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Hypothalamic Sirt1 protects terminal Schwann cells and neuromuscular junctions from age‐related morphological changes 下载免费PDF全文
Alison K. Snyder‐Warwick Akiko Satoh Katherine B. Santosa Shin‐ichiro Imai Albina Jablonka‐Shariff 《Aging cell》2018,17(4)
Neuromuscular decline occurs with aging. The neuromuscular junction (NMJ), the interface between motor nerve and muscle, also undergoes age‐related changes. Aging effects on the NMJ components—motor nerve terminal, acetylcholine receptors (AChRs), and nonmyelinating terminal Schwann cells (tSCs)—have not been comprehensively evaluated. Sirtuins delay mammalian aging and increase longevity. Increased hypothalamic Sirt1 expression results in more youthful physiology, but the relationship between NMJ morphology and hypothalamic Sirt1 was previously unknown. In wild‐type mice, all NMJ components showed age‐associated morphological changes with ~80% of NMJs displaying abnormalities by 17 months of age. Aged mice with brain‐specific Sirt1 overexpression (BRASTO) had more youthful NMJ morphologic features compared to controls with increased tSC numbers, increased NMJ innervation, and increased numbers of normal AChRs. Sympathetic NMJ innervation was increased in BRASTO mice. In contrast, hypothalamic‐specific Sirt1 knockdown led to tSC abnormalities, decreased tSC numbers, and more denervated endplates compared to controls. Our data suggest that hypothalamic Sirt1 functions to protect NMJs in skeletal muscle from age‐related changes via sympathetic innervation. 相似文献
104.
In a quest to identify new ground-state triplet germylenes, the stabilities (singlet–triplet energy differences, ΔES–T) of 96 singlet (s) and triplet (t) M1-Ge-M2-M3 species were compared and contrasted at the B3LYP/6–311++G**, QCISD(T)/6–311++G**, and CCSD(T)/6–311++G** levels of theory (M1?=?H, Li, Na, K; M2?=?Be, Mg, Ca; M3?=?H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M3?=?F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M3?=?Cl or Br). Triplets with M1?=?K (i.e., the K-Ge-M2-M3 series) seem to be more stable than the corresponding triplets with M1?=?H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M3?=?Cl behave similarly to those with M3?=?Br. Conversely, triplets with M3?=?H show similar stabilities and linearities to those with M3?=?F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M1-Ge-M2-M3 become more stable as the electropositivities of the α-substituents (M1 and M2) and the electronegativity of the β-substituent (M3) increase. 相似文献
105.
Md. Zahirul Kabir Hamidah Ghani Saharuddin B. Mohamad Zazali Alias 《Journal of biomolecular structure & dynamics》2018,36(10):2495-2507
Multiple spectroscopic techniques, such as fluorescence, absorption, and circular dichroism along with in silico studies were used to characterize the binding of a potent inhibitor molecule, CCG1423 to the major transport protein, human serum albumin (HSA). Fluorescence and absorption spectroscopic results confirmed CCG1423–HSA complex formation. A strong binding affinity stabilized the CCG1423–HSA complex, as evident from the values of the binding constant (Ka = 1.35 × 106–5.43 × 105 M?1). The KSV values for CCG1423–HSA system were inversely correlated with temperature, suggesting the involvement of static quenching mechanism. Thermodynamic data anticipated that CCG1423–HSA complexation was mainly driven by hydrophobic and van der Waals forces as well as hydrogen bonds. In silico analysis also supported these results. Three-dimensional fluorescence and circular dichroism spectral analysis suggested microenvironmental perturbations around protein fluorophores and structural (secondary and tertiary) changes in the protein upon CCG1423 binding. CCG1423 binding to HSA also showed some protection against thermal denaturation. Site-specific marker-induced displacement results revealed CCG1423 binding to Sudlow’s site I of HSA, which was also confirmed by the computational results. A few common ions were also found to interfere with the CCG1423–HSA interaction. 相似文献
106.
