Competition between physical search and a weak-to-strong transition rate-limits kinesin binding times.

The self-organization of cells relies on the profound complexity of protein-protein interactions. Challenges in directly observing these events have hindered progress toward understanding their diverse behaviors. One notable example is the interaction between molecular motors and cytoskeletal systems that combine to perform a variety of cellular functions. In this work, we leverage theory and experiments to identify and quantify the rate-limiting mechanism of the initial association between a cargo-bound kinesin motor and a microtubule track. Recent advances in optical tweezers provide binding times for several lengths of kinesin motors trapped at varying distances from a microtubule, empowering the investigation of competing models. We first explore a diffusion-limited model of binding. Through Brownian dynamics simulations and simulation-based inference, we find this simple diffusion model fails to explain the experimental binding times, but an extended model that accounts for the ADP state of the molecular motor agrees closely with the data, even under the scrutiny of penalizing for additional model complexity. We provide quantification of both kinetic rates and biophysical parameters underlying the proposed binding process. Our model suggests that a typical binding event is limited by ADP state rather than physical search. Lastly, we predict how these association rates can be modulated in distinct ways through variation of environmental concentrations and physical properties.

Microcystin profiles in European noble crayfish Astacus astacus and water in Lake Steinsfjorden, Norway.

Lake Steinsfjorden, an important noble crayfish (Astacus astacus) habitat, is often affected by blooms of Planktothrix spp. that produce microcystins (MCs). A poor correlation between MCs by ELISA in the water and in crayfish tissue in a study in 2015 prompted further investigation by LC-HRMS. LC-HRMS analyses of filters from water samples and on selected crayfish tissue extracts from the 2015 study revealed the presence of known and previously unreported MCs. Crayfish samples from May and June 2015 were dominated by MCs from the Planktothrix bloom, whereas in September novel MCs that appeared to be metabolites of MC-LR were dominant, even though neither these nor MC-LR were detected in the water in 2015. A water sample from October 2016 also showed MCs typical of Planktothrix (i.e., [d-Asp3]- and [d-Asp3,Dhb7]MC-RR and -LR), but low levels of MC-RR and MC-LR were detected in the lake water for the first time. In late summer and autumn, the MC profiles of crayfish were dominated by the homonorvaline (Hnv) variant MC-LHnv, a putative metabolite of MC-LR. Taken together, ELISA, LC-HRMS and previous PCR analyses showed that although Planktothrix was part of the crayfish diet, it was not the sole source of MCs in the crayfish. Possibly, crayfish in Lake Steinsfjorden may be ingesting MCs from benthic cyanobacteria or from contaminated prey. Therefore, information on the cyanobacterial or MC content in the water column cannot safely be used to make predictions about MC concentrations in the crayfish in Lake Steinsfjorden. Interestingly, the results also show that targeted LC-MS analysis of the crayfish would at times have underestimated their MC content by nearly an order of magnitude, even if all previously reported MC variants had been included in the analysis.

Inferring Stochastic Rates from Heterogeneous Snapshots of Particle Positions.

Many imaging techniques for biological systems-like fixation of cells coupled with fluorescence microscopy-provide sharp spatial resolution in reporting locations of individuals at a single moment in time but also destroy the dynamics they intend to capture. These snapshot observations contain no information about individual trajectories, but still encode information about movement and demographic dynamics, especially when combined with a well-motivated biophysical model. The relationship between spatially evolving populations and single-moment representations of their collective locations is well-established with partial differential equations (PDEs) and their inverse problems. However, experimental data is commonly a set of locations whose number is insufficient to approximate a continuous-in-space PDE solution. Here, motivated by popular subcellular imaging data of gene expression, we embrace the stochastic nature of the data and investigate the mathematical foundations of parametrically inferring demographic rates from snapshots of particles undergoing birth, diffusion, and death in a nuclear or cellular domain. Toward inference, we rigorously derive a connection between individual particle paths and their presentation as a Poisson spatial process. Using this framework, we investigate the properties of the resulting inverse problem and study factors that affect quality of inference. One pervasive feature of this experimental regime is the presence of cell-to-cell heterogeneity. Rather than being a hindrance, we show that cell-to-cell geometric heterogeneity can increase the quality of inference on dynamics for certain parameter regimes. Altogether, the results serve as a basis for more detailed investigations of subcellular spatial patterns of RNA molecules and other stochastically evolving populations that can only be observed for single instants in their time evolution.

