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1.
Biochem Biophys Res Commun ; 725: 150272, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-38901224

ABSTRACT

Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.


Subject(s)
GABAergic Neurons , Interneurons , Ketamine , Parvalbumins , Prefrontal Cortex , Synapses , Animals , Ketamine/pharmacology , Ketamine/administration & dosage , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Parvalbumins/metabolism , Synapses/drug effects , Synapses/metabolism , Male , Interneurons/drug effects , Interneurons/metabolism , Mice , GABAergic Neurons/drug effects , GABAergic Neurons/metabolism , Mice, Inbred C57BL , Excitatory Amino Acid Antagonists/pharmacology
2.
Environ Res ; 258: 119453, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909951

ABSTRACT

Thermophilic anaerobic digestion (AD) of animal manure offers various environmental benefits but the process requires a microbial community acclimatized to high ammonia. In current study, a lab-scale continuous stirred tank reactor (CSTR) fed with chicken manure was operated under thermophilic condition for 450 days in total. Results showed that the volumetric methane production decreased from 445 to 328 and sharply declined to 153 mL L-1·d-1 with feeding total solid (TS) step increased from 5% to 7.5% and 10%, respectively. While, after a long-term stop feeding for 80 days, highly disturbed reactor was able to recover methane generation to 739 mL L-1·d-1 at feeding TS of 10%. Isotope analysis indicted acetate converted to methane through the syntrophic acetate oxidation and hydrogenotrophic methanogenesis (SAO-HM) pathway increased from 33% to 63% as the concentration of ammonium increased from 2493 to 6258 mg L-1. Significant different in the genome expression of the SAO bacterial from 0.09% to 1.23%, combining with main hydrogenotrophic partners (Methanoculleus spp. and Methanothermobacter spp.) contented of 2.1% and 99.9% during inhibitory and recovery stages, respectively. The highly expressed KEGG pathway in level 3 (enzyme genes) for the Recovery sludge combining with the extraordinary high abundance of genera Halocella sp. suggested that Halocella sp. might be a highly efficient hydrolytic and acidogenic microorganism and enhance the process of SAO during carbon metabolic flow to methane. This report will be a basis for further study of AD studies on high nitrogen content of poultry manure.

3.
CNS Neurosci Ther ; 30(2): e14573, 2024 02.
Article in English | MEDLINE | ID: mdl-38421101

ABSTRACT

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. METHODS: The protein acetylation and expression levels were detected by western blotting and co-immunoprecipitation. The stoichiometry of acetylation was measured by home-made and site-specific antibodies against acetylated-CaM (Ac-CaM) at K22, K95, and K116. Hippocampus-dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. RESULTS: We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+ /CaM-dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac-K22, K95-CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus-dependent memory in AD mice. CONCLUSIONS: HDAC9-mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Mice , Humans , Animals , Alzheimer Disease/metabolism , Calmodulin , Mice, Transgenic , Memory Disorders/etiology , Hippocampus/metabolism , Disease Models, Animal , Histone Deacetylases/metabolism , Repressor Proteins/metabolism
4.
Cell Death Dis ; 15(2): 167, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38396027

ABSTRACT

Neuronal nitric oxide synthase (nNOS, gene name Nos1) orchestrates the synthesis of nitric oxide (NO) within neurons, pivotal for diverse neural processes encompassing synaptic transmission, plasticity, neuronal excitability, learning, memory, and neurogenesis. Despite its significance, the precise regulation of nNOS activity across distinct neuronal types remains incompletely understood. Erb-b2 receptor tyrosine kinase 4 (ErbB4), selectively expressed in GABAergic interneurons and activated by its ligand neuregulin 1 (NRG1), modulates GABA release in the brain. Our investigation reveals the presence of nNOS in a subset of GABAergic interneurons expressing ErbB4. Notably, NRG1 activates nNOS via ErbB4 and its downstream phosphatidylinositol 3-kinase (PI3K), critical for NRG1-induced GABA release. Genetic removal of nNos from Erbb4-positive neurons impairs GABAergic transmission, partially rescued by the NO donor sodium nitroprusside (SNP). Intriguingly, the genetic deletion of nNos from Erbb4-positive neurons induces schizophrenia-relevant behavioral deficits, including hyperactivity, impaired sensorimotor gating, and deficient working memory and social interaction. These deficits are ameliorated by the atypical antipsychotic clozapine. This study underscores the role and regulation of nNOS within a specific subset of GABAergic interneurons, offering insights into the pathophysiological mechanisms of schizophrenia, given the association of Nrg1, Erbb4, Pi3k, and Nos1 genes with this mental disorder.


