ABSTRACT
Poly(ethylene oxide) (PEO) electrolytes usually suffer from low room temperature (RT) ionic conductivity and a narrow voltage window, which limits the improvement of energy density and practical applications in all-solid-state batteries. Composite polymer electrolytes (CPEs) are regarded as the common method to reduce the crystallinity of polymers and increase the lithium ion conductivity. Compared with active or inert ceramic material fillers in previous studies, aluminum-lithium alloy fillers are used to prepare composite electrolytes in this study, showing excellent performance at room temperature. The conductivity of the PEO-based electrolytes increases by a factor of 3.62-3.62× 10-4 S cm-1 at RT with 5 wt % Al-Li alloy. The transference number of Li+ is increased to 0.524. The characteristics of the Al-Li alloy and higher conductivity enable the composite electrolyte to stabilize the interface with the electrodes, reducing the polarization of solid-state batteries. The all-solid-state Li/PEO-5%/LiFePO4 cells show the highest initial discharge capacity of 153 mAh g-1 and the highest stable discharge capacity of 147 mAh g-1 with the initial Coulombic efficiency of more than 100%. It also exhibits the best rate capacity and cycle performance (90% capacity retention rate after 100 cycles).
ABSTRACT
Human breast milk contains lactic acid bacteria (LAB), which have an important influence on the composition of the intestinal microbia of infants. In this study, one strain of an α-hemolytic species of the genus Streptococcus, IMAU99199T, isolated from the breast milk of a healthy nursing mother in Hohhot city PR China, was studied to characterise its taxonomic status using phenotypic and molecular taxonomic methods. The results indicated that it represented a member of the mitis-suis clade, pneumoniae subclade of the genus Streptococcus. It is a Gram-stain-positive, catalase-negative and oxidase-negative bacterium, and the cells are globular, paired or arranged in short chains. The results of a phylogenetic analysis of its 16S rRNA gene and two housekeeping genes (gyrB and rpoB) placed it in the genus Streptococcus. A phylogenetic tree based on 135 single-copy genes sequences indicated that IMAU99199T formed a closely related branch well separated from 'Streptococcus humanilactis' IMAU99125, 'Streptococcus bouchesdurhonensis' Marseille Q6994, Streptococcus mitis NCTC 12261T, 'Streptococcus vulneris' DM3B3, Streptococcus toyakuensis TP1632T, Streptococcus pseudopneumoniae ATCC BAA-960T and Streptococcus pneumoniae NCTC 7465T. IMAU99199T and 'S. humanilactis' IMAU99125 had the highest average nucleotide identity (93.7â%) and digital DNA-DNA hybridisation (55.3â%) values, which were below the accepted thresholds for novel species. The DNA G+C content of the draft genome of IMAU99199T was 39.8â%. The main cellular fatty acids components of IMAU99199T were C16â:â0 and C16â:â1ω7. It grew at a temperature range of 25-45â°C (the optimum growth temperature was 37â°C) and a pH range of 5.0-8.0 (the optimum growth pH was 7.0). These data indicate that strain IMAU99199T represents a novel species in the genus Streptococcus, for which the name Streptococcus hohhotensis sp. nov. is proposed. The type strain is IMAU99199T (=GDMCC 1.1874T=KCTC 21155T).
Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Milk, Human , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Streptococcus , RNA, Ribosomal, 16S/genetics , Humans , Female , China , DNA, Bacterial/genetics , Milk, Human/microbiology , Streptococcus/genetics , Streptococcus/isolation & purification , Streptococcus/classification , Fatty Acids/analysis , Nucleic Acid Hybridization , Genes, BacterialABSTRACT
Sarcopenia, a progressive and prevalent neuromuscular disorder, is characterized by age-related muscle wasting and weakening. Despite its widespread occurrence, the molecular underpinnings of this disease remain poorly understood. Herein, we report that levels of Agrin, an extracellular matrix (ECM) protein critical for neuromuscular formation, were decreased with age in the skeletal muscles of mice. The conditional loss of Agrin in myogenic progenitors and satellite cells (SCs) (Pax7 Cre:: Agrin flox/flox) causes premature muscle aging, manifesting a distinct sarcopenic phenotype in mice. Conversely, the elevation of a miniaturized form of Agrin in skeletal muscle through adenovirus-mediated gene transfer induces enhanced muscle capacity in aged mice. Mechanistic investigations suggest that Agrin-mediated improvement in muscle function occurs through the stimulation of Yap signaling and the concurrent upregulation of dystroglycan expression. Collectively, our findings underscore the pivotal role of Agrin in the aging process of skeletal muscles and propose Agrin as a potential therapeutic target for addressing sarcopenia.
