Tubulointerstitial fibrosis (TIF) is the hallmark of chronic kidney disease and best predictor of renal survival. Many different cell types contribute to TIF progression including tubular epithelial ...cells, myofibroblasts, endothelia, and inflammatory cells. Previously, most of the attention has centered on myofibroblasts given their central importance in extracellular matrix production. However, emerging data focuses on how the response of the proximal tubule, a specialized epithelial segment vulnerable to injury, plays a central role in TIF progression. Several proximal tubular responses such as de-differentiation, cell cycle changes, autophagy, and metabolic changes may be adaptive initially, but can lead to maladaptive responses that promote TIF both through autocrine and paracrine effects. This review discusses the current paradigm of TIF progression and the increasingly important role of the proximal tubule in promoting TIF both in tubulointerstitial and glomerular injuries. A better understanding and appreciation of the role of the proximal tubule in TIF has important implications for therapeutic strategies to halt chronic kidney disease progression.
•Tubulointerstitial fibrosis is the common pathway to end-stage renal disease.•Many different cell types contribute to tubulointerstitial fibrosis.•The proximal tubule is targeted in acute and chronic renal injuries.•Many proximal tubule responses are initially adaptive but can become maladaptive.•Proximal tubule responses to chronic injury drive tubulointerstitial fibrosis.
The kidney is a highly metabolically active organ that relies on specialized epithelial cells comprising the renal tubules to reabsorb most of the filtered water and solutes. Most of this ...reabsorption is mediated by the proximal tubules, and high amounts of energy are needed to facilitate solute movement. Thus, proximal tubules use fatty acid oxidation, which generates more adenosine triphosphate (ATP) than glucose metabolism, as its preferred metabolic pathway. After kidney injury, metabolism is altered, leading to decreased fatty acid oxidation and increased lactic acid generation. This review discusses how metabolism differs between the proximal and more distal tubular segments of the healthy nephron. In addition, metabolic changes in acute kidney injury and chronic kidney disease are discussed, as well as how these changes in metabolism may impact tubule repair and chronic kidney disease progression.
Background
Students and teachers in twenty-first century STEM classrooms face significant challenges in preparing for post-secondary education, career, and citizenship. Educators have advocated for ...student-centered instruction as a way to face these challenges, with multiple programs emerging to shape and define such contexts. However, the ways to support teachers as they transition into non-traditional teaching must be developed. The purpose of this study is to explore the impacts on educators of teaching in student-centered, peer-mediated STEM classrooms and preparing student peer leaders for their roles in these classes. Research questions examined how teachers think about themselves as they implement student-centered pedagogy, the difficulties they face as their roles and identities shift, and the ways they grow or resist growth. Qualitative research conducted at two urban secondary schools documents the diverse experiences and responses of teachers in an innovative, student-centered STEM instructional program. The experiences and perceptions of 13 STEM teachers illuminate the possibilities and challenges for teachers in student-centered classrooms.
Results
All participating teachers described multiple benefits of teaching in a student-centered classroom and differences from traditional classrooms. Their transitions to this type of teaching fell into three major categories based upon past identities and current beliefs. Some teachers found the pedagogy consistent with preexisting identities and embraced it without radical change to their concepts of teaching. They described ways in which the model helped them become the teachers they had always wanted to be. Other teachers, who initially identified as deliverers of STEM content, had more difficult experiences adjusting to student-centered instruction. In one case, a teacher resisted change and exited the program, maintaining her identity and deciding not to become student-centered. Other participating teachers made dramatic shifts in their identities in order to implement the program. These teachers described significant learning curves as they shared responsibility for student learning with student leaders.
Conclusions
This study suggests that radically changing the learning environment can affect teachers’ identities and their approaches to teaching in predictable ways that can inform teacher education and professional development programs for STEM teachers, maximizing the success of teachers as they implement student-centered pedagogy.
