Response of soil microbial community to plant composition changes in broad-leaved forests of the karst area in Mid-Subtropical China.

The rapid growth and expansion ofCryptomeria japonica (Thunb. ex L. f.) D. Don in karst area strongly affects plant composition of native deciduous broad-leaved forest, which seriously threat ecosystem function and service. Given the importance of soil microorganisms in regulating nutrients cycling and plant species coexistence, understanding soil microbial attributes and their relationships with soil and vegetation features in forests harboring different C. japonica abundance will help understanding the drivers of ecosystem function changes. Here we examined the diversity and composition of soil bacterial and fungal communities and their correlations with plant diversity as well as soil physicochemical properties in karst broad-leaved forests with different relative abundances of C. japonica (i.e., a high, moderate, low and no proportion level with a stem density of 1,487, 538, 156 and 0 plant/hm2, respectively) in Mid-Subtropical China. We found that soil pH decreased while soil water content (SWC), total nitrogen (TN), total phosphorus (TP) and total potassium (TK) tended to increase with the increase in C. japonica abundance. In contrast, soil available nitrogen (AN), available phosphorus (AP) and available potassium (AK) content declined by 26.1%∼49.3% under the high level of C. japonica abundance. A gradual decrease in relative abundance of Acidobacteria and Chloroflexi while a pronounced increase in relative abundance of Ascomycota and Basidiomycota were observed with increase of C. japonica abundance. Alternations in bacterial composition were closely related to changes in AP and AK, while the change of fungal structure was mainly related to SWC, soil organic carbon (SOC) and pH, indicating that bacterial community was sensitive to declines in soil available nutrients and fungal structure was sensitive to changes in soil physicochemical properties (i.e., pH and SWC) and organic carbon resource. Understory plants had the highest α-diversity in forest containing moderate abundance of C. japonica, which might be related to the high bacterial diversity. Our findings suggest conservation of soil bacterial and fungal taxa that are responsible for nutrients availability and carbon sequestration is of great significance for improving the resistance of natural deciduous broad-leaved forests to the rapid spread of C. japonica in karst areas. Moreover, Acidobacteria, Chloroflexi, Ascomycota and Basidiomycota are potential indicators for soil properties changes, which should be taken into consideration in karst forest managements.

Myocardial Rev-erb-Mediated Diurnal Metabolic Rhythm and Obesity Paradox.

BACKGROUND: The nuclear receptor Rev-erbα/ß, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear. METHODS: We generated mouse lines with cardiac-specific Rev-erbα/ß knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-sequencing, chromatin immunoprecipitation sequencing, proteomics, and metabolomics) analyses, and performed dietary and pharmacological rescue experiments to assess the time-of-the-day effects. We compared the temporal pattern of cardiac clock gene expression with the cardiac dilation severity in failing human hearts. RESULTS: KO mice display progressive dilated cardiomyopathy and lethal heart failure. Inducible ablation of Rev-erbα/ß in adult hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO myocardium, in particular, in the light cycle, precedes contractile dysfunctions with a reciprocal overreliance on carbohydrate utilization, in particular, in the dark cycle. Increasing dietary lipid or sugar supply in the dark cycle does not affect cardiac dysfunctions in KO mice. However, obesity coupled with systemic insulin resistance paradoxically ameliorates cardiac dysfunctions in KO mice, associated with rescued expression of lipid oxidation genes only in the light cycle in phase with increased fatty acid availability from adipose lipolysis. Inhibition of glycolysis in the light cycle and lipid oxidation in the dark cycle, but not vice versa, ameliorate cardiac dysfunctions in KO mice. Altered temporal patterns of cardiac Rev-erb gene expression correlate with the cardiac dilation severity in human hearts with dilated cardiomyopathy. CONCLUSIONS: The study delineates temporal coordination between clock-mediated anticipation and nutrient-induced response in myocardial metabolism at multi-omics levels. The obesity paradox is attributable to increased cardiac lipid supply from adipose lipolysis in the fasting cycle due to systemic insulin resistance and adiposity. Cardiac molecular chronotypes may be involved in human dilated cardiomyopathy. Myocardial bioenergetics downstream of Rev-erb may be a chronotherapy target in treating heart failure and dilated cardiomyopathy.

Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection.

Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABAA receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LHGABA) neurons. This was associated with LHGABA neuron hyperexcitability and impaired hippocampal long-term potentiation, through a monosynaptic LHGABA to CA3GABA projection. Optogenetic activation of this projection caused memory deficits, whereas targeted manipulation of LHGABA or CA3GABA neuron activity reversed memory deficits in NS-V mice. We describe de novo variants in NCOR1, NCOR2 or HDAC3 in patients with intellectual disability or neurodevelopmental disorders. These findings identify a hypothalamus-hippocampus projection that may link endocrine signals with synaptic plasticity through NCOR-mediated regulation of GABA signaling.