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"Larsen, D"
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Mortuary and bioarchaeological perspectives on Bronze Age Arabia
This volume brings together an international consortium of archaeologists and bioarchaeologists at the forefront of mortuary archaeology work across Arabia to examine continuity/change in death and remembrance. While mortuary archaeology and bioarchaeology contribute important perspectives to the interpretation of life/death in ancient Arabia, these subdisciplines are rarely brought together in this region, and only recently have skeletal remains been recognized as a rich source of scientific data complementing burial context. Such joint collaboration highlights the novel, interdisciplinary perspective proposed in this volume, resulting in a synthesis of new ideas and interpretations that will undoubtedly guide future archaeological endeavors in Arabia and beyond.
Book
Transcriptional regulation of Hepatic Stellate Cell activation in NASH
Non-alcoholic steatohepatitis (NASH) signified by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis is a growing cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Hepatic fibrosis resulting from accumulation of extracellular matrix proteins secreted by hepatic myofibroblasts plays an important role in disease progression. Activated hepatic stellate cells (HSCs) have been identified as the primary source of myofibroblasts in animal models of hepatotoxic liver injury; however, so far HSC activation and plasticity have not been thoroughly investigated in the context of NASH-related fibrogenesis. Here we have determined the time-resolved changes in the HSC transcriptome during development of Western diet- and fructose-induced NASH in mice, a NASH model recapitulating human disease. Intriguingly, HSC transcriptional dynamics are highly similar across disease models pointing to HSC activation as a point of convergence in the development of fibrotic liver disease. Bioinformatic interrogation of the promoter sequences of activated genes combined with loss-of-function experiments indicates that the transcriptional regulators ETS1 and RUNX1 act as drivers of NASH-associated HSC plasticity. Taken together, our results implicate HSC activation and transcriptional plasticity as key aspects of NASH pathophysiology.
Journal Article
Floodplains : processes and management for ecosystem services
\"Floodplains provides an overview of floodplains and their management in temperate regions. It synthesizes decades of research on floodplain ecosystems, explaining hydrologic, geomorphic and ecological processes and how these processes can provide a range of benefits to society under appropriate management. Due to the widespread alteration of temperate floodplains, these benefits are often not realized. Drawing on the framework of reconciliation ecology, the authors explore how new concepts for floodplain ecosystem restoration and management can provide a broader range of benefits to society, ranging from healthy fish populations to flood-risk reduction. Case studies from California's Central Valley and elsewhere in temperate regions show how innovative management approaches are reshaping rivers and floodplains around the world.\"--Provided by publisher.
Book
Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis
Mesenchymal (stromal) stem cells (MSCs) constitute populations of mesodermal multipotent cells involved in tissue regeneration and homeostasis in many different organs. Here we performed comprehensive characterization of the transcriptional and epigenomic changes associated with osteoblast and adipocyte differentiation of human MSCs. We demonstrate that adipogenesis is driven by considerable remodeling of the chromatin landscape and de novo activation of enhancers, whereas osteogenesis involves activation of preestablished enhancers. Using machine learning algorithms for in silico modeling of transcriptional regulation, we identify a large and diverse transcriptional network of pro-osteogenic and antiadipogenic transcription factors. Intriguingly, binding motifs for these factors overlap with SNPs related to bone and fat formation in humans, and knockdown of single members of this network is sufficient to modulate differentiation in both directions, thus indicating that lineage determination is a delicate balance between the activities of many different transcription factors.
Transcriptional and epigenomic profiling of osteoblast and adipocyte differentiation shows that adipogenesis is driven by de novo activation of enhancers, whereas osteogenesis involves preestablished enhancers and depends on the activation of pro-osteogenic and antiadipogenic transcription factors.
