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https://www.readbyqxmd.com/read/28212548/branched-chain-amino-acids-prevent-hepatic-fibrosis-and-development-of-hepatocellular-carcinoma-in-a-non-alcoholic-steatohepatitis-mouse-model
#1
Kai Takegoshi, Masao Honda, Hikari Okada, Riuta Takabatake, Naoto Matsuzawa-Nagata, Jean S Campbell, Masashi Nishikawa, Tetsuro Shimakami, Takayoshi Shirasaki, Yoshio Sakai, Taro Yamashita, Toshinari Takamura, Takuji Tanaka, Shuichi Kaneko
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212491/food-ingestion-in-an-upright-sitting-position-increases-post-prandial-amino-acid-availability-when-compared-to-food-ingestion-in-a-lying-down-position
#2
Andrew M Holwerda, Kaatje Lenaerts, Jörgen Bierau, Will K W H Wodzig, Luc J C van Loon
Dietary protein digestion and absorption kinetics determine the post-prandial increase in muscle protein synthesis. We recently demonstrated that body position during feeding can modulate the post-prandial rise in plasma amino acid availability. Here we investigated whether protein ingestion in an upright sitting body position accelerates gastric emptying and improves dietary protein digestion and subsequent amino acid absorption compared with feeding in a supine lying body position. In a crossover design, eight young males (26±1 y, 24...
February 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#3
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211300/wound-healing-effects-of-nanoemulsion-containing-clove-essential-oil
#4
Prawez Alam, Mohammad J Ansari, Md Khalid Anwer, Mohammad Raish, Yoonus K T Kamal, Faiyaz Shakeel
The aim of this study was to investigate the wound healing effects of clove oil (CO) via its encapsulation into nanoemulsion. Optimized nanoemulsion (droplet size of 29.10 nm) was selected for wound healing investigation, collagen determination, and histopathological examination in rats. Optimized nanoemulsion presented significant would healing effects in rats as compared to pure CO. Nanoemulsion also presented significant enhancement in leucine content (0.61 mg/g) as compared to pure CO (0.50 mg/g) and negative control (0...
May 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28209137/transcriptional-analysis-of-defense-mechanisms-in-upland-tetraploid-switchgrass-to-greenbugs
#5
Teresa Donze-Reiner, Nathan A Palmer, Erin D Scully, Travis J Prochaska, Kyle G Koch, Tiffany Heng-Moss, Jeffrey D Bradshaw, Paul Twigg, Keenan Amundsen, Scott E Sattler, Gautam Sarath
BACKGROUND: Aphid infestation of switchgrass (Panicum virgatum) has the potential to reduce yields and biomass quality. Although switchgrass-greenbug (Schizaphis graminum; GB) interactions have been studied at the whole plant level, little information is available on plant defense responses at the molecular level. RESULTS: The global transcriptomic response of switchgrass cv Summer to GB was monitored by RNA-Seq in infested and control (uninfested) plants harvested at 5, 10, and 15 days after infestation (DAI)...
February 16, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28209121/evolution-of-toll-like-receptors-in-the-context-of-terrestrial-ungulates-and-cetaceans-diversification
#6
Edson Ishengoma, Morris Agaba
BACKGROUND: Toll-like receptors (TLRs) are the frontline actors in the innate immune response to various pathogens and are expected to be targets of natural selection in species adapted to habitats with contrasting pathogen burdens. The recent publication of genome sequences of giraffe and okapi together afforded the opportunity to examine the evolution of selected TLRs in broad range of terrestrial ungulates and cetaceans during their complex habitat diversification. Through direct sequence comparisons and standard evolutionary approaches, the extent of nucleotide and protein sequence diversity in seven Toll-like receptors (TLR2, TLR3, TLR4, TLR5, TLR7, TLR9 and TLR10) between giraffe and closely related species was determined...
February 16, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28204810/htlv-1-basic-leucine-zipper-factor-downregulates-cyclin%C3%A2-d1-expression-via-interactions-with-nf-%C3%AE%C2%BAb
#7
Yunyun Ma, Bo Zhang, Dong Wang, Lili Qian, Xianmei Song, Xueyin Wang, Chaokuan Yang, Guoqiang Zhao
Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus. It can cause adult T cell leukemia (ATL) and other diseases. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ), which is encoded by the minus-strand of the provirus, is expressed in all cases of ATL and involved in T cell proliferation. However, the exact mechanism underlying its growth-promoting activity is poorly understood. Herein, we demonstrated that HBZ suppressed cyclin D1 expression by inhibiting the nuclear factor (NF)-κB signaling pathway...
