Validation of the Sexual Discounting Task for Use in Adolescents.

The Sexual Discounting Task (SDT) was developed to evaluate the effects of delay on decision making as it relates to sexual risk-taking behaviors. Though previously validated with other populations, including urban emerging adults, the current study sought to validate the SDT with adolescents. A sample of adolescents (N = 155; 61% female) between ages 14 and 21 (Mage = 19.5 years) was recruited to complete the SDT (involving choices between immediate unprotected sex and delayed sex with a condom with hypothetical sexual partners) and the Delay Discounting Task (a delay discounting task for money outcomes). Additionally, they completed several self-report measures assessing demographics, sexual behavior, and sexual history. If the condom was readily available, respondents were more likely to use a condom for partners who were judged "most likely to have an STI" and for those that participants were "least likely to have sex with." Moreover, when a condom was not immediately available, greater self-reported sexual risk-taking was related to greater sexual discounting (i.e., greater effects of delay on decreasing condom use). Furthermore, sexual discounting was greater among partners deemed more desirable and those judged "least likely to have an STI." Differences in sexual discounting were significant after controlling for immediately available condom use. Findings from the current study suggest that the SDT is clinically meaningful for adolescents and is sensitive to factors that influence real-world decisions to use condoms. Future treatment and prevention should consider delay discounting as an important variable affecting sexual risk behavior.

Using classification trees to identify psychotherapy patients at risk for poor treatment adherence.

To determine the relative importance of a wide variety of personality and psychopathology variables in influencing patients' adherence to psychotherapy treatment.Two classification trees were trained to predict patients' (1) treatment utilization (i.e., their likelihood of missing a given appointment) and (2) termination status (i.e., their likelihood of dropping out of therapy prematurely). Each tree was then validated in an external dataset to examine performance accuracy.Patients' social detachment was most influential in predicting their treatment utilization, followed by affective instability and activity/energy levels. Patients' interpersonal warmth was most influential in predicting their termination status, followed by levels of disordered thought and resentment. The overall accuracy rating for the tree for termination status was 71.4%, while the tree for treatment utilization had a 38.7% accuracy rating.Classification trees are a practical tool for clinicians to determine patients at risk of premature termination. More research is needed to develop trees that predict treatment utilization with high accuracy across different types of patients and settings.

Relations Between Adolescent Sensation Seeking and Risky Sexual Behaviors Across Sex, Race, and Age: A Meta-Analysis.

Sensation seeking (SS)-the seeking of novel and intense sensations or experiences and the willingness to take risks for the sake of such experiences-has been shown to be related to various risky sexual behaviors (RSBs) in areas such as multiple sexual partners, condom use, and sexual initiation. The aims of the current meta-analysis were to examine (1) how SS relates to specific RSBs in adolescents and (2) how the overall relationship between SS and RSB differs across sex, race, and age. Overall, a total of 40 studies met the inclusion criteria for our meta-analysis examining the relationship between SS and RSB, contributing 102 effect sizes. RSB variables included unprotected sex; multiple sexual partners; hazardous sexual activity; sexual initiation; virginity status; and history of sexually transmitted disease (STD) diagnosis. Moderating effects of sex, race, and age were also examined. The overall mean effect size of the correlational relationship between adolescent SS and RSB was statistically significant, as were the mean effect sizes of the relationships between SS and RSB subgroups, except for history of STD diagnosis. Race and age did not significantly moderate the overall relationship between SS and RSB; however, results indicated that SS and RSB relations were stronger in females compared to males. Our findings suggest that adolescents with elevations in SS tendencies tend to engage in more RSBs compared to their peers with lower levels of SS, increasing their risk of unplanned pregnancy and STD acquisition.

A baseline comparison of three diagnostic groups using the Progress Monitoring Tool for Eating Disorders.

Utilisation of intensive inpatient treatment for eating disorders (EDs) has climbed in the last decade, illuminating a need for better consensus on what constitutes effective treatment and context-appropriate progress/outcome monitoring during residential stays. The novel Progress Monitoring Tool for Eating Disorders (PMED) measure is specifically designed for inpatient settings. Previous research supports the factorial validity and internal consistency of the PMED; however, additional work is needed to determine its appropriateness for complex patient populations. This study used measurement invariance (MI) testing to determine if the PMED administered at programme admission measures the same items in similar ways across patients with anorexia nervosa restricting- and binge-purge subtypes (AN-R; AN-BP) and bulimia nervosa (BN, N = 1121; Mage  = 24.33 years, SD = 10.20; 100% female). Progressively constrained models were used to determine the level of invariance upheld between the three groups. Results indicated that, while the PMED meets configural and metric MI, it does not display scalar invariance. Said otherwise, the PMED similarly assesses constructs and items across AN-R, AN-BP, and BN, however the same score overall may reflect different levels of psychopathology for patients in one diagnostic category versus another. Comparisons of severity between different EDs should be made with caution, however the PMED appears to be a sound tool for understanding the baseline functioning of patients with EDs in an inpatient setting.

