Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike.

Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded antibodies from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found seven major antibody competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of antibody-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. Although emerging SARS-CoV-2 variants of concern escaped binding by many members of the groups associated with the most potent neutralizing activity, some antibodies in each of those groups retained affinity-suggesting that otherwise redundant components of a primary immune response are important for durable protection from evolving pathogens. Our results furnish a global atlas of S-specific memory B cell repertoires and illustrate properties driving viral escape and conferring robustness against emerging variants.

Altered coordination in a blue copper protein upon association with redox partner revealed by carbon-deuterium vibrational probes.

Proteins tune the reactivity of metal sites; less understood is the impact of association with a redox partner. We demonstrate the utility of carbon-deuterium labels for selective analysis of delicate metal sites. Introduced into plastocyanin, they reveal substantial strengthening of the key Cu-Cys89 bond upon association with cytochrome f.

Ligand-Controlled Regioinduction in a PHOX-Ni Aryne Complex.

Phosphinooxazoline (PHOX) ligands have been used to control the regio- and enantioselectivity in a wide variety of metal-catalyzed reactions. Despite their widespread use, PHOX ligands have never been studied in metal-aryne complexes. Herein we report the first example of a PHOX-Ni aryne complex. As demonstrated in other systems, the differentiated P versus N donors and different steric environments of the unsymmetric ligand are able to induce regiocontrol. A 81:19 mixture of o-methoxy substituted aryne complexes is observed. Single-crystal X-ray crystallographic analysis, UV/vis spectroscopy, and cyclic voltammetry are used to gain further insight into the molecular and electronic structure of these complexes. Lastly, a methylation/deuteration sequence shows retention of the PHOX ligand-induced regiocontrol in the difunctionalized products and that the regiospecificity of these difunctionalizations is due to the trans influence of the P donor.

Carbon nanofibers/liquid metal composites for high temperature laser ultrasound.

As the demand for clean energy becomes greater worldwide, there will also be an increasing demand for next generation nuclear power plants that incorporate advanced sensors and monitoring equipment. A major challenge posed by nuclear power plants is that, during normal operation, the reactor compartment is subjected to high operating temperatures and radiation flux. Diagnostic sensors monitoring such structures are also subject to temperatures reaching hundreds of degrees Celsius, which puts them at risk for heat degradation. In this work, the ability of carbon nanofibers to work in conjunction with a liquid metal as a photoacoustic transmitter was demonstrated at high temperatures. Fields metal, a Bi-In-Sn eutectic, and gallium are compared as acoustic mediums. Fields metal was shown experimentally to have superior performance over gallium and other reference cases. Under stimulation from a low fluence 6 ns pulse laser at 6 mJ/cm2 with 532 nm green light, the Fields metal transducer transmitted a 200 kHz longitudinal wave with amplitude >5.5 times that generated by a gallium transducer at 300 °C. Each high temperature test was conducted from a hot to cold progression, beginning as high as 300 °C, and then cooling down to 100 °C. Each test shows increasing signal amplitude of the liquid metal transducers as temperature decreases. Carbon nanofibers show a strong improvement over previously used candle-soot nanoparticles in both their ability to produce strong acoustic signals and absorb higher laser fluences up to 12 mJ/cm2.

Noninvasive liquid level sensing with laser generated ultrasonic waves.

This article proposes a noninvasive liquid level sensing technique using laser-generated ultrasound waves for nuclear power plant applications. Liquid level sensors play an important role of managing the coolant system safely and stably in the plant structure. Current sensing techniques are mostly intrusive, performing inside the fluidic structure, which is disadvantageous in terms of the regular maintenance of the plant system. Furthermore, typical intrusive sensors do not perform stably under varying environmental conditions such as temperature and radiation. In this study, sensing units are attached to the outer surface of a liquid vessel to capture guided ultrasound waves in a nonintrusive manner. The signal intensity of the guided wave dissipates when the signal interacts with the internal liquid media. The sensing mechanism is mathematically expressed as an index value to correlate the liquid level with the sensor signal. For the acoustic wave generation, laser-generated ultrasound was adopted instead of using typical contact type transducers. Following the simulation validation of the proposed concept, the performance of the developed sensor was confirmed through experimental results under elevated liquid temperature conditions. The nonlinear multivariable regression exhibited the best-fit to the datasets measured under the variable liquid level and temperature conditions.

