Recognizing that high-stakes competitions tend to pressure coaches toward a maladaptive controlling motivating style, we sought to evaluate the capacity of an intervention to help coaches adopt a ...more autonomy-supportive style as they and their athletes prepared for the 2012 London Paralympic Games.
We adopted a coach-focused experimental research design that longitudinally assessed coaches' and athletes' self-report, rater-scored, and objective dependent measures.
We randomly assigned 33 coaches and their 64 athletes from 10 sports into either an experimental or control group and assessed their motivation and functioning longitudinally.
In the control group, athletes and coaches both showed a significant longitudinal deterioration in all measures of motivation, engagement, and functioning. In the experimental group, none of the measures of motivation, engagement, and functioning deteriorated but, instead, were generally maintained. In terms of performance, athletes of coaches in the experimental group won significantly more Olympic medals than did athletes in the control group.
Enacting an autonomy-supportive coaching style within the context of a high-stakes sports competition functioned as an antidote to coaches' otherwise situationally-induced controlling style.
•Paralympic coaches randomly assigned to an autonomy-supportive intervention.•We assessed coaches' and athletes' motivation, functioning, and performance.•Without the intervention, the high-stakes context undermined all dependent measures.•With the intervention, dependent measures were maintained.•Experimental condition predicted which athletes won an Olympic medal.
Drainage of parenchymal waste through the lymphatic system maintains brain homeostasis. Age-related changes of glymphatic-lymphatic clearance lead to the accumulation beta-amyloid (Aβ) in dementia ...models. In this study, focused ultrasound treatment in combination with microbubbles (FUS-MB) improved Aβ drainage in early dementia model mice, 5XFAD. FUS-MB enhanced solute Aβ clearance from brain, but not plaques, to cerebrospinal fluid (CSF) space and then deep cervical lymph node (dCLN). dCLN ligation exaggerated memory impairment and progress of plaque formation and also the beneficial effects of FUS-MB upon Aβ removal through CSF-lymphatic routes. In this ligation model, FUS-MB improved memory despite accumulation of Aβ in CSF. In conclusion, FUS-MB enhances glymphatic-lymphatic clearance of Aβ mainly by increasing brain-to-CSF Aβ drainage. We suggest that FUS-MB can delay dementia progress in early period and benefits of FUS-MB depend on the effect of Aβ disposal through CSF-lymphatics.
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•Significant age- and sex-dependent accumulation of POPs was found in finless porpoises.•Maternal transport preferentially occurred for lower-molecular-weight POPs.•POP concentrations ...in porpoises decreased significantly from 2003 to 2010.•Almost all POP concentrations in porpoises stabilized during the period of 2010–2015.•Approximately 10–27 % species exceeded ecotoxicological thresholds for PCBs and DDTs.
Accumulation of persistent organic pollutants (POPs) in marine mammals is of great concern and is associated with declining populations. The concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) were measured in blubber of finless porpoises (Neophocaena asiaeorientalis) collected from Korean coastal waters in 2010 and 2015, to assess the concentrations, time trends, and ecotoxicological effects. Among the POPs measured, DDTs were detected at the highest concentrations, followed by PCBs and PBDEs. Significant age- and sex-dependent accumulation of POPs was evident for porpoises collected in 2010, but not for those collected in 2015. This finding may be a function of stabilization of POP concentrations over time. In our study, accumulation patterns of POPs were dependent on consumption patterns and physico-chemical properties of the contaminants, and on the metabolism in the porpoises. Significant reductions of POPs were found between 2003 and 2010, likely reflecting the impact of domestic and global regulation of POPs. However, no changes in most POPs were found between 2010 and 2015, suggesting a trend toward stabilization. Approximately 10 % and 27 % of porpoises exceeded previously proposed threshold levels for PCBs and DDTs, respectively, implying a potential health risk.
Dynamically altered microglia play an important role in the progression of Alzheimer's disease (AD). Here, we found a close association of the metabolic reconfiguration of microglia with increased ...hippocampal glucose uptake on
Ffluorodeoxyglucose (FDG) PET.
We used an AD animal model, 5xFAD, to analyze hippocampal glucose metabolism using both animal FDG PET and ex vivo FDG uptake test. Cells of the hippocampus were isolated to perform single-cell RNA-sequencing (scRNA-seq). The molecular features of cells associated with glucose metabolism were analyzed at a single-cell level. In order to apply our findings to human brain imaging study, brain FDG PET data obtained from the Alzheimer's Disease Neuroimaging Initiative were analyzed. FDG uptake in the hippocampus was compared according to the diagnosis, AD, mild cognitive impairment, and controls. The correlation analysis between hippocampal FDG uptake and soluble TREM2 in cerebrospinal fluid was performed.
