ABSTRACT
Calisthenics is a form of bodyweight exercise that involves dynamic and rhythmic exercises. The physiological responses during and after calisthenics remain unclear. This study examined whether a bout of full-body calisthenics, a form of circuit resistance exercise that involves bodyweight movements, yields greater excess post-exercise oxygen consumption (EPOC) than steady-state exercise (SSE) at matched oxygen consumption. Twenty-two young adults (age = 22.1 ± 2.4 years; four females) participated in two separate, oxygen consumption (VËO2) matched exercise sessions: full-body calisthenics (nine body weight exercises, 15 reps × 4 sets) and SSE (running on a treadmill at 60-90% of VËO2max). Energy expenditure, substrate utilization, and EPOC were measured during exercise and 60 min of recovery. SSE showed higher peak VËO2 and heart rate during exercise than those during calisthenics. However, the post-exercise VËO2 and energy expenditure above baseline level during the first 10 min of recovery were significantly higher with calisthenics than with SSE (0-5 min: 1.7 ± 0.5 vs. 1.0 ± 0.6; 6-10 min: 0.5 ± 0.4 vs. 0.1 ± 0.2 kcal/min; 31-60 min recovery: -0.1 ± 0.3 vs. -0.2 ± 0.2; all p < .05). During calisthenics, participants utilized a significantly higher proportion of energy from carbohydrates (85 vs. 73%; p < .01) but after exercise, they used a greater proportion of fat as the energy source (71 vs. 50%; p < .01) compared to SSE. Full-body calisthenics, a circuit-style bodyweight exercise, may be more effective than VËO2 matched SSE in triggering greater EPOC and fat metabolism. Further efforts are warranted to demonstrate whether different amounts of skeletal muscle mass groups indeed lead to varying EPOC responses and energy use.
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Tectonics is broadly accepted as one of the main factors controlling long-term landscape evolution. The impact of tectonics on short timescales is most often observed through earthquake rupturings that produce localized, metric-scale deformations. Although these deformations significantly affect the landscape, it remains challenging to precisely correlate major landscape changes with these localized earthquake deformations. Therefore, linking instantaneous deformation to long-term morphological changes often involves a thought experiment with potentially limited temporal resolution. At a paleoseismological site along the slow-moving strike-slip Yangsan Fault in South Korea, we employed optically stimulated luminescence (OSL) dating and detrital zircon analysis on all exposed unconsolidated layers in trench walls. The results reveal a significant provenance shift in the sediments accumulating in the trench, indicating a major reorganization of the drainage network. Based on our OSL and detrital zircon data, we estimate that this change occurred around 70 ka. We propose that this drastic drainage reorganization was caused by a combination of very slow, yet continuous, earthquake activity and a temporary reduction in river erosion during the onset of the cold, dry spell characteristic of the MIS4 stage across the Korean Peninsula.
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BACKGROUND AND OBJECTIVES: Although cardiac rehabilitation (CR) is highly recommended in patients with cardiovascular disease (CVD), participation in CR is low mainly due to access barriers. Home-based CR (HBCR) has been recommended to overcome access barriers. Exercise is a core component of CR and should be developed and implemented based on individual characteristics. We aimed to assess physical activity behaviors, exercise preferences, and exercise barriers to understand physical activity characteristics of CVD patients. METHODS: Participants were patients between the ages 19 to 75 years with a history of heart failure with reduced ejection fraction (HFrEF) or myocardial infarction (MI). They completed a cross-sectional survey at a tertiary hospital's outpatient clinic from April to June 2021. Survey data included physical activity levels, patterns, preference, and barriers of exercise. RESULTS: Participants (n=189; 143 males, 46 females, 62.1±12.0 years) were diagnosed as either HFrEF (n=160, 84.7%) or a history of MI (n=97, 51.3%). Only 26.5% of patients engaged in moderate to vigorous exercise for more than 150 minutes per week. Participants preferred exercising alone or with families. Walking (65.6%) and resistance exercises (35.4%) were favored, with outdoor (37%) and home-based (30.2%) settings preferred over fitness centers (10.6%) and hospitals (0.5%). Barriers to exercise included fatigue (34.4%), poor health perception (31.7%), and low fitness levels (30.7%). CONCLUSIONS: The results of this study can be used to develop tailored HBCR programs that consider individual preferences and address specific barriers, facilitating adequate physical activity engagement.
