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| 2. |
- Bach, D, et al.
(författare)
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Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6
- 2005
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:9, s. 2685-2693
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Tidskriftsartikel (refereegranskat)abstract
- The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)α or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFα or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFα and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes.
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| 3. |
- Calvani, P., et al.
(författare)
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Infrared spectroscopy of two-dimensional electron systems
- 2019
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Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 228:3, s. 669-673
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Tidskriftsartikel (refereegranskat)abstract
- © 2019, EDP Sciences, Springer-Verlag GmbH Germany, part of Springer Nature. We have used grazing-angle infrared spectroscopy with polarized radiation to detect the Berreman effect (BE) in the two-dimensional electron systems (2DES) which form spontaneously at two interfaces: one between an amorphous film LaAlO3 and its SrTiO3 substrate (LAO/STO), and another at the interface between the topological insulator (TI) Bi2Se3 and its sapphire substrate. In both systems we have thus extracted the 2DES parameters at different temperatures. In the quasi-2DES under amorphous LAO, the surface density ns is higher than under crystalline LAO, while the mobility is nearly the same and the thickness d is 7 nm. In ultrapure Bi2Se3 on sapphire, preliminary data provided d
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| 4. |
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| 5. |
- Falsetti, E., et al.
(författare)
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High conductivity of ultrathin nanoribbons of SrRuO3 on SrTiO3 probed by infrared spectroscopy
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- SrRuO3(SRO) is a perovskite increasingly used in oxide-based electronics both for its intrinsic metallicity, which remains unaltered in thin films and for the ease of deposition on dielectric perovskites like SrTiO3, (STO) to implement SRO/STO microcapacitors and other devices. In order to test the reliability of SRO/STO also as high-current on-chip conductor, when the SRO dimensions are pushed to the nanoscale, here we have measured the electrodynamic properties of arrays of nanoribbons, fabricated by lithography starting from an ultrathin film of SRO deposited on a STO substrate. The nanoribbons are 6 or 4 nm thick, 400, 200 and 100 nm wide and 5 mm long. The measurements have been performed by infrared spectroscopy, a non-contact weakly perturbing technique which also allows one to separately determine the carrier density and their scattering rate or mobility. Far-infrared reflectivity spectra have been analyzed by Rigorous Coupled-Wave Analysis (RCWA) and by an Effective Medium Theory, obtaining consistent results. With the radiation polarized along the nanoribbons, we obtain a carrier density similar to that of a flat film used as reference, which in turn is similar to that of bulk SRO. Moreover, in the nanoribbons the carrier scattering rate is even smaller than in the unpatterned film by about a factor of 2. This shows that the transport properties of SRO deposited on STO remain at least unaltered down to nanometric dimensions, with interesting perspectives for implementing on-chip nano-interconnects in an oxide-based electronics. When excited in the perpendicular direction, the nanoribbons appear instead virtually transparent to the radiation field, as predicted by RCWA.
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| 6. |
- Gossmann, Toni I., et al.
(författare)
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Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity
- 2019
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 29:10, s. 1712-1720.e7
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 The Author(s) Some species responded successfully to prehistoric changes in climate [1, 2], while others failed to adapt and became extinct [3]. The factors that determine successful climate adaptation remain poorly understood. We constructed a reference genome and studied physiological adaptations in the Alpine marmot (Marmota marmota), a large ground-dwelling squirrel exquisitely adapted to the “ice-age” climate of the Pleistocene steppe [4, 5]. Since the disappearance of this habitat, the rodent persists in large numbers in the high-altitude Alpine meadow [6, 7]. Genome and metabolome showed evidence of adaptation consistent with cold climate, affecting white adipose tissue. Conversely, however, we found that the Alpine marmot has levels of genetic variation that are among the lowest for mammals, such that deleterious mutations are less effectively purged. Our data rule out typical explanations for low diversity, such as high levels of consanguineous mating, or a very recent bottleneck. Instead, ancient demographic reconstruction revealed that genetic diversity was lost during the climate shifts of the Pleistocene and has not recovered, despite the current high population size. We attribute this slow recovery to the marmot's adaptive life history. The case of the Alpine marmot reveals a complicated relationship between climatic changes, genetic diversity, and conservation status. It shows that species of extremely low genetic diversity can be very successful and persist over thousands of years, but also that climate-adapted life history can trap a species in a persistent state of low genetic diversity. Despite being highly abundant and well adapted, Gossmann et al. report that the Alpine marmot is among the least genetically diverse animal species. The low diversity is found to be the consequence of consecutive, climate-related events, including long-term extreme niche adaptation, that also greatly retarded the recovery of its genetic diversity.
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| 7. |
- Nucara, A., et al.
(författare)
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Infrared study of the quasi-two-dimensional electron system at the interface between SrTiO3 and crystalline or amorphous LaAlO3
- 2018
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 97:15
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Tidskriftsartikel (refereegranskat)abstract
- We have used grazing-angle infrared spectroscopy to detect the Berreman effect (BE) in the quasi-two-dimensional electron system (q-2DES) which forms spontaneously at the interface between SrTiO 3 (STO) and a thin film of LaAlO 3 (LAO). From the BE, which allows one to study longitudinal optical excitations in ultrathin films like the q-2DES, we have extracted at different temperatures its thickness, the charge density and mobility of the carriers under crystalline LAO (sample A), and the charge density under amorphous LAO (sample B). The latter quantity turns out to be higher than in sample A, but a comparison with Hall measurements shows that under amorphous LAO the charges are partly localized at low T with a low activation energy (about 190 K in units of kB) and are thermally activated according to a model for large polarons. The thickness of the q-2DES extracted from our spectra turns out to be 4±1 nm for crystalline LAO and 7±2 nm for amorphous LAO.
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| 8. |
- Nucara, A., et al.
(författare)
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Hardening of the soft phonon in bulk SrTiO3 interfaced with LaAlO3 and SrRuO3
- 2016
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 93:22
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Tidskriftsartikel (refereegranskat)abstract
- The low-temperature softening of the TO1 phonon of SrTiO3 (STO), which determines its incipient ferroelectricity, is known to be partially hindered either in the bulk under strong electric fields, or in thin STO films. Here we show, by terahertz (THz) reflectivity measurements, that a similar effect is produced in bulk STO and at zero static field by ultrathin metallic films on its surface, like a 10-nm-thick film of SrRuO3 (SRO), or the two-dimensional electron system (2DES) present at the interface with LaAlO3. In SRO/STO, the observed hardening is well explained by the depolarizing action of the SRO free electrons which follow adiabatically the ion motion. In LAO/STO, a weaker TO1 hardening could be detected by patterning the 2DES in the form of microstripes and using a polarized THz field parallel (E-) or orthogonal (E-) to the stripes. At 10 K, when TO1 is excited together with the free electrons by E-, its absorbance is harder by about 7 cm-1 than that measured when TO1 is coupled to the plasmon-polariton confined within the stripes, being excited by E-.
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| 9. |
- Picca, Anna, et al.
(författare)
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Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA(4977)) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (Fe-56), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score <= 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores >= 11 (high-functioning, HF). The mtDNA(4977) relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.
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