Social conformity is associated with inter-trial electroencephalogram variability.

Human society encompasses diverse social influences, and people experience events differently and may behave differently under such influence, including in forming an impression of others. However, little is known about the underlying neural relevance of individual differences in following others' opinions or social norms. In the present study, we designed a series of tasks centered on social influence to investigate the underlying relevance between an individual's degree of social conformity and their neural variability. We found that individual differences under the social influence are associated with the amount of inter-trial electroencephalogram (EEG) variability over multiple stages in a conformity task (making face judgments and receiving social influence). This association was robust in the alpha band over the frontal and occipital electrodes for negative social influence. We also found that inter-trial EEG variability is a very stable, participant-driven internal state measurement and could be interpreted as mindset instability. Overall, these findings support the hypothesis that higher inter-trial EEG variability may be related to higher mindset instability, which makes participants more vulnerable to exposed external social influence. The present study provides a novel approach that considers the stability of one's endogenous neural signal during tasks and links it to human social behaviors.

Cloning, Prokaryotic Expression and Functional Characterization of NifH Gene from the Associative Nitrogen-Fixing Bacteria Klebsiella Variicola DX120E.

Background: Biological nitrogen fixation (BNF) is a unique mechanism in which microorganisms utilize the nitrogenase enzyme to catalyze the conversion of atmospheric nitrogen (N2) to ammonia (NH3). Fe protein, encoded by the nifH gene, is an essential component of the nitrogenase in Klebsiella variicola DX120E. However, the function of this gene in regulating nitrogen fixing activity is still unclear. Objectives: The objective of this study was to reveal the function of nifH gene in associative nitrogen-fixing bacteria Klebsiella variicola DX120E and micro-sugarcane system by immunoassay and gene editing. Materials and Methods: In the current investigation, the nifH gene was cloned in a pET-30a (+) vector and expressed in Escherichia coli. The NifH protein was purified and used to immunize rabbit, and then the serum was collected and purified to obtain rabbit anti-NifH polyclonal antibodies. The CRISPR-Cas9 system was applied to produce nifH mutant strains, and the nitrogen-fixing enzyme activity, gene, and protein expression were analyzed. Results: Both in vitro and in vivo NifH proteins were detected by Western blotting, which were 43 and 32 kDa respectively. The expression of nifD and nifK genes was decreased, and nitrogenase activity was reduced in the nifH mutant strain. Conclusion: The nifH gene mutant weakened the nitrogenase activity by regulating the expression of Fe protein, which suggests a potential strategy to study the nitrogen fixation-related genes and the interactions between endophytic nitrogen-fixing bacteria and sugarcane.

The Oligodendrocyte Transcription Factor 2 OLIG2 regulates transcriptional repression during myelinogenesis in rodents.

OLIG2 is a transcription factor that activates the expression of myelin-associated genes in the oligodendrocyte-lineage cells. However, the mechanisms of myelin gene inactivation are unclear. Here, we uncover a non-canonical function of OLIG2 in transcriptional repression to modulate myelinogenesis by functionally interacting with tri-methyltransferase SETDB1. Immunoprecipitation and chromatin-immunoprecipitation assays show that OLIG2 recruits SETDB1 for H3K9me3 modification on the Sox11 gene, which leads to the inhibition of Sox11 expression during the differentiation of oligodendrocytes progenitor cells (OPCs) into immature oligodendrocytes (iOLs). Tissue-specific depletion of Setdb1 in mice results in the hypomyelination during development and remyelination defects in the injured rodents. Knockdown of Sox11 by siRNA in rat primary OPCs or depletion of Sox11 in the oligodendrocyte lineage in mice could rescue the hypomyelination phenotype caused by the loss of OLIG2. In summary, our work demonstrates that the OLIG2-SETDB1 complex can mediate transcriptional repression in OPCs, affecting myelination.