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BACKGROUND: Bone marrow stimulation (BMS), a procedure involving the creation of multiple channels in the greater tuberosity, is often performed alongside arthroscopic rotator cuff repair (ARCR). This study evaluated the effect of BMS on clinical and structural outcomes following ARCR. METHOD: This study involved 204 patients with small, medium, and large full-thickness rotator cuff tears. In all, 103 patients who underwent BMS and ARCR made up the BMS group, while the 101 patients who only had ARCR made up the control group with randomization. Clinical and functional outcomes were assessed before and at 3 months, 6 months, 1 year, and 2 years after surgery, using parameters such as range of motion, functional scores (American Shoulder and Elbow Surgeons and Constant score), and clinical scores (Visual Analogue Scale). Tendon integrity was also examined postoperatively via ultrasound at 6 months and 2 years. RESULTS: There were no significant differences between the two groups concerning range of motion, functional scores (American Shoulder and Elbow Surgeons score and Constant score), and clinical score (Visual Analogue Scale) during the 2-year postsurgery period (all P > .05). Similarly, the rotator cuff retear rate, as assessed using ultrasonographic tendon integrity checks over 2 years postsurgery, did not significantly vary between the groups (all P > .05). CONCLUSION: There were no significant disparities in functional scores and clinical outcomes between the BMS and control groups. Further, no significant differences were observed in tendon integrity postsurgery. Therefore, the inclusion or exclusion of BMS is not anticipated to influence the postoperative outcome in ARCR for patients with small, medium, or large rotator cuff tears.
Subject(s)
Arthroscopy , Range of Motion, Articular , Rotator Cuff Injuries , Humans , Rotator Cuff Injuries/surgery , Male , Female , Middle Aged , Arthroscopy/methods , Aged , Rotator Cuff/surgery , Treatment Outcome , Bone MarrowABSTRACT
In past decades, the positive role of self-control in students' academic success has attracted plenty of scholarly attention. However, fewer studies have examined the link between adolescents' neural development of the inhibitory control system and their academic achievement, especially using a longitudinal approach. Moreover, less is known about the role of parents in this link. Using large-scale longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study (N = 9574; mean age = 9.94 years at baseline, SD = .63; 50% girls), the current study took an integrative biopsychosocial approach to explore the longitudinal link between early adolescents' fronto-striatal connectivity and their academic achievement, with attention to the moderating role of parental warmth. Results showed that weaker intrinsic connectivity between the frontoparietal network and the striatum was associated with early adolescents' worse academic achievement over 2 years during early adolescence. Notably, parental warmth moderated the association between fronto-striatal connectivity and academic achievement, such that weaker fronto-striatal connectivity was only predictive of worse academic achievement among early adolescents who experienced low levels of parental warmth. Taken together, the findings demonstrate weaker fronto-striatal connectivity as a risk factor for early adolescents' academic development and highlight parental warmth as a protective factor for academic development among those with weaker connectivity within the inhibitory control system.
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Greater neural similarity between parents and adolescents may reduce adolescent substance use. Among 70 parent-adolescent dyads, we tested a longitudinal path model in which family economic environment is related to adolescent substance use, directly and indirectly through parent-adolescent neural similarity and parental monitoring. Neural similarity was measured as parent-adolescent pattern similarity in functional brain connectivity at Time 1. Parents reported socioeconomic status and parental monitoring at Time 1. Adolescents reported parental monitoring at Time 1 and substance use at Time 2. Higher family socioeconomic status was associated with greater neural similarity. Greater neural similarity was associated with lower adolescent substance use, mediated through greater adolescent-perceived parental monitoring. Parent-adolescent neural similarity may attenuate adolescent substance use by bolstering parental monitoring. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Subject(s)
Parent-Child Relations , Parenting , Social Class , Substance-Related Disorders , Humans , Adolescent , Female , Male , Substance-Related Disorders/psychology , Parenting/psychology , Adolescent Behavior/psychology , Adolescent Behavior/physiology , Adult , Brain/physiology , Longitudinal Studies , Magnetic Resonance Imaging , Parents/psychologyABSTRACT
Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.
