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milk*Microbes play a critical role in soil global biogeochemical circulation and microbe–microbe interactions have also evoked enormous interests in recent years. Utilization of green manures can stimulate microbial activity and affect microbial composition and diversity. However, few studies focus on the microbial interactions or detect the key functional members in communities. With the advances of metagenomic technologies, network analysis has been used as a powerful tool to detect robust interactions between microbial members. Here, random matrix theory-based network analysis was used to investigate the microbial networks in response to four different green manure fertilization regimes (Vicia villosa, common vetch, milk vetch, and radish) over two growth cycles from October 2012 to September 2014. The results showed that the topological properties of microbial networks were dramatically altered by green manure fertilization. Microbial network under milk vetch amendment showed substantially more intense complexity and interactions than other fertilization systems, indicating that milk vetch provided a favorable condition for microbial interactions and niche sharing. The shift of microbial interactions could be attributed to the changes in some major soil traits and the interactions might be correlated to plant growth and production. With the stimuli of green manures, positive interactions predominated the network eventually and the network complexity was in consistency with maize productivity, which suggested that the complex soil microbial networks might benefit to plants rather than simple ones, because complex networks would hold strong the ability to cope with environment changes or suppress soil-borne pathogen infection on plants. In addition, network analyses discerned some putative keystone taxa and seven of them had directly positive interactions with maize yield, which suggested their important roles in maintaining environmental functions and in improving plant growth.

Despite deep interest in how environments shape microbial communities, whether redox conditions influence the sequence composition of genomes is not well known. We predicted that the carbon oxidation state ( Z C ) of protein sequences would be positively correlated with redox potential (Eh). To test this prediction, we used taxonomic classifications for 68 publicly available 16S rRNA gene sequence data sets to estimate the abundances of archaeal and bacterial genomes in river & seawater, lake & pond, geothermal, hyperalkaline, groundwater, sediment, and soil environments. Locally, Z C of community reference proteomes (i.e., all the protein sequences in each genome, weighted by taxonomic abundances but not by protein abundances) is positively correlated with Eh corrected to pH 7 (Eh7) for the majority of data sets for bacterial communities in each type of environment, and global-scale correlations are positive for bacterial communities in all environments. In contrast, archaeal communities show approximately equal frequencies of positive and negative correlations in individual data sets, and a positive pan-environmental correlation for archaea only emerges after limiting the analysis to samples with reported oxygen concentrations. These results provide empirical evidence that geochemistry modulates genome evolution and may have distinct effects on bacteria and archaea. The identification of environmental factors that influence the elemental composition of proteins has implications for understanding microbial evolution and biogeography. Millions of years of genome evolution may provide a route for protein sequences to attain incomplete equilibrium with their chemical environment. We developed new tests of this chemical adaptation hypothesis by analyzing trends of the carbon oxidation state of community reference proteomes for microbial communities in local- and global-scale redox gradients. The results provide evidence for widespread environmental shaping of the elemental composition of protein sequences at the community level and establish a rationale for using thermodynamic models as a window into geochemical effects on microbial community assembly and evolution.

The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth, metabolism, and autophagy. Extensive research has focused on pathways that activate mTORC1 like growth factors and amino acids; however, much less is known about signaling cues that directly inhibit mTORC1 activity. Here, we report that G-protein coupled receptors (GPCRs) paired to Gαs proteins increase cyclic adenosine 3’5’ monophosphate (cAMP) to activate protein kinase A (PKA) and inhibit mTORC1. Mechanistically, PKA phosphorylates the mTORC1 component Raptor on Ser 791, leading to decreased mTORC1 activity. Consistently, in cells where Raptor Ser 791 is mutated to Ala, mTORC1 activity is partially rescued even after PKA activation. Gαs-coupled GPCRs stimulation leads to inhibition of mTORC1 in multiple cell lines and mouse tissues. Our results uncover a signaling pathway that directly inhibits mTORC1, and suggest that GPCRs paired to Gαs proteins may be potential therapeutic targets for human diseases with hyperactivated mTORC1.