Triage Modeling for Differential Diagnosis Between COVID-19 and Human Influenza A Pneumonia: Classification and Regression Tree Analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic has lasted much longer than an influenza season, but the main signs, symptoms, and some imaging findings are similar in COVID-19 and influenza patients. The aim of the current study was to construct an accurate and robust model for initial screening and differential diagnosis of COVID-19 and influenza A. Methods: All patients in the study were diagnosed at Fuyang No. 2 People's Hospital, and they included 151 with COVID-19 and 155 with influenza A. The patients were randomly assigned to training set or a testing set at a 4:1 ratio. Predictor variables were selected based on importance, assessed by random forest algorithms, and analyzed to develop classification and regression tree models. Results: In the optimal model A, the best single predictor of COVID-19 patients was a normal or high level of low-density lipoprotein cholesterol, followed by low level of creatine kinase, then the presence of <3 respiratory symptoms, then a highest temperature on the first day of admission <38°C. In the suboptimal model B, the best single predictor of COVID-19 was a low eosinophil count, then a normal monocyte ratio, then a normal hematocrit value, then a highest temperature on the first day of admission of <37°C, then a complete lack of respiratory symptoms. Conclusions: The two models provide clinicians with a rapid triage tool. The optimal model can be used to developed countries/regions and major hospitals, and the suboptimal model can be used in underdeveloped regions and small hospitals.

Temporarily Epigenetic Repression in Bergmann Glia Regulates the Migration of Granule Cells.

Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensive transcriptome landscape of BG. Here, high temporal-resolution investigation of transcriptomes with FACS-sorted BG revealed the dynamic expression of genes within given functions and pathways enabled BG to assist neural migration and construct neuron-glia network. It is found that the peak time of GCs migration (P7-10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7-10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG's transcriptomic landscapes offer an insight into the mechanism by which BG are in depth integrated in cerebellar neural network.

Analysis of the economic performance of municipal Children's Hospitals in Shanghai: a study on the impacts of policy changes in healthcare service prices.

BACKGROUND: Since the Shanghai municipal government launched the latest round of medical service price reform in 2015, public hospitals have gradually abolished the prices of drugs and consumables, and increased the prices of healthcare services to properly reflect the labor value of medical workers. Under the price reform policy, we should pay more attention to the operation of children's hospitals. METHODS: Literature review: we conducted a systematic review of the economic performance of municipal children's hospitals in Shanghai and the relevant policies on healthcare service price reform. Data analysis: we use the relevant economic performance statistics of municipal children's hospitals and comprehensive hospitals in Shanghai during 2012-2018 to analyze the impacts of healthcare service price reform on children's hospitals based on time series and hospital type. Expert interview: to expand upon the data analysis, we interviewed some experts to discuss solutions for addressing the difficulties in developing municipal children's hospitals. RESULTS: Since the pricing reform, the revenue composition of children's hospitals has dramatically improved. However, the slightly insufficient potential of their business growth exacerbates their losses and hurts their economic performance. CONCLUSIONS: In the future, municipal children's hospitals should strengthen their internal management, sharpen their orientation tuning, improve their healthcare service quality, and improve their operational efficiency. Meanwhile, the government needs to provide relevant policy support and help children's hospitals in their efforts to further improve and grow. Part of the policy recommendations of this study have been included in the next round of important measures for Shanghai's medical reform and planning.

Study on the Deterioration of Concrete under Dry-Wet Cycle and Sulfate Attack.

