Soil microorganisms, spanning diverse phylogenetic lineages, form complex ecological networks wherein various species coexist and contribute to multiple ecosystem services. While microbial networks ...facilitate the understanding of their coexistence and functions in soils, the influence of phylogenetic relatedness among soil microbes themselves on these networks remains largely unknown.
To address this knowledge gap, we conducted a comprehensive survey of soil bacteria and archaea in twenty alpine wetlands on the Tibetan Plateau, characterized by wide edaphic and climatic heterogeneity. Through network and phylogenetic analyses, we evaluated the complexity of network associations and their dependence on phylogenetic relatedness.
Our findings revealed consistencies and discrepancies between phylogenetic relatedness and network associations within soil bacterial and archaeal communities. Specifically, in bacterial networks, both positive and negative complexity were significantly associated with mean phylogenetic distance, whereas in archaeal networks, only negative complexity correlated with mean phylogenetic distance. Even after accounting for the effects of environmental factors, we observed that phylogenetic relatedness still explained variations in the complexities of bacterial and archaeal associations. Furthermore, a multi-threshold analysis indicated that network complexity exhibited phylogenetic signals in both bacterial and archaeal networks, albeit within different associated distance classes, suggesting distinct coexistence mechanisms of soil bacteria and archaea driven by niche and fitness trade-offs.
Overall, our findings underscore the importance of incorporating phylogenetic information when studying microbial communities in complex soil habitats and demonstrate that phylogenetic relatedness crucially shapes coexistence outcomes among soil microbes.
•Network associations of soil microbes exhibit phylogenetic dependence.•Phylogenetic relatedness explains the variation in soil microbial coexistence.•Soil microbial coexistence possesses phylogenetic signals within different classes.
One-sentence summary: Phylogenetic relatedness shapes soil microbial coexistence.
A network meta‐analysis was conducted to compare the short‐term efficacy and adverse events of different drugs for the treatment of postmenopausal osteoporosis (PMO), providing a more effective ...treatment for PMO. We initially searched through various databases like PubMed, Cochrane Library, and EMBASE from inception till October 2016. All randomized controlled trials (RCTs) of drugs for the treatment of PMO were included for direct and indirect comparison. A combination of direct and indirect evidence of different inhibitors of anti‐diabetic drugs for treatment of PMO were considered for calculating the weighted mean difference (WMD) value or odd ratio (OR) value and to draw surface under the cumulative ranking (SUCRA) curves. Twenty‐seven RCTs were ultimately incorporated into this network meta‐analysis comprising of 48 200 patients suffering from PMO. The network meta‐analysis revealed that compared with placebo, alendronate had better efficacy on improving bone mineral density (BMD) at lumbar spine, femoral neck, and total hip. Risedronate and raloxifene had relatively lower incidence of new vertebral fractures. The SUCRA analysis showed that alendronate had better efficacy on improving BMD, risedronate could significantly decrease the incidence of fresh fracture and bazedoxifene was relatively safe. The available evidence suggested that alendronate and risedronate might be the superior choices for the treatment of PMO, while bazedoxifene was a comparatively safer option for patients.
The available evidence suggested that alendronate and risedronate might be the superior choices for the treatment of PMO, while bazedoxifene was a comparatively safer option for patients.
WRKY is an important complex family of transcription factors involved in plant immune responses. Among them, WRKY70 plays an important role in the process of the plant defense response to the ...invasion of pathogens. However, the defense mechanism of PsnWRKY70 is not clear in Populus nigra. In this study, we showed that PsnWRKY70-overexpression lines (OE) had fewer leaf blight symptoms than PsnWRKY70-repressing lines (RE). PsnWRKY70 activated MAP kinase cascade genes (PsnM2K4, PsnMPK3, PsnM3K18), calcium channel proteins-related genes (PsnCNG3, PsnCNGC1, PsnCNG4), and calcium-dependent protein kinases genes (PsnCDPKL, PsnCDPKW, PsnCDPKS, PsnCDPKQ). Furthermore, 129 genes of PsnWRKY70 putative genome-wide direct targets (DTGs) were identified by using transcriptome (RNA-seq) and DNA affinity purification sequencing (DAP-seq). PsnWRKY70 directly binds to the promoters of homologous genes and LRR domain proteins to promote the expression of WRKY6, WRKY18, WRKY22, and WRKY22–1, LRR domain proteins LRR8, LRR-RLK, ADR1-like 2, NB-ARC, etc. Our study suggests that PsnWRKY70 enhances the resistance of A. alternata in poplar by activating genes in both pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI).