Likelihood of Craniofacial Injury and Hospitalization with Alcohol Use While Skateboarding and Scootering.

Study Design: We designed a cross-sectional epidemiologic study to evaluate the influence of substance use on craniofacial injuries in a population of skateboard and scooter users. Objective: The primary outcome of our study was craniofacial injury. The secondary outcome was hospitalization. Methods: We report a cross-sectional study of patients reported to the National Electronic Injury Surveillance System (NEISS) from January 1, 2019, to December 31, 2020, in the United States. Patients were included in our study if they were evaluated in the emergency department (ED) for a skateboard- or scooter-related injury. Results: There were over 5396 total patients who presented to a NEISS-participating ED after skateboard- or scooter- related trauma during the study period. There were 1136 patients with a craniofacial injury (primary endpoint), and patients under the influence of alcohol or drugs had greater odds of experiencing a craniofacial injury than those not under the influence (odds ratio [OR]: 4.16, 95% confidence interval [CI]: 3.24-5.32, P < .0001). Four hundred-thirty patients were hospitalized (secondary endpoint), and patients under the influence had greater odds of being hospitalized than those not under the influence (OR: 2.83, 95% CI: 2.04-3.91, P < .0001). Conclusions: Alcohol and drug use while skateboarding or scootering drastically increases the likelihood of craniofacial injury and subsequent hospitalization and should be avoided whenever possible. The importance of wearing a helmet while operating these devices cannot be overstated.

The structure of plastocyanin tunes the midpoint potential by restricting axial ligation of the reduced copper ion.

Blue copper proteins are models for illustrating how proteins tune metal properties. Nevertheless, the mechanisms by which the protein controls the metal site remain to be fully elucidated. A hindrance is that the closed shell Cu(I) site is inaccessible to most spectroscopic analyses. Carbon deuterium (C-D) bonds used as vibrational probes afford nonperturbative, selective characterization of the key cysteine and methionine copper ligands in both redox states. The structural integrity of Nostoc plastocyanin was perturbed by disrupting potential hydrogen bonds between loops of the cupredoxin fold via mutagenesis (S9A, N33A, N34A), variably raising the midpoint potential. The C-D vibrations show little change to suggest substantial alteration to the Cu(II) coordination in the oxidized state or in the Cu(I) interaction with the cysteine ligand. They rather indicate, along with visible and NMR spectroscopy, that the methionine ligand distinctly interacts more strongly with the Cu(I) ion, in line with the increases in midpoint potential. Here we show that the protein structure determines the redox properties by restricting the interaction between the methionine ligand and Cu(I) in the reduced state.

Analysis and comparison of SARS-CoV-2 variant antibodies and neutralizing activity for 6 months after a booster mRNA vaccine in a healthcare worker population.

Introduction: In the context of recurrent surges of SARS-CoV-2 infections, a detailed characterization of antibody persistence over a 6-month period following vaccine booster dose is necessary to crafting effective public health policies on repeat vaccination. Methods: To characterize the SARS-CoV-2 antibody profile of a healthcare worker population over a 6-month period following mRNA vaccination and booster dose. 323 healthcare workers at an academic medical center in Orange County, California who had completed primary vaccination and booster dose against SARS-CoV-2 were recruited for the study. A total of 690 blood specimens over a 6-month period were collected via finger-stick blood and analyzed for the presence of antibodies against 9 SARS-CoV-2 antigens using a coronavirus antigen microarray. Results: The primary outcome of this study was the average SARS-CoV-2 antibody level as measured using a novel coronavirus antigen microarray. Additional outcomes measured include levels of antibodies specific to SARS-CoV-2 variants including Delta, Omicron BA.1, and BA.2. We also measured SARS-CoV-2 neutralization capacity for a subset of the population to confirm correlation with antibody levels. Although antibodies against SARS-CoV-2 wane throughout the 6-month period following a booster dose, antibody levels remain higher than pre-boost levels. However, a booster dose of vaccine based on the original Wuhan strain generates approximately 3-fold lower antibody reactivity against Omicron variants BA.1 and BA.2 as compared to the vaccine strain. Despite waning antibody levels, neutralization activity against the vaccine strain is maintained throughout the 6-month period. Discussion: In the context of recurrent surges of SARS-CoV-2 infections, our data indicate that breakthrough infections are likely driven by novel variants with different antibody specificity and not by time since last dose of vaccination, indicating that development of vaccinations specific to these novel variants is necessary to prevent future surges of SARS-CoV-2 infections.

