Clouds cover about 70% of Earth's surface and play a dominant role in the energy and water cycle of our planet. Only satellite observations provide a continuous survey of the state of the atmosphere ...over the entire globe and across the wide range of spatial and temporal scales that compose weather and climate variability. Satellite cloud data records now exceed more than 25 years; however, climate data records must be compiled from different satellite datasets and can exhibit systematic biases. Questions therefore arise as to the accuracy and limitations of the various sensors and retrieval methods. The Global Energy and Water Cycle Experiment (GEWEX) Cloud Assessment, initiated in 2005 by the GEWEX Radiation Panel (GEWEX Data and Assessment Panel since 2011), provides the first coordinated intercomparison of publicly available, standard global cloud products (gridded monthly statistics) retrieved from measurements of multispectral imagers (some with multiangle view and polarization capabilities), IR sounders, and lidar. Cloud properties under study include cloud amount, cloud height (in terms of pressure, temperature, or altitude), cloud thermodynamic phase, and cloud radiative and bulk microphysical properties (optical depth or emissivity, effective particle radius, and water path). Differences in average cloud properties, especially in the amount of high-level clouds, are mostly explained by the inherent instrument measurement capability for detecting and/or identifying optically thin cirrus, especially when overlying low-level clouds. The study of long-term variations with these datasets requires consideration of many factors. The monthly gridded database presented here facilitates further assessments, climate studies, and the evaluation of climate models.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Efforts to develop effective disease-modifying drugs to treat osteoarthritis have so far proved unsuccessful with a number of promising drug candidates from pre-clinical studies failing to show ...efficacy in clinical trials. It is therefore timely to re-evaluate our current understanding of osteoarthritis pathogenesis and the similarities and differences in disease development between commonly used pre-clinical mouse models and human patients. There is substantial heterogeneity between patients presenting with osteoarthritis and mounting evidence that the pathways involved in osteoarthritis (e.g. Wnt signalling) differ between patient sub-groups. There is also emerging evidence that the pathways involved in osteoarthritis differ between the STR/ort mouse model (the most extensively studied mouse model of spontaneously occurring osteoarthritis) and injury-induced osteoarthritis mouse models. For instance, while canonical Wnt signalling is upregulated in the synovium and cartilage at an early stage of disease in injury-induced osteoarthritis mouse models, this does not appear to be the case in the STR/ort mouse. Such findings may prove insightful for understanding the heterogeneity in mechanisms involved in osteoarthritis pathogenesis in human disease. However, it is important to recognise that there are differences between mice and humans in osteoarthritis pathogenesis. A much more extensive array of pathological changes are evident in osteoarthritic joints in individual mice with osteoarthritis compared to individual patients. There are also specified differences in the pathways involved in disease development. For instance, although increased TGF-β signalling is implicated in osteoarthritis development in both mouse models of osteoarthritis and human disease, in mice, this is mainly mediated through TGF-β3 whereas in humans, it is through TGF-β1. Studies in other tissues have shown TGF-β1 is more potent than TGF-β3 in inducing the switch to SMAD1/5 signalling that occurs in osteoarthritic cartilage and that TGF-β1 and TGF-β3 have opposing effects on fibrosis. It is therefore possible that the relative contribution of TGF-β signalling to joint pathology in osteoarthritis differs between murine models and humans. Understanding the similarities and differences in osteoarthritis pathogenesis between mouse models and humans is critical for understanding the translational potential of findings from pre-clinical studies.