In this article, we quantify several nonideal characteristics of memristor synaptic devices, such as the limited conductance states, write nonlinearities, and variations, and comprehensively ...investigate their effects on the convolutional neural network (CNN) performance. Our result shows that the available conductance states (N state ), asymmetric write nonlinearities, and cycle-to-cycle (C2C) variation are critical factors to the learning accuracy, while symmetric write nonlinearities and device-to-device variation go trivial. We accordingly propose three strategies to mitigate their impacts on CNN performance: 1) limiting the weight range to improve the utilization of Nstate; 2) adopting a new "with-read" update scheme to mitigate the effects of asymmetric write nonlinearities; and 3) employing multiple memristors for each kernel element to alleviate the impact of C2C variation. Our work would provide guidance for the hardware implementation and optimization of CNN in memristor crossbar.
In this study, we investigated the effect of astragaloside IV on skeletal muscle energy metabolism disorder caused by statins and explored the possible mechanisms. High‐fat diet‐fed apolipoprotein E ...knockout (ApoE−/−) mice performed aerobic exercise and were administered simvastatin, simvastatin + trimetazidine, or simvastatin + astragaloside IV by gavage. At the end of treatment, exercise performance was assessed by the hanging grid test, forelimb grip test, and running tolerance test. Moreover, plasma lipid and creatine kinase concentrations were measured. After sacrifice, the gastrocnemius muscle was used to assess muscle morphology, and energy metabolism was evaluated by determining the concentration of lactic acid and the storage capacity of adenosine triphosphate and glycogen. Mitochondrial function was assessed by measuring mitochondrial complex III and citrate synthase activity and membrane potential. In addition, oxidative stress was assessed by determining the level of hydrogen peroxide. Finally, using western blotting and reverse transcription polymerase chain reaction, we explored the mechanism of astragaloside IV in alleviating simvastatin‐induced muscle injury. Our results demonstrated that astragaloside IV reversed simvastatin‐induced muscle injury without affecting the lipid‐lowering effect of simvastatin. Moreover, astragaloside IV promoted the phosphorylation of AMPK and activated PGC‐1α, which upregulated the expression of NRF1 to enhance energy metabolism and inhibit skeletal muscle cell apoptosis.
The mechanism of astragaloside IV in reversing simvastatin‐induced skeletal muscle injury.
Macrophages are heterogeneous cell populations that are present in all tissues. Macrophages can be divided into classically activated inflammatory macrophages (M1) and alternatively activated ...anti-inflammatory macrophages (M2). It has been generally accepted that M1 macrophages are polarised in an inflammatory environment to produce pro-inflammatory cytokines, whilst M2 macrophages are involved in anti-inflammation and aid tissue repair in wound healing. Bacterial endotoxin (lipopolysaccharide; LPS) is a potent factor in infection, which induces M1 macrophages resulting in higher levels of iNOS, TNFα and IL-12p70 which dictate inflammatory T cell responses. M2 macrophages can be transformed into M1 macrophages following LPS stimulation to promote inflammation. Candida albicans is a commensal fungal microorganism, which has been suggested to induce immune tolerance; however, the mechanism of C. albicans-induced immune tolerance has not been investigated in detail. IL-35 is a recently identified anti-inflammatory cytokine which is a heterodimeric protein consisting of the Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. IL-35 shares the protein subunit p35, with IL-12p70. IL-12p70 is the most potent cytokine to induce Th1 responses during inflammation. In this study, we demonstrate that heat-killed C. albicans (HKC) strongly suppressed LPS-induced IL-12p70 production in M2 macrophages. Candida albicans induced a high level of EBI3 expression in M2 macrophages, which served as a mechanism for IL-12p70 suppression by competitive binding of the common protein subunit (p35) of IL-35 and IL-12p70. To demonstrate that EBI3 expression had the ability to block IL-12p70 production intracellularly, a Chinese Hamster Ovary (CHO) cell line with biscistronic expression of IL-12p40 and p35 was constructed, followed by ectopic over-expression of EBI3. The over-expression of EBI3 in the IL-12p70 producing cell line effectively suppressed IL-12p70 production. IL-35 secretion was also detected in the cell line, with suppressed IL-12p70 production by immune-precipitation Western blotting. However, this secretion was not evident in M2 macrophages following stimulation by HKC. This can be explained by the constitutive expression of IL-35 receptors (gp130 and IL-12Rβ2) in M2 macrophages for cytokine consumption. Our results have indicated that C. albicans can suppress host inflammatory responses in mucosal skin by suppressing LPS-induced IL-12p70 production. Lower IL-12p70 production may avoid an unnecessary Th1 response in order to retain immune tolerance, which may be one of the mechanisms by which C. albicans achieves a successful commensal lifestyle without having a detrimental effect on the host's health.
