ABSTRACT
Pioneer transcription factors (TFs) like SOX2 are vital for stemness and cancer through enhancing gene expression within transcriptional condensates formed with coactivators, RNAs and mediators on super-enhancers (SEs). Despite their importance, how these factors work together for transcriptional condensation and activation remains unclear. SOX2, a pioneer TF found in SEs of pluripotent and cancer stem cells, initiates SE-mediated transcription by binding to nucleosomes, though the mechanism isn't fully understood. To address SOX2's role in SEs, we identified mSE078 as a model SOX2-enriched SE and p300 as a coactivator through bioinformatic analysis. In vitro and cell assays showed SOX2 forms condensates with p300 and SOX2-binding motifs in mSE078. We further proved that SOX2 condensation is highly correlated with mSE078's enhancer activity in cells. Moreover, we successfully demonstrated that p300 not only elevated transcriptional activity but also triggered chromatin acetylation via its direct interaction with SOX2 within these transcriptional condensates. Finally, our validation of SOX2-enriched SEs showcased their contribution to target gene expression in both stem cells and cancer cells. In its entirety, this study imparts valuable mechanistic insights into the collaborative interplay of SOX2 and its coactivator p300, shedding light on the regulation of transcriptional condensation and activation within SOX2-enriched SEs.
Subject(s)
Pluripotent Stem Cells , Transcription Factors , Chromatin/genetics , Enhancer Elements, Genetic , Nucleosomes , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Humans , Pluripotent Stem Cells/metabolismABSTRACT
BACKGROUND: Food allergy (FA) often occurs in early childhood with and without atopic dermatitis (AD). FA can be severe and even fatal. For primary prevention, it is important to find early biomarkers to predict the future onset of FA before any clinical manifestations. OBJECTIVE: Our aim was to find early predictors of future onset of FA in the stratum corneum (SC). METHODS: Skin tape strips were collected from the forearm of newborns (n = 129) at age 2 months, before any signs of clinical FA or AD. Children were clinically monitored until they reached age 2 years to confirm the presence or absence of FA and AD. Skin tape strips were subjected to lipidomic analyses by liquid chromatography-tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. RESULTS: Overall, 9 of 129 infants (7.0%) developed FA alone and 9 of 129 infants (7.0%) developed FA concomitantly with AD. In the stratum corneum of children with future FA and concomitant AD and FA, absolute amounts of unsaturated (N24:1)(C18-sphingosine)ceramide and (N26:1)(C18-sphingosine)ceramide and their relative percentages within the molecular group were increased compared with the amounts and percentages in healthy children, with P values ranging from less than .01 to less than .05 according to ANOVA. The children with future AD had normal levels of these molecules. IL-33 level was upregulated in those infants with future FA but not in those with future AD, whereas thymic stromal lymphopoietin was upregulated in those with future AD but not in those with future FA. Logistic regression analysis revealed strong FA predicting power for the combination of dysregulated lipids and cytokines, with an odds ratio reaching 101.4 (95% CI = 5.4-1910.6). CONCLUSION: Noninvasive skin tape strip analysis at age 2 months can identify infants at risk of FA in the future.
Subject(s)
Biomarkers , Cytokines , Dermatitis, Atopic , Food Hypersensitivity , Humans , Infant , Food Hypersensitivity/immunology , Food Hypersensitivity/diagnosis , Male , Female , Dermatitis, Atopic/immunology , Dermatitis, Atopic/metabolism , Cytokines/metabolism , Infant, Newborn , Skin/immunology , Skin/metabolism , Child, Preschool , Ceramides/metabolism , Ceramides/analysisABSTRACT
Nuclear magnetic resonance (NMR) plays a central role in the elucidation of chemical structures but is often limited by low sensitivity. Dissolution dynamic nuclear polarization (dDNP) emerges as a transformative methodology for both solution-state NMR and metabolic NMR imaging, which could overcome this limitation. Typically, dDNP relies on combining a stable radical with the analyte within a uniform glass under cryogenic conditions. The electron polarization is then transferred through microwave irradiation to the nuclei. The present study explores the use of radicals introduced via γ-irradiation, as bearers of the electron spins that will enhance 1H or 13C nuclides. 1H solid-state NMR spectra of γ-irradiated powders at 1-5 K revealed, upon microwave irradiation, signal enhancements that, in general, were higher than those achieved through conventional glass-based DNP. Transfer of these samples to a solution-state NMR spectrometer via a rapid dissolution driven by a superheated water provided significant enhancements of solution-state 1H NMR signals. Enhancements of 13C signals in the γ-irradiated solids were more modest, as a combined consequence of a low radical concentration and of the dilute concentration of 13C in the natural abundant samples examined. Nevertheless, ca. 700-800-fold enhancements in 13C solution NMR spectra of certain sites recorded at 11.7 T could still be achieved. A total disappearance of the radicals upon performing a dDNP-like aqueous dissolution and a high stability of the samples were found. Overall, the study showcases the advantages and limitations of γ-irradiated radicals as candidates for advancing spectroscopic dDNP-enhanced NMR.
