DataSheet_1_Genome-wide characterization and evolutionary analysis of linker histones in castor bean (Ricinus communis).pdf

H1s, or linker histones, are ubiquitous proteins in eukaryotic cells, consisting of a globular GH1 domain flanked by two unstructured tails. Whilst it is known that numerous non-allelic variants exist within the same species, the degree of interspecific and intraspecific variation and divergence of linker histones remain unknown. The conserved basic binding sites in GH1 and evenly distributed strong positive charges on the C-terminal domain (CTD) are key structural characters for linker histones to bind chromatin. Based on these features, we identified five linker histones from 13 GH1-containing proteins in castor bean (Ricinus communis), which were named as RcH1.1, RcH1.2a, RcH1.2b, RcH1.3, and RcH1.4 based on their phylogenetic relationships with the H1s from five other economically important Euphorbiaceae species (Hevea brasiliensis Jatropha curcas, Manihot esculenta Mercurialis annua, and Vernicia fordii) and Arabidopsis thaliana. The expression profiles of RcH1 genes in a variety of tissues and stresses were determined from RNA-seq data. We found three RcH1 genes (RcH1.1, RcH1.2a, and RcH1.3) were broadly expressed in all tissues, suggesting a conserved role in stabilizing and organizing the nuclear DNA. RcH1.2a and RcH1.4 was preferentially expressed in floral tissues, indicating potential involvement in floral development in castor bean. Lack of non-coding region and no expression detected in any tissue tested suggest that RcH1.2b is a pseudogene. RcH1.3 was salt stress inducible, but not induced by cold, heat and drought in our investigation. Structural comparison confirmed that GH1 domain was highly evolutionarily conserved and revealed that N- and C-terminal domains of linker histones are divergent between variants, but highly conserved between species for a given variant. Although the number of H1 genes varies between species, the number of H1 variants is relatively conserved in more closely related species (such as within the same family). Through comparison of nucleotide diversity of linker histone genes and oil-related genes, we found similar mutation rate of these two groups of genes. Using Tajima’s D and ML-HKA tests, we found RcH1.1 and RcH1.3 may be under balancing selection.</p

DataSheet_2_Genome-wide characterization and evolutionary analysis of linker histones in castor bean (Ricinus communis).xlsx

H1s, or linker histones, are ubiquitous proteins in eukaryotic cells, consisting of a globular GH1 domain flanked by two unstructured tails. Whilst it is known that numerous non-allelic variants exist within the same species, the degree of interspecific and intraspecific variation and divergence of linker histones remain unknown. The conserved basic binding sites in GH1 and evenly distributed strong positive charges on the C-terminal domain (CTD) are key structural characters for linker histones to bind chromatin. Based on these features, we identified five linker histones from 13 GH1-containing proteins in castor bean (Ricinus communis), which were named as RcH1.1, RcH1.2a, RcH1.2b, RcH1.3, and RcH1.4 based on their phylogenetic relationships with the H1s from five other economically important Euphorbiaceae species (Hevea brasiliensis Jatropha curcas, Manihot esculenta Mercurialis annua, and Vernicia fordii) and Arabidopsis thaliana. The expression profiles of RcH1 genes in a variety of tissues and stresses were determined from RNA-seq data. We found three RcH1 genes (RcH1.1, RcH1.2a, and RcH1.3) were broadly expressed in all tissues, suggesting a conserved role in stabilizing and organizing the nuclear DNA. RcH1.2a and RcH1.4 was preferentially expressed in floral tissues, indicating potential involvement in floral development in castor bean. Lack of non-coding region and no expression detected in any tissue tested suggest that RcH1.2b is a pseudogene. RcH1.3 was salt stress inducible, but not induced by cold, heat and drought in our investigation. Structural comparison confirmed that GH1 domain was highly evolutionarily conserved and revealed that N- and C-terminal domains of linker histones are divergent between variants, but highly conserved between species for a given variant. Although the number of H1 genes varies between species, the number of H1 variants is relatively conserved in more closely related species (such as within the same family). Through comparison of nucleotide diversity of linker histone genes and oil-related genes, we found similar mutation rate of these two groups of genes. Using Tajima’s D and ML-HKA tests, we found RcH1.1 and RcH1.3 may be under balancing selection.</p

Data_Sheet_1_Recent estimates and predictions of 5-year survival rate in patients with pancreatic cancer: A model-based period analysis.pdf

BackgroundThe 5-year survival rate for pancreatic cancer (PC) is incredibly low, resulting in this often being a fatal disease. Timely and accurate assessment of the survival rate and prognosis of patients with PC is of great significance for the development of new programs for prevention, monitoring, and treatment.MethodsPeriod analysis and further stratified analysis were used to determine the 5-year relative survival rate (RSR) of patients with PC from 2002 to 2016 using the Surveillance, Epidemiology, and End Results (SEER) project database of the National Cancer Institute. Based on this, a generalized linear model was created to predict the survival rate of patients from 2017 to 2021.ResultDuring 2002–2016, the 5-year RSR of patients with PC increased from 7.9 to 23.7%. The generalized linear model predicted that the survival rate had increased to 33.9% during 2017–2021, and hence, it was still unacceptably low. The survival rate of patients aged ≥75 years at diagnosis was the lowest among all age groups and was predicted to be only 21.4% during 2017–2021. Notably, the survival rate of patients with differentiation grade III at diagnosis remains particularly low at 7.6%.ConclusionThe survival rates of patients with PC, although slightly improved, remain extremely low. Timely assessment of the trend of survival rate changes in patients with PC further improves the prognosis of tumor patients and provides data support for relevant medical works to formulate effective tumor prevention and control policies.</p