Subject(s)
ErbB Receptors , Phosphatidylinositol 3-Kinases , Animals , Humans , Mice , ErbB Receptors/metabolism , gamma-Aminobutyric Acid , Hippocampus/metabolism , Neuregulin-1/genetics , Neurons/metabolism , Nitric Oxide Synthase Type I/genetics , Receptor, ErbB-4/genetics , Receptor, ErbB-4/metabolism
6.
Cell Biosci ; 13(1): 79, 2023 May 05.
Article in English | MEDLINE | ID: mdl-37147705

ABSTRACT

BACKGROUND: Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed. METHODS: Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1Cre/+) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1Cre/+ mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated. RESULTS: In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum. CONCLUSIONS: Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.

7.
Membranes (Basel) ; 12(11)2022 Nov 11.
Article in English | MEDLINE | ID: mdl-36422125

ABSTRACT

Acidogenic fermentation of chicken manure (CM) for production and recovery of volatile fatty acids (VFA) is an interesting biological waste-to-value approach compared to benchmark organic waste management strategies. Considering the wide range of high value applications of VFA, a semi-continuous immersed anaerobic membrane bioreactor (AnMBR) was applied to boost VFA productivity and yield, while reducing downstream processing stages assisting the recovery of VFA. In this regard, the effect of parameters such as pH and organic loading rates (OLR) on the overall bioconversion and filtration performance was investigated. Thermal-shocked CM was applied both as inoculum and substrate. A very high VFA yield (0.90 g-VFA/g-VS) was obtained in the treatment with no pH control (~8.2) at an OLR of 2 g-VS/(L·d), presenting 24% higher yield compared to that of the controlled pH. Batch assays further demonstrated the enhanced hydrolysis and acidogenesis activities at weak alkaline conditions. A long-term (78 days) fermentation and filtration was successfully performed, where stable membrane filtration performance was experienced for about 50 days under high-solid (suspended solid of 37-45 g/L) and high flux (20 L/(m2·h)) conditions. Results suggest that AnMBR of CM is a feasible and promising process for VFA production and recovery.

8.
Sheng Li Xue Bao ; 74(4): 525-533, 2022 Aug 25.
Article in Chinese | MEDLINE | ID: mdl-35993203

ABSTRACT

This study aims to explore the electrophysiological properties and changes in gene expression of basket cells, a unique population of GABAergic interneurons expressing parvalbumin (PV), during the postnatal development of mouse prefrontal cortex (PFC). Toward this goal, we took use of the G42 transgenic mouse line which specifically expresses enhanced green fluorescent protein (EGFP) in basket cells. The brain slices of PFC were prepared from the postnatal 7 (P7), 14 (P14) and 21 days (P42) G42 mice and whole-cell patch clamp recording was performed in basket cells. In addition, we sorted the basket cells by flow cytometry and analyzed their transcription profiling on P7, P14, and P21 using RNA-seq technology. The results showed that the resting membrane potential and membrane input resistance decreased gradually from P7 to P21. The amplitude and duration of action potential of basket cells increased and decreased from P7 to P21, respectively. In contrast, the threshold of action potential of basket cells did not have a significant change from P7 to P21. The frequency of spontaneous excitatory postsynaptic currents (sEPSCs) of basket cells increased gradually, while the amplitudes of sEPSCs of basket cells remained constant from P7 to P21. RNA sequencing from basket cells revealed that the expression of 22 and 660 genes was upregulated and downregulated from P7 to P14, respectively. By contrast, the expression of 107 and 69 genes was upregulated and downregulated from P14 to P21, respectively. The differentially expressed genes in basket cells from P7 to P21 were significantly enriched in pathways such as neuron apoptotic process, mRNA processing, Golgi vesicle transport and axon guidance. Altogether, we characterized electrophysiological properties and changes in gene expression of basket cells during the postnatal development in mouse PFC. These results provide insight into the mechanisms underlying the development of basket cells in mouse cortex.


