| 1. |
|
|
| 2. |
- Amare, Azmeraw, et al.
(författare)
-
Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
-
Ingår i: Research square. - : Research Square Platform LLC.
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
|
|
| 3. |
- Amare, Azmeraw T, et al.
(författare)
-
Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
-
Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
|
|
| 4. |
- Betker, Marie, et al.
(författare)
-
Sprayed Hybrid Cellulose Nanofibril-Silver Nanowire Transparent Electrodes for Organic Electronic Applications
- 2023
-
Ingår i: ACS Applied Nano Materials. - : American Chemical Society (ACS). - 2574-0970. ; 6:14, s. 13677-13688
-
Tidskriftsartikel (refereegranskat)abstract
- In times of climate change and resource scarcity, researchers are aiming to find sustainable alternatives to synthetic polymers for the fabrication of biodegradable, eco-friendly, and, at the same time, high-performance materials. Nanocomposites have the ability to combine several favorable properties of different materials in a single device. Here, we evaluate the suitability of two kinds of inks containing silver nanowires for the fast, facile, and industrial-relevant fabrication of two different types of cellulose-based silver nanowire electrodes via layer-by-layer spray deposition only. The Type I electrode has a layered structure, which is composed of a network of silver nanowires sprayed on top of a cellulose nanofibrils layer, while the Type II electrode consists of a homogeneous mixture of silver nanowires and cellulose nanofibrils. A correlation between the surface structure, conductivity, and transparency of both types of electrodes is established. We use the Haacke figure of merit for transparent electrode materials to demonstrate the favorable influence of cellulose nanofibrils in the spray ink by identifying Type II as the electrode with the lowest sheet resistance (minimum 5 ± 0.04 Ω/sq), while at the same time having a lower surface roughness and shorter fabrication time than Type I. Finally, we prove the mechanical stability of the Type II electrode by bending tests and its long-time stability under ambient conditions. The results demonstrate that the mixed spray ink of silver nanowires and cellulose nanofibrils is perfectly suitable for the fast fabrication of highly conductive organic nanoelectronics on an industrial scale.
|
|
| 5. |
- Billker, Oliver, et al.
(författare)
-
Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the CEACAM receptor family involving Rac1- and Cdc42-dependent and -independent pathways
- 2002
-
Ingår i: EMBO Journal. - : European Molecular Biology Organization. - 0261-4189 .- 1460-2075. ; 21:4, s. 560-571
-
Tidskriftsartikel (refereegranskat)abstract
- Opa adhesins of pathogenic Neisseria species target four members of the human carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) family. CEACAM receptors mediate opsonization-independent phagocytosis of Neisseria gonorrhoeae by human granulocytes and each receptor individually can mediate gonococcal invasion of epithelial cells. We show here that gonococcal internalization occurs by distinct mechanisms depending on the CEACAM receptor expressed. For the invasion of epithelial cell lines via CEACAM1 and CEACAM6, a pathogen-directed reorganization of the actin cytoskeleton is not required. In marked contrast, ligation of CEACAM3 triggers a dramatic but localized reorganization of the host cell surface leading to highly efficient engulfment of bacteria in a process regulated by the small GTPases Rac1 and Cdc42, but not Rho. Two tyrosine residues of a cytoplasmic immune receptor tyrosine-based activating motif of CEACAM3 are essential for the induction of phagocytic actin structures and subsequent gonococcal internalization. The granulocyte-specific CEACAM3 receptor has properties of a single chain phagocytic receptor and may thus contribute to innate immunity by the elimination of Neisseria and other CEACAM-binding pathogens that colonize human mucosal surfaces.
|
|
| 6. |
- Colombo, Christian, et al.
(författare)
-
COST Action IC1402 Runtime Verification Beyond Monitoring
- 2018
-
Ingår i: 18th International Conference on Runtime Verification (RV'18), vol. 11237 of LNCS, pages 18-26. - : Springer.
