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1.
Curr Protoc ; 4(6): e1064, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38837737

ABSTRACT

Caloric restriction has been found to extend the lifespan of many organisms including mammals and other vertebrates. With lifespans exceeding months to years, age-related experiments involving fish and mammals can be overtly costly, both in terms of time and funding. The freshwater crustacean, Daphnia, has a relatively short lifespan (∼50 to 100 days), which makes it a cost-effective alternative animal model for longevity and aging studies. Besides age-specific mortality, there are a suite of physiological responses connected to "healthspan" that can be tracked as these animals age including growth, reproduction, and metabolic rates. These responses can be complemented by assessment of molecular and cellular processes connected to aging and health. Lifespan and metabolism of this model organism is responsive to long studied modulators of aging, such as rearing temperature and nutritional manipulation, but also pharmacological agents that target aging, e.g., rapamycin, which adds to its usefulness as a model organism. Here we describe how to culture Daphnia for aging experiments including maintaining laboratory populations of Daphnia mothers, growing algal food, and manipulating nutrition of these animals. In addition, we provide methods for tracking common physiological and longevity responses of Daphnia. This protocol provides researchers planning to use this model organism with methods to establish and maintain Daphnia populations and to standardize their experimental approaches. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Culturing algae for Daphnia food Basic Protocol 2: General methods for culturing Daphnia Basic Protocol 3: Standardizing and controlling nutrition for experimental Daphnia Basic Protocol 4: Monitoring Daphnia lifespan Basic Protocol 5: Evaluating Daphnia health: Heart rate and respiration, body mass and growth rates, and reproduction.


Subject(s)
Daphnia , Longevity , Animals , Daphnia/physiology , Daphnia/growth & development , Life History Traits , Animal Nutritional Physiological Phenomena , Reproduction/physiology , Aging/physiology
2.
Physiol Rep ; 11(23): e15870, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38040455

ABSTRACT

Cytokinins (CTKs) are a diverse collection of evolutionarily conserved adenine-derived signaling molecules classically studied as phytohormones; however, their roles and production have been less studied in mammalian systems. Skeletal muscles are sensitive to cellular cues such as inflammation and in response, alter their secretome to regulate the muscle stem cell and myofiber niche. Using cultured C2C12 muscle cells, we profiled CTK levels to understand (1) whether CTKs are part of the muscle secretome and (2) whether CTKs are responsive to cellular stress. To induce cellular stress, C2C12 myotubes were treated with lipopolysaccharides (LPS) for 24 h and then media and cell fractions were collected for ultra high-performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC-(ESI+)-HRMS/MS) for metabolomics and CTK profiling. Across LPS-treated and control cells, 11 CTKs were detected in the extracellular space while 6 were detected intracellularly. We found that muscle cells are enriched in isopentenyladenine (iP) species (from free base, riboside to nucleotide forms), and that extracellular levels are increased after LPS treatment. Our study establishes that muscle cells express various forms of CTKs, and that CTK levels are responsive to LPS-induced cell stress, suggesting a role for CTKs in intra- and extracellular signaling of mammalian cells.


Subject(s)
Cytokinins , Lipopolysaccharides , Cytokinins/chemistry , Lipopolysaccharides/pharmacology , Adenine/pharmacology , Muscle Fibers, Skeletal
3.
Pers Soc Psychol Bull ; : 1461672231210465, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37997811

ABSTRACT

Anonymous environments are more accessible than ever. As such, it is important to understand not only how anonymity can change human behavior but also why people are motivated to seek anonymity in online spaces. In four studies, we investigated differences in motivations for seeking anonymity online and their associations with related dispositional factors and online behavior. We found that some people were motivated to seek anonymity to self-express or behave toxically. Both motivations to seek anonymity were associated with low self-concept clarity and high Machiavellianism but differed in their relation to traits such as self-consciousness and psychopathy. Further analyses suggested that people selectively engage in behaviors in anonymous online environments, in line with the specific gratifications they seek through anonymity. We conclude that people seek anonymity to pursue self- or other-related goals that are otherwise more difficult or costly to pursue when identifiable.

