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At least 757 records · Page 42

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Non-NASA Center↗

Influences of chemical sympathectomy, demedullation, and hindlimb suspension on the VO2max of rats

Results from previous studies have shown that the reduction in maximal oxygen consumption (VO2max) with simulated microgravity is attenuated in chemically sympathectomized rats. To determine the contributions of the catecholamines from the adrenal medulla in this process, investigations were conducted with 65 saline injected (SAL) and chemically sympathectomized (SX) female rats that were either surgically demedullated (DM), or intact (IN). Microgravity conditions were simulated by head-down suspension (HDS) while controls were assigned to individual cages (CC). The experimental period was 14 d. The rats were tested for VO2max, treadmill run time (RT), and submaximal mechanical efficiency (ME) prior to suspension and on days 7 and 14. Saline injected rats that had intact adrenal medullas (SAL-IN) exhibited significantly reduced measures of VO2max after 7 and 14 d by 15% and 21%, respectively. No significant reduction in VO2max was observed with HDS in the SX-IN animals. Sympathectomized rats that were demedullated (SX-DM) also exhibited a significant reduction in VO2max (12%). In addition, HDS was associated with a marked and significant reduction in RT in all groups. ME for submaximal exercise was significantly reduced after HDS in SAL-IN rats but not in the SX-IN rats. SX-DM rats experienced significant reductions in ME similar in magnitude to the SAL-IN rats. These results confirm that chemical sympathectomy attenuates the expected decrease in VO2max with HDS and suggests that circulating epinephrine contributes to this response.

Non-NASA Center↗

Exercise training, glucose transporters, and glucose transport in rat skeletal muscles

It was previously found that voluntary wheel running induces an increase in the insulin-sensitive glucose transporter, i.e., the GLUT4 isoform, in rat plantaris muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). The present study was undertaken to determine whether 1) the increase in muscle GLUT4 protein is associated with an increase in maximally stimulated glucose transport activity, 2) a conversion of type IIb to type IIa or type I muscle fibers plays a role in the increase in GLUT4 protein, and 3) an increase in the GLUT1 isoform is a component of the adaptation of muscle to endurance exercise. Five weeks of voluntary wheel running that resulted in a 33% increase in citrate synthase activity induced a 50% increase in GLUT4 protein in epitrochlearis muscles of female Sprague-Dawley rats. The rate of 2-deoxy-glucose transport maximally stimulated with insulin or insulin plus contractions was increased approximately 40% (P less than 0.05). There was no change in muscle fiber type composition, evaluated by myosin ATPase staining, in the epitrochlearis. There was also no change in GLUT1 protein concentration. We conclude that an increase in GLUT4, but not of GLUT1 protein, is a component of the adaptive response of muscle to endurance exercise and that the increase in GLUT4 protein is associated with an increased capacity for glucose transport.

NASA Discipline Cell Biology↗

Radiation protection guidelines for space missions

The current radiation protection guidelines of the National Aeronautics and Space Administration (NASA) were recommended in 1970. The career limit was set at 4.0 Sv (400 rem). Using the same approach as in 1970 but current risk estimates, a considerably lower career limit would obtain today. Also, there is now much more information about the radiation environments that will be experienced in different missions. Furthermore, since 1970 women have joined the ranks of the astronauts. For these and other reasons, it was considered necessary to re-examine the radiation protection guidelines. This task has been undertaken by the National Council on Radiation Protection and Measurements Scientific Committee 75. Within the magnetosphere, the radiation environment varies with altitude and inclination of the orbit. In outer space missions, galactic cosmic rays, with the small but important heavy-ion component, determine the radiation environment. The new recommendations for career dose limits, based on lifetime excess risk of cancer mortality, take into account age at first exposure and sex. The career limits range from 1.0 Sv (100 rem) for a 24-y-old female up to 4.0 Sv (400 rem) for a 55-y-old male, compared with the previous single limit of 4.0 Sv (400 rem). The career limit for the lens of the eye has been reduced from 6.0 Sv (600 rem) to 4.0 Sv (400 rem).

