The gain-of-function MUC5B promoter variant rs35705950 is the dominant risk factor for developing idiopathic pulmonary fibrosis (IPF). Here we show in humans that MUC5B, a mucin thought to be ...restricted to conducting airways, is co-expressed with surfactant protein C (SFTPC) in type 2 alveolar epithelia and in epithelial cells lining honeycomb cysts, indicating that cell types involved in lung fibrosis in distal airspace express MUC5B. In mice, we demonstrate that Muc5b concentration in bronchoalveolar epithelia is related to impaired mucociliary clearance (MCC) and to the extent and persistence of bleomycin-induced lung fibrosis. We also establish the ability of the mucolytic agent P-2119 to restore MCC and to suppress bleomycin-induced lung fibrosis in the setting of Muc5b overexpression. Our findings suggest that mucociliary dysfunction might play a causative role in bleomycin-induced pulmonary fibrosis in mice overexpressing Muc5b, and that MUC5B in distal airspaces is a potential therapeutic target in humans with IPF.
•We offer a “big picture” view of efforts spanning almost a century to improve the biomass cook-stove or chulha used throughout rural India.•We identify motives that galvanize development agents ...(foresters, engineers, feminists, etc.) around a shared goal of improving stoves.•We synthesize technical/applied research and critical/feminist analyses of development to explain failure of improved stove efforts.•Seeking middle ground, we reject the optimism of experts who define problems as technical and the pessimism of their critics.
An estimated 2.7 billion people cook meals on biomass-fueled brick, stone, and clay stoves. Scarcity of wood and negative impacts on health and environment have motivated efforts to design and distribute “improved” cook-stoves in developing countries. In India, adoption is limited despite massive promotion over many decades. Existing research suggests that many rural women in India do not want improved stoves, and those who do face obstacles to adoption. We step back from the many good case studies to examine the broader story of improved cook-stoves (ICs) in India. We do so by bringing together technical research of applied science and narrative critique of social science. Rather than assuming a priori that traditional stoves require replacement, we ask why Indian cook-stoves been a magnet for so much attention, why adoptions rates have remained low, and what lessons might be learned from a broad, multi-disciplinary perspective. Our approach is critical and reflexive, given our own involvement in IC efforts, and puts gender at the center. Our “big picture” review shows that the Indian chulha, for all its problems, is a remarkably successful technology which also satisfies several important household needs. Hence, targeting this device for obsolescence has profound implications that cannot be reduced to energy consumption or environmental hazards. Rural women do not prioritize ICs, but addressing their priorities requires either capital-intensive investment or challenging powerful institutions. In contrast, IC interventions are relatively cheap, decentralized, mechanical and seemingly apolitical, hence their popularity in development programs. Our review of chulha research leads us to reject both the optimism of development planners who frame such problems as technical and the antagonistic pessimism of their critics. Searching for a middle ground requires stepping back from the dogma of efforts to improve biomass cook-stoves.
Natural killer (NK) cells have been reported to control adaptive immune responses that occur in lymphoid organs at the early stages of immune challenge. The physiological purpose of such regulatory ...activity remains unclear, because it generally does not confer a survival advantage. We found that NK cells specifically eliminated activated CD4+ T cells in the salivary gland during chronic murine cytomegalovirus (MCMV) infection. This was dependent on TNF-related apoptosis inducing ligand (TRAIL) expression by NK cells. Although NK cell-mediated deletion of CD4+ T cells prolonged the chronicity of infection, it also constrained viral-induced autoimmunity. In the absence of this activity, chronic infection was associated with a Sjogren’s-like syndrome characterized by focal lymphocytic infiltration into the glands, production of autoantibodies, and reduced saliva and tear secretion. Thus, NK cells are an important homeostatic control that balances the efficacy of adaptive immune responses with the risk of developing autoimmunity.
Display omitted
•A novel TRAIL+ NK cell subset regulates immune responses in chronic viral infection•TRAIL+ NK cells eliminate activated CD4+ T cells, but lack antiviral capacity•Development of autoimmune disease is constrained by TRAIL+ NK cells
Natural killer (NK) cells can regulate adaptive immunity but the physiological purpose of this has been unclear. Degli-Esposti and colleagues demonstrate that NK cells utilize TRAIL to limit CD4+ T cell responses during chronic viral infection to constrain the development of autoimmunity.
Ninety years ago Great Plains archaeologists such as Waldo Wedel and William Duncan Strong made foundational contributions to American archaeology, enabling new discoveries, insights, ...and interpretations. This volume explores how twenty-first-century archaeologists have built upon, remodeled, and sometimes rejected the inferences of these earlier scholars with updated overviews and analyses.
Contributors highlight how Indigenous Plains groups participated in large-scale social networks in which ideas, symbols, artifacts, and people moved across North America over the last 2,000 years. They also discuss cultural transformation, focusing on key demographic, economic, social, and ceremonial factors associated with change, including colonization and integration into the social and political economies of transatlantic societies. Cultural traditions covered include Woodland-era Kansas City Hopewell, late prehistoric Central Plains tradition, and ancestral and early historic Wichita, Pawnee and Arikara, Kanza, Plains Apache, and Puebloan migrants. As the first review of Plains archaeology in more than a decade, this book brings studies of early Indigenous
peoples of the central and southern Plains into a new era.