Blood Glucose Fluctuation in Older Adults with Diabetes Mellitus and End-Stage Renal Disease on Maintenance Hemodialysis - An Observational Study

   Article full text The article associated with this page has been accepted for online publication and is in the final stages of production. The link to the full text will be made available on this page in the next few days. The above summary slide represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, please see the full text online (see “read the peer-reviewed publication” opposite).  © The authors, CC-BY-NC 2022.</p

Metal/metalloid levels and variation in lifetime cancer risks among tissues

Extreme variation in lifetime cancer risk among tissues has been a riddle of cancer etiology. Considering that cancer risks were found to be contributed heavily by environmental factors, levels of environmental carcinogens, such as metal/metalloid in tissues, may be an explanation of the variation. We analyzed the correlations between metal/metalloid concentrations in different tissues and the lifetime cumulative cancer risks of the corresponding tissues using the data of National Health Standards and National Central Cancer Registry of China. Cadmium (Cd) and rubidium (Rb) were found to be correlated with the lifetime cancer risks in a positive linear relationship while a U-shaped relationship was observed for cesium (Cs) and tin (Sn). A positive linear trend between the mixture of metals/metalloids and lifetime cancer risks was observed and cadmium (Cd) may be the main driving element. Our results indicated that Cd-based metal/metalloid levels may be an explanation for the variation in lifetime cancer risk among tissues. Furthermore, the analytical strategy may in turn help identify environmental factors involved in cancer etiology.</p

Multi-omics integration analysis unveils heterogeneity in breast cancer at the individual level

Identifying robust breast cancer subtypes will help to reveal the cancer heterogeneity. However, previous breast cancer subtypes were based on population-level quantitative gene expression, which is affected by batch effects and cannot be applied to individuals. We detected differential gene expression, genomic, and epigenomic alterations to identify driver differential expression at the individual level. The individual driver differential expression reflected the breast cancer patients’ heterogeneity and revealed four subtypes. Mesenchymal subtype as the most aggressive subtype harbored deletion and downregulated expression of genes in chromosome 11q23 region. Specifically, silencing of the SDHD gene in 11q23 promoted the invasion and migration of breast cancer cells in vitro by the epithelial–mesenchymal transition. The immunologically hot subtype displayed an immune-hot microenvironment, including high T-cell infiltration and upregulated PD-1 and CTLA4. Luminal and genomic-unstable subtypes showed opposite macrophage polarization, which may be regulated by the ligand–receptor pairs of CD99. The integration of multi-omics data at the individual level provides a powerful framework for elucidating the heterogeneity of breast cancer.</p

DataSheet_1_Ubiquitin-specific protease 29 attenuates hepatic ischemia-reperfusion injury by mediating TGF-β-activated kinase 1 deubiquitination.docx

Background and aimsIn the course of clinical practice, hepatic ischemia/reperfusion (I/R) injury is a prevalent pathophysiological event and is caused by a combination of complex factors that involve multiple signaling pathways such as MAPK and NF-κB. USP29 is a deubiquitinating enzyme important during the development of tumors, neurological diseases, and viral immunity. However, it is unknown how USP29 contributes to hepatic I/R injury.Methods and resultsWe systematically investigated the role of the USP29/TAK1-JNK/p38 signaling pathway in hepatic I/R injury. We first found reduced USP29 expression in both mouse hepatic I/R injury and the primary hepatocyte hypoxia-reoxygenation (H/R) models. We established USP29 full knockout mice (USP29-KO) and hepatocyte-specific USP29 transgenic mice (USP29-HTG), and we found that USP29 knockout significantly exacerbates the inflammatory infiltration and injury processes during hepatic I/R injury, whereas USP29 overexpression alleviates liver injury by decreasing the inflammatory response and inhibiting apoptosis. Mechanistically, RNA sequencing results showed the effects of USP29 on the MAPK pathway, and further studies revealed that USP29 interacts with TAK1 and inhibits its k63-linked polyubiquitination, thereby preventing the activation of TAK1 and its downstream signaling pathways. Consistently, 5z-7-Oxozeaneol, an inhibitor of TAK1, blocked the detrimental effects of USP29 knockout on H/R-induced hepatocyte injury, further confirming that USP29 plays a regulatory role in hepatic I/R injury by targeting TAK1.ConclusionOur findings imply that USP29 is a therapeutic target with promise for the management of hepatic I/R injury via TAK1-JNK/p38 pathway-dependent processes.</p