NASA Discipline Radiation Health↗

Prediction of functional aerobic capacity without exercise testing

The purpose of this study was to develop functional aerobic capacity prediction models without using exercise tests (N-Ex) and to compare the accuracy with Astrand single-stage submaximal prediction methods. The data of 2,009 subjects (9.7% female) were randomly divided into validation (N = 1,543) and cross-validation (N = 466) samples. The validation sample was used to develop two N-Ex models to estimate VO2peak. Gender, age, body composition, and self-report activity were used to develop two N-Ex prediction models. One model estimated percent fat from skinfolds (N-Ex %fat) and the other used body mass index (N-Ex BMI) to represent body composition. The multiple correlations for the developed models were R = 0.81 (SE = 5.3 ml.kg-1.min-1) and R = 0.78 (SE = 5.6 ml.kg-1.min-1). This accuracy was confirmed when applied to the cross-validation sample. The N-Ex models were more accurate than what was obtained from VO2peak estimated from the Astrand prediction models. The SEs of the Astrand models ranged from 5.5-9.7 ml.kg-1.min-1. The N-Ex models were cross-validated on 59 men on hypertensive medication and 71 men who were found to have a positive exercise ECG. The SEs of the N-Ex models ranged from 4.6-5.4 ml.kg-1.min-1 with these subjects.(ABSTRACT TRUNCATED AT 250 WORDS).

Oxygen Consumption↗

Comparison of different cooling regimes within a shortened liquid cooling/warming garment on physiological and psychological comfort during exercise

The aim of this study was to compare the effectiveness of different cooling regime intensities to maintain physiological and subjective comfort during physical exertion levels comparable to that engaged in during extravehicular activities (EVA) in space. We studied eight subjects (six males, two females) donned in our newly developed physiologically based shortened liquid cooling/warming garment (SLCWG). Rigorous (condition 1) and mild (condition 2) water temperature cooling regimes were compared at physical exertion levels comparable to that performed during EVA to ascertain the effectiveness of a lesser intensity of cooling in maintaining thermal comfort, thus reducing energy consumption in the portable life support system. Exercise intensity was varied across stages of the session. Finger temperature, rectal temperature, and subjective perception of overall body and hand comfort were assessed. Finger temperature was significantly higher in the rigorous cooling condition and showed a consistent increase across exercise stages, likely due to the restriction of heat extraction because of the intensive cold. In the mild cooling condition, finger temperature exhibited an overall decline with cooling, indicating greater heat extraction from the body. Rectal temperature was not significantly different between conditions, and showed a steady increase over exercise stages in both rigorous and mild cooling conditions. Ratings of overall comfort were 30% higher (more positive) and more stable in mild cooling (p<0.001). The mild cooling regime was more effective than rigorous cooling in allowing the process of heat exchange to occur, thus maintaining thermal homeostasis and subjective comfort during physical exertion.

NASA Discipline Life Sciences Technologies↗

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

NASA Discipline Regulatory Physiology↗

Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease

Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ε4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, setting, an participants: In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-β-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures: Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-β PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main outcomes and measures: Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-ε4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results: A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9 [5.5]) were included in the study. In multivariable models, women (standardized β = -0.15, P = .02) and young patients (standardized β = -0.20, P = .006) had greater brain resilience to pathological tau. Higher educational level (standardized β = 0.23, P < .001) and global cortical thickness (standardized β = 0.23, P < .001) were associated with greater cognitive resilience to pathological tau. Linear mixed models indicated a significant interaction of brain resilience × cognitive resilience × time on MMSE (β [SE] = -0.235 [0.111], P = .03), with steepest slopes for individuals with both low brain and cognitive resilience. Conclusions and relevance: Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau. Interindividual differences in resilience to pathological tau may be important to disease progression because participants with both low brain and cognitive resilience had the most rapid cognitive decline over time.

60 APPLIED LIFE SCIENCES↗

Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome

Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)–associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points/year; P = .005). In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aβ or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials.

