The X-zone is a transient cortical region enriched in eosinophilic cells located in the cortical–medullary boundary of the mouse adrenal gland. Similar to the X-zone, the fetal zone in human adrenals ...is also a transient cortical compartment, comprising the majority of the human fetal adrenal gland. During adrenal development, fetal cortical cells are gradually replaced by newly formed adult cortical cells that develop into outer definitive zones. In mice, the regression of this fetal cell population is sexually dimorphic. Many mouse models with mutations associated with endocrine factors have been reported with X-zone phenotypes. Increasing findings indicate that the cell fate of this aged cell population of the adrenal cortex can be manipulated by many hormonal and nonhormonal factors. This review summarizes the current knowledge of this transient adrenocortical zone with an emphasis on genes and signaling pathways that affect X-zone cells.
The use of microbial source tracking (MST) marker genes has grown in recent years due to the need to attribute point and non-point fecal contamination to specific sources. Quantitative microbial risk ...assessment (QMRA) is a modeling approach used to estimate health risks from exposure to feces-contaminated water and associated pathogens. A combination of these approaches quantitative MST (qMST) and QMRA can provide additional pathogen-related information for prioritizing and addressing health risks, compared to reliance on conventional fecal indicator bacteria (FIB). To inform expansion of this approach, a review of published qMST-QMRA studies was conducted to summarize the state of the science and to identify research needs. The reviewed studies primarily aimed to identify what levels of MST marker genes in hypothetical recreational waterbodies would exceed the United States Environmental Protection Agency (USEPA) risk benchmarks for primary contact recreators. The QMRA models calculated relationships between MST marker gene(s) and reference pathogens based on published data in the literature. The development of a robust, accurate relationship was identified as an urgent research gap for qMST-QMRA. This metric requires additional knowledge to quantify the relationship between MST marker genes and the degree of variability in decay of pathogens as a dynamic function of environmental conditions and combinations of fecal sources at multiple spatial and temporal scales. Improved characterization of host shedding rates of host-associated microorganisms (i.e., MST marker genes), as well as fate and transport of these microorganisms and their nucleic acids, would facilitate expansion of this approach to other exposure pathways. Incorporation of information regarding the recovery efficiency, and host-specificity of MST marker genes into QMRA model parameters, and the sensitivity analysis, would greatly improve risk management and site-specific water monitoring criteria.
•qMST and QMRA can provide information for prioritizing health risks.•Accurate relationship was identified as an urgent research gap for qMST-QMRA.•Recovery efficiency, host-specificity and sensitivity analysis need to be considered for QMRA model.
In search of more efficacious and safe pharmacological treatments for atrial fibrillation (AF), atria-selective antiarrhythmic agents have been promoted that target ion channels principally expressed ...in the atria. This concept allows one to engage antiarrhythmic effects in atria, but spares the ventricles from potentially proarrhythmic side effects. It has been suggested that cardiac small conductance Ca
2+
-activated K
+
(SK) channels may represent an atria-selective target in mammals including humans. However, there are conflicting data concerning the expression of SK channels in different stages of AF, and recent findings suggest that SK channels are upregulated in ventricular myocardium when patients develop heart failure. To address this issue, RNA-sequencing was performed to compare expression levels of three SK channels (
KCNN1
,
KCNN2
, and
KCNN3
) in human atrial and ventricular tissue samples from transplant donor hearts (no cardiac disease), and patients with cardiac disease in sinus rhythm or with AF. In addition, for control purposes expression levels of several genes known to be either chamber-selective or differentially expressed in AF and heart failure were determined. In atria, as compared to ventricle from transplant donor hearts, we confirmed higher expression of
KCNN1
and
KCNA5
, and lower expression of
KCNJ2
, whereas
KCNN2
and
KCNN3
were statistically not differentially expressed. Overall expression of
KCNN1
was low compared to
KCNN2
and
KCNN3
. Comparing atrial tissue from patients with AF to sinus rhythm samples we saw downregulation of
KCNN2
in AF, as previously reported. When comparing ventricular tissue from heart failure patients to non-diseased samples, we found significantly increased ventricular expression of
KCNN3
in heart failure, as previously published. The other channels showed no significant difference in expression in either disease. Our results add weight to the view that SK channels are not likely to be an atria-selective target, especially in failing human hearts, and modulators of these channels may prove to have less utility in treating AF than hoped. Whether targeting SK1 holds potential remains to be elucidated.
