Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: A biomechanical study.

Purpose: This study aims to compare the compressive and tensile strengths of bone cement mixed with various concentrations of vancomycin, tobramycin, and combinations of the two. Methods: 12 mm × 6 mm antibiotic bone cement samples were created by vacuum mixing 0-4 g of vancomycin, tobramycin, and combinations of the two in 0.5 g increments per one pouch (40 g) of Palacos LV cement. An Instron 3369 Universal Testing System was used to determine the compressive and tensile strengths. Results: Compressive and tensile strengths of the bone cement without antibiotics were 118 ± 4 MPa and 30.3 ± 12 MPa, respectively. 4 g of vancomycin alone decreased the compressive strength to 108 ± 4 MPa (p-value 0.001) and decreased the tensile strength beginning at 2 g which yielded a strength of 28.1 ± 12 MPa (p-value 0.016). Tobramycin alone decreased the tensile strength beginning at 1.5 g yielding a strength of 27.7 ± 7 MPa (p-value 0.003). Although it decreased compressive strength at 1 g to 117 ± 7 MPa (p-value 0.002), it demonstrated variable effects with increasing concentrations. A combination of vancomycin and tobramycin decreased both the compressive (111 ± 5 MPa, p-value 0.014) and tensile (27.9 ± 8 MPa, p-value 0.007) strengths beginning at 1 g each. Conclusions: Various combinations of vancomycin and tobramycin affect the compressive and tensile strengths of bone cement. Clinicians should be diligent when mixing these antibiotics in bone cement to prevent possible failure of the constructs.

The glymphatic system and multiple sclerosis: An evolving connection.

Multiple sclerosis (MS) is a complex autoimmune disorder that affects the central nervous system, resulting in demyelination and an array of neurological manifestations. Recently, there has been significant scientific interest in the glymphatic system, which operates as a waste-clearance system for the brain. This article reviews the existing literature, and explores potential links between the glymphatic system and MS, shedding light on its evolving significance in the context of MS pathogenesis. The authors consider the pathophysiological implications of glymphatic dysfunction in MS, the impact of disrupted sleep on glymphatic function, and the bidirectional relationship between MS and sleep disturbances. By offering an understanding of the intricate interplay between the glymphatic system and MS, this review provides valuable insights which may lead to improved diagnostic techniques and more effective therapeutic interventions.

PyBEAM: A Bayesian approach to parameter inference for a wide class of binary evidence accumulation models.

Many decision-making theories are encoded in a class of processes known as evidence accumulation models (EAM). These assume that noisy evidence stochastically accumulates until a set threshold is reached, triggering a decision. One of the most successful and widely used of this class is the Diffusion Decision Model (DDM). The DDM however is limited in scope and does not account for processes such as evidence leakage, changes of evidence, or time varying caution. More complex EAMs can encode a wider array of hypotheses, but are currently limited by computational challenges. In this work, we develop the Python package PyBEAM (Bayesian Evidence Accumulation Models) to fill this gap. Toward this end, we develop a general probabilistic framework for predicting the choice and response time distributions for a general class of binary decision models. In addition, we have heavily computationally optimized this modeling process and integrated it with PyMC, a widely used Python package for Bayesian parameter estimation. This 1) substantially expands the class of EAM models to which Bayesian methods can be applied, 2) reduces the computational time to do so, and 3) lowers the entry fee for working with these models. Here we demonstrate the concepts behind this methodology, its application to parameter recovery for a variety of models, and apply it to a recently published data set to demonstrate its practical use.

Predicting molecular docking of per- and polyfluoroalkyl substances to blood protein using generative artificial intelligence algorithm DiffDock.

This study computationally evaluates the molecular docking affinity of various perfluoroalkyl and polyfluoroalkyl substances (PFAs) towards blood proteins using a generative machine-learning algorithm, DiffDock, specialized in protein-ligand blind-docking learning and prediction. Concerns about the chemical pathways and accumulation of PFAs in the environment and eventually in the human body has been rising due to empirical findings that levels of PFAs in human blood has been rising. DiffDock may offer a fast approach in determining the fate and potential molecular pathways of PFAs in human body.

Impacts of Diet on Reproductive Performance of Captive American Alligators (Alligator mississippiensis).