January 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203242/sunlight-modulates-fruit-metabolic-profile-and-shapes-the-spatial-pattern-of-compound-accumulation-within-the-grape-cluster
#8
Noam Reshef, Natasha Walbaum, Nurit Agam, Aaron Fait
Vineyards are characterized by their large spatial variability of solar irradiance (SI) and temperature, known to effectively modulate grape metabolism. To explore the role of sunlight in shaping fruit composition and cluster uniformity, we studied the spatial pattern of incoming irradiance, fruit temperature and metabolic profile within individual grape clusters under three levels of sunlight exposure. The experiment was conducted in a vineyard of Cabernet Sauvignon cv. located in the Negev Highlands, Israel, where excess SI and midday temperatures are known to degrade grape quality...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28203234/inducible-prophage-mutant-of-escherichia-coli-can-lyse-new-host-and-the-key-sites-of-receptor-recognition-identification
#9
Mianmian Chen, Lei Zhang, Sipei Xin, Huochun Yao, Chengping Lu, Wei Zhang
The use of bacteriophages as therapeutic agents is hindered by their narrow and specific host range, and by a lack of the knowledge concerning the molecular mechanism of receptor recognition. Two P2-like coliphages, named P88 and pro147, were induced from Escherichia coli strains K88 and DE147, respectively. A comparison of the genomes of these two and other P2-like coliphages obtained from GenBank showed that the tail fiber protein genes, which are the key genes for receptor recognition in other myoviridae phages, showed more diversity than the conserved lysin, replicase, and terminase genes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202680/cross-talk-between-lrrk2-and-pka-implication-for-parkinson-s-disease
#10
REVIEW
Elisa Greggio, Luigi Bubacco, Isabella Russo
Evidence indicates that leucine-rich repeat kinase 2 (LRRK2) controls multiple processes in neurons and glia cells. Deregulated LRRK2 activity due to gene mutation represents the most common cause of autosomal dominant Parkinson's disease (PD). Protein kinase A (PKA)-mediated signaling is a key regulator of brain function. PKA-dependent pathways play an important role in brain homeostasis, neuronal development, synaptic plasticity, control of microglia activation and inflammation. On the other hand, a decline of PKA signaling was shown to contribute to the progression of several neurodegenerative diseases, including PD...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202674/lrrk2-detection-in-human-biofluids-potential-use-as-a-parkinson-s-disease-biomarker
#11
REVIEW
Jean-Marc Taymans, Eugénie Mutez, Matthieu Drouyer, William Sibran, Marie-Christine Chartier-Harlin
Leucine-rich repeat kinase 2 (LRRK2) is a complex signalling protein that is a key therapeutic target, particularly in Parkinson's disease (PD). In addition, there is now evidence showing that LRRK2 expression and phosphorylation levels have potential as markers of disease or target engagement. Indeed, reports show increases in LRRK2 protein levels in the prefrontal cortex of PD patients relative to controls, suggesting that increase in total LRRK2 protein expression is correlated with disease progression. LRRK2 phosphorylation levels are reduced in experimental systems for most disease mutants, and LRRK2 is also rapidly dephosphorylated upon LRRK2 inhibitor treatment, considered potential therapeutics...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202670/mechanisms-of-lrrk2-dependent-neurodegeneration-role-of-enzymatic-activity-and-protein-aggregation
#12
REVIEW
Md Shariful Islam, Darren J Moore
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD) with autosomal dominant inheritance. Accordingly, LRRK2 has emerged as a promising therapeutic target for disease modification in PD. Since the first discovery of LRRK2 mutations some 12 years ago, LRRK2 has been the subject of intense investigation. It has been established that LRRK2 can function as a protein kinase, with many putative substrates identified, and can also function as a GTPase that may serve in part to regulate kinase activity...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202669/the-lrrk2-macroautophagy-axis-and-its-relevance-to-parkinson-s-disease
#13
REVIEW
Claudia Manzoni
A wide variety of different functions and an impressive array of interactors have been associated with leucine-rich repeat kinase 2 (LRRK2) over the years. Here, I discuss the hypothesis that LRRK2 may be capable of interacting with different proteins at different times and places, therefore, controlling a plethora of diverse functions based on the different complexes formed. Among these, I will then focus on macroautophagy in the general context of the endolysosomal system. First, the relevance of autophagy in Parkinson's disease will be evaluated giving a brief overview of all the relevant Parkinson's disease genes; then, the association of LRRK2 with macroautophagy and the endolysosomal pathway will be analyzed based on the supporting literature...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202668/cellular-effects-mediated-by-pathogenic-lrrk2-homing-in-on-rab-mediated-processes
#14
REVIEW
Jesús Madero-Pérez, Elena Fdez, Belén Fernández, Antonio Jesús Lara Ordóñez, Marian Blanca Ramírez, María Romo Lozano, Pilar Rivero-Ríos, Sabine Hilfiker