Jinbiao Ma Xinlong Xiao Li Li Albino Maggio Dayong Zhang Osama Abdalla Abdelshafy Mohamad Michael Van Oosten Gang Huang Yufang Sun Changyan Tian Yinan Yao 《Acta Physiologiae Plantarum》2018,40(8):140
Glycophytic plants suffer from severe stress and injury when roots are exposed to high salinity in the rhizosphere. In contrast, the euhalophyte Salicornia europaea grows well at 200 mM NaCl and can withstand up to 1000 mM NaCl in the root zone. Analysis of gene expression profiles and the underlying molecular mechanisms responsible for this tolerance have been largely overlooked. Using the Illumina sequencing platform and the short-reads assembly programme Trinity, we generated a total of 40 and 39 million clean reads and further 140,086 and 122,728 unigenes from the 200 mM NaCl and 0 mM NaCl treated tissues of S. europaea roots, respectively. All unigenes in this study were functionally annotated within context of the COG, GO and KEGG pathways. Unigene functional annotation analysis allowed us to identify hundreds of ion transporters related to homeostasis and osmotic adaptation as well as a variety of proteins related to cation, amino acid, lipid and sugar transport. We found significant enrichment in response to stress including the functional categories of “antioxidant activity”, “catalytic activity” and “response to stimuli”. These findings represent for a useful resource for the scientific community working on salt tolerance mechanisms. Conversely, a total of 8639 EST-SSRs from 131,594 unigenes were identified and 4539 non-redundant SSRs primers pairs were developed. These data provide a good foundation for future studies on molecular adaptation mechanisms of euhalophytes roots under saline environments and will likely facilitate the identification of critical salt tolerance traits to be transferred in economically important crops. 相似文献
107.
D. W. Lee Steven F. Oberbauer Baskaran Krishnapilay Marzalina Mansor Haris Mohamad Son Kheong Yap 《Oecologia》1997,110(1):1-9
Seedling developmental responses to understory shade combine the effects of reductions in irradiance and changes in spectral
quality. We studied the seedling development of two Southeast Asian dipterocarp trees in response to differences in irradiance
(photosynthetic photon flux density, PPFD) and spectral quality (red to far-red ratio, R:FR). The two species, Hopea helferei and H. odorata, are taxonomically closely related but differ in their ecological requirements; H. helferei is more drought-tolerant and typically grows in more open habitats. Seedlings were grown in six different replicated shadehouse
treatments varying in percentage of solar PPFD and R:FR. The two species differed in the influence of light variables on most
seedling characters, particularly for final height, internode distance, branch/trunk internodes, stem length/mass, leaf area/stem
length, petiole length, and growth/mol of photons received. Most of the characters in both taxa were primarily influenced
by PPFD, but spectral quality also influenced some characters – more so for H. odorata. The latter species grew more rapidly, particularly in the low PPFD treatments, and its leaves were capable of higher photosynthesis
rates. However, growth in H. helferei was not reduced in direct sunlight. The growth of this taxon may be constrained by adaptations, particularly in leaves, for
drought tolerance.
Received: 14 April 1996 / Accepted: 8 October 1996 相似文献
108.
Endah Dwi Hartuti Daniel Ken Inaoka Keisuke Komatsuya Yukiko Miyazaki Russell J. Miller Wang Xinying Mohamad Sadikin Erwahyuni Endang Prabandari Danang Waluyo Marie Kuroda Eri Amalia Yuichi Matsuo Nuki B. Nugroho Hiroyuki Saimoto Amila Pramisandi Yoh-Ichi Watanabe Mihoko Mori Kazuro Shiomi Kiyoshi Kita 《BBA》2018,1859(3):191-200
Plasmodium falciparum is an apicomplexan parasite that causes the most severe malaria in humans. Due to a lack of effective vaccines and emerging of drug resistance parasites, development of drugs with novel mechanisms of action and few side effects are imperative. To this end, ideal drug targets are those essential to parasite viability as well as absent in their mammalian hosts. The mitochondrial electron transport chain (ETC) of P. falciparum is one source of such potential targets because enzymes, such as L-malate:quinone oxidoreductase (PfMQO), in this pathway are absent humans. PfMQO catalyzes the oxidation of L-malate to oxaloacetate and the simultaneous reduction of ubiquinone to ubiquinol. It is a membrane protein, involved in three pathways (ETC, the tricarboxylic acid cycle and the fumarate cycle) and has been shown to be essential for parasite survival, at least, in the intra-erythrocytic asexual stage. These findings indicate that PfMQO would be a valuable drug target for development of antimalarial with novel mechanism of action. Up to this point in time, difficulty in producing active recombinant mitochondrial MQO has hampered biochemical characterization and targeted drug discovery with MQO. Here we report for the first time recombinant PfMQO overexpressed in bacterial membrane and the first biochemical study. Furthermore, about 113 compounds, consisting of ubiquinone binding site inhibitors and antiparasitic agents, were screened resulting in the discovery of ferulenol as a potent PfMQO inhibitor. Finally, ferulenol was shown to inhibit parasite growth and showed strong synergism in combination with atovaquone, a well-described anti-malarial and bc1 complex inhibitor. 相似文献
109.