Agent-based modeling of nuclear chromosome ensembles identifies determinants of homolog pairing during meiosis.

During meiosis, pairing of homologous chromosomes (homologs) ensures the formation of haploid gametes from diploid precursor cells, a prerequisite for sexual reproduction. Pairing during meiotic prophase I facilitates crossover recombination and homolog segregation during the ensuing reductional cell division. Mechanisms that ensure stable homolog alignment in the presence of an excess of non-homologous chromosomes have remained elusive, but rapid chromosome movements appear to play a role in the process. Apart from homolog attraction, provided by early intermediates of homologous recombination, dissociation of non-homologous associations also appears to contribute to homolog pairing, as suggested by the detection of stable non-homologous chromosome associations in pairing-defective mutants. Here, we have developed an agent-based model for homolog pairing derived from the dynamics of a naturally occurring chromosome ensemble. The model simulates unidirectional chromosome movements, as well as collision dynamics determined by attractive and repulsive forces arising from close-range physical interactions. Chromosome number and size as well as movement velocity and repulsive forces are identified as key factors in the kinetics and efficiency of homologous pairing in addition to homolog attraction. Dissociation of interactions between non-homologous chromosomes may contribute to pairing by crowding homologs into a limited nuclear area thus creating preconditions for close-range homolog attraction. Incorporating natural chromosome lengths, the model accurately recapitulates efficiency and kinetics of homolog pairing observed for wild-type and mutant meiosis in budding yeast, and can be adapted to nuclear dimensions and chromosome sets of other organisms.

Agent-based modeling of nuclear chromosome ensemble identifies determinants of homolog pairing during meiosis.

During meiosis, pairing of homologous chromosomes (homologs) ensures the formation of haploid gametes from diploid precursor cells, a prerequisite for sexual reproduction. Pairing during meiotic prophase I facilitates crossover recombination and homolog segregation during the ensuing reductional cell division. Mechanisms that ensure stable homolog alignment in the presence of an excess of non-homologous chromosomes have remained elusive, but rapid chromosome movements during prophase I appear to play a role in the process. Apart from homolog attraction, provided by early intermediates of homologous recombination, dissociation of non-homologous associations also appears to contribute to homolog pairing, as suggested by the detection of stable non-homologous chromosome associations in pairing-defective mutants. Here, we have developed an agent-based model for homolog pairing derived from the dynamics of a naturally occurring chromosome ensemble. The model simulates unidirectional chromosome movements, as well as collision dynamics determined by attractive and repulsive forces arising from close-range physical interactions. In addition to homolog attraction, chromosome number and size as well as movement velocity and repulsive forces are identified as key factors in the kinetics and efficiency of homologous pairing. Dissociation of interactions between non-homologous chromosomes may contribute to pairing by crowding homologs into a limited nuclear area thus creating preconditions for close-range homolog attraction. Predictions from the model are readily compared to experimental data from budding yeast, parameters can be adjusted to other cellular systems and predictions from the model can be tested via experimental manipulation of the relevant chromosomal features.

Monitoring long-term vegetation condition dynamics in persistent semi-arid wetland communities using time series of Landsat data.

Wetlands in arid and semi-arid regions are characterized by dry- and wet-phase vegetation expression which responds to variable water resources. Monitoring condition trends in these wetlands is challenging because transitions may be rapid and short-lived, and identification of meaningful condition change requires longitudinal study. Remotely-sensed data provide cost effective, multi-decadal information with sufficient temporal and spatial scale to explore wetland condition. In this study, we used a time series of Enhanced Vegetation Index (EVI) derived from 34 years (1988-2021) of Landsat imagery, to investigate the long-term condition dynamics of six broad vegetation groups (communities) in a large floodplain wetland system, the Macquarie Marshes in Australia. These communities were persistently mapped as River Red Gum wetland, Black Box/Coolibah woodland, Lignum shrubland, Semi-permanent wetland, Terrestrial grassland and Terrestrial woodland. We used generalized additive models (GAM) to explore the response of vegetation to seasonality, river flow and climatic conditions. We found that EVI was a useful metric to monitor both wetland condition and response to climatic and hydrological drivers. Wetland communities were particularly responsive to river flow and seasonality, while terrestrial communities were responsive to climate and seasonality. Our results indicate asymptotic condition responses, and therefore evidence of hydrological thresholds, by some wetland communities to river flows. We did not observe a long-term trend of declining condition although an apparent increase in condition variability towards the end of the time series requires continued monitoring. Our remotely-sensed, landscape-scale monitoring approach merits further ground validation. We discuss how it can be used to provide a management tool which continuously assesses short and long-term wetland condition and informs conservation decisions about water management for environmental flows.