Litter inputs can influence soil respiration directly through labile C availability and, indirectly, through the activity of soil microorganisms and modifications in soil microclimate; however, their relative contributions and the magnitude of any effect remain poorly understood. We synthesized 66 recently published papers on forest ecosystems using a meta‐analysis approach to investigate the effect of litter inputs on soil respiration and the underlying mechanisms involved. Our results showed that litter inputs had a strong positive impact on soil respiration, labile C availability, and the abundance of soil microorganisms, with less of an impact related to soil moisture and temperature. Overall, soil respiration was increased by 36% and 55%, respectively, in response to natural and doubled litter inputs. The increase in soil respiration induced by litter inputs showed a tendency for coniferous forests (50.7%)> broad‐leaved forests (41.3%)> mixed forests (31.9%). This stimulation effect also depended on stand age with 30‐ to 100‐year‐old forests (53.3%) and ≥100‐year‐old forests (50.2%) both 1.5 times larger than ≤30‐year‐old forests (34.5%). Soil microbial biomass carbon and soil dissolved organic carbon increased by 21.0%‐33.6% and 60.3%‐87.7%, respectively, in response to natural and doubled litter inputs, while soil respiration increased linearly with corresponding increases in soil microbial biomass carbon and soil dissolved organic carbon. Natural and doubled litter inputs increased the total phospholipid fatty acid (PLFA) content by 6.6% and 19.7%, respectively, but decreased the fungal/bacterial PLFA ratio by 26.9% and 18.7%, respectively. Soil respiration also increased linearly with increases in total PLFA and decreased linearly with decreases in the fungal/bacterial PLFA ratio. The contribution of litter inputs to an increase in soil respiration showed a trend of total PLFA > fungal/bacterial PLFA ratio > soil dissolved organic carbon > soil microbial biomass carbon. Therefore, in addition to forest type and stand age, labile C availability and soil microorganisms are also important factors that influence soil respiration in response to litter inputs, with soil microorganisms being more important than labile C availability. Soil respiration, labile C availability, and soil microorganisms (e.g., microbial quantity and community structure) were significantly influenced by litter inputs. The increase in soil respiration in response to litter inputs was closely related to labile C availability and soil microorganisms. Soil microorganisms had a greater effect than labile C availability influence soil respiration in response to litter inputs.

Bacterial wilt, caused by Ralstonia solanacearum, occurs occasionally during tobacco planting and potentially brings huge economic losses in affected areas. Soil microbes in different management stages play important roles in influencing bacterial wilt incidence. Studies have focused on the impacts of species diversity and composition during cropping periods on disease morbidity; however, the effects of the soil bacterial biomass, species diversity, species succession, and population interactions on morbidity remain unclear during non-cropping periods. In this study, we explored the soil bacterial communities in the non-cropping winter fallow (WF) and cropping late growing (LG) periods under consecutive monoculture systems using 16S ribosomal RNA gene sequencing and qPCR and further analyzed their effects on tobacco bacterial wilt incidence. We found that the bacterial communities in the WF period were significantly different from those in the LG period based on detrended correspondence analysis and dissimilarity tests. Crop morbidity was significantly related to bacterial community structure and to the presence of some genera during WF and LG periods. These genera, such as Arthrobacter, Pseudomonas, Acidobacteria GP6, and Pasteuria, may be potential biological control agents for bacterial wilt. Further analysis indicated that low soil bacterial diversity during the WF period, decrease of bacterial interactions from the WF to LG periods, and low soil biomass during the LG period all have the potential to increase morbidity. In conclusion, an increase of soil bacterial diversity and control of some bacterial abundances in the WF period might be an effective approach in controlling bacterial wilt incidence.

A new small molecule that targets the vacuolar H + -ATPase activates autophagy, inhibits mTORC1 signaling, and displays potential for clearing toxic protein aggregates involved in neurodegenerative diseases.

Background and Aims It is not clear how plants adjust the rate of root water uptake to that of shoot water loss. The aim of this study on rice was to test the idea that root aquaporins (AQPs) and xylem tension play a role in this adjustment. Methods Three-week-old rice (Oryza sativa L.) plants, which were grown hydroponically, had their entire shoot system removed, and root hydraulic conductivity (exudation analyses) and gene expression (quantitative real-time PCR) of root plasma membrane intrinsic aquaporin proteins (PIPs) was followed within 60 min after shoot excision. Key Results All three PIP1 genes (OsPIP1;1, OsPIP1;2 and OsPIP1;3) and three of the six PIP2 genes tested (OsPIP2;1, OsPIP2;4 and OsPIP2;5) showed a rapid (5 min) and lasting (60 min) decrease in gene expression. Expression decreased by up to 85 % within 60 min. The other three PIP2 genes tested (OsPIP2;2, OsPIP2;3 and OsPIP2;6) showed a varied response, with expression decreasing either only initially (5 min) or after 60 min, or not changing at all. In a follow-up experiment, plants had their shoot system removed and the detached root system immediately connected to a vacuum pump through which some tension (80 kPa) was applied. This application of tension prevented any significant decrease in PIP expression. Conclusions Shoot removal leads to a rapid decrease in expression of all PIP1s and some PIP2s in roots of rice. Xylem tension plays some role in this process.

