ABSTRACT
MOTIVATION: The rapid development of high-throughput biomedical technologies can provide researchers with detailed multi-omics data. The multi-omics integrated analysis approach based on machine learning contributes a more comprehensive perspective to human disease research. However, there are still significant challenges in representing single-omics data and integrating multi-omics information. RESULTS: This article presents HyperTMO, a Trusted Multi-Omics integration framework based on Hypergraph convolutional network for patient classification. HyperTMO constructs hypergraph structures to represent the association between samples in single-omics data, then evidence extraction is performed by hypergraph convolutional network, and multi-omics information is integrated at an evidence level. Last, we experimentally demonstrate that HyperTMO outperforms other state-of-the-art methods in breast cancer subtype classification and Alzheimer's disease classification tasks using multi-omics data from TCGA (BRCA) and ROSMAP datasets. Importantly, HyperTMO is the first attempt to integrate hypergraph structure, evidence theory, and multi-omics integration for patient classification. Its accurate and robust properties bring great potential for applications in clinical diagnosis. AVAILABILITY AND IMPLEMENTATION: HyperTMO and datasets are publicly available at https://github.com/ippousyuga/HyperTMO.
Subject(s)
Alzheimer Disease , Breast Neoplasms , Humans , Female , Multiomics , Breast , Breast Neoplasms/genetics , Machine LearningABSTRACT
This study investigated the effects of diurnal nap in the recognition memory for faces in habitual nappers. Thirty volunteers with habitual midday napping (assigned as the sleep group) and 28 non-nappers (assigned as the wake group) participated in this study. Participants were instructed to memorize faces, and subsequently to perform two recognition tasks before and after nap/wakefulness, i.e., an immediate recognition and a delayed recognition. There were three experimental conditions: same faces with the same view angle (S-S condition); same faces with a different view angle (22.5°) (S-D condition); and novel faces (NF condition). A mixed repeated-measures ANOVA revealed that the sleep group exhibited significantly longer reaction times (RT) following their nap compared to those of the wake group; no significant between-group differences were observed in accuracy or sensitivity (d'). Furthermore, both groups were more conservative in the delayed recognition task compared to the immediate recognition task, but the sleep group was more conservative after their nap (vs pre-nap), reflected by the criterion (ß, Ohit/Ofalse alarm). Further stepwise regression analysis revealed a positive relationship between duration of stage N3 sleep and normalized RT difference before/after nap on the S-S condition. These findings suggest that an immediate nap following face learning is associated with memory reorganization during N3 sleep in habitual nappers, rendering the memories not readily accessible.
ABSTRACT
OBJECTIVE: Estrogen is correlated to the lower mortality and disease severity of female than that of male, which indicates the potential therapeutic role of estrogen supplement therapy in sepsis. The structure of Daidzein is similar to that of 17ß estradiol (E2), an estrogen in human body, causing the exogenous Daidzein can interact with estrogen receptor as well as E2 in the body. We aim to explore the therapeutic role of estrogen in sepsis-induced vascular dysfunction. Also, we wonder if estrogen regulates blood pressure via glucocorticoid-mediated vascular reactivity. METHODS: Female SD rats received ovariectomy (OVX) to induce estrogen deficiency. After 12 weeks of administration, cecal ligation and puncture (CLP) was used to establish the in vivo model of sepsis. Lipopolysaccharide (LPS) was used to construct the in vitro model of sepsis in vascular smooth muscle cells (VSMCs). E2 and Daidzein were used for estrogen supplement therapy. RESULTS: E2 and Daidzein significantly inhibited inflammation infiltration and histopathological injury in thoracic aorta in the rat model with CLP. E2 and Daidzein improved carotid pressure and vascular hyporeactivity in sepsis rats with OVX. Importantly, E2 and Daidzein promoted glucocorticoid permissive action and increased glucocorticoid receptor α (GRα) expression in thoracic aorta smooth muscle cells. E2 and Daidzein upregulated GRα, and inhibits cytokine production, proliferative phenotype and cell migration in LPS-induced VSMCs. CONCLUSION: Estrogen improved vascular hyporeactivity in thoracic aorta induced by sepsis via permissive effect of GRα expression.
