| 1. |
- Cheng, Arthur J., et al.
(författare)
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Intact single muscle fibres from SOD1(G93A) amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training-like adaptations
- 2019
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Ingår i: Journal of Physiology. - : Cambridge University Press. - 0022-3751 .- 1469-7793. ; 597:12, s. 3133-3146
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Tidskriftsartikel (refereegranskat)abstract
- Key points:How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated.Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force.On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance.These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype.Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125–150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+] ([Ca2+]i), and resting [Ca2+]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.
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| 2. |
- Hedlund, Sebastian, et al.
(författare)
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Dendritic cell activation by sensing Mycobacterium tuberculosis-induced apoptotic neutrophils via DC-SIGN
- 2010
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Ingår i: HUMAN IMMUNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0198-8859 .- 1879-1166. ; 71:6, s. 535-540
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium tuberculosis (Mtb) manipulates cells of the innate immune system to provide the bacteria with a sustainable intracellular niche. Mtb spread through aerosol carrying them deep into the lungs, where they are internalized by phagocytic cells, such as neutrophils (PMNs), dendritic cells (DCs), and macrophages. PMNs undergo accelerated apoptosis after interaction with the bacterium, and apoptotic cells are sequestered by neighboring phagocytes. Removal of aged apoptotic cells because of natural tissue turnover is described as an immunologically silent process facilitating resolution of inflammation and inhibition of DC maturation. Silencing of immune cells could be favorable for intracellular bacteria. The aim of this study was to clarify the interaction between Mtb-induced apoptotic PMNs and DCs, and evaluate whether this interaction follows the proposed anti-inflammatory pathway. In contrast to aged apoptotic cells, Mtb-induced apoptotic PMNs induced functional DC maturation. We found that the cell fraction from Mtb-induced apoptotic PMNs contained almost all stimulatory capacity, suggesting that cell-cell interaction is crucial for DC activation. Inhibitory studies showed that this cell contact-dependent activation required binding of the PMN Mac-1 (CD11b/CD18) to the DC via DC-SIGN and endocytic activity involving the alpha(v)beta(5) but did not involve the scavenger receptor CD36. Taken together, this study demonstrates that the DCs can distinguish between normal and infected apoptotic PMNs via cellular crosstalk, where the DCs can sense the presence of danger on the Mtb-infected PMNs and modulate their response accordingly.
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| 3. |
- Hedlund, Sebastian R., et al.
(författare)
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Dendritic cell activation by sensing Mycobacterium tuberculosis-induced apoptotic neutrophils via DC-SIGN
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In Mycobacterium tuberculosis (Mtb)-infected individuals cells of the innate immune system accumulate in the spleen and in granulomas, but how this relates to the protection against Mtb or in the pathogenesis is unknown. Mtb is internalized in the lung by phagocytic cells, such as neutrophils (PMNs), dendritic cells (DCs) and macrophages. PMNs undergo accelerated apoptosis after internalization of the bacterium and are subsequently sequestered by neighbouring phagocytes. Removal of aged apoptotic cells is an immunologically silent process and the aim of this study was to clarify the interaction between Mtb-induced apoptotic PMNs and DCs, and evaluate if this interaction induced functional maturation of the DCs. In fact, Mtb-induced apoptotic PMNs induced DC maturation, whereas exposure to spontaneous apoptotic PMNs had no effect on DCs maturation status. We found that the cell fraction contained almost all stimulatory capacity, suggesting that the cell-cell interaction is crucial for DC activation. Inhibitory studies showed that this cell contact-dependent activation required binding of the PMN Mac-1 (CD11b/CD18) to the DC via DC-SIGN and endocytic activity. Taken together, this study proves that the DCs can distinguish between normal and infected apoptotic PMNs via cellular cross talk, where the DCs can sense the presence of danger on the Mtb-infected PMNs and modulate their response accordingly.
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| 4. |
- Hennenberg, Martin, et al.
(författare)
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α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue
- 2011
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 108:6, s. 922-928
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:• To test whether β1-adrenoceptor activation leads to phosphorylation of the β2-adrenoceptor in human prostate tissue.PATIENTS AND METHODS:• Prostate tissue from patients undergoing radical prostatectomy was stimulated in vitro with the α1-adrenergic agonist phenylephrine (10 µM).• α2-adrenoceptor phosphorylation at serines 345/346 was studied using Western blot analysis with a phospho-specific antibody.• The role of second messenger kinases was assessed by studying the effects of the protein kinase C (PKC) inhibitor Ro 31-8425 and the protein kinase A (PKA) inhibitor H89 on phenylephrine-induced phosphorylation.• The expression of G protein-coupled receptor kinases (GRKs) 2/3 was analysed using quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry.RESULTS:• Stimulation of prostate tissue with phenylephrine resulted in phosphorylation of the β2-adrenoceptor (5, 10 and 20 min after stimulation).• This α1-adrenoceptor-induced phosphorylation of β2-adrenoceptors was resistant to inhibition of PKC and PKA.• Changes in phosphorylation levels were not attributable to changes in receptor levels, as these remained constant during stimulation.• RT-PCR and Western blot analysis showed expression of GRK2/3 in human prostate tissues.• Immunohistochemical staining showed that GRK2/3 expression in human prostate tissue is located to stromal and smooth muscle cells.CONCLUSIONS:• Activation of α1-adrenoceptors causes phosphorylation of β2-adrenoceptors in the human prostate. This may enhance α1-adrenergic contraction and is possibly mediated by GRK2, which is expressed in prostate smooth muscle.• Mutual regulation between different adrenergic receptors might be involved in the therapeutic effects of α1-blockers in patients with benign prostate hyperplasia.