Leucine-rich repeat kinase 2 (LRRK2) is a key player in the pathogenesis of Parkinson's disease. Mutations in LRRK2 are associated with increased kinase activity that correlates with cytotoxicity, indicating that kinase inhibitors may comprise promising disease-modifying compounds. However, before embarking on such strategies, detailed knowledge of the cellular deficits mediated by pathogenic LRRK2 in the context of defined and pathologically relevant kinase substrates is essential. LRRK2 has been consistently shown to impair various intracellular vesicular trafficking events, and recent studies have shown that LRRK2 can phosphorylate a subset of proteins that are intricately implicated in those processes...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202667/lrrk2-from-kinase-to-gtpase-to-microtubules-and-back
#15
REVIEW
Marian Blanca Ramírez, Antonio Jesús Lara Ordóñez, Elena Fdez, Sabine Hilfiker
Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene are intimately linked to both familial and sporadic Parkinson's disease. LRRK2 is a large protein kinase able to bind and hydrolyse GTP. A wealth of in vitro studies have established that the distinct pathogenic LRRK2 mutants differentially affect those enzymatic activities, either causing an increase in kinase activity without altering GTP binding/GTP hydrolysis, or displaying no change in kinase activity but increased GTP binding/decreased GTP hydrolysis...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202666/lrrk2-in-peripheral-and-central-nervous-system-innate-immunity-its-link-to-parkinson-s-disease
#16
REVIEW
Heyne Lee, William S James, Sally A Cowley
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are found in familial and idiopathic cases of Parkinson's disease (PD), but are also associated with immune-related disorders, notably Crohn's disease and leprosy. Although the physiological function of LRRK2 protein remains largely elusive, increasing evidence suggests that it plays a role in innate immunity, a process that also has been implicated in neurodegenerative diseases, including PD. Innate immunity involves macrophages and microglia, in which endogenous LRRK2 expression is precisely regulated and expression is strongly up-regulated upon cell activation...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202665/neuronal-death-signaling-pathways-triggered-by-mutant-lrrk2
#17
REVIEW
Hardy J Rideout
Autosomal dominantly inherited mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. While considerable progress has been made in understanding its function and the many different cellular activities in which it participates, a clear understanding of the mechanism(s) of the induction of neuronal death by mutant forms of LRRK2 remains elusive. Although several in vivo models have documented the progressive loss of dopaminergic neurons of the substantia nigra, more complete interrogations of the modality of neuronal death have been gained from cellular models...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202664/lrrk2-mouse-models-dissecting-the-behavior-striatal-neurochemistry-and-neurophysiology-of-pd-pathogenesis
#18
REVIEW
Mattia Volta, Heather Melrose
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD), resembling the sporadic disorder. Intensive effort has been directed toward LRRK2 mouse modeling and investigation, aimed at reproducing the human disease to inform mechanistic studies of pathogenesis and design of neuroprotective therapies. The physiological function of LRRK2 is still under exploration, but a clear role in striatal neurophysiology and animal behavior has emerged. Alterations in LRRK2 impair dopamine (DA) transmission, regulation and signaling, in addition to corticostriatal synaptic plasticity...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202528/distinct-levels-of-radioresistance-in-lgr5-colonic-epithelial-stem-cells-versus-lgr5-small-intestinal-stem-cells
#19
Guoqiang Hua, Chu Wang, Yan Pan, Zhaoshi Zeng, Sang Gyu Lee, Maria Laura Martin, Adriana Haimovitz-Friedman, Zvi Fuks, Philip B Paty, Richard N Kolesnick
While small and large intestines possess seemingly similar Wnt-driven Leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5)+ adult epithelial stem cells, we report here that the two organs exhibit distinct mechanisms of tissue response to ionizing radiation. Employing Lgr5-lacZ transgenic mice and Lgr5 in situ hybridization, we found colonic epithelial stem cells (CESC) markedly more radioresistant in vivo than small intestinal crypt base columnar stem cells (CBC) (D0 6.0±0.3 Gy vs. 1.3±0.1, respectively; p0...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202345/circulating-human-leucine-rich-%C3%AE-2-glycoprotein-1-mrna-and-protein-levels-to-detect-acute-appendicitis-in-patients-with-acute-abdominal-pain
#20
T H Rainer, L Y Leung, Cpy Chan, Y K Leung, N M Cheng, Pbs Lai, Y S Cheung, C A Graham
BACKGROUND: Elevated levels of circulating plasma and urine leucine-rich-2-glycoprotein-1 (LRG1) protein has been found in patients with acute appendicitis (AA) and may be useful for diagnosis. This study aimed to investigate whether combined tests including circulating LRG1 mRNA levels improves the early diagnosis of AA. METHODS: Between December 2011 and October 2012, a prospective study was conducted on patients aged 18years or older presenting to the ED with acute abdominal pain (<7days of symptom onset)...
February 12, 2017: Clinical Biochemistry
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