Screening and Referral for Behavioral Health Symptoms in Collegiate Athletes.

OBJECTIVE: We aim to investigate the prevalence of behavioral health symptoms in collegiate athletes and the frequency of referrals prompted by a preparticipation behavioral health screener. DESIGN: Athletes completed a screening battery to detect behavioral health symptoms and sports psychology clinicians designed criteria for intervention based on the severity of symptoms reported. Data from the screener was retrospectively de-identified and analyzed. SETTING: National Collegiate Athletic Association Division-I university. PARTICIPANTS: All athletes on active rosters were required to complete the screener as a component of the preparticipation examination. INTERVENTIONS: Sports psychology clinicians created a protocol for intervention based on the number and severity of symptoms reported on the screener. MAIN OUTCOME MEASURES: Communication with athletes and referrals made to behavioral health services. RESULTS: Of the 1126 surveys completed, 39% had behavioral health symptoms necessitating behavioral health referral. Twelve percent required a safety check-in, given the severity of their symptoms. Seven percent of the respondents were newly established with behavioral health services. CONCLUSIONS: Symptoms of behavioral health disorders are common among athletes and yet, for a myriad of reasons, many choose to forgo treatment. By implementing a behavioral health screening battery, the prevalence of behavioral health symptoms among athletes at our institution was elucidated and many athletes were newly established with behavioral health services. The tiered intervention protocol in this study allowed for appropriate assessment and triage of high-risk individuals, while simultaneously providing lower-risk individuals with appropriate resources. Surveillance for behavioral health symptoms among college athletes using a screening battery with a tiered intervention protocol can ensure at-risk athletes are identified, contacted, and referred to behavioral health services, potentially improving their athletic performance and overall well-being, while averting poor outcomes.

Preparation of 18O-labelled azaspiracids for accurate quantitation using liquid chromatography-mass spectrometry.

Azaspiracids (AZAs) are a group of polyether marine algal toxins known to accumulate in shellfish, posing a risk to human health and the seafood industry. Analysis of AZAs is typically performed using LC-MS, which can suffer from matrix effects that significantly impact the accuracy of measurement results. While the use of isotopic internal standards is an effective approach to correct for these effects, isotopically labelled standards for AZAs are not currently available. In this study, 18O-labelled AZA1, AZA2, and AZA3 were prepared by reaction with H218O under acidic conditions, and the reaction kinetics and sites of incorporation were studied using LC-HRMS/MS aided by mathematical analysis of their isotope patterns. Analysis of the isotopic incorporation in AZA1 and AZA3 indicated the presence of four exchangeable oxygen atoms. Excessive isomerization occurred during preparation of 18O-labelled AZA2, suggesting a role for the 8-methyl group in the thermodynamic stability of AZAs. Neutralized mixtures of 18O-labelled AZA1 and AZA3 were found to maintain their isotopic and isomeric integrities when stored at -20 °C and were used to develop an isotope-dilution LC-MS method which was applied to reference materials of shellfish matrices containing AZAs, demonstrating high accuracy and excellent reproducibility. Preparation of isotopically labelled compounds using the isotopic exchange method, combined with the kinetic analysis, offers a feasible way to obtain isotopically labelled internal standards for a wide variety of biomolecules to support reliable quantitation.

Liquid chromatography-high-resolution tandem mass spectrometry of anatoxins, including new conjugates and reduction products.

Anatoxins (ATXs) are a potent class of cyanobacterial neurotoxins for which only a handful of structural analogues have been well characterized. Here, we report the development of an LC-HRMS/MS method for the comprehensive detection of ATXs. Application of this method to samples of benthic cyanobacterial mats and laboratory cultures showed detection of several new ATXs. Many of these result from nucleophilic addition to the olefinic bond of the α,ß-unsaturated ketone functional group of anatoxin-a (ATX) and homoanatoxin-a (hATX), analogous to the conjugation chemistry of microcystins, which contain similar α,ß-unsaturated amide functionality. Conjugates with glutathione, γ-glutamylcysteine, methanethiol, ammonia, methanol and water were detected, as well as putative C-10 alcohol derivatives. Structural confirmation was obtained by simple and selective analytical-scale semisynthetic reactions starting from available ATX standards. Methanol, water and ammonia conjugates were found to result primarily from sample preparation. Reduction products were found to result from enzymatic reactions occurring primarily after cell lysis in laboratory cultures of Kamptonema formosum and Cuspidothrix issatschenkoi. The relative contributions of the identified analogues to the anatoxin profiles in a set of 22 benthic-cyanobacterial-mat field samples were estimated, showing conjugates to account for up to 15% of total ATX peak area and 10-hydroxyanatoxins up to 38%. The developed methodology, new analogues and insight into the chemical and enzymatic reactivity of ATXs will enable a more comprehensive study of the class than possible previously.