Subject(s)
Aorta, Thoracic , Sepsis , Rats , Animals , Male , Female , Humans , Aorta, Thoracic/metabolism , Glucocorticoids/pharmacology , Lipopolysaccharides/pharmacology , Rats, Sprague-Dawley , Estrogens/metabolism , Sepsis/complications , Sepsis/drug therapy , Sepsis/metabolism , Estradiol/pharmacology , Estradiol/therapeutic use , Estradiol/metabolismABSTRACT
AIMS: This study aimed to investigate the status quo of nurses' spiritual care competency and their relationship with perceived professional benefit. BACKGROUND: Spiritual care has always been considered a vitally important part of holistic nursing. Understanding the spiritual care competency of nurses during the COVID-19 pandemic can help nursing managers understand the weak links in spiritual care practice and improve the quality of nursing service. As a positive emotional experience and cognitive evaluation of the profession, perceived professional benefit can serve to adjust work pressure, relieve job burnout and promote an individual's overall growth. However, the relationship between perceived professional benefit among nurses and spiritual care competency remains unclear. METHODS: A total of 372 nurses were recruited from 15 separate Chinese hospitals. An online questionnaire was used to assess nurses' sociodemographic, spiritual care competency and perceived professional benefit. Statistical analyses were performed using Pearson's correlation analysis, t test, analysis of variance (ANOVA) and multiple stepwise linear regression analysis. RESULTS: The total mean score of spiritual care competency (99.43 ± 21.10) among nurses was found to be moderate. Nurses' spiritual care competency was positively correlated with perceived professional benefit (P < .01). The multiple stepwise linear regression model (n = 372) had an explained variance (R2 = 0.218) and showed that perceived professional benefit and the manner of receiving spiritual training were the main influencing factors of nurses' spiritual care competency (P < .001). CONCLUSION: The study findings indicated that nurses need to improve their spiritual care competency by improving their perceived professional benefit. IMPLICATION FOR NURSING MANAGERS: Our study evaluated the spiritual care competency of nurses and explored the correlation between perceived professional benefit and spiritual care competency among nurses. The results of this study can help nursing managers to carry out relevant interventions, thus improving nurses' spiritual care competency and optimizing the quality of nursing.
Subject(s)
COVID-19 , Spiritual Therapies , Humans , Cross-Sectional Studies , Pandemics , Spirituality , Surveys and QuestionnairesABSTRACT
Layered Li-rich Ni, Mn, Co (NMC) oxide cathodes in Li-ion batteries provide high specific capacities (>250 mAh/g) via O-redox at high voltages. However, associated high-voltage interfacial degradation processes require strategies for effective electrode surface passivation. Here, we show that an acidic surface treatment of a Li-rich NMC layered oxide cathode material leads to a substantial suppression of CO2 and O2 evolution, â¼90% and â¼100% respectively, during the first charge up to 4.8 V vs Li+/0. CO2 suppression is related to Li2CO3 removal as well as effective surface passivation against electrolyte degradation. This treatment does not result in any loss of discharge capacity and provides superior long-term cycling and rate performance in comparison to as-received, untreated materials. We also quantify the extent of lattice oxygen participation in charge compensation ("O-redox") during Li+ removal by a novel ex situ acid titration. Our results indicate that the peroxo-like species resulting from O-redox originate on the surface at least 300 mV earlier than the activation plateau region at around 4.5 V. X-ray photoelectron spectra and Mn L-edge X-ray absorption spectra of the cathode powders reveal a Li+ deficiency and a partial reduction of Mn ions on the surface of the acid-treated material. More interestingly, although the irreversible oxygen evolution is greatly suppressed through the surface treatment, O K-edge resonant inelastic X-ray scattering shows that the lattice O-redox behavior is largely sustained. The acidic treatment, therefore, only optimizes the surface of the Li-rich material and almost eliminates the irreversible gas evolution, leading to improved cycling and rate performance. This work therefore presents a simple yet effective approach to passivate cathode surfaces against interfacial instabilities during high-voltage battery operation.