4.
Front Psychol ; 14: 1211023, 2023.
Article in English | MEDLINE | ID: mdl-37885740

ABSTRACT

Online trolling is often linked to sadism and psychopathy. Yet, little research has assessed why people high in these traits seek online environments to achieve their nefarious goals. We employ a functionalist approach to examine whether people high in sadism and psychopathy are motivated to seek the affordances of online environments (e.g., anonymity) to reveal their malevolent self-aspects by engaging in trolling behavior. A sample of 515 university undergraduates (Mage = 20.47) read vignettes depicting trolling incidents and rated the acceptability of the perpetrators' actions and whether they had ever written similar comments. Participants then completed measures of psychopathy, sadism, and toxic anonymous motivations. We find that toxic anonymous motivations partially mediate the relationship between psychopathy and sadism, and online trolling. Whereas trolling is often understood through its underlying personality traits, toxic motivations to seek anonymity may be a more proximal predictor of who is likely to troll online.

5.
Am J Physiol Heart Circ Physiol ; 323(4): H609-H627, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35960634

ABSTRACT

Cardiac cachexia is a catabolic muscle-wasting syndrome observed in approximately 1 in 10 patients with heart failure. Increased skeletal muscle atrophy leads to frailty and limits mobility, which impacts quality of life, exacerbates clinical care, and is associated with higher rates of mortality. Heart failure is known to exhibit a wide range of prevalence and severity when examined across individuals of different ages and with comorbidities related to diabetes, renal failure, and pulmonary dysfunction. It is also recognized that men and women exhibit striking differences in the pathophysiology of heart failure, as well as skeletal muscle homeostasis. Given that both skeletal muscle and heart failure physiology are in part sex-dependent, the diagnosis and treatment of cachexia in patients with heart failure may depend on a comprehensive examination of how these organs interact. In this review, we explore the potential for sex-specific differences in cardiac cachexia. We summarize advantages and disadvantages of clinical methods used to measure muscle mass and function and provide alternative measurements that should be considered in preclinical studies. In addition, we summarize sex-dependent effects on muscle wasting in preclinical models of heart failure, disuse, and cancer. Lastly, we discuss the endocrine function of the heart and outline unanswered questions that could directly impact patient care.


Subject(s)
Cachexia , Heart Failure , Cachexia/etiology , Female , Humans , Male , Muscle, Skeletal/metabolism , Muscular Atrophy/etiology , Muscular Atrophy/metabolism , Quality of Life
6.
Cyberpsychol Behav Soc Netw ; 25(8): 527-533, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35647884

ABSTRACT

Past research found that compassionate goals were associated with more responsive behaviors on Facebook, which in turn were associated with greater social capital. The current study aimed to examine whether compassionate goals were associated with greater well-being, through greater efforts to visibly attend to Facebook friends and feeling more connected to Facebook friends. We predicted that there would be an indirect effect of compassionate goals on satisfaction with life through Facebook relationship maintenance behaviors and Facebook social connectedness. Two hundred sixty-two adult Facebook users completed an online questionnaire containing measures of compassionate goals, Facebook relationship maintenance behaviors, Facebook social connectedness, satisfaction with life, and various control variables (Big Five personality traits, self-image goals, frequency and duration of Facebook use, number of Facebook friends, age, and gender). A serial mediation analysis revealed a significant indirect effect of compassionate goals on satisfaction with life through Facebook relationship maintenance behaviors and Facebook social connectedness. Higher levels of compassionate goals predicted more Facebook relationship maintenance behaviors, more Facebook relationship maintenance behaviors predicted greater Facebook social connectedness, and greater Facebook social connectedness predicted higher satisfaction with life. The indirect effect was significant with and without controlling for other aspects of Facebook use, self-image goals, Big Five personality traits, gender, age, and recruitment method. These findings replicate and extend past research by establishing new pathways and outcomes associated with compassionate goals. Overall, this study contributes important insights into supportive and beneficial ways of using social media.


