Merrillbarefoot8907

Energetic challenges match intestinal size to dietary intake but less is known about how the intestine responds to specific macronutrient challenges. We examined how intestinal size responds to insufficient dietary protein at the microscopic level. Villi, enterocytes, and surface area were measured across the length of the small intestine in non-reproductive and lactating Mus musculus fed isocaloric control or protein-deficient diets. Lactating mice on the protein-deficient diet exhibited a 24% increase in villus height and a 30% increase in enterocyte width in the proximal small intestine and an overall similar increase in surface area; on the control diet changes in villus height were localized in the mid region. Flexibility localized to the proximal small intestine suggests that enterokinase, a localized enzyme, may be a candidate enzyme that could promote compensation for a protein-deficient diet. Such flexibility could allow species to persist in the face of anthropogenically-induced changing dietary profiles. © 2020. Published by The Company of Biologists Ltd.PURPOSE Diffuse intrinsic pontine glioma (DIPG) is an incurable type of pediatric brain cancer, which in the majority of cases is driven by mutations in genes encoding histone 3 (H3K27M). We here determined the preclinical therapeutic potential of combined AXL and HDAC inhibition in these tumors to reverse their mesenchymal, therapy-resistant, phenotype. EXPERIMENTAL DESIGN We used public databases and patient-derived DIPG cells to identify putative drivers of the mesenchymal transition in these tumors. Patient-derived neurospheres, xenografts and allografts were used to determine the therapeutic potential of combined AXL/HDAC inhibition for the treatment of DIPG. RESULTS We identified AXL as a therapeutic target and regulator of the mesenchymal transition in DIPG. Combined AXL and HDAC inhibition had a synergistic and selective antitumor effect on H3K27M DIPG cells. Treatment of DIPG cells with the AXL inhibitor BGB324 and the HDAC inhibitor panobinostat resulted in a decreased expression of mesenchymal and stem cell genes. Moreover, this combination treatment decreased expression of DNA damage repair genes in DIPG cells, strongly sensitizing them to radiation. Pharmacokinetic studies showed that BGB324, like panobinostat, crosses the blood-brain barrier. Consequently, treatment of patient-derived DIPG xenograft and murine DIPG allograft-bearing mice with BGB324 and panobinostat resulted in a synergistic antitumor effect and prolonged survival. CONCLUSION Combined inhibition of AXL and HDACs in DIPG cells results in a synergistic antitumor effect by reversing their mesenchymal, stem cell-like, therapy-resistant phenotype. As such, this treatment combination may serve as part of a future multimodal therapeutic strategy for DIPG. Copyright ©2020, American Association for Cancer Research.Spin-orbit coupling has proven indispensable in the realization of topological materials and, more recently, Ising pairing in two-dimensional superconductors. This pairing mechanism relies on inversion symmetry-breaking and sustains anomalously large in-plane polarizing magnetic fields whose upper limit is predicted to diverge at low temperatures. Here, we show that the recently discovered superconductor few-layer stanene, epitaxially strained gray tin (α-Sn), exhibits a distinct type of Ising pairing between carriers residing in bands with different orbital indices near the Γ-point. The bands are split as a result of spin-orbit locking without the participation of inversion symmetry-breaking. The in-plane upper critical field is strongly enhanced at ultralow temperature and reveals the predicted upturn. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.BACKGROUND Identifying biomarkers to predict kidney transplant failure and to define new therapeutic targets requires more comprehensive understanding of the immune response to chronic allogeneic stimulation. METHODS We investigated the frequency and function of CD8+ T cell subsets-including effector memory (EM) and terminally differentiated EM (TEMRA) CD8+ T cells-in blood samples from 284 kidney transplant recipients recruited 1 year post-transplant and followed for a median of 8.3 years. We also analyzed CD8+ T cell reactivity to donor-specific PBMCs in 24 patients who had received living-donor kidney transplants. RESULTS Increased frequency of circulating TEMRA CD8+ T cells at 1 year post-transplant associated with increased risk of graft failure during follow-up. This association remained after adjustment for a previously reported composite of eight clinical variables, the Kidney Transplant Failure Score. In contrast, increased frequency of EM CD8+ T cells associated with reduced risk of graft failure. Aology.Malignant pleural effusion is common and causes disabling symptoms such as breathlessness. Treatments are palliative and centred around improving symptoms and quality of life but an optimal management strategy is yet to be universally agreed. selleck products A novel pump system, allowing fluid to be moved from the pleural space to the urinary bladder, may have a role for the management of recurrent malignant pleural effusion. We hereby describe the first animal study using this device and the results of the first application in patients. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.We consider the question of how sensory networks enable the detection of sensory stimuli in a combinatorial coding space. We are specifically interested in the olfactory system, wherein recent experimental studies have reported the existence of rich, enigmatic response patterns associated with stimulus onset and offset. This study aims to identify the functional relevance of such response patterns, i.e., what benefits does such neural activity provide in the context of detecting stimuli in a natural environment. We study this problem through the lens of normative, optimization-based modeling. Here, we define the notion of a low dimensional latent representation of stimulus identity, which is generated through action of the sensory network. The objective of our optimization framework is to ensure high fidelity tracking of a nominal representation in this latent space in an energy efficient manner. It turns out that the optimal motifs emerging from this framework possess morphological similarity with prototypical onset and offset responses observed in vivo in locusts (Schistocerca americana) of either sex.