Subject(s)
Camellia sinensis , Catechin , Humans , Secondary Metabolism , Exons , Chromosomes, Human, Pair 15 , Camellia sinensis/genetics , TeaABSTRACT
The current dataset aims to support and enhance the research reliability of neuromelanin regions in the brainstem, such as locus coeruleus (LC), by offering raw neuromelanin-sensitive images. The dataset includes raw neuromelanin-sensitive images from 157 healthy individuals (8-64 years old). In addition, leveraging individual neuromelanin-sensitive images, a non-linear neuromelanin-sensitive atlas, generated through an iterative warping process, is included to tackle the common challenge of a limited field of view in neuromelanin-sensitive images. Finally, the dataset encompasses a probabilistic LC atlas generated through a majority voting approach with pre-existing multiple atlas-based segmentations. This process entails warping pre-existing atlases onto individual spaces and identifying voxels with a majority consensus of over 50 % across the atlases. This LC probabilistic atlas can minimize uncertainty variance associated with choosing a specific single atlas.
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BACKGROUND: Cardiac rehabilitation (CR) is recommended for patients with cardiovascular disease. However, the participation and completion rates for hospital-based CR are low, and home-based CR has been suggested as an alternative. This study aimed to develop a home-based CR program and assess the feasibility of the program over a 6-week period in patients with left ventricular dysfunction or a history of myocardial infarction. METHODS: This feasibility study consisted of two phases. The initial phase (Study 1) focused on developing the home-based exercise protocol. Systematic approaches to developing evidence-based home-based exercise intervention were implemented including systematic review, patient surveys, and expert consensus. Study 2 aimed to evaluate the feasibility of a 6-week home-based CR program that was based on the results of Study 1. Study 2 included two exercise education sessions and four telephone counseling sessions. During this stage of the exercise program, the participants exercised on two separate days and their experiences while performing the aerobic and resistance exercises were surveyed. Eight participants participated in Study 1 and 16 participated in Study 2. RESULTS: Participants expressed overall satisfaction with the exercise program in Study 1. Heart rate increased in response to exercise, but this did not correspond with perceived exertion. The aim of the home-based CR exercise program was for participants to achieve exercise goals (≥150 min/week of aerobic type exercises as well as at least twice weekly resistance exercise using own body weights). We aimed to increase compliance and adherence to the home-based CR program. In Study 2, 13 out of 16 participants (81.3%) completed the 6-week home-based CR program, with a participation rate of 100% in both exercise education and phone counseling sessions. Adherence to the home-based exercise protocol was 83.1% and no serious adverse events were observed. At the beginning of the study, only three out of 13 participants (23.1%) met the requirements for both aerobic and resistance exercises, but at the end of the 6-week program, 10 out of 13 participants (76.9%) fulfilled the requirements. CONCLUSION: The exercise program developed in this study was safe and feasible, and the 6-week home-based CR program was feasible for patients with cardiovascular disease without any reported adverse effects.