ABSTRACT
Binuclear Mg ketol-acid reductoisomerase (KARI), which converts (S)-2-acetolactate into (R)-2,3-dihydroxyisovalerate, is responsible for the second step of the biosynthesis of branched-chain amino acids in plants and microorganisms and thus serves as a key inhibition target potentially without effects on mammals. Here, through the use of density functional calculations and a chemical model, the KARI-catalyzed reaction has been demonstrated to include the initial deprotonation of the substrate C2 hydroxy group, bridged by the two Mg ions, alkyl migration from the C2-alkoxide carbon atom to the C3-carbonyl carbon atom, and hydride transfer from a nicotinamide adenine dinucleotide phosphate [NAD(P)H] cofactor to C2. A dead-end mechanism with a hydride transferred to the C3 carbonyl group has been ruled out. The nucleophilicity (migratory aptitude) of the migrating carbon atom and the provision of additional negative charge to the di-Mg coordination sphere have significant effects on the steps of alkyl migration and hydride transfer, respectively. Other important mechanistic characteristics are also revealed. Inspired by the mechanism, an inhibitor (2-carboxylate-lactic acid) was designed and predicted by barrier analysis to be effective in inactivating KARI, hence probably enriching the antifungal and antibacterial library. Two types of slow substrate analogues (2-trihalomethyl acetolactic acids and 2-glutaryl lactic acid) were also found.
Subject(s)
Amino Acids, Branched-Chain/antagonists & inhibitors , Carboxylic Acids/pharmacology , Enzyme Inhibitors/pharmacology , Ketol-Acid Reductoisomerase/antagonists & inhibitors , Lactic Acid/pharmacology , Magnesium/metabolism , Amino Acids, Branched-Chain/biosynthesis , Carboxylic Acids/chemical synthesis , Carboxylic Acids/chemistry , Crystallography, X-Ray , Density Functional Theory , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Ketol-Acid Reductoisomerase/chemistry , Ketol-Acid Reductoisomerase/metabolism , Lactic Acid/chemical synthesis , Lactic Acid/chemistry , Magnesium/chemistry , Models, Molecular , Molecular StructureABSTRACT
Reactivation renders consolidated memory labile again, and the ensuing temporary reconsolidation process is highly susceptible to mnemonic modification. Here, we show that memories in such an unstable state could be influenced by sheer behavioral means, bypassing the need for pharmacological intervention. Across several experiments using a "face-location association" paradigm in which participants experienced a "Learning - New-learning - Final-test" procedure, we demonstrate that reactivated memory traces were hampered when the new learning was strategically administered at between 0-min and 20-min delay. Using fMRI, we further advance our theoretical understanding that this lability can be mechanistically explained by the differential activation in the hippocampal-amygdala memory system implicated by the post-activation new-learning whereas the mnemonic intrusion caused by newly learned memories is efficaciously reconciled by the left inferior frontal gyrus.
Subject(s)
Amygdala/physiology , Association Learning/physiology , Hippocampus/physiology , Memory Consolidation/physiology , Mental Recall/physiology , Adult , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Male , Time Factors , Young AdultABSTRACT
Several studies have shown that long non-coding RNAs (lncRNAs) may play an essential role in Epithelial-Mesenchymal Transition (EMT), which is an important step in tumor metastasis; however, little is known about the global change of lncRNA transcriptome during EMT. To investigate how lncRNA transcriptome alterations contribute to EMT progression regulation, we deep-sequenced the whole-transcriptome of MCF10A as the cells underwent TGF-ß-induced EMT. RESULTS: Deep-sequencing results showed that the long RNA transcriptome of MCF10A had undergone global changes as early as 8h after treatment with TGF-ß. The expression of 3403 known and novel lncRNAs, and 570 known and novel circRNAs were altered during EMT. To identify the key lncRNA-regulator, we constructed the co-expression network and found all junction nodes in the network are lncRNAs. One junction node, RP6-65G23.5, was further verified as a key regulator of EMT. Intriguingly, we identified 216 clusters containing lncRNAs which were located in "gene desert" regions. The expressions of all lncRNAs in these clusters changed concurrently during EMT, strongly suggesting that these clusters might play important roles in EMT. Our study reveals a global reprogramming of lncRNAs transcriptome during EMT and provides clues for the future study of the molecular mechanism of EMT.
