Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma

Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, “CKS2,” “RIMS3,” “TRAC,” “FMOD,” CALML5,” and “SPINK7,” were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan–Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the “pRRophetic” package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC

Identification of important charged residues for alkali cation exchange or pH regulation of NhaH, a Na+/H+ antiporter of Halobacillus dabanensis

AbstractNhaH is a novel Na+/H+ antiporter identified from the moderate halophile Halobacillus dabanensis. In this study, six conserved charged residues located in the putative transmembrane segments (TMS) including TMSV, TMSVI, TMSVIII and TMSXI of NhaH as well as two His residues in Loop III were replaced by site-directed mutagenesis for the identification of their potential roles in the antiport activity and pH regulation. Substitutions D137A, D166A and R325A caused a complete loss of Na+(Li+)/H+ antiport activity, revealing that D137, D166 and R325 are indispensable for the antiport activity. Substitution D137E led to a significant increase of the apparent Km values for Na+ and Li+ without affecting the changes of pH profile, confirming that D137 plays vital roles in alkali cation binding/translocation. Substitution D166E resulted in not only a significant increase of the apparent Km values for Na+ and Li+ but also an alkaline shift of pH profile, suggesting that D166 is involved in alkali cation binding/translocation as well as H+ binding or pH regulation. Substitutions E161N, D224A and D224E caused a significant increase of Km for Na+ and Li+, indicating that E161 and D224 partly contribute to alkali cation binding/translocation. Substitution E229K caused an over 50% elevation of the apparent Km for Li+, without affecting that for Na+, suggesting that E229 may be mainly responsible for Li+ binding/translocation. Substitutions H87A and H88A resulted in an acidic shift of pH profile without an effect on Km for Na+ and Li+, indicating that H87 and H88 are involved in H+ binding or pH regulation

HairBrush for Immersive Data-Driven Hair Modeling

International audienceWhile hair is an essential component of virtual humans, it is also one of the most challenging digital assets to create. Existing automatic techniques lack the generality and flexibility to create rich hair variations, while manual authoring interfaces often require considerable artistic skills and efforts, especially for intricate 3D hair structures that can be difficult to navigate. We propose an interactive hair modeling system that can help create complex hairstyles in minutes or hours that would otherwise take much longer with existing tools. Modelers, including novice users, can focus on the overall hairstyles and local hair deformations, as our system intelligently suggests the desired hair parts. Our method combines the flexibility of manual authoring and the convenience of data-driven automation. Since hair contains intricate 3D structures such as buns, knots, and strands, they are inherently challenging to create using traditional 2D interfaces. Our system provides a new 3D hair author-ing interface for immersive interaction in virtual reality (VR). Users can draw high-level guide strips, from which our system predicts the most plausible hairstyles via a deep neural network trained from a professionally curated dataset. Each hairstyle in our dataset is composed of multiple variations, serving as blend-shapes to fit the user drawings via global blending and local deformation. The fitted hair models are visualized as interactive suggestions that the user can select, modify, or ignore. We conducted a user study to confirm that our system can significantly reduce manual labor while improve the output quality for modeling a variety of head and facial hairstyles that are challenging to create via existing techniques

Novel Quasi‐Liquid K‐Na Alloy as a Promising Dendrite‐Free Anode for Rechargeable Potassium Metal Batteries

Rechargeable potassium metal batteries are promising energy storage devices with potentially high energy density and markedly low cost. However, eliminating dendrite growth and achieving a stable electrode/electrolyte interface are the key challenges to tackle. Herein, a novel "quasi-liquid" potassium-sodium alloy (KNA) anode comprising only 3.5 wt% sodium (KNA-3.5) is reported, which exhibits outstanding electrochemical performance able to be reversibly cycled at 4 mA cm-2 for 2000 h. Moreover, it is demonstrated that adding a small amount of sodium hexafluorophosphate (NaPF6 ) into the potassium bis(fluorosulfonyl)imide electrolyte allows for the formation of the "quasi-liquid" KNA on electrode surface. Comprehensive experimental studies reveal the formation of an unusual metastable KNa2 phase during plating, which is believed to facilitate simultaneous nucleation and suppress the growth of dendrites, thereby improving the electrode's cycle lifetime. The "quasi-liquid" KNA-3.5 anode demonstrates markedly enhanced electrochemical performance in a full cell when pairing with Prussian blue analogs or sodium rhodizonate dibasic as the cathode material, compared to the pristine potassium anode. Importantly, unlike the liquid KNA reported before, the "quasi-liquid" KNA-3.5 exhibits good processability and can be readily shaped into sheet electrodes, showing substantial promise as a dendrite-free anode in rechargeable potassium metal batteries.Z.T. acknowledges the financial support of Maria Curie COFUND fellowship (Grant No. 713640). Z.L. thanks the financial support of China Scholarship Council (Grant No. 201 806 400 066). This project was partly funded by the “Baterias 2030” project through the Mobilizadore Programme by the National Innovation Agency of Portugal (Grant No. POCI-01-0247- FEDER-046109). G.Y. acknowledges the financial support from the Welch Foundation Award F-1861. The authors thank Dr. Artur Martins for his assistance in mechanical property measurement.info:eu-repo/semantics/publishedVersio

Photoperiod-responsive changes in chromatin accessibility in phloem companion and epidermis cells of Arabidopsis leaves

