It remains unclear whether and how cardiomyocytes contribute to the inflammation in chronic heart failure (CHF). We recently reviewed the capacity of cardiomyocytes to initiate inflammation, by means ...of expressing certain immune receptors such as toll‐like receptors (TLRs) that respond to pathogen‐ and damage‐associated molecular patterns (PAMP and DAMP). Previous studies observed TLR4‐mediated inflammation within days of myocardial infarction (MI). This study examined TLR4 expression and function in cardiomyocytes of failing hearts after 4 weeks of MI in rats. The increases of TLR4 mRNA and proteins, as well as inflammatory cytokine production, were observed in both the infarct and remote myocardium. Enhanced immunostaining for TLR4 was observed in cardiomyocytes but not infiltrating leucocytes. The injection of lentivirus shRNA against TLR4 into the infarcted heart decreased inflammatory cytokine production and improved heart function in vivo. Accordingly, in cardiomyocytes isolated from CHF hearts, increases of TLR4 mRNA and proteins were detected. More robust binding of TLR4 with lipopolysaccharide (LPS), a PAMP ligand for TLR4, and heat shock protein 60 (HSP60), a DAMP ligand for TLR4, was observed in CHF cardiomyocytes under a confocal microscope. The maximum binding capacity (Bmax) of TLR4 was increased for LPS and HSP60, whereas the binding affinity (Kd) was not significantly changed. Furthermore, both LPS and HSP60 induced more robust production of inflammatory cytokines in CHF cardiomyocytes, which was reduced by TLR4‐blocking antibodies. We conclude that the expression, ligand‐binding capacity and pro‐inflammatory function of cardiomyocyte TLR4 are up‐regulated after long‐term MI, which promote inflammation and exacerbate heart failure.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are ...unclear. In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b-regulated rice immunity against the blast fungus Magnaporthe oryzae. Out of the four target genes of miR398b, mutations in Cu/Zn-Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H
O
) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H
O
production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity. Our results demonstrate the roles of different SODs in miR398b-regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H
O
concentration and thereby improve disease resistance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Cycads are the most ancient lineage of living seed plants, but the design of their leaves has received little study. We tested whether cycad leaves are governed by the same fundamental design ...principles previously established for ferns, conifers and angiosperms, and characterized the uniqueness of this relict lineage in foliar trait relationships. Leaf structure, photosynthesis, hydraulics and nutrient composition were studied in 33 cycad species from nine genera and three families growing in two botanical gardens. Cycads varied greatly in leaf structure and physiology. Similarly to other lineages, light‐saturated photosynthetic rate per mass (Aₘ) was related negatively to leaf mass per area and positively to foliar concentrations of chlorophyll, nitrogen (N), phosphorus and iron, but unlike angiosperms, leaf photosynthetic rate was not associated with leaf hydraulic conductance. Cycads had lower photosynthetic N use efficiency and higher photosynthetic performance relative to hydraulic capacity compared with other lineages. These findings extend the relationships shown for foliar traits in angiosperms to the cycads. This functional convergence supports the modern synthetic understanding of leaf design, with common constraints operating across lineages, even as they highlight exceptional aspects of the biology of this key relict lineage.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are ...unclear.
In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b-regulated rice immunity against the blast fungus Magnaporthe oryzae.
Out of the four target genes of miR398b, mutations in Cu/Zn-Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H₂O₂) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H₂O₂ production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity.
Our results demonstrate the roles of different SODs in miR398b-regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H₂O₂ concentration and thereby improve disease resistance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Many diseases have been associated with intestinal microbial dysbiosis. Host–microbial interactions regulate immune function, which influences the development of gastric cancer.
Aims
The ...aims were to investigate the characteristics of intestinal microbiota composition in gastric cancer patients and correlations between the intestinal microbiota and cellular immunity.
Methods
Fecal samples were collected from 116 gastric cancer patients and 88 healthy controls from Shanxi Province, China. The intestinal microbiota was investigated by 16S rRNA gene sequencing. Peripheral blood samples were also collected from the 66 gastric cancer patients and 46 healthy controls. The populations of peripheral T lymphocyte subpopulations and NK cells were analyzed by flow cytometry.
Results
The intestinal microbiota in gastric cancer patients was characterized by increased species richness, decreased butyrate-producing bacteria, and the enrichment of other symbiotic bacteria, especially
Lactobacillus
,
Escherichia,
and
Klebsiella
.
Lactobacillus
and
Lachnospira
were key species in the network of gastric cancer-associated bacterial genera. The combination of the genera
Lachnospira
,
Lactobacillus
,
Streptococcus
,
Veillonella,
and
Tyzzerella_3
showed good performance in distinguishing gastric cancer patients from healthy controls. There was no significant difference in enterotype distribution between healthy controls and gastric cancer patients. The percentage of CD3
+
T cells was positively correlated with the abundance of
Lactobacillus
and
Streptococcus
, and CD3
+
T cells, CD4
+
T cells, and NK cells were associated with Lachnospiraceae taxa.