In the animal study, 8- and 12-month-old 5xFAD mice showed higher FDG uptake in the hippocampus than wild-type mice. Cellular FDG uptake tests showed that FDG activity in hippocampal microglia was increased in the AD model, while FDG activity in non-microglial cells of the hippocampus was not different between the AD model and wild-type. scRNA-seq data showed that changes in glucose metabolism signatures including glucose transporters, glycolysis and oxidative phosphorylation, mainly occurred in microglia. A subset of microglia with higher glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. In the human imaging study, we found a positive association between soluble TREM2 and hippocampal FDG uptake. FDG uptake in the hippocampus at the baseline scan predicted mild cognitive impairment conversion to AD.
We identified the reconfiguration of microglial glucose metabolism in the hippocampus of AD, which could be evaluated by FDG PET as a feasible surrogate imaging biomarker for microglia-mediated inflammation.
Brain organoids are valuable research models for human development and disease since they mimic the various cell compositions and structures of the human brain; however, they have challenges in ...presenting aging phenotypes for degenerative diseases. This study analyzed the association between aging and the gut metabolite trimethylamine
N
-oxide (TMAO), which is highly found in the midbrain of elderly and Parkinson’s disease (PD) patients. TMAO treatment in midbrain organoid induced aging-associated molecular changes, including increased senescence marker expression (
P21, P16
), p53 accumulation, and epigenetic alterations. In addition, TMAO-treated midbrain organoids have shown parts of neurodegeneration phenotypes, including impaired brain-derived neurotrophic factor (BDNF) signaling, loss of dopaminergic neurons, astrocyte activation, and neuromelanin accumulation. Moreover, we found TMAO treatment-induced pathophysiological phosphorylation of α-synuclein protein at Ser-129 residues and Tau protein at Ser202/Thr205. These results suggest a role of TMAO in the aging and pathogenesis of the midbrain and provide insight into how intestinal dysfunction increases the risk of PD. Furthermore, this system can be utilized as a novel aging model for induced pluripotent stem cell (iPSC)-based modeling of late-onset diseases.
Telomeric repeat binding factor 1 (TRF1) plays an essential role in maintaining telomere length. Here, we established TRF1-knockout human pluripotent stem cells (hPSCs; hTRF1-KO) using the ...CRISPR/Cas9 technology. The hTRF1-KO cell lines expressed pluripotency markers and demonstrated a normal karyotype (46, XX) and DNA profile. In addition, hTRF1-KOcells spontaneously differentiated into all three germ layers in vitro. Thus, these cell lines could be useful models in various research fields.
Long QT syndrome type 2 (LQT2) is a heart disorder caused by a loss-of-function mutation in the KCNH2 gene that is an essential factor in cardiac repolarization and affects the heart rate. This study ...has generated a human-induced stem cell line (KSCBi014-A) carrying the KCNH2 (c.453delC) mutation from an LQT2 patient. The non-integrative Sendai virus-mediated induced pluripotent stem cell (iPSC) reprogramming method was used for iPSC line generation. The KSCBi014-A line maintained stem cell-like morphology, normal karyotype, and pluripotency, and could differentiate into three germ layers in vitro.
Alveolar organoids (AOs), derived from human pluripotent stem cells (hPSCs) exhibit lung-specific functions. Therefore, the application of AOs in pulmonary disease modeling is a promising tool for ...understanding disease pathogenesis. However, the lack of immune cells in organoids limits the use of human AOs as models of inflammatory diseases. In this study, we generated AOs containing a functional macrophage derived from hPSCs based on human fetal lung development using biomimetic strategies. We optimized culture conditions to maintain the iMACs (induced hPSC-derived macrophages) AOs for up to 14 days. In lipopolysaccharide (LPS)-induced inflammatory conditions, IL-1β, MCP-1 and TNF-α levels were significantly increased in iMAC-AOs, which were not detected in AOs. In addition, chemotactic factor IL-8, which is produced by mononuclear phagocytic cells, was induced by LPS treatment in iMACs-AOs. iMACs-AOs can be used to understand pulmonary infectious diseases and is a useful tool in identifying the mechanism of action of therapeutic drugs in humans. Our study highlights the importance of immune cell presentation in AOs for modeling inflammatory pulmonary diseases.
We report a fully integrated, pathogen-specific DNA extraction device utilizing centrifugal microfluidics on a polymer based CD platform. By use of the innovative laser irradiated Ferrowax microvalve ...(LIFM) together with the rapid cell lysis method using laser irradiation on magnetic particles, we could, for the first time, demonstrate a fully integrated pathogen specific DNA extraction from whole blood on a CD. As a model study, DNA extraction experiments from whole blood spiked with Hepatitis B virus (HBV) and E.coli were conducted. The total process of the plasma separation, mixing with magnetic beads conjugated with target specific antibodies, removal of plasma residual, washing and DNA extraction was finished within 12 min with only one manual step, the loading of 100 microL of whole blood. Real-time PCR results showed that the concentration of DNA prepared on a CD using a portable sample preparation device was as good as those by conventional bench top protocol. It demonstrates that our novel centrifugal microfluidics platform enables a full integration of complex biological reactions that require multi-step fluidic control.
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