative syndrome marked by early impairments in visuospatial processing and visual object recognition. We asked whether PCA would therefore also be marked by deficits in visual imagery, tested using objective forced-choice questionnaires, and whether imagery deficits would be selective for certain properties. We recruited four patients with PCA and a patient with integrative visual agnosia due to bilateral occipitotemporal strokes for comparison. We administered a test battery probing imagery for object shape, size, colour lightness, hue, upper-case letters, lower-case letters, word shape, letter construction, and faces. All subjects showed significant impairments in visual imagery, with imagery for lower-case letters most likely to be spared. We conclude that PCA subjects can show severe deficits in visual imagery. Further work is needed to establish how frequently this occurs and how early it can be found.

Structural Analysis of Non-native Peptide-Based Catalysts Using 2D NMR-Guided MD Simulations.

Proteins and enzymes generally achieve their functions by creating well-defined 3D architectures that pre-organize reactive functionalities. Mimicking this approach to supramolecular pre-organization is leading to the development of highly versatile artificial chemical environments, including new biomaterials, medicines, artificial enzymes, and enzyme-like catalysts. The use of ß-turn and α-helical motifs is one approach that enables the precise placement of reactive functional groups to enable selective substrate activation and reactivity/selectivity that approaches natural enzymes. Our recent work has demonstrated that helical peptides can serve as scaffolds for pre-organizing two reactive groups to achieve enzyme-like catalysis. In this study, we used CYANA and AmberTools to develop a computational approach for determining how the structure of our peptide catalysts can lead to enhancements in reactivity. These results support our hypothesis that the bifunctional nature of the peptide enables catalysis by pre-organizing the two catalysts in reactive conformations that accelerate catalysis by proximity. We also present evidence that the low reactivity of monofunctional peptides can be attributed to interactions between the peptide-bound catalyst and the helical backbone, which are not observed in the bifunctional peptide.

Features in children's counting books that lead dyads to both count and label sets during shared book reading.

This study examined how book features influence talk during shared book reading. We used data from a study in which parent-child dyads (n = 157; child's Mage  = 43.99 months; 88 girls, 69 boys; 91.72% of parents self-reported as white) were randomly assigned to read two number books. The focus was comparison talk (i.e., talk in which dyads count a set and also label its total), as this type of talk has been shown to promote children's understanding of cardinality. Replicating previous findings, dyads produced relatively low levels of comparison talk. However, book features influenced the talk. Books containing a greater number of numerical representations (e.g., number word, numeral, and non-symbolic set) and a greater word count elicited more comparison talk.

Global mosquito observations dashboard (GMOD): creating a user-friendly web interface fueled by citizen science to monitor invasive and vector mosquitoes.

BACKGROUND: Mosquitoes and the diseases they transmit pose a significant public health threat worldwide, causing more fatalities than any other animal. To effectively combat this issue, there is a need for increased public awareness and mosquito control. However, traditional surveillance programs are time-consuming, expensive, and lack scalability. Fortunately, the widespread availability of mobile devices with high-resolution cameras presents a unique opportunity for mosquito surveillance. In response to this, the Global Mosquito Observations Dashboard (GMOD) was developed as a free, public platform to improve the detection and monitoring of invasive and vector mosquitoes through citizen science participation worldwide. METHODS: GMOD is an interactive web interface that collects and displays mosquito observation and habitat data supplied by four datastreams with data generated by citizen scientists worldwide. By providing information on the locations and times of observations, the platform enables the visualization of mosquito population trends and ranges. It also serves as an educational resource, encouraging collaboration and data sharing. The data acquired and displayed on GMOD is freely available in multiple formats and can be accessed from any device with an internet connection. RESULTS: Since its launch less than a year ago, GMOD has already proven its value. It has successfully integrated and processed large volumes of real-time data (~ 300,000 observations), offering valuable and actionable insights into mosquito species prevalence, abundance, and potential distributions, as well as engaging citizens in community-based surveillance programs. CONCLUSIONS: GMOD is a cloud-based platform that provides open access to mosquito vector data obtained from citizen science programs. Its user-friendly interface and data filters make it valuable for researchers, mosquito control personnel, and other stakeholders. With its expanding data resources and the potential for machine learning integration, GMOD is poised to support public health initiatives aimed at reducing the spread of mosquito-borne diseases in a cost-effective manner, particularly in regions where traditional surveillance methods are limited. GMOD is continually evolving, with ongoing development of powerful artificial intelligence algorithms to identify mosquito species and other features from submitted data. The future of citizen science holds great promise, and GMOD stands as an exciting initiative in this field.