Conclusions
Our study revealed a dysbiotic intestinal microbiota in gastric cancer patients. The abundance of some intestinal bacterial genera was correlated with the population of peripheral immune cells.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•We propose a three-way decision (3WD) based sampling method for rapid attribute reduction problem.•A novel tripartition strategy is defined for large-scale data sampling.•The neighborhood ...self-information as evaluation metric for attribute significance is applied to interpret the heuristic of attribute reduction.•15 UCI datasets are used to validate the model in terms of both effectiveness and efficiency.•Comparison study shows that three-way sampling based rapid attribute reduction model is a reasonable and minimum-time-cost approach for practical applications.
As data dimensions and volume rapidly increase, attribute reduction using the original data becomes computationally infeasible. Large data frequently contain various redundant attributes and types of noise. This leads to the problems of overfitting and inefficiency in data processing. To address these problems, this paper proposes a general sampling method for attribute reduction by introducing three-way decisions, namely, three-way sampling (3WS), which is the first sampling method that describes the decision boundary accurately while improving the data quality significantly. To improve the effectiveness and efficiency of attribute reduction, we designed a rapid attribute reduction method based on three-way sampling (3WS-RAR). The 3WS-RAR method consists of three main steps: data sampling, attribute reduction, and model effectiveness evaluation. For data sampling, we define the three regions of the 3WS using support vectors to describe the data and use the boundary region as the sampling results. For the attribute reduction, we compute the neighborhood self-information for each attribute while considering the upper and lower approximations. For the effectiveness evaluation, we conducted experiments on 15 relatively large-scale datasets and analysed the influence of parameters. The experimental results reveal that, compared with state-of-the-art attribute reduction models, 3WS-RAR performs better on public benchmark datasets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for ...excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.
Fitness cost is a common phenomenon in rice blast disease-resistance breeding. MiR396 is a highly conserved microRNA (miRNA) family targeting
Growth Regulating Factor
(
OsGRF
) genes. Mutation at the ...target site of miR396 in certain
OsGRF
gene or blocking miR396 expression leads to increased grain yield. Here we demonstrated that fitness cost can be trade-off in miR396-
OsGRF
s module via balancing growth and immunity against the blast fungus. The accumulation of miR396 isoforms was significantly increased in a susceptible accession, but fluctuated in a resistant accession upon infection of
Magnaporthe oryzae
. The transgenic lines over-expressing different miR396 isoforms were highly susceptible to
M. oryzae
. In contrast, overexpressing target mimicry of miR396 to block its function led to enhanced resistance to
M. oryzae
in addition to improved yield traits. Moreover, transgenic plants overexpressing
OsGRF6
,
OsGRF7
,
OsGRF8
, and
OsGRF9
exhibited enhanced resistance to
M. oryzae
, but showed different alteration of growth. While overexpression of
OsGRF7
led to defects in growth, overexpression of
OsGRF6
,
OsGRF8
, and
OsGRF9
resulted in better or no significant change of yield traits. Collectively, our results indicate that miR396 negatively regulates rice blast disease- resistance via suppressing multiple
OsGRF
s, which in turn differentially control growth and yield. Therefore, miR396-
OsGRFs
could be a potential module to demolish fitness cost in rice blast disease-resistance breeding.
The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey ...wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.
The study of drug-target interactions (DTIs) affinity plays an important role in safety assessment and pharmacology. Currently, quantitative structure-activity relationship (QSAR) and molecular ...docking (MD) are most common methods in research of DTIs affinity. However, they often built for a specific target or several targets, and most QSAR and MD methods were based either on structure of drug molecules or on structure of receptors with low accuracy and small scope of application. How to construct quantitative prediction models with high accuracy and wide applicability remains a challenge. To this end, this paper screened molecular descriptors based on molecular vibrations and took molecule-target as a whole system to construct prediction models with high accuracy-wide applicability based on dissociation constant (Kd) and concentration for 50% of maximal effect (EC50), and to provide reference for quantifying affinity of DTIs. After comprehensive comparison, the results showed that RF models are optimal models to analyze and predict DTIs affinity with coefficients of determination (R.sup.2) are all greater than 0.94. Compared to the quantitative models reported in literatures, the RF models developed in this paper have higher accuracy and wide applicability. In addition, E-state molecular descriptors associated with molecular vibrations and normalized Moreau-Broto autocorrelation (G3), Moran autocorrelation (G4), transition-distribution (G7) protein descriptors are of higher importance in the quantification of DTIs. Through screening molecular descriptors based on molecular vibrations and taking molecule-target as whole system, we obtained optimal models based on RF with more accurate-widely applicable, which indicated that selection of molecular descriptors associated with molecular vibrations and the use of molecular-target as whole system are reliable methods for improving performance of models. It can provide reference for quantifying affinity of DTIs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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