Organismal diversification can be modeled as the gain of new cell types.Just as the variation that arises during embryonic development can drive the emergence of new adult forms, so, too, can ...intracellular variation serve as a driver of cell type biodiversity.Examining phenomena, such as heterochrony, homeosis, and plasticity, in individual cells encourages the development of testable, mechanistic hypotheses regarding the emergence of new cell types.Application of new sequencing technologies to organisms from across the tree of life provides increased resolution for evaluating hypotheses about the relationship between genotype and phenotype at the individual cell level.The development of new tools for manipulating genomes frees us from the limited phenotypes that evolution has produced, allowing us to generate new cell phenotypes and explore the boundaries of cellular novelty.
Organisms are complex assemblages of cells, cells that produce light, shoot harpoons, and secrete glue. Therefore, identifying the mechanisms that generate novelty at the level of the individual cell is essential for understanding how multicellular life evolves. For decades, the field of evolutionary developmental biology (Evo-Devo) has been developing a framework for connecting genetic variation that arises during embryonic development to the emergence of diverse adult forms. With increasing access to new single cell ‘omics technologies and an array of techniques for manipulating gene expression, we can now extend these inquiries inward to the level of the individual cell. In this opinion, I argue that applying an Evo-Devo framework to single cells makes it possible to explore the natural history of cells, where this was once only possible at the organismal level.
Organisms are complex assemblages of cells, cells that produce light, shoot harpoons, and secrete glue. Therefore, identifying the mechanisms that generate novelty at the level of the individual cell is essential for understanding how multicellular life evolves. For decades, the field of evolutionary developmental biology (Evo-Devo) has been developing a framework for connecting genetic variation that arises during embryonic development to the emergence of diverse adult forms. With increasing access to new single cell ‘omics technologies and an array of techniques for manipulating gene expression, we can now extend these inquiries inward to the level of the individual cell. In this opinion, I argue that applying an Evo-Devo framework to single cells makes it possible to explore the natural history of cells, where this was once only possible at the organismal level.
Primates and rodents, which descended from a common ancestor around 90 million years ago
, exhibit profound differences in behaviour and cognitive capacity; the cellular basis for these differences ...is unknown. Here we use single-nucleus RNA sequencing to profile RNA expression in 188,776 individual interneurons across homologous brain regions from three primates (human, macaque and marmoset), a rodent (mouse) and a weasel (ferret). Homologous interneuron types-which were readily identified by their RNA-expression patterns-varied in abundance and RNA expression among ferrets, mice and primates, but varied less among primates. Only a modest fraction of the genes identified as 'markers' of specific interneuron subtypes in any one species had this property in another species. In the primate neocortex, dozens of genes showed spatial expression gradients among interneurons of the same type, which suggests that regional variation in cortical contexts shapes the RNA expression patterns of adult neocortical interneurons. We found that an interneuron type that was previously associated with the mouse hippocampus-the 'ivy cell', which has neurogliaform characteristics-has become abundant across the neocortex of humans, macaques and marmosets but not mice or ferrets. We also found a notable subcortical innovation: an abundant striatal interneuron type in primates that had no molecularly homologous counterpart in mice or ferrets. These interneurons expressed a unique combination of genes that encode transcription factors, receptors and neuropeptides and constituted around 30% of striatal interneurons in marmosets and humans.
To determine the relationship between the amount and intensity of physical activity performed by older adults in North America (United States and Canada) and their depression and anxiety symptoms ...while currently under social distancing guidelines (SDG) for the COVID-19 pandemic.
Descriptive cross-sectional study.
Online survey conducted between April 9 and April 30, 2020, during the COVD-19 pandemic.
About 1,046 older adults over the age of 50 who live in North America.
Participants were asked about their basic demographic information, current health status, and the impact of the current SDG on their subjective state of mental health. Participants completed the Physical Activity Scale for the Elderly, to determine the amount and intensity of physical activity performed, as well as both the Geriatric Depression Scale and Geriatric Anxiety Scale, to ascertain the extent of their depression and anxiety-like symptoms.
Ninety-seven percent of participants indicated that they adhered to current SDG "Most of the time" or "Strictly." Participants who performed greater levels of physical activity experienced lower levels of depression-like symptoms when age, sex, and education were accounted for; however, no relationship between physical activity and anxiety-like symptoms was found. A hierarchical regression analysis that incorporated the intensity of physical activity performed (light, moderate, and vigorous) in the model indicated that greater light and strenuous activity, but not moderate, predicted lower depression-like symptoms.
