Recovery from desensitization in GluA2 AMPA receptors is affected by a single mutation in the N-terminal domain interface.

AMPA-type ionotropic glutamate receptors (AMPARs) are central to various neurological processes, including memory and learning. They assemble as homo- or heterotetramers of GluA1, GluA2, GluA3, and GluA4 subunits, each consisting of an N-terminal domain (NTD), a ligand-binding domain, a transmembrane domain, and a C-terminal domain. While AMPAR gating is primarily controlled by reconfiguration in the ligand-binding domain layer, our study focuses on the NTDs, which also influence gating, yet the underlying mechanism remains enigmatic. In this investigation, we employ molecular dynamics simulations to evaluate the NTD interface strength in GluA1, GluA2, and NTD mutants GluA2-H229N and GluA1-N222H. Our findings reveal that GluA1 has a significantly weaker NTD interface than GluA2. The NTD interface of GluA2 can be weakened by a single point mutation in the NTD dimer-of-dimer interface, namely H229N, which renders GluA2 more GluA1-like. Electrophysiology recordings demonstrate that this mutation also leads to slower recovery from desensitization. Moreover, we observe that lowering the pH induces more splayed NTD states and enhances desensitization in GluA2. We hypothesized that H229 was responsible for this pH sensitivity; however, GluA2-H229N was also affected by pH, meaning that H229 is not solely responsible and that protons exert their effect across multiple domains of the AMPAR. In summary, our work unveils an allosteric connection between the NTD interface strength and AMPAR desensitization.

A Histological Assessment Tool for Breast Implant Capsules Validated in 480 Patients with and Without Capsular Contracture.

BACKGROUND: Understanding the impact of breast implants on the histological response in the surrounding fibrous capsule is important; however, consensus is lacking on how to analyze implant capsules histologically. We aimed to develop a standardized histological assessment tool to be used in research potentially improving diagnostic accuracy and treatment strategies for capsular contracture. METHODS: Biopsies of breast implant capsules from 480 patients who had undergone breast augmentation or reconstruction were collected and stained with hematoxylin and eosin. Initially, biopsies from 100 patients were analyzed to select histological parameters demonstrating the highest relevance and reproducibility. Then, biopsies from the remaining 380 patients were used to determine intra- and interobserver agreements of two blinded observers and agreement with a pathologist. Finally, we tested the association between the parameters and capsular contracture. RESULTS: The histological assessment tool included ten parameters assessing the inflammatory, fibrotic, and foreign-body reaction to breast implants, each graded on two-, three-, or four-point scales. Intra- and interobserver agreements were almost perfect (0.83 and 0.80), and agreement with the pathologist was substantial (0.67). Four parameters were significantly correlated with capsular contracture, namely chronic inflammation with lymphocyte infiltration (p < 0.01), thickness of the collagen layer (p < 0.0001), fiber organization (p < 0.01), and calcification (p < 0.001). CONCLUSIONS: This is the first validated histological assessment tool for breast implant capsules. The validated tool not only advances our understanding of capsular contracture but also sets a new standard for histological evaluation in breast implant research and clinical diagnostics. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Development and Validation of a Diagnostic Histopathological Scoring System for Capsular Contracture Based on 720 Breast Implant Capsules.

BACKGROUND: Capsular contracture is traditionally evaluated with the Baker classification, but this has notable limitations regarding reproducibility and objectivity. OBJECTIVES: The aim of this study was to develop and validate procedure-specific histopathological scoring systems to assess capsular contracture severity. METHODS: Biopsies of breast implant capsules were used to develop histopathological scoring systems for patients following breast augmentation and breast reconstruction. Ten histological parameters were evaluated by multivariable logistic regression to identify those most associated with capsular contracture. Significant parameters (P < .05) were selected for the scoring systems and assigned weighted scores (1-10). Validation was assessed from the area under the curve (AUC) and the mean absolute error (MAE). RESULTS: A total of 720 biopsies from 542 patients were included. Four parameters were selected for the augmentation scoring system, namely, collagen layer thickness, fiber organization, inflammatory infiltration, and calcification, providing a combined maximum score of 26. The AUC and MAE for the augmentation scoring system were 81% and 0.8%, which is considered strong. Three parameters were selected for the reconstruction scoring system, namely, fiber organization, collagen layer cellularity, and inflammatory infiltration, providing a combined maximum score of 19. The AUC and MAE of the reconstruction scoring system were 72% and 7.1%, which is considered good. CONCLUSIONS: The new histopathological scoring systems provide an objective, reproducible, and accurate assessment of capsular contracture severity. We propose these novel scoring systems as a valuable tool for confirming capsular contracture diagnosis in the clinical setting, for research, and for implant manufacturers and insurance providers in need of a confirmed capsular contracture diagnosis.

Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles.

Different amphiphilic co-polymers have been introduced to produce polymer-lipid particles with nanodisc structure composed of an inner lipid bilayer and polymer chains self-assembled as an outer belt. These particles can be used to stabilize membrane proteins in solution and enable their characterization by means of biophysical methods, including small-angle X-ray scattering (SAXS). Some of these co-polymers have also been used to directly extract membrane proteins together with their associated lipids from native membranes. Styrene/maleic acid and diisobutylene/maleic acid are among the most commonly used co-polymers for producing polymer-lipid particles, named SMALPs and DIBMALPs, respectively. Recently, a new co-polymer, named Glyco-DIBMA, was produced by partial amidation of DIBMA with the amino sugar N-methyl-d-glucosamine. Polymer-lipid particles produced with Glyco-DIBMA, named Glyco-DIBMALPs, exhibit improved structural properties and stability compared to those of SMALPs and DIBMALPs while retaining the capability of directly extracting membrane proteins from native membranes. Here, we characterize the structure and lipid composition of Glyco-DIBMALPs produced with either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Glyco-DIBMALPs were also prepared with mixtures of either POPC or DMPC and cholesterol at different mole fractions. We estimated the lipid content in the Glyco-DIBMALPs and determined the particle structure and morphology by SAXS. We show that the Glyco-DIBMALPs are nanodisc-like particles whose size and shape depend on the polymer/lipid ratio. This is relevant for designing nanodisc particles with a tunable diameter according to the size of the membrane protein to be incorporated. We also report that the addition of >20 mol % cholesterol strongly perturbed the formation of Glyco-DIBMALPs. Altogether, we describe a detailed characterization of the Glyco-DIBMALPs, which provides relevant inputs for future application of these particles in the biophysical investigation of membrane proteins.

Factors Influencing Patient Satisfaction With Breast Augmentation: A BREAST-Q Effect of Magnitude Analysis.

BACKGROUND: Breast augmentation is one of the most performed cosmetic surgeries. Despite this, patient satisfaction following breast augmentation is poorly understood. OBJECTIVES: The aim of this study was to investigate what patient and surgical factors influence patient satisfaction following primary breast augmentation. METHODS: The BREAST-Q Augmentation module was sent to all females undergoing primary breast augmentation at a single private clinic (Amalieklinikken, Copenhagen, Denmark) between 2012 and 2019. Patient and surgical characteristics at the time of surgery were obtained from the patients' medical records, and data on factors that occurred after the surgery (eg, breastfeeding) were obtained by patient contact. Multivariate linear regression modeled the impact of these factors on BREAST-Q outcomes. RESULTS: A total of 554 females with a mean follow-up time of 5 years after primary breast augmentation were included in this study. Implant type and volume did not affect patient satisfaction. However, higher patient age was associated with significantly higher postoperative patient satisfaction, psychosocial well-being, and sexual well-being (P < .05). Conversely, higher patient BMI, postoperative weight gain, and breastfeeding were associated with significantly lower satisfaction (P < .05). Additionally, subglandular implant placement was associated with significantly lower satisfaction than submuscular implant placement (P < .05). CONCLUSIONS: Implant type and volume did not affect patient satisfaction with breast augmentation. However, young age, higher BMI, subglandular implant placement, and postoperative weight gain were associated with lower patient satisfaction. These factors should be considered when aligning outcome expectations with breast augmentation.

Membrane-binding mechanism of the EEA1 FYVE domain revealed by multi-scale molecular dynamics simulations.