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When attempts to lose body fat mass frequently fail, breath acetone (BA) monitoring may assist fat mass loss during a low-carbohydrate diet as it can provide real-time body fat oxidation levels. This randomized controlled study aimed to evaluate the effectiveness of monitoring BA levels and providing feedback on fat oxidation during a three-week low-carbohydrate diet intervention. Forty-seven participants (mean age = 27.8 ± 4.4 years, 53.3% females, body mass index = 24.1 ± 3.4 kg m-2) were randomly assigned to three groups (1:1:1 ratio): daily BA assessment with a low-carbohydrate diet, body weight assessment (body scale (BS)) with a low-carbohydrate diet, and low-carbohydrate diet only. Primary outcome was the change in fat mass and secondary outcomes were the changes in body weight and body composition. Forty-five participants completed the study (compliance rate: 95.7%). Fat mass was significantly reduced in all three groups (allP< 0.05); however, the greatest reduction in fat mass was observed in the BA group compared to the BS (differences in changes in fat mass, -1.1 kg; 95% confidence interval: -2.3, -0.2;P= 0.040) and control (differences in changes in fat mass, -1.3 kg; 95% confidence interval: -2.1, -0.4;P= 0.013) groups. The BA group showed significantly greater reductions in body weight and visceral fat mass than the BS and control groups (allP< 0.05). In addition, the percent body fat and skeletal muscle mass were significantly reduced in both BA and BS groups (allP< 0.05). However, no significant differences were found in changes in body fat percentage and skeletal muscle mass between the study groups. Monitoring BA levels, which could have motivated participants to adhere more closely to the low-carbohydrate diet, to assess body fat oxidation rates may be an effective intervention for reducing body fat mass (compared to body weight assessment or control conditions). This approach could be beneficial for individuals seeking to manage body fat and prevent obesity.
Subject(s)
Acetone , Weight Loss , Female , Humans , Young Adult , Adult , Male , Breath Tests , Body Composition/physiology , Body Weight , Adipose TissueABSTRACT
Although increase in physical activity is important to improve prognosis of cardiac patients in addition to hospital-based exercise cardiac rehabilitation, their physical activity levels are not properly understood. This study aimed to examine domain- and intensity-specific physical activity in individuals with coronary heart disease (CHD) and compare them with non-CHD individuals. Data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2019 were analyzed, including 1083 CHD patients and 38,532 non-CHD individuals. The inclusion criteria were age 19 years or older and data not missing for CHD information. Before and after propensity score matching (PSM) for age, sex, body mass index, education, household income, alcohol intake, and smoking status, domain (leisure, work, transportation)-and intensity (moderate, vigorous) -specific physical activity participation levels were compared between individuals with and without CHD. Before PSM, CHD individuals were older, less educated, more sedentary, and participated less in PAs compared to non-CHD individuals. After PSM, CHD individuals had similar levels of domain-specific PAs. However, they had higher work-related PA levels (29.7 ± 209.6 vs. 42.1 ± 291.3 min/week p = 0.022) and more sedentary time (487.2 ± 224.2 vs. 514.1 ± 228.7. p = 0.003) than those without CHD. Subgroup analysis revealed lower leisure-related PA in men with CHD (63.5 ± 165.5 vs. 47.3 ± 140.2, p < 0.05) and higher work-related PA in women with CHD (18.9 ± 159.7 vs. 57.1 ± 397.5, p < 0.01). Among those < 65 years of age, individuals with CHD spent more time sedentary than individuals without CHD. CHD individuals are not physically inactive compared with non-CHD individuals who are similar in sociodemographic status and lifestyle. CHD patients' PA levels may have been underestimated.
Subject(s)
Cardiac Rehabilitation , Coronary Disease , Male , Humans , Female , Young Adult , Adult , Nutrition Surveys , Surveys and Questionnaires , Exercise , Coronary Disease/epidemiologyABSTRACT
Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly and represents a major clinical challenge in the ageing society. Neuropathological hallmarks of AD include neurofibrillary tangles composed of hyperphosphorylated tau, senile plaques derived from the deposition of amyloid-ß (Aß) peptides, brain atrophy induced by neuronal loss, and synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) is ubiquitously expressed in the central nervous system. Dysregulation of DAPK1 has been shown to contribute to various neurological diseases including AD, ischemic stroke and Parkinson's disease (PD). We have established an upstream effect of DAPK1 on Aß and tau pathologies and neuronal apoptosis through kinase-mediated protein phosphorylation, supporting a causal role of DAPK1 in the pathophysiology of AD. In this review, we summarize current knowledge about how DAPK1 is involved in various AD pathological changes including tau hyperphosphorylation, Aß deposition, neuronal cell death and synaptic degeneration. The underlying molecular mechanisms of DAPK1 dysregulation in AD are discussed. We also review the recent progress regarding the development of novel DAPK1 modulators and their potential applications in AD intervention. These findings substantiate DAPK1 as a novel therapeutic target for the development of multifunctional disease-modifying treatments for AD and other neurological disorders.
