Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species

Dynamic Repositioning of CD4 and CD8 Genes during T Cell Development

Although stable repression of CD4 and CD8 genes is a central feature of T cell lineage commitment, we lack detailed information about the timing and mechanism of this repression. Stable gene repression has been linked to the position of genes within the nucleus. Therefore, information about the nuclear position of CD4 and CD8 genes during T cell development could provide insights into both the mechanism of regulation of CD4 and CD8 genes, and the process of lineage commitment. Here, we report that lineage-specific repression of CD4 and CD8 genes is associated with the repositioning of alleles close to heterochromatin. We also provide evidence that the relocalization of CD4 and CD8 genes to heterochromatin can occur as an early response to positive selection signals. We discuss our results in terms of our current knowledge of CD4 and CD8 gene regulation and CD4 versus CD8 lineage commitment

Streptococcus Mutans Membrane Vesicles Enhance Candida albicans Pathogenicity and Carbohydrate Metabolism

Streptococcus mutans and Candida albicans, as the most common bacterium and fungus in the oral cavity respectively, are considered microbiological risk markers of early childhood caries. S. mutans membrane vesicles (MVs) contain virulence proteins, which play roles in biofilm formation and disease progression. Our previous research found that S. mutans MVs harboring glucosyltransferases augment C. albicans biofilm formation by increasing exopolysaccharide production, but the specific impact of S. mutans MVs on C. albicans virulence and pathogenicity is still unknown. In the present study, we developed C. albicans biofilms on the surface of cover glass, hydroxyapatite discs and bovine dentin specimens. The results showed that C. albicans can better adhere to the tooth surface with the effect of S. mutans MVs. Meanwhile, we employed C. albicans biofilm-bovine dentin model to evaluate the influence of S. mutans MVs on C. albicans biofilm cariogenicity. In the S. mutans MV-treated group, the bovine dentin surface hardness loss was significantly increased and the surface morphology showed more dentin tubule exposure and broken dentin tubules. Subsequently, integrative proteomic and metabolomic approaches were used to identify the differentially expressed proteins and metabolites of C. albicans when cocultured with S. mutans MVs. The combination of proteomics and metabolomics analysis indicated that significantly regulated proteins and metabolites were involved in amino acid and carbohydrate metabolism. In summary, the results of the present study proved that S. mutans MVs increase bovine dentin demineralization provoked by C. albicans biofilms and enhance the protein and metabolite expression of C. albicans related to carbohydrate metabolism

Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species

NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.

N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this study, we investigated the regulation of NMI on CSCs traits in breast cancer and uncovered the underlying molecular mechanisms. We found that NMI was lowly expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of NMI promoted CSCs traits while its overexpression inhibited CSCs traits, including the expression of CSC-related markers, the number of CD44+CD24- cell populations and the ability of mammospheres formation. We also found that NMI-mediated regulation of BCSCs traits was at least partially realized through the modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while its overexpression downregulated hTERT in breast cancer cells, and the changes in CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The in vivo study also validated that NMI knockdown promoted breast cancer growth by upregulating hTERT signaling in a mouse model. Moreover, further analyses for the clinical samples demonstrated that NMI expression was negatively correlated with hTERT expression and the low NMI/high hTERT expression was associated with the worse status of clinical TNM stages in breast cancer patients. Furthermore, we demonstrated that the interaction of YY1 protein with NMI and its involvement in NMI-mediated transcriptional regulation of hTERT in breast cancer cells. Collectively, our results provide new insights into understanding the regulatory mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a potential therapeutic target for breast cancers

Self-powered on-line ion concentration monitor in water transportation driven by triboelectric nanogenerator

The final publication is available at Elsevier via https://doi.org/10.1016/j.nanoen.2019.05.029. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Ion concentration in water is a key criterion for evaluating water quality. In this work, we developed a self-powered on-line ion concentration monitor in water transportation based on impedance matching effect of triboelectric nanogenerator (TENG). A rotary disc-shaped TENG (RD-TENG) and an ion concentration sensor were fabricated based on the industrial printed circuit board (PCB) technology. Flowing water in the pipeline acts as the energy source to drive the RD-TENG and generate an open-circuit (Voc) of 210 V. The ion concentration sensor exhibits a nearly pure resistance characteristic under the alternating current (AC) signal with the frequency below 500 Hz, corresponding to the rotation speed of 250 rpm for the RD-TENG. The impedance matching relationship between the RD-TENG and the ion concentration sensor was experimentally studied and applied to elucidate the sensing mechanism. Finally, a self-powered sensing system integrated with an alarm circuit was assembled which exhibits excellent responsibility and high sensitivity. The change of ion concentration with only 1 × 10−5 mol/L can light up an alarm LED.Natural Science and Engineering Research CouncilCanada Research ChairsNational Natural Science Foundation of China, no. 61804103National Key R&D Program of China, no. 2017YFA0205002Natural Science Foundation of the Jiangsu Higher Education Institutions of China, no. 18KJA535001, no. 14KJB150020Natural Science Foundation of Jiangsu Province of China, no. BK20170343, no. BK20180242China Postdoctoral Science Foundation, no. 2017M610346Collaborative Innovation Center of Suzhou Nano Science & TechnologyPriority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)111 Projec