Subject(s)
Agrin , Sarcopenia , Animals , Mice , Agrin/genetics , Agrin/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/metabolism , Sarcopenia/genetics , Signal TransductionABSTRACT
Anxiety disorder is one of the most common mental disorders worldwide, affecting nearly 30% of adults. However, its underlying molecular mechanisms are still unclear. Here we subjected mice to chronic restraint stress (CRS), a paradigm known to induce anxiety-like behavior in mice. CRS mice exhibited anxiety-like behavior and reduced synaptic transmission in the medial prefrontal cortex (mPFC). Notably, Wisteria Floribunda agglutinin (WFA) staining showed a reduction of perineuronal nets (PNNs) expression in the mPFC of CRS mice. And the mRNA and protein levels of aggrecan (ACAN), a core component of PNNs, were also reduced. Parallelly, enzymatic digestion of PNNs in the mPFC by injecting Chondroitinase ABC (chABC) resulted in anxiety-like behavior in mice. Fluoxetine (FXT) is a clinically prescribed antidepressant/anxiolytic drug. FXT treatment in CRS mice not only ameliorated their deficits in behavior and synaptic transmissions, but also prevented CRS-induced reduction of PNNs and ACAN expressions. This study demonstrates that proper PNNs level is critical to brain functions, and their decline may serve as a pathological mechanism of anxiety disorders.
Subject(s)
Extracellular Matrix , Parvalbumins , Humans , Adult , Mice , Animals , Parvalbumins/metabolism , Extracellular Matrix/metabolism , Aggrecans/metabolism , Anxiety , Synaptic TransmissionABSTRACT
Perineuronal nets (PNN) is condensed extracellular matrix (ECM) in the central nervous system (CNS), which surrounds cell soma, axon initial segments, and synapses. In the brain, most neurons surrounded by PNN are interneurons, especially the parvalbumin-expressing interneurons (PVI). The formation of PNN is involved in the PVI maturation as well as the onset and closure of critical periods for developmental plasticity end. Dysfunction of PVI can lead to some neurological disorders, such as schizophrenia, bipolar depression, and Alzheimer's disease. Similarly, PNN assembling abnormalities are often observed in human patients and animal disease models. PNN is thought to have a neuroprotective effect and interact with signaling molecules to regulate synaptic plasticity and neuronal activity. In this review, we provide an overview of the composition, structure, and functions of PNN. In addition, we highlight abnormal changes in PNN components in pathological conditions. Understanding the roles of different components of PNN will bring us a new perspective on brain plasticity and neurological disorders.
ABSTRACT
BACKGROUND: Dendritic spines are the sites of excitatory synapses on pyramidal neurons, and their development is crucial for neural circuits and brain functions. The spine shape, size, or number alterations are associated with neurological disorders, including schizophrenia. DiGeorge syndrome critical region gene 2 (DGCR2) is one of the deleted genes within the 22q11.2 deletion syndrome (22q11DS), which is a high risk for developing schizophrenia. DGCR2 expression was reduced in schizophrenics. However, the pathophysiological mechanism of DGCR2 in schizophrenia or 22q11DS is still unclear. RESULTS: Here, we report that DGCR2 expression was increased during the neurodevelopmental period and enriched in the postsynaptic densities (PSDs). DGCR2-deficient hippocampal neurons formed fewer spines. In agreement, glutamatergic transmission and synaptic plasticity were decreased in the hippocampus of DGCR2-deficient mice. Further molecular studies showed that the extracellular domain (ECD) of DGCR2 is responsible for its transcellular interaction with cell adhesion molecule Neurexin1 (NRXN1) and spine development. Consequently, abnormal behaviors, like anxiety, were observed in DGCR2-deficient mice. CONCLUSIONS: These observations indicate that DGCR2 is a novel cell adhesion molecule required for spine development and synaptic plasticity, and its deficiency induces abnormal behaviors in mice. This study provides a potential pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders.