Subject(s)
Alzheimer Disease , Aged , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Death-Associated Protein Kinases/genetics , Amyloid beta-Peptides , Central Nervous System , Neurofibrillary TanglesABSTRACT
PURPOSE: Infertility affects 10% to 15% of couples, and male factor accounts for 50% of the cases. The relevant male genetic factors, which account for at least 15% of male infertility, include Y-chromosome microdeletions. We investigated clinical data and patterns of Y-chromosome microdeletions in Korean infertile men. MATERIALS AND METHODS: A total of 919 infertile men whose sperm concentration was ≤5 million/mL in two consecutive analyses were investigated for Y-chromosome microdeletion. Among them, 130 infertile men (14.1%) demonstrated Y-chromosome microdeletions. Medical records were retrospectively reviewed. RESULTS: In 130 men with Y-chromosome microdeletions, 90 (69.2%) had azoospermia and 40 (30.8%) had severe oligozoospermia. The most frequent microdeletions were in the azoospermia factor (AZF) c region (77/130, 59.2%), followed by the AZFb+c (30/130, 23.1%), AZFa (8/130, 6.2%), AZFb (7/130, 5.4%), AZFa+b+c (7/130, 5.4%), and AZFa+c (1/130, 0.7%) regions. In men with oligozoospermia, 37 (92.5%) had AZFc microdeletion. Chromosomal abnormalities were detected in 30 patients (23.1%). Higher follicle-stimulating hormone level (23.2±13.5 IU/L vs. 15.1±9.0 IU/L, p<0.001), higher luteinizing hormone level (9.7±4.6 IU/L vs. 6.0±2.2 IU/L, p<0.001), and lower testis volume (10.6±4.8 mL vs. 13.3±3.8 mL, p<0.001) were observed in azoospermia patients compared to severe oligozoospermia patients. CONCLUSIONS: Y-chromosome microdeletion is a common genetic cause of male infertility. Therefore, Y-chromosome microdeletion test is recommended for the accurate diagnosis of men with azoospermia or severe oligozoospermia. Appropriate genetic counseling is mandatory before the use of assisted reproduction technique in men with Y-chromosome microdeletion.
Subject(s)
Azoospermia , Infertility, Male , Oligospermia , Male , Humans , Azoospermia/genetics , Oligospermia/genetics , Retrospective Studies , Semen , Infertility, Male/genetics , Republic of KoreaABSTRACT
BACKGROUND: Socioecological factors such as family environment and parenting behaviors contribute to the development of substance use. While biobehavioral synchrony has been suggested as the foundation for resilience that can modulate environmental effects on development, the role of brain similarity that attenuates deleterious effects of environmental contexts has not been clearly understood. We tested whether parent-adolescent neural similarity-the level of pattern similarity between parent-adolescent functional brain connectivity representing the level of attunement within each dyad-moderates the longitudinal pathways in which household chaos (a stressor) predicts adolescent substance use directly and indirectly via parental monitoring. METHODS: In a sample of 70 parent-adolescent dyads, similarity in resting-state brain activity was identified using multipattern connectivity similarity estimation. Adolescents and parents reported on household chaos and parental monitoring, and adolescent substance use was assessed at a 1-year follow-up. RESULTS: The moderated mediation model indicated that for adolescents with low neural similarity, but not high neural similarity, greater household chaos predicted higher substance use over time directly and indirectly via lower parental monitoring. Our data also indicated differential susceptibility in the overall association between household chaos and substance use: Adolescents with low neural similarity exhibited high substance use under high household chaos but low substance use under low household chaos. CONCLUSIONS: Neural similarity acts as a protective factor such that the detrimental effects of suboptimal family environment and parenting behaviors on the development of adolescent health risk behaviors may be attenuated by neural similarity within parent-adolescent bonds.