These results suggest that performing even light physical activity during the COVID-19 pandemic may help alleviate some of the negative mental health impacts that older adults may be experiencing while isolated and adhering to SDG during the COVID-19 pandemic.
Abstract
The endoplasmic reticulum (ER) mediates the first steps of protein assembly within the secretory pathway and is the site where protein folding and quality control are initiated. The storage ...and release of Ca2+ are critical physiological functions of the ER. Disrupted ER homeostasis activates the unfolded protein response (UPR), a pathway which attempts to restore cellular equilibrium in the face of ER stress. Unremitting ER stress, and insufficient compensation for it results in beta-cell apoptosis, a process that has been linked to both type 1 diabetes (T1D) and type 2 diabetes (T2D). Both types are characterized by progressive beta-cell failure and a loss of beta-cell mass, although the underlying causes are different. The reduction of mass occurs secondary to apoptosis in the case of T2D, while beta cells undergo autoimmune destruction in T1D. In this review, we examine recent findings that link the UPR pathway and ER Ca2+ to beta cell dysfunction. We also discuss how UPR activation in beta cells favors cell survival versus apoptosis and death, and how ER protein chaperones are involved in regulating ER Ca2+ levels.
Abbreviations: BiP, Binding immunoglobulin Protein ER; endoplasmic reticulum; ERAD, ER-associated protein degradation; IFN, interferon; IL, interleukin; JNK, c-Jun N-terminal kinase; KHE, proton-K+ exchanger; MODY, maturity-onset diabetes of young; PERK, PRKR-like ER kinase; SERCA, Sarco/Endoplasmic Reticulum Ca2+-ATPases; T1D, type 1 diabetes; T2D, type 2 diabetes; TNF, tumor necrosis factor; UPR, unfolded protein response; WRS, Wolcott–Rallison syndrome.
Synthetic chemists have developed robust methods to synthesize discrete molecules, linear and branched polymers, and disordered cross-linked networks. However, two-dimensional polymers (2DPs) ...prepared from designed monomers have been long missing from these capabilities, both as objects of chemical synthesis and in nature. Recently, new polymerization strategies and characterization methods have enabled the unambiguous realization of covalently linked macromolecular sheets. Here we review 2DPs and 2D polymerization methods. Three predominant 2D polymerization strategies have emerged to date, which produce 2DPs either as monolayers or multilayer assemblies. We discuss the fundamental understanding and scope of each of these approaches, including: the bond-forming reactions used, the synthetic diversity of 2DPs prepared, their multilayer stacking behaviors, nanoscale and mesoscale structures, and macroscale morphologies. Additionally, we describe the analytical tools currently available to characterize 2DPs in their various isolated forms. Finally, we review emergent 2DP properties and the potential applications of planar macromolecules. Throughout, we highlight achievements in 2D polymerization and identify opportunities for continued study.
The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and ...adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs).
Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols.
The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options.
This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis.
= 25-hydroxyvitamin D;
= American Association of Clinical Endocrinologists;
= American College of Endocrinology;
= atypical femoral fracture;
= American Society for Bone and Mineral Research;
= best evidence level;
= bone mineral density;
= bone turnover marker;
= confidence interval;
= clinical practice guideline;
= C-terminal telopeptide type-I collagen;
= dual-energy X-ray absorptiometry;
= evidence level;
= U.S. Food and Drug Administration;
= Fracture Risk Assessment Tool;
= gastrointestinal;
= Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly Pivotal Fracture Trial (zoledronic acid and zoledronate are equivalent terms);
= International Society for Clinical Densitometry;
= international units;
= intravenous;
= least significant change;
= National Osteoporosis Foundation;
= osteonecrosis of the jaw;
= serum amino-terminal propeptide of type-I collagen;
= parathyroid hormone;
= recommendation;
= region of interest;
= relative risk;
= standard deviation;
= trabecular bone score;
= vertebral fracture assessment;
= World Health Organization.
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