In order to study the deterioration and mechanism of dry-wet cycles and sulfate attack on the performance of concrete in seaside and saline areas, the deterioration of compressive strength of concrete with different water cement ratios under different erosion environments (sodium sulfate soaking at room temperature and coupling of dry-wet cycling and sodium sulfate) was studied here. At the same time, ICT (industrial computed tomography) and NMR (nuclear magnetic resonance) techniques were used to analyze the internal pore structure of concrete under different erosion environments. The results show that the compressive strength under different erosion environments increases first and then decreases, and the dry-wet cycle accelerates the sulfate erosion. With the increase of dry and wet cycles, larger pores are filled with erosion products and developed into small pores in the early stage of erosion; in the later stage of erosion, the proportion of larger pores increases, and cracks occur inside the sample. In the process of sulfate soaking and erosion, the smaller pores in the concrete account for the majority. As the sulfate erosion continues, the T2 spectrum distribution curve gradually moves right, and the signal intensity of the larger pores increases.

Effect of Polyvinyl Alcohol on the Rheological Properties of Cement Mortar.

Polyvinyl alcohol (PVA) is a kind of water-soluble polymer, which has been widely used in different industries due to its excellent mechanical and chemical properties. In this paper, the effects of polyvinyl alcohol with different hydrolysis and polymerization degrees on the rheological properties of cement mortar are studied. The results show that the rheological properties of PVA-modified cement mortar can be described by the modified Bingham model. The yield stress of modified cement mortar is less than that of unmodified mortar when the degree of polymerization and the content of PVA are small. With the increase of polyvinyl alcohol content and polymerization degree, the yield stress and plastic viscosity of modified cement mortar increase sharply, which are larger than those of the unmodified cement mortar. However, the effect of hydrolysis degree of PVA on yield stress and plastic viscosity of modified cement mortar is not obvious.

The Effects of Nano-SiO2 and Nano-TiO2 Addition on the Durability and Deterioration of Concrete Subject to Freezing and Thawing Cycles.

The objective of this manuscript is to study the effects of nano-particle addition on the durability and internal deterioration of concrete subject to freezing and thawing cycles (FTCs). Fifteen nm of SiO2, 30 nm of SiO2, and 30 nm of TiO2 were added to concrete to prepare specimens with different contents. All the specimens were subjected to FTCs from 0 to 75. The mass of each specimen was measured once the FTCs reached 25, 50, and 75. Then the freezing and thawing resistance of the concrete was evaluated by computing the mass loss ratio. The pore fluid size distribution of the concrete was detected using nuclear magnetic resonance (NMR). The deterioration of the concrete subjected to FTCs was detected by industrial computed tomography (CT). The effect of different nano-particle sizes, different contents of nano-particles, and different types of nano-particles on the freezing and thawing resistance, the pore size, distribution, and the deterioration of the concrete were analyzed. The effects of FTCs on the pore size distribution and the internal deterioration of concrete were also studied. Compared to 30 nm-Nono-SiO2 (NS), 15 nm-NS had a better effect in improving the internal structure for concrete, and 30 nm-Nano-TiO2 (NT) also had a better effect in preventing pore and crack expansion.

Anticancer effects of curzerenone against drug-resistant human lung carcinoma cells are mediated via programmed cell death, loss of mitochondrial membrane potential, ROS, and blocking the ERK/MAPK and NF-κB signaling pathway.

PURPOSE: The main objective of the current study was to examine the anticancer effects of Curzerenone - a naturally occurring sesquiterpene against gemcitabine-resistant lung carcinoma cells. The effects of Curzerenone on mitochondrial-mediated apoptosis, ROS, and ERK/MAPK and NF-kB signalling pathways were also investigated in the present study. METHODS: Cell proliferation was evaluated by MTT assay. Apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) and DAPI staining as well as flow cytometry using annexin V apoptosis assay. The effects on reactive oxygen species (ROS) as well as mitochondrial membrane potential (MMP) were examined by flow cytometry. Protein expression was examined by western blotting. RESULTS: It was found that Curzerenone induced potent antiproliferative effects against the gemcitabine-resistant lung cancer cells and exhibited an IC50 of 24 µM. The anticancer effects of curzerenone were due to the induction of apoptosis which was also associated with alteration of apoptosis-related proteins (Bax,Bcl-2). Curzerenone also caused ROS-mediated alterations in the MMP. Curzerenone induced cell death in gemcitabine-resistant lung cancer cells by activating p38 MAPK/ERK signalling pathway while NF-kB pathway was inhibited in a dose-dependent manner. CONCLUSIONS: In conclusion, the current results strongly indicate that Curzerenone may prove a potential anticancer drug candidate against drug-resistant lung cancer.

Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination.

Nucleoporins (Nups) are involved in neural development, and alterations in Nup genes are linked to human neurological diseases. However, physiological functions of specific Nups and the underlying mechanisms involved in these processes remain elusive. Here, we show that tissue-specific depletion of the nucleoporin Seh1 causes dramatic myelination defects in the CNS. Although proliferation is not altered in Seh1-deficient oligodendrocyte progenitor cells (OPCs), they fail to differentiate into mature oligodendrocytes, which impairs myelin production and remyelination after demyelinating injury. Genome-wide analyses show that Seh1 regulates a core myelinogenic regulatory network and establishes an accessible chromatin landscape. Mechanistically, Seh1 regulates OPCs differentiation by assembling Olig2 and Brd7 into a transcription complex at nuclear periphery. Together, our results reveal that Seh1 is required for oligodendrocyte differentiation and myelination by promoting assembly of an Olig2-dependent transcription complex and define a nucleoporin as a key player in the CNS.

Pygo2 Regulates Adiposity and Glucose Homeostasis via ß-Catenin-Axin2-GSK3ß Signaling Pathway.

Wnt/ß-catenin signaling plays a key role in regulating adipogenesis through indirectly inhibiting the expression of C/EBPα and peroxisome proliferator-activated receptor γ (PPARγ); however, the detailed molecular mechanism remains poorly understood. Moreover, the factor(s) that determines the Wnt/ß-catenin output level during adipogenesis is also not completely defined. In this study, we showed that Pygo2 exhibited a declined expression pattern during adipocyte differentiation, resulting in an attenuated Wnt/ß-catenin output level. The mechanism study indicated that Pygo2 inhibition led to the downregulation of Axin2, a constitutive Wnt target, in the cytoplasm. Consequently, Axin2-bound GSK3ß was released and translocated into the nucleus to phosphorylate C/EBPß and Snail, resulting in an increase in the DNA binding activity of C/EBPß and decreased protein stability of Snail, which subsequently activated the expression of C/EBPα and PPARγ. Consistent with this, embryonic fibroblasts from Pygo2-/- mice exhibited spontaneous adipocyte differentiation, and adipocyte precursor-specific Pygo2-deficient mice exhibited increased adiposity with decreased energy expenditure. We further showed impaired glucose tolerance and decreased systemic insulin sensitivity in Pygo2-deficient mice. Our study revealed an association between Pygo2 function and obesity or diabetes.

Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation.

Astrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte-specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We observed enhanced NF-κB activation and IL-1ß production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-κB inhibitor or IL-1ß receptor antagonist. Importantly, we identified a SNP, rs375804228, in human MEN1, where G503D substitution is associated with a higher risk of MDD onset. G503D substitution abolished menin-p65 interactions, thereby enhancing NF-κB activation and IL-1ß production. Our results reveal a distinct astroglial role for menin in regulating neuroinflammation in depression, indicating that menin may be an attractive therapeutic target in MDD.

Leptospiral LruA is required for virulence and modulates an interaction with mammalian apolipoprotein AI.