Trajectories of interpersonal problems in residential eating disorder treatment: Exploring the influence of primary diagnosis.

Baseline interpersonal problems have been associated with treatment outcome in eating disorders (ED) and are important for understanding ED maintenance and aetiology. Despite this evidence, little is known about trajectories of change in interpersonal problems in the context of treatment, particularly in intensive ED treatment. This study examined the trajectory of total interpersonal problems in residential ED treatment, as well as two subdomains previously highlighted in ED research of being overly Cold (interpersonally distant) or overly Domineering (interpersonally controlling), as a function of different primary presenting ED diagnoses: anorexia nervosa restricting subtype (AN-R), binge-purge subtype (AN-BP), and bulimia nervosa or binge eating (BN/BED). Interpersonal problem data were collected at admission, discharge, and 6-month follow-up. Trajectories were analysed with multilevel models. Results showed small-to-medium statistically significant reductions in interpersonal problems across diagnostic groups from admission to discharge for total interpersonal scores, and gains appeared to be maintained at follow-up for both AN groups. Patients diagnosed with primary AN experienced steeper declines in total interpersonal problems from admission to follow-up compared with patients diagnosed with BN/BED, with AN-R experiencing the steepest trajectory. Planned contrasts indicated anyone with relevant binge eating behaviours had higher average levels of both Cold, as well as Domineering problems. Exploratory contrasts suggested that patients who had more Domineering problems also exhibited more binge symptoms and were typically slower to improve. Overall, results suggest interpersonal problems are generally malleable in residential ED treatment, yet change patterns differ by presenting ED symptoms and interpersonal problem subdomain.

Implementation Science and Practice-Oriented Research: Convergence and Complementarity.

Implementation science is the scientific study of methods to promote the uptake of research findings and other evidence-based practices in routine care, with the goal of improving the quality and effectiveness of health services (Bauer et al., 2015). In addition to this common goal, practice-oriented psychotherapy research (and researchers) and implementation science (and scientists) share a common focus on the people and the places where treatment happens. Thus, there exists strong potential for combining these two approaches. In this article, we provide a primer on implementation science for psychotherapy researchers and highlight important areas and examples of convergence and complementarity between implementation science and practice-oriented psychotherapy research. Specifically, we (a) define and describe the core features of implementation science; (b) discuss similarities and areas of complementarity between implementation science and practice-oriented psychotherapy research; (c) discuss a case example that exemplifies the integration of implementation science and practice-oriented research; and (d) propose directions for future research and collaborations that leverage both implementation science and practice-oriented research.

Positive Urgency, Drinking Preoccupation, and Alcohol Problems in College Students.

OBJECTIVE: Individuals high in positive urgency (i.e., impulsiveness stemming from high positive mood) may be more preoccupied with alcohol-related cognitions. Our aim was to examine how positive urgency, drinking preoccupation, and consumption patterns concurrently influence the endorsement of alcohol-related problems. METHOD: We sampled 756 students enrolled in a large, public U.S. university, who completed a cross-sectional survey online. Their mean age was 19.6 (SD = 1.72), 71.3% identified as female, and participants largely identified as Caucasian (65.5%) and Hispanic/Latinx (22.1%). Self-report measurements of trait positive urgency and drinking preoccupation and retrospective data of alcohol use and alcohol-related problems were collected. A series of linear regressions tested for a hypothesized indirect effect between variables. RESULTS: We discovered an indirect effect in the relationship between positive urgency and alcohol-related problems via drinking preoccupation. A significant conditional effect showed that this relationship was influenced by past 30-day alcohol consumption, with the effect gaining strength as consumption days increased. CONCLUSIONS: Students with high positive urgency may be more engrossed with alcohol-related drinking cognitions, leading to negative consequences as their alcohol consumption increases. This potential association can inform tailored intervention plans for college student alcohol control, such as successfully managing intense positive moods and alcohol-related cognitions and triggers.