Subject(s)
Parenting , Substance-Related Disorders , Humans , Adolescent , Protective Factors , Family Characteristics , BrainABSTRACT
AIMS: The autophagy-lysosomal pathway is important for maintaining cellular proteostasis, while dysfunction of this pathway has been suggested to drive the aberrant intraneuronal accumulation of tau protein, leading to synaptic damage and cognitive impairment. Previous studies have demonstrated that the activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin has a positive impact on cognition and AD-related biomarkers. However, the effect and mechanism of TPRV1 activation on neuronal tau homeostasis remain elusive. METHODS: A mouse model of tauopathy was established by overexpressing full-length human tau in the CA3 area. Mice were fed capsaicin diet (0.0125%) or normal diet for 9 weeks. The cognitive ability, synaptic function, tau phosphorylation levels, and autophagy markers were detected. In vitro, capsaicin-induced alterations in cellular autophagy and tau degradation were characterized using two cell models. Besides, various inhibitors were applied to validate the role of TRPV1-mediated autophagy enhancement in tau clearance. RESULTS: We observed that TRPV1 activation by capsaicin effectively mitigates hippocampal tau accumulation-induced synaptic damages, gliosis, and cognitive impairment in vivo. Capsaicin promotes the degradation of abnormally accumulated tau through enhancing autophagic function in neurons, which is dependent on TRPV1-mediated activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR). Blocking AMPK activation abolishes capsaicin-induced autophagy enhancement and tau degradation in neurons. CONCLUSION: Our findings reveal that capsaicin-induced TRPV1 activation confers neuroprotection by restoring neuronal tau homeostasis via modulating cellular autophagy and provides additional evidence to support the potential of TRPV1 as a therapeutic target for tauopathies.
Subject(s)
Antineoplastic Agents , Cognitive Dysfunction , Animals , Humans , Mice , AMP-Activated Protein Kinases/metabolism , Autophagy , Capsaicin/pharmacology , Cognitive Dysfunction/drug therapy , Mammals/metabolism , tau Proteins/metabolism , TRPV Cation Channels/metabolismABSTRACT
Death-associated protein kinase 1 (DAPK1) is a stress-responsive calcium/calmodulin (CaM)-regulated serine/threonine protein kinase that is actively involved in stress-induced cell death. The dysregulation of DAPK1 has been established in various neurological disorders such as epilepsy, Alzheimer's disease (AD), and Parkinson's disease (PD). Recent research indicates a synaptic localization of DAPK1 in neurons, suggesting a potential role of DAPK1 in modulating synaptic structure and function. However, the key molecules and pathways underlying the influence of DAPK1 on synapses remain elusive. We utilized quantitative proteomic and phosphoproteomic analyses to compare the differences in protein expression and phosphorylation in hippocampal tissues of wild-type (WT) and DAPK1-knockout (KO) mice. Bioinformatic analysis of differentially expressed proteins and phosphoproteins revealed a preferential enrichment of proteins involved in regulating synaptic function, cytoskeletal structure, and neurotransmission. Gene set enrichment analysis (GESA) highlighted altered presynaptic functions including synaptic vesicle priming and glutamate secretion in KO mice. Besides, we observed that proteins with potential phosphorylation motifs of ERK and DAPK1 were overrepresented among the differential phosphoproteins and were highly enriched in neuronal function-related pathways. Furthermore, Western blot analysis validated differences in the expression of several proteins closely associated with presynaptic organization, dendrites and calcium transmembrane transport between KO and WT mice, further corroborating the potential involvement of DAPK1 in the regulation of synaptic functions. Overall, our data provide molecular evidence to elucidate the physiological links between DAPK1 and neuronal functions and help clarify the role of DAPK1 in the pathogenesis of neurodevelopmental and neurodegenerative diseases.
