This article summarizes correlational, case-control, quasi-experimental, and experimental studies that have examined whether sleep during childhood and adolescence is related to daytime functioning. ...Published findings suggest that inadequate sleep quality and/or quantity can cause sleepiness, inattention and, very likely, other cognitive and behavioral deficits that significantly impact children and adolescents in functional settings. This article then integrates findings from longitudinal studies within a developmental psychopathology model. Important questions remain, but evidence supports the integration of sleep screening and interventions into routine clinical care and also supports advocacy for public policy changes to improve the sleep of children and adolescents.
This review covers publications ranging from 2005 to 2017 concerning the organic reactions of aromatic ligands η2-coordinated to tungsten or molybdenum and the use of these reactions in the synthesis ...of novel organic substances. An emphasis is placed on C–C bond-forming reactions using conventional building blocks of organic synthesis such as acetals, enolates, Michael acceptors, acylating reagents, and activated aromatics. Substrates activated by the metal include arenes, pyridines, pyrroles, pyrimidines, furans, and thiophenes. General reactivity patterns are elucidated, as well as stereochemical preferences. These trends are compared to those of osmium and rhenium forebears as well as to the reactivity patterns of other methods of stoichiometric transition-metal-based dearomatization (i.e., η6-arene complexes).
MYC regulates the transcription of thousands of genes required to coordinate a range of cellular processes, including those essential for proliferation, growth, differentiation, apoptosis and ...self-renewal. Recently, MYC has also been shown to serve as a direct regulator of ribosome biogenesis. MYC coordinates protein synthesis through the transcriptional control of RNA and protein components of ribosomes, and of gene products required for the processing of ribosomal RNA, the nuclear export of ribosomal subunits and the initiation of mRNA translation. We discuss how the modulation of ribosome biogenesis by MYC may be essential to its physiological functions as well as its pathological role in tumorigenesis.
The MYC proto-oncogenes encode a family of transcription factors that are among the most commonly activated oncoproteins in human neoplasias. Indeed, MYC aberrations or upregulation of MYC-related ...pathways by alternate mechanisms occur in the vast majority of cancers. MYC proteins are master regulators of cellular programmes. Thus, cancers with MYC activation elicit many of the hallmarks of cancer required for autonomous neoplastic growth. In preclinical models, MYC inactivation can result in sustained tumour regression, a phenomenon that has been attributed to oncogene addiction. Many therapeutic agents that directly target MYC are under development; however, to date, their clinical efficacy remains to be demonstrated. In the past few years, studies have demonstrated that MYC signalling can enable tumour cells to dysregulate their microenvironment and evade the host immune response. Herein, we discuss how MYC pathways not only dictate cancer cell pathophysiology but also suppress the host immune response against that cancer. We also propose that therapies targeting the MYC pathway will be key to reversing cancerous growth and restoring antitumour immune responses in patients with MYC-driven cancers.
The MYC proto-oncogene is a gene product that coordinates the transcriptional regulation of a multitude of genes that are essential to cellular programs required for normal as well as neoplastic ...cellular growth and proliferation, including cell cycle, self-renewal, survival, cell growth, metabolism, protein and ribosomal biogenesis, and differentiation. Here, we propose that MYC regulates these programs in a manner that is coordinated with a global influence on the host immune response. MYC had been presumed to contribute to tumorigenesis through tumor cell–intrinsic influences. More recently, MYC expression in tumor cells has been shown to regulate the tumor microenvironment through effects on both innate and adaptive immune effector cells and immune regulatory cytokines. Then, MYC was shown to regulate the expression of the immune checkpoint gene products CD47 and programmed death-ligand 1. Similarly, other oncogenes, which are known to modulate MYC, have been shown to regulate immune checkpoints. Hence, MYC may generally prevent highly proliferative cells from eliciting an immune response. MYC-driven neoplastic cells have coopted this mechanism to bypass immune detection. Thus, MYC inactivation can restore the immune response against a tumor. MYC-induced tumors may be particularly sensitive to immuno-oncology therapeutic interventions.
The MYC oncogene codes for a transcription factor that is overexpressed in many human cancers. Here we show that MYC regulates the expression of two immune checkpoint proteins on the tumor cell ...surface: the innate immune regulator CD47 (cluster of differentiation 47) and the adaptive immune checkpoint PD-L1 (programmed death–ligand 1). Suppression of MYC in mouse tumors and human tumor cells caused a reduction in the levels of CD47 and PD-L1 messenger RNA and protein. MYC was found to bind directly to the promoters of the Cd47 and Pd-l1 genes. MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response. In contrast, when MYC was inactivated in tumors with enforced expression of CD47 or PD-L1, the immune response was suppressed, and tumors continued to grow. Thus, MYC appears to initiate and maintain tumorigenesis, in part, through the modulation of immune regulatory molecules.
•Vegetative biomass, percent groundcover, and spectral reflectance were measured on six winter cover crop fields over the 2012–2013 growing season.•Relationships between groundcover, biomass and 10 ...spectral vegetation indices were explored.•Restriction of analysis to early sampling dates strengthened relationships due to issues associated with yellowing and frost damage on leaves.•Different vegetation indices should be used for low and high biomass ranges to account for index saturation, and to account for greater sensitivity of some indices to low biomass vegetation.
