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At least 217 records · Page 12

Differential mGluR5 expression in response to the same stress causes individually adapted hippocampal network activity

Highlights: • Individuals show different changes in mGluR5 expression in response to the same stress. • Repetitive restraint stress causes theta EEG activity in the hippocampus. • Hippocampal mGluR5 expression determines the theta EEG response to repetitive restraint stress. Individual differences in stress vulnerability and resilience have been observed even within a single cohort of inbred rats or mice. Stress phenotypes are typically quantified as changes in the behavior of experimental animals, which is the outcome of altered electrical activity of the brain network. Although mGluR5 is associated with individual vulnerability to stress and can act as a sensitive biomarker of stress adaptation, our understanding of mGluR5-dependent modifications to neural network activities in vivo remains limited. Here, we examined individual rats for changes in hippocampal mGluR5 expression induced by restraint stress and found that these changes cause accompanying changes in hippocampal electroencephalography (EEG) activity. We found six days of restraint stress caused variable changes in hippocampal mGluR5 expression, ranging from 20.9% to 210.7% of the control group. The low mGluR5 protein group (LE) showed increased methylation of the mGluR5 CpG island, reduced mGluR5 mRNA levels, and unaltered basal EEG theta spectral power between stress day 1 and 6. In contrast, the high mGluR5 protein group (HE) showed reduced methylation of CpG sites, increased mGluR5 mRNA expression, and reduced basal theta spectral power on stress day 6. We also found that injection of lentiviruses expressing mGluR5-specific shRNAs into the hippocampus rescued this reduction in baseline theta power in HE rats. These data suggest a causal relationship between individual differences in the changes in hippocampal mGluR5 expression induced by repetitive restraint stress and the accompanying changes in ensemble neural activity in the hippocampus.

60 APPLIED LIFE SCIENCES↗

Critical differences in 3D atomic structure of individual ligand-protected nanocrystals in solution

Precise three-dimensional (3D) atomic structure determination of individual nanocrystals is a prerequisite for understanding and predicting their physical properties. Nanocrystals from the same synthesis batch display what are often presumed to be small but possibly important differences in size, lattice distortions, and defects, which can only be understood by structural characterization with high spatial 3D resolution. We solved the structures of individual colloidal platinum nanocrystals by developing atomic-resolution 3D liquid-cell electron microscopy to reveal critical intrinsic heterogeneity of ligand-protected platinum nanocrystals in solution, including structural degeneracies, lattice parameter deviations, internal defects, and strain. These differences in structure lead to substantial contributions to free energies, consequential enough that they must be considered in any discussion of fundamental nanocrystal properties or applications.

Kim, Byung Hyo↗

Emergency department visits in California associated with wildfire PM 2.5 : differing risk across individuals and communities

The threats to human health from wildfires and wildfire smoke (WFS) in the United States (US) are increasing due to continued climate change. A growing body of literature has documented important adverse health effects of WFS exposure, but there is insufficient evidence regarding how risk related to WFS exposure varies across individual or community level characteristics. To address this evidence gap, we utilized a large nationwide database of healthcare utilization claims for emergency department (ED) visits in California across multiple wildfire seasons (May through November, 2012–2019) and quantified the health impacts of fine particulate matter <2.5 μm (PM 2.5 ) air pollution attributable to WFS, overall and among subgroups of the population. We aggregated daily counts of ED visits to the level of the Zip Code Tabulation Area (ZCTA) and used a time-stratified case-crossover design and distributed lag non-linear models to estimate the association between WFS and relative risk of ED visits. We further assessed how the association with WFS varied across subgroups defined by age, race, social vulnerability, and residential air conditioning (AC) prevalence. Over a 7 day period, PM 2.5 from WFS was associated with elevated risk of ED visits for all causes (1.04% (0.32%, 1.71%)), non-accidental causes (2.93% (2.16%, 3.70%)), and respiratory disease (15.17% (12.86%, 17.52%)), but not with ED visits for cardiovascular diseases (1.06% (–1.88%, 4.08%)). Analysis across subgroups revealed potential differences in susceptibility by age, race, and AC prevalence, but not across subgroups defined by ZCTA-level Social Vulnerability Index scores. These results suggest that PM 2.5 from WFS is associated with higher rates of all cause, non-accidental, and respiratory ED visits with important heterogeneity across certain subgroups. Notably, lower availability of residential AC was associated with higher health risks related to wildfire activity.

