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1.
Hum Genet ; 143(3): 233-261, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38421405

ABSTRACT

The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the temporal response to lipopolysaccharide (LPS). However, the basal or LPS-inducible expression of individual genes varied independently by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) in macrophages was associated with HLA genotype. Correlation analysis indicated the downstream impacts of variation in the immediate early response to LPS. For example, variation in early expression of IL1B was significantly associated with local SNV genotype and with subsequent peak expression of target genes including IL23A, CXCL1, CXCL3, CXCL8 and NLRP3. Similarly, variation in early IFNB1 expression was correlated with subsequent expression of IFN target genes. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu is associated with genetic susceptibility to IBD.


Subject(s)
Genetic Predisposition to Disease , Inflammatory Bowel Diseases , Lipopolysaccharides , Macrophages , Humans , Inflammatory Bowel Diseases/genetics , Macrophages/metabolism , Macrophages/immunology , Lipopolysaccharides/pharmacology , Male , Genome-Wide Association Study , Female , Gene Expression Regulation , Genotype , Transcriptome
2.
ACS Appl Energy Mater ; 5(11): 13971-13980, 2022 Nov 28.
Article in English | MEDLINE | ID: mdl-36465259

ABSTRACT

Zn1-x Sn x O y (ZTO) deposited by atomic layer deposition has shown promising results as a buffer layer material for kesterite Cu2ZnSnS4 (CZTS) thin film solar cells. Increased performance was observed when a ZTO buffer layer was used as compared to the traditional CdS buffer, and the performance was further increased after an air annealing treatment of the absorber. In this work, we study how CZTS absorber surface treatments may influence the chemical and electronic properties at the ZTO/CZTS interface and the reactions that may occur at the absorber surface prior to atomic layer deposition of the buffer layer. For this, we have used a combination of microscopy and synchrotron-based spectroscopies with variable information depths (X-ray photoelectron spectroscopy, high-energy X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy), allowing for an in-depth analysis of the CZTS near-surface regions and bulk material properties. No significant ZTO buffer thickness variation is observed for the differently treated CZTS absorbers, and no differences are observed when comparing the bulk properties of the samples. However, the formation of SnO x and compositional changes observed toward the CZTS surface upon an air annealing treatment may be linked to the modified buffer layer growth. Further, the results indicate that the initial N2 annealing step integrated in the buffer layer growth by atomic layer deposition, which removes Na-CO x species from the CZTS surface, may be useful for the ZTO/CZTS device performance.

3.
ACS Appl Energy Mater ; 5(1): 461-468, 2022 Jan 24.
Article in English | MEDLINE | ID: mdl-35098042

ABSTRACT

Ag alloying and the introduction of alkali elements through a postdeposition treatment are two approaches to improve the performance of Cu(In,Ga)Se2 (CIGS) thin film solar cells. In particular, a postdeposition treatment of an alkali metal fluoride of the absorber has shown a beneficial effect on the solar cells performance due to an increase in the open circuit voltage (V OC) for both (Ag,Cu)(In,Ga)Se2 (ACIGS) and CIGS based solar cells. Several reasons have been suggested for the improved V OC in CIGS solar cells including absorber surface and interface effects. Less works investigated how the applied postdeposition treatment influences the ACIGS absorber surface and interface properties and the subsequent buffer layer growth. In this work we employed hard X-ray photoelectron spectroscopy to study the chemical and electronic properties at the real functional interface between a CdS buffer and ACIGS absorbers that have been exposed to different alkali metal fluoride treatments during preparation. All samples show an enhanced Ag content at the CdS/ACIGS interface as compared to ACIGS bulk-like composition, and it is also shown that this enhanced Ag content anticorrelates with Ga content. The results indicate that the absorber composition at the near-surface region changes depending on the applied alkali postdeposition treatment. The Cu and Ga decrease and the Ag increase are stronger for the RbF treatment as compared to the CsF treatment, which correlates with the observed device characteristics. This suggests that a selective alkali postdeposition treatment could change the ACIGS absorber surface composition, which can influence the solar cell behavior.

4.
Pharmacol Res ; 148: 104344, 2019 10.
Article in English | MEDLINE | ID: mdl-31400403

ABSTRACT

The inflammatory bowel diseases (IBDs) are chronic inflammatory conditions, which are increasing in prevalence worldwide. The IBDs are thought to result from an aberrant immune response to gut microbes in genetically susceptible individuals. Dysbiosis of the gut microbiome, both functional and compositional, promotes patient susceptibility to colonization by pathobionts. Manipulating gut microbial communities and gut microbiota-immune system interactions to restore gut homeostasis or reduce inflammation are appealing therapeutic models. We discuss the therapeutic potential of precision microbiota editing, natural and engineered probiotics, the use of gut microbiota-derived metabolites in colitogenic phenotypes, and intestinal stem cells, in maintaining gut microbiota balance, restoring the mucosal barrier, and having positive immunomodulatory effects in experimental IBD. This review highlights that we are only just beginning to understand the complexity of the microbiota and how it can be manipulated for health benefits, including treatment and prevention of the clinical IBDs in future.


Subject(s)
Gastrointestinal Microbiome/physiology , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/therapy , Animals , Gastrointestinal Microbiome/immunology , Humans , Immune System/drug effects , Inflammation/immunology , Inflammation/microbiology , Inflammation/therapy , Inflammatory Bowel Diseases/immunology , Probiotics/therapeutic use
5.
Phys Rev Lett ; 107(3): 036102, 2011 Jul 15.
Article in English | MEDLINE | ID: mdl-21838378

ABSTRACT

From an interplay of atom-resolved noncontact atomic force microscopy, surface x-ray diffraction experiments, and density functional theory calculations, we reveal the detailed atomic-scale structure of the (100) surface of an insulating ternary metal oxide, MgAl2O4 (spinel). We surprisingly find that the MgAl2O4(100) surface is terminated by an Al and O-rich structure with a thermodynamically favored amount of Al atoms interchanged with Mg. This finding implies that so-called Mg-Al antisites, which are defects in the bulk of MgAl2O4, become a thermodynamically stable and integral part of the surface.

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