59 BASIC BIOLOGICAL SCIENCES↗

Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans

Importance: Suicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown. Objective: To identify novel, replicable genomic risk loci for SITB. Design, Setting, and Participants: This genome-wide association study included 633 778 US military veterans with and without SITB, as identified through electronic health records. GWAS was performed separately by ancestry, controlling for sex, age, and genetic substructure. Cross-ancestry risk loci were identified through meta-analysis. Study enrollment began in 2011 and is ongoing. Data were analyzed from November 2021 to August 2022. Main Outcome and Measures: SITB. Results: A total of 633 778 US military veterans were included in the analysis (57 152 [9%] female; 121 118 [19.1%] African ancestry, 8285 [1.3%] Asian ancestry, 452 767 [71.4%] European ancestry, and 51 608 [8.1%] Hispanic ancestry), including 121 211 individuals with SITB (19.1%). Meta-analysis identified more than 200 GWS (P < 5 × 10 -8 ) cross-ancestry risk single-nucleotide variants for SITB concentrated in 7 regions on chromosomes 2, 6, 9, 11, 14, 16, and 18. Top single-nucleotide variants were largely intronic in nature; 5 were independently replicated in ISGC, including rs6557168 in ESR1, rs12808482 in DRD2, rs77641763 in EXD3, rs10671545 in DCC, and rs36006172 in TRAF3. Associations for FBXL19 and AC018880.2 were not replicated. Gene-based analyses implicated 24 additional GWS cross-ancestry risk genes, including FURIN, TSNARE1, and the NCAM1-TTC12-ANKK1-DRD2 gene cluster. Cross-ancestry enrichment analyses revealed significant enrichment for expression in brain and pituitary tissue, synapse and ubiquitination processes, amphetamine addiction, parathyroid hormone synthesis, axon guidance, and dopaminergic pathways. Seven other unique European ancestry–specific GWS loci were identified, 2 of which (POM121L2 and METTL15/LINC02758) were replicated. Two additional GWS ancestry-specific loci were identified within the African ancestry (PET112/GATB) and Hispanic ancestry (intergenic locus on chromosome 4) subsets, both of which were replicated. Further, no GWS loci were identified within the Asian ancestry subset; however, significant enrichment was observed for axon guidance, cyclic adenosine monophosphate signaling, focal adhesion, glutamatergic synapse, and oxytocin signaling pathways across all ancestries. Within the European ancestry subset, genetic correlations (r > 0.75) were observed between the SITB phenotype and a suicide attempt-only phenotype, depression, and posttraumatic stress disorder. Additionally, polygenic risk score analyses revealed that the Million Veteran Program polygenic risk score had nominally significant main effects in 2 independent samples of veterans of European and African ancestry.

60 APPLIED LIFE SCIENCES↗

Hearing impairment and tinnitus among older construction workers employed at DOE facilities

Few studies have defined the risk of hearing impairment and tinnitus after retirement. This report measures hearing impairment and tinnitus prevalence among older construction trades workers. The study cohort included 21,340 participants in a national medical screening program. Audiometric hearing impairment was classified according to the Global Burden of Disease Study. Tinnitus was determined by self-report. An internal subcohort of nonconstruction trades workers served as a reference group. Stratified analyses and multivariate analyses were used to measure the prevalence of hearing impairment and tinnitus by age, sex, and job category. Prevalence of any hearing impairment was 55.2% (males, 57.7%; females, 26.8%) and increased rapidly with age. Construction trades workers were 40% more likely to have hearing impairment than the reference group. The overall prevalence of tinnitus was 46.52% and followed patterns similar to hearing impairment. Workers with hearing impairment were more likely to also have tinnitus, but tinnitus was frequently reported in the absence of measured hearing impairment. Hearing impairment and tinnitus prevalence were much higher in this study than in previous research. A significant reason for the difference is that BTMed follows participants after they have retired. To draw conclusions about the risk for work-related chronic diseases and disorders it is important to monitor workers through their lifetimes. Also, tinnitus by itself should be given greater significance. We report the findings reinforce the need to promote noise reduction and hearing conservation in construction.

60 APPLIED LIFE SCIENCES↗

Behavioral and neuroinflammatory changes caused by glyphosate: Base herbicide in mice offspring

Abstract Background Glyphosate is a pesticide considered of low toxicity, but scientific evidences show it can be harmful to health. This study aimed to evaluate the toxicity in mice offspring exposed to glyphosate‐based herbicide (GBH) during the intrauterine period. Methods Female matrices received glyphosate 0.3 mg/kg daily per oral throughout the gestational period, which was variable between 18 and 22 days. From the 25th until the 28th days post‐birth, mice offspring were subjected to behavioral tests, and the prefrontal cortex was processed for immunohistochemical analysis. Results Two significant behavioral changes were observed: anxiety in the GLIF0.3 group, increase in the behavior burying marbles in the marble‐burying test and hyperactivity, expressed by the significant increase of the crossing number in the open field test. The increased microglia, TNF‐alpha, and astrocyte expression were also observed in the prefrontal cortex of offspring treated with GLIF0.3. Conclusion Exposure to GBH during mice intrauterine development induces hyperactive and anxious behavior, evidencing neuroinflammation.

