Environmental Stress Exposure Research Articles

Consider the context: understanding how individual, interpersonal, and environmental stress exposures impact sleep

Consider the context: understanding how individual, interpersonal, and environmental stress exposures impact sleep

Single domain von Willebrand factor type C "cytokines" and the regulation of the stress/immune response in insects.

The single domain von Willebrand factor type C (SVWC) appears in small secreted peptides that are arthropod-specific and are produced following environmental stress or pathogen exposure. Most research has focused on proteins with SVWC domain that are induced after virus infection and are hypothesized to function as "cytokines" to regulate the innate immune response. The expansion of SVWC genes in insect species indicates that many other functions remain to be discovered. Research in shrimp has elucidated the adaptability of Vago-like peptides in the innate immune response against bacteria, fungi and viruses after activation by Jak-STAT and/or Toll/Imd pathways in which they can act as pathogen-recognition receptors or cytokine-like signaling molecules. SVWC factors also appear in scorpion venoms and tick saliva, underlining their versatility to acquire new functions. This review discusses the discovery and function of SVWC peptides from insects to crustaceans and chelicerates and reveals the enormous gaps in knowledge that remain to be filled to understand this enigmatic group of secreted peptides.

Environmental and genealogical effects on DNA methylation in a widespread apomictic dandelion lineage.

DNA methylation in plant genomes occurs in different sequences and genomic contexts that have very different properties. DNA methylation that occurs in CG (mCG) sequence context shows transgenerational stability and high epimutation rate, and can thus provide genealogical information at short time scales. However, due to meta-stability and because mCG variants may arise due to other factors than epimutation, such as environmental stress exposure, it is not clear how well mCG captures genealogical information at micro-evolutionary time scales. Here, we analysed DNA methylation variation between accessions from a geographically widespread, apomictic common dandelion (Taraxacum officinale) lineage when grown experimentally under different light conditions. Using a reduced-representation bisulphite sequencing approach, we show that the light treatment induced differentially methylated cytosines (DMCs) in all sequence contexts, with a bias towards transposable elements. Accession differences were associated mainly with DMCs in CG context. Hierarchical clustering of samples based on total mCG profiles revealed a perfect clustering of samples by accession identity, irrespective of light conditions. Using microsatellite information as a benchmark of genetic divergence within the clonal lineage, we show that genetic divergence between accessions correlates strongly with overall mCG profiles. However, our results suggest that environmental effects that do occur in CG context may produce a heritable signal that partly dilutes the genealogical signal. Our study shows that methylation information in plants can be used to reconstruct micro-evolutionary genealogy, providing a useful tool in systems that lack genetic variation such as clonal and vegetatively propagated plants.

FMR1 CGG Repeats and Stress Influence Self-Reported Cognitive Functioning in Mothers.

Variation in the FMR1 gene may affect aspects of cognition, such as executive function and memory. Environmental factors, such as stress, may also negatively impact cognitive functioning. Participants included 1,053 mothers of children with and without developmental disabilities. Participants completed self-report measures of executive function, memory, and stress (i.e., life events, parenting status), and provided DNA to determine CGG repeat length (ranging from 7 to 192 CGGs). Stress exposure significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems. Cubic CGG effects independently predicted executive function and memory difficulties, suggesting effects of both genetic variation and environmental stress exposure on cognitive functioning.

Condition assessment of cable insulation materials in advanced reactor environments