Cold stress (CS) severely affects several physiological, biochemical, and molecular mechanisms and limits the growth and production of rapeseed (
L.). Trehalose (Tre) acts as a growth modulator, ...which is extensively used to improve the tolerance to multiple plant stresses. Further, Tre also serves as an external force in inducing plant signaling molecules, regulating the expression of stress-responsive genes, and enhancing the CS tolerance in plants. Nevertheless, the importance of exogenous Tre in improving the CS tolerance in rapeseed is still unclear. Therefore, the current study was designed to get mechanistic insights into Tre-mediated CS tolerance in rapeseed seedlings. To explore the Tre role, we designed four treatments control (CK), CK + 20 mM L
Tre, Cold, and Cold + 20 mM L
Tre and three CS conditions (4, 0, and -4°C). The results showed that Tre treatments significantly mitigated the adverse effects of CS on the seedlings and increased the survival rate of Tre-treated seedlings under CS conditions. The exogenous Tre dramatically increased the contents of osmoprotectants, including the soluble sugar (SS), soluble protein (SP), and proline (Pro), and the activities of antioxidant enzymes, such as catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX) were also increased under CS conditions. Additionally, Tre decreased the malondialdehyde (MDA) contents to protect the rapeseed seedlings. Moreover, Tre also remarkably augmented the expression levels of antioxidant genes (
, and
), CS-responsive marker genes (
, and
), and Tre-biosynthesis genes (
, and
). Briefly, exogenous Tre not only regulates the antioxidant and osmotic balance, but it also significantly participates in Tre metabolism and signaling network to improve the CS tolerance in rapeseed. Thus, Tre-induced supervisory connections between physiological or/and biochemical attributes provide information to dissect the mechanisms of Tre-mediated CS tolerance.
We propose PreCanCell, a novel algorithm for predicting malignant and non-malignant cells from single-cell transcriptomes. PreCanCell first identifies the differentially expressed genes (DEGs) ...between malignant and non-malignant cells commonly in five common cancer types-associated single-cell transcriptome datasets. The five common cancer types include renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), melanoma, lung adenocarcinoma (LUAD), and breast cancer (BC). With each of the five datasets as the training set and the DEGs as the features, a single cell is classified as malignant or non-malignant by k-NN (k = 5). Finally, the single cell is determined as malignant or non-malignant by the majority vote of the five k-NN classification results. We tested the predictive performance of PreCanCell in 19 single-cell datasets, and reported classification accuracy, sensitivity, specificity, balanced accuracy (the average of sensitivity and specificity) and the area under the receiver operating characteristic curve (AUROC). In all these datasets, PreCanCell achieved above 0.8 accuracy, sensitivity, specificity, balanced accuracy and AUROC. Finally, we compared the predictive performance of PreCanCell with that of seven other algorithms, including CHETAH, SciBet, SCINA, scmap-cell, scmap-cluster, SingleR, and ikarus. Compared to these algorithms, PreCanCell displays the advantages of higher accuracy and simpler implementation. We have developed an R package for the PreCanCell algorithm, which is available at https://github.com/WangX-Lab/PreCanCell.
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•PreCanCell is an algorithm for predicting cancer and non-cancer cells from single-cell transcriptomes.•PreCanCell is a simple and effective ensemble learning algorithm.•PreCanCell uses well-annotated and high-quality cancer single-cell transcriptomes as the training set.•PreCanCell does not require users to provide gene markers and training or reference datasets.•PreCanCell displays better performance in predicting cancer and non-cancer cells than most established algorithms.