54 ENVIRONMENTAL SCIENCES↗

ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner

Highlights: • ACBD3 is up-regulated in gastric cancer. • ACBD3 regulates cell-cycle of gastric cancer in an AKT-dependent manner. It has been reported that ACBD3 is closely related to the malignant process of cells, but its role in gastric cancer has not been elucidated. This study aims to investigate the expression and function of ACBD3 in human gastric cancer. The Cancer Genome Atlas (TCGA) database were selected to analyze mRNA levels of ACBD3 in gastric cancer tissues and normal gastric epithelial tissues. qPCR and Western blot were conducted to detect the expression of ACBD3 in two normal gastric epithelial cell lines and five gastric cancer cell lines which were cultured in our laboratory. To exclude differences in individual background between different patients, we further detected the expression of ACBD3 in 8 pairs of malignant/non-malignant clinical gastric tissues. Through the establishment of stable cells, in vitro cell experiments and in vivo xenotransplantation models in mice, the role of ACBD3 in the proliferation of gastric cancer cells has been further explored. AKT inhibitors were used to deeply explore the molecular regulation mechanism of ACBD3. The results showed that the elevated ACBD3 in gastric cancer tissue were positively correlated with the clinical grade and prognosis of gastric cancer. In terms of molecular function, we found that ACBD3 can enhance the production and growth of gastric cancer cells. At the same time, the activation of AKT kinase played an important role in ACBD3's promotion of G1-to-S transition. The experiments generally indicate that ACBD3 is expected to become a potential diagnostic molecule or therapeutic target for gastric cancer.

60 APPLIED LIFE SCIENCES↗

Vision Changes after Space Flight Are Related to Alterations in Folate-Dependent One-Carbon Metabolism

About 20% of astronauts on International Space Station missions have developed measurable ophthalmic changes after flight. This study was conducted to determine whether the folate-dependent 1-carbon pathway is altered in these individuals. Data were modeled to evaluate differences between individuals with ophthalmic changes (n=5) and those without them (n=15). We also correlated mean preflight serum concentrations of the 1-carbon metabolites with changes in measured refraction after flight. Serum homocysteine (HCy), cystathionine, 2-methylcitric acid, and methylmalonic acid concentrations were 25%-45% higher (P<0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum HCy and cystathionine, and in-flight serum folate, were significantly (P<0.05) correlated with postflight change in refraction, and preflight serum concentrations of 2-methylcitric acid tended to be associated (P=0.06) with ophthalmic changes. The biochemical differences observed in those with vision issues strongly suggests impairment of the folate-dependent 1-carbon transfer pathway. Impairment of this pathway, by polymorphisms, diet or other means, may interact with components of the microgravity environment to influence these pathophysiologic changes. This study was funded by the NASA Human Research Program.

Smith, Scott M.↗

Tyramine and its Amtyr1 receptor modulate attention in honey bees (Apis mellifera)

Animals must learn to ignore stimuli that are irrelevant to survival and attend to ones that enhance survival. When a stimulus regularly fails to be associated with an important consequence, subsequent excitatory learning about that stimulus can be delayed, which is a form of nonassociative conditioning called ‘latent inhibition’. Honey bees show latent inhibition toward an odor they have experienced without association with food reinforcement. Moreover, individual honey bees from the same colony differ in the degree to which they show latent inhibition, and these individual differences have a genetic basis. To investigate the mechanisms that underly individual differences in latent inhibition, we selected two honey bee lines for high and low latent inhibition, respectively. We crossed those lines and mapped a Quantitative Trait Locus for latent inhibition to a region of the genome that contains the tyramine receptor gene Amtyr1 [We use Amtyr1 to denote the gene and AmTYR1 the receptor throughout the text.]. We then show that disruption of Amtyr1 signaling either pharmacologically or through RNAi qualitatively changes the expression of latent inhibition but has little or slight effects on appetitive conditioning, and these results suggest that AmTYR1 modulates inhibitory processing in the CNS. Electrophysiological recordings from the brain during pharmacological blockade are consistent with a model that AmTYR1 indirectly regulates at inhibitory synapses in the CNS. Our results therefore identify a distinct Amtyr1 -based modulatory pathway for this type of nonassociative learning, and we propose a model for how Amtyr1 acts as a gain control to modulate hebbian plasticity at defined synapses in the CNS. We have shown elsewhere how this modulation also underlies potentially adaptive intracolonial learning differences among individuals that benefit colony survival. Finally, our neural model suggests a mechanism for the broad pleiotropy this gene has on several different behaviors.