While existing cable insulation materials are sufficient for use in the current reactor fleet, environmental conditions inside some advanced reactors, such as small modular reactors, will be substantially harsher. The work herein was conducted to assess the performance and overall survivability of several high-temperature, radiation resistant insulation polymers in a simulated small modular reactor environment. The materials evaluated under this research include polyether ether ketone, polyimide, and silicone rubber. These polymers were subjected to 1000 h of environmental stress exposure under two different conditions: 1) high temperature (i.e., 250 °C) in atmospheric pressure and 2) high temperature in a low-pressure vacuum (i.e., less than 2 psia). During the environmental exposure process, each insulation was periodically tested using several materials characterization techniques including Fourier transform infrared spectroscopy, oxidation induction time, and oxidation induction temperature. The objective of this testing was to assess and monitor changes that occurred in the thermal and chemical properties of the materials during the environmental exposures. The overall survivability of each insulation was assessed based on these property changes. The results of this research revealed that the polyimide and polyether ether ketone insulations had significantly better thermal and chemical stability than the silicone rubber during both the high-temperature atmospheric and vacuum exposures. Both polyimide and polyether ether ketone experienced minimal reductions in their chemical and thermal properties over the course of 1000 h in the simulated environments. Based on this research, polyimide and polyether ether ketone show promise as potential base materials for small modular reactor cable insulation.

Indication of the impact of environmental stress on the responses of the bivalve mollusk Unio tumidus to ibuprofen and microplastics based on biomarkers of reductive stress and apoptosis

The vulnerability of bivalve mollusks to micropollutants is estimated mainly in single model exposures. However, chronic environmental stress and complex exposures can modulate their responses. To evaluate the impact of population-dependent adaptations on the ability to react to common micropollutants, we compared freshwater bivalves Unio tumidus from two distinct populations, pure (Pr) and contaminated (Ct), in their exposures to microplastics (MP, 1 mg L−1, size 0.1–0.5 mm), pharmaceutical ibuprofen (IBU, 0.8 μg L−1), or their combination (Mix) for 14 days. Control groups from both sites showed remarkable differences, with lower levels of total antioxidant capacity (TAC), metallothionein protein (MTSH), NADH and NAD+, cytochrome P450-related EROD, glutathione-S transferase (GST), and citrate synthase (CS) but higher levels of GSH, GSSG, caspase-3 and cathepsin D (CTD) in the Ct-control group. These data indicate a chronic stress impact in the Ct population. Under exposures, we found an almost common strategy in both populations for NAD+/NADH and MTSH suppression and CTD induction. Additionally, Mix exposure caused an increase in CS, and IBU did not change GSH in both populations. However, the expected response to IBU – the suppression of caspase-3 – was indicated only in PrIBU- and PrMix-mollusks. CTD efflux increased dramatically only in PrMP- and PrMix- groups, and suppression of EROD and GST was detected in the PrMix-group. According to discriminant analysis, exposed Pr-groups were highly differentiated from control, whereas Ct-control and exposed groups had common localization demonstrating high resistance to environmental stress. Thus, the same exposures resulted in different adverse outcome pathways depending on the population.

Engineering astaxanthin accumulation reduces photoinhibition and increases biomass productivity under high light in Chlamydomonas reinhardtii

BackgroundAstaxanthin is a highly valuable ketocarotenoid with strong antioxidative activity and is natively accumulated upon environmental stress exposure in selected microorganisms. Green microalgae are photosynthetic, unicellular organisms cultivated in artificial systems to produce biomass and industrially relevant bioproducts. While light is required for photosynthesis, fueling carbon fixation processes, application of high irradiance causes photoinhibition and limits biomass productivity.ResultsHere, we demonstrate that engineered astaxanthin accumulation in the green alga Chlamydomonas reinhardtii conferred high light tolerance, reduced photoinhibition and improved biomass productivity at high irradiances, likely due to strong antioxidant properties of constitutively accumulating astaxanthin. In competitive co-cultivation experiments, astaxanthin-rich Chlamydomonas reinhardtii outcompeted its corresponding parental background strain and even the fast-growing green alga Chlorella vulgaris.ConclusionsMetabolic engineering inducing astaxanthin and ketocarotenoids accumulation caused improved high light tolerance and increased biomass productivity in the model species for microalgae Chlamydomonas reinhardtii. Thus, engineering microalgal pigment composition represents a powerful strategy to improve biomass productivities in customized photobioreactors setups. Moreover, engineered astaxanthin accumulation in selected strains could be proposed as a novel strategy to outperform growth of other competing microalgal strains.