de Castro Vieira Carneiro, Carla Larissa↗

Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders

ABSTRACT Objective Caseinolytic protease B (ClpB) produced by Enterobacteria , such as Escherichia coli , has been identified as a conformational mimetic of α‐melanocyte‐stimulating hormone (α‐MSH), an anorexigenic and anxiogenic neuropeptide. In mice, ClpB induces α‐MSH cross‐reactive antibodies and activates anorexigenic brain neurons. In patients with eating disorders (ED), anti‐ClpB and anti‐α‐MSH antibodies correlate with psychopathological traits. However, it is not known if ClpB is present in human plasma including ED patients. Methods Plasma concentrations of ClpB were measured using a recently developed ClpB immunoassay in female patients with anorexia nervosa, bulimia nervosa, and binge‐eating disorder and compared with healthy participants, all characterized by the Eating Disorder Inventory‐2 (EDI‐2) scale. Results We found that ClpB was readably detectable in plasma of healthy participants and ED patients and that its concentrations were elevated in ED patients, without significant differences in patient's subgroups. Plasma ClpB concentrations correlated with the EDI‐2 scores, with α‐MSH as well as with plasma levels of anti‐ClpB and anti‐α‐MSH antibodies. Discussion These data revealed that bacterial ClpB is naturally present in human plasma and that its concentrations can be elevated in ED patients and associated with ED‐related psychopathological traits. These results support a link between bacterial ClpB and the ED pathophysiology. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:805–808)

Breton, Jonathan↗

A new approach to estimate fecundity rate from inter‐birth intervals

Abstract Accurate estimates of fecundity rate are key to population assessments and effectively direct conservation efforts. We present a new approach to estimate fecundity rate based on the probability of a female giving birth, conditional on a previous birth t years ago, from which an expected inter‐birth interval ( IBI ) can be estimated. We use generalized linear mixed‐effects models to account for individual and temporal variability and apply the approach to individual reproductive histories of bottlenose dolphins ( Tursiops truncatus ) from the east coast of Scotland. We estimate a fecundity rate of 0.222 (95% CI = 0.218–0.253) and an expected IBI of 4.49 yr (95% CI = 3.94–4.93 yr). We use simulated data samples to show that the approach produces estimates with a minimum bias of <3%. Simulations are also used to investigate the effect of the most common data‐driven biases in the estimates of birth intervals and fecundity rate; we recommend longitudinal studies of at least 10 yr and capture probabilities of at least 0.3 when using this methodology. The approach may be modified to incorporate other parameters of interest and should be applicable to any population with comprehensive data on birth intervals.

Arso Civil, Mònica↗

Co-occurrence of native white-tailed deer and invasive wild pigs: Evidence for competition?

Understanding whether invasive and native species compete for shared resources where they co-occur is essential for mitigating the negative impacts of invasive species on native ecosystems. Here, we examined how the presence and density of an invasive species, wild pigs (Sus scrofa), affect native white-tailed deer (Odocoileus virginianus; hereafter, deer) on the Savannah River Site, SC, USA. We examined potential changes in deer areas of use, temporal overlap, and occupancy to evaluate the effects of wild pig occurrence and density on deer space use, diel activity, and co-occurrence with wild pigs across 9 months during 2018 and 2019. Wild pig density had the strongest effect on deer space use in high- and moderate-use areas. Declines in deer space use in response to wild pig density were most pronounced in March and October 2018 and April 2019 for females, while male space use declined in response to wild pig density in October and December 2018. Both species were largely nocturnal with high overlap in diel activity across months. Deer occupancy responses to wild pig density varied across months, with negative responses in May and October 2018 and positive responses in July 2018 and April 2019. Deer and wild pigs co-occurred at 30%–59% of camera stations across months, with broadscale co-occurrence patterns being unaffected by changes in shared cover or wild pig occurrence. Overall, our results suggest that deer make fine-scale behavioral adjustments to avoid wild pigs, providing evidence that competition is likely occurring even where wild pig density is relatively low. Such fine-scale behavioral plasticity in deer appears to mitigate the costs of competition with wild pigs and may be a mechanism enabling long-term co-existence of deer and wild pigs. Our study provides novel insight on the complexities of spatiotemporal relationships between invasive wild pigs and native deer and suggests that the negative effects of interactions between deer and wild pigs may be more pronounced when deer life history needs are particularly demanding. In areas where eradication of invasive wild pigs may be impossible, maintaining low wild pig densities may help mitigate, but may not eliminate, the negative effects of wild pigs on deer.

resource partitioning↗

A prospective study on myocardial injury after BNT162b2 mRNA COVID ‐19 fourth dose vaccination in healthy persons

