| 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. |
- Aye, Cho-Cho, et al.
(författare)
-
CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells
- 2023
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:4
-
Tidskriftsartikel (refereegranskat)abstract
- CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.
|
|
| 4. |
- Rodriguez-Cuenca, Sergio, et al.
(författare)
-
Allostatic hypermetabolic response in PGC1α/β heterozygote mouse despite mitochondrial defects
- 2021
-
Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:9
-
Tidskriftsartikel (refereegranskat)abstract
- Aging, obesity, and insulin resistance are associated with low levels of PGC1α and PGC1β coactivators and defective mitochondrial function. We studied mice deficient for PGC1α and PGC1β [double heterozygous (DH)] to investigate their combined pathogenic contribution. Contrary to our hypothesis, DH mice were leaner, had increased energy dissipation, a pro-thermogenic profile in BAT and WAT, and improved carbohydrate metabolism compared to wild types. WAT showed upregulation of mitochondriogenesis/oxphos machinery upon allelic compensation of PGC1α4 from the remaining allele. However, DH mice had decreased mitochondrial OXPHOS and biogenesis transcriptomes in mitochondria-rich organs. Despite being metabolically healthy, mitochondrial defects in DH mice impaired muscle fiber remodeling and caused qualitative changes in the hepatic lipidome. Our data evidence first the existence of organ-specific compensatory allostatic mechanisms are robust enough to drive an unexpected phenotype. Second, optimization of adipose tissue bioenergetics is sufficient to maintain a healthy metabolic phenotype despite a broad severe mitochondrial dysfunction in other relevant metabolic organs. Third, the decrease in PGC1s in adipose tissue of obese and diabetic patients is in contrast with the robustness of the compensatory upregulation in the adipose of the DH mice.
|
|
| 5. |
- Andersen, Gregers Stig Tig, et al.
(författare)
-
The DEXLIFE study methods : identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals
- 2014
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 106:2, s. 383-389
-
Tidskriftsartikel (refereegranskat)abstract
- The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.
|
|
| 6. |
- Bhardwaj, Anshuman, et al.
(författare)
-
UAV Imaging of a Martian Brine Analogue Environment in a Fluvio-Aeolian Setting
- 2019
-
Ingår i: Remote Sensing. - : MDPI. - 2072-4292. ; 11:18
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding extraterrestrial environments and landforms through remote sensing and terrestrial analogy has gained momentum in recent years due to advances in remote sensing platforms, sensors, and computing efficiency. The seasonal brines of the largest salt plateau on Earth in Salar de Uyuni (Bolivian Altiplano) have been inadequately studied for their localized hydrodynamics and the regolith volume transport across the freshwater-brine mixing zones. These brines have recently been projected as a new analogue site for the proposed Martian brines, such as recurring slope lineae (RSL) and slope streaks. The Martian brines have been postulated to be the result of ongoing deliquescence-based salt-hydrology processes on contemporary Mars, similar to the studied Salar de Uyuni brines. As part of a field-site campaign during the cold and dry season in the latter half of August 2017, we deployed an unmanned aerial vehicle (UAV) at two sites of the Salar de Uyuni to perform detailed terrain mapping and geomorphometry. We generated high-resolution (2 cm/pixel) photogrammetric digital elevation models (DEMs) for observing and quantifying short-term terrain changes within the brines and their surroundings. The achieved co-registration for the temporal DEMs was considerably high, from which precise inferences regarding the terrain dynamics were derived. The observed average rate of bottom surface elevation change for brines was ~1.02 mm/day, with localized signs of erosion and deposition. Additionally, we observed short-term changes in the adjacent geomorphology and salt cracks. We conclude that the transferred regolith volume via such brines can be extremely low, well within the resolution limits of the remote sensors that are currently orbiting Mars, thereby making it difficult to resolve the topographic relief and terrain perturbations that are produced by such flows on Mars. Thus, the absence of observable erosion and deposition features within or around most of the proposed Martian RSL and slope streaks cannot be used to dismiss the possibility of fluidized flow within these features
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Hernández-Alvarez, María Isabel, et al.