Estimated Atherosclerotic Cardiovascular Disease Risk: Disparities and Severe COVID-19 Outcomes (from the National COVID Cohort Collaborative).

Although cardiovascular disease risk factors relate to COVID-19, the association of estimated atherosclerotic cardiovascular disease (ASCVD) risk with severe COVID-19 is not established. We examined the relation of the pooled-cohort ASCVD risk score to severe COVID-19 among 28,646 subjects from the National COVID Cohort Collaborative database who had positive SARS-CoV-2 test results from April 1, 2020 to April 1, 2021. In addition, 10-year ASCVD risk scores were calculated, and subjects were stratified into low-risk (<5%), borderline-risk (5% to <7.5%), intermediate-risk (7.5% to <20%), and high-risk (>=20%) groups. Severe COVID-19 outcomes (including death, remdesivir treatment, COVID-19 pneumonia, acute respiratory distress syndrome, and mechanical ventilation) occurring during follow-up were examined individually and as a composite in relation to ASCVD risk group across race and gender. Multiple logistic regression, adjusted for age, gender, and race, examined the relation of ASCVD risk group to the odds of severe COVID-19 outcomes. Our subjects had a mean age of 59.4 years; 14% were black and 57% were female. ASCVD risk group was directly related to severe COVID-19 prevalence. The adjusted odds ratio of the severe composite COVID-19 outcome by risk group (vs the low-risk group) was 1.8 (95% confidence interval 1.5 to 2.2) for the borderline-risk, 2.7 (2.3 to 3.2) for the intermediate-risk, and 4.6 (3.7 to 5.6) for the high-risk group. Black men and black women in the high-risk group showed higher severe COVID-19 prevalence compared with nonblack men and nonblack women. Prevalence of severe COVID-19 outcomes was similar in intermediate-risk black men and high-risk nonblack men (approximately 12%). In conclusion, although further research is needed, the 10-year ASCVD risk score in adults ages 40 to 79 years may be used to identify those who are at highest risk for COVID-19 complications and for whom more intensive treatment may be warranted.

Analysis and comparison of SARS-CoV-2 variant antibodies and neutralizing activity for 6 months after a booster mRNA vaccine in a healthcare worker population.

In the context of recurrent surges of SARS-CoV-2 infections, a detailed characterization of antibody persistence over a 6-month period following vaccine booster dose is necessary to crafting effective public health policies on repeat vaccination. To characterize the SARS-CoV-2 antibody profile of a healthcare worker population over a 6-month period following mRNA vaccination and booster dose. 323 healthcare workers at an academic medical center in Orange County, California who had completed primary vaccination and booster dose against SARS-CoV-2 were recruited for the study. A total of 690 blood specimens over a 6-month period were collected via finger-stick blood and analyzed for the presence of antibodies against 9 SARS-CoV-2 antigens using a coronavirus antigen microarray. The primary outcome of this study was the average SARS-CoV-2 antibody level as measured using a novel coronavirus antigen microarray. Additional outcomes measured include levels of antibodies specific to SARS-CoV-2 variants including Delta, Omicron BA.1, and BA.2. We also measured SARS-CoV-2 neutralization capacity for a subset of the population to confirm correlation with antibody levels. Although antibodies against SARS-CoV-2 wane throughout the 6-month period following a booster dose, antibody levels remain higher than pre-boost levels. However, a booster dose of vaccine generates approximately 3-fold lower antibody reactivity against Omicron variants BA.1 and BA.2 as compared to the original Wuhan strain. Despite waning antibody levels, neutralization activity against the original Wuhan strain is maintained throughout the 6-month period. In the context of recurrent surges of SARS-CoV-2 infections despite vaccination with booster doses, our data indicate that breakthrough infections are likely driven by novel variants with different antibody specificity and not by time since last dose of vaccination, indicating that development of vaccinations specific to these novel variants is necessary to prevent future surges of SARS-CoV-2 infections.