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Cervical cancer (CC) is a frequent disease in women whose development is related with miRNA disorder. MiR-377-5p plays a negative role in the development of some tumors, while few studies have revealed its role in CC. In this study, the functions of miR-377-5p in CC were investigated by bioinformatics. Briefly, the expression and survival curve of miR-377-5p in CC was analyzed with the Cancer Genome Atlas (TCGA) database, and the abundance of miR-377-5p in clinical samples and CC cell lines were measured by qRT-PCR. Moreover, the MicroRNA Data Integration Portal (miRDIP) database was used to predict targets of miR-377-5p, and the Database for Annotation Visualization and Integrated Discovery (David) was used for enrichment analysis of the functions of the miR-377-5p. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to screen the hub targets of miR-377-5p. Moreover, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the abundance of the genes in CC. Results showed that decreased miR-377-5p was found in the CC tissues and cell lines, and low miR-377-5p was connected with poor prognosis of patients. Besides, the targets of miR-377-5p were enriched in the PI3K/AKT, MAPK and RAS signaling pathways. Moreover, CDC42, FLT1, TPM3 and CAV1 were screened as hub nodes in the targets of miR-377-5p, and increased CDC42, FLT1, TPM3 and CAV1 also indicated the poor survival rates of the patients in the long term. In conclusion, this study suggests that miR-377-5p downregulation is a biomarker event for CC progression.
ABSTRACT
Histidine phosphorylation (pHis), occurring on the histidine of substrate proteins, is a hidden phosphoproteome that is poorly characterized in mammals. LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) is one of the histidine phosphatases and its encoding gene was recently identified as a susceptibility gene for major depressive disorder (MDD). However, little is known about how LHPP or pHis contributes to depression. Here, by using integrative approaches of genetics, behavior and electrophysiology, we observed that LHPP in the medial prefrontal cortex (mPFC) was essential in preventing stress-induced depression-like behaviors. While genetic deletion of LHPP per se failed to affect the mice's depression-like behaviors, it markedly augmented the behaviors upon chronic social defeat stress (CSDS). This augmentation could be recapitulated by the local deletion of LHPP in mPFC. By contrast, overexpressing LHPP in mPFC increased the mice's resilience against CSDS, suggesting a critical role of mPFC LHPP in stress-induced depression. We further found that LHPP deficiency increased the levels of histidine kinases (NME1/2) and global pHis in the cortex, and decreased glutamatergic transmission in mPFC upon CSDS. NME1/2 served as substrates of LHPP, with the Aspartic acid 17 (D17), Threonine 54 (T54), or D214 residue within LHPP being critical for its phosphatase activity. Finally, reintroducing LHPP, but not LHPP phosphatase-dead mutants, into the mPFC of LHPP-deficient mice reversed their behavioral and synaptic deficits upon CSDS. Together, these results demonstrate a critical role of LHPP in regulating stress-related depression and provide novel insight into the pathogenesis of MDD.
Subject(s)
Depressive Disorder, Major , Animals , Mice , Depressive Disorder, Major/metabolism , Depression , Histidine/metabolism , Proteins/metabolism , Risk Factors , Stress, Psychological/metabolism , Mice, Inbred C57BL , Prefrontal Cortex/metabolism , Mammals/metabolismABSTRACT
BACKGROUND: Low-density lipoprotein receptor-related protein 4 (LRP4) plays a critical role in the central nervous system (CNS), including hippocampal synaptic plasticity, maintenance of excitatory synaptic transmission, fear regulation, as well as long-term potentiation (LTP). RESULTS: In this study, we found that Lrp4 was highly expressed in layer II of the piriform cortex. Both body weight and brain weight decreased in Lrp4ECD/ECD mice without TMD (Transmembrane domain) and ICD (intracellular domain) of LRP4. However, in the piriform cortical neurons of Lrp4ECD/ECD mice, the spine density increased, and the frequency of both mEPSC (miniature excitatory postsynaptic current) and sEPSC (spontaneous excitatory postsynaptic current) was enhanced. Intriguingly, finding food in the buried food-seeking test was prolonged in both Lrp4ECD/ECD mice and Lrp4 cKO (conditional knockout of Lrp4 in the piriform cortex) mice. CONCLUSIONS: This study indicated that the full length of LRP4 in the piriform cortex was necessary for maintaining synaptic plasticity and the integrity of olfactory function.