The mammalian target of rapamycin complex 1 (mTORC1) senses multiple stimuli to regulate anabolic and catabolic processes. mTORC1 is typically hyperactivated in multiple human diseases such as cancer and type 2 diabetes. Extensive research has focused on signaling pathways that can activate mTORC1 such as growth factors and amino acids. However, less is known about signaling cues that can directly inhibit mTORC1 activity. Here, we identify A-kinase anchoring protein 13 (AKAP13) as an mTORC1 binding protein, and a crucial regulator of mTORC1 inhibition by G-protein coupled receptor (GPCR) signaling. GPCRs paired to Gα s proteins increase cyclic adenosine 3’5’ monophosphate (cAMP) to activate protein kinase A (PKA). Mechanistically, AKAP13 acts as a scaffold for PKA and mTORC1, where PKA inhibits mTORC1 through the phosphorylation of Raptor on Ser 791. Importantly, AKAP13 mediates mTORC1-induced cell proliferation, cell size, and colony formation. AKAP13 expression correlates with mTORC1 activation and overall lung adenocarcinoma patient survival, as well as lung cancer tumor growth in vivo . Our study identifies AKAP13 as an important player in mTORC1 inhibition by GPCRs, and targeting this pathway may be beneficial for human diseases with hyperactivated mTORC1.

Background: Cerebral ischemia-reperfusion injury (CIRI) represents the most critical pathological event in the evolution of ischemic stroke (IS). Apoptosis is particularly important in CIRI pathophysiology. The interleukin-7 receptor (IL7R) is involved in various disease regulatory mechanisms; however, its specific role during CIRI remains unclear. We investigated the mechanistic function of IL7R in CIRI through a mouse model in vivo and through an astrocyte model in vitro. Methods: C57BL/6 mice were randomly allocated to one of five groups: (1) sham; (2) transient middle cerebral artery occlusion (tMCAO); (3) tMCAO + IL7R treatment; (4) tMCAO + negative control (NC); or (5) tMCAO + IL7R + the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor (LY294002) (n = 3–7 per group) to evaluate the role of IL7R in CIRI. The in vitro study groups were (1) control; (2) oxygen-glucose deprivation/reoxygenation (OGD/R); (3) OGD/R + IL7R; (4) OGD/R + NC; and (5) OGD/R + IL7R + LY294002 groups. After IL7R overexpression was induced, the resulting changes in infarct volume, neurological score, cell viability, and expression of apoptosis-related proteins were assessed. Results: IL7R overexpression significantly attenuated CIRI-induced apoptosis. In vivo, this intervention improved neurological function, alleviated cerebral edema, and decreased infarct volume in tMCAO mice. In vitro, after the overexpression of IL7R, flow cytometry analysis revealed a reduction in apoptosis rates post-OGD/R, whereas transmission electron microscopy revealed fewer morphological alterations associated with apoptosis. In addition, the level of Bcl-2-associated X protein (Bax) and cysteine-dependent aspartate-specific Protease-3 (caspase-3) were decreased, whereas that of B-cell lymphoma-2 (Bcl-2) was increased; these effects were reversed by LY294002. Conclusion: Overexpression of IL7R was shown to alleviate CIRI by suppressing apoptosis. These findings indicate IL7R as a novel target for IS treatment.

Background: Hemorrhagic transformation (HT) is a common complication of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) and may lead to neurological deterioration. This article discusses whether monocyte count to high-density lipoprotein ratio (MHR) level is associated with HT in AIS patients. Materials and methods: The clinical data of AIS patients who underwent rt-PA IVT treatment were continuously collected. According to whether HT occurred, patients were divided into HT group and non-HT group. Potential association between MHR and HT in different subtypes AIS was explored by using logistic regression. Results: A total of 444 AIS patients were retrospective analyzed. The MHR level was lower in HT group compared with the non-HT group in all AIS patients (0.28 vs 0.36, P = .031) and in large-artery atherosclerosis (LAA) type AIS patients (0.31 vs 0.37, P = .032). Low MHR was independently related to HT (OR:0.035, 95%CI:0.003−0.390, P = .006). Among all TOAST subtypes, low MHR was only independently associated with HT in patients of LAA-type AIS after adjusting for confounding factors (OR:0.01, 95%CI:0.00−0.62, P = .031), with an optimal cut-off value of 0.41, sensitivity of 85.7%, and specificity of 43.1%. MHR was not correlated with SVO, VE, and CE subtype AIS. Conclusion: Low MHR may be an independent predictor of HT in patients with AIS and this conclusion only existed in LAA-type AIS.