The Contribution of the Lower Third of the Face to Perceived Age: Do Masks Make You Appear Younger?

BACKGROUND: There is evidence that changes to the midface and lower third of the face in isolation contribute significantly to one's perception of the overall facial age. Since the spread of the coronavirus disease 2019 (COVID-19), mask wearing has become commonplace. To date, there have been no studies that explore how covering the lower third of the face impacts the perception of age. OBJECTIVES: The authors hypothesized that covering the lower third of the face with a mask will make a person appear younger. METHODS: One hundred consecutive plastic surgery patients were photographed in a standardized fashion, both masked and unmasked. A questionnaire for factors known to contribute to facial aging was administered. These photographs were randomized to 6 judges who estimated the patients' age and also quantified facial rhytids with the validated Lemperle wrinkle assessment score of 6. Data were analyzed using PROC MIXED analysis. RESULTS: Masked patients on average appeared 6.17% younger (mean difference = 3.16 years, P < 0.0001). Wrinkle assessment scores were 9.81% lower in the masked group (mean difference = 0.21, P = 0.0003). All subgroups appeared younger in a mask except for patients aged 18 to 40 years chronological age (P = 0.0617) and patients BMI > 35 (P = 0.5084). CONCLUSIONS: The mask group appeared younger and had lower overall and visible wrinkle assessment scores when compared with the unmasked group. This has implications for our understanding of the contributions of the lower third of the face to overall perceived facial age.

Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike.

Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.

Exogenous insulin enhances humoural immune responses in short-day, but not long-day, Siberian hamsters (Phodopus sungorus).

Many animals experience marked seasonal fluctuations in environmental conditions. In response, animals display adaptive alterations in physiology and behaviour, including seasonal changes in immune function. During winter, animals must reallocate finite energy stores from relatively costly, less exigent systems (e.g. reproduction and immunity) to systems critical for immediate survival (e.g. thermoregulation). Seasonal changes in immunity are probably mediated by neuroendocrine factors signalling current energetic state. One potential hormonal candidate is insulin, a metabolic hormone released in response to elevated blood glucose levels. The aim of the present study was to explore the potential role of insulin in signalling energy status to the immune system in a seasonally breeding animal, the Siberian hamster (Phodopus sungorus). Specifically, exogenous insulin was administered to male hamsters housed in either long 'summer-like' or short 'winter-like' days. Animals were then challenged with an innocuous antigen and immune responses were measured. Insulin treatment significantly enhanced humoural immune responses in short, but not long days. In addition, insulin treatment increased food intake and decreased blood glucose levels across photoperiodic treatments. Collectively, these data support the hypothesis that insulin acts as an endocrine signal integrating seasonal energetic changes and immune responses in seasonally breeding rodents.

Does lacking information about your affordances impact your perception of others' affordances? A test of the embodied simulation hypothesis.

It has been argued that observers perceive actors' affordances via embodied simulation, that is, first perceiving their own affordance, which serves as a model for the actor's affordance, and then adjusting that model to account for differences between themselves and the actor. If so, then preventing observers from picking up information about their own affordances should cause several effects. Specifically, observers should make more errors about the actor's affordance compared to when the observer is free to pick up information about their own affordance. In addition, judgments about the actor's affordance should align better with the observer's affordance than with the actor's affordance, and increase in error as differences between the observer's and actor's affordances increase. The present study tested those predictions. To do so, observers (participants) made judgments about the farthest distance that an actor (a confederate) could reach. The observer's arms were either free to move or were immobilized by having the participant hold them behind their back. The present results did not support the predictions. The present research introduces a novel means for evaluating the Embodied Simulation Hypothesis, provides initial tests of related predictions, and corroborates prior research. In addition, it motivates important questions about embodied simulation and affordance perception.

