Warming, watering and elevated atmospheric CO₂-concentration effects have been extensively studied separately; however, their combined impact on plants is not well understood. In the current ...research, we examined plant growth and physiological responses of three dominant species from the Eurasian Steppe with different functional traits to a combination of elevated CO₂, high temperature, and four simulated precipitation patterns. Elevated CO₂ stimulated plant growth by 10.8–41.7 % for a C₃ leguminous shrub, Caragana microphylla, and by 33.2–52.3 % for a C₃ grass, Stipa grandis, across all temperature and watering treatments. Elevated CO₂, however, did not affect plant biomass of a C₄ grass, Cleistogenes squarrosa, under normal or increased precipitation, whereas a 20.0–69.7 % stimulation of growth occurred with elevated CO₂ under drought conditions. Plant growth was enhanced in the C₃ shrub and the C₄ grass by warming under normal precipitation, but declined drastically with severe drought. The effects of elevated CO₂ on leaf traits, biomass allocation and photosynthetic potential were remarkably species-dependent. Suppression of photosynthetic activity, and enhancement of cell peroxidation by a combination of warming and severe drought, were partly alleviated by elevated CO₂. The relationships between plant functional traits and physiological activities and their responses to climate change were discussed. The present results suggested that the response to CO₂ enrichment may strongly depend on the response of specific species under varying patterns of precipitation, with or without warming, highlighting that individual species and multifactor dependencies must be considered in a projection of terrestrial ecosystem response to climatic change.
Normal epithelial cells are stably connected to each other via the apical junctional complex (AJC). AJCs, however, tend to be disrupted during tumor progression, and this process is implicated in ...cancer dissemination. Here, using colon carcinoma cells that fail to form AJCs, we investigated molecular defects behind this failure through a search for chemical compounds that could restore AJCs, and found that microtubule-polymerization inhibitors (MTIs) were effective. MTIs activated GEF-H1/RhoA signaling, causing actomyosin contraction at the apical cortex. This contraction transmitted force to the cadherin-catenin complex, resulting in a mechanosensitive recruitment of vinculin to cell junctions. This process, in turn, recruited PDZ-RhoGEF to the junctions, leading to the RhoA/ROCK/LIM kinase/cofilin-dependent stabilization of the junctions. RhoGAP depletion mimicked these MTI-mediated processes. Cells that normally organize AJCs did not show such MTI/RhoA sensitivity. Thus, advanced carcinoma cells require elevated RhoA activity for establishing robust junctions, which triggers tension-sensitive reorganization of actin/adhesion regulators.
Adverse climate change attributed to elevated atmospheric carbon dioxide concentration (CO₂) and increased temperature components of global warming has been a central issue affecting economic and ...social development. Climate change, particularly global warming, imposes a severe impact on the terrestrial ecosystem. Elevated CO₂, drought, and high temperature have been extensively documented individually; however, relatively little is known about how plants respond to the interaction of these factors. To summarize current knowledge on the response of plants to global change factors, we focus on the interactive effects of CO₂ enrichment, warming, and drought on plant growth, carbon allocation, and photosynthesis. Stimulation due to elevated CO₂ might be suppressed under other negative climatic/environmental stresses such as drought, high temperature, and their combination. However, elevated CO₂ could alleviate deleterious effects of moderate drought via reducing stomatal conductance, altering leaf surface, and regulating gene expression. High CO₂ levels and rising temperatures may result in opposite responses in plant water use efficiency. Stimulation of plant growth due to elevated CO₂ for C₃ species occurs regardless of water conditions, but only under a water deficit for C₄ species. The positive effect of elevated CO₂ on C₄ species is derived mainly from the improved water status. Plant adaptive or maladaptive responses to multivariate environments are interactive; thus, researchers need to explore the ecological underpinnings involved in such responses to the multiple factors involved in climate change.
Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative ...colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with
as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (
,
,
,
, and
) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71,
= 2 × 10
). Five genes (
,
,
,
, and
) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.
At the early stage of cancer development, oncogenic mutations often cause multilayered epithelial structures. However, the underlying molecular mechanism still remains enigmatic. By performing a ...series of screenings targeting plasma membrane proteins, we have found that collagen XVII (COL17A1) and CD44 accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells. In addition, the expression of COL17A1 and CD44 is also regulated by cell density and upon apical cell extrusion. We further demonstrate that the expression of COL17A1 and CD44 is profoundly upregulated at the upper layers of multilayered, transformed epithelia in vitro and in vivo. The accumulated COL17A1 and CD44 suppress mitochondrial membrane potential and reactive oxygen species (ROS) production. The diminished intracellular ROS level then promotes resistance against ferroptosis-mediated cell death upon cell extrusion, thereby positively regulating the formation of multilayered structures. To further understand the functional role of COL17A1, we performed comprehensive metabolome analysis and compared intracellular metabolites between RasV12 and COL17A1-knockout RasV12 cells. The data imply that COL17A1 regulates the metabolic pathway from the GABA shunt to mitochondrial complex I through succinate, thereby suppressing the ROS production. Moreover, we demonstrate that CD44 regulates membrane accumulation of COL17A1 in multilayered structures. These results suggest that CD44 and COL17A1 are crucial regulators for the clonal expansion of transformed cells within multilayered epithelia, thus being potential targets for early diagnosis and preventive treatment for precancerous lesions.