Evaluation of a large-scale health department naloxone distribution program: Per capita naloxone distribution and overdose morality.

OBJECTIVES: To report per-capita distribution of take-home naloxone to lay bystanders and evaluate changes in opioid overdose mortality in the county over time. METHODS: Hamilton County Public Health in southwestern Ohio led the program from Oct 2017-Dec 2019. Analyses included all cartons distributed within Hamilton County or in surrounding counties to people who reported a home address within Hamilton County. Per capita distribution was estimated using publicly available census data. Opioid overdose mortality was compared between the period before (Oct 2015-Sep 2017) and during (Oct 2017-Sep 2019) the program. RESULTS: A total of 10,416 cartons were included for analyses, with a total per capita distribution of 1,275 cartons per 100,000 county residents (average annual rate of 588/100,000). Median monthly opioid overdose mortality in the two years before (28 persons, 95% CI 25-31) and during (26, 95% CI 23-28) the program did not differ significantly. CONCLUSIONS: Massive and rapid naloxone distribution to lay bystanders is feasible. Even large-scale take-home naloxone distribution may not substantially reduce opioid overdose mortality rates.

Sampling and recovery of infectious SARS-CoV-2 from high-touch surfaces by sponge stick and macrofoam swab.

Effective sampling for severe acute respiratory syndrome 2 (SARS-CoV-2) is a common approach for monitoring disinfection efficacy and effective environmental surveillance. This study evaluated sampling efficiency and limits of detection (LODs) of macrofoam swab and sponge stick sampling methods for recovering infectious SARS-CoV-2 and viral RNA (vRNA) from surfaces. Macrofoam swab and sponge stick methods were evaluated for collection of SARS-CoV-2 suspended in a soil load from 6-in2 coupons composed of four materials: stainless steel (SS), acrylonitrile butadiene styrene (ABS) plastic, bus seat fabric, and Formica. Recovery of infectious SARS-CoV-2 was more efficient than vRNA recovery on all materials except Formica (macrofoam swab sampling) and ABS (sponge stick sampling). Macrofoam swab sampling recovered significantly more vRNA from Formica than ABS and SS, and sponge stick sampling recovered significantly more vRNA from ABS than Formica and SS, suggesting that material and sampling method choice can affect surveillance results. Time since initial contamination significantly affected infectious virus recovery from all materials, with vRNA recovery showing limited to no difference, suggesting that SARS-CoV-2 vRNA can remain detectable after viral infectivity has dissipated. This study showed that a complex relationship exists between sampling method, material, time from contamination to sampling, and recovery of SARS-CoV-2. In conclusion, data show that careful consideration be used when selecting surface types for sampling and interpreting SARS-CoV-2 vRNA recovery with respect to presence of infectious virus.

Fluid-structure interaction modelling of neighboring tubes with primary cilium analysis.

We have developed a numerical model of two osculating cylindrical elastic renal tubules to investigate the impact of neighboring tubules on the stress applied to a primary cilium. We hypothesize that the stress at the base of the primary cilium will depend on the mechanical coupling of the tubules due to local constrained motion of the tubule wall. The objective of this work was to determine the in-plane stresses of a primary cilium attached to the inner wall of one renal tubule subject to the applied pulsatile flow, with a neighboring renal tube filled with stagnant fluid in close proximity to the primary tubule. We used the commercial software COMSOLⓇ to model the fluid-structure interaction of the applied flow and tubule wall, and we applied a boundary load to the face of the primary cilium during this simulation to produces a stress at its base. We confirm our hypothesis by observing that on average the in-plane stresses are greater at the base of the cilium when there is a neighboring renal tube versus if there is no neighboring tube at all. In combination with the hypothesized function of a cilium as a biological fluid flow sensor, these results indicate that flow signaling may also depend on how the tubule wall is constrained by neighboring tubules. Our results may be limited in their interpretation due to the simplified nature of our model geometry, and further improvements to the model may potentially lead to the design of future experiments.