A survey of Dinophysis spp. and their potential to cause diarrhetic shellfish poisoning in coastal waters of the United States.

Multiple species of the genus Dinophysis produce diarrhetic shellfish toxins (okadaic acid and Dinophysis toxins, OA/DTXs analogs) and/or pectenotoxins (PTXs). Only since 2008 have DSP events (illnesses and/or shellfish harvesting closures) become recognized as a threat to human health in the United States. This study characterized 20 strains representing five species of Dinophysis spp. isolated from three US coastal regions that have experienced DSP events: the Northeast/Mid-Atlantic, the Gulf of Mexico, and the Pacific Northwest. Using a combination of morphometric and DNA-based evidence, seven Northeast/Mid-Atlantic isolates and four Pacific Northwest isolates were classified as D. acuminata, a total of four isolates from two coasts were classified as D. norvegica, two isolates from the Pacific Northwest coast were identified as D. fortii, and three isolates from the Gulf of Mexico were identified as D. ovum and D. caudata. Toxin profiles of D. acuminata and D. norvegica varied by their geographical origin within the United States. Cross-regional comparison of toxin profiles was not possible with the other three species; however, within each region, distinct species-conserved profiles for isolates of D. fortii, D. ovum, and D. caudata were observed. Historical and recent data from various State and Tribal monitoring programs were compiled and compared, including maximum recorded cell abundances of Dinophysis spp., maximum concentrations of OA/DTXs recorded in commercial shellfish species, and durations of harvesting closures, to provide perspective regarding potential for DSP impacts to regional public health and shellfish industry.

Coarse-grained dynamics of transiently bound fast linkers.

Transient bonds between fast linkers and slower particles are widespread in physical and biological systems. Despite their diverse structure and function, a commonality is that the linkers diffuse on timescales much faster compared to the overall motion of the particles they bind to. This limits numerical and theoretical approaches that need to resolve these diverse timescales with high accuracy. Many models, therefore, resort to effective, yet ad hoc, dynamics, where linker motion is only accounted for when bound. This paper provides a mathematical justification for such coarse-grained dynamics that preserves detailed balance at equilibrium. Our derivation is based on multiscale averaging techniques and is broadly applicable. We verify our results with simulations on a minimal model of fast linker binding to a slow particle. We show how our framework can be applied to various systems, including those with multiple linkers, stiffening linkers upon binding, or slip bonds with force-dependent unbinding. Importantly, the preservation of detailed balance only sets the ratio of the binding to the unbinding rates, but it does not constrain the detailed expression of binding kinetics. We conclude by discussing how various choices of binding kinetics may affect macroscopic dynamics.

Head Impact Exposure in Female Collegiate Soccer by Activity Type.

Soccer, one of the most popular sports in the world, has one of the highest rates of sports-related concussions. Additionally, soccer players are frequently exposed to nonconcussive impacts from intentionally heading the ball, a fundamental component of the sport. There have been many studies on head impact exposure in soccer, but few focus on soccer practices or practice activities. This study aimed to characterize the frequency and magnitude of head impacts in National Collegiate Athletic Association Division I female soccer practice activities using a custom-fit instrumented mouthpiece. Sixteen players were instrumented over the course of 54 practice sessions. Video analysis was performed to verify all mouthpiece-recorded events and classify practice activities. Category groupings of practice activities include technical training, team interaction, set pieces, position-specific, and other. Differences in head impact rates and peak resultant kinematics were observed across activity types and category groupings. Technical training had the highest impact rate compared to other category groupings. Impacts occurring during set piece activities had the highest mean kinematic values. Understanding drill exposure can help inform coaches on training plans aimed to reduce head impact exposure for their athletes.

Characterization of Head Acceleration Exposure During Youth Football Practice Drills.