-
Konferensbidrag (refereegranskat)abstract
- In this paper we report on COST Action IC1402 which studies Runtime Verification approaches beyond Monitoring. COST Actions are funded by the European Union and are an efficient networking instrument for researchers, engineers and scholars to cooperate and coordinate research activities. This COST action IC1402 lasted over the past four years, involved researchers from 27 different European countries and Australia and allowed to have many different working group meetings, workshops and individual visits.
|
|
| 7. |
- Fan, Lichao, et al.
(författare)
-
Active metabolic pathways of anaerobic methane oxidation in paddy soils
- 2021
-
Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 156
-
Tidskriftsartikel (refereegranskat)abstract
- Anaerobic oxidation of methane (AOM) is a globally important CH4 sink. However, the AOM pathways in paddy soils, the largest agricultural source of methane emissions (31 Mio tons per year) are not yet well described. Here, a combination of C-13 isotope tracer, phospholipid fatty acids (PLFA) analyses, and microbial community analysis was used to identify AOM pathways in fertilized (pig manure, biochar, NPK, and the control) paddy soils amended with alternative electron acceptors (AEAs) (NO3-, Fe3+, SO42-, humic acids, and the reference without AEAs addition). After 84 days of anaerobic incubation, the microbial co-occurrence network got tightened and became more complex relative to unincubated samples. Fertilization and AEAs addition led to a strong divergence of the microbial community structure as indicated by abundances of AOM-related microbiota and C-13 incorporation into microbial PLFA, thus suggesting an environmental niche differentiation of AOM-involved microorganisms. Comparative analyses revealed a set of major and minor AOM pathways with synergistic relations to complementary anaerobic microbial groups. NO3--driven AOM, performed by members of the candidate group ANME-2d, was the major AOM pathway. Minor AOM pathways involved NO2- reduction by NC10, reduction of humic acids and Fe3+ by Geobacter species, and SO42- reduction by sulfate-reducing bacteria linked with anaerobic methanotrophs. As identified by the network analysis, these active AOM pathways compensated a fraction of CH4 produced during ongoing methanogenesis. From a broader ecological perspective, nitrogendriven AOM will become a more important methane sink in the future with the increases of nitrogen fertilization and deposition.
|
|
| 8. |
|
|
| 9. |
- Hans, Marcus, et al.
(författare)
-
Stress-Dependent Elasticity of TiAlN Coatings
- 2019
-
Ingår i: Coatings. - : MDPI. - 2079-6412. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the effect of continuous vs. periodically interrupted plasma exposure during cathodic arc evaporation on the elastic modulus as well as the residual stress state of metastable cubic TiAlN coatings. Nanoindentation reveals that the elastic modulus of TiAlN grown at floating potential with continuous plasma exposure is 7%-11% larger than for coatings grown with periodically interrupted plasma exposure due to substrate rotation. In combination with X-ray stress analysis, it is evident that the elastic modulus is governed by the residual stress state. The experimental dependence of the elastic modulus on the stress state is in excellent agreement with ab initio predictions. The macroparticle surface coverage exhibits a strong angular dependence as both density and size of incorporated macroparticles are significantly lower during continuous plasma exposure. Scanning transmission electron microscopy in combination with energy dispersive X-ray spectroscopy reveals the formation of underdense boundary regions between the matrix and TiN-rich macroparticles. The estimated porosity is on the order of 1% and a porosity-induced elastic modulus reduction of 5%-9% may be expected based on effective medium theory. It appears reasonable to assume that these underdense boundary regions enable stress relaxation causing the experimentally determined reduction in elastic modulus as the population of macroparticles is increased.
|
|
| 10. |
- Horn, Lars-Christian, et al.
(författare)
-
Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia
- 2008
-
Ingår i: American Journal of Surgical Pathology. - 1532-0979. ; 32:4, s. 502-512
-
Tidskriftsartikel (refereegranskat)abstract
- The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), K value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16(INK4a)-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16(INK4a) test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively). P-16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology.
|
|