Large-scale evaluation of microorganism inactivation by bipolar ionization and photocatalytic devices.

The COVID-19 pandemic has raised awareness in the spread of disease via airborne transmission. As a result, there has been increasing interest in technologies that claim to reduce concentrations of airborne pathogens in indoor environments. The efficacy of many of these emerging technologies is not fully understood, and the testing that has been done is often conducted at a small scale and not representative of applied settings. There is currently no standard test method for evaluating air treatment technologies, making it difficult to compare results across studies or technology types. Here, a consistent testing approach in an operational-scale test chamber with a mock recirculating heating, ventilation, and air conditioning (HVAC) system was used to evaluate the efficacy of bipolar ionization and photocatalytic devices against the non-enveloped bacteriophage MS2 in the air and on surfaces. Statistically significant differences between replicate sets of technology tests and control tests (without technologies active) are apparent after 1 h, ranging to a maximum of 0.88 log10 reduction for the bipolar ionization tests and 1.8 log10 reduction for the photocatalytic device tests. It should be noted that ozone concentrations were elevated above background concentrations in the test chamber during the photocatalytic device testing. No significant differences were observed between control and technology tests in terms of the amount of MS2 deposited or inactivated on surfaces during testing. A standardized, large-scale testing approach, with replicate testing and time-matched control conditions, is necessary for contextualizing laboratory efficacy results, translating them to real-world conditions, and for facilitating technology comparisons.

Impact of test methodology on the efficacy of triethylene glycol (Grignard Pure) against bacteriophage MS2.

The COVID-19 pandemic has raised interest in using chemical air treatments as part of a strategy to reduce the risk of disease transmission, but more information is needed to characterize their efficacy at scales translatable to applied settings and to develop standardized test methods for characterizing the performance of these products. Grignard Pure, a triethylene glycol (TEG) active ingredient air treatment, was evaluated using two different test protocols in a large bioaerosol test chamber and observed to inactivate bacteriophage MS2 in air (up to 99.9% at 90 min) and on surfaces (up to 99% at 90 min) at a concentration of approximately 1.2 - 1.5 mg/m3. Introducing bioaerosol into a TEG-charged chamber led to overall greater reductions compared to when TEG was introduced into a bioaerosol-charged chamber, although the differences in efficacy against airborne MS2 were only significant in the first 15 min. Time-matched control conditions (no TEG present) and replicate tests for each condition were essential for characterizing treatment efficacy. These findings suggest that chemical air treatments could be effective in reducing the air and surface concentrations of infectious pathogens in occupied spaces, although standard methods are needed for evaluating their efficacy and comparing results across studies. The potential health impacts of chronic exposure to chemicals should also be considered, but those were not evaluated here.

The space between us: Modeling spatial heterogeneity in synthetic microbial consortia dynamics.

A central endeavor in bioengineering concerns the construction of multistrain microbial consortia with desired properties. Typically, a gene network is partitioned between strains, and strains communicate via quorum sensing, allowing for complex behaviors. Yet a fundamental question of how emergent spatiotemporal patterning in multistrain microbial consortia affects consortial dynamics is not understood well. Here, we propose a computationally tractable and straightforward modeling framework that explicitly allows linking spatiotemporal patterning to consortial dynamics. We validate our model against previously published results and make predictions of how spatial heterogeneity impacts interstrain communication. By enabling the investigation of spatial patterns effects on microbial dynamics, our modeling framework informs experimentalists, helps advance the understanding of complex microbial systems, and supports the development of applications involving them.

Residual antimicrobial coating efficacy against SARS-CoV-2.