Many head acceleration events (HAEs) observed in youth football emanate from a practice environment. This study aimed to evaluate HAEs in youth football practice drills using a mouthpiece-based sensor, differentiating between inertial and direct HAEs. Head acceleration data were collected from athletes participating on 2 youth football teams (ages 11-13 y) using an instrumented mouthpiece-based sensor during all practice sessions in a single season. Video was recorded and analyzed to verify and assign HAEs to specific practice drill characteristics, including drill intensity, drill classification, and drill type. HAEs were quantified in terms of HAEs per athlete per minute and peak linear and rotational acceleration and rotational velocity. Mixed-effects models were used to evaluate the differences in kinematics, and generalized linear models were used to assess differences in HAE frequency between drill categories. A total of 3237 HAEs were verified and evaluated from 29 football athletes enrolled in this study. Head kinematics varied significantly between drill categorizations. HAEs collected at higher intensities resulted in significantly greater kinematics than lower-intensity drills. The results of this study add to the growing body of evidence informing evidence-based strategies to reduce head impact exposure and concussion risk in youth football practices.

Role of the electrocardiogram in differentiating genetically determined dilated cardiomyopathy from athlete's heart.

BACKGROUND: Physiological cardiac remodelling in highly trained athletes may overlap with dilated cardiomyopathy (DCM). OBJECTIVES: The aim of this study was to investigate the role of the electrocardiogram (ECG) in differentiating between physiological and pathological remodelling. METHODS: The study population consisted of 30 patients with DCM who revealed a pathogenic variant at genetic testing and 30 elite athletes with significant cardiac remodelling defined by a left ventricular (LV) end-diastolic diameter >62 mm and/or LV ejection fraction between 45% and 50%. RESULTS: The ECG was abnormal in 22 (73%) patients with DCM. The most common abnormalities were low voltages (n = 14, 47%), lateral T-wave inversion (TWI) (n = 6, 20%), ventricular ectopic beats (n = 5, 17%) and anterior TWI (n = 4, 13). Two athletes revealed an abnormal ECG: complete left bundle branch block (LBBB) in one case and atrial flutter in the other. The sensitivity, specificity and accuracy of the ECG in differentiating DCM from physiological adaptation to exercise in athletes was 73% (confidence interval [CI]: 54%-88%), 93% (CI: 78%-99%) and 0.83 (CI: 0.71-0.92) respectively. CONCLUSIONS: While the ECG is usually normal in athletes exhibiting significant LV dilatation and/or systolic dysfunction, this test is often abnormal in patients with DCM harbouring a pathogenic variant. Low voltages in the limb leads and lateral TWI are the most common abnormalities.

Thermal stability of cannabinoids in dried cannabis: a kinetic study.

This study was undertaken to quantitatively explore the effect of temperature on the degradation of cannabinoids in dried cannabis flower. A total of 14 cannabinoids were monitored using liquid chromatography and tandem mass spectrometry in temperature environments from - 20 to + 40 ∘C lasting up to 1 year. We find that a network of first-order degradation reactions is well-suited to model the observed changes for all cannabinoids. While most studies focus on high-temperature effects on the cannabinoids, this study provides high-precision quantitative assessment of room temperature kinetics with applications to shelf-life predictions and age estimates of cannabis products.

Lipid bilayers as potential ice nucleating agents.

Cellular damage is a key issue in the context of cryopreservation. Much of this damage is believed to be caused by extracellular ice formation at temperatures well above the homogeneous freezing point of pure water. Hence the question: what initiates ice nucleation during cryopreservation? In this paper, we assess whether cellular membranes could be responsible for facilitating the ice nucleation process, and what characteristics would make them good or bad ice nucleating agents. By means of molecular dynamics simulations, we investigate a number of phospholipids and lipopolysaccharide bilayers at the interface with supercooled liquid water. While these systems certainly appear to act as ice nucleating agents, it is likely that other impurities might also play a role in initiating extracellular ice nucleation. Furthermore, we elucidate the factors which affect a bilayer's ability to act as an ice nucleating agent; these are complex, with specific reference to both chemical and structural factors. These findings represent a first attempt to pinpoint the origin of extracellular ice nucleation, with important implications for the cryopreservation process.

Mechanical Torque Promotes Bipolarity of the Mitotic Spindle Through Multi-centrosomal Clustering.