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•CD44 and COL17A1 accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells•Accumulated CD44/COL17A1 enhance resistance against ferroptosis upon cell extrusion•CD44 up-regulates the membrane localization of COL17A1 in multilayered epithelia•CD44/COL17A1 promote the formation of multilayered, transformed epithelia
Kozawa, Sekai et al. demonstrate that CD44 and COL17A1 accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells. The accumulated CD44/COL17A1 diminish extrusion-induced ferroptosis by regulating various metabolic pathways and suppressing the production of ROS, leading to the formation of multilayered, transformed epithelial structures.
Cryptomeria japonica trees in the area surrounding Fukushima, Japan, intercepted 137Cs present in atmospheric deposits soon after the Fukushima nuclear accident in March 2011. To study the uptake and ...translocation of 137Cs in C. japonica leaves, we analyzed activity concentrations of 137Cs and the concentration ratios of 137Cs to 133Cs (137Cs/133Cs) in old and new leaves of C. japonica collected from a forest on Mount Tsukuba between 9 and 15months after the accident. Both isotopes were also analyzed in throughfall, bulk precipitation and soil extracts. Water of atmospheric and soil origin were used as proxies for deciphering the absorption from leaf surfaces and root systems, respectively. Results indicate that 20–40% of foliar 137Cs existed inside the leaf, while 60–80% adhered to the leaf surface. The 137Cs/133Cs ratios inside leaves that had sprouted before the accident were considerably higher than that of the soil extract and lower than that of throughfall and bulk precipitation. Additionally, more than 80% of 137Cs in throughfall and bulk precipitation was present in the dissolved form, which is available for foliar uptake, indicating that a portion of the 137Cs inside old leaves was presumably absorbed from the leaf surface. New leaves that sprouted after the accident had similar 137Cs/133Cs ratios to that of the old leaves, suggesting that internal 137Cs was translocated from old to new leaves. For 17 species of woody plants other than C. japonica, new leaves that sprouted after the accident also contained 137Cs, and their 137Cs/133Cs ratios were equal to or higher than that of the soil extract. These results suggested that foliar uptake and further translocation of 137Cs is an important vector of contamination in various tree species during or just after radioactive fallout.
•137Cs was absorbed into cedar leaves from the leaf surface.•137Cs in new leaves of cedar trees was mainly supplied by translocation.•Over 80% of 137Cs in rainwater was present in the dissolved form.
Epithelial junctions comprise two subdomains, the apical junctional complex (AJC) and the adjacent lateral membrane contacts (LCs), that span the majority of the junction. The AJC is lined with ...circumferential actin cables, whereas the LCs are associated with less-organized actin filaments whose roles are elusive. We found that DAAM1, a formin family actin regulator, accumulated at the LCs, and its depletion caused dispersion of actin filaments at these sites while hardly affecting circumferential actin cables. DAAM1 loss enhanced the motility of LC-forming membranes, leading to their invasion of neighboring cell layers, as well as disruption of polarized epithelial layers. We found that components of the WAVE complex and its downstream targets were required for the elevation of LC motility caused by DAAM1 loss. These findings suggest that the LC membranes are motile by nature because of the WAVE complex, but DAAM1-mediated actin regulation normally restrains this motility, thereby stabilizing epithelial architecture, and that DAAM1 loss evokes invasive abilities of epithelial cells.
Summary
The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel ...agents. This study was a systematic review and network meta‐analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end‐point was progression‐free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p‐score was used to rank treatments. Of a total of 1136 s screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08–0.20; p‐score 0.9796). There was no evidence of significant heterogeneity (I2, 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three‐drug regimens including anti‐CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T‐cell treatments and bispecific T‐cell engager therapies.
High-dose methotrexate (MTX) is widely used for the treatment of hematological malignancies. Despite the application of routine supportive care measures, such as intensive fluid hydration and urine ...alkalinization, nephrotoxicity is still a problem. The present study aimed to evaluate the risk factors for MTX-induced nephrotoxicity. We retrospectively reviewed 88 patients who received a regimen consisting of high-dose MTX (1000 mg/m
2
) and cytosine arabinoside between 2006 and 2018. Nephrotoxicity (≥ grade 2) was observed in 11 patients. Nephrotoxicity was observed only in patients with a high MTX concentration. Other than the MTX concentration, the serum uric acid level and urine pH at day 1 were associated with nephrotoxicity. A multivariate analysis revealed that urine pH was an independent risk factor for MTX-induced nephrotoxicity. Urine pH < 7.0 at day 1 was a significant risk factor for nephrotoxicity (odds ratio, 8.05; 95% confidence interval 1.95–33.3) and was also a predictor of delayed MTX elimination at 72 h after injection. Among pre-treatment factors, a low serum calcium level predicted urine pH < 7.0 at day 1. In conclusion, the present study suggests that low urine pH at day 1 is an independent risk factor for MTX-induced nephrotoxicity.
To evaluate the mobility and bioavailability of 137Cs in soils, we compared the extraction of 137Cs with stable Cs and ammonium solutions from 137Cs-contaminated minerals and soils. The extraction ...yields of 137Cs with stable Cs were significantly lower than those with ammonium for minerals with frayed edge sites, but such differences were not observed for minerals without frayed edge sites. The amount of 137Cs extracted with stable Cs from soils was lower than, or equal to, that extracted with ammonium. The above results suggest that stable Cs extracted the 137Cs from easily accessible sites. Plant available 137Cs was assessed using Kochia (Bassia scoparia) cultivated in pots of contaminated soils, and compared with soil parameters including extractable 137Cs and K, and radiocesium intercept potential. The 137Cs/K ratio extracted with stable Cs solution was found to be a potential index for evaluation of the easily mobile and bioavailable fraction of 137Cs in soil.
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