AIMS: This study evaluated the residual efficacy of commercially available antimicrobial coatings or films against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on non-porous surfaces. METHODS AND RESULTS: Products were applied to stainless steel or ABS plastic coupons and dried overnight. Coupons were inoculated with SARS-CoV-2 in the presence of 5% soil load. Recovered infectious SARS-CoV-2 was quantified by TCID50 assay. Tested product efficacies ranged from <1.0 to >3.0 log10 reduction at a 2-h contact time. The log10 reduction in recovered infectious SARS-CoV-2 ranged from 0.44 to 3 log10 reduction on stainless steel and 0.25 to >1.67 log10 on ABS plastic. The most effective products tested contained varying concentrations (0.5%-1.3%) of the same active ingredient: 3-(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride. Products formulated with other quaternary ammonium compounds were less effective against SARS-CoV-2 in this test. CONCLUSIONS: The residual antimicrobial products tested showed varied effectiveness against SARS-CoV-2 as a function of product tested. Several products were identified as efficacious against SARS-CoV-2 on both stainless steel and ABS plastic surfaces under the conditions evaluated. Differences in observed efficacy may be due to variation in active ingredient formulation; efficacy is, therefore, difficult to predict based upon listed active ingredient and its concentration. SIGNIFICANCE AND IMPACT: This study highlights the formulation-specific efficacy of several products against SARS-CoV-2 and may inform future development of residual antiviral products for use on non-porous surfaces. The identification of antimicrobial coatings or films showing promise to inactivate SARS-CoV-2 suggests that these products may be worth future testing and consideration.

Virucidal efficacy of antimicrobial surface coatings against the enveloped bacteriophage Φ6.

AIMS: Antimicrobial coatings, for use in combination with routine cleaning and disinfection, were evaluated for their effectiveness in reducing virus concentration on stainless steel surfaces. METHODS: Twenty antimicrobial coating products, predominantly composed of organosilane quaternary ammonium compounds, were applied to stainless steel coupons, dried overnight and evaluated for efficacy against Φ6, an enveloped bacteriophage. Additionally, two peel and stick polymer-based films, a copper-based film and three copper alloys were evaluated. Efficacy was determined by comparison of recoveries from uncoated (positive control) and coated (test) surfaces. RESULTS: The results indicated that some of the coating products initially demonstrated >3-log reduction of Φ6; no direct correlation of efficacy was observed with an active ingredient or its concentration. The peel and stick films and copper alloys each demonstrated efficacy in initial testing. However, none of the spray-based products retained efficacy after subjecting the coating to abrasion with either a hypochlorite or quaternary ammonium-based solution applied in accordance with EPA Interim Guidance for Evaluating the Efficacy of Antimicrobial Surface Coatings. Of the products tested for this durability, only one peel and stick polymeric film retained efficacy; the copper alloys were not tested for their durability in this study. CONCLUSIONS: These results suggest that while some organosilane quaternary ammonium compound-based products demonstrate antiviral efficacy, more research and development is needed to understand effective formulations with sufficient durability to perform as supplements to routine cleaning and disinfection.

Efficacy of detergent-based cleaning methods against coronavirus MHV-A59 on porous and non-porous surfaces.

This study evaluated the efficacy of detergent-based surface cleaning methods against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV (5% soil load in culture medium or simulated saliva) was inoculated onto four different high-touch materials [stainless steel (SS), Acrylonitrile Butadiene Styrene plastic (ABS), Formica, seat fabric (SF)]. Immediately and 2-hr post-inoculation, coupons were cleaned (damp wipe wiping) with and without pretreatment with detergent solution or 375 ppm hard water. Results identified that physical removal (no pretreatment) removed >2.3 log10 MHV on ABS, SS, and Formica when surfaces were cleaned immediately. Pretreatment with detergent or hard water increased effectiveness over wet wiping 2-hr post-inoculation; pretreatment with detergent significantly increased (p ≤ 0.05) removal of MHV in simulated saliva, but not in culture media, over hard water pretreatment (Formica and ABS). Detergent and hard water cleaning methods were ineffective on SF under all conditions. Overall, efficacy of cleaning methods against coronaviruses are material- and matrix-dependent; pre-wetting surfaces with detergent solutions increased efficacy against coronavirus suspended in simulated saliva. This study provides data highlighting the importance of incorporating a pre-wetting step prior to detergent cleaning and can inform cleaning strategies to reducing coronavirus surface transmission.