Intracellular forces shape cellular organization and function. One example is the mitotic spindle, a cellular machine consisting of multiple chromosomes and centrosomes which interact via dynamic microtubule filaments and motor proteins, resulting in complicated spatially dependent forces. For a cell to divide properly, it is important for the spindle to be bipolar, with chromosomes at the center and multiple centrosomes clustered into two 'poles' at opposite sides of the chromosomes. Experimental observations show that in unhealthy cells, the spindle can take on a variety of patterns. What forces drive each of these patterns? It is known that attraction between centrosomes is key to bipolarity, but what prevents the centrosomes from collapsing into a monopolar configuration? Here, we explore the hypothesis that torque rotating chromosome arms into orientations perpendicular to the centrosome-centromere vector promotes spindle bipolarity. To test this hypothesis, we construct a pairwise-interaction model of the spindle. On a continuum version of the model, an integro-PDE system, we perform linear stability analysis and construct numerical solutions which display a variety of spatial patterns. We also simulate a discrete particle model resulting in a phase diagram that confirms that the spindle bipolarity emerges most robustly with torque. Altogether, our results suggest that rotational forces may play an important role in dictating spindle patterning.

Exercise medicine and physical activity promotion: core curricula for US medical schools, residencies and sports medicine fellowships: developed by the American Medical Society for Sports Medicine and endorsed by the Canadian Academy of Sport and Exercise Medicine.

Regular physical activity provides a variety of health benefits and is proven to treat and prevent several non-communicable diseases. Specifically, physical activity enhances muscular and osseous strength, improves cardiorespiratory fitness, and reduces the risk of hypertension, coronary heart disease, stroke, type 2 diabetes, mental health disorders, cognitive decline and several cancers. Despite these well-known benefits, physical activity promotion in clinical practice is underused due to insufficient training during medical education. Medical trainees in the USA receive relatively few hours of instruction in sports and exercise medicine (SEM). One reason for this shortage of instruction is a lack of curricular resources at each level of medical education. To address this need, the American Medical Society for Sports Medicine (AMSSM) assembled a group of SEM experts to develop curricular guidance for exercise medicine and physical activity promotion at the medical school, residency and sports medicine fellowship levels of training. After an evidence review of existing curricular examples, we performed a modified Delphi process to create curricula for medical students, residents and sports medicine fellows. Three training level-specific curricula emerged, each containing Domains, General Learning Areas, and Specific Learning Areas; options for additional training and suggestions for assessment and evaluation were also provided. Review and comment on the initial curricula were conducted by three groups: a second set of experts in exercise medicine and physical activity promotion, sports medicine fellowship directors representing a variety of fellowship settings and the AMSSM Board of Directors. The final curricula for each training level were prepared based on input from the review groups. We believe enhanced medical education will enable clinicians to better integrate exercise medicine and physical activity promotion in their clinical practice and result in healthier, more physically active patients.

Characterization of Head Impact Exposure in Women's Collegiate Soccer.

Soccer players are regularly exposed to head impacts by intentionally heading the ball. Evidence suggests repetitive subconcussive head impacts may affect the brain, and females may be more vulnerable to brain injury than males. This study aimed to characterize head impact exposure among National Collegiate Athletic Association women's soccer players using a previously validated mouthpiece-based sensor. Sixteen players were instrumented during 72 practices and 24 games. Head impact rate and rate of risk-weighted cumulative exposure were compared across session type and player position. Head kinematics were compared across session type, impact type, player position, impact location, and ball delivery method. Players experienced a mean (95% confidence interval) head impact rate of 0.468 (0.289 to 0.647) head impacts per hour, and exposure rates varied by session type and player position. Headers accounted for 89% of head impacts and were associated with higher linear accelerations and rotational accelerations than nonheader impacts. Headers in which the ball was delivered by a long kick had greater peak kinematics (all P < .001) than headers in which the ball was delivered by any other method. Results provide increased understanding of head impact frequency and magnitude in women's collegiate soccer and may help inform efforts to prevent brain injury.

Musculoskeletal injury symptoms among hired Latinx child farmworkers in North Carolina.

