Telomere Recombination Accelerates Cellular Aging in Saccharomyces cerevisiae

Telomeres are nucleoprotein structures located at the linear ends of eukaryotic chromosomes. Telomere integrity is required for cell proliferation and survival. Although the vast majority of eukaryotic species use telomerase as a primary means for telomere maintenance, a few species can use recombination or retrotransposon-mediated maintenance pathways. Since Saccharomyces cerevisiae can use both telomerase and recombination to replicate telomeres, budding yeast provides a useful system with which to examine the evolutionary advantages of telomerase and recombination in preserving an organism or cell under natural selection. In this study, we examined the life span in telomerase-null, post-senescent type II survivors that have employed homologous recombination to replicate their telomeres. Type II recombination survivors stably maintained chromosomal integrity but exhibited a significantly reduced replicative life span. Normal patterns of cell morphology at the end of a replicative life span and aging-dependent sterility were observed in telomerase-null type II survivors, suggesting the type II survivors aged prematurely in a manner that is phenotypically consistent with that of wild-type senescent cells. The shortened life span of type II survivors was extended by calorie restriction or TOR1 deletion, but not by Fob1p inactivation or Sir2p over-expression. Intriguingly, rDNA recombination was decreased in type II survivors, indicating that the premature aging of type II survivors was not caused by an increase in extra-chromosomal rDNA circle accumulation. Reintroduction of telomerase activity immediately restored the replicative life span of type II survivors despite their heterogeneous telomeres. These results suggest that telomere recombination accelerates cellular aging in telomerase-null type II survivors and that telomerase is likely a superior telomere maintenance pathway in sustaining yeast replicative life span

Four-leg converters with improved common current sharing and selective voltage-quality enhancement for islanded microgrids

Four-leg dc-ac power converters are widely used for the power grids to manage grid voltage unbalance caused by the interconnection of single-phase or three-phase unbalanced loads. These converters can further be connected in parallel to increase the overall power rating. The control of these converters poses a particular challenge if they are placed far apart with no links between them (e.g., in islanded microgrids). This challenge is studied in this paper with each four-leg converter designed to have improved common current sharing and selective voltage-quality enhancement. The common current sharing, including zero sequence component, is necessary since loads are spread over the microgrid and they are hence the common responsibility of all converters. The voltage-quality enhancement consideration should however be more selective since different loads have different sensitivity levels towards voltage disturbances. Converters connected to the more sensitive load buses should therefore be selectively triggered for compensation when voltage unbalances at their protected buses exceed the predefined thresholds. The proposed scheme is therefore different from conventional centralized schemes protecting only a common bus. Simulation and experimental results obtained have verified the effectiveness of the proposed scheme when applied to a four-wire islanded microgrid

Effect of congenital ptosis on astigmatism and axis length

AIM: To investigate the effects of congenital ptosis degree on total astigmatism, corneal astigmatism, intraocular astigmatism and axis length, and to discuss the relation with amblyopia. <p>METHODS: Fifty patients(100 eyes)with congenital ptosis were selected and divided into four groups: 33 eyes in group Ⅰ(normal); 20 eyes in group Ⅱ(mild); 17 eyes in group Ⅲ(moderate); 30 eyes in group Ⅳ(severity). Firstly, they received standardized medical optometry. Absolute value of astigmatism was recorded as total astigmatism. Then, corneal topography was used to measure double eyes for at least 3 times, and the best results were used to record the SimK. Define absolute value of △SimK as corneal astigmatism. Finally, axial length was measured for 5 times by A super-measurement, and take the mean value. Formula: intraocular astigmatism=total astigmatism-corneal astigmatism.<p>RESULTS: There was a significance difference between total astigmatism and cornea astigmatism(<i>P</i>=0.000, 0.002<0.05). Also they were positive correlation with severity of ptosis(Spearman <i>r</i>_s=0.514, 0.721,<i>P</i><0.05), but there was not significance difference in axial orientation, intraocular astigmatism and axial length(all <i>P</i>>0.05). The axial orientation, intraocular astigmatism had no correlation with severity of ptosis.<p>CONCLUSION: The congenital ptosis affects on eye astigmatism through the change of cornea astigmatism, which is related to severity of ptosis, but has no effect on axial length. The rate of amblyopia is higher than normal on congenital ptosisespecially severity. Amblyopia is related to high astigmatism which is moderate astigmatism with rule