Historically, there has been little success with the captive breeding of American alligators (Alligator mississippiensis) for both commercial and conservative purposes. This study, conducted at Golden Ranch in Gheens, LA, between 2016 and 2022, utilized a newly formulated commercial feed and practical dietary supplementation (crawfish waste products) to enhance egg production, fertility, and hatch rates. The primary focus of this study was to compare the outcome of this captive breeding program at Golden Ranch with a program conducted at Rockefeller Refuge (RR) between 1979 and 1984. Notable success was achieved in terms of reproductive performance in comparison to the captive breeding program conducted at Rockefeller Refuge. In this study, 16.1 hatchlings were produced per nest on Golden Ranch from captive breeders. Additionally, when wild nests from Golden Ranch were incubated in the same controlled environmental chambers, they produced an average of 16.3 hatchlings per nest. This comparison emphasizes the similarity in egg production between captive-bred A. mississippiensis and their wild counterparts. The findings of this study suggest that a closed farming system for A. mississippiensis can be established by employing captive breeders derived from artificially incubated wild eggs. Furthermore, American alligators raised in controlled environmental chambers during their initial three years of life demonstrated adaptability to captive conditions and tolerated stocking rates associated with farming conditions and served as breeding stock.

A Phase 2 Randomized Trial Evaluating the Antiviral Activity and Safety of the Direct-Acting Antiviral Bemnifosbuvir in Ambulatory Patients with Mild or Moderate COVID-19 (MOONSONG Study).

Bemnifosbuvir is an oral antiviral drug with a dual mechanism of action targeting viral RNA polymerase, with in vitro activity against SARS-CoV-2. We conducted a phase 2, double-blind study evaluating the antiviral activity, safety, efficacy, and pharmacokinetics of bemnifosbuvir in ambulatory patients with mild/moderate COVID-19. Patients were randomized 1:1 to bemnifosbuvir 550 mg or placebo (cohort A) and 3:1 to bemnifosbuvir 1,100 mg or placebo (cohort B); all doses were given twice daily for 5 days. The primary endpoint was a change from baseline in the amount of nasopharyngeal SARS-CoV-2 viral RNA by reverse transcription PCR (RT-PCR). The modified intent-to-treat infected population comprised 100 patients (bemnifosbuvir 550 mg, n = 30; bemnifosbuvir 1,100 mg, n = 30; cohort A placebo, n = 30; cohort B placebo, n = 10). The primary endpoint was not met: the difference in viral RNA adjusted means at day 7 was -0.25 log10 copies/mL between bemnifosbuvir 550 mg and cohort A placebo (80% confidence interval [CI], -0.66 to 0.16; P = 0.4260), and -0.08 log10 copies/mL between bemnifosbuvir 1,100 mg and pooled placebo (80% CI, -0.48 to 0.33; P = 0.8083). Bemnifosbuvir 550 mg was well tolerated. Incidence of nausea and vomiting was higher with bemnifosbuvir 1,100 mg (10.0% and 16.7% of patients, respectively) than pooled placebo (2.5% nausea, 2.5% vomiting). In the primary analysis, bemnifosbuvir did not show meaningful antiviral activity on nasopharyngeal viral load as measured by RT-PCR compared with placebo in patients with mild/moderate COVID-19. The trial is registered at ClinicalTrials.gov under registration number NCT04709835. IMPORTANCE COVID-19 continues to be a major global public health challenge, and there remains a need for effective and convenient direct-acting antivirals that can be administered outside health care settings. Bemnifosbuvir is an oral antiviral with a dual mechanism of action and potent in vitro activity against SARS-CoV-2. In this study, we evaluated the antiviral activity, safety, efficacy, and pharmacokinetics of bemnifosbuvir in ambulatory patients with mild/moderate COVID-19. In the primary analysis, bemnifosbuvir did not show meaningful antiviral activity compared with placebo as assessed by nasopharyngeal viral loads. The negative predictive value of nasopharyngeal viral load reduction for clinical outcomes in COVID-19 is currently unclear, and further evaluation of bemnifosbuvir for COVID-19 may be warranted despite the findings observed in this study.

Application of diffusion weighted multiple boli ASL to a murine model of human African trypanosomiasis.

Human African Trypanosomiasis (HAT) is a parasitic disease originating in sub-Saharan Africa. There is limited information about the changes in the blood brain barrier (BBB) during this infection. This study is the first to apply diffusion weighted ASL (DWASL) to examine changes in BBB impairment. No significant changes in water exchange across the BBB were found during the infection, even when a loss of barrier integrity was seen using Contrast Enhanced MRI (Gd-DTPA) during the late stage of the disease. Furthermore, using multiple boli ASL (mbASL), changes in cerebral blood flow (CBF) were found during the course of infection. Overall, this study highlights the need for further study of the BBB during HAT infection to understand the complex mechanisms behind impairment.