Resistance and Resilience of Sulfidogenic Communities in the Face of the Specific Inhibitor Perchlorate.

Hydrogen sulfide is a toxic and corrosive gas, produced by the activity of sulfate-reducing microorganisms (SRM). Owing to the environmental, economic and human-health consequences of sulfide, there is interest in developing specific inhibitors of SRM. Recent studies have identified perchlorate as a promising emerging inhibitor. The aim of this work is to quantitatively dissect the inhibitory dynamics of perchlorate. Sulfidogenic mixed continuous-flow systems were treated with perchlorate. SRM number, sulfide production and community structure were monitored pre-, during and post-treatment. The data generated was compared to a simple mathematical model, where SRM growth slows as a result of inhibition. The experimental data supports the interpretation that perchlorate largely acts to suppress SRM growth rates, rendering planktonic SRM increasingly susceptible to wash-out. Surface-attachment was identified as an important parameter preventing SRM wash-out and thus governing inhibitory dynamics. Our study confirmed the lesser depletion of surface-attached SRM as compared to planktonic SRM during perchlorate treatment. Indirect effects of perchlorate (bio-competitive exclusion of SRM by dissimilatory perchlorate-reducing bacteria, DPRB) were also assayed by amending reactors with DPRB. Indeed, low concentrations of perchlorate coupled with DRPB amendment can drive sulfide concentrations to zero. Further, inhibition in a complex community was compared to that in a pure culture, highlighting similarities and differences between the two scenarios. Finally, we quantified susceptibility to perchlorate across SRM in various culture conditions, showing that prediction of complex behavior in continuous systems from batch results is possible. This study thus provides an overview of the sensitivity of sulfidogenic communities to perchlorate, as well as mechanisms underlying these patterns.

Enantioselective Synthesis of (-)-Vallesine: Late-Stage C17-Oxidation via Complex Indole Boronation.

The first enantioselective total synthesis of (-)-vallesine via a strategy that features a late-stage regioselective C17-oxidation followed by a highly stereoselective transannular cyclization is reported. The versatility of this approach is highlighted by the divergent synthesis of the archetypal alkaloid of this family, (+)-aspidospermidine, and an A-ring-oxygenated derivative, (+)-deacetylaspidospermine, the precursor to (-)-vallesine, from a common intermediate.

Leptin Manipulation Reduces Appetite and Causes a Switch in Mating Preference in the Plains Spadefoot Toad (Spea bombifrons).

Condition- or context-dependent mate choice occurs when females modify their mate preferences depending on their internal or external environment. While the ecological and evolutionary factors that favor the evolution of such plasticity are emerging, relatively little is known of the mechanisms underlying such choice. Here we evaluated whether leptin, a protein hormone involved in the regulation of appetite, might affect the expression of condition-dependent mate choice decisions. To do so, we administered leptin to spadefoot toads, Spea bombifrons, which exhibit condition-dependent mate choice for males of their own species versus congeneric males of S. multiplicata. In particular, poor-condition S. bombifrons are more likely than are good-condition S. bombifrons to prefer S. multiplicata males, but only in environments where hybridization between the two species is beneficial. We found that our leptin treatment reduced appetite in S. bombifrons adults, as was expected from leptin's known effects on appetite. However, although we predicted that leptin would reduce female preferences for heterospecific males, we found the opposite. In particular, our leptin treatment generated a consistent, repeatable preference for heterospecifics in an environment where females generally prefer conspecifics regardless of condition. These results indicate that leptin has the potential to affect female mate choice, but that it might do so in non-intuitive ways.

Modulation of Epstein-Barr virus glycoprotein B (gB) fusion activity by the gB cytoplasmic tail domain.