Efficacy of chemical disinfectants against SARS-CoV-2 on high-touch surface materials.

AIMS: This study aimed to provide operationally relevant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface disinfection efficacy information. METHODS AND RESULTS: Three EPA-registered disinfectants (Vital Oxide, Peroxide, and Clorox Total 360) and one antimicrobial formulation (CDC bleach) were evaluated against SARS-CoV-2 on material coupons and were tested using Spray (no touch with contact time) and Spray & Wipe (wipe immediately post-application) methods immediately and 2 h post-contamination. Efficacy was evaluated for infectious virus, with a subset tested for viral RNA (vRNA) recovery. Efficacy varied by method, disinfectant, and material. CDC bleach solution showed low efficacy against SARS-CoV-2 (log reduction < 1.7), unless applied via Spray & Wipe. Additionally, mechanical wiping increased the efficacy of treatments against SARS-CoV-2. The recovery of vRNA post-disinfection suggested that vRNA may overestimate infectious virus remaining. CONCLUSIONS: Efficacy depends on surface material, chemical, and disinfection procedure, and suggests that mechanical wiping alone has some efficacy at removing SARS-CoV-2 from surfaces. We observed that disinfectant treatment biased the recovery of vRNA over infectious virus. SIGNIFICANCE AND IMPACT OF STUDY: These data are useful for developing effective, real-world disinfection procedures, and inform public health experts on the utility of PCR-based surveillance approaches.

A Smartphone-Smartcard Platform for Implementing Contingency Management in Buprenorphine Maintenance Patients With Concurrent Stimulant Use Disorder.

Background and Objectives: Opioid agonist pharmacotherapies are effective in the treatment of opioid use disorder (OUD) but concurrent stimulant use is common and can lead to relapse and treatment drop out. Contingency management in combination with opioid agonist pharmacotherapy has broad beneficial effects in polysubstance users, including promoting drug abstinence and treatment retention, but clinic-based implementation can be burdensome. The present study was conducted to evaluate a contingency management intervention delivered via a smartphone-smartcard platform in OUD patients who had concurrent stimulant use disorder. Methods: Retrospective comparison of (n = 124) patients; half received the contingency management intervention and half were matched controls. Drug use and clinic attendance outcomes over four consecutive 30-day periods were analyzed with regression. Results: The intervention group showed consistently higher rates of drug abstinence and clinic attendance which were significant at the latter two timepoints. Discussion: Smartphone-smartcard platforms can facilitate dissemination of contingency management by surmounting or obviating key barriers to adoption. They appear to be convenient for all stakeholders, are easy to use, and facilitate high-fidelity implementation. Delivering contingency management via a smartphone-smartcard platform produces effects consistent with those observed when the intervention is delivered with substantially costlier and more burdensome in-person procedures.

Heterogeneous bacterial swarms with mixed lengths.

Heterogeneous systems of active matter exhibit a range of complex emergent dynamical patterns. In particular, it is difficult to predict the properties of the mixed system based on its constituents. These considerations are particularly significant for understanding realistic bacterial swarms, which typically develop heterogeneities even when grown from a single cell. Here, mixed swarms of cells with different aspect ratios are studied both experimentally and in simulations. In contrast with previous theory, there is no macroscopic phase segregation. However, locally, long cells act as nucleation cites, around which aggregates of short, rapidly moving cells can form, resulting in enhanced swarming speeds. On the other hand, high fractions of long cells form a bottleneck for efficient swarming. Our results suggest a physical advantage for the spontaneous heterogeneity of bacterial swarm populations.

A smartphone-smartcard platform for contingency management in an inner-city substance use disorder outpatient program.