ABSTRACT
Owing to the wavelength-dependent limits of the deep ultraviolet exposure process, the semiconductor industry introduced extreme ultraviolet (EUV) lithography operating at a 13.5 nm wavelength. Traditional photomasks employ pellicles for protection; however, EUV-specific pellicles are not widely applicable to commercial processes, requiring the development of a EUV photomask cleaning method. In this study, a wet cleaning method for Ta-based EUV photomasks at room temperature was systematically examined in terms of key parameters, including the pattern step height, surface topography, and particulate count, via atomic force microscopy and x-ray reflectivity. Post sulfuric acid-hydrogen peroxide mixture (SPM) treatment, the photomask exhibited a stable step height, indicating minimal pattern degradation. Additionally, discernible alterations in the surface roughness and a decrease in particle count were observed, further indicating to the effectiveness of SPM-mediated cleaning. Conversely, following standard clean-1 (SC-1) treatment, while the pattern step height remained relatively unchanged, a notable increase in surface irregularities and macroscopic particulates was observed, suggesting a suboptimal cleaning efficiency of the SC-1 solution despite its potential for pattern structure preservation. Our room temperature wet cleaning method efficiently reduces wear-out and successfully eliminates contaminants, potentially prolonging the EUV photomask's productivity and durability.
ABSTRACT
BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.
Subject(s)
Carcinoma , Epstein-Barr Virus Infections , Stomach Neoplasms , Female , Humans , Male , Stomach Neoplasms/pathology , Herpesvirus 4, Human , Prognosis , Carcinoma/complicationsABSTRACT
Research in neuroscience often assumes universal neural mechanisms, but increasing evidence points toward sizeable individual differences in brain activations. What remains unclear is the extent of the idiosyncrasy and whether different types of analyses are associated with different levels of idiosyncrasy. Here we develop a new method for addressing these questions. The method consists of computing the within-subject reliability and subject-to-group similarity of brain activations and submitting these values to a computational model that quantifies the relative strength of group- and subject-level factors. We apply this method to a perceptual decision-making task (n = 50) and find that activations related to task, reaction time, and confidence are influenced equally strongly by group- and subject-level factors. Both group- and subject-level factors are dwarfed by a noise factor, though higher levels of smoothing increases their contributions relative to noise. Overall, our method allows for the quantification of group- and subject-level factors of brain activations and thus provides a more detailed understanding of the idiosyncrasy levels in brain activations.
Subject(s)
Brain , Magnetic Resonance Imaging , Reproducibility of Results , Magnetic Resonance Imaging/methods , Brain/physiology , Brain Mapping/methods , Mental ProcessesABSTRACT
The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82 and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.
Subject(s)
Chromosomal Proteins, Non-Histone , Nuclear Proteins , RNA, Antisense , Transcription, Genetic , Transcriptional Elongation Factors , Humans , Chromosomal Proteins, Non-Histone/metabolism , Nuclear Proteins/metabolism , Phosphorylation , RNA Polymerase II/genetics , RNA Polymerase II/metabolism , RNA, Antisense/genetics , RNA, Antisense/metabolism , Transcription Factors/metabolism , Transcriptional Elongation Factors/metabolismABSTRACT
Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.
Subject(s)
Food Hypersensitivity , Quality of Life , Child , Humans , Food Hypersensitivity/therapy , Food , Diphenhydramine , Immunotherapy , ParentsABSTRACT
Life-threatening airway obstruction is a major concern in patients with Pierre-Robin sequence. Tongue-lip adhesion (TLA) has been used to manage airway obstruction. The authors present the case of a female neonate with Pierre-Robin sequence who presented with airway obstruction and a cleft palate. She underwent a TLA procedure with modified tongue base suspension (TBS). Endoscopy was used to check and control the traction of the tongue base to enable unobstructed self-ventilation. Positive outcomes including improved O2 saturation and weight gain were noted. The effectiveness of TLA was enhanced by using TBS with real-time endoscopy to evaluate the oropharyngeal airway space required to alleviate airway obstruction. The use of endoscopy enabled us to check and determine how much the tongue base should be tracted by manipulating the tongue anteriorly and posteriorly. The authors report transoral endoscopy-assisted TLA and modified TBS.
