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Modeling the impact of extreme weather events and future climate on the radiologically contaminated sites of Enewetak Atoll
Confinement and Catalysis within <i>De Novo</i> Designed Peptide Barrels
Atlantic overturning inferred from air-sea heat fluxes indicates no decline since the 1960s
Artemisia capillaris with two novel active compounds, Kawarayomogin I and II, inhibits HYBID (KIAA1199) expression as well as hyaluronic acid degradation
Abstract Hyaluronic acid (HA) is an important component of the skin’s extracellular matrix, and its degradation leads to wrinkles. Hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID) is the main factor responsible for HA degradation in dermis. This study aimed to identify natural plant materials that can effectively suppress HYBID expression and protect HA from degradation. Screening of various plant extracts was performed for the inhibition of histamine-induced mRNA expression of HYBID in normal human dermal fibroblasts (NHDF). The molecular size distribution of HA was evaluated by incubating fluorescein isothiocyanate (FITC)-labeled large HA (1200–1600 kDa) in NHDF for certain time followed by measuring different sizes of FITC-labeled HA in the cultured medium by HPLC. Among 380 plant extracts, we found that Artemisia capillaris flower extract (ACFE) was the most effective agent in both suppressing HYBID expression as well as protecting large HA from degradation. Subsequent mechanism elucidation studies showed that ACFE epigenetically regulates the expression of HYBID by modulating the expression of a specific miRNA, miR-486-5p, which is known to directly target and inhibit HYBID expression. Our active compound search identified 1-caffeoyl-3-hydroxybutane and 3-caffeoyl-1-hydroxybutane in ACFE as new compounds, which we named Kawarayomogin I and Kawarayomogin II, respectively. This is the first report to show that Artemisia capillaris with two novel active compounds inhibits HYBID expression as well as hyaluronic acid degradation, and therefore, could be used as possible agent for cosmeceutical potential.
Observation of a rare beta decay of the charmed baryon with a Graph Neural Network
Integrating single-cell RNA-Seq and bulk RNA-Seq data to explore the key role of fatty acid metabolism in hepatocellular carcinoma
Structural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex
Abstract Kinetoplastids are a clade of eukaryotic protozoans that include human parasitic pathogens like trypanosomes and Leishmania species. In these organisms, protein-coding genes are transcribed as polycistronic pre-mRNAs, which need to be processed by the coupled action of trans-splicing and polyadenylation to yield monogenic mature mRNAs. During trans-splicing, a universal RNA sequence, the spliced leader RNA (SL RNA) mini-exon, is added to the 5’-end of each mRNA. The 5’-end of this mini-exon carries a hypermethylated cap structure and is bound by a trypanosomatid-specific cap-binding complex (CBC). The function of three of the kinetoplastid CBC subunits is unknown, but an essential role in cap-binding and trans-splicing has been suggested. Here, we report cryo-EM structures that reveal the molecular architecture of the Trypanosoma brucei CBC (TbCBC) complex. We find that TbCBC interacts with two distinct features of the SL RNA. The TbCBP20 subunit interacts with the m7G cap while TbCBP66 recognizes double-stranded portions of the SL RNA. Our findings pave the way for future research on mRNA maturation in kinetoplastids. Moreover, the observed structural similarities and differences between TbCBC and the mammalian cap-binding complex will be crucial for considering the potential of TbCBC as a target for anti-trypanosomatid drug development.
Anomaly detection in multidimensional time series for water injection pump operations based on LSTMA-AE and mechanism constraints
Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis
Abstract A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions. Correlative profiling of pathway activity and VSMC phenotype at the single-cell level shows that phenotypic modulation of contractile VSMCs to chondrocyte-like plaque cells during atherogenesis is associated with a switch from ANP/GC‑A to CNP/GC‑B signaling. Silencing of the CNP/GC-B axis in VSMCs results in an increase of chondrocyte-like plaque cells. These findings indicate that the CNP/GC-B/cGMP pathway is a marker and atheroprotective regulator of modulated VSMCs, limiting their transition to chondrocyte-like cells. Overall, this study highlights the plasticity of cGMP signaling in VSMCs and suggests analogies between CNP-dependent remodeling of bone and blood vessels.
Efficient pressure regulation in nonlinear shell-and-tube steam condensers via a Novel TDn(1 + PIDn) controller and DCSA algorithm
Author Correction: ChromaFold predicts the 3D contact map from single-cell chromatin accessibility
A functional integral approach to magnon mediated plasmon friction
Understanding the spread of agriculture in the Western Mediterranean (6th-3rd millennia BC) with Machine Learning tools
Abstract The first Neolithic farmers arrived in the Western Mediterranean area from the East. They established settlements in coastal areas and over time migrated to new environments, adapting to changing ecological and climatic conditions. While farming practices and settlements in the Western Mediterranean differ greatly from those known in the Eastern Mediterranean and central Europe, the extent to which these differences are connected to the local environment and climate is unclear. Here, we tackle this question by compiling data and proxies at a superregional and multi-scale level, including archaeobotanical information, radiocarbon dates and paleoclimatic models, then applying a machine learning approach to investigate the impact of ecological and climatic constraints on the first Neolithic humans and crops. This approach facilitates calculating the pace of spread of farming in the Western Mediterranean area, modelling and estimating the potential areas suitable for settlement location, and discriminating distinct types of crop cultivation under changing climatic conditions that characterized the period 5900 – 2300 cal. BC. The results of this study shed light onto the past climate variability and its influence on human distribution in the Western Mediterranean area, but also discriminate sensitive parameters for successful agricultural practices.
Impact of aspirin on biochemical recurrence of prostate cancer after robot assisted radical prostatectomy in a multicenter retrospective cohort study
Neuronal segmentation in cephalopod arms
MRI-guided focused ultrasound for treating Parkinson’s disease with human mesenchymal stem cells
Author Correction: Allostery can convert binding free energies into concerted domain motions in enzymes
Improving the thermal performance of PVC windows with pultruded thermoplastic reinforcement
CPK1 activates CNGCs through phosphorylation for Ca2+ signaling to promote root hair growth in Arabidopsis
Abstract Cyclic nucleotide-gated channel 5 (CNGC5), CNGC6, and CNGC9 (CNGC5/6/9 for simplicity) control Arabidopsis root hair (RH) growth by mediating the influx of external Ca2+ to establish and maintain a sharp cytosolic Ca2+ gradient at RH tips. However, the underlying mechanisms for the regulation of CNGCs remain unknown. We report here that calcium dependent protein kinase 1 (CPK1) directly activates CNGC5/6/9 to promote Arabidopsis RH growth. The loss-of-function mutants cpk1-1, cpk1-2, cngc5-1 cngc6-2 cngc9-1 (shrh1/short root hair 1), and cpk1 shrh1 show similar RH phenotypes, including shorter RHs, more RH branching, and dramatically attenuated cytosolic Ca2+ gradients at RH tips. The main CPK1-target sites are identified as Ser20, Ser27, and Ser26 for CNGC5/6/9, respectively, and the corresponding alanine substitution mutants fail to rescue RH growth in shrh1 and cpk1-1, while phospho-mimic versions restore the cytosolic Ca2+ gradient at RH apex and rescue the RH phenotypes in the same Arabidopsis mutants. Thus we discover the CPK1-CNGC modules essential for the Ca2+ signaling regulation and RH growth in Arabidopsis.