Subject(s)
Calcium , Proteomics , Animals , Mice , Death-Associated Protein Kinases/metabolism , Hippocampus/metabolism , Mice, Knockout , Phosphoproteins/metabolism , Synapses/metabolismABSTRACT
BACKGROUND AND OBJECTIVES: Use of psychotropic substances in childhood has been associated with both impulsivity and other manifestations of poor executive function as well as escalation over time to use of progressively stronger substances. However, how this relationship may start in earlier childhood has not been well explored. Here, we investigated the neurobehavioral correlates of daily caffeinated soda consumption in preadolescent children and examined whether caffeinated soda intake is associated with a higher risk of subsequent alcohol initiation. METHODS: Using Adolescent Brain Cognitive Development study data (N = 2,092), we first investigated cross-sectional relationships between frequent caffeinated soda intake and well-known risk factors of substance misuse: impaired working memory, high impulsivity, and aberrant reward processing. We then examined whether caffeinated soda intake at baseline predicts more alcohol sipping at 12 months follow-up using a machine learning algorithm. RESULTS: Daily consumption of caffeinated soda was cross-sectionally associated with neurobehavioral risk factors for substance misuse such as higher impulsivity scores and lower working memory performance. Furthermore, caffeinated soda intake predicted a 2.04 times greater likelihood of alcohol sipping after 12 months, even after controlling for rates of baseline alcohol sipping rates. CONCLUSIONS: These findings suggest that previous linkages between caffeine and substance use in adolescence also extend to younger initiation, and may stem from core neurocognitive features thought conducive to substance initiation.
Subject(s)
Beverages , Carbonated Beverages , Adolescent , Humans , Child , Beverages/adverse effects , Caffeine , Risk FactorsABSTRACT
Alzheimer's disease (AD) is a complex multifactorial disorder that poses a substantial burden on patients, caregivers, and society. Considering the increased aging population and life expectancy, the incidence of AD will continue to rise in the following decades. However, the molecular pathogenesis of AD remains controversial, superior blood-based biomarker candidates for early diagnosis are still lacking, and effective therapeutics to halt or slow disease progression are urgently needed. As powerful genetic regulators, microRNAs (miRNAs) are receiving increasing attention due to their implications in the initiation, development, and theranostics of various diseases, including AD. In this review, we summarize miRNAs that directly target microtubule-associated protein tau (MAPT), amyloid precursor protein (APP), and ß-site APP-cleaving enzyme 1 (BACE1) transcripts and regulate the alternative splicing of tau and APP. We also discuss related kinases, such as glycogen synthase kinase (GSK)-3ß, cyclin-dependent kinase 5 (CDK5), and death-associated protein kinase 1 (DAPK1), as well as apolipoprotein E, that are directly targeted by miRNAs to control tau phosphorylation and amyloidogenic APP processing leading to Aß pathologies. Moreover, there is evidence of miRNA-mediated modulation of inflammation. Furthermore, circulating miRNAs in the serum or plasma of AD patients as noninvasive biomarkers with diagnostic potential are reviewed. In addition, miRNA-based therapeutics optimized with nanocarriers or exosomes as potential options for AD treatment are discussed.
Subject(s)
Alzheimer Disease , MicroRNAs , Humans , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Amyloid Precursor Protein Secretases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Aspartic Acid Endopeptidases/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , tau Proteins/genetics , tau Proteins/metabolism , Phosphorylation , Amyloid beta-Peptides/metabolismABSTRACT
Breast cancer is one of the major malignancies in women, and most related deaths are due to recurrence, drug resistance, and metastasis. The expression of the mouse double minute 2 (MDM2) oncogene is upregulated in breast cancer; however, its regulatory mechanism has yet to be fully elucidated. Herein, we identified the tumor suppressor death-associated protein kinase 1 (DAPK1) as a novel MDM2 regulator by unbiased peptide library screening. DAPK1 is directly bound to MDM2 and phosphorylates it at Thr419. DAPK1-mediated MDM2 phosphorylation promoted its protein degradation via the ubiquitin-proteasome pathway, resulting in upregulated p53 expression. DAPK1 overexpression, but not its kinase activity-deficient form, decreased colony formation and increased doxorubicin-induced cell death; however, DAPK1 knockdown produced the opposite effects in human breast cancer cells. In a xenograft tumorigenesis assay, DAPK1 overexpression significantly reduced tumor formation, whereas inhibition of DAPK1 kinase activity reduced its antitumorigenic effect. Finally, DAPK1 expression was negatively correlated with MDM2 levels in human breast cancer tissues. Thus, these results suggest that DAPK1-mediated MDM2 phosphorylation and its protein degradation may contribute to its antitumorigenic function in breast cancer.