Subject(s)
Airway Obstruction , Larynx , Pierre Robin Syndrome , Infant, Newborn , Humans , Female , Pierre Robin Syndrome/surgery , Tongue/surgery , Endoscopy , Treatment OutcomeABSTRACT
BACKGROUND: Atopic dermatitis (AD) commonly occurs in children and can progress into severe phenotypes or atopic march, causing significant impairment in quality of life. It is important to find early biomarkers of future onset of AD before any clinical manifestations. OBJECTIVE: We sought to find early predictors of future onset of AD in skin stratum corneum (SC). METHODS: Skin tape strips were collected from the forearm of newborns (n = 111) with and without family history of atopic diseases at the age of 2 months before any signs of clinical AD. Children were clinically monitored until they reached age 2 years to ensure the presence or absence of AD. Skin tape strips were subjected to lipidomic analyses by the liquid chromatography electrospray ionization tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. RESULTS: Overall, 22 of 74 (29.7%) and 5 of 37 (13.5%) infants developed AD in the risk group and the control group, respectively. In the SC of future AD children, protein-bound ceramides were decreased (P < .001), whereas unsaturated sphingomyelin species (P < .0001) and "short-chain" nonhydroxy fatty acid sphingosine and alpha-hydroxy fatty acid sphingosine ceramides were elevated (P < .01 and .05, respectively) as compared with healthy children. Thymic stromal lymphopoietin and IL-13 levels were increased in the SC of future AD subjects (by 74.5% and 78.3%, P = .0022 and P < .0001, respectively). Multivariable logistic regression analysis revealed strong AD predicting power of the combination of family history, type 2 cytokines, and dysregulated lipids, with an odds ratio reaching 54.0 (95% CI, 9.2-317.5). CONCLUSIONS: Noninvasive skin tape strip analysis at age 2 months can identify asymptomatic children at risk of future AD development with a high probability.
Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/diagnosis , Cytokines/analysis , Sphingosine , Quality of Life , Skin/chemistry , Ceramides , Fatty Acids , Biomarkers/analysisABSTRACT
In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure to air pollutants can occur during breathing, posing a considerable risk to those with environmental health vulnerabilities. Among vulnerable individuals, maternal exposure can negatively impact the mother and child in utero. The developing fetus is particularly vulnerable to environmentally hazardous substances, with potentially greater implications. Among air pollutants, toluene is neurotoxic, and its effects have been widely explored. However, the impact of low-level toluene exposure in daily life remains unclear. Herein, we evaluated 194 mothers and infants from the Growing children's health and Evaluation of Environment (GREEN) cohort to determine the possible effects of early-life toluene exposure on the nervous system. Using Omics experiments, the effects of toluene were confirmed based on epigenetic changes and altered mRNA expression. Various epigenetic changes were identified, with upregulated expression potentially contributing to diseases such as glioblastoma and Alzheimer's, and downregulated expression being associated with structural neuronal abnormalities. These findings were detected in both maternal and infant groups, suggesting that maternal exposure to environmental hazardous substances can negatively impact the fetus. Our findings will facilitate the establishment of environmental health policies, including the management of environmentally hazardous substances for vulnerable groups.
Subject(s)
Maternal Exposure , Toluene , Humans , Toluene/toxicity , Female , Infant , Maternal Exposure/adverse effects , Pregnancy , Adult , Nervous System/drug effects , Nervous System/embryology , Nervous System/metabolism , Nervous System/growth & development , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Epigenesis, Genetic/drug effects , Male , Mothers , Air Pollutants/toxicity , Infant, NewbornABSTRACT
Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.
Subject(s)
Dermatitis, Atopic , Phenols , Pregnant Women , Humans , Female , Pregnancy , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/genetics , Phosphatidylinositol 3-Kinases , Leukocytes, Mononuclear , DNA Methylation , Benzhydryl Compounds/toxicity , Epigenesis, GeneticABSTRACT
Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of the M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. The oslrr-rlp2 mutant, generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.