Subject(s)
Breast Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , High-Throughput Nucleotide Sequencing , RNA, Long Noncoding/biosynthesis , Breast Neoplasms/pathology , Cell Line, Tumor , Cellular Reprogramming/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Metastasis , RNA, Long Noncoding/genetics , Transcriptome/geneticsABSTRACT
BACKGROUND/AIMS: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca2+-activated K+ (BK) channels in offspring mesenteric arteries following prenatal hypoxia. METHODS: Pregnant rats were exposed to normoxic control (21% O2, Con) or hypoxic (10.5% O2, Hy) conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR. RESULTS: Prenatal hypoxia increased pressor responses and vasoconstrictions to phenylephrine in the offspring. Whole-cell currents density of BK channels and amplitude of spontaneous transient outward currents (STOCs), not the frequency, were significantly reduced in Hy vascular myocytes. The sensitivity of BK channels to voltage, Ca2+, and tamoxifen were reduced in Hy myocytes, whereas the number of channels per patch and the single-channel conductance were unchanged. Prenatal hypoxia impaired NS1102- and tamoxifen-mediated relaxation in mesenteric arteries precontracted with phenylephrine in the presence of Nω-nitro-L-arginine methyl ester. The mRNA and protein expression of BK channel ß1, not the α-subunit, was decreased in Hy mesenteric arteries. CONCLUSIONS: Impaired BK channel ß1-subunits in vascular smooth muscle cells contributed to vascular dysfunction in the offspring exposed to prenatal hypoxia.
Subject(s)
Fetal Hypoxia , Large-Conductance Calcium-Activated Potassium Channels/metabolism , Mesenteric Arteries/metabolism , Animals , Blood Pressure/drug effects , Down-Regulation , Female , Gestational Age , Large-Conductance Calcium-Activated Potassium Channels/genetics , Male , Membrane Potentials/drug effects , Mesenteric Arteries/cytology , Mesenteric Arteries/drug effects , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/physiology , Patch-Clamp Techniques , Peptides/pharmacology , Phenylephrine/pharmacology , Pregnancy , Protein Subunits/genetics , Protein Subunits/metabolism , Rats , Rats, Sprague-Dawley , Tamoxifen/pharmacology , Tetrazoles/pharmacology , Thiourea/analogs & derivatives , Thiourea/pharmacology , Vasoconstriction/drug effectsABSTRACT
Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group. Electrophysiological studies demonstrated that BKCa current density and single-channel current were reduced in the vascular smooth muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1 subunits in mesenteric arteries was decreased in the HS offspring, indicating that both activity and number of BKCa channels in HS offspring were reduced. Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated. Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was weakened and the reduced currents in the VSMCs were improved with altered protein kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit the offspring vascular BKCa channel activity via AKT pathway.
Subject(s)
Dietary Sucrose/adverse effects , Large-Conductance Calcium-Activated Potassium Channels/metabolism , Reactive Oxygen Species/metabolism , Animals , Blood Glucose/metabolism , Diet , Female , Large-Conductance Calcium-Activated Potassium Channels/biosynthesis , Male , Mesenteric Arteries/metabolism , Muscle, Smooth, Vascular/drug effects , NADPH Oxidase 4/metabolism , Oncogene Protein v-akt/metabolism , Peptides/pharmacology , Phenylephrine/pharmacology , Potassium Channel Blockers/pharmacology , Pregnancy , Prenatal Exposure Delayed Effects , Rats , Rats, Sprague-Dawley , Vasoconstrictor Agents/pharmacologyABSTRACT
BACKGROUND: Mechanical ventilation worsens acute respiratory distress syndrome, but this secondary "ventilator-associated" injury is variable and difficult to predict. The authors aimed to visualize the propagation of such ventilator-induced injury, in the presence (and absence) of a primary underlying lung injury, and to determine the predictors of propagation. METHODS: Anesthetized rats (n = 20) received acid aspiration (hydrochloric acid) followed by ventilation with moderate tidal volume (V(T)). In animals surviving ventilation for at least 2 h, propagation of injury was quantified by using serial computed tomography. Baseline lung status was assessed by oxygenation, lung weight, and lung strain (V(T)/expiratory lung volume). Separate groups of rats without hydrochloric acid aspiration were ventilated with large (n = 10) or moderate (n = 6) V(T). RESULTS: In 15 rats surviving longer than 2 h, computed tomography opacities spread outward from the initial site of injury. Propagation was associated with higher baseline strain (propagation vs. no propagation [mean ± SD]: 1.52 ± 0.13 vs. 1.16 ± 0.20, P < 0.01) but similar oxygenation and lung weight. Propagation did not occur where baseline strain was less than 1.29. In healthy animals, large V(T) caused injury that was propagated inward from the lung periphery; in the absence of preexisting injury, propagation did not occur where strain was less than 2.0. CONCLUSIONS: Compared with healthy lungs, underlying injury causes propagation to occur at a lower strain threshold and it originates at the site of injury; this suggests that tissue around the primary lesion is more sensitive. Understanding how injury is propagated may ultimately facilitate a more individualized monitoring or management.