Subject(s)
Social Media , Adult , Empathy , Friends , Goals , Humans , Self Concept
7.
Cyberpsychol Behav Soc Netw ; 25(5): 310-315, 2022 May.
Article in English | MEDLINE | ID: mdl-35506934

ABSTRACT

Video games can satisfy people's basic psychological needs of autonomy, competence, and relatedness. This may lead them to develop a passion for the activity, which can be harmonious or obsessive. These different types of passions are associated with different well-being outcomes: harmonious passion (HP) is associated with positive effects such as Satisfaction with Life (SWL), obsessive passion (OP) is associated with adverse effects such as psychological distress. Although time spent playing video games has sometimes been found to be a predictor of poor well-being, there is a lack of understanding in its role in explaining the relationship between passion and well-being compared with other factors. Self-regulation is an important factor in predicting habits, including video game play. In this cross-sectional study (N = 182), we investigated whether self-regulation or playtime better mediated the associations between different passion orientations and well-being (i.e., SWL, global subjective well-being, and psychological distress) among video game players. A path analysis revealed that people with higher HP for video games reported higher levels of self-regulation and those with higher OP for video games reported lower levels of self-regulation. Our findings also indicate that self-regulation provides a more comprehensive explanation for the relationship between passion and well-being. Overall, this study provides further support for the importance of self-regulation as a determinant of well-being in video game players rather than more arguably surface-level metrics such as time spent playing. These findings have implications for game developers and clinicians who design interventions for individuals who may experience unregulated video game play.


Subject(s)
Self-Control , Video Games , Cross-Sectional Studies , Humans , Motivation , Surveys and Questionnaires , Video Games/psychology
8.
Cyberpsychol Behav Soc Netw ; 25(6): 377-383, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35594292

ABSTRACT

Research assessing online trolling-a behavior designed to trigger or antagonize other users for entertainment-has largely focused on identifying individual differences that underlie the behavior. Less attention has been given to how situational factors influence trolling, such as the disinhibiting effects of anonymity. In this study, we evaluated the roles of both individual differences and levels of anonymity in online trolling. We assessed these through experimentation, a relatively novel approach in trolling research. Australian undergraduate students (n = 242, 167 women, 75 men, Mage = 21.18) were allocated to one of three conditions: an anonymous condition where they were not visible to one another, an identifiable condition where they were visible to one another, or an external condition where they completed the study outside of a controlled laboratory environment. Participants first read a short news article before interacting in an online group discussion where participants could chat freely. The first comment participants wrote was later coded for trolling. Participants also completed assessments of psychopathy, sadism, and a global assessment of trolling. As predicted, participants in the anonymous condition trolled more than those in the identifiable condition. No differences were seen between these two conditions and the external condition. Analyses also revealed that sadism and global trolling were positively associated with trolling in the chat room, but psychopathy showed no association. These results demonstrate the importance of both individual differences and the disinhibiting effects of anonymity when investigating the complex nature of trolling.


Subject(s)
Antisocial Personality Disorder , Sadism , Adult , Attention , Australia , Female , Humans , Male , Students , Young Adult
9.
PLoS One ; 17(4): e0265806, 2022.
Article in English | MEDLINE | ID: mdl-35385493

ABSTRACT

The aim of this preregistered study was to identify dispositional predictors of podcast listening and examine the associations between aspects of podcast listening, dispositional predictors, and psychological outcomes. Three hundred and six adults from a range of countries completed an online questionnaire that assessed individual difference predictors (the Big Five personality factors, curiosity, need for cognition, need to belong, age, and gender), aspects of podcast listening (amount, format, setting, device, and social aspects), and potential outcomes (autonomy, competence, relatedness, meaning, mindfulness, and smartphone addiction). As predicted, openness to experience, interest-based curiosity, and need for cognition positively predicted podcast listening. Contrary to predictions, need to belong negatively predicted podcast listening, and time spent listening to podcasts was not associated with autonomy, competence, relatedness, meaning, mindfulness, or smartphone addiction. However, certain aspects of podcast listening (e.g., parasocial relationships and social engagement) were related to positive outcomes and to our predictor variables. Furthermore, neuroticism negatively predicted podcast listening. Overall, the findings support the idea that informational motives can play a role in podcast listening, and that some aspects of listening are associated with positive outcomes.