Combined analysis of transcriptome and metabolome reveals that sugar, lipid, and phenylpropane metabolism are essential for male fertility in temperature-induced male sterile rice

Photoperiod- and thermosensitive genic male sterility (PTGMS) rice is a vital germplasm resource consisting of two-line hybrid rice in which light and temperature strictly control their fertility changes. Variable environmental conditions present huge risks to the two-lines hybrid seed production. Explaining the regulatory mechanism of male fertility in rice PTGMS lines is an essential prerequisite to ensuring food security production. A group of near-isogenic lines (NILs) of a rice PTGMS line unique to this research group was used for this study. These lines have the same genetic background and regulate male fertility by responding to different temperature changes. Transcriptomic analysis revealed that 315 upregulated genes and 391 regulated genes regulated male fertility in response to temperature changes, and differentially expressed genes (DEGs) were mainly characterized in enrichment analysis as having roles in the metabolic pathways of sugar, lipid and phenylpropanoid. Electron microscopy analysis revealed that a lack of starch accumulation in sterile pollen grains induced by high temperature, with an abnormal exine development and a lack of inner pollen grains. Defective processes for sporopollenin synthesis, sporopollenin transport and pollen wall formation in sterile anthers were verified using qPCR. Targeted metabolomics analysis revealed that most lipids (phospholipids, sphingolipids and fatty acids) and flavonoids (flavones and flavanones) were upregulated in fertile anthers and involved in pollen wall development and male fertility formation, while lignin G units and C-type lignin were the major contributors to pollen wall development. The coding genes for trehalose 6-phosphate phosphatase, beta-1,3-glucanase, phospholipase D and 4-coumarate-CoA ligase are considered essential regulators in the process of male fertility formation. In conclusion, our results indicated that the expression of critical genes and accumulation of metabolites in the metabolism of sugar, lipid, and phenylpropanoid are essential for male fertility formation. The results provide new insights for addressing the negative effects of environmental variation on two-line hybrid rice production

Association between dietary habits and the risk of migraine: a Mendelian randomization study

ObjectiveThe important contribution of dietary triggers to migraine pathogenesis has been recognized. However, the potential causal roles of many dietary habits on the risk of migraine in the whole population are still under debate. The objective of this study was to determine the potential causal association between dietary habits and the risk of migraine (and its subtypes) development, as well as the possible mediator roles of migraine risk factors.MethodsBased on summary statistics from large-scale genome-wide association studies, we conducted two-sample Mendelian randomization (MR) and bidirectional MR to investigate the potential causal associations between 83 dietary habits and migraine and its subtypes, and network MR was performed to explore the possible mediator roles of 8 migraine risk factors.ResultsAfter correcting for multiple testing, we found evidence for associations of genetically predicted coffee, cheese, oily fish, alcohol (red wine), raw vegetables, muesli, and wholemeal/wholegrain bread intake with decreased risk of migraine, those odds ratios ranged from 0.78 (95% CI: 0.63–0.95) for overall cheese intake to 0.61 (95% CI: 0.47–0.80) for drinks usually with meals among current drinkers (yes + it varies vs. no); while white bread, cornflakes/frosties, and poultry intake were positively associated with the risk of migraine. Additionally, genetic liability to white bread, wholemeal/wholegrain bread, muesli, alcohol (red wine), cheese, and oily fish intake were associated with a higher risk of insomnia and (or) major depression disorder (MDD), each of them may act as a mediator in the pathway from several dietary habits to migraine. Finally, we found evidence of a negative association between genetically predicted migraine and drinking types, and positive association between migraine and cups of tea per day.SignificanceOur study provides evidence about association between dietary habits and the risk of migraine and demonstrates that some associations are partly mediated through one or both insomnia and MDD. These results provide new insights for further nutritional interventions for migraine prevention

The Role of Elements Partition and Austenite Grain Size in the Ferrite-Bainite Banding Formation during Hot Rolling

The partitioning and diffusion of solute elements in hot rolling and the effect of the partitioning and diffusion on the ferrite-bainite banding formation after hot rolling in the 20CrMnTi steel were experimentally examined by EPMA (electron probe microanalysis) technology and simulated by DICTRTA and MATLAB software. The austenite grain size related to the hot rolling process and the effect of austenite grain size on the ferrite-bainite banding formation were studied. The results show that experimental steel without banding has the most uniform hardness distribution, which is taken from the edge of the cast slab and 1/4 diameter position of the cast slab, heating at 1100 °C for 2 h and above 1200 °C for 2–4 h during the hot rolling, respectively. Cr, Mn, and Si diffuse and inhomogeneously concentrate in austenite during hot rolling, while C homogeneously concentrates in austenite. After the same hot rolling process, ΔAe3 increases and ferrite-bainite banding intensifies with increasing initial segregation width and segregation coefficient K of solute elements. Under the same initial segregation of solute elements, ΔAe3 drops and ferrite-bainite banding reduces with increasing heating temperature and extension heating time. When ΔAe3 drops below 14 °C, ferrite-bainite banding even disappears. What is more, the austenite grain size increases with increasing heating temperature and extension heating time. When the austenite grain size is above 21 μm, the experimental steel will not appear to have a banded structure after hot rolling