Assessing residual consciousness and cognitive abilities in unresponsive patients is a major clinical concern and a challenge for cognitive neuroscience. Although neuroimaging studies have ...demonstrated a potential for informing diagnosis and prognosis in unresponsive patients, these methods involve sophisticated brain imaging technologies, which limit their clinical application. In this study, we adopted a new language paradigm that elicited rhythmic brain responses tracking the single-word, phrase and sentence rhythms in speech, to examine whether bedside electroencephalography (EEG) recordings can help inform diagnosis and prognosis. EEG-derived neural signals, including both speech-tracking responses and temporal dynamics of global brain states, were associated with behavioral diagnosis of consciousness. Crucially, multiple EEG measures in the language paradigm were robust to predict future outcomes in individual patients. Thus, EEG-based language assessment provides a new and reliable approach to objectively characterize and predict states of consciousness and to longitudinally track individual patients' language processing abilities at the bedside.
The lack of effective therapies that slow the progression of Alzheimer's disease (AD) and related tauopathies highlights the need for a more comprehensive understanding of the fundamental cellular ...mechanisms underlying these diseases. Model organisms, including yeast, worms, and flies, provide simple systems with which to investigate the mechanisms of disease. The evolutionary conservation of cellular pathways regulating proteostasis and stress response in these organisms facilitates the study of genetic factors that contribute to, or protect against, neurodegeneration. Here, we review genetic modifiers of neurodegeneration and related cellular pathways identified in the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, and the fruit fly Drosophila melanogaster, focusing on models of AD and related tauopathies. We further address the potential of simple model systems to better understand the fundamental mechanisms that lead to AD and other neurodegenerative disorders.
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential ...to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure. Activating the senescence pathway, either genetically or pharmacologically, in young beige progenitors induces premature cellular senescence and blocks their potential to form cold-induced beige adipocytes. Conversely, genetically or pharmacologically reversing cellular aging by targeting the p38/MAPK-p16Ink4a pathway in aged mouse or human beige progenitor cells rejuvenates cold-induced beiging. This in turn increases glucose sensitivity. Collectively, these data indicate that anti-aging or senescence modalities could be a strategy to induce beiging, thereby improving metabolic health in aging humans.
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•Cellular aging of beige progenitors prevents cold-induced beiging in older mammals•Inducing premature aging in young beige progenitors is sufficient to block beiging•Genetically reversing beige progenitor senescence rejuvenates beiging•Pharmacologically targeting aging rejuvenates progenitors and beiging potential
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes, but this process fails during aging. Berry et al. show that beige progenitors undergo an age-associated, senescence-like phenotype that accounts for this age-dependent beiging failure. Targeting the p38/Ink4a-Arf pathway rejuvenates beige progenitors and restores beiging potential.
Abstract
This research investigates how secrecy (i.e., a state in which people have an active intention to conceal information from others) affects individuals’ consumption behavior. Six studies ...reveal that making consumers’ secrets salient increases their tendency to conform in their consumption and show that this effect is driven by the desire to avoid social attention. This effect is moderated by consumers’ perceived self-control capacity. This research uncovers a novel downstream consequence of secrecy on consumer behavior and provides insight into when conforming consumption can serve as a strategy to help consumers avoid unwanted social attention. This research has important practical implications concerning using notions of secrecy in marketing strategies and promoting conforming products.
Surface browning after harvest is the primary constraint affecting the storage life and market circulation of rambutans. In this study, rambutan fruits were soaked in sodium nitroprusside at ...different concentrations and stored at 25°C for 8 days to explore the effects on postharvest quality and browning. The weight loss, browning index and superoxide anion radical, hydrogen peroxide and malondialdehyde contents of the treated fruits were reduced compared to those of the control fruits (soaked in distilled water). And fruits treated with sodium nitroprusside had a higher total phenolic content and lower polyphenol oxidase and peroxidase activity. In addition, compared with the control, the treated fruits exhibited higher phenylalanine ammonia lyase, ascorbate peroxidase and superoxide dismutase activities; titratable acidity; and soluble solid, vitamin C and protein contents, indicating high fruit quality. Overall, sodium nitroprusside treatment at 200 μmol L
demonstrated the most positive preservation effects. Therefore, sodium nitroprusside treatment, particularly at 200 μmol L
, can be used as an eco-friendly, safe and convenient method for postharvest quality management and high-efficiency preservation of rambutan fruits.
Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA)-mural cell-fate mapping, and conditional PPARγ deletion ...to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult progenitors are specified during the developmental period and express PPARγ, they have distinct microanatomical, functional, morphogenetic, and molecular profiles. Furthermore, the two compartments derive from different lineages; whereas adult adipose progenitors fate-map from an SMA+ mural lineage, developmental progenitors do not. Remarkably, the adult progenitor compartment appears to be specified earlier than the developmental cells and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide a discrete therapeutic target for childhood and adult obesity.