ABSTRACT
The precise control of the nervous system function under the vitality of synapses is extremely critical. Efforts have been taken to explore the underlying cellular and molecular mechanisms for synapse formation. Cell adhesion molecules have been found important for synapse assembly in the brain. Many trans-adhesion complexes have been identified to modulate excitatory synapse formation. However, little is known about the synaptogenic mechanisms for inhibitory synapses. ErbB4 is a receptor tyrosine kinase enriched in interneurons. Here, we showed that overexpressing ErbB4 in HEK293T cells induced gephyrin or GABAAR α1 puncta in co-cultured primary hippocampal neurons. This induction of ErbB4 was independent of its kinase activity. K751M, a kinase-dead mutant of ErbB4, can also induce gephyrin or GABAAR α1 puncta in the co-culture system. We further constructed K751M knock-in mice and found that the homozygous were viable at birth and fertile without changes in gross brain structure. The number of interneurons and inhibitory synapses onto pyramidal neurons (PyNs) were comparable between K751M and wild-type mice but decreased in ErbB4-Null mice. Moreover, ErbB4 can interact in trans with Slitrk3, a transmembrane postsynaptic protein at inhibitory synapses, through the extracellular RLD domain of ErbB4. The deletion of RLD diminished the induction of gephyrin or GABAAR α1 puncta by ErbB4. Finally, disruption of ErbB4-Slitrk3 interaction through neutralization of Slitrk3 by secretable RLD decreased inhibitory synapses onto PyNs and impaired GABAergic transmission. These results identify that ErbB4, as a cell adhesion molecule, promotes inhibitory synapse formation onto PyNs by interacting with Slitrk3 and in a kinase-independent manner, providing an unexpected mechanism of ErbB4 in inhibitory synapse formation.
Subject(s)
Neurogenesis , Synapses , Animals , Cell Adhesion , HEK293 Cells , Hippocampus , Humans , Mice , Receptor, ErbB-4/geneticsABSTRACT
Low-density lipoprotein receptor-related protein 4 (Lrp4) is a critical protein involved in the Agrin-Lrp4-MuSK signaling pathway that drives the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). Many studies have shown that Lrp4 also functions in kidney development, bone formation, nervous system development, etc. However, whether Lrp4 participates in nerve regeneration in mammals remains unknown. Herein, we show that Lrp4 is expressed in SCs and that conditional knockout (cKO) of Lrp4 in SCs promotes peripheral nerve regeneration. In Lrp4 cKO mice, the demyelination of SCs was accelerated, and the proliferation of SCs was increased in the injured nerve. Furthermore, we identified that two myelination-related genes, Krox-20 and Mpz, were downregulated more dramatically in the cKO group than in the control group. Our results elucidate a novel role of Lrp4 in peripheral nerve regeneration and thereby provide a potential therapeutic target for peripheral nerve recovery.
ABSTRACT
BACKGROUND: The neuromuscular junction (NMJ) is a peripheral synapse critical to muscle contraction. Like acetylcholine receptors (AChRs), many essential proteins of NMJ are extremely concentrated at the postjunctional membrane. However, the mechanisms of synapse-specific concentration are not well understood; furthermore, it is unclear whether signaling molecules critical to NMJ formation and maintenance are also locally transcribed. RESULTS: We studied the ß-gal activity encoded by a lacZ cassette driven by the promoter of the Lrp4 gene. As reported for Lrp4 mRNA, ß-gal was in the central region in embryonic muscles and at the NMJ after its formation. However, ß-gal was no longer in the central areas of muscle fibers in Lrp4 or MuSK mutant mice, indicating a requirement of Lrp4/MuSK signaling. This phenotype could be rescued by transgenic expression of LRP4 with a transmembrane domain but not soluble ECD in Lrp4 mutant mice. ß-gal and AChR clusters were distributed in a broader region in lacZ/ECD than that of heterozygous lacZ/+ mice, indicating an important role of the transmembrane domain in Lrp4 signaling. Synaptic ß-gal activity became diffused after denervation or treatment with µ-conotoxin, despite its mRNA was increased, indicating synaptic Lrp4 mRNA enrichment requires muscle activity. ß-gal was also diffused in aged mice but became re-concentrated after muscle stimulation. Finally, Lrp4 mRNA was increased in C2C12 myotubes by Wnt ligands in a manner that could be inhibited by RKI-1447, an inhibitor of ROCK in Wnt non-canonical signaling. Injecting RKI-1447 into muscles of adult mice diminished Lrp4 synaptic expression. CONCLUSIONS: This study demonstrates that synapse-specific enrichment of Lrp4 mRNA requires a coordinated interaction between Lrp4/MuSK signaling, muscle activity, and Wnt non-canonical signaling. Thus, the study provides a new mechanism for Lrp4 mRNA enrichment. It also provides a potential target for the treatment of NMJ aging and other NMJ-related diseases.