Financial constraint and perceptions of COVID-19.

In early March 2020, two crises emerged: the COVID-19 public health crisis and a corresponding economic crisis resulting from business closures and skyrocketing job losses. While the link between socioeconomic status and infectious disease is well-documented, the psychological relationships among economic considerations, such as financial constraint and economic anxiety, and health considerations, such as perceptions of disease spread and preventative actions, is not well understood. Despite past research illustrating the strong link between financial fragility and a wide range of behaviors, surprisingly little research has examined the psychological relationship between the economic crisis and beliefs and behaviors related to the co-occurring health crisis. We show that financial constraint predicts people's beliefs about both their personal risk of infection and the national spread of the virus as well as their social distancing behavior. In addition, we compare the predictive utility of financial constraint to two other commonly studied factors: political partisanship and local disease severity. We also show that negative affect partially mediates the relationship between financial constraint and COVID-19 beliefs and social distancing behaviors. These results suggest the economic crisis created by COVID-19 spilled over into people's beliefs about the health crisis and their behaviors.

The effect of a novel AQP4 facilitator, TGN-073, on glymphatic transport captured by diffusion MRI and DCE-MRI.

The glymphatic system is a low resistance pathway, by which cerebrospinal fluid enters the brain parenchyma along perivascular spaces via AQP4 channels. It is hypothesised that the resulting convective flow of the interstitial fluid provides an efficient mechanism for the removal of waste toxins from the brain. Therefore, enhancing AQP4 function might protect against neurodegenerative diseases such as Alzheimer's disease (AD), in which the accumulation of harmful proteins and solutes is a hallmark feature. Here, we test the effect of a putative AQP4 facilitator, TGN-073, on glymphatic transport in a normal rat brain by employing different MRI techniques. Surgical procedures were undertaken to catheterise the cisterna magna, thereby enabling infusion of the MRI tracer. Followed by the intraperitoneal injection of either TGN-073, or the vehicle. Using a paramagnetic contrast agent (Gd-DTPA) as the MRI tracer, dynamic 3D T1 weighted imaging of the glymphatic system was undertaken over two hours. Further, the apparent diffusion coefficient was measured in different brain regions using diffusion-weighted imaging (DWI). While physiological parameters and arterial blood gas analysis were monitored continuously. We found that rats treated with TGN-073 showed the distribution of Gd-DTPA was more extensive and parenchymal uptake was higher compared with the vehicle group. Water diffusivity was increased in the brain of TGN-073 treated group, which indicates greater water flux. Also, MRI showed the glymphatic transport and distribution in the brain is naturally heterogeneous, which is consistent with previous studies. Our results indicate that compounds such as TGN-073 can improve glymphatic function in the brain. Since glymphatic impairment due to AQP4 dysfunction is potentially associated with several neurological disorders such as AD, dementia and traumatic brain injury, enhancing AQP4 functionality might be a promising therapeutic target.

A review of PFAS adsorption from aqueous solutions: Current approaches, engineering applications, challenges, and opportunities.

Per- and polyfluoroalkyl substances (PFAS) have drawn great attention due to their wide distribution in water bodies and toxicity to human beings. Adsorption is considered as an efficient treatment technique for meeting the increasingly stringent environmental and health standards for PFAS. This paper systematically reviewed the current approaches of PFAS adsorption using different adsorbents from drinking water as well as synthetic and real wastewater. Adsorbents with large mesopores and high specific surface area adsorb PFAS faster, their adsorption capacities are higher, and the adsorption process are usually more effective under low pH conditions. PFAS adsorption mechanisms mainly include electrostatic attraction, hydrophobic interaction, anion exchange, and ligand exchange. Various adsorbents show promising performances but challenges such as requirements of organic solvents in regeneration, low adsorption selectivity, and complicated adsorbent preparations should be addressed before large scale implementation. Moreover, the aid of decision-making tools including response surface methodology (RSM), techno-economic assessment (TEA), life cycle assessment (LCA), and multi criteria decision analysis (MCDA) were discussed for engineering applications. The use of these tools is highly recommended prior to scale-up to determine if the specific adsorption process is economically feasible and sustainable. This critical review presented insights into the most fundamental aspects of PFAS adsorption that would be helpful to the development of effective adsorbents for the removal of PFAS in future studies and provide opportunities for large-scale engineering applications.

