| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 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. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
-
Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
- 2015
-
Ingår i: Cell Host & Microbe. - Cambridge : Elsevier BV. - 1931-3128 .- 1934-6069. ; 17:5, s. 690-703
-
Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
|
|
| 4. |
- Pang, Jun-Feng, et al.
(författare)
-
mtDNA data indicate a single origin for dogs south of Yangtze River, less than 16,300 years ago, from numerous wolves.
- 2009
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 26:12, s. 2849-64
-
Tidskriftsartikel (refereegranskat)abstract
- There is no generally accepted picture of where, when, and how the domestic dog originated. Previous studies of mitochondrial DNA (mtDNA) have failed to establish the time and precise place of origin because of lack of phylogenetic resolution in the so far studied control region (CR), and inadequate sampling. We therefore analyzed entire mitochondrial genomes for 169 dogs to obtain maximal phylogenetic resolution and the CR for 1,543 dogs across the Old World for a comprehensive picture of geographical diversity. Hereby, a detailed picture of the origins of the dog can for the first time be suggested. We obtained evidence that the dog has a single origin in time and space and an estimation of the time of origin, number of founders, and approximate region, which also gives potential clues about the human culture involved. The analyses showed that dogs universally share a common homogenous gene pool containing 10 major haplogroups. However, the full range of genetic diversity, all 10 haplogroups, was found only in southeastern Asia south of Yangtze River, and diversity decreased following a gradient across Eurasia, through seven haplogroups in Central China and five in North China and Southwest (SW)Asia, down to only four haplogroups in Europe. The mean sequence distance to ancestral haplotypes indicates an origin 5,400-16,300 years ago (ya) from at least 51 female wolf founders. These results indicate that the domestic dog originated in southern China less than 16,300 ya, from several hundred wolves. The place and time coincide approximately with the origin of rice agriculture, suggesting that the dogs may have originated among sedentary hunter-gatherers or early farmers, and the numerous founders indicate that wolf taming was an important culture trait.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Ganapathy, S., et al.
(författare)
-
Chromium IV exposure, via Src/Ras signaling, promotes cell transformation
- 2017
-
Ingår i: Molecular Carcinogenesis. - : Wiley. - 0899-1987. ; 56:7, s. 1808-1815
-
Tidskriftsartikel (refereegranskat)abstract
- Hexavalent chromium [Cr(VI)] is a well-known environment carcinogen. The exposure of Cr(VI) through contaminated soil, air particles, and drinking water is a strong concern for the public health worldwide. While many studies have been done, it remains unclear which intracellular molecules transduce Cr(VI)-mediated carcinogenic signaling in cells to promote cancer. In this study, we demonstrated that upon Cr(VI) treatment, the intracellular receptor src was activated, which further upregulated Ras activity, leading to the augmentation of ROS and onset of ER stress in human lung epithelial BEAS-2B or keratinocytes. These cells were formed colonies in soft agar cultures following the persistent Cr(VI) treatment. Furthermore, anti-apoptotic factor Bcl-2 was upregulated and activated in the colonies. Thus, our study suggests that Cr(VI), though activating the src and Ras signaling axis, perturbs redox state and invokes ER stress for the establishment of carcinogenic actions in the cells. In this process, Bcl-2 appears playing an important role. By uncovering these intracellular targets, our study may help developing novel strategies for better environmental protection, especially in areas contaminated or polluted by Cr(VI) as well as for effective cancer treatments. © 2017 Wiley Periodicals, Inc.
|
|
| 8. |
- Ganapathy, Suthakar, et al.
(författare)
-
Low doses of arsenic, via perturbing p53, promotes tumorigenesis.
- 2016
-
Ingår i: Toxicology and applied pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 306, s. 98-104
-
Tidskriftsartikel (refereegranskat)abstract
- In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.
|
|
| 9. |
- Hilander, Taru, et al.
(författare)
-
Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria.
- 2018
-
Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 46:2
-
Tidskriftsartikel (refereegranskat)abstract
- Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms.
|
|
| 10. |
- Jiang, Sheng, et al.
(författare)
-
Field-Free High-Frequency Exchange-Spring Spin-Torque Nano- Oscillators
- 2023
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 23:4, s. 1159-1166
-
Tidskriftsartikel (refereegranskat)abstract
- Spin-torque nano-oscillators (STNOs) are a type of nanoscale microwave auto-oscillators utilizing spin-torque to generate magnetodynamics with great promise for applications in microwaves, magnetic memory, and neuromorphic computing. Here, we report the first demonstration of exchange-spring STNOs, with an exchange-spring ([Co/Pd]-Co) reference layer and a perpendicular ([Co/Ni]) free layer. This magnetic configuration results in high-frequency (>10 GHz) microwave emission at a zero magnetic field and exchange-spring dynamics in the reference layer and the observation of magnetic droplet solitons in the free layer at different current polarities. Our demonstration of bipolar and field-free exchange-spring-based STNOs operating over a 20 GHz frequency range greatly extends the design freedom and functionality of the current STNO technology for energy -efficient high-frequency spintronic and neuromorphic applications.
|
|