Monitoring shallow coral reef exposure to environmental stressors using satellite earth observation: the reef environmental stress exposure toolbox (RESET)

AbstractCoral reefs are significantly threatened by multiple environmental stressors associated with climate change. While there is growing recognition of the importance of interacting stressors on coral reefs, so far this has been primarily limited to in situ studies. Satellite remote sensing has potential for investigating coral reef exposure to multiple environmental stressors at a global scale over multiple years; however, current satellite monitoring is primarily focused on thermal stress. Here we collate nine environmental variables (cloud cover, current, depth, salinity, wind, and four sea surface temperature‐based metrics) from readily available satellite datasets using the Google Earth Engine geospatial processing platform. Using ecological and health‐based thresholds obtained from the literature, we developed, using fuzzy logic (discontinuous functions), a Reef Environmental Stress Exposure Toolbox (RESET) for monitoring environmental stress exposure at multiple scales. Stress exposure scores for 3157 reefs were generated and mapped globally across 12 coral reef ecosystem regions. RESET was also applied to three case‐study reefs, previously well monitored for stress and disturbance using other methods. PCA analysis indicated that depth, current, sea surface temperature (SST) and SST anomaly accounted for the greatest contribution to the variance in environmental stress exposure in these three regions. Depth, degree heating weeks, and SST anomaly were identified as the potential drivers of inter‐ and intra‐region variation in environmental stress exposure. Individual variables were then integrated into a multi‐metric index of combined stress exposure which corroborated temporal and spatial differences due to known disturbance events. RESET provides a open access, easily interpretable set of tools and associated indices for monitoring environmental stress exposure on coral reefs, designed to inform conservation and management decisions. As such RESET has broad potential to assist in the monitoring of our increasingly imperilled coral ecosystems, in particular, those that are remote or inaccessible.

Partial recovery of voiding function in female mice following repeated psychological stress exposure.

Psychological stress causes bladder dysfunction in humans and in rodent models, with increased urinary frequency and altered contractile responses evident following repeated environmental stress exposure. However, whether these changes persist after removal of the stressor is unknown, and the aim of this study was to determine if stress-induced changes in voiding behaviour and bladder function recover following removal of the stressor. Adult female mice were allocated to three groups: Unstressed, Stressed or Stressed + Recovery. Animals in the stressed groups were exposed to water avoidance stress for 1h/day for 10-days, with unstressed animals age-matched and housed under normal conditions. For recovery studies, animals were housed without stress exposure for an additional 10-days. Voiding behaviour was assessed periodically and animals sacrificed on day 10 (Unstressed and Stressed) or day 20 (Unstressed and Stressed + Recovery). Isolated whole bladder studies were used to assess compliance, urothelial mediator release and contractile responses. Exposure to stress increased plasma corticosterone levels almost three-fold (P<0.05) but this returned to baseline during the recovery period. Contractile responses of the bladder to carbachol and KCl were also increased following stress, and again fully recovered after a 10-day stress-free period. In contrast, stress increased urinary frequency four-fold (P<0.001), but this did not return fully to baseline during the recovery period. Bladder compliance was unchanged by stress; however, it was increased in the stressed + recovery group (P<0.05). Thus, following a stress-free period there is partial recovery of voiding behaviour, with an increase in bladder compliance possibly contributing to the compensatory mechanisms.

Sugar transporters and their molecular tradeoffs during abiotic stress responses in plants.