(författare)
-
Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease
- 2019
-
Ingår i: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 177:4, s. 881-895.e17
-
Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Martin-Torres, Javier, et al.
(författare)
-
The HABIT (HabitAbility: Brine Irradiation and Temperature) environmental instrument for the ExoMars 2022 Surface Platform
- 2020
-
Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 190
-
Tidskriftsartikel (refereegranskat)abstract
- The HABIT (HabitAbility: Brine Irradiation and Temperature) instrument is a European payload of the ExoMars 2022 Surface Platform Kazachok that will characterize the present-day habitability at its landing place in Oxia Planum, Mars. HABIT consists of two modules: (i) EnvPack (Environmental Package) that monitors the thermal environment (air and ground), the incident ultraviolet radiation, the near surface winds and the atmospheric dust cycle; and (ii) BOTTLE (Brine Observation Transition To Liquid Experiment), an In-situ Resource Utilization instrument to produce liquid water for future Mars exploration. BOTTLE will be used also to investigate the electrical conductivity properties of the martian atmosphere, the present-day atmospheric-ground water cycle and to evaluate if liquid water can exist on Mars in the form of brines, and for how long. These variables measured by HABIT are critical to determine the present and future habitability of the martian surface. In this paper, we describe in detail the HABIT instrument and sensors, together with the calibration of its Flight Model (FM) and the Engineering Qualification Model (EQM) versions. The EnvPack module has heritage from previous missions operating on the surface of Mars, and the environmental observations of its sensors will be directly comparable to those delivered by those missions. HABIT can provide information of the local temperature with ±0.2 °C accuracy, local winds with ±0.3 m/s, surface brightness temperature with ±0.8 °C, incident UV irradiance with 10% error of its absolute value in the UV-A, UV-B, UV-C ranges, as well as in the total UV-ABC range, and two additional wavebands, dedicated to ozone absorption. The UV observations can be used to derive the total opacity column and thus monitor the dust and ozone cycles. BOTTLE can demonstrate the hydration state of a set of four deliquescent salts, which have been found on Mars (calcium chloride, ferric sulphate, magnesium perchlorate and sodium perchlorate) by monitoring their electric conductivity (EC). The EC of the air and the dry salts under Earth ambient, clean room conditions is of the order of 0.1 μScm−1. We have simulated HABIT operations, within an environmental chamber, under martian conditions similar to those expected at Oxia Planum. For dry, CO2 atmospheric conditions at martian pressures, the air EC can be as low as 10−8 μScm−1, however it increases with the relative humidity (RH) percentage. The laboratory experiments show that after an increase from 0 to 60% RH within a few hours, the EC of the air increased up to 10−1 μScm−1, magnesium perchlorate hydrated and reached values of 10 μScm-1, whereas calcium chloride deliquesced forming a liquid state with EC of 102 μScm−1. HABIT will operate with a regular cadence, through day and night. The Electronic Unit (EU) is protected with a heater that is activated when its temperature is below −33 °C and disabled if the temperature of the surface platform rises above −30 °C. Additionally, the heaters of the BOTTLE unit can be activated to dehydrate the salts and reset the experiment. HABIT weighs only 918 g. Its power consumption depends on the operation mode and internal temperature, and it varies between 0.7 W, for nominal operation, and 13.1 W (when heaters are turned on at full intensity). HABIT has a baseline data rate of 1.5 MB/sol. In addition to providing critical environmental observations, this light and robust instrument, will be the first demonstrator of a water capturing system on the surface of Mars, and the first European In-Situ Resource Utilization in the surface of another planet.
|
|
| 13. |
- Martorell, José Antonio Gordillo, et al.