Winter cover crops are an essential part of managing nutrient and sediment losses from agricultural lands. Cover crops lessen sedimentation by reducing erosion, and the accumulation of nitrogen in aboveground biomass results in reduced nutrient runoff. Winter cover crops are planted in the fall and are usually terminated in early spring, making them susceptible to senescence, frost burn, and leaf yellowing due to wintertime conditions. This study sought to determine to what extent remote sensing indices are capable of accurately estimating the percent groundcover and biomass of winter cover crops, and to analyze under what critical ranges these relationships are strong and under which conditions they break down. Cover crop growth on six fields planted to barley, rye, ryegrass, triticale or wheat was measured over the 2012–2013 winter growing season. Data collection included spectral reflectance measurements, aboveground biomass, and percent groundcover. Ten vegetation indices were evaluated using surface reflectance data from a 16-band CROPSCAN sensor. Restricting analysis to sampling dates before the onset of prolonged freezing temperatures and leaf yellowing resulted in increased estimation accuracy. There was a strong relationship between the normalized difference vegetation index (NDVI) and percent groundcover (r2=0.93) suggesting that date restrictions effectively eliminate yellowing vegetation from analysis. The triangular vegetation index (TVI) was most accurate in estimating high ranges of biomass (r2=0.86), while NDVI did not experience a clustering of values in the low and medium biomass ranges but saturated in the higher range (>1500kg/ha). The results of this study show that accounting for index saturation, senescence, and frost burn on leaves can greatly increase the accuracy of estimates of percent groundcover and biomass for winter cover crops.
Chemical doping with foreign atoms is an effective method to intrinsically modify the properties of host materials. Among them, nitrogen doping plays a critical role in regulating the electronic ...properties of carbon materials. Recently, graphene, as a true two-dimensional carbon material, has shown fascinating applications in bioelectronics and biosensors. In this paper, we report a facile strategy to prepare N-doped graphene by using nitrogen plasma treatment of graphene synthesized via a chemical method. Meanwhile, a possible schematic diagram has been proposed to detail the structure of N-doped graphene. By controlling the exposure time, the N percentage in host graphene can be regulated, ranging from 0.11 to 1.35%. Moreover, the as-prepared N-doped graphene has displayed high electrocatalytic activity for reduction of hydrogen peroxide and fast direct electron transfer kinetics for glucose oxidase. The N-doped graphene has further been used for glucose biosensing with concentrations as low as 0.01 mM in the presence of interferences.
Background
The relationship between inadequate sleep and mood has been well‐established in adults and is supported primarily by correlational data in younger populations. Given that adolescents often ...experience shortened sleep on school nights, we sought to better understand the effect of experimentally induced chronic sleep restriction on adolescents’ mood and mood regulation.
Methods
Fifty healthy adolescents, ages 14–17, completed a 3‐week sleep manipulation protocol involving a baseline week, followed by a sleep restriction (SR) condition (6.5 hr in bed per night for five nights) and healthy sleep duration (HS) condition (10 hr in bed per night for five nights). The study used a randomized, counterbalanced, crossover experimental design. Participants’ sleep was monitored at home via self‐report and actigraphy. At the end of each condition, participants and their parents completed questionnaires of mood and mood regulation. To assess for expectancy effects, we also analyzed parent and teen ratings of hyperactivity/impulsivity, which prior research suggests is not sensitive to SR in adolescents. Wilcoxon Signed Rank tests compared questionnaire outcomes across the two conditions.
Results
Participants averaged 2.5 more hours of sleep per night during HS relative to SR. Compared with HS, adolescents rated themselves as significantly more tense/anxious, angry/hostile, confused, and fatigued, and as less vigorous (p = .001–.01) during SR. Parents and adolescents also reported greater oppositionality/irritability and poorer emotional regulation during SR compared with HS (p < .05). There were no cross‐condition differences in depression or hyperactivity/impulsivity (p > .05).
Conclusions
Findings complement prior correlational study results to show that after only a few days of shortened sleep, at a level of severity that is experienced regularly by millions of adolescents on school nights, adolescents have worsened mood and decreased ability to regulate negative emotions.
Metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Here we investigated metabolic dependencies in a panel of ccRCC cell lines using nutrient depletion, ...functional RNAi screening and inhibitor treatment. We found that ccRCC cells are highly sensitive to the depletion of glutamine or cystine, two amino acids required for glutathione (GSH) synthesis. Moreover, silencing of enzymes of the GSH biosynthesis pathway or glutathione peroxidases, which depend on GSH for the removal of cellular hydroperoxides, selectively reduced viability of ccRCC cells but did not affect the growth of non-malignant renal epithelial cells. Inhibition of GSH synthesis triggered ferroptosis, an iron-dependent form of cell death associated with enhanced lipid peroxidation. VHL is a major tumour suppressor in ccRCC and loss of VHL leads to stabilisation of hypoxia inducible factors HIF-1α and HIF-2α. Restoration of functional VHL via exogenous expression of pVHL reverted ccRCC cells to an oxidative metabolism and rendered them insensitive to the induction of ferroptosis. VHL reconstituted cells also exhibited reduced lipid storage and higher expression of genes associated with oxidiative phosphorylation and fatty acid metabolism. Importantly, inhibition of β-oxidation or mitochondrial ATP-synthesis restored ferroptosis sensitivity in VHL reconstituted cells. We also found that inhibition of GSH synthesis blocked tumour growth in a MYC-dependent mouse model of renal cancer. Together, our data suggest that reduced fatty acid metabolism due to inhibition of β-oxidation renders renal cancer cells highly dependent on the GSH/GPX pathway to prevent lipid peroxidation and ferroptotic cell death.
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