Photoperiod plays a key role in controlling the phase transition from vegetative to reproductive growth in flowering plants. Leaves are the major organs perceiving day-length signals, but how specific leaf cell types respond to photoperiod remains unknown. We integrated photoperiod-responsive chromatin accessibility and transcriptome data in leaf epidermis and vascular companion cells of Arabidopsis thaliana by combining isolation of nuclei tagged in specific cell/tissue types with assay for transposase-accessible chromatin using sequencing and RNA-sequencing. Despite a large overlap, vasculature and epidermis cells responded differently. Long-day predominantly induced accessible chromatin regions (ACRs); in the vasculature, more ACRs were induced and these were located at more distal gene regions, compared with the epidermis. Vascular ACRs induced by long days were highly enriched in binding sites for flowering-related transcription factors. Among the highly ranked genes (based on chromatin and expression signatures in the vasculature), we identified TREHALOSE-PHOSPHATASE/SYNTHASE 9 (TPS9) as a flowering activator, as shown by the late flowering phenotypes of T-DNA insertion mutants and transgenic lines with phloem-specific knockdown of TPS9. Our cell-type-specific analysis sheds light on how the long-day photoperiod stimulus impacts chromatin accessibility in a tissue-specific manner to regulate plant development

Bifurcation of Arabidopsis NLR Immune Signaling via Ca2+-Dependent Protein Kinases

Nucleotide-binding domain leucine-rich repeat (NLR) protein complexes sense infections and trigger robust immune responses in plants and humans. Activation of plant NLR resistance (R) proteins by pathogen effectors launches convergent immune responses, including programmed cell death (PCD), reactive oxygen species (ROS) production and transcriptional reprogramming with elusive mechanisms. Functional genomic and biochemical genetic screens identified six closely related Arabidopsis Ca2+-dependent protein kinases (CPKs) in mediating bifurcate immune responses activated by NLR proteins, RPS2 and RPM1. The dynamics of differential CPK1/2 activation by pathogen effectors controls the onset of cell death. Sustained CPK4/5/6/11 activation directly phosphorylates a specific subgroup of WRKY transcription factors, WRKY8/28/48, to synergistically regulate transcriptional reprogramming crucial for NLR-dependent restriction of pathogen growth, whereas CPK1/2/4/11 phosphorylate plasma membrane-resident NADPH oxidases for ROS production. Our studies delineate bifurcation of complex signaling mechanisms downstream of NLR immune sensors mediated by the myriad action of CPKs with distinct substrate specificity and subcellular dynamics

Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6), CD14+ monocytes (P ≤ 2.74 × 10−4) and CD19+ B cells (P ≤ 2.00 × 10−6), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10−6). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE

Glacial-interglacial evolution of seasonal cooling events documented by land-snail eggs from Chinese loess

The alternations of glacial and interglacial cycles are a classical feature of Quaternary climatic evolution and have been demonstrated to be closely related to seasonal insolation changes at high northern latitudes. Therefore, seasonal features may provide insights into glacial-interglacial cycles. However, mainly due to the lack of long time series of seasonally sensitive proxies, little is known about seasonal changes on the glacial-interglacial scale. The unhatched eggs preserved in sediments can serve as a proxy of seasonal cooling events (e.g., cold spells) since biological principles indicate that egg hatching is sensitive to temperature changes, and cooling-event-induced low temperatures during the reproductive season are unfavorable for eggs to hatch. Vertebrate eggs are well documented in the geological records, but they rarely provide continuous records through time. Here we present a high-resolution time series of land-snail eggs from the Chinese Loess Plateau, spanning the last three glacial-interglacial cycles. The results show that seasonal cooling events, indicated by peaks in egg abundance, are strong during glacial inceptions and climate cooling shifts of the marine isotope stages (MIS) 7e/7d, MIS 5e/5d, MIS 5c/5b and MIS 3/2. They tend not to occur during deglacials. They may result in low temperatures unfavorable for egg hatching during the reproductive season. Although several factors may be involved, seasonal cooling events in the Chinese Loess Plateau seem to be positively and more closely related to high-northernlatitude ice sheet growth. This finding may provide a new perspective for understanding glacialinterglacial evolution

Macrophage‐derived MMP‐9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits

Matrix metalloproteinase‐9 (MMP‐9), or gelatinase B, has been hypothesized to be involved in the progression of atherosclerosis. In the arterial wall, accumulated macrophages secrete considerable amounts of MMP‐9 but its pathophysiological functions in atherosclerosis have not been fully elucidated. To examine the hypothesis that macrophage‐derived MMP‐9 may affect atherosclerosis, we created MMP‐9 transgenic (Tg) rabbits to overexpress the rabbit MMP‐9 gene under the control of the scavenger receptor A enhancer/promoter and examined their susceptibility to cholesterol diet‐induced atherosclerosis. Tg rabbits along with non‐Tg rabbits were fed a cholesterol diet for 16 and 28 weeks, and their aortic and coronary atherosclerosis was compared. Gross aortic lesion areas were significantly increased in female Tg rabbits at 28 weeks; however, pathological examination revealed that all the lesions of Tg rabbits fed a cholesterol diet for either 16 or 28 weeks were characterized by increased monocyte/macrophage accumulation and prominent lipid core formation compared with those of non‐Tg rabbits. Macrophages isolated from Tg rabbits exhibited higher infiltrative activity towards a chemoattractant, MCP‐1 in vitro and augmented capability of hydrolysing extracellular matrix in granulomatous tissue. Surprisingly, the lesions of Tg rabbits showed more advanced lesions with remarkable calcification in both aortas and coronary arteries. In conclusion, macrophage‐derived MMP‐9 facilitates the infiltration of monocyte/macrophages into the lesions thereby enhancing the progression of atherosclerosis. Increased accumulation of lesional macrophages may promote vascular calcification.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154927/1/jcmm15087-sup-0001-FigS1-S13.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154927/2/jcmm15087.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154927/3/jcmm15087_am.pd