Early Endosomal Antigen 1 (EEA1) is a key protein in endosomal trafficking and is implicated in both autoimmune and neurological diseases. The C-terminal FYVE domain of EEA1 binds endosomal membranes, which contain phosphatidylinositol-3-phosphate (PI(3)P). Although it is known that FYVE binds PI(3)P specifically, it has not previously been described of how FYVE attaches and binds to endosomal membranes. In this study, we employed both coarse-grained (CG) and atomistic (AT) molecular dynamics (MD) simulations to determine how FYVE binds to PI(3)P-containing membranes. CG-MD showed that the dominant membrane binding mode resembles the crystal structure of EEA1 FYVE domain in complex with inositol-1,3-diphospate (PDB ID 1JOC). FYVE, which is a homodimer, binds the membrane via a hinge mechanism, where the C-terminus of one monomer first attaches to the membrane, followed by the C-terminus of the other monomer. The estimated total binding energy is ~70 kJ/mol, of which 50-60 kJ/mol stems from specific PI(3)P-interactions. By AT-MD, we could partition the binding mode into two types: (i) adhesion by electrostatic FYVE-PI(3)P interaction, and (ii) insertion of amphipathic loops. The AT simulations also demonstrated flexibility within the FYVE homodimer between the C-terminal heads and coiled-coil stem. This leads to a dynamic model whereby the 200 nm long coiled coil attached to the FYVE domain dimer can amplify local hinge-bending motions such that the Rab5-binding domain at the other end of the coiled coil can explore an area of 0.1 µm2 in the search for a second endosome with which to interact.

Molecular Dynamics Simulations of Curved Lipid Membranes.

Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and thereby be trafficked to specific locations. The description of curvature sensing is another fundamental challenge. Curved lipid membranes and their interplay with membrane-associated proteins can be investigated with molecular dynamics (MD) simulations. Various methods for simulating curved membranes with MD are discussed here, including tools for setting up simulation of vesicles and methods for sustaining membrane curvature. The latter are divided into methods that exploit scaffolding virtual beads, methods that use curvature-inducing molecules, and methods applying virtual forces. The variety of simulation tools allow researcher to closely match the conditions of experimental studies of membrane curvatures.

Combining molecular dynamics simulations with small-angle X-ray and neutron scattering data to study multi-domain proteins in solution.

Many proteins contain multiple folded domains separated by flexible linkers, and the ability to describe the structure and conformational heterogeneity of such flexible systems pushes the limits of structural biology. Using the three-domain protein TIA-1 as an example, we here combine coarse-grained molecular dynamics simulations with previously measured small-angle scattering data to study the conformation of TIA-1 in solution. We show that while the coarse-grained potential (Martini) in itself leads to too compact conformations, increasing the strength of protein-water interactions results in ensembles that are in very good agreement with experiments. We show how these ensembles can be refined further using a Bayesian/Maximum Entropy approach, and examine the robustness to errors in the energy function. In particular we find that as long as the initial simulation is relatively good, reweighting against experiments is very robust. We also study the relative information in X-ray and neutron scattering experiments and find that refining against the SAXS experiments leads to improvement in the SANS data. Our results suggest a general strategy for studying the conformation of multi-domain proteins in solution that combines coarse-grained simulations with small-angle X-ray scattering data that are generally most easy to obtain. These results may in turn be used to design further small-angle neutron scattering experiments that exploit contrast variation through 1H/2H isotope substitutions.

Histological Analyses of Capsular Contracture and Associated Risk Factors: A Systematic Review.

BACKGROUND: Capsular contracture is a severe complication to breast surgery with implants. Previous studies suggest multiple risk factors are associated with capsular contracture, but the etiology is still unknown. We performed a literature review to investigate existing studies on histological analyses of breast implant capsules and how clinical risk factors impact the capsule morphology. METHODS: The literature search was conducted in PubMed. Studies that performed histological analyses of breast implant capsules were included. Animal studies or studies with a study population of less than five patients were excluded. RESULTS: Fifty-two studies were included. The histological analyses showed that the breast implant capsules were organized in multiple layers with an inner layer of synovial-like metaplasia which was reported to diminish in capsules with capsular contracture. The remaining layers of the capsule mostly consisted of collagen. The alignment of the collagen fibers differed between contracted and non-contracted capsules, and capsules with higher Baker grade were generally thickest and contained more tissue inflammation. Studies investigating capsules affected by radiotherapy found a more pronounced inflammatory response and the capsules were generally thicker and fibrotic compared with nonirradiated capsules. CONCLUSIONS: The included studies offer valuable insights into the histological changes caused by capsular contracture and their relation to clinical risk factors. Further studies with larger sample sizes and more strict inclusion criteria are needed to further investigate implant capsules and the role of the synovial-like metaplasia for the development of capsular contracture. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Deskinning in Inverted-T Mastopexy and Augmentation Mastopexy: A Retrospective Cohort Study.