Formulation of a Simulated Wastewater Influent Composition for Use in the Research of Technologies for Managing Wastewaters Generated during Manned Long-Term Space Exploration and Other Similar Situations-Literature-Based Composition Development.

The prospect of humans inhabiting planetary bodies is gaining interest among research and development communities, with the moon being considered as a transitory base camp and Mars the next planet humans will inhabit. NASA's Mission to Mars program is set to have humans inhabiting Mars within on-planet space camps by the Year 2030, which has tremendously increased research and development for space exploration-including research oriented toward human life support in long-term planetary lodging camps. The sustenance of human life on Mars will not be trivial due to the unavailability of an appropriate atmosphere and usable water. This situation requires a self-sustaining human life support system that can provide the basic needs such are breathable air, potable water, food, and energy. The feasibility of sending a payload with resources adequate to support long-term human inhabitation is not reasonable, which means every resource within a Mars space camp is valuable, including human-produced wastes. A biorefinery system that treats wastewater and can also produce valuable products such as oxygen, food, and energy offers a form of circular utilization of valuable resources. To conduct research for such systems requires a wastewater influent that is representative of the wastewater to be generated by the space crew within this isolated, confined environment, which is different from what is generated on Earth due to limited variability in diet, human activity, and lifestyle in this confined area. Collection of actual wastewater influent from an isolated environment supporting humans is challenging. Additionally, to ensure a safe working environment in the laboratory and avoid the imposed threat of handling actual human feces, the proposed synthetic, non-human feces containing wastewater influent formulation offers an easy-to-produce and safer-to-handle option. This paper reviews several synthetic wastewater compositions that have been formulated for space exploration purposes. None of the formulations were found to be realistic nor adequate for a space-camp-type scenario. Thus, the formulation of a synthetic wastewater for simulating a wastewater influent from a human space-based camp is proposed in this paper. In addition, the physical, chemical, and biodegradation characteristics of the final formulation designed are presented to illustrate the value of the proposed influent formulation.

Selective and Concentrative Enteropancreatic Recirculation of Antibiotics by Pigs.

Antibiotics that are efficacious for infectious pancreatitis are present in pancreatic exocrine secretion (PES) after intravenous administration and above minimal inhibitory concentrations. We measured concentrations of four antibiotics by tandem liquid chromatography-mass spectroscopy in plasma and PES after enteral administration to juvenile pigs with jugular catheters and re-entrant pancreatic-duodenal catheters. Nystatin, which is not absorbed by the intestine nor used for infectious pancreatitis (negative control), was not detected in plasma or PES. Concentrations of amoxicillin increased in plasma after administration (p = 0.035), but not in PES (p = 0.51). Metronidazole and enrofloxacin that are used for infectious pancreatitis increased in plasma after enteral administration and even more so in PES, with concentrations in PES averaging 3.1 (±0.5)- and 2.3 (±0.6)-fold higher than in plasma, respectively (p's < 0.001). The increase in enrofloxacin in PES relative to plasma was lower after intramuscular administration (1.8 ± 0.5; p = 0.001). The present results demonstrate the presence of a selective and concentrative enteropancreatic pathway of secretion for some antibiotics. Unlike the regulated secretion of bile, the constitutive secretion of PES and intestinal reabsorption may provide a continuous exposure of pancreas tissue and the small intestine to recirculated antibiotics and potentially other therapeutic molecules. There is a need to better understand the enteropancreatic recirculation of antibiotics and the associated mechanisms.

Serial magnetic resonance imaging of splenomegaly in the Trypanosoma brucei infected mouse.

Splenomegaly, an enlargement of the spleen, is a known clinical sign of the parasitic disease, human African trypanosomiasis. This study follows the development of splenomegaly in a group of mice over multiple infection points, using a non-invasive imaging modality, magnetic resonance imaging (MRI). CD-1 mice infected with GVR35 T.b. brucei demonstrated a significant increase in spleen size from day 7 post-infection, with changes in the spleen tracked in individual animals over five time points. At the final time point, the mean spleen weight calculated using the spleen volume from the MR images was compared with the post-mortem gross spleen weight. No significant difference was detected between the two methods (1.62 ± 0.06g using MRI and 1.51 ± 0.04g gross weight, p = 0.554). Haematology and histological analysis were also performed, giving additional insight into splenomegaly for the GVR35 strain of infection. The study demonstrates that MRI is a useful tool when examining changes in organ volume throughout HAT infection and may be applicable in the investigation of a range of conditions where changes in organ volume occur and MRI has not been used previously.