Monitoring Cardiac Biomarkers with Aptamer-Based Molecular Pendulum Sensors.

Reagent-free electronic biosensors capable of analyzing disease markers directly in unprocessed body fluids will enable the development of simple & affordable devices for personalized healthcare monitoring. Here we report a powerful and versatile nucleic acid-based reagent-free electronic sensing system. The signal transduction is based on the kinetics of an electrode-tethered molecular pendulum-a rigid double stranded DNA with one of the strands displaying an analyte-binding aptamer and the other featuring a redox probe-that exhibits field-induced transport modulated by receptor occupancy. Using chronoamperometry, which enables the sensor to circumvent the conventional Debye length limitation, the binding of an analyte can be monitored as these species increase the hydrodynamic drag. The sensing platform demonstrates a low femtomolar quantification limit and minimal cross-reactivity in analyzing cardiac biomarkers in whole blood collected from patients with chronic heart failure.

Functional network properties derived from wide-field calcium imaging differ with wakefulness and across cell type.

To improve 'bench-to-bedside' translation, it is integral that knowledge flows bidirectionally-from animal models to humans, and vice versa. This requires common analytical frameworks, as well as open software and data sharing practices. We share a new pipeline (and test dataset) for the preprocessing of wide-field optical fluorescence imaging data-an emerging mode applicable in animal models-as well as results from a functional connectivity and graph theory analysis inspired by recent work in the human neuroimaging field. The approach is demonstrated using a dataset comprised of two test-cases: (1) data from animals imaged during awake and anesthetized conditions with excitatory neurons labeled, and (2) data from awake animals with different genetically encoded fluorescent labels that target either excitatory neurons or inhibitory interneuron subtypes. Both seed-based connectivity and graph theory measures (global efficiency, transitivity, modularity, and characteristic path-length) are shown to be useful in quantifying differences between wakefulness states and cell populations. Wakefulness state and cell type show widespread effects on canonical network connectivity with variable frequency band dependence. Differences between excitatory neurons and inhibitory interneurons are observed, with somatostatin expressing inhibitory interneurons emerging as notably dissimilar from parvalbumin and vasoactive polypeptide expressing cells. In sum, we demonstrate that our pipeline can be used to examine brain state and cell-type differences in mesoscale imaging data, aiding translational neuroscience efforts. In line with open science practices, we freely release the pipeline and data to encourage other efforts in the community.

Capillary-Assisted Molecular Pendulum Bioanalysis.

The development of robust biosensing strategies that can be easily implemented in everyday life remains a challenge for the future of modern biosensor research. While several reagentless approaches have attempted to address this challenge, they often achieve user-friendliness through sacrificing sensitivity or universality. While acceptable for certain applications, these trade-offs hinder the widespread adoption of reagentless biosensing technologies. Here, we report a novel approach to reagentless biosensing that achieves high sensitivity, rapid detection, and universality using the SARS-CoV-2 virus as a model target. Universality is achieved by using nanoscale molecular pendulums, which enables reagentless electrochemical biosensing through a variable antibody recognition element. Enhanced sensitivity and rapid detection are accomplished by incorporating the coffee-ring phenomenon into the sensing scheme, allowing for target preconcentration on a ring-shaped electrode. Using this approach, we obtained limits of detection of 1 fg/mL and 20 copies/mL for the SARS-CoV-2 nucleoproteins and viral particles, respectively. In addition, clinical sample analysis showed excellent agreement with Ct values from PCR-positive SARS-CoV-2 patients.

CoreCruncher: Fast and Robust Construction of Core Genomes in Large Prokaryotic Data Sets.

The core genome represents the set of genes shared by all, or nearly all, strains of a given population or species of prokaryotes. Inferring the core genome is integral to many genomic analyses, however, most methods rely on the comparison of all the pairs of genomes; a step that is becoming increasingly difficult given the massive accumulation of genomic data. Here, we present CoreCruncher; a program that robustly and rapidly constructs core genomes across hundreds or thousands of genomes. CoreCruncher does not compute all pairwise genome comparisons and uses a heuristic based on the distributions of identity scores to classify sequences as orthologs or paralogs/xenologs. Although it is much faster than current methods, our results indicate that our approach is more conservative than other tools and less sensitive to the presence of paralogs and xenologs. CoreCruncher is freely available from: https://github.com/lbobay/CoreCruncher. CoreCruncher is written in Python 3.7 and can also run on Python 2.7 without modification. It requires the python library Numpy and either Usearch or Blast. Certain options require the programs muscle or mafft.