Development and Validation of a Validity Scale for Use with the UPPS-P and Short UPPS-P Impulsive Behavior Scales.

Two of the most widely used self-report measures of impulsivity are the UPPS-P Impulsive Behavior Scale and its shortened version, the SUPPS-P, which currently are limited by their inability to detect careless and/or random responding. The present study develops and cross-validates an inconsistency scale for use with the UPPS-P and SUPPS-P in order to accurately screen for data quality and better detect invalid responding. A total of 443 participants were recruited from Amazon's MTurk online data collection service to serve as the derivation sample and 231 undergraduates were recruited to serve as the cross-validation sample. The inconsistency scale demonstrated good classification accuracy in differentiating between genuine and random protocols and moderated the relationships between the UPPS-P/SUPPS-P and a criterion measure of impulsivity, the Barratt Impulsiveness Scale-11 (BIS-11). Thus, the inconsistency scale shows promise as an indicator of variable response inconsistency for use with both the UPPS-P and SUPPS-P in community and undergraduate research samples.

Characterization of Type-I IFN subtype autoantibodies and activity in SLE serum and urine.

BACKGROUND/OBJECTIVE: Type-I interferons contribute to pathogenesis in systemic lupus erythematosus, including nephritis. Interferons consist of a family of 16 proteins yet are often characterized in patients without knowledge of the specific interferon subtypes involved. Different interferons may function in the kidneys, and other organs, relative to what is often measured in patient blood. Moreover, antibodies to interferons may potentially modulate systemic or organ-specific interferon activity. The aim of this study was to characterize global interferon activity levels and identify autoantibodies to the 12 interferon α subtypes in patient serum and urine. METHODS: Interferon activity levels in serum and urine were measured using an interferon bioassay. Anti-interferon and anti-cytokine autoantibodies were measured by ELISA. Serum and urine samples were also characterized for their ability to neutralize the biological activity of exogenously added interferons. RESULTS: Serum interferon activity was increased in 62% of systemic lupus erythematosus patient samples, relative to healthy donor controls, whereas binding interferon α autoantibodies to at least one interferon α subtype were found in 68% of the samples evaluated. High Systemic Lupus Erythematosus Disease Activity Index scores were significantly (p = 0.001) associated with patient samples containing interferon α autoantibodies to three or more interferon α subtypes in their serum. Interferon α autoantibodies that potently block interferon activity were rare (∼5% of samples), but collectively bound to all 12 interferon α subtypes. Urine interferon activity and interferon α autoantibody profiles did not correlate with their serum counterparts, suggesting immune responses in systemic lupus erythematosus kidneys can be distinct from those measured in serum. Analysis of autoantibodies to 15 additional cytokines in serum identified higher frequencies of granulocyte-macrophage colony-stimulating factor and interleukin 17A autoantibodies, suggesting these signaling pathways may potentially contribute, with interferons, to systemic lupus erythematosus pathogenesis. CONCLUSIONS: The measurement of autoantibodies to multiple interferon subtypes in serum and urine may provide an alternative method for following interferon-mediated systemic lupus erythematosus disease activity. The results suggest autoantibodies might be used for patient monitoring and/or identifying additional cytokine signaling pathways that are functioning in different systemic lupus erythematosus patients.

Sensation seeking, sexual orientation, and drug abuse symptoms in a community sample of emerging adults.

Increased use of drugs is associated with a number of factors including high sensation seeking and sexual minority status (through group-specific minority stress). We sought to examine how personality traits like sensation seeking may influence drug abuse among sexual minority individuals. Participants were 217 emerging adults (Mage = 20.23, SD = 0.85) recruited from Amazon Mechanical Turk (MTurk). Of these participants, 67.7% identified as heterosexual, 9.7% as gay or lesbian, 21.2% as bisexual, and 1.4% indicated other sexual orientations. Sensation seeking and drug abuse were self-reported using the Brief Sensation Seeking Scale and the Drug Abuse Screening Test, respectively. A preliminary multiple analysis of variance indicated no significant mean differences for these variables as a function of sex or sexual orientation. Next, sexual minority status, Brief Sensation Seeking Scale scores, sex and their interactions were entered into a linear regression predicting Drug Abuse Screening Test scores. Results revealed a significant moderation, such that the positive relationship between Brief Sensation Seeking Scale total scores and Drug Abuse Screening Test total scores was stronger for sexual minorities (ß = 0.14, P = 0.00) compared to heterosexuals (ß = 0.04, P = 0.04), controlling for sex. These results demonstrate, while sensation seeking and sexual minority status may selectively indicate risk for drug use, sexual minorities high in sensation seeking may be at especially high risk for problems related to drug abuse. More research examining the addiction etiology of sexual minority individuals would inform targeted interventions for this population.