59 BASIC BIOLOGICAL SCIENCES↗

Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’s regional difference and global difference, were used to test for regional differences that diverge from the global difference. For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

15q11.2 BP1-BP2↗

The Fecal Microbial Community of Breast-fed Infants from Armenia and Georgia

Multiple factors help shape the infant intestinal microbiota early in life. Environmental conditions such as the presence of bioactive molecules from breast milk dictate gut microbial growth and survival. Infants also receive distinct, personalized, bacterial exposures leading to differential colonization. Microbial exposures and gut environmental conditions differ between infants in different locations, as does the typical microbial community structure in an infant’s gut. Here we evaluate potential influences on the infant gut microbiota through a longitudinal study on cohorts of breast-fed infants from the neighboring countries of Armenia and Georgia, an area of the world for which the infant microbiome has not been previously investigated. Marker gene sequencing of 16S ribosomal genes revealed that the gut microbial communities of infants from these countries were dominated by bifidobacteria, were different from each other, and were marginally influenced by their mother’s secretor status. Species-level differences in the bifidobacterial communities of each country and birth method were also observed. These community differences suggest that environmental variation between individuals in different locations may influence the gut microbiota of infants.

54 ENVIRONMENTAL SCIENCES↗

Engineering, Life Sciences, and Health/Medicine Synergy in Aerospace Human Systems Integration: The Rosetta Stone Project

In the realm of aerospace engineering and the physical sciences, we have developed laws of physics based on empirical and research evidence that reliably guide design, research, and development efforts. For instance, an engineer designs a system based on data and experience that can be consistently and repeatedly verified. This reproducibility depends on the consistency and dependability of the materials on which the engineer works and is subject to physics, geometry and convention. In life sciences and medicine, these apply as well, but individuality introduces a host of variables into the mix, resulting in characteristics and outcomes that can be quite broad within a population of individuals. This individuality ranges from differences at the genetic and cellular level to differences in an individuals personality and abilities due to sex and gender, environment, education, etc.

Medicine↗

Sequence polymorphism in an insect RNA virus field population: A snapshot from a single point in space and time reveals stochastic differences among and within individual hosts

Population structure of Homalodisca coagulata Virus-1 (HoCV-1) among and within field-collected insects sampled from a single point in space and time was examined. Polymorphism in complete consensus sequences among single-insect isolates was dominated by synonymous substitutions. The mutant spectrum of the C2 helicase region within each single-insect isolate was unique and dominated by nonsynonymous singletons. Bootstrapping was used to correct the within-isolate nonsynonymous:synonymous arithmetic ratio (N:S) for RT-PCR error, yielding an N:S value ~one log-unit greater than that of consensus sequences. Probability of all possible single-base substitutions for the C2 region predicted N:S values within 95% confidence limits of the corrected within-isolate N:S when the only constraint imposed was viral polymerase error bias for transitions over transversions. These results indicate that bottlenecks coupled with strong negative/purifying selection drive consensus sequences toward neutral sequence space, and that most polymorphism within single-insect isolates is composed of newly-minted mutations sampled prior to selection. -- Highlights: •Sampling protocol minimized differential selection/history among isolates. •Polymorphism among consensus sequences dominated by negative/purifying selection. •Within-isolate N:S ratio corrected for RT-PCR error by bootstrapping. •Within-isolate mutant spectrum dominated by new mutations yet to undergo selection.