Subject(s)
Ascomycota , Magnaporthe , Oryza , Magnaporthe/physiology , Plant Breeding , Proteins/metabolism , Disease Resistance/genetics , Leucine-Rich Repeat Proteins , Oryza/microbiology , Plant Diseases/microbiology , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
BACKGROUND: Wheat allergy is one of the most prevalent allergens in Korea, decreasing quality of life and causing nutritional repercussions. OBJECTIVE: We aimed to investigate the efficacy and safety of the home-based wheat oral immunotherapy (OIT) using wheat noodles in children with a wheat allergy. METHODS: We conducted a retrospective study involving 72 children aged 3 to 17 years diagnosed with a wheat allergy. Patients received wheat OIT using wheat noodles (n = 50) and were compared with a historical control group (n = 22). Baseline characteristics, adverse events, and immunological changes were assessed. Predictors of successful desensitization were identified using logistic regression analysis. RESULTS: Among 50 patients completing the up-dosing phase, 82.0% achieved desensitization to 2,400 mg of wheat protein, compared to 4.5% in the control group (p < 0.001). During the up-dosing period, the median number of adverse reactions per person was 2, and anaphylaxis occurred in 30.0% (15/50). However, there were no life-threatening adverse events. In multivariable analysis, the presence of asthma (adjusted odds ratio [aOR], 8.88; 95% confidence interval [CI], 1.10-71.97; p = 0.041) and a higher ratio of specific IgE (sIgE) to ω-5-gliadin and total IgE (aOR 19.09, 95%CI 1.21-300.80, p = 0.036) were significantly associated with treatment outcomes of wheat OIT. CONCLUSION: Our study showed the safety and efficacy of home-based wheat OIT using boiled noodles in Korean children with wheat allergies. Careful consideration is warranted for patients with elevated baseline sIgE to ω-5-gliadin to total IgE ratio and a history of asthma.
ABSTRACT
Magnetization transfer experiments are versatile nuclear magnetic resonance (NMR) tools providing site-specific information. We have recently discussed how saturation magnetization transfer (SMT) experiments could leverage repeated repolarizations arising from exchanges between labile and water protons to enhance connectivities revealed via the nuclear Overhauser effect (NOE). Repeated experience with SMT has shown that a number of artifacts may arise in these experiments, which may confound the information being sought - particularly when seeking small NOEs among closely spaced resonances. One of these pertains to what we refer to as "spill-over" effects, originating from the use of long saturation pulses leading to changes in the signals of proximate peaks. A second, related but in fact different effect, derives from what we describe as NOE "oversaturation", a phenomenon whereby the use of overtly intense RF fields overwhelms the cross-relaxation signature. The origin and ways to avoid these two effects are described. A final source of potential artifact arises in applications where the labile 1Hs of interest are bound to 15N-labeled heteronuclei. SMT's long 1H saturation times will then be usually implemented while under 15N decoupling based on cyclic schemes leading to decoupling sidebands. Although these sidebands usually remain invisible in NMR, they may lead to a very efficient saturation of the main resonance when touched by SMT frequencies. All of these phenomena are herein experimentally demonstrated, and solutions to overcome them are proposed.
ABSTRACT
The Children's Oncology Group AHOD0831 study used a positron emission tomography (PET) response-adapted approach in high-risk Hodgkin lymphoma, whereby slow early responders (SERs) received more intensive therapy than rapid early responders (RERs). We explored if baseline PET-based characteristics would improve risk stratification. Of 166 patients enrolled in the COG AHOD0831 study, 94 (57%) had baseline PET scans evaluable for quantitative analysis. For these patients, total body metabolic tumour volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax ) and peak SUV (SUVpeak ) were obtained. MTV/TLG thresholds were an SUV of 2.5 (MTV2.5 /TLG2.5 ) and 40% of the tumour SUVmax (MTV40% /TLG40% ). TLG2.5 was associated with event-free survival (EFS) in the complete cohort (p = 0.04) and in RERs (p = 0.01), but not in SERs (p = 0.8). The Youden index cut-off for TLG2.5 was 1841. Four-year EFS was 92% for RER/TLG2.5 up to 1841, 60% for RER/TLG2.5 greater than 1841, 74% for SER/TLG2.5 up to 1841 and 79% for SER/TLG2.5 greater than 1841. Second EFS for RER/TLG2.5 up to 1841 was 100%. Thus, RERs with a low baseline TLG2.5 experienced excellent EFS with less intensive therapy, whereas RERs with a high baseline TLG2.5 experienced poor EFS. These findings suggest that patients with a high upfront tumour burden may benefit from intensified therapy, even if they achieve a RER.