Leptospirosis is a worldwide zoonosis caused by spirochetes of the genus Leptospira. While understanding of pathogenesis remains limited, the development of mutagenesis in Leptospira has provided a powerful tool for identifying novel virulence factors. LruA is a lipoprotein that has been implicated in leptospiral uveitis as a target of the immune response. In this study, two lruA mutants, M754 and M765, generated by transposon mutagenesis from Leptospira interrogans serovar Manilae, were characterized. In M754, the transposon inserted in the middle of lruA, resulting in no detectable expression of LruA. In M765, the transposon inserted toward the 3' end of the gene, resulting in expression of a truncated protein. LruA was demonstrated to be on the cell surface in M765 and the wild type (WT). M754, but not M765, was attenuated in a hamster model of acute infection. A search for differential binding to human serum proteins identified a serum protein of around 30 kDa bound to the wild type and the LruA deletion mutant (M754), but not to the LruA truncation mutant (M765). Two-dimensional separation of proteins from leptospiral cells incubated with guinea pig serum identified the 28-kDa apolipoprotein A-I (ApoA-I) as a major mammalian serum protein that binds Leptospira in vitro. Interestingly, M754 (with no detectable LruA) bound more ApoA-I than did the LruA-expressing strains Manilae wild type and M765. Our data thus identify LruA as a surface-exposed leptospiral virulence factor that contributes to leptospiral pathogenesis, possibly by modulating cellular interactions with serum protein ApoA-I.

Enhanced succinic acid production by Actinobacillus succinogenes after genome shuffling.

Succinic acid is an important platform chemical for synthesis of C4 compounds. We applied genome shuffling to improve fermentative production of succinic acid by A. succinogenes. Using a screening strategy composed of selection in fermentation broth, cultured in 96-deep-well plates, and condensed HPLC screening, a starting population of 11 mutants producing a higher succinic acid concentration was selected and subjected to recursive protoplasts fusion. After three rounds of genome shuffling, strain F3-II-3-F was obtained, producing succinic acid at 1.99 g/l/h with a yield of 95.6 g/l. The genome shuffled strain had about a 73 % improvement in succinic acid production compared to the parent strain after 48 h in fed-batch fermentation. The genomic variability of F3-II-3-F was confirmed by amplified fragment-length polymorphism. The activity levels of key enzymes involved in end-product formation from glucose and metabolic flux distribution during succinic acid production were compared between A. succinogenes CGMCC 1593 and F3-II-3-F. Increased activity of glucokinase, fructose-1,6-bisphosphate aldolase, PEP carboxykinase and fumarase, as well as decreased activity of pyruvate kinase, pyruvate formate-lyase, and acetate kinase explained the enhanced succinic acid production and decreased acetic acid formation. Metabolic flux analysis suggested that increased flux to NADH was the main reason for increased activity of the C4 pathway resulting in increased yields of succinic acid. The present work will be propitious to the development of a bio-succinic acid fermentation industry.

Carbohydrate transporting membrane proteins of the rumen bacterium, Butyrivibrio proteoclasticus.

The research was aimed at finding which membrane proteins of the rumen bacterium Butyrivibrio proteoclasticus are involved in the uptake of carbohydrates resulting from extracellular enzymatic degradation of hemicellulose and fructan. The proteomic analysis of cells grown with fructose or xylan as the sole substrate identified 13 membrane proteins predicted to function as carbohydrate transporters. One protein detected was the membrane component of a fructose-specific phosphoenolpyruvate:sugar phosphotransferase system believed to be involved in the fructose uptake following extracellular fructan breakdown. The other 12 proteins were all ABC transport system substrate-binding proteins, nine of which belong to functional category COG1653 that includes proteins predicted to transport oligosaccharides. Four of the SBPs were significantly upregulated in xylan grown cells, and three of these were found in polysaccharide utilisation loci where they are clustered with other genes involved in hemicellulose breakdown and metabolism. It is possible that the carbon source available regulates a wider network of genes. The information on the mechanisms used by rumen bacteria to take up carbohydrates from their environment may improve our understanding of the ruminant digestion and facilitate strategies for improved pasture and stored feed utilisation.

Cross-protective immunity against leptospirosis elicited by a live, attenuated lipopolysaccharide mutant.