Subject(s)
Motivation , Personality , Adult , Auditory Perception , Humans , Neuroticism , Surveys and Questionnaires
10.
Aging (Albany NY) ; 13(11): 14687-14708, 2021 06 04.
Article in English | MEDLINE | ID: mdl-34088884

ABSTRACT

Bone marrow mononuclear cell therapy improves cardiac repair after myocardial infarction (MI), in-part through signaling to resident cardiac cells, such as fibroblasts, which regulate scar formation. The efficacy of cell therapy declines with age, as aging of both donor and recipient cells decreases repair responses. Autophagy regulates the microenvironment by both extracellular vesicle (EV)-dependent and independent secretion pathways. We hypothesized that age-related autophagy changes in bone marrow cells (BMCs) alter paracrine signaling, contributing to lower cell therapy efficacy. Here, we demonstrate that young Sca-1+ BMCs exhibited a higher LC3II/LC3I ratio compared to old Sca-1+ BMCs, which was accentuated when BMCs were cultured under hypoxia. To examine the effect on paracrine signaling, old cardiac fibroblasts were cultured with conditioned medium (CM) from young and old Sca-1+ BMCs. Young, but not old CM, enhanced fibroblast proliferation, migration, and differentiation, plus reduced senescence. These beneficial effects were lost when autophagy or EV secretion in BMCs was blocked pharmacologically, or by siRNA knockdown of Atg7. Therefore, both EV-dependent and -independent paracrine signaling from young BMCs is responsible for paracrine stimulation of old cardiac fibroblasts. In vivo, bone marrow chimerism of old mice with young BMCs increased the number of LC3b+ cells in the heart compared to old mice reconstituted with old BMCs. These data suggest that the deterioration of autophagy with aging negatively impacts the paracrine effects of BMCs, and provide mechanistic insight into the age-related decline in cell therapy efficacy that could be targeted to improve the function of old donor cells.


Subject(s)
Aging/pathology , Autophagy , Bone Marrow Cells/metabolism , Leukocytes, Mononuclear/metabolism , Paracrine Communication , Animals , Antigens, Ly/metabolism , Autophagy/drug effects , Autophagy-Related Protein 7/metabolism , Culture Media, Conditioned/pharmacology , Extracellular Vesicles/drug effects , Extracellular Vesicles/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Leukocytes, Mononuclear/drug effects , Membrane Proteins/metabolism , Mice, Inbred C57BL , Myocardium/pathology , Paracrine Communication/drug effects , Transforming Growth Factor beta1/pharmacology
11.
Aging Cell ; 20(2): e13312, 2021 02.
Article in English | MEDLINE | ID: mdl-33511781

ABSTRACT

Recruited immune cells play a critical role in muscle repair, in part by interacting with local stem cell populations to regulate muscle regeneration. How aging affects their communication during myogenesis is unclear. Here, we investigate how aging impacts the cellular function of these two cell types after muscle injury during normal aging or after immune rejuvenation using a young to old (Y-O) or old to old (O-O) bone marrow (BM) transplant model. We found that skeletal muscle from old mice (20 months) exhibited elevated basal inflammation and possessed fewer satellite cells compared with young mice (3 months). After cardiotoxin muscle injury (CTX), old mice exhibited a blunted inflammatory response compared with young mice and enhanced M2 macrophage recruitment and IL-10 expression. Temporal immune and cytokine responses of old mice were partially restored to a young phenotype following reconstitution with young cells (Y-O chimeras). Improved immune responses in Y-O chimeras were associated with greater satellite cell proliferation compared with O-O chimeras. To identify how immune cell aging affects myoblast function, conditioned media (CM) from activated young or old macrophages was applied to cultured C2C12 myoblasts. CM from young macrophages inhibited myogenesis while CM from old macrophages reduced proliferation. These functional differences coincided with age-related differences in macrophage cytokine expression. Together, this study examines the infiltration and proliferation of immune cells and satellite cells after injury in the context of aging and, using BM chimeras, demonstrates that young immune cells retain cell autonomy in an old host to increase satellite cell proliferation.


Subject(s)
Cellular Senescence/immunology , Muscle Development/immunology , Satellite Cells, Skeletal Muscle/immunology , Animals , Cardiotoxins/pharmacology , Cellular Senescence/drug effects , Mice , Muscle Development/drug effects , Satellite Cells, Skeletal Muscle/drug effects
12.
Front Cell Dev Biol ; 8: 600304, 2020.
Article in English | MEDLINE | ID: mdl-33330489