BACKGROUND: Most surgeons choose to de-epithelialize when performing a mastopexy to minimize the risk of nipple-areola-complex (NAC) necrosis. Preservation of the dermis and thus the subdermal plexus is thought to be crucial for the survival of the NAC. However, this has never been scientifically proven. Deskinning involves resection of the epidermis and the dermis and is a timesaving alternative to de-epithelialization. In this study, we present data from mastopexy patients with or without implant surgery with total deskinning of the Wise pattern. METHODS: From September 2012 to March 2020, a single surgeon performed all inverted-T mastopexies using the deskinning technique. The patients were included retrospectively, and data were collected by reviewing the patients' medical records with emphasis on NAC necrosis. RESULTS: The cohort consisted of 274 consecutive patients who underwent bilateral mastopexy. Of these, 134 patients underwent mastopexy as the only procedure and 140 patients underwent mastopexy in combination with implant surgery. The median follow-up was 29 months (IQR 13-40 months). No complete NAC-necrosis occurred. Unilateral, partial NAC necrosis occurred in three patients who underwent mastopexy in combination with implant surgery. CONCLUSION: The NAC necrosis rate following inverted-T mastopexy using the deskinning technique is comparable to the rate of NAC-necrosis reported in the literature following mastopexy using the de-epithelialization technique. Our findings support that the use of deskinning is a safe and time-efficient method for patients undergoing inverted-T mastopexy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the table of Contents or the online Instructions to Authors www.springer.com/00266.

Development of the annual incidence rate of fracture in children 1980-2018: a population-based study of 32,375 fractures.

Background and purpose - Pediatric fractures are a common cause of morbidity. So far, no larger Danish study has described the development in the incidence rates. Therefore, we describe the development in the incidence rates of pediatric fractures in the time period 1980-2018 and the frequency of the most common type of fractures.Patients and methods - This is a retrospective register study of all children aged 0-15 years with a fracture treated in the Emergency Department at Odense University Hospital, Denmark, between 1980 and 2018. For all cases, information on age, sex, date of treatment, diagnosis, and treatment was obtained from the patient registration system. Based on official public population counts we estimated age and sex-specific annual incidence rates.Results - 32,375 fractures were included. In the study period the incidence rate decreased by 12%. The incidence increased until the early 1990s. Thereafter incidence rates decreased until 2004-09, from then onward increasing towards the end of the study period. The highest age-specific incidence rate in boys of 522 per 10,000 person-years was at 13 years of age. In girls the age of the highest incidence rate decreased from 11 years in 1980 to 10 years in 2018. Fracture of the lower end of the forearm, the clavicle, and the lower end of the humerus had the highest single fracture incidence rates.Interpretation - The incidence rate of pediatric fractures decreased in the study period by 12%. The highest single fracture incidence rates were for fracture of the lower end of the forearm, the clavicle, and the lower end of the humerus. As the first longitudinal Danish study of pediatric fractures this study is a baseline for evaluating future interventions and future studies.

Structure and Dynamics of the Central Lipid Pool and Proteins of the Bacterial Holo-Translocon.