Successful cloning by somatic cell nuclear transfer (SCNT) requires overcoming significant epigenetic barriers. Genomic imprinting is not generally regarded as such a barrier, although ...H3K27me3-dependent imprinting is differentially distributed in E6.5 epiblast and extraembryonic tissues. Here we report significant enhancement of SCNT efficiency by deriving somatic donor cells carrying simultaneous monoallelic deletion of four H3K27me3-imprinted genes from haploid mouse embryonic stem cells. Quadruple monoallelic deletion of Sfmbt2, Jade1, Gab1, and Smoc1 normalized H3K27me3-imprinted expression patterns and increased fibroblast cloning efficiency to 14% compared with a 0% birth rate from wild-type fibroblasts while preventing the placental and body overgrowth defects frequently observed in cloned animals. Sfmbt2 deletion was the most effective of the four individual gene deletions in improving SCNT. These results show that lack of H3K27me3 imprinting in somatic cells is an epigenetic barrier that impedes post-implantation development of SCNT embryos and can be overcome by monoallelic imprinting gene deletions in donor cells.
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•Increased SCNT cloning by monoallelic deletion of four H3K27me3-imprinted genes•H3K27me3-imprinted gene deletion normalized body and placental weights in cloned pups•Sfmbt2 deletion is the most effective monoallelic deletion for improving SCNT
Wang et al. report significantly increased cloning efficiencies from fibroblasts by engineering monoallelic deletions of four placenta-specific H3K27me3 imprinting genes. Editing in and deriving donor cells from haploid embryonic stem cells enabled derivation of cloned pups with normalized body and placental weights.
Unisexual reproduction is widespread among lower vertebrates, but not in mammals. Deletion of the H19 imprinted region in immature oocytes produced bimaternal mice with defective growth; however, ...bipaternal reproduction has not been previously achieved in mammals. We found that cultured parthenogenetic and androgenetic haploid embryonic stem cells (haESCs) display DNA hypomethylation resembling that of primordial germ cells. Through MII oocyte injection or sperm coinjection with hypomethylated haploid ESCs carrying specific imprinted region deletions, we obtained live bimaternal and bipaternal mice. Deletion of 3 imprinted regions in parthenogenetic haploid ESCs restored normal growth of fertile bimaternal mice, whereas deletion of 7 imprinted regions in androgenetic haploid ESCs enabled production of live bipaternal mice that died shortly after birth. Phenotypic analyses of organ and body size of these mice support the genetic conflict theory of genomic imprinting. Taken together, our results highlight the factors necessary for crossing same-sex reproduction barriers in mammals.
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•Haploid ESCs display PGC-like methylation profiles following in vitro cultivation•Parthenogenetic and androgenetic haploid ESCs show different demethylation dynamics•phESCs carrying 3 deleted imprinted regions support normal growth of bimaternal mice•ahESCs carrying 7 deleted imprinted regions produce live full-term bipaternal mice
Li et al. utilize haploid ESCs to overcome the uniparental reproductive barriers in mice. They found parent-specific erasure of DNA methylation between parthenogenetic and androgenetic haploid ESCs. After combining gametes and hypomethylated haploid ESCs with certain imprinted region deletions, the authors generated normally growing bimaternal mice and live bipaternal mice.
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