Human interferon-ϵ and interferon-κ exhibit low potency and low affinity for cell-surface IFNAR and the poxvirus antagonist B18R.

IFNϵ and IFNκ are interferons that induce microbial immunity at mucosal surfaces and in the skin. They are members of the type-I interferon (IFN) family, which consists of 16 different IFNs, that all signal through the common IFNAR1/IFNAR2 receptor complex. Although IFNϵ and IFNκ have unique expression and functional properties, their biophysical properties have not been extensively studied. In this report, we describe the expression, purification, and characterization of recombinant human IFNϵ and IFNκ. In cellular assays, IFNϵ and IFNκ exhibit ∼1000-fold lower potency than IFNα2 and IFNω. The reduced potency of IFNϵ and IFNκ are consistent with their weak affinity for the IFNAR2 receptor chain. Despite reduced IFNAR2-binding affinities, IFNϵ and IFNκ exhibit affinities for the IFNAR1 chain that are similar to other IFN subtypes. As observed for cellular IFNAR2 receptor, the poxvirus antagonist, B18R, also exhibits reduced affinity for IFNϵ and IFNκ, relative to the other IFNs. Taken together, our data suggest IFNϵ and IFNκ are specialized IFNs that have evolved to weakly bind to the IFNAR2 chain, which allows innate protection of the mucosa and skin and limits neutralization of IFNϵ and IFNκ biological activities by viral IFN antagonists.

Cytokine Activation by Antibody Fragments Targeted to Cytokine-Receptor Signaling Complexes.

Exogenous cytokine therapy can induce systemic toxicity, which might be prevented by activating endogenously produced cytokines in local cell niches. Here we developed antibody-based activators of cytokine signaling (AcCS), which recognize cytokines only when they are bound to their cell surface receptors. AcCS were developed for type I interferons (IFNs), which induce cellular activities by binding to cell surface receptors IFNAR1 and IFNAR2. As a potential alternative to exogenous IFN therapy, AcCS were shown to potentiate the biological activities of natural IFNs by ∼100-fold. Biochemical and structural characterization demonstrates that the AcCS stabilize the IFN-IFNAR2 binary complex by recognizing an IFN-induced conformational change in IFNAR2. Using IFN mutants that disrupt IFNAR1 binding, AcCS were able to enhance IFN antiviral potency without activating antiproliferative responses. This suggests AcCS can be used to manipulate cytokine signaling for basic science and possibly for therapeutic applications.

The cohesin acetyltransferase Eco1 coordinates rDNA replication and transcription.

Eco1 is the acetyltransferase that establishes sister-chromatid cohesion during DNA replication. A budding yeast strain with an eco1 mutation that genocopies Roberts syndrome has reduced ribosomal DNA (rDNA) transcription and a transcriptional signature of starvation. We show that deleting FOB1--a gene that encodes a replication fork-blocking protein specific for the rDNA region--rescues rRNA production and partially rescues transcription genome-wide. Further studies show that deletion of FOB1 corrects the genome-wide replication defects, nucleolar structure, and rDNA segregation that occur in the eco1 mutant. Our study highlights that the presence of cohesin at the rDNA locus has a central role in controlling global DNA replication and gene expression.

Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines.

Interleukin 20 (IL-20) is a pleotropic IL-10 family cytokine that protects epithelial surfaces from pathogens. However, dysregulated IL-20 signaling is implicated in several human pathologies including psoriasis, rheumatoid arthritis, atherosclerosis, and osteoporosis. IL-20, and related cytokines IL-19 and IL-24, designated IL-20 subfamily cytokines (IL-20SFCs), induce cellular responses through an IL-20R1/IL-20R2 (type I) receptor heterodimer, whereas IL-20 and IL-24 also signal through the IL-22R1/IL-20R2 (type II) receptor complex. The crystal structure of the IL-20/IL-20R1/IL-20R2 complex reveals how type I and II complexes discriminate cognate from noncognate ligands. The structure also defines how the receptor-cytokine interfaces are affinity tuned to allow distinct signaling through a receptor complex shared by three different ligands. Our results provide unique insights into the complexity of IL-20SFC signaling that may be critical in the design of mechanistic-based inhibitors of IL-20SFC-mediated inflammatory disease.