The bacterial Sec translocon, SecYEG, associates with accessory proteins YidC and the SecDF-YajC subcomplex to form the bacterial holo-translocon (HTL). The HTL is a dynamic and flexible protein transport machine capable of coordinating protein secretion across the membrane and efficient lateral insertion of nascent membrane proteins. It has been hypothesized that a central lipid core facilitates the controlled passage of membrane proteins into the bilayer, ensuring the efficient formation of their native state. By performing small-angle neutron scattering on protein solubilized in "match-out" deuterated detergent, we have been able to interrogate a "naked" HTL complex, with the scattering contribution of the surrounding detergent micelle rendered invisible. Such an approach has allowed the confirmation of a lipid core within the HTL, which accommodates between 8 and 29 lipids. Coarse-grained molecular dynamics simulations of the HTL also demonstrate a dynamic, central pool of lipids. An opening at this lipid-rich region between YidC and the SecY lateral gate may provide an exit gateway for newly synthesized, correctly oriented, membrane protein helices, or even small bundles of helices, to emerge from the HTL.

Dimeric peptides with three different linkers self-assemble with phospholipids to form peptide nanodiscs that stabilize membrane proteins.

Three dimers of the amphipathic α-helical peptide 18A have been synthesized with different interhelical linkers inserted between the two copies of 18A. The dimeric peptides were denoted 'beltides' where Beltide-1 refers to the 18A-dimer without a linker, Beltide-2 is the 18A-dimer with proline (Pro) as a linker and Beltide-3 is the 18A-dimer linked by two glycines (Gly-Gly). The self-assembly of the beltides with the phospholipid DMPC was studied with and without the incorporated membrane protein bacteriorhodopsin (bR) through a combination of coarse-grained MD simulations, size-exclusion chromatography (SEC), circular dichroism (CD) spectroscopy, small-angle scattering (SAS), static light scattering (SLS) and UV-Vis spectroscopy. For all three beltides, MD and combined small-angle X-ray and -neutron scattering were consistent with a disc structure composed by a phospholipid bilayer surrounded by a belt of peptides and with a total disc diameter of approximately 10 nm. CD confirmed that all three beltides were α-helical in the free form and with DMPC. However, as shown by SEC the different interhelical linkers clearly led to different properties of the beltides. Beltide-3, with the Gly-Gly linker, was very adaptable such that peptide nanodiscs could be formed for a broad range of different peptide to lipid stoichiometries and therefore also possible disc-sizes. On the other hand, both Beltide-2 with the Pro linker and Beltide-1 without a linker were less adaptable and would only form discs of certain peptide to lipid stoichiometries. SLS revealed that the structural stability of the formed peptide nanodiscs was also highly affected by the linkers and it was found that Beltide-1 gave more stable discs than the other two beltides. With respect to membrane protein stabilization, each of the three beltides in combination with DMPC stabilizes the seven-helix transmembrane protein bacteriorhodopsin significantly better than the detergent octyl glucoside, but no significant difference was observed between the three beltides. We conclude that adaptability, size, and structural stability can be tuned by changing the interhelical linker while maintaining the properties of the discs with respect to membrane protein stabilization.

Understanding cytokinesis interaction by interaction.

In this issue of Structure, Hall et al.1 investigate the binding modes of anillin-like Mid1. During cytokinesis, Mid1 connects the contractile ring to the plasma membrane. Using computer simulations, the authors demonstrated how this connection is established via the L3 loop of the C2 domain.

A Comparison of the Efficacy of Four Repositioning Maneuvers in the Treatment of Posterior Benign Paroxysmal Positional Vertigo.

PURPOSE: The purpose of the present review was to report the effectiveness of Epley maneuver compared to other manual repositioning maneuvers (RM) for treatment of posterior benign paroxysmal positional vertigo (P-BPPV). A systematic search of PubMed, Embase, and the Cochrane Library was conducted up until June 30, 2023. RESULTS: Primary outcomes focused on complete resolution of vertiginous symptoms measured by either a Visual Analog Scale (VAS) or the Dix-Hallpike (DH) test. Secondary outcomes included conversion of a positive DH test to a negative DH test exclusively looking at positional nystagmus and assessment of side effects (cervical/back pain, posttreatment dizziness, and nausea). Both outcomes were assessed within a maximum of 4-week follow-up. Following systematic search and review, nine randomized controlled trials (RCTs; p = .413) were found. The studies reported on the effectiveness of the Epley maneuver compared to three other specific RM: Semont, Li, and Gans maneuvers. Results revealed a low to very low certainty of evidence. With the primary outcomes, Epley maneuver was superior to Gans maneuver 24-hr posttreatment but not after 1 week. No significant differences were found between the remaining maneuvers. CONCLUSIONS: In summary, evidence of low to very low certainty indicates that Epley maneuver is comparable with Semont, Gans, and Li maneuvers for vertiginous symptoms in patients with P-BPPV. Further high-quality studies are needed.