Journal Article
Administrative records for survey methodology
ADMINISTRATIVE RECORDS FOR SURVEY METHODOLOGY Addresses the international use of administrative records for large-scale surveys, censuses, and other statistical purposes Administrative Records for Survey Methodology is a comprehensive guide to improving the quality, cost-efficiency, and interpretability of surveys and censuses using administrative.
eBook
RCB initiates Arabidopsis thermomorphogenesis by stabilizing the thermoregulator PIF4 in the daytime
Daytime warm temperature elicits thermomorphogenesis in
Arabidopsis
by stabilizing the central thermoregulator PHYTOCHROME INTERACTING transcription FACTOR 4 (PIF4), whose degradation is otherwise promoted by the photoreceptor and thermosensor phytochrome B. PIF4 stabilization in the light requires a transcriptional activator, HEMERA (HMR), and is abrogated when HMR’s transactivation activity is impaired in
hmr-22
. Here, we report the identification of a
hmr-22
suppressor mutant,
rcb-101
, which surprisingly carries an A275V mutation in REGULATOR OF CHLOROPLAST BIOGENESIS (RCB).
rcb-101/hmr-22
restores thermoresponsive PIF4 accumulation and reverts the defects of
hmr-22
in chloroplast biogenesis and photomorphogenesis. Strikingly, similar to
hmr
, the null
rcb-10
mutant impedes PIF4 accumulation and thereby loses the warm-temperature response.
rcb-101
rescues
hmr-22
in an allele-specific manner. Consistently, RCB interacts directly with HMR. Together, these results unveil RCB as a novel temperature signaling component that functions collaboratively with HMR to initiate thermomorphogenesis by selectively stabilizing PIF4 in the daytime.
The Arabidopsis PIF4 transcription factor is stabilized during the daytime in response to warm temperature and regulates thermomorphogenesis. Here the authors show that the response to warm temperature depends on the concerted action of the HMR and RCB proteins that act collaboratively to stabilize PIF4.
Journal Article
Identification of a central role for complement in osteoarthritis
Osteoarthritis, the breakdown of cartilage in synovial joints, has long been viewed as the result of 'wear and tear', but this report shows that dysregulation of the complement system has an active role in the pathogenesis of this disease.
Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'
1
. Although low-grade inflammation is detected in osteoarthritis, its role is unclear
2
,
3
,
4
. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis.
Journal Article
Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells
Over half of cutaneous melanoma tumors have BRAFV600E/K mutations. Acquired resistance to BRAF inhibitors (BRAFi) remains a major hurdle in attaining durable therapeutic responses. In this study we demonstrate that ~50–60% of melanoma cell lines with vemurafenib resistance acquired in vitro show activation of RhoA family GTPases. In BRAFi-resistant melanoma cell lines and tumors, activation of RhoA is correlated with decreased expression of melanocyte lineage genes. Using a machine learning approach, we built gene expression-based models to predict drug sensitivity for 265 common anticancer compounds. We then projected these signatures onto the collection of TCGA cutaneous melanoma and found that poorly differentiated tumors were predicted to have increased sensitivity to multiple Rho kinase (ROCK) inhibitors. Two transcriptional effectors downstream of Rho, MRTF and YAP1, are activated in the RhoHigh BRAFi-resistant cell lines, and resistant cells are more sensitive to inhibition of these transcriptional mechanisms. Taken together, these results support the concept of targeting Rho-regulated gene transcription pathways as a promising therapeutic approach to restore sensitivity to BRAFi-resistant tumors or as a combination therapy to prevent the onset of drug resistance.
Journal Article
One simulation, different conclusions-the baseline period makes the difference!
The choice of the baseline period, intentionally chosen or not, as a reference for assessing future changes of any projected variable can play an important role for the resulting statement. In regional climate impact studies, well-established or arbitrarily chosen baselines are often used without being questioned. Here we investigated the effects of different baseline periods on the interpretation of discharge simulations from eight river basins in the period 1960-2099. The simulations were forced by four bias-adjusted and downscaled Global Climate Modelsunder two radiative forcing scenarios (RCP 2.6 and RCP 8.5). To systematically evaluate how far the choice of different baselines impacts the simulation results, we developed a similarity index that compares two time series of projected changes. The results show that 25% of the analyzed simulations are sensitive to the choice of the baseline period under RCP 2.6 and 32% under RCP 8.5. In extreme cases, change signals of two time series show opposite trends. This has serious consequences for key messages drawn from a basin-scale climate impact study. To address this problem, an algorithm was developed to identify flexible baseline periods for each simulation individually, which better represent the statistical properties of a given historical period.
Journal Article