Subject(s)
Interneurons , Parvalbumins , Animals , Gene Expression , Interneurons/metabolism , Mice , Mice, Transgenic , Parvalbumins/metabolism , Prefrontal Cortex/metabolism
9.
Proc Natl Acad Sci U S A ; 119(11): e2118570119, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35263227

ABSTRACT

SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain relatively unexplored. Here we show that dopamine D2 receptor (DRD2) is expressed in the cilia and somata of mature olfactory sensory neurons (OSNs), while nasal dopamine (DA) is mainly released from the sympathetic nerve terminals, which innervate the mouse olfactory mucosa (OM). We further demonstrate that DA-DRD2 signaling in the nose plays important roles in regulating olfactory function using genetic and pharmacological approaches. Moreover, the local DA synthesis in mouse OM is reduced during hunger, which contributes to starvation-induced olfactory enhancement. Altogether, we demonstrate that nasal DA and DRD2 receptor can serve as the potential peripheral targets for olfactory modulation.


Subject(s)
Dopamine , Olfactory Receptor Neurons , Receptors, Dopamine D2 , Animals , Dopamine/metabolism , Dopamine D2 Receptor Antagonists/pharmacology , Humans , Mice , Olfactory Receptor Neurons/metabolism , Receptors, Dopamine D2/genetics , Receptors, Dopamine D2/metabolism , Signal Transduction , Smell
10.
Bioengineered ; 13(1): 1249-1275, 2022 01.
Article in English | MEDLINE | ID: mdl-34738864

ABSTRACT

Sustainable provision of chemicals and materials is undoubtedly a defining factor in guaranteeing economic, environmental, and social stability of future societies. Among the most sought-after chemical building blocks are volatile fatty acids (VFAs). VFAs such as acetic, propionic, and butyric acids have numerous industrial applications supporting from food and pharmaceuticals industries to wastewater treatment. The fact that VFAs can be produced synthetically from petrochemical derivatives and also through biological routes, for example, anaerobic digestion of organic mixed waste highlights their provision flexibility and sustainability. In this regard, this review presents a detailed overview of the applications associated with petrochemically and biologically generated VFAs, individually or in mixture, in industrial and laboratory scale, conventional and novel applications.


Subject(s)
Fatty Acids, Volatile/chemical synthesis , Fatty Acids, Volatile/metabolism , Anaerobiosis , Bioreactors , Drug Industry , Fermentation , Food Industry , Oil and Gas Industry , Water Purification
11.
Nat Commun ; 12(1): 6444, 2021 11 08.
Article in English | MEDLINE | ID: mdl-34750364

ABSTRACT

Synaptic pruning during adolescence is important for appropriate neurodevelopment and synaptic plasticity. Aberrant synaptic pruning may underlie a variety of brain disorders such as schizophrenia, autism and anxiety. Dopamine D2 receptor (Drd2) is associated with several neuropsychiatric diseases and is the target of some antipsychotic drugs. Here we generate self-reporting Drd2 heterozygous (SR-Drd2+/-) rats to simultaneously visualize Drd2-positive neurons and downregulate Drd2 expression. Time course studies on the developing anterior cingulate cortex (ACC) from control and SR-Drd2+/- rats reveal important roles of Drd2 in regulating synaptic pruning rather than synapse formation. Drd2 also regulates LTD, a form of synaptic plasticity which includes some similar cellular/biochemical processes as synaptic pruning. We further demonstrate that Drd2 regulates synaptic pruning via cell-autonomous mechanisms involving activation of mTOR signaling. Deficits of Drd2-mediated synaptic pruning in the ACC during adolescence lead to hyper-glutamatergic function and anxiety-like behaviors in adulthood. Taken together, our results demonstrate important roles of Drd2 in cortical synaptic pruning.


Subject(s)
Gyrus Cinguli/physiology , Neuronal Plasticity/physiology , Receptors, Dopamine D2/physiology , Signal Transduction/physiology , Animals , Animals, Genetically Modified , Dendritic Spines/genetics , Dendritic Spines/physiology , Gene Knockout Techniques , Gyrus Cinguli/cytology , Gyrus Cinguli/metabolism , Heterozygote , Inhibitory Postsynaptic Potentials/genetics , Inhibitory Postsynaptic Potentials/physiology , Mutation , Neuronal Plasticity/genetics , Neurons/cytology , Neurons/metabolism , Neurons/physiology , Patch-Clamp Techniques/methods , Rats, Sprague-Dawley , Receptors, Dopamine D2/genetics , Signal Transduction/genetics , Synapses/genetics , Synapses/physiology , Time Factors
12.
J Biol Chem ; 297(3): 101044, 2021 09.
Article in English | MEDLINE | ID: mdl-34358562