60 APPLIED LIFE SCIENCES↗

Spatial and Temporal Uncertainty of Crop Yield Aggregations

The aggregation of simulated gridded crop yields to national or regional scale requires information on temporal and spatial patterns of crop-specific harvested areas. This analysis estimates the uncertainty of simulated gridded yield time series related to the aggregation with four different harvested area data sets. We compare aggregated yield time series from the Global Gridded Crop Model Inter-comparison project for four crop types from 14 models at global, national, and regional scale to determine aggregation-driven differences in mean yields and temporal patterns as measures of uncertainty. The quantity and spatial patterns of harvested areas differ for individual crops among the four datasets applied for the aggregation. Also simulated spatial yield patterns differ among the 14 models. These differences in harvested areas and simulated yield patterns lead to differences in aggregated productivity estimates, both in mean yield and in the temporal dynamics. Among the four investigated crops, wheat yield (17% relative difference) is most affected by the uncertainty introduced by the aggregation at the global scale. The correlation of temporal patterns of global aggregated yield time series can be as low as for soybean (r = 0.28).For the majority of countries, mean relative differences of nationally aggregated yields account for10% or less. The spatial and temporal difference can be substantial higher for individual countries. Of the top-10 crop producers, aggregated national multi-annual mean relative difference of yields can be up to 67% (maize, South Africa), 43% (wheat, Pakistan), 51% (rice, Japan), and 427% (soybean, Bolivia).Correlations of differently aggregated yield time series can be as low as r = 0.56 (maize, India), r = 0.05∗Corresponding (wheat, Russia), r = 0.13 (rice, Vietnam), and r = −0.01 (soybean, Uruguay). The aggregation to sub-national scale in comparison to country scale shows that spatial uncertainties can cancel out in countries with large harvested areas per crop type. We conclude that the aggregation uncertainty can be substantial for crop productivity and production estimations in the context of food security, impact assessment, and model evaluation exercises.

Aggregation uncertainty↗

The structure-activity relationship of ginsenosides on hypoxia-reoxygenation induced apoptosis of cardiomyocytes

Highlights: • Ginsenosides have cardioprotective effects on hypoxia and reoxygenation-induced damage. • There is a structure-activity relationship regarding ginsenosides' inhibition of apoptosis. • AMPK could be an important mediator for ginsenosides' cardioprotection against hypoxic injury. Ginsenosides have been studied extensively in recent years due to their therapeutic effects in cardiovascular diseases. While most studies examined the different ginsenosides individually, few studies compare the therapeutic effects among the different types. This study examined how effective protopanaxadiol, protopanaxatriol ginsenosides Rh2, Rg3, Rh1, and Rg2 of the ginsenoside family are in protecting H9c2 cardiomyocytes from damage caused by hypoxia/reoxygenation. In the current study, a model of myocardial ischemia and reperfusion was induced in H9c2 cardiomyocytes by oxygen deprivation via a hypoxia chamber followed by reoxygenation. Our data show that structures similar to that of protopanaxadiol, which lacked the hydroxide group at C6, were more effective in lowering apoptosis than structures similar to protopanaxatriol with a hydroxide group at C6. As the compounds increased in size and complexity, the cardioprotective effects diminished. In addition, the S enantiomer proved to be more effective in cardioprotection than the R enantiomer. Furthermore, the immunoblotting analysis demonstrated that ginsenosides activate AMPK but suppress JNK signaling pathways during hypoxia/reoxygenation. Thus, ginsenosides treatment attenuated hypoxia/reoxygenation-induced apoptosis via modulating cardioprotective AMPK and inflammation-related JNK signaling pathways.