UNLABELLED: Epstein-Barr virus (EBV), along with other members of the herpesvirus family, requires a set of viral glycoproteins to mediate host cell attachment and entry. Viral glycoprotein B (gB), a highly conserved glycoprotein within the herpesvirus family, is thought to be the viral fusogen based on structural comparison of EBV gB and herpes simplex virus (HSV) gB with the postfusion crystal structure of vesicular stomatitis virus fusion protein glycoprotein G (VSV-G). In addition, mutational studies indicate that gB plays an important role in fusion function. In the current study, we constructed a comprehensive library of mutants with truncations of the C-terminal cytoplasmic tail domain (CTD) of EBV gB. Our studies indicate that the gB CTD is important in the cellular localization, expression, and fusion function of EBV gB. However, in line with observations from other studies, we conclude that the degree of cell surface expression of gB is not directly proportional to observed fusion phenotypes. Rather, we conclude that other biochemical or biophysical properties of EBV gB must be altered to explain the different fusion phenotypes observed. IMPORTANCE: Epstein-Barr virus (EBV), like all enveloped viruses, fuses the virion envelope to a cellular membrane to allow release of the capsid, resulting in virus infection. To further characterize the function of EBV glycoprotein B (gB) in fusion, a comprehensive library of mutants with truncations in the gB C-terminal cytoplasmic tail domain (CTD) were made. These studies indicate that the CTD of gB is important for the cellular expression and localization of gB, as well as for the function of gB in fusion. These studies will lead to a better understanding of the mechanism of EBV-induced membrane fusion and herpesvirus-induced membrane fusion in general, which will ultimately lead to focused therapies guided at preventing viral entry into host cells.

Productivity, carbon utilization, and energy content of mass in scalable microalgae systems.

This study was designed to examine carbon utilization within scalable microalgae production systems. Neochloris oleoabundans was produced in replicated troughs containing BG11 nutrient formulation. Atmospheric CO(2) was supplemented with ∼5% CO(2) or with NaHCO(3), and the pH of troughs receiving NaHCO(3) was adjusted with HCl or H(3)PO(4). Peak biomass concentrations reached 950, 1140, or 850 mg L(-1) and biomass productivities of 109, 96, and 74 mg L(-1) day(-1) were achieved in the CO(2), NaHCO(3):HCl and NaHCO(3):H(3)PO(4) troughs, respectively. The highest productivity is expected in a scaled-up continuous batch process of the CO(2) supplemented system, which was projected to yield 8948 L lipids ha(-1)yr(-1). Carbon utilization in the CO(2), NaHCO(3):HCl and NaHCO(3):H(3)PO(4) systems was ∼0.5, 15.5, and 12.9%, while the energy content of the combustible biomass was 26.7, 13.2, and 15.4 MJ kg(-1), respectively. Techno-economic analyses of microalgal production systems should consider efficiencies and cost-benefit of various carbon sources.

The glutamate agonist NMDA blocks gonadal regression and enhances antibody response to an immune challenge in Siberian hamsters (Phodopus sungorus).

Seasonal variation in behavior and physiology, including changes in immune function, are common. This variability is elicited by changes in photoperiod and often covaries with fluctuations in both energy reserves and reproductive state. It is unclear, however, whether changes in either variable alone drive seasonal changes in immunity. We investigated the relative contributions of reproduction and energy balance to changes in immune function. To accomplish this, we uncoupled seasonal changes in reproduction from those related to energy balance via daily injections of N-methyl-D: -aspartate (NMDA) in Siberian hamsters (Phodopus sungorus). NMDA is a glutamatergic agonist that blocks short day-induced gonadal regression, while leaving short-day declines in body mass unaffected. In Experiment 1, we examined the effect of differing doses of NMDA on testosterone production as a proxy for NMDA effects on reproduction; a dose-dependent rise in testosterone was observed. In Experiment 2, animals were maintained on long or short days and received daily injections of NMDA. After 8 weeks, all animals underwent a humoral immune challenge. Short-day animals receiving daily injections of NMDA maintained long day-like gonads; however, contrary to our predictions, no trade-off between reproduction or energy balance and immune function was observed. Unexpectedly, NMDA treatment increased immunoglobulin levels in all groups, suggesting that NMDA may provide an immunomodulatory signal, presumably through actions on peripheral glutamate receptors. These results support a previous finding that NMDA blocks reproductive regression. In addition, these findings demonstrate a general immunoenhancing effect of NMDA that appears independent of changes in reproductive or energetic state of the animal.