IL-33, an IL-1 family member and ligand for the IL-1 receptor-related protein ST2, has been associated with induction of Th2 cytokines such as IL-4, IL-5, and IL-13. Here, we report that IL-33 can ...initiate IL-9 protein secretion in vitro in human CD4+ T cells and basophils isolated from peripheral blood. TGF-β has been described as a critical factor for IL-9 induction in Th2 cells; however, we found that TGF-β also induces co-production of IL-9 in purified, naïve (>99%) CD4(+)CD45RA(+)CD45RO(-)CD25(-) T cells differentiated towards a Th1 profile. Subsequently, it was demonstrated that TGF-β is important, although not an absolute requirement, for IL-9 production in CD4+ T cells. IL-9 production by purified (>95%) human basophils, cultured for 24 h with IL-3 or IL-33, was found, with a strong synergy between the two, likely to be explained by the IL-3 upregulated ST2 expression. Collectively, these data indicate that barrier functioning cells are important for the regulation of IL-9 production by immune cells in inflamed tissue.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary We performed a meta-analysis of cross-sectional studies on serum 25(OH)D status globally. Serum 25(OH)D levels on average were 54 nmol/l, were higher in women than men, and higher in ...Caucasians than in non-Caucasians. There was no trend in serum 25(OH)D level with latitude. Vitamin D deficiency was widespread. Introduction We studied vitamin D status (expressed as serum 25-hydroxy-vitamin D 25(OH)D) in native subjects worldwide. Methods Meta-analysis and meta-regression of studies reporting on 25(OH)D in healthy subjects retrieved from Pubmed, Embase and Web of Science using the terms “serum”, “25-hydroxy-vitamin D”, “cholecalciferol”, and “human”. A total of 394 studies were included. Results The mean 25(OH)D level was 54 nmol/l (95% CI: 52-57 nmol/l). Women had borderline significantly higher 25(OH)D levels than men, and Caucasians had higher levels than non-Caucasians. 25(OH)D levels were higher in subjects aged >15 years than in younger subjects. Unadjusted there was no significant decrease in 25(OH)D with latitude (slope of curve -0.03 ± 0.12 nmol/l per degree latitude north or south of equator, p = 0.8). There was a significant decline with latitude for Caucasians (-0.69 ± 0.30 nmol/l per degree, p = 0.02), but not for non-Caucasians (0.03 ± 0.39 nmol/l per degree, p = 0.14). After adjustment for age, gender, and ethnicity, no overall correlation was present between 25(OH)D and latitude (-0.29 ± 0.24 nmol/l per degree, p = 0.23). Conclusion There was no overall influence of latitude on 25(OH)D. However, in separate analyses 25(OH)D decreased with latitude in Caucasians but not in non-Caucasians. A widespread global vitamin D insufficiency was present compared with proposed threshold levels.
Proxy data constraining land and ocean surface paleo‐temperatures indicate that the Middle Miocene Climate Optimum (MMCO), a global warming event at ∼15 Ma, had a global annual mean surface ...temperature of 18.4°C, about 3°C higher than present and equivalent to the warming predicted for the next century. We apply the latest National Center for Atmospheric Research (NCAR) Community Atmosphere Model CAM3.1 and Land Model CLM3.0 coupled to a slab ocean to examine sensitivity of MMCO climate to varying ocean heat fluxes derived from paleo sea surface temperatures (SSTs) and atmospheric carbon dioxide concentrations, using detailed reconstructions of Middle Miocene boundary conditions including paleogeography, elevation, vegetation and surface temperatures. Our model suggests that to maintain MMCO warmth consistent with proxy data, the required atmospheric CO2 concentration is about 460–580 ppmv, narrowed from the most recent estimate of 300–600 ppmv.
Two of the studies have shown efficacy in nasal provocations for grass pollen2 and cat dander.3 One small study combining patients with grass and birch pollen allergy has demonstrated an improved ...global evaluation of seasonal symptoms.4 However, no double-blind, placebo-controlled studies have yet been published looking at efficacy based on seasonal symptom and medication scores, as proposed by the US Food and Drug Administration and the European Medical Agency (EMA).5,6 To study the efficacy based on patients' seasonal diaries, we performed a randomized, double-blind, placebo-controlled study testing 3 and 6 preseasonal injections of intralymphatic immunotherapy (ILIT) with alum-adsorbed Phleum pratense. The amount of allergen could be increased because in immunotherapy the allergen dose is linked to efficacy generally.1 However, on the basis of our study, it is not recommendable to increase the amount of allergen without an updosing regimen because systemic side effects were seen in 9% of the patients.\n1) 1 Influenza 4 (28.6) 4 4 (26.7) 4 7 (50) 7 Gastrointestinal infection 4 (28.6) 4 2 (13.3) 2 4 (28.6) 4 Cough 3 (21.4) 3 3 (20) 3 3 (21.4) 3 Table E1 Demographics, baseline characteristics, and adverse events There were no significant demographic differences before treatment among the 3 groups with respect to sex and age, a global evaluation score (the visual analog scale) of the pretreatment season, seasonal asthma, concomitant birch allergy, and steroid treatment in the 2010 season.VAS, Visual analog scale.
