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101.
Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi’s sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.
相似文献
102.
103.
Estella A. Newcombe Kiersten M. Ruff Ashish Sethi Angelique R. Ormsby Yasmin M. Ramdzan Archa Fox Anthony W. Purcell Paul R. Gooley Rohit V. Pappu Danny M. Hatters 《Journal of molecular biology》2018,430(10):1442-1458
Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington's disease. To uncover the physical basis of this toxicity, we performed structural studies of soluble Httex1 for wild-type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence for conformational rigidity across the polyQ region. In contrast, hydrogen–deuterium exchange shows absence of backbone amide protection, suggesting negligible persistence of hydrogen bonds. The seemingly conflicting results are explained by all-atom simulations, which show that Httex1 adopts tadpole-like structures with a globular head encompassing the N-terminal amphipathic and polyQ regions and the tail encompassing the C-terminal proline-rich region. The surface area of the globular domain increases monotonically with polyQ length. This stimulates sharp increases in gain-of-function interactions in cells for expanded polyQ, and one of these interactions is with the stress-granule protein Fus. Our results highlight plausible connections between Httex1 structure and routes to neurotoxicity. 相似文献
104.
Exploitation of biological resources and the harvest of population species are commonly practiced in fisheries, forestry and
wild life management. Estimation of maximum harvesting effort has a great impact on the economics of fisheries and other bio-resources.
The present paper deals with the problem of a bioeconomic fishery model under environmental variability. A technique for finding
the maximum harvesting effort in fluctuating environment has been developed in a two-species competitive system, which shows
that under realistic environmental variability the maximum harvesting effort is less than what is estimated in the deterministic
model. This method also enables us to find out the safe regions in the parametric space for which the chance of extinction
of the species is minimized. A real life fishery problem has been considered to obtain the inaccessible parameters of the
system in a systematic way. Such studies may help resource managers to get an idea for controlling the system. 相似文献
105.
Lee MS Kao SC Lemere CA Xia W Tseng HC Zhou Y Neve R Ahlijanian MK Tsai LH 《The Journal of cell biology》2003,163(1):83-95
Amyloid-beta peptide (Abeta) aggregate in senile plaque is a key characteristic of Alzheimer's disease (AD). Here, we show that phosphorylation of amyloid precursor protein (APP) on threonine 668 (P-APP) may play a role in APP metabolism. In AD brains, P-APP accumulates in large vesicular structures in afflicted hippocampal pyramidal neurons that costain with antibodies against endosome markers and the beta-secretase, BACE1. Western blot analysis reveals increased levels of T668-phosphorylated APP COOH-terminal fragments in hippocampal lysates from many AD but not control subjects. Importantly, P-APP cofractionates with endosome markers and BACE1 in an iodixanol gradient and displays extensive colocalization with BACE1 in rat primary cortical neurons. Furthermore, APP COOH-terminal fragments generated by BACE1 are preferentially phosphorylated on T668 verses those produced by alpha-secretase. The production of Abeta is significantly reduced when phosphorylation of T668 is either abolished by mutation or inhibited by T668 kinase inhibitors. Together, these results suggest that T668 phosphorylation may facilitate the BACE1 cleavage of APP to increase Abeta generation. 相似文献
106.
A convenient synthesis of [1-14C]-mono-trans fatty acid using olefin inversion as a key-step is described. This methodology allows for a facile synthesis of [1-14C]-labelled mono-trans analogues of oleic, linoleic and linolenic acids. As an example, only eleven steps were necessary to obtain the [1-14C]-mono-E isomers of linolenic acid from its commercial all-Z form. In the first step, Barton's decarboxylation procedure yielded a bromo intermediate. Epoxidation of this compound resulted in the formation of three monoepoxides, which could be separated by HPLC. After identification by 1H NMR and MS, the pure monoepoxides were then subjected to inversion consisting of a stereospecific deoxygenation followed by a beta-elimination step. Finally, the labelling was introduced by substitution of the bromine by a [14C]-cyano group followed by hydrolysis. 相似文献
107.
108.
Multi-Target approach is particularly promising way to drug discovery against Alzheimer's disease. In the present study, we synthesized a series of compounds comprising the carbazole backbone linked to the benzyl piperazine, benzyl piperidine, pyridine, quinoline, or isoquinoline moiety through an aliphatic linker and evaluated as cholinesterase inhibitors. The synthesized compounds showed IC50 values of 0.11–36.5 µM and 0.02–98.6 µM against acetyl- and butyrylcholinesterase (AChE and BuChE), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 3s could bind effectively to the peripheral anionic binding site (PAS) and anionic site of the enzyme with mixed-type inhibition. Compound 3s was the most potent compound against AChE and BuChE and showed acceptable inhibition potency for self- and AChE-induced Aβ1-42 aggregation. Moreover, compound 3s could significantly protect PC12 cells against H2O2-induced toxicity. The results suggested that the compounds 3s could be considered as a promising multi-functional agent for further drug discovery development against Alzheimer's disease. 相似文献
109.
Changiz Geula Sara R. Dunlop Ivan Ayala Allegra S. Kawles Margaret E. Flanagan Tamar Gefen Marek-Marsel Mesulam 《Journal of neurochemistry》2021,158(6):1394-1411
110.
Michael A. Huffman Raveendra Kumara Yoshi Kawamoto Prasad M. Jayaweera Massimo Bardi Charmalie A. D. Nahallage 《American journal of primatology》2020,82(3):e23113
Allen's rule (1877) predicts ecogeographical anatomical variation in appendage proportions as a function of body temperature regulation. This phenomenon has been tested in a variety of animal species. In macaques, relative tail length (RTL) is one of the most frequently measured appendages to test Allen's rule. These studies have relied on museum specimens or the invasive and time-consuming capturing of free-ranging individuals. To augment sample size and lessen these logistical limitations, we designed and validated a novel noninvasive technique using digitalized photographs processed using LibreCAD, an open-source 2D-computer-aided design (CAD) application. This was used to generate pixelated measurements to calculate an RTL equivalent, the Tail to Trunk Index (TTI) = (tail [tail base to anterior tip] pixel count/trunk [neck to tail base] pixel count). The TTI of 259 adult free-ranging toque macaques (Macaca sinica) from 36 locations between 7 and 2,087 m above sea level (m.a.s.l.) was used in the analysis. Samples were collected from all three putative subspecies (M. s. sinica, aurifrons, and opisthomelas), at locations representing all altitudinal climatic zones where they are naturally distributed. These data were used to test whether toque macaque tail length variation across elevation follows Allen's rule, predicting that RTL decreases with increasing elevation and lower temperature. Our results strongly supported this prediction. There was also a statistically significant, negative correlation between elevation and annual average temperature. The best predictor for the TTI index was elevation. Significant subspecies differences in RTL are linked in part to their ecological and altitudinal niche separation, but overall the variation is seen as the species' adaptation to climate. The method developed for the quick morphometric assessment of relative body proportions, applicable for use on unhabituated free-ranging animals, widens the range of materials available for research studying morphological characteristics and their evolution in primates. 相似文献