(författare)
-
Metabolizing science from the laboratory to the classroom : The Metabolt Educational Experience
- 2019
-
Ingår i: Journal of Engineering Science and Technology. - : STEM Publishers. ; 2:7, s. 9-26
-
Tidskriftsartikel (refereegranskat)abstract
- The present article summarizes a pilot knowledge co-creation process experience done with a group of 15 eleven and twelve years old students of Porsöskolan, a public school near Luleå Tekniska Universitet from September 2018 to January 2019. The experience is based on a true research project of the Group of Atmospheric Science (GAS) called METABOLT, an instrument to investigate the metabolic activity of microorganisms in soils by measuring the electrochemical and gaseous bio signatures. In this paper, we explain how we have designed, developed, applied and evaluated a complete learning and engagement strategy to bring science from the laboratory to the classroom. The experience adapts the scientific method to the primary classroom level, taking as practical case the METABOLT experiment: identification of a problem, hypothesis design, experiment creation to get results, analysis and confrontation with the hypothesis and provisional conclusions to verify or discard them. After the experience a set of surveys were given to all the stakeholders, students, teachers and researchers to evaluate their perception of the effects of the activity. One unexpected result is the difference in perception between the teachers and students on the learning experience. This project demonstrates that professional researchers with the adequate communication strategy, training and tracking can promote a relevant learning process and achieve a social impact in different audiences
|
|
| 14. |
- Martorell, José Antonio Gordillo, et al.
(författare)
-
The Infinite Learning Chain. Flipped Professional Labs for Learning and Knowledge Co-Creation
- 2019
-
Ingår i: Open Education Studies. - : Walter de Gruyter. - 2544-7831. ; 1, s. 151-176
-
Tidskriftsartikel (refereegranskat)abstract
- Nowadays universities and other classical research institutions are changing their role in knowledge creation. In general terms we can characterize this transition as the path from "Closed Science"to "Open Science"as a part of a deeper and structural phenomenon known as "knowledge democratization", where different stakeholders as students, makers and other tech and science enthusiasts are able to create knowledge learning from the researchers and cooperating with them. In this process, science engagement of these new actors is a key point to stimulate their creativity, get some important research skills learnt directly from the researchers and be able to apply these skills teaching others in a continuous "learning chain". In this article, we introduce some main features and preliminary results of an experiment called "The infinite learning chain"done in cooperation with Arduino, focused on sensing science and based in a real research project of Group of Atmospheric Science (GAS) called Luleå Environmental Monitoring Stations (LEMS). We debate some interesting questions related to the impact of the format in terms of science engagement, STEM skills acquisition and cooperative learning involvement. We used as "learning ecosystem"a professional Lab, the INSPIRE Lab a complete multidisciplinary facility for space and environmental research and exploration.
|
|
| 15. |
- Navarro‐González, Rafael, et al.
(författare)
-
Abiotic Input of Fixed Nitrogen by Bolide Impacts to Gale Crater During the Hesperian : Insights From the Mars Science Laboratory
- 2019
-
Ingår i: Journal of Geophysical Research - Planets. - : John Wiley & Sons. - 2169-9097 .- 2169-9100. ; 124:1, s. 94-113
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular hydrogen (H2) from volcanic emissions is suggested to warm the Martian surface when carbon dioxide (CO2) levels dropped from the Noachian (4100 to 3700 Myr) to the Hesperian (3700 to 3000 Myr). Its presence is expected to shift the conversion of molecular nitrogen (N2) into different forms of fixed nitrogen (N). Here we present experimental data and theoretical calculations that investigate the efficiency of nitrogen fixation by bolide impacts in CO2‐N2 atmospheres with or without H2. Surprisingly, nitric oxide (NO) was produced more efficiently in 20% H2 in spite of being a reducing agent and not likely to increase the rate of nitrogen oxidation. Nevertheless, its presence led to a faster cooling of the shock wave raising the freeze‐out temperature of NO resulting in an enhanced yield. We estimate that the nitrogen fixation rate by bolide impacts varied from 7 × 10−4 to 2 × 10−3 g N·Myr−1·cm−2 and could imply fluvial concentration to explain the nitrogen (1.4 ± 0.7 g N·Myr−1·cm−2) detected as nitrite (NO2−) and nitrate (NO3−) by Curiosity at Yellowknife Bay. One possible explanation is that the nitrogen detected in the lacustrine sediments at Gale was deposited entirely on the crater's surface and was subsequently dissolved and transported by superficial and ground waters to the lake during favorable wet climatic conditions. The nitrogen content sharply decreases in younger sediments of the Murray formation suggesting a decline of H2 in the atmosphere and the rise of oxidizing conditions causing a shortage in the supply to putative microbial life.