Subject(s)
Lung/diagnostic imaging , Lung/physiopathology , Tomography, X-Ray Computed , Ventilator-Induced Lung Injury/diagnostic imaging , Ventilator-Induced Lung Injury/physiopathology , Acute Disease , Animals , Disease Models, Animal , Male , Rats , Rats, Sprague-Dawley , Respiratory Function Tests/statistics & numerical dataABSTRACT
There is increasing interest in both the cumulative and long-term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the impact of SES on neural development in children before age 2. This paper examines the effect of SES, indexed by income-to-needs (ITN) and maternal education, on cortical gray, deep gray, and white matter volumes in term, healthy, appropriate for gestational age, African-American, female infants. At 5 weeks postnatal age, unsedated infants underwent MRI (3.0T Siemens Verio scanner, 32-channel head coil). Images were segmented based on a locally constructed template. Utilizing hierarchical linear regression, SES effects on MRI volumes were examined. In this cohort of healthy African-American female infants of varying SES, lower SES was associated with smaller cortical gray and deep gray matter volumes. These SES effects on neural outcome at such a young age build on similar studies of older children, suggesting that the biological embedding of adversity may occur very early in development.
Subject(s)
Black or African American , Nervous System , Social Class , Child Development/physiology , Female , Gray Matter/growth & development , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Maternal Inheritance , Nervous System/growth & development , White Matter/growth & developmentABSTRACT
Mutations in the Aristaless-Related Homeobox (ARX) gene cause structural anomalies of the brain, epilepsy, and neurocognitive deficits in children. During forebrain development, Arx is expressed in both pallial and subpallial progenitor cells. We previously demonstrated that elimination of Arx from subpallial-derived cortical interneurons generates an epilepsy phenotype with features overlapping those seen in patients with ARX mutations. In this report, we have selectively removed Arx from pallial progenitor cells that give rise to the cerebral cortical projection neurons. While no discernable seizure activity was recorded, these mice exhibited a peculiar constellation of behaviors. They are less anxious, less social, and more active when compared with their wild-type littermates. The overall cortical thickness was reduced, and the corpus callosum and anterior commissure were hypoplastic, consistent with a perturbation in cortical connectivity. Taken together, these data suggest that some of the structural and behavioral anomalies, common in patients with ARX mutations, are specifically due to alterations in pallial progenitor function. Furthermore, our data demonstrate that some of the neurobehavioral features found in patients with ARX mutations may not be due to on-going seizures, as is often postulated, given that epilepsy was eliminated as a confounding variable in these behavior analyses.
