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41.
Niacin supplementation induces type II to type I muscle fiber transition in skeletal muscle of sheep
Muckta?Khan Aline?Couturier Johanna?F?Kubens Erika?Most Frank-Christoph?Mooren Karsten?Krüger Robert?Ringseis Klaus?EderEmail author 《Acta veterinaria Scandinavica》2013,55(1):85
Background
It was recently shown that niacin supplementation counteracts the obesity-induced muscle fiber transition from oxidative type I to glycolytic type II and increases the number of type I fibers in skeletal muscle of obese Zucker rats. These effects were likely mediated by the induction of key regulators of fiber transition, PPARδ (encoded by PPARD), PGC-1α (encoded by PPARGC1A) and PGC-1β (encoded by PPARGC1B), leading to type II to type I fiber transition and upregulation of genes involved in oxidative metabolism. The aim of the present study was to investigate whether niacin administration also influences fiber distribution and the metabolic phenotype of different muscles [M. longissimus dorsi (LD), M. semimembranosus (SM), M. semitendinosus (ST)] in sheep as a model for ruminants. For this purpose, 16 male, 11 wk old Rhoen sheep were randomly allocated to two groups of 8 sheep each administered either no (control group) or 1 g niacin per day (niacin group) for 4 wk.Results
After 4 wk, the percentage number of type I fibers in LD, SM and ST muscles was greater in the niacin group, whereas the percentage number of type II fibers was less in niacin group than in the control group (P?<?0.05). The mRNA levels of PPARGC1A, PPARGC1B, and PPARD and the relative mRNA levels of genes involved in mitochondrial fatty acid uptake (CPT1B, SLC25A20), tricarboxylic acid cycle (SDHA), mitochondrial respiratory chain (COX5A, COX6A1), and angiogenesis (VEGFA) in LD, SM and ST muscles were greater (P?<?0.05) or tended to be greater (P?<?0.15) in the niacin group than in the control group.Conclusions
The study shows that niacin supplementation induces muscle fiber transition from type II to type I, and thereby an oxidative metabolic phenotype of skeletal muscle in sheep as a model for ruminants. The enhanced capacity of skeletal muscle to utilize fatty acids in ruminants might be particularly useful during metabolic states in which fatty acids are excessively mobilized from adipose tissue, such as during the early lactating period in high producing cows.42.
43.
Anja Drinkut Karsten Tillack Durga P Meka Jorg B Schulz Sebastian Kügler Edgar R Kramer 《Cell death & disease》2016,7(9):e2359
Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF''s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF''s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD.Glial cell line-derived neurotrophic factor (GDNF) is the founding member of the four ligands in the GDNF family, which belong to the transforming growth factor-β superfamily.1 GDNF was characterized as a potent survival factor for many neurons in culture such as dopaminergic, motor, sympathetic, parasympathetic, sensory and enteric neurons.1, 2 In addition, in dopaminergic neuron cultures GDNF stimulates neuronal differentiation, neurite outgrowth, synapse formation and dopamine release.1, 2As degeneration of midbrain dopaminergic neurons in the substantia nigra pars compacta (SNpc) represents a major hallmark of Parkinson disease (PD), the most common neurodegenerative movement disorder, GDNF has raised considerable interest as a therapeutic molecule for the treatment of PD.3, 4, 5 PD affects >2% of individuals over the age of 60 years, but no curative treatment is available to date, mainly due to a lack of understanding disease etiology.6, 7, 8 Preclinical studies in the established 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) rodent and primate models of PD demonstrated a substantial neuroprotection and regeneration effect by striatal provided GDNF or its close relative neurturin.3, 4, 9 However, clinical phase II trials on PD patients using GDNF or neurturin did so far not convincingly recapitulate their beneficial effects on the dopaminergic system in humans most likely due to technical problems and the selection of advanced PD patients.10, 11, 12, 13GDNF signaling is highly complex as this neurotrophic factor can bind to a variety of receptors, thus being able to induce pleiotropic effects. GDNF efficiently binds to the GPI-linked GDNF family receptor α1 (GFRα1).1, 2 It has been shown that the GDNF/GFRα1 complex can activate not only the canonical GDNF receptor Ret, a receptor tyrosine kinase which signals through the sarcoma protein (Src)/rat sarcoma (Ras)/mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt, NF-κB (nuclear factor ''kappa-light-chain-enhancer'' of activated B cells), JNK (c-Jun N-terminal kinases) and PLCγ (phospholipase γ) pathway, but also with other signaling inducing receptors.1, 2, 4, 5, 13 So far, at least four alternative GDNF receptors have been described which are all expressed in midbrain dopaminergic neurons, NCAM,14, 15 the integrins αV and βI,14, 16 syndecan 317 and N-cadherin.18 Interestingly, Ret is not essential during pre- and postnatal development of the mouse dopaminergic system,19, 20, 21, 22, 23 but specifically required for the maintenance of SNpc dopaminergic neurons and their striatal innervation in aged mice.23, 24, 25 In contrast, GDNF seems most likely under physiological conditions to be dispensable during development and maintenance of midbrain dopaminergic neurons in mice, although conflicting results exist.26, 27, 28 Thus, Ret might be activated by a GDNF-independent mechanism to stimulate SNpc dopaminergic neuron survival. In addition, the in vivo function of the alternative GDNF receptors in the dopaminergic