ABSTRACT

BACKGROUND: Several long non-coding RNAs (lncRNAs) have been associated with cell senescence, termed senescence-associated lncRNAs (SAL-RNAs). However, the mechanisms involved for SAL-RNAs in aging are not fully elucidated. In the present study, we investigated the effects of SAL-RNAs on aged human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and the possible means to counteract such effects to improve the regenerative capacity of aged hBM-MSCs. METHODS: By comparing the lncRNAs expression of hBM-MSCs derived from young and old individuals, lnc-CYP7A1-1 was identified as being significantly increased with age. Using predictive software, the expression of Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1), was found to be decreased with age. Next, through lentiviral constructs, we downregulated the expression of lnc-CYP7A1-1 or SYNE1 in hBM-MSCs separately. Additionally, hBM-MSCs proliferation, survival, migration, and senescence were investigated in vitro. In vivo, lnc-CYP7A1-1 downregulated aged hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI), and cardiac function was measured. Through lentivirus-mediated downregulation of lnc-CYP7A1-1 in aged hBM-MSCs, we revealed that cell senescence was decreased, whereas cell proliferation, migration, and survival were increased. On the other hand, downregulation of SYNE1, the target gene of lnc-CYP7A1-1, in young hBM-MSCs increased cell senescence, yet decreased cell proliferation, migration, and survival. Downregulation of lnc-CYP7A1-1 in aged hBM-MSCs induced cell rejuvenation, yet this effect was attenuated by repression of SYNE1. In vivo, transplantation of lnc-CYP7A1-1 downregulated old hBM-MSCs improved cardiac function after MI. CONCLUSION: Down-regulation of lnc-CYP7A1-1 rejuvenated aged hBM-MSCs and improved cardiac function when implanted into the infarcted mouse hearts, possibly through its target gene SYNE1.

13.
Cells ; 9(8)2020 08 13.
Article in English | MEDLINE | ID: mdl-32823583

ABSTRACT

The importance of the immune system for cardiac repair following myocardial infarction is undeniable; however, the complex nature of immune cell behavior has limited the ability to develop effective therapeutics. This limitation highlights the need for a better understanding of the function of each immune cell population during the inflammatory and resolution phases of cardiac repair. The development of reliable therapies is further complicated by aging, which is associated with a decline in cell and organ function and the onset of cardiovascular and immunological diseases. Aging of the immune system has important consequences on heart function as both chronic cardiac inflammation and an impaired immune response to cardiac injury are observed in older individuals. Several studies have suggested that rejuvenating the aged immune system may be a valid therapeutic candidate to prevent or treat heart disease. Here, we review the basic patterns of immune cell behavior after myocardial infarction and discuss the autonomous and nonautonomous manners of hematopoietic stem cell and immune cell aging. Lastly, we identify prospective therapies that may rejuvenate the aged immune system to improve heart function such as anti-inflammatory and senolytic therapies, bone marrow transplant, niche remodeling and regulation of immune cell differentiation.


Subject(s)
Cellular Senescence/immunology , Lymphocytes/immunology , Myeloid Cells/immunology , Myocardial Infarction/immunology , Myocardial Infarction/therapy , Aged , Animals , Anti-Inflammatory Agents/therapeutic use , Female , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/metabolism , Humans , Male , Mice , Rejuvenation
14.
Cyberpsychol Behav Soc Netw ; 23(8): 562-566, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32478571

ABSTRACT

Past research has revealed positive associations between attachment anxiety and problematic social networking site (SNS) use and between attachment anxiety and sensitivity to feedback on an SNS. The aim of this study was to examine whether feedback sensitivity could account for the association between attachment anxiety and problematic SNS use. Two hundred eighty-three adults completed an online survey containing measures of adult attachment style in close relationships, sensitivity to feedback on Facebook, problematic Facebook use, and various control variables (Big Five personality traits, self-esteem, and demographics). A mediation analysis revealed the predicted indirect effect of attachment anxiety on problematic Facebook use through feedback sensitivity. Higher levels of attachment anxiety predicted greater sensitivity to feedback on Facebook, which in turn predicted higher levels of problematic Facebook use. Full mediation was observed with the control variables (attachment avoidance, extraversion, agreeableness, conscientiousness, neuroticism, openness to experience, self-esteem, age, and gender) in the model, and partial mediation was observed without the control variables. These findings replicate past research on attachment anxiety and extend our understanding by establishing a positive association between sensitivity to comments and likes on Feedback and problematic Facebook use.