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| 5. |
- Jaramillo, Fernando, et al.
(författare)
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Priorities and Interactions of Sustainable Development Goals (SDGs) with Focus on Wetlands
- 2019
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Ingår i: Water. - : MDPI. - 2073-4441. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Wetlands are often vital physical and social components of a country’s natural capital, as well as providers of ecosystem services to local and national communities. We performed a network analysis to prioritize Sustainable Development Goal (SDG) targets for sustainable development in iconic wetlands and wetlandscapes around the world. The analysis was based on the information and perceptions on 45 wetlandscapes worldwide by 49 wetland researchers of the Global Wetland Ecohydrological Network (GWEN). We identified three 2030 Agenda targets of high priority across the wetlandscapes needed to achieve sustainable development: Target 6.3—“Improve water quality”; 2.4—“Sustainable food production”; and 12.2—“Sustainable management of resources”. Moreover, we found specific feedback mechanisms and synergies between SDG targets in the context of wetlands. The most consistent reinforcing interactions were the influence of Target 12.2 on 8.4—“Efficient resource consumption”; and that of Target 6.3 on 12.2. The wetlandscapes could be differentiated in four bundles of distinctive priority SDG-targets: “Basic human needs”, “Sustainable tourism”, “Environmental impact in urban wetlands”, and “Improving and conserving environment”. In general, we find that the SDG groups, targets, and interactions stress that maintaining good water quality and a “wise use” of wetlandscapes are vital to attaining sustainable development within these sensitive ecosystems.
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| 6. |
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| 7. |
- Månberg, Anna, 1985-, et al.
(författare)
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Altered perivascular fibroblast activity precedes ALS disease onset
- 2021
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Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 27:4, s. 640-646
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Tidskriftsartikel (refereegranskat)abstract
- Apart from well-defined factors in neuronal cells1, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia2,3 and blood vessels4. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response. Notably, during the presymptomatic stage, perivascular fibroblast cells showed the strongest gene enrichments, and their marker proteins SPP1 and COL6A1 accumulated in enlarged perivascular spaces in patients with sporadic ALS. Moreover, in plasma of 574 patients with ALS from four independent cohorts, increased levels of SPP1 at disease diagnosis repeatedly predicted shorter survival with stronger effect than the established risk factors of bulbar onset or neurofilament levels in cerebrospinal fluid. We propose that the activity of the recently discovered perivascular fibroblast can predict survival of patients with ALS and provide a new conceptual framework to re-evaluate definitions of ALS etiology.
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| 8. |
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| 9. |
- Omanakuttan, Giriprasanth, et al.
(författare)
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Surface emitting 1.5 mu m multi-quantum well LED on epitaxial lateral overgrowth InP/Si
- 2020
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Ingår i: Optical Materials Express. - : The Optical Society. - 2159-3930. ; 10:7, s. 1714-1723
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate a surface emitting 1.5 mu m multi-quantum well (MQW) light-emitting diode (LED) on a 3-inch epitaxial lateral overgrowth (ELOG) InP/Si wafer. The enhanced crystalline quality of ELOG InP/Si is revealed by various characterization techniques, which gives rise to a MQW with high photoluminescence intensity at 1.5 mu m and interference fringes arising from the vertical Fabry-Perot cavity. The LED devices exhibited strong electroluminescence intensity that increased with pump current. Moreover, transparency current measurements indicate optical gain in the 1.5 mu m MQW on InP/Si. The results are encouraging for obtaining wafer scale 1.5 mu m surface emitting laser structures on silicon with further optimization.
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| 10. |
- Persson, Alexander, 1978-, et al.
(författare)
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Dendritic cell activation by sensing Mycobacterium tuberculosis-induced apoptotic neutrophils via DC-SIGN
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In Mycobacterium tuberculosis (Mtb)-infected individuals cells of the innate immune system accumulate in the spleen and in granulomas, but how this relates to the protection against Mtb or in the pathogenesis is unknown. Mtb is internalized in the lung by phagocytic cells, such as neutrophils (PMNs), dendritic cells (DCs) and macrophages. PMNs undergo accelerated apoptosis after internalization of the bacterium and are subsequently sequestered by neighbouring phagocytes. Removal of aged apoptotic cells is an immunologically silent process and the aim of this study was to clarify the interaction between Mtb-induced apoptotic PMNs and DCs, and evaluate if this interaction induced functional maturation of the DCs. In fact, Mtb-induced apoptotic PMNs induced DC maturation, whereas exposure to spontaneous apoptotic PMNs had no effect on DCs maturation status. We found that the cell fraction contained almost all stimulatory capacity, suggesting that the cell-cell interaction is crucial for DC activation. Inhibitory studies showed that this cell contact-dependent activation required binding of the PMN Mac-1 (CD11b/CD18) to the DC via DC-SIGN and endocytic activity. Taken together, this study proves that the DCs can distinguish between normal and infected apoptotic PMNs via cellular cross talk, where the DCs can sense the presence of danger on the Mtb-infected PMNs and modulate their response accordingly.
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