Lytic polysaccharide monooxygenases (LPMOs) are industrially important copper-dependent enzymes that oxidatively cleave polysaccharides. Here we present a functional and structural characterization ...of two closely related AA9-family LPMOs from Lentinus similis (LsAA9A) and Collariella virescens (CvAA9A). LsAA9A and CvAA9A cleave a range of polysaccharides, including cellulose, xyloglucan, mixed-linkage glucan and glucomannan. LsAA9A additionally cleaves isolated xylan substrates. The structures of CvAA9A and of LsAA9A bound to cellulosic and non-cellulosic oligosaccharides provide insight into the molecular determinants of their specificity. Spectroscopic measurements reveal differences in copper co-ordination upon the binding of xylan and glucans. LsAA9A activity is less sensitive to the reducing agent potential when cleaving xylan, suggesting that distinct catalytic mechanisms exist for xylan and glucan cleavage. Overall, these data show that AA9 LPMOs can display different apparent substrate specificities dependent upon both productive protein-carbohydrate interactions across a binding surface and also electronic considerations at the copper active site.
Peripheral circadian clocks control cell proliferation and survival, but little is known about their role and regulation in megakaryocytic cells. N-methyl-D-aspartate receptor (NMDAR) regulates the ...central clock in the brain. The purpose of this study was to determine whether NMDAR regulates the megakaryocytic cell clock and whether the megakaryocytic clock regulates cell proliferation and cell death. We found that both the Meg-01 megakaryocytic cell line and native murine megakaryocytes expressed circadian clock genes. Megakaryocyte-directed deletion of Grin1 in mice caused significant disruption of the circadian rhythm pathway at the transcriptional level and increased expression of BMAL1 at the protein level. Similarly, both pharmacological (MK-801) and genetic (GRIN
-/-
) inhibition of NMDAR in Meg-01 cells in vitro resulted in widespread changes in clock gene expression including increased expression of BMAL1, the core clock transcription factor. BMAL1 overexpression reduced Meg-01 cell proliferation and altered the time-dependent expression of the cell cycle regulators MYC and WEE1, whereas BMAL1 knockdown led to increased cell death in Meg-01-GRIN1
-/-
cells. Our results demonstrate that NMDAR regulates the circadian clock in megakaryocytic cells and that the circadian clock component BMAL1 contributes to the control of Meg-01 cell proliferation and survival.
Why was the study done?
Time of day impacts platelet function and production. Our bodies are informed about external time by the brain, but all other cells including platelet precursors megakaryocytes also have their own clock.
Circadian disruption contributes to disorders such as thrombosis (e.g. stroke and heart attacks) and blood cancers (e.g. leukemia). However, the mechanism of circadian control in megakaryocytes remains poorly elucidated.
N-methyl-D-aspartate receptor (NMDAR) regulates circadian clock in the brain and is expressed in megakaryocytes, thus we hypothesized that NMDAR also regulates circadian clock in megakaryocytic cells.
What did the researchers do and find?
We used Meg-01 cell line, its genetically modified version with deleted NMDAR, and data from murine megakaryocytes to determine the NMDAR impact on the clock in these cells.
We found that megakaryocytic cells had all the machinery required to maintain their own circadian clock. NMDAR deletion disrupted circadian clock in megakaryocytic cells.
Manipulation of circadian clock in Meg-01 cells (through BMAL1 overexpression) impacted proliferation and survival of cells.
What do the results mean?
Megakaryocytic cells have their own circadian clock regulated by NMDAR, and its disruption impacts cell proliferation.
What is the objective influence on the wider field?