|
|
| 16. |
- Sam, Lydia, et al.
(författare)
-
Small Lava Caves as Possible Exploratory Targets on Mars : Analogies Drawn from UAV Imaging of an Icelandic Lava Field
- 2020
-
Ingår i: Remote Sensing. - : MDPI. - 2072-4292. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- Volcanic-aeolian interactions and processes have played a vital role in landscape evolution on Mars. Martian lava fields and associated caves have extensive geomorphological, astrobiological, and in-situ resource utilization (ISRU) implications for future Mars missions which might be focused on subsurface exploration. Although several possible cave “skylights” of tens to >100 m diameter have been spotted in lava fields of Mars, there is a possibility of prevalence of meter-scale features which are an order of magnitude smaller and difficult to identify but could have vital significance from the scientific and future exploration perspectives. The Icelandic volcanic-aeolian environment and fissure volcanoes can serve as analogs to study lava flow-related small caves such as surface tubes, inflationary caves, liftup caves, and conduits. In the present work, we have tried to explore the usability of unmanned aerial vehicle (UAV)-derived images for characterizing a solidified lava flow and designing a sequential methodology to identify small caves in the lava flow. In the mapped area of ~0.33 km2, we were able to identify 81 small cave openings, five lava flow morphologies, and five small cave types using 2 cm/pixel high-resolution images. The results display the usefulness of UAV imaging for such analogous research, and also highlight the possibility of the widespread presence of similar small cave openings in Martian lava fields. Such small openings can facilitate optimal air circulation within the caves while sheltering the insides from physical weathering and harmful radiations. Using the available best resolution remote sensing images, we extend the analogy through the contextual and geomorphological analysis of several possible pit craters in the Tharsis region of Mars, in a region of extremely vesicular and fragile lava crust with pahoehoe-type morphology. We report two possible pit craters in this region, with diameters as small as ~20 m. The possibility that such small cave openings can lead to vast subterranean hollow spaces on Mars cannot be ruled out considering its low gravity.
|
|
| 17. |
- Sebastián, David, et al.
(författare)
-
Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis
- 2012
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:14, s. 5523-5528
-
Tidskriftsartikel (refereegranskat)abstract
- Mitochondria are dynamic organelles that play a key role in energy conversion. Optimal mitochondrial function is ensured by a quality-control system tightly coupled to fusion and fission. In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2 diabetic patients. Here, we provide in vivo evidence that Mfn2 plays an essential role in metabolic homeostasis. Liver-specific ablation of Mfn2 in mice led to numerous metabolic abnormalities, characterized by glucose intolerance and enhanced hepatic gluconeogenesis. Mfn2 deficiency impaired insulin signaling in liver and muscle. Furthermore, Mfn2 deficiency was associated with endoplasmic reticulum stress, enhanced hydrogen peroxide concentration, altered reactive oxygen species handling, and active JNK. Chemical chaperones or the antioxidant N-acetylcysteine ameliorated glucose tolerance and insulin signaling in liver-specific Mfn2 KO mice. This study provides an important description of a unique unexpected role of Mfn2 coordinating mitochondria and endoplasmic reticulum function, leading to modulation of insulin signaling and glucose homeostasis in vivo.
|
|