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•PPARγ+ progenitors are essential for adipose tissue organogenesis and homeostasis•Developmental and adult adipose progenitors show diverse features•Adult, but not developmental, adipocytes fate-map from a mural cell lineage•Adult progenitors are embryonically specified before developmental progenitors
Adipose tissue development and progenitor cell specification are unclear. Jiang et al. identify two types of adipose progenitor cells, developmental and adult, that participate in organogenesis and homeostasis, respectively. Only adult progenitors fate-map from a smooth muscle actin mural lineage and are specified during embryogenesis, highlighting a potential therapeutic target for childhood and adult obesity.
Harvesting energy through water motion on solid surface is significantly important due to the energy generation intermittency of the usually used energy transducers. In this paper,
n
-type silicon ...thin film is fabricated through magnetron sputtering followed by rapid thermal processing under different temperatures. The influence of the annealing temperatures on film crystallinity, phase, conductivity and conductivity activation energy is systematically investigated. Moreover, the voltage outputs on different silicon films through the sliding of NaCl solution droplet are systematically discussed. With increasing the annealing temperature from 300 to 900 °C, the voltage value increases firstly and then decreases, achieving a highest value of 1060 mV on the sample annealed at 600 °C, which is much higher than that of the mostly reported carbon materials. Finally, a schematic model, which is based on the combined effect of contact potential change between NaCl solution droplet and silicon film accompanied with the variation of the film conductivity, is proposed to unveil the underlying mechanism behind voltage output on various silicon films. All the findings provide not only a platform for achieving a higher output voltage but also a mechanism for a better understanding of the water motion induced energy harvesting.
Sex steroids modulate the distribution of mammalian white adipose tissues. Moreover, WAT remodeling requires adipocyte progenitor cells. Nevertheless, the sex-dependent mechanisms regulating ...adipocyte progenitors remain undetermined. Here, we uncover Cxcr4 acting in a sexually dimorphic manner to affect a pool of proliferating cells leading to restriction of female fat mass. We find that deletion of Cxcr4 in Pparγ-expressing cells results in female, not male, lipodystrophy, which cannot be restored by high-fat diet consumption. Additionally, Cxcr4 deletion is associated with a loss of a pool of proliferating adipocyte progenitors. Cxcr4 loss is accompanied by the upregulation of estrogen receptor alpha in adipose-derived PPARγ-labelled cells related to estradiol hypersensitivity and stalled adipogenesis. Estrogen removal or administration of antiestrogens restores WAT accumulation and dynamics of adipose-derived cells in Cxcr4-deficient mice. These findings implicate Cxcr4 as a female adipogenic rheostat, which may inform strategies to target female adiposity.Sex steroid receptor activity controls the distribution and growth of adipose tissues. Here, the authors reveal that Cxcr4 regulates the Pparg-marked adipose lineage to restrict female fat mass by modifying estrogen receptor expression and activity.
A potential therapeutic target to curb the obesity and diabetes epidemic is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. ...Here, we define the critical role of Cdkn2a as a molecular pedal for the beige-to-white transition. Beige adipocytes lacking Cdkn2a exhibit prolonged lifespan, and mice are more resistant to diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistic studies demonstrate that Cdkn2a promotes the expression and activity of BECN1 by directly binding to its mRNA and its negative regulator BCL2L1, activating autophagy and accelerating the beige-to-white transition. Notably, reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by Cdkn2a-ablation. Furthermore, hyperactive BECN1 alone significantly accelerates the beige-to-white transition. Collectively, these findings show that Cdkn2a-mediated autophagy serves as a brake system for beige adipocyte maintenance and is a highly promising target for anti-obesity and antidiabetes therapy.
Keywords: Beige adipocyte, UCP1, Cdkn2a, BECN1, Autophagy, Obesity
Disclosure
Y. Jiang: None.
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (K01DK11177, R03DK127149, R01DK132398); Diabetes Research and Training Center (P30DK020595)
Adipocytes arise from distinct progenitor populations during developmental and adult stages but little is known about how developmental progenitors differ from adult progenitors. Here, we investigate ...the role of platelet-derived growth factor receptor alpha (PDGFRα) in the divergent regulation of the two different adipose progenitor cells (APCs). Using in vivo adipose lineage tracking and deletion mouse models, we found that developmental PDGFRα+ cells are adipogenic and differentiated into mature adipocytes, and the deletion of
in developmental adipose lineage disrupted white adipose tissue (WAT) formation. Interestingly, adult PDGFRα+ cells do not significantly contribute to adult adipogenesis, and deleting
in adult adipose lineage did not affect WAT homeostasis. Mechanistically, embryonic APCs require PDGFRα for fate maintenance, and without PDGFRα, they underwent fate change from adipogenic to fibrotic lineage. Collectively, our findings indicate that PDGFRα+ cells and
gene itself are differentially required for WAT development and adult WAT homeostasis.
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