Cohesin proteins promote ribosomal RNA production and protein translation in yeast and human cells.

Cohesin is a protein complex known for its essential role in chromosome segregation. However, cohesin and associated factors have additional functions in transcription, DNA damage repair, and chromosome condensation. The human cohesinopathy diseases are thought to stem not from defects in chromosome segregation but from gene expression. The role of cohesin in gene expression is not well understood. We used budding yeast strains bearing mutations analogous to the human cohesinopathy disease alleles under control of their native promoter to study gene expression. These mutations do not significantly affect chromosome segregation. Transcriptional profiling reveals that many targets of the transcriptional activator Gcn4 are induced in the eco1-W216G mutant background. The upregulation of Gcn4 was observed in many cohesin mutants, and this observation suggested protein translation was reduced. We demonstrate that the cohesinopathy mutations eco1-W216G and smc1-Q843Δ are associated with defects in ribosome biogenesis and a reduction in the actively translating fraction of ribosomes, eiF2α-phosphorylation, and (35)S-methionine incorporation, all of which indicate a deficit in protein translation. Metabolic labeling shows that the eco1-W216G and smc1-Q843Δ mutants produce less ribosomal RNA, which is expected to constrain ribosome biogenesis. Further analysis shows that the production of rRNA from an individual repeat is reduced while copy number remains unchanged. Similar defects in rRNA production and protein translation are observed in a human Roberts syndrome cell line. In addition, cohesion is defective specifically at the rDNA locus in the eco1-W216G mutant, as has been previously reported for Roberts syndrome. Collectively, our data suggest that cohesin proteins normally facilitate production of ribosomal RNA and protein translation, and this is one way they can influence gene expression. Reduced translational capacity could contribute to the human cohesinopathies.

tmVar: a text mining approach for extracting sequence variants in biomedical literature.

MOTIVATION: Text-mining mutation information from the literature becomes a critical part of the bioinformatics approach for the analysis and interpretation of sequence variations in complex diseases in the post-genomic era. It has also been used for assisting the creation of disease-related mutation databases. Most of existing approaches are rule-based and focus on limited types of sequence variations, such as protein point mutations. Thus, extending their extraction scope requires significant manual efforts in examining new instances and developing corresponding rules. As such, new automatic approaches are greatly needed for extracting different kinds of mutations with high accuracy. RESULTS: Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society. By doing so, we cover several important types of mutations that were not considered in past studies. Using a novel CRF label model and feature set, our method achieves higher performance than a state-of-the-art method on both our corpus (91.4 versus 78.1% in F-measure) and their own gold standard (93.9 versus 89.4% in F-measure). These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature. AVAILABILITY: tmVar software and its corpus of 500 manually curated abstracts are available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/pub/tmVar

Epstein-Barr virus IL-10 engages IL-10R1 by a two-step mechanism leading to altered signaling properties.

Human interleukin-10 (hIL-10) is a pleiotropic cytokine that is able to suppress or activate cellular immune responses to protect the host from invading pathogens. Epstein-Barr virus (EBV) encodes a viral IL-10 (ebvIL-10) in its genome that has retained the immunosuppressive activities of hIL-10 but lost the ability to induce immunostimulatory activities on some cells. These functional differences are at least partially due to the ∼1000-fold difference in hIL-10 and ebvIL-10 binding affinity for the IL-10R1·IL-10R2 cell surface receptors. Despite weaker binding to IL-10R1, ebvIL-10 is more active than hIL-10 in inducing B-cell proliferation. To explore this counterintuitive observation further, a series of monomeric and dimeric ebvIL-10·hIL-10 chimeric proteins were produced and characterized for receptor binding and cellular proliferation on TF-1/hIL-10R1 cells that express high levels of the IL-10R1 chain. On this cell line, monomeric chimeras elicited cell proliferation in accordance with how tightly they bound to the IL-10R1 chain. In contrast, dimeric chimeras exhibiting the highest affinity for IL-10R1 exhibited reduced proliferative activity. These distinct activity profiles are correlated with kinetic analyses that reveal that the ebvIL-10 dimer is impaired in its ability to form a 1:2 ebvIL-10·IL-10R1 complex. As a result, the ebvIL-10 dimer functions like a monomer at low IL-10R1 levels, which prevents efficient signaling. At high IL-10R1 levels, the ebvIL-10 dimer is able to induce signaling responses greater than hIL-10. Thus, the ebvIL-10 dimer scaffold is essential to prevent activation of cells with low IL-10R1 levels but to maintain or enhance activity on cells with high IL-10R1 levels.