Removal of perfluorooctanoic acid via polyethyleneimine modified graphene oxide: Effects of water matrices and understanding mechanisms.

This research aimed to evaluate the adsorption behaviors and mechanisms of perfluorooctanoic acid (PFOA) onto polyethyleneimine modified graphene oxide (GO-PEI) from aqueous solutions. The adsorption capacity was significantly improved by doping polyethyleneimine (PEI) onto graphene oxide (GO). The Brunauer-Emmett-Teller (BET) isotherm model was considered as the best isotherm model in describing the PFOA adsorption onto GO-PEI3 (wPEI/wGO = 3). GO-PEI3 exhibited high adsorption capacity (qe = 368.2 mg/g, calculated from BET isotherm model) and excellent stability. The maximum monolayer amount of PFOA adsorption onto GO-PEI3 (qm = 231.2 mg/g) was successfully evaluated. The calculated saturated concentration (Cs = 169.9 mg/L) of PFOA on GO-PEI3 closely agrees with its critical micelle concentration (CMC = 157.0 mg/L), suggesting the formation of multilayer hemi-micelles or micelles PFOA structures on the surface of GO-PEI3. PFOA adsorption onto GO-PEI3 was inhibited by several factors including: the presence of humic acid (HA) by competing with the adsorption sites, background salts through the double-layer compression effect, and the competition from soluble ions for the amine or amide functional groups on GO-PEI3. Finally, both the FT-IR and XPS results confirmed that the adsorption of PFOA onto GO-PEI3 was through electrostatic attraction and hydrophobic interaction (physical adsorption), but not chemical adsorption. This work provides fundamental knowledge both in understanding the adsorption behavior through the BET isotherm model and in developing a stable adsorbent for PFOA adsorption. In addition, the findings highlight the potential of PFOA remediation from wastewater systems using GO-PEI in engineering applications.

Archetype tasks link intratumoral heterogeneity to plasticity and cancer hallmarks in small cell lung cancer.

Small cell lung cancer (SCLC) tumors comprise heterogeneous mixtures of cell states, categorized into neuroendocrine (NE) and non-neuroendocrine (non-NE) transcriptional subtypes. NE to non-NE state transitions, fueled by plasticity, likely underlie adaptability to treatment and dismal survival rates. Here, we apply an archetypal analysis to model plasticity by recasting SCLC phenotypic heterogeneity through multi-task evolutionary theory. Cell line and tumor transcriptomics data fit well in a five-dimensional convex polytope whose vertices optimize tasks reminiscent of pulmonary NE cells, the SCLC normal counterparts. These tasks, supported by knowledge and experimental data, include proliferation, slithering, metabolism, secretion, and injury repair, reflecting cancer hallmarks. SCLC subtypes, either at the population or single-cell level, can be positioned in archetypal space by bulk or single-cell transcriptomics, respectively, and characterized as task specialists or multi-task generalists by the distance from archetype vertex signatures. In the archetype space, modeling single-cell plasticity as a Markovian process along an underlying state manifold indicates that task trade-offs, in response to microenvironmental perturbations or treatment, may drive cell plasticity. Stifling phenotypic transitions and plasticity may provide new targets for much-needed translational advances in SCLC. A record of this paper's Transparent Peer Review process is included in the supplemental information.

Merging of ventral fibers at adhesions drives the remodeling of cellular contractile systems in fibroblasts.

Ventral stress fibers (VSFs) are contractile actin fibers dynamically attached to cell-matrix focal adhesions. VSFs are critical in cellular traction force production and migration. VSFs vary from randomly oriented short, thinner fibers to long, thick fibers that span along the whole long axis of a cell. De novo VSF formation was shown to occur by cortical actin mesh condensation or by crosslinking of dorsal stress fibers and transverse arcs at the cell front. However, the formation of long VSFs that extend across the whole cell axis is not well understood. Here, we report a novel phenomenon of VSF merging in migratory fibroblast cells, which is guided by mechanical force balance and contributes to VSF alignment along the long cell axis. The mechanism of VSF merging involves two steps: connection of two ventral fibers by an emerging myosin II bridge at an intervening adhesion and intervening adhesion dissolution. Our data indicate that these two steps are interdependent: slow adhesion disassembly leads to the slowing of the myosin bridge formation. Cellular data and computational modeling show that the contact angle between merging fibers decides successful merging, with shallow angles leading to merge failure. Our data and modeling further show that merging increases the share of uniformly aligned long VSFs, likely contributing to directional traction force production. Thus, we characterize merging as a process for dynamic reorganization of VSFs with functional significance for directional cell migration.