Aims To prospectively evaluate the incidence of myocardial injury after the administration of the fourth dose BNT162b2 mRNA vaccine (Pfizer‐BioNTech) against COVID‐19. Methods and results Health care workers who received the BNT162b2 vaccine during the fourth dose campaign had blood samples collected for high‐sensitivity cardiac troponin (hs‐cTn) during vaccine administration and 2–4 days afterward. Vaccine‐related myocardial injury was defined as hs‐cTn elevation above the 99th percentile upper reference limit and >50% increase from baseline measurement. Participants with evidence of myocardial injury underwent assessment for possible myocarditis. Of 324 participants, 192 (59.2%) were female and the mean age was 51.8 ± 15.0 years. Twenty‐one (6.5%) participants had prior COVID‐19 infection, the mean number of prior vaccine doses was 2.9 ± 0.4, and the median time from the last dose was 147 (142–157) days. Reported vaccine‐related adverse reactions included local pain at injection site in 57 (17.59%), fatigue in 39 (12.04%), myalgia in 32 (9.88%), sore throat in 21 (6.48%), headache in 18 (5.5%), fever ≥38°C in 16 (4.94%), chest pain in 12 (3.7%), palpitations in 7 (2.16%), and shortness of breath in one (0.3%) participant. Vaccine‐related myocardial injury was demonstrated in two (0.62%) participants, one had mild symptoms and one was asymptomatic; both had a normal electrocardiogram and echocardiography. Conclusion In a prospective investigation, an increase in serum troponin levels was documented among 0.62% of healthy health care workers receiving the fourth dose BNT162b2 vaccine. The two cases had mild or no symptoms and no clinical sequela. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05308680.

Levi, Nir↗

Transient Copper Exposure During Embryogenesis and Temperature Affect Developmental Rate, Survival, and Fin Regeneration in Japanese Medaka ( Oryzias latipes )

Combined environmental stressors that an organism experiences can have both immediate and lasting consequences. In this paper we exposed medaka (Oryzias latipes) embryos to sublethal copper sulfate (CuSO 4 ) (0, 10, and 100 ppb) in combination with different rearing temperatures (27, 30, and 33°C) to assess acute and latent effects on development, growth, and regenerative capacity. Embryos exposed to CuSO 4 and/or higher temperatures hatched significantly earlier. At 4 months post-exposure, fish exposed to low levels of CuSO 4 during development had higher survival, while fish exposed to both 100 ppb CuSO 4 and 33°C temperatures had significantly lower survival. Additionally, a sex-specific effect of embryonic CuSO 4 exposure was observed as female mass decreased with increasing copper dose. We also assessed caudal fin regenerative capabilities in both embryo-exposed fish at 4 months of age and adult medaka that were exposed to 0, 10, and 100 ppb CuSO 4 at room temperature during a 14- day trial. Whereas fin regeneration was unaffected by adult exposure to copper, fish transiently exposed during embryogenesis displayed an initial increase in fin growth rate and an increased incidence of abnormal fin morphology following regrowth. Collectively, these data suggest that developmental copper exposure has the potential to exert long lasting impacts to organismal growth, survival, and function.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Degradation-Resistant Hypoxia Inducible Factor-2α in Murine Osteocytes Promotes a High Bone Mass Phenotype

Molecular oxygen levels vary during development and disease. Adaptations to decreased oxygen bioavailability (hypoxia) are mediated by hypoxia-inducible factor (HIF) transcription factors. HIFs are composed of an oxygen-dependent α subunit (HIF-α), of which there are two transcriptionally active isoforms (HIF-1α and HIF-2α), and a constitutively expressed β subunit (HIFβ). Under normoxic conditions, HIF-α is hydroxylated via prolyl hydroxylase domain (PHD) proteins and targeted for degradation via Von Hippel-Lindau (VHL). Under hypoxic conditions, hydroxylation via PHD is inhibited, allowing for HIF-α stabilization and induction of target transcriptional changes. Our previous studies showed that Vhl deletion in osteocytes (Dmp1-cre; Vhlf/f) resulted in HIF-α stabilization and generation of a high bone mass (HBM) phenotype. The skeletal impact of HIF-1α accumulation has been well characterized; however, the unique skeletal impacts of HIF-2α remain understudied. Because osteocytes orchestrate skeletal development and homeostasis, we investigated the role of osteocytic HIF-α isoforms in driving HBM phenotypes via osteocyte-specific loss-of-function and gain-of-function HIF-1α and HIF-2α mutations in C57BL/6 female mice. Deletion of Hif1a or Hif2a in osteocytes showed no effect on skeletal microarchitecture. Constitutively stable, degradation-resistant HIF-2α (HIF-2α cDR), but not HIF-1α cDR, generated dramatic increases in bone mass, enhanced osteoclast activity, and expansion of metaphyseal marrow stromal tissue at the expense of hematopoietic tissue. Our studies reveal a novel influence of osteocytic HIF-2α in driving HBM phenotypes that can potentially be harnessed pharmacologically to improve bone mass and reduce fracture risk.

59 BASIC BIOLOGICAL SCIENCES↗