Subject(s)
Brain Waves/genetics , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Mutation/genetics , Telencephalon/growth & development , Telencephalon/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Animals , Choice Behavior/physiology , Conditioning, Psychological/physiology , Dark Adaptation/genetics , Developmental Disabilities/genetics , Disease Models, Animal , Epilepsy/genetics , Exploratory Behavior/physiology , Gene Expression Regulation, Developmental/genetics , Humans , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Motor Activity/genetics , Muscle Strength/genetics , Phenotype , Smell/geneticsABSTRACT
Layered lithium-rich oxides have several serious shortcomings such as fast voltage fading and poor cyclic stability of energy density which greatly hinder their practical applications. Fabrication of a stable framework of layered lithium-rich oxides during charging-discharging is crucial for addressing the above problems. In this work, we show that Ti modification is a promising way to realize this target with bifunctional roles. For example, it is able to substitute Mn in the lattice framework and form a stable surface layer. It therefore leads to an improved retention of energy density of the Ti-modified Li1.2Mn0.54-xTixNi0.13Co0.13O2 (x = 0.04, 0.08, and 0.15) materials during cycling. The evolution of dQ/dV curves show that the layered/spinel phase transformation is suppressed owing to the introduction of strong Ti-O bonds in the framework. In addition, SEM, TEM, and EIS results confirm that a more uniform and stable interface layer is formed on Ti-modified Li1.2Mn0.54-xTixNi0.13Co0.13O2 (x = 0.04, 0.08, and 0.15) materials compared with the Ti-free counterpart. The stable interface layer on the lithium-rich oxides is also beneficial for further reducing side reactions, resulting in stable interface layer resistance. Therefore, the improved cycling performance of the material is due to both contribution of the more stable framework and enhanced electrode/electrolyte interface by Ti modification.
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OBJECTIVE: Visualizing implanted subdural electrodes in three-dimensional (3D) space can greatly aid in planning, executing, and validating resection in epilepsy surgery. Coregistration software is available, but cost, complexity, insufficient accuracy, or validation limit adoption. We present a fully automated open-source application, based on a novel method using postimplant computerized tomography (CT) and postimplant magnetic resonance (MR) images, for accurately visualizing intracranial electrodes in 3D space. METHODS: CT-MR rigid brain coregistration, MR nonrigid registration, and prior-based segmentation were carried out on seven patients. Postimplant CT, postimplant MR, and an external labeled atlas were then aligned in the same space. The coregistration algorithm was validated by manually marking identical anatomic landmarks on the postimplant CT and postimplant MR images. Following coregistration, distances between the center of the landmark masks on the postimplant MR and the coregistered CT images were calculated for all subjects. Algorithms were implemented in open-source software and translated into a "drag and drop" desktop application for Apple Mac OS X. RESULTS: Despite postoperative brain deformation, the method was able to automatically align intrasubject multimodal images and segment cortical subregions, so that all electrodes could be visualized on the parcellated brain. Manual marking of anatomic landmarks validated the coregistration algorithm with a mean misalignment distance of 2.87 mm (standard deviation 0.58 mm)between the landmarks. Software was easily used by operators without prior image processing experience. SIGNIFICANCE: We demonstrate an easy to use, novel platform for accurately visualizing subdural electrodes in 3D space on a parcellated brain. We rigorously validated this method using quantitative measures. The method is unique because it involves no preprocessing, is fully automated, and freely available worldwide. A desktop application, as well as the source code, are both available for download on the International Epilepsy Electrophysiology Portal (https://www.ieeg.org) for use and interactive refinement.
Subject(s)
Brain/pathology , Electronic Data Processing , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Subdural Space/pathology , Tomography, X-Ray Computed , Adult , Electrodes , Epilepsy/diagnosis , Female , Humans , Male , Young AdultABSTRACT
Chloroplast genomes, as an essential source of phylogenetic information, are increasingly utilized in the evolutionary study of angiosperms. Gnaphalieae is a medium-sized tribe of the sunflower family of Asteraceae, with about 2,100 species in 178 genera distributed in temperate habitats worldwide. There has been considerable progress in our understanding of their phylogenetic evolution using both nuclear and chloroplast sequences, but no focus on chloroplast genomic data. In this study, we performed sequencing, assembly, and annotation of 16 representative chloroplast genomes from all the major lineages of Gnaphalieae. Our results showed that the plastomes exhibited a typical circular tetrad structure with similar genomic structure gene content. But there were differences in genome size, SSRs, and codon usage within the tribe. Phylogenetic analysis revealed Relhania clade is the earliest diverged lineages with the Lasiopogon clade and the Gnaphalium s.s. clade diverged subsequently. The core group includes FLAG clade sister to the HAP and Australasian group. Compared with the outgroup species, chloroplast genome size of the FLAG clade is much reduced whereas those of Australasian, HAP, Gnaphalium s.s., Lasiopogon and Relhania clades are relatively expanded. Insertions and deletions in the intergenic regions associated with repetitive sequence variations are supposed to be the main factor leading to length variations in the chloroplast genomes of Gnaphalieae. The comparative analyses of chloroplast genomes would provide useful implications into understanding the taxonomic and evolutionary history of Gnaphalieae.