Subject(s)
Hodgkin Disease , Humans , Child , Hodgkin Disease/diagnostic imaging , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Tumor Burden , Fluorodeoxyglucose F18/metabolism , Positron-Emission Tomography/methods , Risk Assessment , Prognosis , Retrospective Studies , Radiopharmaceuticals , Positron Emission Tomography Computed Tomography , GlycolysisABSTRACT
2D NOESY and TOCSY play central roles in contemporary NMR. We have recently discussed how solvent-driven exchanges can significantly enhance the sensitivity of such methods when attempting correlations between labile and nonlabile protons. This study explores two scenarios where similar sensitivity enhancements can be achieved in the absence of solvent exchange: the first one involves biomolecular paramagnetic systems, while the other involves small organic molecules in natural abundance. It is shown that, in both cases, the effects introduced by either differential paramagnetic shift and relaxation or by polarization sharing among networks of protons can provide a similar sensitivity boost, as previously discussed for solvent exchange. The origin and potential of the resulting enhancements are analyzed, and experiments that demonstrate them in protein and natural products are exemplified. Limitations and future improvements of these approaches are also briefly discussed.
ABSTRACT
The magnetic anisotropy of low-dimensional Mott systems exhibits unexpected magnetotransport behavior useful for spin-based quantum electronics. Yet, the anisotropy of natural materials is inherently determined by the crystal structure, highly limiting its engineering. The magnetic anisotropy modulation near a digitized dimensional Mott boundary in artificial superlattices composed of a correlated magnetic monolayer SrRuO3 and nonmagnetic SrTiO3 , is demonstrated. The magnetic anisotropy is initially engineered by modulating the interlayer coupling strength between the magnetic monolayers. Interestingly, when the interlayer coupling strength is maximized, a nearly degenerate state is realized, in which the anisotropic magnetotransport is strongly influenced by both the thermal and magnetic energy scales. The results offer a new digitized control for magnetic anisotropy in low-dimensional Mott systems, inspiring promising integration of Mottronics and spintronics.
ABSTRACT
The origin of the partial suppression of the electronic density states in the enigmatic pseudogap behavior, which is at the core of understanding high-T_{c} superconductivity, has been hotly contested as either a hallmark of preformed Cooper pairs or an incipient order of competing interactions nearby. Here, we report the quasiparticle scattering spectroscopy of the quantum critical superconductor CeCoIn_{5}, where a pseudogap with energy Δ_{g} was manifested as a dip in the differential conductance (dI/dV) below the characteristic temperature of T_{g}. When subjected to external pressure, T_{g} and Δ_{g} gradually increase, following the trend of increase in quantum entangled hybridization between the Ce 4f moment and conduction electrons. On the other hand, the superconducting (SC) energy gap and its phase transition temperature shows a maximum, revealing a dome shape under pressure. The disparate dependence on pressure between the two quantum states shows that the pseudogap is less likely involved in the formation of SC Cooper pairs, but rather is controlled by Kondo hybridization, indicating that a novel type of pseudogap is realized in CeCoIn_{5}.
ABSTRACT
BACKGROUND: Staphylococcus (S) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how S. aureus induces aberrant epidermal lipid composition and skin barrier dysfunction. METHODS: Skin tape strips (STS) and swabs were obtained from 24 children with AD (6.0 ± 4.4 years) and 16 healthy children (7.0 ± 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. Skin levels of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) were evaluated. The effects of MSSA and MRSA were evaluated in primary human keratinocytes (HEKs) and organotypic skin cultures. RESULTS: AD and organotypic skin colonized with MRSA significantly increased the proportion of lipid species with nonhydroxy fatty acid sphingosine ceramide with palmitic acid ([N-16:0 NS-CER], sphingomyelins [16:0-18:0 SM]), and lysophosphatidylcholines [16:0-18:0 LPC], but significantly reduced the proportion of corresponding very long-chain fatty acids (VLCFAs) species (C22-28) compared to the skin without S. aureus colonization. Significantly increased transepidermal water loss (TEWL) was found in MRSA-colonized AD skin. S. aureus indirectly through interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and IL-33 inhibited expression of fatty acid elongase enzymes (ELOVL3 and ELOVL4) in HEKs. ELOVL inhibition was more pronounced by MRSA and resulted in TEWL increase in organotypic skin. CONCLUSION: Aberrant skin lipid profiles and barrier dysfunction are associated with S. aureus colonization in AD patients. These effects are attributed to the inhibition of ELOVLs by S. aureus-induced IL-1ß, TNF-α, IL-6, and IL-33 seen in keratinocyte models and are more prominent in MRSA than MSSA.