ABSTRACT

Protein acetylation is a reversible posttranslational modification, which is regulated by lysine acetyltransferase (KAT) and lysine deacetyltransferase (KDAC). Although protein acetylation has been shown to regulate synaptic plasticity, this was mainly for histone protein acetylation. The function and regulation of nonhistone protein acetylation in synaptic plasticity and learning remain largely unknown. Calmodulin (CaM), a ubiquitous Ca2+ sensor, plays critical roles in synaptic plasticity such as long-term potentiation (LTP). During LTP induction, activation of NMDA receptor triggers Ca2+ influx, and the Ca2+ binds with CaM and activates calcium/calmodulin-dependent protein kinase IIα (CaMKIIα). In our previous study, we demonstrated that acetylation of CaM was important for synaptic plasticity and fear learning in mice. However, the KAT responsible for CaM acetylation is currently unknown. Here, following an HEK293 cell-based screen of candidate KATs, steroid receptor coactivator 3 (SRC3) is identified as the most active KAT for CaM. We further demonstrate that SRC3 interacts with and acetylates CaM in a Ca2+ and NMDA receptor-dependent manner. We also show that pharmacological inhibition or genetic downregulation of SRC3 impairs CaM acetylation, synaptic plasticity, and contextual fear learning in mice. Moreover, the effects of SRC3 inhibition on synaptic plasticity and fear learning could be rescued by 3KQ-CaM, a mutant form of CaM, which mimics acetylation. Together, these observations demonstrate that SRC3 acetylates CaM and regulates synaptic plasticity and learning in mice.


Subject(s)
Brain/metabolism , Calmodulin/metabolism , Fear , Learning , Nuclear Receptor Coactivator 3/metabolism , Acetylation , Animals , Calcium/metabolism , Calmodulin/genetics , Male , Mice , Mice, Inbred C57BL , Neuronal Plasticity , Nuclear Receptor Coactivator 3/genetics
13.
J Biol Chem ; 297(3): 101034, 2021 09.
Article in English | MEDLINE | ID: mdl-34339735

ABSTRACT

Synaptic plasticity is critical for brain function, including learning and memory. It is regulated by gene transcription and protein synthesis as well as posttranslational modifications at synapses. Although protein acetylation has been shown to be involved in the regulation of synaptic plasticity, this was mainly for histone protein acetylation. To investigate whether acetylation of nonhistone proteins is important for synaptic plasticity, we analyzed mouse brain acetylome and found that calmodulin (CaM), a ubiquitous Ca2+ sensor, was acetylated on three lysine residues, which were conserved across species. NMDA receptor-dependent long-term potentiation (LTP) is considered the most compelling form of synaptic plasticity. During LTP induction, activation of NMDA receptor triggers Ca2+ influx, and the Ca2+ binds with CaM and activates calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), which is essential for LTP induction. By using home-generated and site-specific antibodies against acetylated CaM, we show that CaM acetylation is upregulated by neural activities in an NMDA receptor-dependent manner. Moreover, mutation of acetyllysines in CaM1 proteins disrupts synaptic plasticity and fear learning in a mouse model. We further demonstrate that acetylation of CaM reduces the binding free energy and increases the binding affinity toward CaMKIIα, a protein kinase pivotal to synaptic plasticity and learning. Taken together, our results demonstrate importance of CaM acetylation in regulating synaptic plasticity and learning.


Subject(s)
Calmodulin/metabolism , Fear , Learning , Neuronal Plasticity , Acetylation , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calmodulin/genetics , Hippocampus/enzymology , Hippocampus/metabolism , Hippocampus/physiology , In Vitro Techniques , Long-Term Synaptic Depression , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic
14.
Neurosci Bull ; 37(12): 1645-1657, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34228315

ABSTRACT

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3+/- mice, hippocampus-dependent functions such as short-term memory and spatial memory were impaired. We further demonstrated that the deficient learning and memory in Src3+/- mice was strongly associated with the impairment of long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses. Mechanistic studies indicated that Src3+/- mutation altered the composition of N-methyl-D-aspartate receptor subunits in the postsynaptic densities of hippocampal neurons. Finally, we showed that SRC3 regulated synaptic plasticity and learning mainly dependent on its lysine acetyltransferase activity. Taken together, these results reveal previously unknown functions of SRC3 in the hippocampus and thus may provide insight into how steroid hormones regulate brain function.


