2,448 research outputs found

    Agriculture handbook

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    2001 handbook for the faculty of Agricultur

    The role of PGC-1α and PGC-1β during inflammatory processes in skeletal muscle

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    Transcription is a fundamental cellular process which is tightly regulated by transcription factors and cofactors to maintain homeostasis, even under changing conditions. The family of peroxisome proliferator-activated receptor (PPAR) coactivator (PGC) 1 transcription cofactors comprises PGC-1, PGC-1 and PRC, which all induce oxidative metabolism including mitochondrial biogenesis and fatty acid oxidation. PGC-1 and PGC-1 have been studied in greater detail than PRC and are predominantly expressed in tissues with high oxidative capacity like brown adipose tissue (BAT), heart and skeletal muscle. Inflammation is the protective response of the body to infection and injury involving tissue as well as immune cells. During this process, a complex cytokine network governs communication between cells, coordinates elimination of pathogens, regeneration and finally drives resolution of the inflammatory reaction. If persistently active, inflammation however becomes detrimental and in fact, accompanies a large number of chronic diseases like type 2 diabetes. In skeletal muscle of diabetic patients, levels of PGC-1 and PGC-1 are diminished and a mouse model with skeletal muscle-specific deletion of PGC-1 shows elevated inflammatory markers both locally and systemically. These findings suggest a causal role of PGC-1 coactivators in counteracting inflammation. The work presented here explored the relationship of those coactivators with inflammatory reactions in skeletal muscle in vitro and in vivo. In vitro, PGC-1 and PGC-1 were expressed using adenoviral vectors in a C2C12 myotube model. Tumour necrosis factor (TNF) , different toll-like receptor agonists and free fatty acids all elicited pro-inflammatory cytokine expression that was diminished by both coactivators in a stimulus- and gene-dependent manner. To further elucidate the mechanism behind this repressive action, TNtreatment was chosen as paradigm. A microarray experiment with subsequent bioinformatic analysis revealed that the NF-B pathway, which is a major driver of inflammatory reactions, plays an important role in PGC-1-controlled inflammatory gene expression. This prediction was validated as NF-B reporter gene activity was inhibited by both PGC-1 and PGC-1. However, neither changes in mRNA nor in protein expression of components of the NF-B signalling pathway explained the repression. Rather, PGC-1 coactivators affected the post-translational modification of p65, a NF-B subunit. Diminished phosphorylation at serine 536 precluded complete transcriptional activation by p65 leading to lower cytokine levels.

    Using reporters of different misfolded proteins reveals differential strategies in processing protein aggregates

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    The accumulation of misfolded proteins is a hallmark of aging and many neurodegenerative diseases, making it important to understand how the cellular machinery recognizes and processes such proteins. A key question in this respect is whether misfolded proteins are handled in a similar way regardless of their genetic origin. To approach this question, we compared how three different misfolded proteins, guk1-7, gus1-3, and pro3-1, are handled by the cell. We show that all three are nontoxic, even though highly overexpressed, highlighting their usefulness in analyzing the cellular response to misfolding in the absence of severe stress. We found significant differences between the aggregation and disaggregation behavior of the misfolded proteins. Specifically, gus1-3 formed some aggregates that did not efficiently recruit the protein disaggregase Hsp104 and did not colocalize with the other misfolded reporter proteins. Strikingly, while all three misfolded proteins generally coaggregated and colocalized to specific sites in the cell, disaggregation was notably different; the rate of aggregate clearance of pro3-1 was faster than that of the other misfolded proteins, and its clearance rate was not hindered when pro3-1 colocalized with a slowly resolved misfolded protein. Finally, we observed using super-resolution light microscopy as well as immunogold labeling EM in which both showed an even distribution of the different misfolded proteins within an inclusion, suggesting that misfolding characteristics and remodeling, rather than spatial compartmentalization, allows for differential clearance of these misfolding reporters residing in the same inclusion. Taken together, our results highlight how properties of misfolded proteins can significantly affect processing

    Using reporters of different misfolded proteins reveals differential strategies in processing protein aggregates

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    The accumulation of misfolded proteins is a hallmark of aging and many neurodegenerative diseases, making it important to understand how the cellular machinery recognizes and processes such proteins. A key question in this respect is whether misfolded proteins are handled in a similar way regard less of their genetic origin. To approach this question, we compared how three different misfolded proteins, guk1-7,gus1-3, and pro3-1, are handled by the cell. We show that all three are nontoxic, even though highly overexpressed, high-lighting their usefulness in analyzing the cellular response to misfolding in the absence of severe stress. We found significant differences between the aggregation and disaggregation behavior of the misfolded proteins. Specifically, gus1-3 formed some aggregates that did not efficiently recruit the proteindisaggregase Hsp104 and did not colocalize with the other misfolded reporter proteins. Strikingly, while all three misfolded proteins generally coaggregated and colocalized to specific sites in the cell, disaggregation was notably different; the rate of aggregate clearance of pro3-1 was faster than that of the other misfolded proteins, and its clearance rate was nothindered when pro3-1 colocalized with a slowly resolved mis-folded protein. Finally, we observed using super-resolutionlight microscopy as well as immunogold labeling EM in which both showed an even distribution of the different mis-folded proteins within an inclusion, suggesting that misfolding characteristics and remodeling, rather than spatial compart-mentalization, allows for differential clearance of these mis-folding reporters residing in the same inclusion. Taken together, our results highlight how properties of misfolded proteins can significantly affect processing

    Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1α-controlled BNP

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    Activation of resident and infiltrating immune cells is a central event in training adaptation and other contexts of skeletal muscle repair and regeneration. A precise orchestration of inflammatory events in muscle fibers and immune cells is required after recurrent contraction-relaxation cycles. However, the mechanistic aspects of this important regulation remain largely unknown. We now demonstrate that besides a dominant role in controlling cellular metabolism, the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) also has a profound effect on cytokine expression in muscle tissue. Muscle PGC-1α expression results in activation of tissue-resident macrophages, at least in part mediated by PGC-1α-dependent B-type natriuretic peptide (BNP) production and secretion. Positive effects of exercise in metabolic diseases and other pathologies associated with chronic inflammation could accordingly involve the PGC-1α-BNP axis and thereby provide novel targets for therapeutic approaches

    Baryon stopping and strange baryon/antibaryon production at SPS energies

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    The amount of proton stopping in central Pb+Pb collisions from 20-160 AGeV as well as hyperon and antihyperon rapidity distributions are calculated within the UrQMD model in comparison to experimental data at 40, 80 and 160 AGeV taken recently from the NA49 collaboration. Furthermore, the amount of baryon stopping at 160 AGeV for Pb+Pb collisions is studied as a function of centrality in comparison to the NA49 data. We find that the strange baryon yield is reasonably described for central collisions, however, the rapidity distributions are somewhat more narrow than the data. Moreover, the experimental antihyperon rapidity distributions at 40, 80 and 160 AGeV are underestimated by up to factors of 3 - depending on the annihilation cross section employed - which might be addressed to missing multi-meson fusion channels in the UrQMD model.Comment: 18 pages, including 7 eps figures, to be published in Phys. Rev.

    On the IYB-property in some solvable groups

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    A finite group G is called Involutive Yang-Baxter (IYB) if there exists a bijective 1-cocycle χ:G⟶M for some ZG -module M. It is known that every IYB-group is solvable, but it is still an open question whether the converse holds. A characterization of the IYB property by the existence of an ideal I in the augmentation ideal ωZG complementing the set 1−G leads to some speculation that there might be a connection with the isomorphism problem for ZG . In this paper we show that if N is a nilpotent group of class two and H is an IYB-group of order coprime to that of N, then N⋊H is IYB. The class of groups that can be obtained in that way (and hence are IYB) contains in particular Hertweck’s famous counterexample to the isomorphism conjecture as well as all of its subgroups. We then investigate what an IYB structure on Hertweck’s counterexample looks like concretely

    Stratigraphy of the Pleistocene, phonolitic Cão Grande Formation on Santo Antão, Cape Verde

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    Highlights: • Two new phonolitic tephra units complementing the two previously known. • First radiometric ages of the CGF. • Contemporaneously evolution of the CGF and the Tope de Coroa. • Marine correlations improve tephra volume estimations for CG I and II. Abstract: The Cão Grande Formation (CGF) on the western plateau of Santo Antão Island is part of the younger volcanic sequence that originated from both, basanitic and nephelinitic magmatic suites, respectively called COVA and COROA suites. Based on our detailed revised stratigraphy of the CGF, including two yet unknown tephra units, we can show that both suites produced multiple, highly differentiated eruptions over a contemporaneous period. Correlations of CGF tephras with marine ash layers provide distal dispersal data for Cão Grande I (CG I) and also identify two highly explosive, phonolitic eruptions that pre-date the CGF tephra deposits known on land. Within the CGF, the lowermost, 220±7 ka old unit Canudo Tephra (CT; COVA suite) comprises phonolitic fall deposits and ignimbrites; it is partly eroded and overlain by debris flow deposits marking a hiatus in highly differentiated eruptions. The phonolitic CG I Tephra (COROA suite) consists of an initial major plinian fall deposit and associated ignimbrite and terminal surge deposits. This is immediately overlain by the phonolitic to phono-tephritic Cão Grande II (CG II; COVA suite), a complex succession of numerous fallout layers and density-current deposits. CG I and CG II have radiometric ages of 106±3 ka and 107±15 ka, respectively, that are identical within their error limits. The youngest CGF unit, the Furninha Tephra (FT; COROA suite), consists of three foidic-phonolitic fall deposits interbedded with proximal scoria deposits from a different vent. The phonolitic eruptions switched to and fro between both magmatic suites, in each case with a stronger first followed by a weaker second eruption. Each eruption evolved from stable to unstable eruption columns. During their terminal phases, both magma systems also leaked evolved dome-forming lavas next to the tephras. Distal ashes increase the CG I tephra volume to ~ 10 km3, about twice the previously published estimate. The tephra volume of CG II is ~ 3 km3; CT and FT are too poorly exposed for volume estimation. The characteristics of the CGF tephra units outline hazard conditions that may be expected from future evolved explosive eruptions on the western plateau of Santo Antão
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