Biochar and compost are seen as two attractive waste management options and are used for soil amendment and pollution remediation. The interaction between biochar and composting may improve the ...potential benefits of biochar and compost. We investigated soil physicochemical properties, bacterial community, bacterial
16S rRNA
, and functional marker genes of nitrogen cycling of the soil remedied with nothing (S), compost (SC), biochar (SB), a mixture of compost and biochar (SBC), composted biochar (SBced), and a composted mixture of biochar and biomass (SBCing). The results were that all amendments (1) increased the bacterial community richness (except SB) and SBCing showed the greatest efficiency; (2) increased the bacterial community diversity (SBCing > SBC > SC > SBced > SB > S); and (3) changed the gene copy numbers of
16S rRNA
,
nirK
,
nirS
, and
nosZ
genes of bacteria,
ammonia-oxidizing archaea
(
AOA
), and
ammonia-oxidizing bacteria
(
AOB
). All amendments (except SB) could increase the gene copy number of
16S rRNA
, and SBCing had the greatest efficiency. The changes of soil bacterial community richness and diversity and the gene copy numbers of
16S rRNA, nirK, nirS, nosZ, AOA
, and
AOB
would affect carbon and nitrogen cycling of the ecosystem and also implied that BCing had the greatest efficiency on soil amendment.
Accumulating evidence has highlighted the effects of natural killer (NK) cells on shaping anti-tumor immunity. This study aimed to construct an NK cell marker gene signature (NKMS) to predict ...prognosis and therapeutic response of clear cell renal cell carcinoma (ccRCC) patients.
Publicly available single-cell and bulk RNA profiles with matched clinical information of ccRCC patients were collected from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), ArrayExpress, and International Cancer Genome Consortium (ICGC) databases. A novel NKMS was constructed, and its prognostic value, associated immunogenomic features and predictive capability to immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies were evaluated in ccRCC patients.
We identified 52 NK cell marker genes by single-cell RNA-sequencing (scRNA-seq) analysis in GSE152938 and GSE159115. After least absolute shrinkage and selection operator (LASSO) and Cox regression, the most prognostic 7 genes (
and
) composed NKMS using bulk transcriptome from TCGA. Survival and time-dependent receiver operating characteristic (ROC) analysis exhibited exceptional predictive capability of the signature in the training set and two independent validation cohorts (E-MTAB-1980 and RECA-EU cohorts). The seven-gene signature was able to identify patients within high Fuhrman grade (G3-G4) and American Joint Committee on Cancer (AJCC) stage (III-IV). Multivariate analysis confirmed the independent prognostic value of the signature, and a nomogram was built for clinical utility. The high-risk group was characterized by a higher tumor mutation burden (TMB) and greater infiltration of immunocytes, particularly CD8
T cells, regulatory T (Treg) cells and follicular helper T (Tfh) cells, in parallel with higher expression of genes negatively regulating anti-tumor immunity. Moreover, high-risk tumors exhibited higher richness and diversity of T-cell receptor (TCR) repertoire. In two therapy cohorts of ccRCC patients (PMID32472114 and E-MTAB-3267), we demonstrated that high-risk group showed greater sensitivity to ICIs, whereas the low-risk group was more likely to benefit from anti-angiogenic therapy.
We identified a novel signature that can be utilized as an independent predictive biomarker and a tool for selecting the individualized treatment for ccRCC patients.