Subject(s)
Hippocampus , Nuclear Receptor Coactivator 3 , Animals , Long-Term Potentiation , Mice , Neuronal Plasticity , Nuclear Receptor Coactivator 3/genetics , Synapses
15.
Bioresour Technol ; 330: 124992, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33744736

ABSTRACT

Although the high nitrogen content of chicken manure (CM) poses major challenges for methane production through anaerobic digestion, on the bright side, it has a great potential for production of value-added intermediate products, such as volatile fatty acids (VFAs). However, in order to enhance VFAs yield, methane formation should be substantially suppressed. In the current research, individual and multiple effects of initial pH, heat-shock pretreatment, chemical methanogens inhibitor and the inoculum to substrate ratio (ISR) on optimization VFAs fermentation from CM were evaluated via batch assays. In this regard, the highest net VFAs yield, 0.53 g-VFA/g-VS, was achieved at conditions with heat-shocked inoculum and CM at ISR 1:6 and pH uncontrolled. Acetate dominated the VFAs mixture, accounting for up to 75% of total. Increased inoculum content enhanced the bioconversion efficiency to 78% at ISR 1:3. The study results suggest that alkalinity is a key promoter of VFAs production from CM.


Subject(s)
Chickens , Manure , Anaerobiosis , Animals , Bioreactors , Fatty Acids, Volatile , Fermentation , Methane
16.
Nat Commun ; 12(1): 278, 2021 01 12.
Article in English | MEDLINE | ID: mdl-33436636

ABSTRACT

Cortical disinhibition is a common feature of several neuropsychiatric diseases such as schizophrenia, autism and intellectual disabilities. However, the underlying mechanisms are not fully understood. To mimic increased expression of Nrg1, a schizophrenia susceptibility gene in GABAergic interneurons from patients with schizophrenia, we generated gtoNrg1 mice with overexpression of Nrg1 in GABAergic interneurons. gtoNrg1 mice showed cortical disinhibition at the cellular, synaptic, neural network and behavioral levels. We revealed that the intracellular domain of NRG1 interacts with the cytoplasmic loop 1 of Nav1.1, a sodium channel critical for the excitability of GABAergic interneurons, and inhibits Nav currents. Intriguingly, activation of GABAergic interneurons or restoring NRG1 expression in adulthood could rescue the hyperactivity and impaired social novelty in gtoNrg1 mice. These results identify mechanisms underlying cortical disinhibition related to schizophrenia and raise the possibility that restoration of NRG1 signaling and GABAergic function is beneficial in certain neuropsychiatric disorders.


Subject(s)
Interneurons/metabolism , Neural Inhibition , Neuregulin-1/metabolism , Prefrontal Cortex/metabolism , gamma-Aminobutyric Acid/metabolism , Action Potentials , Animals , Behavior, Animal , Dependovirus/metabolism , Genotype , Ion Channel Gating , Male , Mice, Transgenic , Nerve Net/metabolism , Neuregulin-1/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Schizophrenia/genetics , Schizophrenia/physiopathology , Sodium Channels/metabolism
17.
Bioresour Technol ; 310: 123470, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32387977

ABSTRACT

The slow hydrolysis rate and ammonia inhibition effects significantly limit the performance of anaerobic digestion (AD) of nitrogen rich wastes. An innovative two-stage AD was therefore investigated for chicken manure by combining hyper-thermophilic (70 °C) pretreatment and a anaerobic membrane bioreactor (AnMBR). An in-situ stripping unit was assembled into the AnMBR to remove the ammonium-N, thus alleviating the inhibition effects. Through the 120-day experiment, the hydraulic retention time was optimized at 15 days for AnMBR with a constant retention 4 days for pretreatment. The hydrolysis efficiency and methane yield reached 72.4% and 352 mL-CH4/g-VSin respectively. About 3000 mg/L ammonium-N was removed through stripping, attributing to methane yield increased by 139 mL-CH4/g-VSin and volatile fatty acids decreased by 2683 mg/L compared to the control. No significant fouling was observed for the membrane. Conclusively, the combined two-stage AD process may offer an alternative approach for the treatment of nitrogen rich organic waste.