Breast reconstruction with mentor anatomical implants and the risk of implant rotation: A retrospective study of 1134 women.

BACKGROUND: Implant rotation is a known complication to breast reconstruction using anatomical implants. However, there is a lack of large studies investigating the risk of implant rotation and potential predisposing risk factors. METHOD: We reviewed the medical records of all patients who underwent breast reconstruction with Mentor anatomical implants from 2010 to 2021 at two Danish hospitals. We compared the risk of implant rotation between one- and two-stage breast reconstruction using univariate logistic regression. We analyzed the effect of biological mesh, immediate versus delayed reconstruction, and use of a higher final expander volume than the permanent implant volume on the risk of implant rotation. Finally, we analyzed the success rate of revision surgery for implant rotation. RESULTS: In total, 1134 patients were enrolled. Patients who underwent two-stage breast reconstruction (n = 720) had a significantly higher risk of implant rotation than those who underwent one-stage breast reconstruction (n = 426; 11% vs. 5%, p < 0.01). There was no significant association between implant rotation and the use of biological mesh, immediate breast reconstruction, or use of a higher final expander volume than the permanent implant volume. The success rate of revision surgery after implant rotation was 73% (62/85 rotations). CONCLUSIONS: Two-stage breast reconstruction significantly increased the risk of implant rotation compared to one-stage breast reconstruction. The overall risk of implant rotation was low and success rate of revision surgery was high. These findings suggest that anatomical implants are safe to use for breast reconstruction. However, surgeons and patients should be aware of the increased risk of implant rotation after two-stage reconstruction.

Silicone Leakage from Breast Implants Is Determined by Silicone Cohesiveness: A Histological Study of 493 Patients.

BACKGROUND: Silicone leakage from breast implants is a concern with potential implications for patient health. This study aimed to quantify and model silicone leakage from implants to the breast implant capsule and to investigate whether silicone cohesiveness affected the silicone leakage rate. METHODS: Silicone content in the breast implant capsule was quantified histologically by measuring the area of silicone deposits. This was used to model silicone leakage over time based on the time of implantation. The effect of cohesiveness on silicone leakage was investigated across all implant brands with declared cohesiveness and in a subanalysis comparing only Mentor cohesive I implants with cohesive II and III implants. RESULTS: The study included 493 patients with 872 breasts and a median time of implantation of 13.0 years (range 0.4 to 51 years). The modeling of silicone leakage from intact implants showed that leakage and the acceleration of the leakage rate were significantly higher in low-cohesive implants than in highly cohesive implants (p<0.05). This was confirmed when analyzing only Mentor implants (p<0.05) and in the case of implant rupture (p<0.01) where low-cohesive implants also leaked significantly more than highly cohesive implants. CONCLUSIONS: Our results suggest that highly cohesive implants are superior to low-cohesive implants in preventing silicone leakage. Due to the accelerating rate of silicone leakage especially found in low-cohesive implants, we propose that exchange of low-cohesive implants could be discussed with patients 10 to 15 years after implantation to minimize silicone leakage even in the absence of implant rupture.

Shape2SAS -- a web application to simulate small-angle scattering data and pair distance distributions from user-defined shapes.

Shape2SAS is a web application that allows researchers and students to build intuition and understanding of small-angle scattering. It is available at https://somo.chem.utk.edu/shape2sas. The user defines a model of arbitrary shape by combining geometrical subunits, and Shape2SAS then calculates and displays the scattering intensity, the pair distance distribution as well as a visualization of the user-defined shape. Simulated data with realistic noise are also generated. We demonstrate how Shape2SAS can calculate and display the different scattering patterns for various geometrical shapes, such as spheres and cylinders. We also demonstrate how the effect of structure factors can be visualized. Finally, we show how multi-contrast particles can readily be generated, and how the calculated scattering may be used to validate and visualize analytical models generated in analysis software for fitting small-angle scattering data.