BACKGROUND: Although children 10-17 years can be hired to work in agriculture, little research has addressed possible musculoskeletal injuries. Children may be at particular risk for these injuries because of the repetitive and load bearing nature of work tasks. Existing research relies on child workers to self-report musculoskeletal injuries. METHODS: In 2017, 202 Latinx child farmworkers ages 10-17 employed across North Carolina completed survey interviews. In 2018, 145 of these children (94 [64.8%] current farmworkers) completed a physical examination and second interview. The examination obtained findings for upper and lower extremity as well as back injuries. RESULTS: Positive indicators for musculoskeletal symptoms were few in either current or former child farmworkers. The knee was most common site for positive indicators with 15.4% of children having at least one. Combining all anatomical sites, 29.0% of children had at least one positive indicator, with no significant difference between current and former farmworkers. Overall, boys had significantly more indicators of knee injuries than girls (21.3% vs. 4.1%), indicators of ankle injuries were found only in the youngest workers (9.5% of children 11-13 years), and significantly fewer current farmworkers had indicators of lower back injuries than former farmworkers (6.4% vs. 17.7%). CONCLUSIONS: Expectations of injuries come from previous studies using child farmworker self-reports, adult farmworker injury rates, and sports medicine pediatric findings. Hired child farmworkers may not perform activities as repetitious and load-bearing as children in sports training or adult farmworkers. Additional research using physical examination is needed to confirm these findings.

Pediatric Obesity and Sports Medicine: A Narrative Review and Clinical Recommendations.

OBJECTIVE: To review what is known about sports medicine and pediatric obesity, with a focus on injuries and MSK concerns. DATA SOURCES: Systematically searched MEDLINE (PubMed) for all years, using search combinations to best identify potential publications. Manuscripts were reviewed, summarized, and discussed in detail. Experienced clinicians in sports medicine and pediatric obesity reviewed the final searches for substantive content. Inclusion criteria include English language publications, children ≤18 years old, related to the practice of sports medicine and pediatric obesity. Publications excluded that dealt with non-sports medicine aspects of pediatric obesity, such as increasing physical activity or exercise, or the prevention or treatment of obesity. MAIN RESULTS: Twenty-eight publications were included for review. Papers fell into 5 groupings: (1) MSK-increased incidence of MSK injury in children with obesity, hypothesized to be a result of changes in biomechanics; (2) weight management-gradual loss while maintaining proper hydration and nutrition for sports performance; (3) fitness/conditioning-children with overweight/obese showed decreased fitness measures and cardiopulmonary conditioning; (4) exertional heat illness-a concern for adolescent athletes with obesity, specifically in football; and (5) differential diagnoses-3 key differential diagnoses were identified for increased awareness: slipped capital femoral epiphysis, Blount's disease, and pes planus. Clinical topics pertinent to sports medicine and pediatric obesity were discussed. CONCLUSIONS: Sports medicine clinicians should be aware of the common MSK and sports-related conditions in children with obesity. Few studies have focused investigations on issues related to children with obesity participating in sports and other physical activities.

Characterization of On-Field Head Impact Exposure in Youth Soccer.

The objective of this research was to characterize head impacts with a validated mouthpiece sensor in competitive youth female soccer players during a single season with a validated mouthpiece sensor. Participants included 14 youth female soccer athletes across 2 club-level teams at different age levels (team 1, ages 12-13 y; team 2, ages 14-15 y). Head impact and time-synchronized video data were collected for 66 practices and games. Video data were reviewed to characterize the type and frequency of contact experienced by each athlete. A total of 2216 contact scenarios were observed; heading the ball (n = 681, 30.7%) was most common. Other observed contact scenarios included collisions, dives, falls, and unintentional ball contact. Team 1 experienced a higher rate of headers per player per hour of play than team 2, while team 2 experienced a higher rate of collisions and dives. A total of 935 video-verified contact scenarios were concurrent with recorded head kinematics. While headers resulted in a maximum linear acceleration of 56.1g, the less frequent head-to-head collisions (n = 6) resulted in a maximum of 113.5g. The results of this study improve the understanding of head impact exposure in youth female soccer players and inform head impact exposure reduction in youth soccer.

Receptor Organization Determines the Limits of Single-Cell Source Location Detection.

Many types of cells require the ability to pinpoint the location of an external stimulus from the arrival of diffusing signaling molecules at cell-surface receptors. How does the organization (number and spatial configuration) of these receptors shape the limit of a cell's ability to infer the source location? In the idealized scenario of a spherical cell, we apply asymptotic analysis to compute splitting probabilities between individual receptors and formulate an information-theoretic framework to quantify the role of receptor organization. Clustered configurations of receptors provide an advantage in detecting sources aligned with the clusters, suggesting a possible multiscale mechanism for single-cell source inference.