Contingency management (CM) is an efficacious incentive-based intervention for promoting drug abstinence, but treatment providers have not widely adopted it. Smartphone and smart debit card technologies can deliver automated, patient-centered, high-fidelity CM and related services, including cognitive behavioral therapy and appointment reminders. This study evaluated clinical outcomes associated with an integrated smartphone-smartcard platform in an inner-city outpatient clinic. We enrolled adults with opioid use disorder (n = 85) over nine weeks, and they received CM services for four months. We retrospectively compared them to matched controls who received services at the same time, from the same provider at a similar, nearby clinic in the same city. The platform was associated with significantly higher rates of counseling appointment attendance in study months 2 to 4 (9.6%-18.0% increases) and an odds ratio of 4.84 for increased proportion of urine samples consistent with drug abstinence and adherence to prescribed medication, compared to controls at 120 days (P < 0.05). Overwhelmingly, participants reported that they found the platform acceptable. These results suggest that the platform is an effective method for remote delivery of CM services that could overcome key logistical barriers to widespread adoption of CM among treatment providers.

Interaction of red crabs with yellow crazy ants during migration on Christmas Island.

Invasive species have had a profound impact on ecosystems all over the world. Their presence can lead to fundamental changes in the biodiversity of a given ecosystem as well as the extinction of native species. In particular, this work looks at the effect on the Gecarcoidea natalis (Red Crab) population on Christmas Island due to the presence of vast arrays of supercolonies containing Anoplolepis gracilipes (Yellow Crazy Ant). We primarily study the inter-species interaction occurring during the crab migration to the island coast. We propose a microscopic model for the dynamics of the crabs and ants with the goal of increasing crab survival. Through analysis of the model, we investigate a range of potential preventative measures that could be taken to preserve the native crab population dependent on their locations. The main result of this work is that by considering the locations of ant supercolonies incorporated into Monte Carlo simulations of the model, we can identify the order that the supercolonies need to be removed to provide the greatest chance at survival for the crabs per migration cycle.

Role of hydrodynamic interactions in chemotaxis of bacterial populations.

How bacteria sense local chemical gradients and decide to move has been a fascinating area of recent study. Chemotaxis of bacterial populations has been traditionally modeled using either individual-based models describing the motion of a single bacterium as a velocity jump process, or macroscopic PDE models that describe the evolution of the bacterial density. In these models, the hydrodynamic interaction between the bacteria is usually ignored. However, hydrodynamic interaction has been shown to induce collective bacterial motion and self-organization resulting in larger mesoscale structures. In this paper, the role of hydrodynamic interactions in bacterial chemotaxis is investigated by extending a hybrid computational model that incorporates hydrodynamic interactions and adding components from a classical velocity jump model. It is shown that by including hydrodynamic interactions, a suspension with a low initial volume fraction can exhibit locally high concentrations in bacterial aggregates. Also, it is shown that hydrodynamic interactions enhance the merging of the small aggregates into larger ones and lead to qualitatively different aggregate behavior than possible with pure chemotaxis models. Namely, differences in the shape, number, and dynamics of these emergent clusters.

Charged Nanoparticles Quench the Propulsion of Active Janus Colloids.

Active colloidal particles regularly interact with surfaces in applications ranging from microfluidics to sensing. Recent work has revealed the complex nature of these surface interactions for active particles. Herein, we summarize experiments and simulations that show the impact of charged nanoparticles on the propulsion of an active colloid near a boundary. Adding charged nanoparticles not only decreased the average separation distance of a passive colloid because of depletion attraction as expected but also decreased the apparent propulsion of a Janus colloid to near zero. Complementary agent-based simulations considering the impact of hydrodynamics for active Janus colloids were conducted in the range of separation distances inferred from experiment. These simulations showed that propulsion speed decreased monotonically with decreasing average separation distance. Although the trend found in experiments and simulations was in qualitative agreement, there was still a significant difference in the magnitude of speed reduction. The quantitative difference was attributed to the influence of charged nanoparticles on the conductivity of the active particle suspension. Follow-up experiments delineating the impact of depletion and conductivity showed that both contribute to the reduction of speed for an active Janus particle. The experimental and simulated data suggests that it is necessary to consider the synergistic effects between various mechanisms influencing interactions experienced by an active particle near a boundary.