Subject(s)
Ammonia , Manure , Anaerobiosis , Animals , Bioreactors , Chickens , Methane
18.
Cell Biosci ; 9: 89, 2019.
Article in English | MEDLINE | ID: mdl-31700606

ABSTRACT

BACKGROUND: Schizophrenia is a common psychiatric disease with high hereditary. The identification of schizophrenia risk genes (SRG) has shed light on its pathophysiological mechanisms. Mouse genetic models have been widely used to study the function of SRG in the brain with a cell type specific fashion. However, whether the cellular expression pattern of SRG is conserved between human and mouse brain is not thoroughly studied. RESULTS: We analyzed the single-cell transcription of 180 SRG from human and mouse primary visual cortex (V1). We compared the percentage of glutamatergic, GABAergic and non-neuronal cells that express each SRG between mouse and human V1 cortex. Thirty percent (54/180) of SRG had significantly different expression rate in glutamatergic neurons between mouse and human V1 cortex. By contrast, only 5.6% (10/180) of SRG showed significantly different expression in GABAergic neurons, which is similar with the ratio of SRG (15/180) with species difference in total cell populations. Strikingly, the percentage of non-neuronal cells expressing all SRG are indistinguishable between human and mouse V1 cortex. We further analyzed the biological significance of differentially expressed SRG by gene ontology. The species-different SRG in glutamatergic neurons are highly expressed in dendrite and axon. They are enriched in the biological process of response to stimulus. However, the differentially expressed SRG in GABAergic neurons are enriched in the regulation of organelle organization. CONCLUSION: GABAergic neurons are more conserved in the expression of SRG than glutamatergic neurons while the non-neuronal cells show the species conservation for the expression of all SRG. It should be cautious to use mouse models to study those SRG which show different cellular expression pattern between human and mouse cortex.

19.
Bioresour Technol ; 287: 121470, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31121449

ABSTRACT

Hydrolysis is normally the rate limiting step for anaerobic digestion (AD). In this study, hyper-thermophilic (70 °C) pre-treatment of chicken manure under HRTs of 10, 5, 3, 2 and 1 d(s) was investigated to enhance the hydrolysis efficiency for biogas production. In-situ phase gas stripping was integrated into the pre-treatment reactor to remove ammonia-N and to enhance the hydrolysis performance. The results showed that in-situ gas stripping removed 18%-31% of ammonia-N and improved hydrolysis by 2.6%-31.1%. The methane yield of pre-hydrolyzed chicken manure reached 518 mL g-VS-1 under optimal HRT 3 days, which was 54.6% higher than that obtained from the control reactor. However, shortening HRTs below 3 days resulted in a significant reduction in hydrolysis efficiency. The percent of hydrolysis and acidogenesis bacteria reduced to 40.6% at HRT 1 d. 16sRNA results indicated existence of methanogens in pre-hydrolysis reactor. Further optimizing of ammonia stripping was thus needed for hydrolysis pre-treatment.


Subject(s)
Biofuels , Manure , Ammonia , Anaerobiosis , Animals , Bioreactors , Chickens , Hydrolysis , Methane
20.
Brain Struct Funct ; 224(3): 1035-1049, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30604007

ABSTRACT

The D2 dopamine receptor (Drd2) is implicated in several brain disorders such as schizophrenia, Parkinson's disease, and drug addiction. Drd2 is also the primary target of both antipsychotics and Parkinson's disease medications. Although the expression pattern of Drd2 is relatively well known in mouse brain, the temporal and spatial distribution of Drd2 is lesser clear in rat brain due to the lack of Drd2 reporter rat lines. Here, we used CRISPR/Cas9 techniques to generate two knockin rat lines: Drd2::Cre and Rosa26::loxp-stop-loxp-tdTomato. By crossing these two lines, we produced Drd2 reporter rats expressing the fluorescence protein tdTomato under the control of the endogenous Drd2 promoter. Using fluorescence imaging and unbiased stereology, we revealed the cellular expression pattern of Drd2 in adult and postnatal rat forebrain. Strikingly, the Drd2 expression pattern differs between Drd2 reporter rats and Drd2 reporter mice generated by BAC transgene in prefrontal cortex and hippocampus. These results provide fundamental information needed for the study of Drd2 function in rat forebrain. The Drd2::Cre rats generated here may represent a useful tool to study the function of neuronal populations expressing Drd2.


Subject(s)
Gene Expression Regulation/genetics , Neurons/metabolism , Prosencephalon/metabolism , Receptors, Dopamine D2/metabolism , Animals , Brain/cytology , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Glutamate Decarboxylase/metabolism , In Vitro Techniques , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Male , Mice, Transgenic , Olfactory Marker Protein/metabolism , Parvalbumins/metabolism , Phosphopyruvate Hydratase/metabolism , Prosencephalon/cytology , Rats , Rats, Sprague-Dawley , Rats, Transgenic , Receptors, Dopamine D2/genetics , Transduction, Genetic
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