Subject(s)
Anxiety/psychology , Feedback, Sensory , Social Media , Adult , Humans , Personality , Self Concept , Surveys and Questionnaires
15.
Cyberpsychol Behav Soc Netw ; 23(4): 257-263, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32096657

ABSTRACT

This study sought to examine whether interpersonal goals can help us understand who engages in social-capital-building responsive behaviors and envy-eliciting passive behaviors on Facebook. One hundred eighty-eight adults completed measures of interpersonal goals (compassionate and self-image), Facebook use (posting, responding, and searching), social capital sources and benefits, social comparison, and envy, along with various control measures. Serial mediation analyses revealed that compassionate goals significantly predicted four distinct social capital benefits (offline participation, emotional support, horizon broadening, and networking value) through greater Facebook responding and sources of social capital. Furthermore, self-image goals significantly predicted envy through greater Facebook searching and social comparison. These effects were significant with and without controlling for age, gender, Facebook friends, Facebook frequency, Facebook hours, self-esteem, attachment style, social desirability, and the other interpersonal goal and Facebook behaviors. Consistent with research on interpersonal goals in offline interactions, compassionate goals predicted more responsive behaviors and better social outcomes, while self-image goals predicted a competitive mindset and negative emotion. These findings extend the social networking site (SNS) literature by identifying a relevant new individual difference associated with SNS use and key outcomes related to well-being.


Subject(s)
Goals , Interpersonal Relations , Jealousy , Social Capital , Social Media/statistics & numerical data , Adult , Empathy , Female , Friends/psychology , Humans , Male , Motivation , Self Concept , Social Desirability , Social Networking
16.
J Neuroinflammation ; 17(1): 51, 2020 Feb 07.
Article in English | MEDLINE | ID: mdl-32028989

ABSTRACT

BACKGROUND: Radiotherapy is widely used and effective for treating brain tumours, but inevitably impairs cognition as it arrests cellular processes important for learning and memory. This is particularly evident in the aged brain with limited regenerative capacity, where radiation produces irreparable neuronal damage and activation of neighbouring microglia. The latter is responsible for increased neuronal death and contributes to cognitive decline after treatment. To date, there are few effective means to prevent cognitive deficits after radiotherapy. METHODS: Here we implanted hematopoietic stem cells (HSCs) from young or old (2- or 18-month-old, respectively) donor mice expressing green fluorescent protein (GFP) into old recipients and assessed cognitive abilities 3 months post-reconstitution. RESULTS: Regardless of donor age, GFP+ cells homed to the brain of old recipients and expressed the macrophage/microglial marker, Iba1. However, only young cells attenuated deficits in novel object recognition and spatial memory and learning in old mice post-irradiation. Mechanistically, old recipients that received young HSCs, but not old, displayed significantly greater dendritic spine density and long-term potentiation (LTP) in CA1 neurons of the hippocampus. Lastly, we found that GFP+/Iba1+ cells from young and old donors were differentially polarized to an anti- and pro-inflammatory phenotype and produced neuroprotective factors and reactive nitrogen species in vivo, respectively. CONCLUSION: Our results suggest aged peripherally derived microglia-like cells may exacerbate cognitive impairments after radiotherapy, whereas young microglia-like cells are polarized to a reparative phenotype in the irradiated brain, particularly in neural circuits associated with rewards, learning, and memory. These findings present a proof-of-principle for effectively reinstating central cognitive function of irradiated brains with peripheral stem cells from young donor bone marrow.


Subject(s)
Cognitive Dysfunction/therapy , Hematopoietic Stem Cell Transplantation , Maze Learning/physiology , Radiotherapy/adverse effects , Recovery of Function/physiology , Animals , Behavior, Animal/physiology , Cognitive Dysfunction/etiology , Dendritic Spines/physiology , Hippocampus/physiology , Humans , Long-Term Potentiation/physiology , Memory/physiology , Mice , Neurons/physiology , Spinocerebellar Ataxias/genetics , Treatment Outcome
17.
J Mol Cell Cardiol ; 132: 71-83, 2019 07.
Article in English | MEDLINE | ID: mdl-31047984