The functions of 1, 25-dihydroxyvitamin D (1, 25-(OH)2D3) in regulating adipogenesis, adipocyte differentiation and key adipogenic gene expression were studied in 3T3-L1 preadipocytes. Five ...concentrations (0.01, 0.1, 1, 10, 100 nM) of 1, 25-(OH)2D3 were studied and lipid accumulation measured by Oil Red O staining and expression of adipogenic genes quantified using quantitative real-time PCR. Adipogenic responses to 1, 25-(OH)2D3 were determined on 6, and 12 h, and days 1-10 after induction of adipogenesis by a hormonal cocktail with or without 1, 25-(OH)2D3. In response to 1, 25-(OH)2D3 (1, 10, and 100 nM), lipid accumulation and the expression of PPARγ, C/EBPα, FABP4 and SCD-1 were inhibited through day 10, and vitamin D receptor expression was inhibited in the early time points. The greatest inhibitory effect was upon expression of FABP4. Expression of SREBP-1c was only affected on day 2. The lowest concentrations of 1, 25-(OH)2D3 tested did not affect adipocyte differentiation or adipogenic gene expression. The C/EBPα promoter activity response to 1, 25-(OH)2D3 was also tested, with no effect detected. These results indicate that 1, 25-(OH)2D3 inhibited adipogenesis via suppressing adipogenic-specific genes, and is invoked either during PPARγ activation or immediately up-stream thereof. Gene expression down-stream of PPARγ especially FABP4 was strongly inhibited, and we suggest that the role of 1, 25-(OH)2D3 in regulating adipogenesis will be informed by further studies of adipogenic-specific gene promoter activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Following the near extinction of bison (Bison bison) from its historic range across North America in the late 19th century, novel bison conservation efforts in the early 20th century catalyzed a ...popular widespread conservation movement to protect and restore bison among other species and places. Since Allen's initial delineation (1876) of the historic distribution of North American bison, subsequent attempts have been hampered by knowledge gaps about bison distribution and abundance prior to and following colonial arrival and settlement. For the first time, we applied a multidisciplinary approach to assemble a comprehensive, integrated geographic database and meta‐analysis of bison occurrence over the last 200,000 years, with particular emphasis on the 450 years before present. We combined paleontology, archaeology, and historical ecology data for our database, which totaled 6438 observations. We derived the observations from existing online databases, published literature, and first‐hand exploration journal entries. To illustrate the conservative maximum historical extent of occurrence of bison, we created a concave hull using observations occurring over the last 450 years (n = 3379 observations), which is the broadly accepted historical benchmark at 1500 CE covering 59% of the North American continent. Although this distribution represents a historic extent of occurrence—merely delineating the maximum margins of the near‐continental distribution—it does not replace a density‐based approach reconstructing potential historical range distributions, which identifies core and marginal ranges. However, we envision the observations contained in this database will contribute to further research in the increasingly evidence‐based disciplines of bison ecology, evolution, rewilding, management, and conservation. There are no copyright or proprietary restrictions on these data, and this data paper should be cited when the data are reused.
In situ exploration of Uranus has been limited to a single flyby encounter by the Voyager 2 spacecraft in January 1986. Nonetheless, new investigation has led to significant questions about the ...origin of energetic ions observed in the region between its moons Miranda and Ariel. Radial and pitch angle diffusion modeling suggests that typical magnetospheric sources cannot explain the observed characteristics of these energetic ions. We suggest that these are likely being introduced by a source from one of these moons and give rise to waves that could result in the observed particle distribution characteristics. This may reveal that internal plasma sources in the system may be important for Uranus' magnetospheric dynamics and may contribute to its unexpectedly strong radiation belts.
Plain Language Summary
Uranus is an oddity in the solar system for a variety of reasons, but mostly as a result of its perpendicular rotation relative to the rest of the planets in the solar system. During its approximately 3‐day flyby of Uranus in 1986, Voyager 2 captured the only in situ observations of the planet and its system. New analysis of these three‐decade‐old observations have revealed a mysterious source of energetic ions in the planet's magnetosphere. These ions were originally explained by dynamics of the system, but new understanding suggests that this is probably unlikely. New simple modeling of the expected behavior of such energetic particles show that sustaining such a population requires a very strong source and specific energization mechanism. Both would potentially be consistent with the ions originating from either Miranda or Ariel. This potentially hints that the Uranian magnetosphere may harbor an ocean world like those known or believed to exist at the other Giant Planets.
Key Points
Analysis of Voyager 2 observations revealed a localized source of energetic ions in the region between the moons Miranda and Ariel
Diffusive transport modeling suggests that typical magnetospheric sources cannot explain the observed characteristics of the energetic ions
Additional in situ ion composition and plasma wave observations are necessary to confirm whether these ions are coming from an active moon
PDF