Subject(s)
Asteraceae , Genome, Chloroplast , Asteraceae/genetics , Phylogeny , Repetitive Sequences, Nucleic Acid , ChloroplastsABSTRACT
Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.
ABSTRACT
BACKGROUND: In this study, we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis (LN) who underwent repeated renal biopsy. CASE SUMMARY: Clinical data of three diffuse proliferative LN patients with different pathological characteristics (case 1 was LN IV-G (A), case 2 was LN IV-G (A) + V, and case 3 was LN IV-G (A) + thrombotic microangiopathy) were reviewed. All patients underwent repeated renal biopsies 6 mo later, and renal biopsy specimens were studied. Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining, and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage. After treatment, Case 1 changed to LN III-(A), Case 2 remained as type V LN lesions, and Case 3, which changed to LN IV-S (A), had the worst prognosis. We observed reduced macrophage infiltration after therapy. However, two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium. Before treatment, the three patients showed discontinuous expression of podocin. Notably, the integrity of podocin was restored after treatment in Case 1. CONCLUSION: It may be possible to reverse podocyte damage and decrease the infiltrating macrophages in LN patients through effective treatment.
ABSTRACT
PURPOSE: To develop a valid, reliable, and simple-to-use semiquantitative visual scale of fetal brain maturation for use in clinical fetal MR imaging assessment and interpretation. MATERIALS AND METHODS: This is a retrospective assessment of data from a previous study that was prospective, institutional review board approved, and HIPAA compliant. Forty-eight normal pregnancies with a gestational age (GA) of 25 to 35 weeks were studied. A fetal total maturation score (fTMS) was developed by utilizing six subscores that evaluated cortical sulcation, myelination, and the germinal matrix and provided a single combined numerical value to be evaluated as a marker of brain maturity. The fTMS was correlated with GA and segmented brain volume. A regression model that associated GA based on the visual fTMS scoring was determined. The model was validated with a leave-one-out cross validation procedure. RESULTS: Mean GA was 29.3 weeks ± 2.9 (standard deviation) (range, 25.2-35.3 weeks) and mean fTMS was 8.6 ± 3.7 (range, 4-16). The intraclass correlation coefficient between the three readers (independent and blinded) was 0.948 (P < .001). The correlations were as follows: GA and brain volume, r = 0.964 (P < .001); fTMS and brain volume, r = 0.970 (P < .001); and GA and fTMS, r = 0.975 (P < .001). A regression model to calculate GA based on fTMS yielded the following equation: calculated GA (weeks) = 22.86 + 0.748 fTMS (P < .001; adjusted R(2) = 0.946). The standard error of the model for calculation of fetal GA from the visual fTMS scale was ± 4.8 days. CONCLUSION: If validated further, the fTMS scale might be used to assess morphologic brain maturity of fetuses between 25 and 35 weeks GA on a single-case basis in a clinical setting.
Subject(s)
Brain Mapping/methods , Brain/embryology , Magnetic Resonance Imaging/methods , Case-Control Studies , Female , Gestational Age , Heart Defects, Congenital , Humans , Longitudinal Studies , Male , Pregnancy , Regression Analysis , Retrospective StudiesABSTRACT
Childhood socioeconomic status (SES) predicts executive function performance and measures of prefrontal cortical function, but little is known about its anatomical correlates. Structural MRI and demographic data from a sample of 283 healthy children from the NIH MRI Study of Normal Brain Development were used to investigate the relationship between SES and prefrontal cortical thickness. Specifically, we assessed the association between two principal measures of childhood SES, family income and parental education, and gray matter thickness in specific subregions of prefrontal cortex and on the asymmetry of these areas. After correcting for multiple comparisons and controlling for potentially confounding variables, parental education significantly predicted cortical thickness in the right anterior cingulate gyrus and left superior frontal gyrus. These results suggest that brain structure in frontal regions may provide a meaningful link between SES and cognitive function among healthy, typically developing children.