ABSTRACT

Bicuspid aortic valve (BAV) disease is a congenital abnormality that is associated with ascending aortic aneurysm yet many of the molecular mechanisms remain unknown. To identify novel molecular mechanisms of aneurysm formation we completed microarray analysis of the proximal (severely dilated) and distal (less dilated) regions of the ascending aorta from five patients with BAV. We identified 180 differentially expressed genes, 40 of which were validated by RT-qPCR. Most genes had roles in inflammation and endothelial cell function including cytokines and growth factors, cell surface receptors and the Activator Protein 1 (AP-1) transcription factor family (FOS, FOSB and JUN) which was chosen for further study. AP-1 was differentially expressed within paired BAV aneurysmal samples (n = 8) but not Marfan patients (n = 5). FOS protein was significantly enriched in BAV aortas compared to normal aortas but unexpectedly, ERK1/2 activity, an upstream regulator of FOS was reduced. ERK1/2 activity was restored when BAV smooth muscle cells were cultured in vitro. An mRNA-miRNA network within paired patient samples identified AP-1 as a central hub of miRNA regulation. FOS knockdown in BAV SMCs increased expression of miR-27a, a stretch responsive miRNA. AP-1 and miR-27a were also dysregulated in a mouse model of aortic constriction. In summary, this study identified a central role for AP-1 signaling in BAV aortic dilatation by using paired mRNA-miRNA patient sample. Upstream analysis of AP-1 regulation showed that the ERK1/2 signaling pathway is dysregulated and thus represents a novel chain of mediators of aortic dilatation in BAV which should be considered in future studies.


Subject(s)
Aortic Aneurysm/pathology , Aortic Diseases/pathology , Aortic Valve/abnormalities , Biomarkers/metabolism , Dilatation, Pathologic/pathology , Heart Valve Diseases/pathology , Animals , Aortic Aneurysm/genetics , Aortic Aneurysm/metabolism , Aortic Diseases/genetics , Aortic Diseases/metabolism , Aortic Valve/physiopathology , Bicuspid Aortic Valve Disease , Dilatation, Pathologic/genetics , Dilatation, Pathologic/metabolism , Disease Progression , Female , Gene Expression Profiling , Heart Valve Diseases/genetics , Heart Valve Diseases/metabolism , Heart Valve Diseases/physiopathology , Humans , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Signal Transduction
18.
Am J Physiol Heart Circ Physiol ; 315(4): H733-H744, 2018 10 01.
Article in English | MEDLINE | ID: mdl-29949381

ABSTRACT

Cell therapy has received significant attention as a therapeutic approach to restore cardiac function after myocardial infarction. Accumulating evidence supports that beneficial effects observed with cell therapy are due to paracrine secretion of multiple factors from transplanted cells, which alter the tissue microenvironment and orchestrate cardiac repair processes. Of these paracrine factors, extracellular vesicles (EVs) have emerged as a key effector of cell therapy. EVs regulate cellular function through the transfer of cargo, such as microRNAs and proteins, which act on multiple biological pathways within recipient cells. These discoveries have led to the development of cell-free therapies using EVs to improve cardiac repair after a myocardial infarction. Here, we present an overview of the current use of EVs to enhance cardiac repair after myocardial infarction. We also discuss the emerging use of EVs for rejuvenation-based therapies. Finally, future directions for the use of EVs as therapeutic agents for cardiac regenerative medicine are also discussed.


Subject(s)
Extracellular Vesicles/metabolism , Heart/physiology , Myocardium/metabolism , Regeneration , Animals , Extracellular Vesicles/transplantation , Humans
19.
Front Mol Neurosci ; 11: 126, 2018.
Article in English | MEDLINE | ID: mdl-29706867

ABSTRACT

Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running's genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

20.
J Soc Psychol ; 158(4): 496-507, 2018.
Article in English | MEDLINE | ID: mdl-29558267

ABSTRACT

People occasionally choose to cut themselves off from their online social network by taking extended breaks from Facebook. This study investigated whether abstaining from Facebook reduces stress but also reduces subjective well-being because of the resulting social disconnection. Participants (138 active Facebook users) were assigned to either a condition in which they were instructed to give up Facebook for 5 days or continue to use Facebook as normal. Perceived stress and well-being, as well as salivary cortisol, were measured before and after the test period. Relative to those in the Facebook Normal condition, those in the No Facebook condition experienced lower levels of cortisol and life satisfaction. Our results suggest that the typical Facebook user may occasionally find the large amount of social information available to be taxing, and Facebook vacations could ameliorate this stress-at least in the short term.


Subject(s)
Interpersonal Relations , Personal Satisfaction , Social Isolation/psychology , Social Media , Social Networking , Stress, Psychological/psychology , Adult , Female , Humans , Male
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