ABSTRACT
BACKGROUND: Our study aims to analyze the expression and significance of estrogen receptor (ER) and progesterone receptor (PR) in endometrial tissues of patients with intrauterine adhesion (IUA). METHODS: Fifty-four patients with IUAs examined in our hospital from January 2017 to January 2019 were selected as the research object (observation group), 54 healthy women who had physical examinations during the same period were selected as the control group, and the immunohistochemical EnVision was used. Two-step and real-time fluorescent quantitative PCR methods were used to detect the expression levels of ER and PR in the endometrial tissues of the two groups of subjects. RESULTS: The immunohistochemical test results showed that ER's expression level in the observation group was significantly higher than that in the control group, and the difference between the two groups was statistically significant (P<0.05). The difference in PR expression levels between the two groups was insignificant (P<0.05). Real-time fluorescent quantitative PCR results showed ER and PR's expression levels in the observation group were significantly higher than those in the control group, and the difference between the two groups was statistically significant (P<0.05). CONCLUSIONS: After IUA can detect ER and PR expression, we can formulate a personalized hormone treatment plan to improve the clinical treatment effect.
ABSTRACT
Although symmetry, averageness, and sexual dimorphism are usually considered important to facial attractiveness, there are mixed findings regarding whether and how symmetry influences facial attractiveness. The present study introduced "facial normality" to explain the inconsistency of previous research. We hypothesized that symmetry only increased facial attractiveness when it improved facial normality. We manipulated symmetry and normality simultaneously on sixteen Chinese male faces and asked participants to rate the perceived symmetry, perceived normality, and facial attractiveness. The results demonstrated an interactive effect of symmetry and normality on facial attractiveness. The structural equation model results showed two paths from symmetry to facial attractiveness: (1) Symmetry reduced facial attractiveness by decreasing perceived normality; (2) Symmetry increased facial attractiveness by increasing the perceived symmetry and then improving perceived normality. In other words, perceived normality acted as a mediator between symmetry and facial attractiveness. The present study provides a solution to the different effects of symmetry on facial attractiveness in previous studies and suggests that future studies on symmetry and facial attractiveness should consider the mediating role of normality.
Subject(s)
Face , Sex Characteristics , Asian People , Beauty , Humans , Male , Models, TheoreticalABSTRACT
Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disease characterized by progressive muscle weakness and wasting. Stimulation of AMP-activated protein kinase (AMPK) has been demonstrated to increase muscle function and protect muscle against damage in dystrophic mice. Metformin is a widely used anti-hyperglycemic drug and has been shown to be an indirect activator of AMPK. Based on these findings, we sought to determine the effects of metformin on neuromuscular deficits in mdx murine model of DMD. In this study, we found metformin treatment increased muscle strength accompanied by elevated twitch and tetanic force of tibialis anterior (TA) muscle in mdx mice. Immunofluorescence and electron microscopy analysis of metformin-treated mdx muscles revealed an improvement in muscle fiber membrane integrity. Electrophysiological studies showed the amplitude of miniature endplate potentials (mEPP) was increased in treated mice, indicating metformin also improved neuromuscular transmission of the mdx mice. Analysis of mRNA and protein levels from muscles of treated mice showed an upregulation of AMPK phosphorylation and dystrophin-glycoprotein complex protein expression. In conclusion, metformin can indeed improve muscle function and diminish neuromuscular deficits in mdx mice, suggesting its potential use as a therapeutic drug in DMD patients.
ABSTRACT
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease characterized by progressive wasting of skeletal muscles. The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, critical for the control of muscle contraction. The NMJ decline is observed in DMD patients, but the mechanism is unclear. LRP4 serves as a receptor for agrin, a proteoglycan secreted by motor neurons to induce NMJ, and plays a critical role in NMJ formation and maintenance. Interestingly, we found that protein levels of LRP4 were reduced both in muscles of the DMD patients and DMD model mdx mice. We explored whether increasing LRP4 is beneficial for DMD and crossed muscle-specific LRP4 transgenic mice with mdx mice (mdx; HSA-LRP4). The LRP4 transgene increased muscle strength, together with improved neuromuscular transmission in mdx mice. Furthermore, we found the LRP4 expression mitigated NMJ fragments and denervation in mdx mice. Mechanically, we showed that overexpression of LRP4 increased the activity of MuSK and expression of dystrophin-associated glycoprotein complex proteins in the mdx mice. Overall, our findings suggest that increasing LRP4 improves both function and structure of NMJ in the mdx mice and Agrin signaling might serve as a new therapeutic strategy in DMD.