Collaboration between the University of Michigan Taubman Health Sciences library and the University of Michigan Medical School Office of Research.

Librarians have traditionally facilitated research development resulting in grants through performing biomedical literature searches for researchers. The librarians at the Taubman Health Sciences Library of the University of Michigan have taken additional steps forward by instituting a proactive approach to assisting investigators. To accomplish this, the librarians have taken part in a collaborative effort with the University of Michigan Medical School Office of Research. Through this partnership, both units have created and adopted various techniques intended to facilitate the submission of grants, thus allowing researchers more time to conduct their primary activities.

Outcome trajectories in a county mental health clinic before and after telemental health: a retrospective COVID-19 cohort study.

Background/objectives: Telemental health (TMH) care has received increased attention, most recently due to the COVID-19 pandemic. Many treatment settings and clinicians were forced to rapidly shift to TMH modalities, including clinicians with limited exposure to and possibly negative attitudes toward alternative treatment delivery formats. With the shift to new modalities, effectiveness research is necessary to understand if patients are receiving the same quality of care as before the pandemic and their receipt of mostly in person services. This study compared the naturalistic treatment outcome trajectories for a cohort of patients who received in-person services prior to the pandemic and a distinct cohort of patients who received TMH services after the onset of the pandemic, in a community mental health setting with limited exposure to TMH prior to the COVID-19 pandemic. Materials and methods: We adopted a retrospective cohort design to examine treatment modality as a between-group moderator of symptom change trajectory on the self-report Patient Health Questionnaire (PHQ-9) in a sample of N = 958 patients in the Northeast United States. Treatment durations differed in the naturalistic treatment setting and we examined patient-reported outcomes up to a maximum of one year. Results: Statistically significant average decreases in symptom severity were found over the course of up to one year of treatment, yet the average outcome trajectory was not significantly different between two modality cohorts (in person delivery before the pandemic versus TMH delivery after pandemic onset). Conclusion: These findings suggest that even in a setting with limited exposure to or training in TMH, the average outcome trajectory for patients who received TMH was statistically similar to the outcome trajectory for patients in an earlier cohort who received in-person services prior to the pandemic onset. Overall, the results appear to support continued use of TMH services in community treatment settings.

Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern.

Severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) causes coronavirus disease 2019 (COVID19) that is responsible for short and long-term disease, as well as death, in susceptible hosts. The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) protein binds to cell surface angiotensin converting enzyme type-II (ACE2) to initiate viral attachment and ultimately viral pathogenesis. The SARS-CoV-2 S RBD is a major target of neutralizing antibodies (NAbs) that block RBD - ACE2 interactions. In this report, NAb-RBD binding epitopes in the protein databank were classified as C1, C1D, C2, C3, or C4, using a RBD binding profile (BP), based on NAb-specific RBD buried surface area and used to predict the binding epitopes of a series of uncharacterized NAbs. Naturally occurring SARS-CoV-2 RBD sequence variation was also quantified to predict NAb binding sensitivities to the RBD-variants. NAb and ACE2 binding studies confirmed the NAb classifications and determined whether the RBD variants enhanced ACE2 binding to promote viral infectivity, and/or disrupted NAb binding to evade the host immune response. Of 9 single RBD mutants evaluated, K417T, E484K, and N501Y disrupted binding of 65% of the NAbs evaluated, consistent with the assignment of the SARS-CoV-2 P.1 Japan/Brazil strain as a variant of concern (VoC). RBD variants E484K and N501Y exhibited ACE2 binding equivalent to a Wuhan-1 reference SARS-CoV-2 RBD. While slightly less disruptive to NAb binding, L452R enhanced ACE2 binding affinity. Thus, the L452R mutant, associated with the SARS-CoV-2 California VoC (B.1.427/B.1.429-California), has evolved to enhance ACE2 binding, while simultaneously disrupting C1 and C2 NAb classes. The analysis also identified a non-overlapping antibody pair (1213H7 and 1215D1) that bound to all SARS-CoV-2 RBD variants evaluated, representing an excellent therapeutic option for treatment of SARS-CoV-2 WT and VoC strains.