Identification and pharmacokinetics of saponins in Rhizoma Anemarrhenae after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MS

Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, Tmax value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies

Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization

Scope: Obesity is closely related to the imbalance of white adipose tissue storing excess calories, and brown adipose tissue dissipating energy to produce heat in mammals. Recent studies revealed that acquisition of brown characteristics by white adipocytes, termed “browning,” may positively contribute to cellular bioenergetics and metabolism homeostasis. The goal was to investigate the putative effects of natural antioxidant sulforaphane (1-isothiocyanate-4-methyl-sulfonyl butane; SFN) on browning of white adipocytes. Methods and Results: 3T3-L1 mature white adipocytes were treated with SFN for 48 h, and then the mitochondrial content, function, and energy utilization were assessed. SFN was found to induce 3T3-L1 adipocytes browning based on the increased mitochondrial content and activity of respiratory chain enzymes, whereas the mechanism involved the upregulation of nuclear factor E2-related factor 2/ sirtuin1/ peroxisome proliferator-activated receptor gamma coactivator 1 alpha signaling. SFN enhanced uncoupling protein 1 expression, a marker for brown adipocyte, leading to the decrease in cellular ATP. SFN also enhanced glucose uptake and oxidative utilization, lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Conclusion: SFN-induced browning of white adipocytes enhanced the utilization of cellular fuel, and the application of SFN is a promising strategy to combat obesity and obesity-related metabolic disorder

Alternative O-GlcNAcylation/O-Phosphorylation of Ser16 Induce Different Conformational Disturbances to the N Terminus of Murine Estrogen Receptor β

SummarySerine and threonine residues in many proteins can be modified by either phosphorylation or GlcNAcylation. To investigate the mechanism of O-GlcNAc and O-phosphate's reciprocal roles in modulating the degradation and activity of murine estrogen receptor β (mER-β), the conformational changes induced by O-GlcNAcylation and O-phosphorylation of Ser16 in 17-mer model peptides corresponding to the N-terminal intrinsically disordered (ID) region of mER-β were studied by NMR techniques, circular dichroism (CD), and molecular dynamics simulations. Our results suggest that O-phosphorylation discourages the turn formation in the S15STG18 fragment. In contrast, O-GlcNAcylation promotes turn formation in this region. Thus, we postulate that the different changes of the local structure in the N-terminal S15STG18 fragment of mER-β caused by O-phosphate or O-GlcNAc modification might lead to the disturbances to the dynamic ensembles of the ID region of mER-β, which is related to its modulatory activity

KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration

Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by adeno-associated virus 2 (AAV2)-KLF7 in vitro. Mice were allografted by an acellular nerve (ANA) with either an injection of DMEM (ANA group), SCs (ANA + SCs group) or AAV2-KLF7-transfected SCs (ANA + KLF7-SCs group) to assess repair of a sciatic nerve gap. The results indicate that KLF7 overexpression promoted the proliferation of both transfected SCs and native SCs. The neurite length of the dorsal root ganglia (DRG) explants was enhanced. Several beneficial effects were detected in the ANA + KLF7-SCs group including an increase in the compound action potential amplitude, sciatic function index score, enhanced expression of PKH26-labeling transplant SCs, peripheral myelin protein 0, neurofilaments, S-100, and myelinated regeneration nerve. Additionally, HRP-labeled motoneurons in the spinal cord, CTB-labeled sensory neurons in the DRG, motor endplate density and the weight ratios of target muscles were increased by the treatment while thermal hyperalgesia was diminished. Finally, expression of KLF7, NGF, GAP43, TrkA and TrkB were enhanced in the grafted SCs, which may indicate that several signal pathways may be involved in conferring the beneficial effects from KLF7 overexpression. We concluded that KLF7-overexpressing SCs promoted axonal regeneration of the peripheral nerve and enhanced myelination, which collectively proved KLF-SCs as a novel therapeutic strategy for injured nerves