At the heart of the canonical Wnt signaling pathway is the beta-catenin destruction complex, which functions in the absence of Wnt signaling to keep the cytosolic and nuclear levels of beta-catenin ...very low by promoting the phosphorylation and ubiquitination of beta-catenin. Structural studies, combined with other experimental approaches, have begun to provide important insights into the mechanism of the destruction complex. We suggest a working model for the destruction complex based on the existing structural and experimental data, and focus on the questions that this model and other studies have raised about the function of the complex in both the normal and Wnt-inhibited states.
Studies suggest that the Mediterranean-style diet (MSD) may improve glucose metabolism in patients with type 2 diabetes (T2D), but the results are inconsistent. We conducted a meta-analysis of ...randomized controlled trials (RCTs) to explore the effects of MSD on glycemic control, weight loss and cardiovascular risk factors in T2D patients.
We performed searches of EMBASE, Cochrane Library and PubMed databases up to February 2014. We included RCTs that compared the MSD with control diets in patients with T2D. Effect size was estimated as mean difference with 95% confidence interval (CI) by using random effect models.
The meta-analysis included nine studies with 1178 patients. Compared with control diets, MSD led to greater reductions in hemoglobin A1c (mean difference, -0.30; 95% CI, -0.46 to -0.14), fasting plasma glucose (-0.72 mmol/l; CI, -1.24 to -0.21), fasting insulin (-0.55 μU/ml; CI, -0.81 to -0.29), body mass index (-0.29 kg/m(2); CI, -0.46 to -0.12) and body weight (-0.29 kg; CI, -0.55 to -0.04). Likewise, concentrations of total cholesterol and triglyceride were decreased (-0.14 mmol/l; CI, -0.19 to -0.09 and -0.29 mmol/l; CI, -0.47 to -0.10, respectively), and high-density lipoprotein was increased (0.06 mmol/l; CI, 0.02 to 0.10). In addition, MSD was associated with a decline of 1.45 mm Hg (CI, -1.97 to -0.94) for systolic blood pressure and 1.41 mm Hg (CI, -1.84 to -0.97) for diastolic blood pressure.
The present meta-analysis provides evidence that MSD improves outcomes of glycemic control, body weight and cardiovascular risk factors in T2D patients.
We observe the emergence of a disorder-induced insulating state in a strongly interacting atomic Fermi gas trapped in an optical lattice. This closed quantum system, free of a thermal reservoir, ...realizes the disordered Fermi-Hubbard model, which is a minimal model for strongly correlated electronic solids. We observe disorder-induced localization of a metallic state through measurements of mass transport. By varying the lattice potential depth, we detect interaction-driven delocalization of the disordered insulating state. We also measure localization that persists as the temperature of the gas is raised. These behaviors are consistent with many-body localization, which is a novel paradigm for understanding localization in interacting quantum systems at nonzero temperature.
•A deep convolutional neural network is established to measure PACBED parameters including size, center, rotation, thickness and tilt.•The convolutional neural network automatically analyzes PACBED ...patterns at a rate of 0.1 s/pattern, orders of magnitude faster than brute force methods.•The method is demonstrated to be well suited for big data analysis.•A methodology to evaluate the convolutional neural network response is proposed and explored.•A convolutional neural network/least squares hybrid method is proposed for further generalization and to accelerate processing.
We establish a series of deep convolutional neural networks to automatically analyze position averaged convergent beam electron diffraction patterns. The networks first calibrate the zero-order disk size, center position, and rotation without the need for pretreating the data. With the aligned data, additional networks then measure the sample thickness and tilt. The performance of the network is explored as a function of a variety of variables including thickness, tilt, and dose. A methodology to explore the response of the neural network to various pattern features is also presented. Processing patterns at a rate of ∼ 0.1 s/pattern, the network is shown to be orders of magnitude faster than a brute force method while maintaining accuracy. The approach is thus suitable for automatically processing big, 4D STEM data. We also discuss the generality of the method to other materials/orientations as well as a hybrid approach that combines the features of the neural network with least squares fitting for even more robust analysis. The source code is available at https://github.com/subangstrom/DeepDiffraction.
Electrical current in conventional metals is carried by electrons that retain their individual character. Bad metals, such as the normal state of some high-temperature superconductors, violate this ...scenario, and the complete picture for their behavior remains unresolved. Here, we report phenomena consistent with bad-metal behaviour in an optical-lattice Hubbard model by measuring the transport lifetime for a mass current excited by stimulated Raman transitions. We demonstrate incompatibility with weak-scattering theory and key characteristics of bad metals: anomalous resistivity scaling consistent with T-linear behavior, the onset of incoherent transport, and the approach to the Mott-Ioffe-Regel limit. Our work demonstrates a direct method for determining the transport lifetime, which is critical to theory but difficult to measure in materials, and exposes minimal ingredients for bad-metal behavior.
This study examines the persistent impacts of historical racebased discriminatory housing policies on contemporary urban environments in the United States. Specifically, we examine the relationships ...between Home Owners' Loan Corporation (HOLC) grades assigned to neighborhoods in the 1930s and the current distribution of tree canopy and level of exposure to air pollution hazards. Our results indicate a clear gradient in tree canopy by HOLC grade, with better neighborhood grades associated with significantly higher percentage of tree canopy coverage. The pattern also exists for airborne carcinogens and respiratory hazards, with worse neighborhood grades associated with significantly higher hazards exposure. Our findings indicate that early 20th century discriminatory housing policies exert a contemporary influence on patterns of green space exposure in American cities, with implications for health and health inequities. Our findings suggest that, in order to achieve equitable access to the benefits of urban greenspace, we must acknowledge these historical influences and consider policies and practices that directly counter these influences, for example, through targeted greenspace development in areas historically identified as unfit for investment.
•Increasing urban tree canopy is a recognized strategy to reduce air pollutants.•There is a systematic disparity in spatial distributions of urban tree canopy.•Current levels of tree canopy reflect a gradient established by the HOLC maps.•There is a similar gradient in airborne carcinogens and respiratory hazards.
SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, ...however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein levels in human gastric cancer tissues, and SALL4 level was highly correlated with lymph node metastasis. Enforced expression of SALL4 enhanced the proliferation and migration of human gastric cancer cells, whereas knockdown of SALL4 by siRNA led to the opposite effects. In addition, SALL4 overexpression promoted the growth and metastasis of gastric xenograft tumor in vivo. SALL4 overexpression induced epithelial-mesenchymal transition (EMT) in gastric cancer cells, with increased expression of Twist1, N-cadherin and decreased expression of E-cadherin. Moreover, SALL4 promoted the acquirement of stemness in gastric cancer cells through the induction of Bmi-1 and Lin28B. Taken together, our findings indicate that SALL4 has oncogenic roles in gastric cancer through the modulation of EMT and cell stemness, suggesting SALL4 as a novel target for human gastric cancer diagnosis and therapy.
Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH). Here, we show that microglia mediate this process and its functional impact. ...Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs), only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.
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•Saturated fats build up specifically in the hypothalamus when consumed in excess•Hypothalamic microglia directly and specifically sense saturated fatty acids•Microglia orchestrate hypothalamic inflammation due to excess saturated fat intake•Microglia dictate the impact of high dietary saturated fat on hypothalamic function
High-fat diets stimulate inflammation in the brain that is implicated in obesity. Here, Valdearcos et al. identify hypothalamic microglia as sensors of saturated fat that orchestrate local inflammation when dietary intake is high. In this context, microglia mediate the impact of saturated fat on leptin responsiveness and regulate food intake.
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