BACKGROUND: Leptospira species cause leptospirosis, a zoonotic disease found worldwide. Current vaccines against leptospirosis provide protection only against closely related serovars. METHODS: We evaluated an attenuated transposon mutant of Leptospira interrogans serovar Manilae (M1352, defective in lipopolysaccharide biosynthesis) as a live vaccine against leptospirosis. Hamsters received a single dose of vaccine and were challenged with the homologous serovar (Manilae) and a serologically unrelated heterologous serovar (Pomona). Comparisons were made with killed vaccines. Potential cross-protective antigens against leptospirosis were investigated. RESULTS: Live M1352 vaccine induced superior protection in hamsters against homologous challenge. The live vaccine also stimulated cross-protection against heterologous challenge, with 100% survival (live M1352) versus 40% survival (killed vaccine). Hamsters receiving either vaccine responded to the dominant membrane proteins LipL32 and LipL41. Hamsters receiving the live vaccine additionally recognized LA3961/OmpL36 (unknown function), Loa22 (OmpA family protein, recognized virulence factor), LA2372 (general secretory protein G), and LA1939 (hypothetical protein). Manilae LigA was recognized by M1352 vaccinates, whereas LipL36 was detected in Pomona. CONCLUSION: This study demonstrated that a live, attenuated vaccine can stimulate cross-protective immunity to L. interrogans and has identified antigens that potentially confer cross-protection against leptospirosis.

Membrane proteins of Pseudoalteromonas tunicata during the transition from planktonic to extracellular matrix-adherent state.

Pseudoalteromonas tunicata is a marine bacterium that was originally isolated from the surface of the tunicate Ciona intestinalis. Since C. intestinalis expresses extracellular matrix (ECM) and P. tunicata has a gene encoding a functional ECM-binding protein, we hypothesized that P. tunicata could adhere to this host via protein-ECM interactions and as a result change its membrane proteome. An in vitro adhesion assay was developed to show that P. tunicata adheres strongly to ECM. To further study the adhesion biology of P. tunicata, two-dimensional (2D) electrophoresis was used to explore the membrane-associated sub-proteome of P. tunicata during planktonic, adherent and non-adherent states. More than 30 proteins were resolved using blue native (BN)/SDS 2D PAGE, many of which were identified by mass spectrometry. BN/SDS PAGE also allowed the identification of several novel protein complexes, which indicate structural and functional relationships for these proteins and related proteins in several other organisms. A proteomic change associated with adhesion was identified by comparison of 2D gels from the three model states. Collectively, these studies explore the membrane proteome of P. tunicata during the transition from planktonic to ECM-adherent states.

Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans.

Leptospira interrogans is responsible for leptospirosis, a zoonosis of worldwide distribution. LipL32 is the major outer membrane protein of pathogenic leptospires, accounting for up to 75% of total outer membrane protein. In recent times LipL32 has become the focus of intense study because of its surface location, dominance in the host immune response, and conservation among pathogenic species. In this study, an lipL32 mutant was constructed in L. interrogans using transposon mutagenesis. The lipL32 mutant had normal morphology and growth rate compared to the wild type and was equally adherent to extracellular matrix. Protein composition of the cell membranes was found to be largely unaffected by the loss of LipL32, with no obvious compensatory increase in other proteins. Microarray studies found no obvious stress response or upregulation of genes that may compensate for the loss of LipL32 but did suggest an association between LipL32 and the synthesis of heme and vitamin B(12). When hamsters were inoculated by systemic and mucosal routes, the mutant caused acute severe disease manifestations that were indistinguishable from wild-type L. interrogans infection. In the rat model of chronic infection, the LipL32 mutant colonized the renal tubules as efficiently as the wild-type strain. In conclusion, this study showed that LipL32 does not play a role in either the acute or chronic models of infection. Considering the abundance and conservation of LipL32 among all pathogenic Leptospira spp. and its absence in saprophytic Leptospira, this finding is remarkable. The role of this protein in leptospiral biology and pathogenesis thus remains elusive.