60 APPLIED LIFE SCIENCES↗

Chapter 9: Human Behavior Dynamics in Sustainability

Human behavior dynamics and actions play a direct and significant role in shaping pathways toward sustainability, resulting in many sustainability challenges. A social dilemma arose when a hypothetical Colorado rural town closed down most of its medicine take-back stations as a result of reduced tax revenue. The current discourse discusses a scenario in which an individual "plays" against everyone else concerning whether to drive to the take-back station to dispose of unused medication (i.e., cooperating) or to flush it or throw it in the landfill (i.e., defecting). Using the structure of the pay-off matrix, this study analyzed unwanted medication disposal from a social dilemma perspective to provide insight into an individual's motivations to cooperate or defect and techniques for encouraging cooperation. The pay-off matrix encompasses four scenarios, namely, win-win when everyone cooperates, you're the sucker when only the individual cooperates, free rider when only the individual defects, and the tragedy of the commons when everyone defects. Reasons for an individual to cooperate include sharing the high moral value with everyone else, valuing social conformity, and taking great pride in doing the right thing, even when cooperating is costly. On the other hand, the individual who defects believes that cooperating will likely make little difference. The individual is selfish or insufficiently motivated by altruism and feels that the bad action will not get caught. When everyone defects, it likely results from participants not wanting to be a "sucker" and a lack of accountability (e.g., no punishment) associated with bad behavior. One solution to the free-rider problem is to appeal to the free rider's altruism. It is important to convince the individual that doing things for the benefit of others can also benefit themselves. Furthermore, a way to fix the social dilemma is to make the defectors pay for their actions that cause the negative externality (i.e., town water contaminated with pharmaceutical chemicals from unwanted medications). The higher the financial incentive for cooperative behavior, the lower the defecting propensity. By including punishment (e.g., discipline and penalty), people tend to defect less often, and highly cooperative outcomes emerge.

ENERGY PLANNING, POLICY, AND ECONOMY↗

Comparison of Vehicle-Broadcasted Fuel Consumption Rates against Precise Fuel Measurements for Medium- and Heavy-Duty Vehicles and Engines

Vehicles continuously report real-time fuel consumption estimates over their data bus, known as the controller area network (CAN). However, the accuracy of these fueling estimates is uncertain to researchers who collect these data from any given vehicle. To assess the accuracy of these estimates, CAN-reported fuel consumption data are compared against fuel measurements from precise instrumentation. The data analyzed consisted of eight medium/heavy-duty vehicles and two medium-duty engines. Varying discrepancies between CAN fueling rates and the more accurate measurements emerged but without a vehicular trend-for some vehicles the CAN under-reported fuel consumption and for others the CAN over-reported fuel consumption. Furthermore, a qualitative real-time analysis revealed that the operating conditions under which these fueling discrepancies arose varied among vehicles. A drive cycle analysis revealed that while CAN fueling estimate accuracy differs for individual vehicles, that CAN estimates capture the relative fuel consumption differences between drive cycles within 4% for all vehicles and even more accurately for some vehicles. Furthermore, in situations where only CAN-reported data are available, CAN fueling estimates can provide relative fuel consumption trends but not accurate or precise fuel consumption rates.

30 DIRECT ENERGY CONVERSION↗

Changes in total body water during spaceflight

Total body water (TBW) changes occurring in humans as a consequence of prolonged exposure to microgravity were measured in five male crewmembers of Space Shuttle missions STS-61C and STS-26. It was found that the inflight mean TBW values were significantly different from the preflight and postflight values, while the preflight TBW values were not significantly different from the postflight values. It was also found that individuals may differ in the rate at which they respond to weightlessness. Of the three crewmen who reported experiencing no symptoms of space motion sickness (SMS), two had not exhibited a decrease of TBW at the time of measurements (24 hrs after launch), while the two crewmen who reported SMS of intermediate severity showed a decrease of several kg by 24 hrs, suggesting that dehydration might be an important factor affecting the rate of TBW decrease.

Leach, Carolyn S.↗

Effect of Interlayer Time-Lapse and Workability Retention on Printed Concrete Performance

The rapid advancement of additive manufacturing technologies for concrete construction requires further understanding of material performance and its relationship with print parameters such as interlayer time-lapse and workability retention during the print. Here this study addresses the effects of the time delay between consecutive extruded layers on the mechanical performance of printed concrete using a mix designed by Quikrete. A series of specimens were prepared with printing delays of 10, 15, 30, and 60 min. This work correlates the change in fracture properties, mechanical performance, and workability retention with the interlayer time-lapse between two consecutive concrete layers. Interlayer time-lapse is defined as the time difference in printing of two consequent layers of concrete. It affects individual properties differently based on the loading direction and test types, but it is consistent in terms of interlayer performance. The understanding of the effect of interlayer time-lapse on the fracture properties between two consecutive printed layers fills the knowledge gaps in printed concrete research. Therefore, this study can help researchers perform required optimization and safely estimate the performance of printed concrete.

3D printing↗