Surface-bound hydroxyl radical-dominated degradation of sulfamethoxazole in the amorphous FeOOH/ peroxymonosulfate system: The key role of amorphous structure enhancing electron transfer.

In this study, activation of peroxymonosulfate (PMS) by amorphous FeOOH to degrade sulfamethoxazole (SMX) was investigated. The amorphous FeOOH showed a better performance in the decomposition of PMS and the degradation of SMX than the crystallized α-FeOOH and ß-FeOOH. The quenching experiments and EPR measurements suggested that the mechanism of PMS activation by amorphous FeOOH was mainly the surface-bound radicals (●OH and SO4●-). Basically, the surface-bound ●OH radicals were the dominate reactive oxide species in this system, which were mainly generated via the decomposition of amorphous FeOOH-PMS complexes. The degradation of SMX was significantly inhibited with the presence of H2PO4-, and this adverse impact was negligibly affected by the increase of H2PO4- concentration, implying that the inhibition of SMX degradation was caused by competitive adsorption. Consequently, the Fe-OH bonds on the amorphous FeOOH were proposed as the reactive sites for forming amorphous FeOOH-PMS complexes. Besides, the amorphous FeOOH showed a better performance in the degradation of SMX in the acid conditions than that in the base conditions due to the surface charge of amorphous FeOOH. More importantly, the reduction efficiency of Fe(III) was significantly enhanced due to the excellent conductivity of amorphous FeOOH.

Biophysical Models of PAR Cluster Transport by Cortical Flow in C. elegans Early Embryogenesis.

The clustering of membrane-bound proteins facilitates their transport by cortical actin flow in early Caenorhabditis elegans embryo cell polarity. PAR-3 clustering is critical for this process, yet the biophysical processes that couple protein clusters to cortical flow remain unknown. We develop a discrete, stochastic agent-based model of protein clustering and test four hypothetical models for how clusters may interact with the flow. Results show that the canonical way to assess transport characteristics from single-particle tracking data used thus far in this area, the Péclet number, is insufficient to distinguish these hypotheses and that all models can account for transport characteristics quantified by this measure. However, using this model, we demonstrate that these different cluster-cortex interactions may be distinguished using a different metric, namely the scalar projection of cluster displacement on to the flow displacement vector. Our results thus provide a testable way to use existing single-particle tracking data to test how endogenous protein clusters may interact with the cortical flow to localize during polarity establishment. To facilitate this investigation, we also develop both improved simulation and semi-analytic methodologies to quantify motion summary statistics (e.g., Péclet number and scalar projection) for these stochastic models as a function of biophysical parameters.

Cortical tension initiates the positive feedback loop between cadherin and F-actin.

Adherens junctions physically link two cells at their contact interface via extracellular binding between cadherin molecules and intracellular interactions between cadherins and the actin cytoskeleton. Cadherin and actomyosin cytoskeletal dynamics are regulated reciprocally by mechanical and chemical signals, which subsequently determine the strength of cell-cell adhesions and the emergent organization and stiffness of the tissues they form. However, an understanding of the integrated system is lacking. We present a new mechanistic computational model of intercellular junction maturation in a cell doublet to investigate the mechanochemical cross talk that regulates adherens junction formation and homeostasis. The model couples a two-dimensional lattice-based simulation of cadherin dynamics with a reaction-diffusion representation of the reorganising actomyosin network through its regulation by Rho signalling at the intracellular junction. We demonstrate that local immobilization of cadherin induces cluster formation in a cis-less-dependent manner. We then recapitulate the process of cell-cell contact formation. Our model suggests that cortical tension applied on the contact rim can explain the ring distribution of cadherin and actin filaments (F-actin) on the cell-cell contact of the cell doublet. Furthermore, we propose and test the hypothesis that cadherin and F-actin interact like a positive feedback loop, which is necessary for formation of the ring structure. Different patterns of cadherin distribution were observed as an emergent property of disturbances of this positive feedback loop. We discuss these findings in light of available experimental observations on underlying mechanisms related to cadherin/F-actin binding and the mechanical environment.