system under physiological and pathophysiological conditions, like PD, and their dependence on GDNF has not yet been addressed in detail. This raised the important question which GDNF receptor might be required to mediate GDNF''s reported neuroprotective and regenerative effect in the dopaminergic system in PD animal models and potentially in PD patients.5, 29Previously, we showed in dopaminergic neuron-specific Ret knockout mice that Ret receptor loss does not result in a higher vulnerability of midbrain dopaminergic neurons against MPTP but to less resprouting of left over dopaminergic neuron axons in the striatum after MPTP intoxication.30 In adult mice endogenous GDNF levels are rather low.26, 31 Therefore, we could not rule out in that study the possibility, that higher levels of GDNF—as also used in the clinical GDNF trials in PD patients—might have neuroprotective and regenerating effects even in the absence of the Ret receptor. Here we addressed now this question by viral overexpression of GDNF in MPTP-treated mice lacking expression of Ret again specifically in dopaminergic neurons.23, 30 We found that in the absence of Ret in dopaminergic neurons even a substantial overexpression of GDNF in the striatum does not have a neuroprotective and regenerative effect. Thus, despite the expression of alternative GDNF receptors on midbrain dopaminergic neurons, the presence of the canonical GDNF receptor Ret seems to be mandatory for mediating GDNF''s beneficial survival and axonal resprouting effect in these neurons. 相似文献
44.
Sidsel L. Domazet Jakob Tarp Tao Huang Anne K?r Gejl Lars Bo Andersen Karsten Froberg Anna Bugge 《PloS one》2016,11(1)
Objectives
To examine objectively measured physical activity level, organized sports participation and active commuting to school in relation to mathematic performance and inhibitory control in adolescents.Methods
The design was cross-sectional. A convenient sample of 869 sixth and seventh grade students (12–14 years) was invited to participate in the study. A total of 568 students fulfilled the inclusion criteria and comprised the final sample for this study. Mathematic performance was assessed by a customized test and inhibitory control was assessed by a modified Eriksen flanker task. Physical activity was assessed with GT3X and GT3X+ accelerometers presented in sex-specific quartiles of mean counts per minute and mean minutes per day in moderate-to-vigorous physical activity. Active commuting and sports participation was self-reported. Mixed model regression was applied. Total physical activity level was stratified by bicycling status in order to bypass measurement error subject to the accelerometer.Results
Non-cyclists in the 2nd quartile of counts per minute displayed a higher mathematic score, so did cyclists in the 2nd and 3rd quartile of moderate-to-vigorous physical activity relative to the least active quartile. Non-cyclists in the 3rd quartile of counts per minute had an improved reaction time and cyclists in the 2nd quartile of counts per minute and moderate-to-vigorous physical activity displayed an improved accuracy, whereas non-cyclists in the 2nd quartile of counts per minute showed an inferior accuracy relative to the least active quartile. Bicycling to school and organized sports participation were positively associated with mathematic performance.Conclusions
Sports participation and bicycling were positively associated with mathematic performance. Results regarding objectively measured physical activity were mixed. Although, no linear nor dose-response relationship was observed there was no indication of a higher activity level impairing the scholastic or cognitive performance. 相似文献45.
Anne Mayer-Scholl Jayaseelan Murugaiyan Jennifer Neumann Peter Bahn Sabine Reckinger Karsten N?ckler 《PloS one》2016,11(3)
Human trichinellosis occurs through consumption of raw or inadequately processed meat or meat products containing larvae of the parasitic nematodes of the genus Trichinella. Currently, nine species and three genotypes are recognized, of which T. spiralis, T. britovi and T. pseudospiralis have the highest public health relevance. To date, the differentiation of the larvae to the species and genotype level is based primarily on molecular methods, which can be relatively time consuming and labor intensive. Due to its rapidness and ease of use a matrix assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF MS) reference spectra database using Trichinella strains of all known species and genotypes was created. A formicacid/acetonitrile protein extraction was carried out after pooling 10 larvae of each Trichinella species and genotype. Each sample was spotted 9 times using α-cyano 4-hydoxy cinnamic acid matrix and a MicroFlex LT mass spectrometer was used to acquire 3 spectra (m/z 2000 to 20000 Da) from each spot resulting in 27 spectra/species or genotype. Following the spectra quality assessment, Biotyper software was used to create a main spectra library (MSP) representing nine species and three genotypes of Trichinella. The evaluation of the spectra generated by MALDI-TOF MS revealed a classification which was comparable to the results obtained by molecular methods. Also, each Trichinella species utilized in this study was distinct and distinguishable with a high confidence level. Further, different conservation methods such as freezing and conservation in alcohol and the host species origin of the isolated larvae did not have a significant influence on the generated spectra. Therefore, the described MALDI-TOF MS can successfully be implemented for both genus and species level identification and represents a major step forward in the use of this technique in foodborne parasitology. 相似文献
46.