Sugars as photosynthates are well known as energy providers and as building blocks of various structural components of plant cells, tissues and organs. Additionally, as a part of various sugar signaling pathways, they interact with other cellular machinery and influence many important cellular decisions in plants. Sugar signaling is further reliant on the differential distribution of sugars throughout the plant system. The distribution of sugars from source to sink tissues or within organelles of plant cells is a highly regulated process facilitated by various sugar transporters located in plasma membranes and organelle membranes, respectively. Sugar distribution, as well as signaling, is impacted during unfavorable environments such as extreme temperatures, salt, nutrient scarcity, or drought. Here, we have discussed the mechanism of sugar transport via various types of sugar transporters as well as their differential response during environmental stress exposure. The functional involvement of sugar transporters in plant's abiotic stress tolerance is also discussed. Besides, we have also highlighted the challenges in engineering sugar transporter proteins as well as the undeciphered modules associated with sugar transporters in plants. Thus, this review provides a comprehensive discussion on the role and regulation of sugar transporters during abiotic stresses and enables us to target the candidate sugar transporter(s) for crop improvement to develop climate-resilient crops.

In vivo study of dose-dependent antioxidant efficacy of functionalized core\u2013shell yttrium oxide nanoparticles

Herein, we assess the dose-dependent antioxidant efficacy of ultrafine spherical functionalized core–shell yttrium oxide nanoparticles (YNPs) with a mean size of 7–8 nm and modified with poly EGMP (ethylene glycol methacrylate phosphate) and N-Fluorescein Acrylamide. The antioxidant properties of these nanoparticles were investigated in three groups of Sprague–Dawley rats (10 per group) exposed to environmental stress daily for 1 week and one control group. Groups 2 and 3 were intravenously injected twice a week with YNPs at 0.3 and 0.5 mg at 2nd and 5th day of environmental stress exposure respectively. Different samples of blood and serum were collected from all experimental groups at end of the experiment to measure oxidative biomarkers such as total antioxidant capacity (TAC), hydroxyl radical antioxidant capacity (HORAC), oxygen radical antioxidant capacity (ORAC), malondialdehyde (MDA), and oxidants concentration as hydrogen peroxide (H2O2). The liver, brain, and spleen tissues were collected for fluorescence imaging and histopathological examination in addition to brain tissue examination by transmission electron microscope (TEM). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to estimate YNPs translocation and concentration in tissues which is consecutively dependent on the dose of administration. Depending on all results, poly EGMP YNPs (poly EGMP yttrium oxide nanoparticles) can act as a potent direct antioxidant in a dose-dependent manner with good permeability through blood–brain barrier (BBB). Also, the neuroprotective effect of YNPs opening the door to a new therapeutic approach for modulating oxidative stress–related neural disorders.Highlights• The dose-dependent antioxidant efficacy of ultrafine spherical functionalized core–shell yttrium oxide nanoparticles (YNPs) with a mean size of 7–8 nm and modified with poly EGMP (ethylene glycol methacrylate phosphate) and N-Fluorescein Acrylamide was assessed.• The dose of administration directly affecting the brain, liver, and spleen tissues distribution, retention, and uptake of YNPs and direct correlation between the absorbed amount and higher dose administered.• YNPs can act as a potent direct antioxidant in a dose-dependent manner with good permeability through blood–brain barrier (BBB).Graphical abstract

Characterizing sustained social anxiety in individuals at clinical high risk for psychosis: trajectory, risk factors, and functional outcomes.

While comorbidity of clinical high-risk for psychosis (CHR-P) status and social anxiety is well-established, it remains unclear how social anxiety and positive symptoms covary over time in this population. The present study aimed to determine whether there are more than one covariant trajectory of social anxiety and positive symptoms in the North American Prodrome Longitudinal Study cohort (NAPLS 2) and, if so, to test whether the different trajectory subgroups differ in terms of genetic and environmental risk factors for psychotic disorders and general functional outcome. In total, 764 CHR individuals were evaluated at baseline for social anxiety and psychosis risk symptom severity and followed up every 6 months for 2 years. Application of group-based multi-trajectory modeling discerned three subgroups based on the covariant trajectories of social anxiety and positive symptoms over 2 years. One of the subgroups showed sustained social anxiety over time despite moderate recovery in positive symptoms, while the other two showed recovery of social anxiety below clinically significant thresholds, along with modest to moderate recovery in positive symptom severity. The trajectory group with sustained social anxiety had poorer long-term global functional outcomes than the other trajectory groups. In addition, compared with the other two trajectory groups, membership in the group with sustained social anxiety was predicted by higher levels of polygenic risk for schizophrenia and environmental stress exposures. Together, these analyses indicate differential relevance of sustained v. remitting social anxiety symptoms in the CHR-P population, which in turn may carry implications for differential intervention strategies.

Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity

Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype.

Inhibition of DNA methylation in newborns reprograms ischemia-sensitive biomarkers resulting in development of a heart ischemia-sensitive phenotype late in life

Adverse environmental stress exposure at critical perinatal stages can alter cardiovascular development, which could persist into adulthood and develop a cardiovascular dysfunctional phenotype late in life. However, the underlying molecular mechanisms remain largely unknown. The present study provided a direct evidence that DNA methylation is a key epigenetic mechanism contributing to the developmental origins of adult cardiovascular disease. We hypothesized that DNA hypomethylation at neonatal stage alters gene expression patterns in the heart, leading to development of a cardiac ischemia-sensitive phenotype late in life. To test this hypothesis, a DNA methylation inhibitor 5-Aza-2-deoxycytidine (5-Aza) was administered in newborn rats from postnatal day 1–3. Cardiac function and related key genes were measured in 2-week- and 2-month-old animals, respectively. 5-Aza treatment induced an age- and sex-dependent inhibition of global and gene-specific DNA methylation levels in left ventricles, resulting in a long-lasting growth restriction but an asymmetry increase in the heart-to-body weight ratio. In addition, treatment with 5-Aza enhanced ischemia and reperfusion-induced cardiac dysfunction and injury in adults as compared with the saline controls, which was associated with up-regulations of miRNA-181a and angiotensin II receptor type 1 & 2 gene expressions, but down-regulations of PKCε, Atg5, and GSK3β gene expressions in left ventricles. In conclusion, our results provide compelling evidence that neonatal DNA methylation deficiency is a key mechanism contributing to differentially reprogram cardiac gene expression patterns, leading to development of a heart ischemia-sensitive phenotype late in life.

Ecotoxicological effects of erythromycin on a multispecies biofilm model, revealed by metagenomic and metabolomic approaches.

The presence of antibiotics such as erythromycin, even in trace amounts, has long been acknowledged for negatively impacting ecosystems in freshwater environments. Although many studies have focused on the impact of antibiotic pollution at a macroecological level, the impact of erythromycin on microecosystems, such as freshwater biofilms, is still not fully understood. This knowledge gap may be attributed to the lack of robust multispecies biofilm models for fundamental investigations. Here, we used a lab-cultured multispecies biofilm model to elucidate the holistic response of a microbial community to erythromycin exposure using metagenomic and metabolomic approaches. Metagenomic analyses revealed that biofilm microbial diversity did not alter following erythromycin exposure. Notably, certain predicted metabolic pathways such as cell-cell communication pathways, amino acid metabolism, and peptidoglycan biosynthesis, mainly by the phyla Actinobacteria, Alpha/Beta-proteobacteria, Bacteroidetes, and Verrucomicrobia, were found to be involved in the maintenance of homeostasis-like balance in the freshwater biofilm. Further untargeted metabolomics data highlighted changes in lipid metabolism and linoleic acid metabolism and their related molecules as a direct consequence of erythromycin exposure. Overall, the study presented a unique picture of how multispecies biofilms respond to single environmental stress exposures. Moreover, the study demonstrated the feasibility of using lab simulated multispecies biofilms for investigating their interaction and reactivity of specific bioactive compounds or pollutants at a fundamental level.

Fetal growth restriction mice are more likely to exhibit depression-like behaviors due to stress-induced loss of dopaminergic neurons in the VTA.