It is possible that deregulated function of megakaryocytes that occurs in disease can be corrected through the modulation of NMDAR or other components of the cellular circadian clock, thus further studies to develop and test such strategies in disease models are warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Measurements of oxygen and hydrogen stable isotope ratios (δ18O and δD) in meteoric waters provide insight to overlapping effects of evaporation, precipitation, and mixing on basin scale hydrology. ...This study of waters collected between 2016 and 2021 in the Turkana Basin, northern Kenya, uses δ18O and δD to understand water balance in Lake Turkana, a large, low‐latitude, alkaline desert lake. The Omo River, a major river system in the Ethiopian Highlands, is historically understood to provide approximately 90% of the water input to Lake Turkana. Discharge of the Omo is prohibitively difficult to measure, but stable isotope ratios in the lake may provide a meaningful method for monitoring the lake's response to changes in input. Precipitation in the Turkana Basin is low (<200 mm/year) with negligible rainfall on the lake's surface, and all water loss from the lake is evaporative. We compare new measurements with previous data from the region and records of lake height and precipitation from the same time period. We show that a Bayesian approach to modeling evaporation using atmospheric conditions and river δ18O and δD yields results consistent with published water balance models. Continued sampling of lake and meteoric waters in the Turkana Basin will be a useful way to monitor the lake's response to regional and global climate change.
Plain Language Summary
Lake Turkana is the largest desert lake in the world, in one of the hottest and driest places on Earth. Studying and preserving the lake are important because people and ecosystems depend on it, but information is lacking because it is remote and irregularly monitored. Most of the water in Lake Turkana comes from the Omo River, which flows through the Ethiopian Highlands. Lake Turkana has no outlet; therefore, evaporation is the only process that removes water from the lake. In this study, we analyzed samples of lake water as well as rain, river, surface, and ground waters and developed a model that uses measurements of oxygen and hydrogen stable isotopes in the water to help us understand how much evaporation occurs in Lake Turkana. Future lake water monitoring efforts should consider stable isotope methods to record how the basin hydrology responds to climate change.
Key Points
New measurements of meteoric waters from the Turkana Basin in northern Kenya plot along the meteoric water line
A lake water evaporation line is developed using Bayesian modeling applied to a terminal lake mass balance model
The model enables predictions of lake water δ values under past and future climate change scenarios
Cellular senescence is an irreversible side effect of some pharmaceuticals which can contribute to tissue degeneration.
To determine whether pharmaceutical glucocorticoids induce senescence in ...tenocytes.
Features of senescence (β-galactosidase activity at pH 6 (SA-β-gal) and active mammalian/mechanistic target of rapamycin (mTOR) in cell cycle arrest) as well as the activity of the two main pathways leading to cell senescence were examined in glucocorticoid-treated primary human tenocytes. Evidence of senescence-inducing pathway induction in vivo was obtained using immunohistochemistry on tendon biopsy specimens taken before and 7 weeks after subacromial Depo-Medrone injection.
Dexamethasone treatment of tenocytes resulted in an increased percentage of SA-βgal-positive cells. Levels of phosphorylated p70S6K did not decrease with glucocorticoid treatment indicating mTOR remained active. Increased levels of acetylated p53 as well as increased RNA levels of its pro-senescence effector p21 were evident in dexamethasone-treated tenocytes. Levels of the p53 deacetylase sirtuin 1 were lower in dexamethasone-treated cells compared with controls. Knockdown of p53 or inhibition of p53 activity prevented dexamethasone-induced senescence. Activation of sirtuin 1 either by exogenous overexpression or by treatment with resveratrol or low glucose prevented dexamethasone-induced senescence. Immunohistochemical analysis of tendon biopsies taken before and after glucocorticoid injection revealed a significant increase in the percentage of p53-positive cells (p=0.03). The percentage of p21-positive cells also tended to be higher post-injection (p=0.06) suggesting glucocorticoids activate the p53/p21 senescence-inducing pathway in vivo as well as in vitro.
As cell senescence is irreversible in vivo, glucocorticoid-induced senescence may result in long-term degenerative changes in tendon tissue.
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