BMI-for-age graphs with severe obesity percentile curves: Tools for plotting cross-sectional and longitudinal youth BMI data

Abstract Background Severe obesity is an important and distinct weight status classification that is associated with disease risk and is increasing in prevalence among youth. The ability to graphically present population weight status data, ranging from underweight through severe obesity class 3, is novel and applicable to epidemiologic research, intervention studies, case reports, and clinical care. Methods The aim was to create body mass index (BMI) graphing tools to generate sex-specific BMI-for-age graphs that include severe obesity percentile curves. We used the Centers for Disease Control and Prevention youth reference data sets and weight status criteria to generate the percentile curves. The statistical software environments SAS and R were used to create two different graphing options. Results This article provides graphing tools for creating sex-specific BMI-for-age graphs for males and females ages 2 to <20 years. The novel aspects of these graphing tools are an expanded BMI range to accommodate BMI values ˃35 kg/m2, inclusion of percentile curves for severe obesity classes 2 and 3, the ability to plot individual data for thousands of children and adolescents on a single graph, and the ability to generate cross-sectional and longitudinal graphs. Conclusions These new BMI graphing tools will enable investigators, public health professionals, and clinicians to view and present youth weight status data in novel and meaningful ways

Dynamics of methane ebullition from a peat monolith revealed from a dynamic flux chamber system

Methane (CH4) ebullition in northern peatlands is poorly quantified in part due to its high spatiotemporal variability. In this study, a dynamic flux chamber (DFC) system was used to continuously measure CH4 fluxes from a monolith of near‐surface Sphagnum peat at the laboratory scale to understand the complex behavior of CH4 ebullition. Coincident transmission ground penetrating radar measurements of gas content were also acquired at three depths within the monolith. A graphical method was developed to separate diffusion, steady ebullition, and episodic ebullition fluxes from the total CH4 flux recorded and to identify the timing and CH4 content of individual ebullition events. The results show that the application of the DFC had minimal disturbance on air‐peat CH4 exchange and estimated ebullition fluxes were not sensitive to the uncertainties associated with the graphical model. Steady and episodic ebullition fluxes were estimated to be averagely 36 ± 24% and 38 ± 24% of the total fluxes over the study period, respectively. The coupling between episodic CH4 ebullition and gas content within the three layers supports the existence of a threshold gas content regulating CH4 ebullition. However, the threshold at which active ebullition commenced varied between peat layers with a larger threshold (0.14 m3 m−3) observed in the deeper layers, suggesting that the peat physical structure controls gas bubble dynamics in peat. Temperature variation (23°C to 27°C) was likely only responsible for small episodic ebullition events from the upper peat layer, while large ebullition events from the deeper layers were most likely triggered by drops in atmospheric pressure

Trans-Neptunian Objects Transiently Stuck in Neptune's Mean Motion Resonances: Numerical simulations of the current population

A substantial fraction of our solar system's trans-Neptunian objects (TNOs) are in mean motion resonance with Neptune. Many of these objects were likely caught into resonances by planetary migration---either smooth or stochastic---approximately 4 Gyr ago. Some, however, gravitationally scattered off of Neptune and became transiently stuck in more recent events. Here, we use numerical simulations to predict the number of transiently-stuck objects, captured from the current actively scattering population, that occupy 111 resonances at semimajor axes $a=$30--100 au. Our source population is an observationally constrained model of the currently-scattering TNOs. We predict that, integrated across all resonances at these distances, the current transient sticking population comprises 40\% of total transiently-stuck+scattering TNOs, suggesting that these objects should be treated as a single population. We compute the relative distribution of transiently-stuck objects across all $p$:$q$ resonances with $1/6 \le q/p < 1$, $p<40$, and $q<20$, providing predictions for the population of transient objects with $H_r < 8.66$ in each resonance. We find that the relative populations are approximately proportional to each resonance's libration period and confirm that the importance of transient sticking increases with semimajor axis in the studied range. We calculate the expected distribution of libration amplitudes for stuck objects and demonstrate that observational constraints indicate that both the total number and the amplitude-distribution of 5:2 resonant TNOs are inconsistent with a population dominated by transient sticking from the current scattering disk. The 5:2 resonance hence poses a challenge for leading theories of Kuiper belt sculpting

Synaptic vesicle dynamics in mouse rod bipolar cells.

To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of 7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time constant that ranged from 2 to 21 s depending on the magnitude of the preceding Ca2+ transient. In addition, a brief, calcium-dependent delay often preceded the start of onset of membrane recovery. Thus, several aspects of synaptic vesicle dynamics appear to be conserved between rod-dominant bipolar cells of fish and mammalian rod bipolar cells. A major difference is that the number of vesicles available for release is significantly smaller in the mouse rod bipolar cell, both as a function of the total number per neuron and on a per active zone basis

Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity.

Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis

MYC is a critical target of FBXW7

MYC deregulation is a driver of many human cancers. Altering the balance of MYC protein levels at the level of transcription, protein stability, or turnover is sufficient to transform cells to a tumorigenic phenotype. While direct targeting of MYC is difficult, specific genetic vulnerabilities of MYC-deregulated cells could be exploited to selectively inhibit their growth. Using a genome-wide shRNA screen, we identified 78 candidate genes, which are required for survival of human mammary epithelial cells with elevated MYC levels. Among the candidates, we validated and characterized FBXW7, a component of the SCF-like ubiquitin ligase complex that targets MYC for proteasomal degradation. Down-regulation of FBXW7 leads to synergistic accumulation of cellular and active chromatin-bound MYC, while protein levels of other FBXW7 targets appear unaffected. Over a four-week time course, continuous FBXW7 down-regulation and MYC activation together cause an accumulation of cells in S-phase and G2/M-phase of the cell cycle. Under these conditions, we also observe elevated chromatin-bound levels of CDC45, suggesting increased DNA replication stress. Consistent with these results, FBXW7 down-regulation alone decreases the survival of T47D breast cancer cells. These results establish that FBXW7 downregulation is synthetic lethal with MYC, and that MYC is a critical target of FBXW7 in breast epithelial cells