Fetal growth restriction (FGR) is a severe perinatal complication that can increase risk for mental illness. To investigate the mechanism by which FGR mice develop mental illness in adulthood, we established the FGR mouse model and the FGR mice did not display obvious depression-like behaviors, but after environmental stress exposure, FGR mice were more likely to exhibit depression-like behaviors than control mice. Moreover, FGR mice had significantly fewer dopaminergic neurons in the ventral tegmental area but no difference in serotoninergic neurons in the dorsal raphe. RNA-seq analysis showed that the downregulated genes in the midbrain of FGR mice were associated with many mental diseases and were especially involved in the regulation of NMDA-selective glutamate receptor (NMDAR) activity. Furthermore, the NMDAR antagonist memantine can relieve the stress-induced depression-like behaviors of FGR mice. In summary, our findings provide a theoretical basis for future research and treatment of FGR-related depression.

Predicting Late Adolescent Anxiety From Early Adolescent Environmental Stress Exposure: Cognitive Control as Mediator.

Early exposure to stressful life events is associated with greater risk of chronic diseases and mental health problems, including anxiety. However, there is significant variation in how individuals respond to environmental adversity, perhaps due to individual differences in processing and regulating emotional information. Differences in cognitive control – processes necessary for implementing goal directed behavior – have been linked to both stress exposure and anxiety, but the directionality of these links is unclear. The present study investigated the longitudinal pathway of environmental stress exposure during early adolescence on later adolescent anxiety, and the possible mediating mechanism of cognitive control. Participants were 674 Mexican-origin adolescents (meanage = 10.8 years, 50% male) enrolled in the California Families Project, an ongoing longitudinal study of Mexican-origin families. In the current analysis, we examined self-reports of environmental stressors at age 14 (Time 1), cognitive control at age 16 (Time 2), and anxiety at age 18 (Time 3). Structural equation modeling revealed that environmental stressors (Time 1) had both direct and indirect effects on later anxiety (Time 3) through their effects on cognitive control (Time 2), even when accounting for prior levels of anxiety (Time 2). Cognitive control accounted for 18% of the association between environmental stressors and adolescent anxiety: an increase in stressors decreased cognitive control (β = −0.20, p < 0.001), however, cognitive control buffers against anxiety (β = −0.10, p = 0.004). These findings deepen our understanding of the mechanisms underlying the development of anxiety and highlight the importance of cognitive control as a potential protective factor.

Using Electron Paramagnetic Resonance Spectroscopy to Determine the Role of Free‐Radical Protection in Tardigrade Survival Mechanisms

As aeronautic technology advances, so does the possibility of long‐term space travel and exploration. However, in order to make significant strides, it is first necessary to determine how to survive the antagonistic space environment, including temperature extremes, UVC radiation, and vacuum pressures, among others. Tardigrades are microscopic invertebrates that possess the ability to adapt to extreme environments through the formation of a tun, a dormant structure resulting from the downregulation of metabolism. This ability to survive under extreme conditions, including arctic temperatures, extreme heat, and a pure vacuum, makes tardigrades a useful model organism for space survival. By increasing our understanding of their survival mechanisms on a fundamental level, we may be able to generate technologies that protect humans in space from diseases caused by ROS and the damaging effects of oxidative stress.Previous research has examined the physiological response of tardigrades subjected to freezes and irradiation that model outer Earth conditions. In these studies, tardigrades were shown to enter tun formation through cryptobiosis, especially in response to physical stressors causing desiccation. Another study assessed tardigrades’ intergalactic survival capability by sending a culture into the vacuum of space, after which the cultures showed no loss of viability. We hypothesize that tardigrades have a specific, protective mechanism to respond to oxidative stress through the increased expression of superoxide dismutases (SODs) to break down potentially harmful ROS, which is supported by previous studies showing both the formation of superoxide radicals as well as an increase in SODs in desiccated animals.In this study, X‐band continuous wave electron paramagnetic resonance (EPR) spectroscopy was used to measure the presence of superoxide radicals in the tardigrade Hypsibius exemplaris before and after exposure to environmental stressors. Tardigrades were subjected to a combination of UVA and UVB irradiation before the addition of a spin probe, and the resulting EPR spectrum was compared to a nonirradiated H. exemplaris control. Results show that the tardigrades generated less ROS following environmental stress exposure, supporting the hypothesis of a protective mechanism to mediate radical production when subject to harsh conditions. Studies concerning other physical and chemical stressors, as well as examining radical production in tardigrades upon inducing tun formation, are ongoing. Further experiments also include determining specific activities of proteinaceous antioxidants like SOD before and after these exposures.Support or Funding InformationJ.R.C was supported the SURE Program funded through the West Virginia Research Challenge Fund, and administered by the West Virginia HEPC, DSR, Award Number DSR.17.09,the WV NASA Space Grant Consortium's NASA WV Space Grant Undergraduate Fellowship Program and from a Marshall University Creative Discover &amp; Undergraduate Research Award.D.R.J.K. and A.L.S. were supported by the National Science Foundation under Cooperative Agreement No. OIA‐1458952.

Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome.

Wound-healing is a dynamic skin reparative process that results in a sequence of events, including inflammation, proliferation, and migration of different cell types as fibroblasts. Fibroblasts play a crucial role in repairing processes, from the late inflammatory phase until the fully final epithelization of the injured tissue. Within this context, identifying tools able to implement cell proliferation and migration could improve tissue regeneration. Recently, plants species from all over the world are coming out as novel tools for therapeutic applications thanks to their phytochemicals, which have antioxidant properties and can promote wound healing. In this paper, we aimed at investigating antioxidant activity of waste extracts from different medicinal plants, endemic of the Mediterranean area, on fibroblast proliferation and wound healing. We determined the amount of total phenols and anti-oxidant activity by ABTS assay. We then evaluated the cytotoxicity of the compounds and the proliferative capabilities of fibroblasts by scratch assay. Our results showed that waste extracts retain antioxidant and regenerative properties, inducing tissue re-establishment after environmental stress exposure. Taken together, our findings suggest that waste material could be used in the future also in combinations to stimulate wound healing processes and antioxidant responses in damaged skin.

Fetal Growth Restriction Mice Are More Likely to Exhibit Depression-Like Behaviors&nbsp;Due to Stress-Induced Loss of Dopamine Neurons in the VTA

Background: Fetal growth restriction (FGR) is a severe perinatal complication that can cause increased risk for mental illness, while the mechanism is still unclear. We used FGR mouse model to study the mental state of the FGR offspring in adulthood. Methods: FGR mouse model was conducted as following: pregnant C57BL/6J mice were injected with dexamethasone (1 mg/kg) intraperitoneally from E14.5 to E18.5 or restricted with low-protein diet. Adult FGR mice were examined in a series of behavioral tests pre-and post- environmental stress. Immunofluorescent staining and HPLC were used to detect the neuron number and neurotransmitter level. Furthermore, RNA sequencing was used to capture transcriptome-wide alterations in the midbrain of neonatal FGR mice compared to the control ones. Findings: The FGR mice were more likely to exhibit depression-like behaviors than control mice after environmental stress exposure. The main cause of that was significantly fewer dopaminergic neurons in the ventral tegmental area (VTA) induced by environmental stress. Abnormal regulation of NMDAR activity in FGR mice caused the loss of midbrain VTA dopaminergic neurons exposed to environmental stress. Consistently, the NMDA receptor antagonist memantine inhibited neuronal apoptosis and relieved the stress-induced depression-like behaviors of FGR mice. Interpretation: We demonstrated abnormal regulation of NMDAR activity in FGR mice caused the loss of midbrain VTA dopaminergic neurons and depression-like behaviors exposed to environmental stress, and memantine can ameliorate stress-induced depression-like behaviors of FGR mice. Funding Statement: This work was supported by the National Natural Science Foundation of China (grants 81530042, 31871495, 31571529, 31571519), the Ministry of Science and Technology (grant 2016YFA0101300). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All procedures involving animals were approved by the Laboratory Animal Care Committee of Tongji University in accordance with the Guide for the Care and Use of Laboratory Animals (NIH).