Browse Articles
Discover research articles across all indexed journals
Spatial management of poverty-biodiversity interactions in semi-arid ecosystems
Fourier-modulated CLIP for zero-shot vehicle counting
Effects of construction disturbances on tunnel displacement and the protective role of soil reinforcement in metro tunnels
Why we should protect the high seas from all extraction, forever
Changes in anaerobic digestion performance and microbial community by increasing SRT through sludge recycling in food waste leachate treatment
Comparative evaluation of the effectiveness of various intracanal medicaments in eliminating Enterococcus faecalis from simulated internal resorption cavities
How I’m bringing the voices of local fishers into ocean policies
A Nd@C82–polymer interface for efficient and stable perovskite solar cells
A novel pThr217 tau monoclonal antibody reveals neuropathological heterogeneity in tauopathies
Bone, dentin and cementum differentially influence the differentiation of osteoclast-like cells
Abstract Our aim was to investigate how different oral hard tissues determine the differentiation of osteoclast-like cells. Murine macrophage cells were stimulated for 12 day with RANKL and M-CSF on dentin slices. Morphological changes of cells and hard tissues were examined by electron microscopy and toluidine blue staining. Cells were stimulated with RANKL and M-CSF on pulverized bone, dentin, cementum or polystyrene—with and without stimulation. TRAP staining was performed. To elucidate total gene expression, RNA sequencing was carried out. Four target genes (CXCL2, IGF-1, GDF15, HSPA1b) were selected and their expression was analyzed by RT-PCR and ELISA. Statistics comprised One-way ANOVA and Tukey’s test ( P < 0.05). Stimulation induced differentiation of mouse macrophages into TRAP-positive osteoclast-like cells forming resorption pits on dentin. Gene expression analysis revealed that 1930, 446 and 87 genes were differentially regulated by cultivation on cementum, bone or dentin respectively compared to polystyrene. Culture on bone or dentin caused CXCL2 upregulation. In all stimulated groups IGF-1 was downregulated while GDF15 expression was elevated in cultures on dentin. Cultivation of cells on cementum resulted in an upregulated HSPA1b expression. Our results indicate that extracellular matrix of different oral hard tissues plays an important role in differentiation processes of osteoclast-like cells.
Old carbon routed from land to the atmosphere by global river systems
Abstract Rivers and streams are an important pathway in the global carbon cycle, releasing carbon dioxide (CO2) and methane (CH4) from their water surfaces to the atmosphere1,2. Until now, CO2 and CH4 emitted from rivers were thought to be predominantly derived from recent (sub-decadal) biomass production and, thus, part of ecosystem respiration3–6. Here we combine new and published measurements to create a global database of the radiocarbon content of river dissolved inorganic carbon (DIC), CO2 and CH4. Isotopic mass balance of our database suggests that 59 ± 17% of global river CO2 emissions are derived from old carbon (millennial or older), the release of which is linked to river catchment lithology and biome. This previously unrecognized release of old, pre-industrial-aged carbon to the atmosphere from long-term soil, sediment and geologic carbon stores through lateral hydrological routing equates to 1.2 ± 0.3 Pg C year−1, similar in magnitude to terrestrial net ecosystem exchange. A consequence of this flux is a greater than expected net loss of carbon from aged organic matter stores on land. This requires a reassessment of the fate of anthropogenic carbon in terrestrial systems and in global carbon cycle budgets and models.
Assessing individual head and neck squamous cell carcinoma patient response to therapy through integration of functional and genomic data
Abstract Even though head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, there are only two PD-1 targeted immunotherapies (pembrolizumab and nivolumab) and one tumor intrinsic EGFR targeted therapy (cetuximab) that are FDA approved for treatment of HNSCC. Taking advantage of a high throughput inhibitor assay and computational tools originally showing success in leukemia, we designed and employed HNSCC-specific inhibitor panels that capture the diversity of aberrational pathways in HNSCC to test viable cells derived from patients’ HNSCC tumors. This provides a functional context to the multi-omic readouts conducted on these samples (mutations, protein expression and copy number alterations). In addition to generating these deeply characterized functional genomics datasets, we also developed additional visual analytics that have the potential to provide greater insight into HNSCC drug response patterns and potentially aid precision oncology tumor boards in evaluation and assessment of effective targeted therapeutic agents.
Development of a two-layer 3D equine endometrial tissue model using genipin-crosslinked collagen scaffolds and 3D printing
Robust super-twisting algorithm-based single-phase sliding mode frequency controller in power systems integrating wind turbines and energy storage systems
Optimized unit commitment for peak load management with solar PV and storage under load uncertainty
‘I don’t have the bandwidth’: how to juggle dating alongside a PhD
Microbial metabolite drives ageing-related clonal haematopoiesis via ALPK1
Abstract Clonal haematopoiesis of indeterminate potential (CHIP) involves the gradual expansion of mutant pre-leukaemic haematopoietic cells, which increases with age and confers a risk for multiple diseases, including leukaemia and immune-related conditions1. Although the absolute risk of leukaemic transformation in individuals with CHIP is very low, the strongest predictor of progression is the accumulation of mutant haematopoietic cells2. Despite the known associations between CHIP and increased all-cause mortality, our understanding of environmental and regulatory factors that underlie this process during ageing remains rudimentary. Here we show that intestinal alterations, which can occur with age, lead to systemic dissemination of a microbial metabolite that promotes pre-leukaemic cell expansion. Specifically, ADP-d-glycero-β-d-manno-heptose (ADP-heptose), a biosynthetic bi-product specific to Gram-negative bacteria3–5, is uniquely found in the circulation of older individuals and favours the expansion of pre-leukaemic cells. ADP-heptose is also associated with increased inflammation and cardiovascular risk in CHIP. Mechanistically, ADP-heptose binds to its receptor, ALPK1, triggering transcriptional reprogramming and NF-κB activation that endows pre-leukaemic cells with a competitive advantage due to excessive clonal proliferation. Collectively, we identify that the accumulation of ADP-heptose represents a direct link between ageing and expansion of rare pre-leukaemic cells, suggesting that the ADP-heptose–ALPK1 axis is a promising therapeutic target to prevent progression of CHIP to overt leukaemia and immune-related conditions.
Studying the properties of solidified oil-contaminated soil by magnesium oxychloride cement
Population screening of adults identifies novel genetic variants associated with celiac disease
Abstract Celiac disease (CeD) is an autoimmune disease driven by a complex genetic interplay within and beyond the human leukocyte antigen (HLA) region. Despite this, half of its heritability remains unexplained, with most of the unidentified variants located in non-protein coding regions. Here we performed a genome-wide association study among 52,342 adults screened for CeD, including 465 previously undiagnosed and 361 already diagnosed cases, which mitigated the likely disease misclassification present in previous studies. Genotyping and imputation yielded approximately 24.9 million variants for analysis. The study identified 15 novel associations (P < 5E-08) in 12 loci in addition to all the previously associated loci at lower significance thresholds (P < 5E-03). The 5p15.33 locus in the long non-coding RNA gene (LINC01019) showed the highest potential for a true association with CeD. Notably, variants in 5p15.33 has also been associated with rheumatoid arthritis, suggesting a new shared autoimmune locus.