| 1. |
|
|
| 2. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 3. |
- Kim, Min-Jeong, et al.
(författare)
-
Independent enhancement of the in-plane Seebeck effect in 2D PtSe2/PtSe2 homostructures via a facile interface tuning method
- 2024
-
Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 268
-
Tidskriftsartikel (refereegranskat)abstract
- Atomically thin two-dimensional (2D) transition-metal dichalcogenide (TMDC) films have emerged as promising semiconducting materials for use in thermoelectric (TE) applications. However, the utilization of such materials remains challenging owing to the relatively high intrinsic resistance as the size of the TMDC thin films increases to the centimeter scale. These 2D TMDC films can also form vertically stacked homo- or heterostructures at large interfaces with other 2D TMDC films, resulting in unique TE properties at room temperature. This article reports on the in-plane TE properties when the interfaces formed within a PtSe2/PtSe2 (3 nm/3 nm) homostructure are modulated as a function of O2 plasma treatment time. The results show enhanced Seebeck coefficients compared with that of the single-layer PtSe2 with the same thickness. The independent enhancement in the Seebeck coefficient while keeping the electrical conductivity leads to a substantial increase in the power factor. Such extra Seebeck voltage in 2D PtSe2/PtSe2 homostructures is mainly as a result of momentum exchange by charge carriers caused by the temperature gradient in the vertical direction, which occurs in-plane Seebeck coefficient measurements, at the interface between the PtSe2 layers in the in-plane temperature gradient along the samples. These results resemble the characteristics of the phonon drag effect at low temperatures, which can independently increase the Seebeck coefficient at room temperature.
|
|
| 4. |
- Kim, Min-Jeong, et al.
(författare)
-
Intrinsic Seebeck coefficients of 2D polycrystalline PtSe2 semiconducting films through two-step annealing
- 2023
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 11:11, s. 5714-5724
-
Tidskriftsartikel (refereegranskat)abstract
- Because of the high contact resistance between a metal and a film, evaluating the intrinsic Seebeck coefficient of large-area two-dimensional (2D) semiconducting films with high-resistance is challenging. Here, we report a simple scheme to measure the large-area Seebeck coefficients of 2D polycrystalline platinum diselenide (PtSe2) thin films, whose electrical resistance (>2 M omega) is too high to measure the thermoelectric (TE) properties, by thermal annealing. As-prepared PtSe2 thin films deposited on sapphire substrates and treated by a two-step thermal annealing process at 574 K exhibited an intrinsic Seebeck coefficient > similar to 160 mu V K-1, which is 400% higher than that of the single-crystalline PtSe2 bulk, under a temperature gradient of up to 5 K along the samples. In addition, we confirm that the in-plane Seebeck coefficient of the two-step annealed samples was independent of the metal electrode. In addition, the role of thermal annealing in intrinsically-high-resistance 2D PtSe2 semiconducting films based on the atomic-scale crystallographic characteristics of these films and the measured contact resistance between the metal and PtSe2 layer is further discussed. Our finding represents an important achievement in understanding and measuring the Seebeck effect of high-TE-performance 2D layered transition metal dichalcogenide materials.
|
|
| 5. |
- Choi, Jae Won, et al.
(författare)
-
Interface-driven seebeck effect in two-dimensional trilayer-stacked PtTe2/MoS2/MoS2 heterostructures via electron-electron interactions
- 2023
-
Ingår i: Nano Energy. - : Elsevier. - 2211-2855 .- 2211-3282. ; 115
-
Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional (2D) platinum telluride (PtTe2), which is one of the promising metallic transition metal dichalcogenides, has been proven as an essential candidate for electronic devices, magnetic devices, type-II Dirac fermions, topological superconductors, and other optoelectronic applications. However, the formation and thermal transport as important thermoelectric (TE) device applications have not been realized in large-area 2D PtTe2 films due to their semi-metallic properties. Here, we report an innovative approach to enhance the in-plane TE power factors by piling the metallic PtTe2 films on high-resistance (> 10 MO) intrinsic MoS2 films to form bilayer-PtTe2/MoS2 (5 nm/7 nm)//sapphire and trilayer-PtTe2/MoS2/MoS2 (5 nm/7 nm/7 nm)//sapphire heterostructures via wet-transfer stacking method. Such approaches can be achieved by utilizing 2D/2D heterostructure to increase the electron effective mass due to the strong electron-electron interaction at interface under temperature gradient along the samples and ultimately increase Seebeck coefficients via interface-driven Seebeck effect along with a metallic high-conductivity top-PtTe2 films. The trilayer-stacked PtTe2/MoS2/MoS2 heterostructures exhibit an extremely high Seebeck coefficient of 21.6 mu V/K and power factor of similar to 0.2 mW/m.K-2, which are 231 % and similar to 727 %, higher than those of the metallic 5-nm-thick single PtTe2 film on the sapphire substrate, respectively. Our new physics and observation can pave the way toward an effective strategy for understating 2D/2D TMDC heterostructure materials for high Fig.-of-merit TE energy harvesting devices.
|
|
| 6. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 7. |
- Cho, Wonkyung, et al.
(författare)
-
Design of salmon calcitonin particles for nasal delivery using spray-drying and novel supercritical fluid-assisted spray-drying processes
- 2015
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 478:1, s. 288-296
-
Tidskriftsartikel (refereegranskat)abstract
- The overall aim of this study was to prepare a nasal powder formulation of salmon calcitonin (sCT) using an absorption enhancer to improve its bioavailability. In this work, powder formulations for nasal delivery of sCT were studied using various absorption enhancers and stabilizers. Powders were prepared by two different methods: conventional spray-drying (SD) and novel supercritical fluid-assisted spray-drying (SASD) to investigate the role of CO2 in the particle formation process. The prepared sCT powder formulations were characterized by several analyses; powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), and the Fourier transform infrared (FT-IR) spectroscopy method. The particle size distribution was also evaluated. In vivo absorption tests were carried out in Sprague-Dawley rat using the prepared powder formulations, and the results were compared to those of raw sCT. Quantitative analysis by high-performance liquid chromatography (HPLC) indicated that sCT was chemically stable after both the SD and SASD processes. Results of PXRD, SEM, and FT-IR did not indicate a strong interaction or defragmentation of sCT. The in vivo absorption test showed that SD- and SASD-processed sCT powders increased the bioavailability of the drug when compared to the nasal administration of raw sCT. In addition, SASD-processed sCT exhibited higher nasal absorption when compared with SD-processed sCT in all formulations due to a reduction of particle size. The results from this study illustrate that the preparation of nasal powders using the SASD process could be a promising approach to improve nasal absorption of sCT.
|
|
| 8. |
- Jung, Min-Sook, et al.
(författare)
-
Bioavailability of indomethacin-saccharin cocrystals
- 2010
-
Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 62:11, s. 1560-1568
-
Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee (R).MethodsScale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.Key findingsThe bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee (R) at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P < 0.05) than that of IND but not significantly different from Indomee (R) (ANOVA, P > 0.05).ConclusionsThe study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.
|
|
| 9. |
|
|
| 10. |
- Biancari, Fausto, et al.
(författare)
-
Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation : Systematic Review and Individual Patient Data Meta-Analysis
- 2022
-
Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:24
-
Forskningsöversikt (refereegranskat)abstract
- Background: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle. Results: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08–1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04–1.76, I2 21%). Conclusions: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO.
|
|