Subject(s)
LDL-Receptor Related Proteins/metabolism , Muscular Dystrophy, Duchenne/genetics , Animals , Autoantibodies/genetics , Autoantibodies/metabolism , China , Disease Models, Animal , Dystrophin/metabolism , Humans , LDL-Receptor Related Proteins/genetics , Mice , Mice, Inbred mdx , Mice, Transgenic , Muscle Contraction , Muscle Fibers, Skeletal/metabolism , Muscle Strength , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/metabolism , Neuromuscular Junction/metabolism , Regeneration , Synaptic TransmissionABSTRACT
The genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1-LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.
Subject(s)
Lim Kinases/metabolism , Neuregulin-1/metabolism , Neurons/metabolism , Spine/metabolism , Animals , Excitatory Postsynaptic Potentials/physiology , Hippocampus/metabolism , Mice , Neuregulin-1/genetics , Neuronal Plasticity/physiology , Receptor, ErbB-4/metabolism , Spine/pathology , Synapses/metabolismABSTRACT
The low-density lipoprotein receptor-related protein 4 (LRP4) is essential for inducing the neuromuscular junction (NMJ) formation in muscle fibers, and LRP4 plays a critical role in dendritic development and synaptogenesis in the central nervous system (CNS). As a single transmembrane protein, LRP4 contains an enormously sizeable extracellular domain (ECD), containing multiple LDLα repeats in the N-terminal of ECD. LRP4 only with extracellular domain acts as a similar mechanism of full-length LRP4 in muscles to stimulate acetylcholine receptor clustering. In this study, we elucidated that LDLα repeats of LRP4 maintained the body weight and survival rate. Dendritic branches of the pyramidal neurons in Lrp4-null mice with LRP4 LDLα repeats residue were more than in Lrp4-null mice without residual LRP4 domain. Supplement with conditioned medium from LRP4 LDLα overexpression cells, the primary culture pyramidal neurons achieved strong dendritic arborization ability. Besides, astrocytes with LRP4 LDLα repeats residue could promote pyramidal neuronal dendrite arborization in the primary co-cultured system. These observations signify that LRP4 LDLα repeats play a prominent underlying role in dendrite arborization.
Subject(s)
Astrocytes/metabolism , Dendrites/metabolism , LDL-Receptor Related Proteins/chemistry , LDL-Receptor Related Proteins/metabolism , Repetitive Sequences, Amino Acid , Animals , Body Weight , Cells, Cultured , Cerebral Cortex/pathology , HEK293 Cells , Humans , Mice, Knockout , Protein Domains , Pyramidal Cells/metabolism , Survival AnalysisABSTRACT
Koumiss is a traditional fermented raw mare's milk product. It contains high nutritional value and is well-known for its health-promoting effect as an alimentary supplement. This study aimed to investigate the bacterial diversity, especially lactic acid bacteria (LAB), in koumiss and raw mare's milk. Forty-two samples, including koumiss and raw mare's milk, were collected from the pastoral area in Yili, Kazakh Autonomous Prefecture, Xinjiang Uygur Autonomous Region in China. This work applied PacBio single-molecule real-time (SMRT) sequencing to profile full-length 16S rRNA genes, which was a powerful technology enabling bacterial taxonomic assignment to the species precision. The SMRT sequencing identified 12 phyla, 124 genera, and 227 species across 29 koumiss samples. Eighteen phyla, 286 genera, and 491 species were found across 13 raw mare's milk samples. The bacterial microbiota diversity of the raw mare's milk was more complex and diverse than the koumiss. Raw mare's milk was rich in LAB, such as Lactobacillus (L.) helveticus, L. plantarum, Lactococcus (Lc.) lactis, and L. kefiranofaciens. In addition, raw mare's milk also contained sequences representing pathogenic bacteria, such as Staphylococcus succinus, Acinetobacter lwoffii, Klebsiella (K.) oxytoca, and K. pneumoniae. The koumiss microbiota mainly comprised LAB, and sequences representing pathogenic bacteria were not detected. Meanwhile, the koumiss was enriched with secondary metabolic pathways that were potentially beneficial for health. Using a Random Forest model, the two kinds of samples could be distinguished with a high accuracy 95.2% [area under the curve (AUC) = 0.98] based on 42 species and functions. Comprehensive depiction of the microbiota in raw mare's milk and koumiss might help elucidate evolutionary and functional relationships among the bacterial communities in these dairy products. The current work suffered from the limitation of a low sample size, so further work would be required to verify our findings.