Applying phosphate-solubilizing bacteria (PSB) as biofertilizers has enormous potential for sustainable agriculture. Despite this, there is still a lack of information regarding the expression of key ...genes related to phosphate-solubilization (PS) and efficient formulation strategies. In this study, we investigated rock PS by
sp. SSR (DSM 109610) by relating it to bacterial gene expression and searching for an efficient formulation. The quantitative PCR (qPCR) primers were designed for PS marker genes glucose dehydrogenase (
), pyrroloquinoline quinone biosynthesis protein C (
), and phosphatase (
). The SSR-inoculated soil supplemented with rock phosphate (RP) showed a 6-fold higher expression of
and
compared to inoculated soil without RP. Additionally, an increase in plant phosphorous (P) (2%), available soil P (4.7%), and alkaline phosphatase (6%) activity was observed in PSB-inoculated plants supplemented with RP. The root architecture improved by SSR, with higher root length, diameter, and volume.
sp. SSR was further used to design bioformulations with two well-characterized PS,
spp. DSM 109592 and DSM 109593, using the four organic amendments, biochar, compost, filter mud (FM), and humic acid. All four carrier materials maintained adequate survival and inoculum shelf life of the bacterium, as indicated by the field emission scanning electron microscopy analysis. The FM-based bioformulation was most efficacious and enhanced not only wheat grain yield (4-9%) but also seed P (9%). Moreover, FM-based bioformulation enhanced soil available P (8.5-11%) and phosphatase activity (4-5%). Positive correlations were observed between the PSB solubilization in the presence of different insoluble P sources, and soil available P, soil phosphatase activity, seed P content, and grain yield of the field grown inoculated wheat variety Faisalabad-2008, when di-ammonium phosphate fertilizer application was reduced by 20%. This study reports for the first time the marker gene expression of an inoculated PSB strain and provides a valuable groundwork to design field scale formulations that can maintain inoculum dynamics and increase its shelf life. This may constitute a step-change in the sustainable cultivation of wheat under the P-deficient soil conditions.
There is a growing move towards using the quantitative polymerase chain (qPCR)-based sewage-associated marker genes to assess surface water quality. However, a lack of understanding about the ...persistence of many sewage-associated markers creates uncertainty for those tasked with investigating microbial water quality. In this study, we investigated the decay of two qPCR FIB E. coli (EC), and Enterococcus spp. (ENT) 23S rRNA genes and four sewage-associated microbial source tracking (MST) marker genes human Bacteroides HF183 16S rRNA, adenovirus (HAdV), and polyomavirus (HPyV), and crAssphage, a recently described bacteriophage in feces, in outdoor mesocosms containing fresh and marine waters and their corresponding sediments. Decay rates of EC 23S rRNA, ENT 23S rRNA, and HF183 16S rRNA were significantly (p < 0.05) faster than the HAdV, HPyV and crAssphage markers in water samples from all mesocosms. In general, decay rates of bacterial targets were similar in the water columns of the studied mesocosms. Similarly, decay rates of viral targets were also alike in mesocosm water columns in relation to each other. The decay rates of FIB and sewage-associated markers were significantly faster in water samples compared to sediments in all three mesocosms. In the event of resuspension, FIB and marker genes from sediments can potentially recontaminate overlying waters. Thus, care should be taken when interpreting the occurrence of FIB and sewage-associated MST markers in water, which may have originated from sediments. The differential decay of these targets may also influence health outcomes and need to be considered in risk assessment models.
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•Decay rates of bacterial gene markers were significantly faster than the viruses.•Markers decay rates were significantly faster in water samples compared to sediments.•Decay rates of marker genes were similar for both fresh and marine waters.•Markers decay positively correlated with water temperature, TOC, and turbidity.
On single-cell RNA-sequencing data, we consider the problem of assigning cells to known cell types, assuming that the identities of cell-type-specific marker genes are given but their exact ...expression levels are unavailable, that is, without using a reference dataset. Based on an observation that the expected over-expression of marker genes is often absent in a nonnegligible proportion of cells, we develop a method called scSorter. scSorter allows marker genes to express at a low level and borrows information from the expression of non-marker genes. On both simulated and real data, scSorter shows much higher power compared to existing methods.
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