47.
Anne-Marie Lundsgaard Jacob B. Holm Kim A. Sjøberg Kirstine N. Bojsen-Møller Lene S. Myrmel Even Fjære Benjamin A.H. Jensen Trine S. Nicolaisen Janne R. Hingst Sine L. Hansen Sophia Doll Philip E. Geyer Atul S. Deshmukh Jens J. Holst Lise Madsen Karsten Kristiansen Jørgen F.P. Wojtaszewski Erik A. Richter Bente Kiens 《Cell metabolism》2019,29(1):50-63.e4
48.
Guangyi Fan Yaolei Zhang Xiaochuan Liu Jiahao Wang Zeguo Sun Shuai Sun He Zhang Jianwei Chen Meiqi Lv Kai Han Xiaoxuan Tan Jie Hu Rui Guan Yuanyuan Fu Shanshan Liu Xi Chen Qiwu Xu Yating Qin Longqi Liu Jie Bai Ou Wang Jingbo Tang Haorong Lu Zhouchun Shang Bo Wang Guohai Hu Xia Zhao Yan Zou Ao Chen Meihua Gong Wenwei Zhang Simon M.‐Y. Lee Songhai Li Junnian Liu Zhen Li Yishan Lu Jamal S. M. Sabir Mumdooh J. Sabir Muhummadh Khan Nahid H. Hajrah Ye Yin Karsten Kristiansen Huanming Yang Jian Wang Xun Xu Xin Liu 《Molecular ecology resources》2019,19(4):944-956
Marine mammals are important models for studying convergent evolution and aquatic adaption, and thus reference genomes of marine mammals can provide evolutionary insights. Here, we present the first chromosome‐level marine mammal genome assembly based on the data generated by the BGISEQ‐500 platform, for a stranded female sperm whale (Physeter macrocephalus). Using this reference genome, we performed chromosome evolution analysis of the sperm whale, including constructing ancestral chromosomes, identifying chromosome rearrangement events and comparing with cattle chromosomes, which provides a resource for exploring marine mammal adaptation and speciation. We detected a high proportion of long interspersed nuclear elements and expanded gene families, and contraction of major histocompatibility complex region genes which were specific to sperm whale. Using comparisons with sheep and cattle, we analysed positively selected genes to identify gene pathways that may be related to adaptation to the marine environment. Further, we identified possible convergent evolution in aquatic mammals by testing for positively selected genes across three orders of marine mammals. In addition, we used publicly available resequencing data to confirm a rapid decline in global population size in the Pliocene to Pleistocene transition. This study sheds light on the chromosome evolution and genetic mechanisms underpinning sperm whale adaptations, providing valuable resources for future comparative genomics. 相似文献
49.
Natalia Poplavskaya Anna Bannikova Karsten Neumann Marina Pavlenko Irina Kartavtseva Yuriy Bazhenov Pavel Bogomolov Alexey Abramov Alexey Surov Vladimir Lebedev 《Journal of Zoological Systematics and Evolutionary Research》2019,57(3):679-694
Striped hamsters (Cricetulus barabensis sensu lato) represent a complex of chromosomally distinct allopatric lineages/taxa of either species or subspecies rank. They are widely distributed across the steppes of eastern and central Palearctic. Phylogenetic analysis of cytochrome b gene sequences based on 496 specimens from 112 localities revealed five well‐supported lineages divergent at 2%–4%. Two of them correspond to “griseus” (2n = 22) and “pseudogriseus” (2n = 24) karyomorphs and are placed as sister taxa. The “barabensis” (2n = 20) karyomorph is represented by three other branches and appears non‐monophyletic. All mtDNA lineages are distributed allopatrically or parapatrically; no indications of gene flow between populations of different chromosomal races were found. The results of the molecular clock analysis suggest that the main lineages diverged in the late Middle Pleistocene. The inferred evolutionary scenario implies that the common ancestor of the recent lineages belonged to the 2n = 20 karyomorph and originated in the eastern part of the contemporary range. 相似文献
50.
Regulatory T cells (Treg) were originally described by their suppressive function exerted on effector T cells, but recent evidence also reveals interactions with antigen presenting cells (APCs). In general, all major subpopulations of APCs, i.e., dendritic cells (DC), B cells and monocytes/macrophages (Mvarphi), respond to exposure to Treg by down regulation of their antigen presenting function, upregulation of immunosuppressive molecules and secretion of immunosuppressive cytokines. Thus, Treg gain influence on the innate immune system and are able to augment their immunosuppressive capacities by blocking the effective priming of T effector cells by APCs. Conversely, APCs have an important role in nurturing peripheral Treg populations, since it has been shown that immature DC, as well as alternatively activated Mvarphi, are able to induce Treg de novo. These properties are dependent on the expression of surface molecules (CTLA-4, F4/80) and the production of soluble factors such as IL-10 and Indoleamine 2,3-dioxygenase by the APC subpopulations. On the whole, the mutual interaction of Treg and APCs enables Treg to sustain their immunosuppressive functions which, in healthy individuals, may be crucial for the maintenance of peripheral tolerance. 相似文献