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https://www.readbyqxmd.com/read/29035969/effects-of-medical-food-leucine-content-in-the-management-of-methylmalonic-and-propionic-acidemias
#1
Jennifer G Myles, Irini Manoli, Charles P Venditti
PURPOSE OF REVIEW: The current review highlights the varied effects of medical foods high in leucine (Leu) and devoid of valine (Val) and isoleucine (Ile) in the management of methylmalonic acidemia (MMA) and propionic acidemia and cobalamin C (cblC) deficiency, aiming to advance dietary practices. RECENT FINDINGS: Leu is a key metabolic regulator with a multitude of effects on different organ systems. Recent observational studies have demonstrated that these effects can have unintended consequences in patients with MMA as a result of liberal use of medical foods...
October 14, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29035420/modeling-the-secondary-structures-of-the-peptaibols-antiamoebin-i-and-zervamicin-ii-modified-with-d-amino-acids-and-proline-analogues
#2
Tarsila G Castro, Nuno M Micaêlo, Manuel Melle-Franco
Antiamoebin I (AAM-I) and zervamicin II (Zrv-IIB) are peptaibols that exert antibiotic activity through the insertion/disruption of cell membranes. In this study, we investigated how the folding of these peptaibols are affected when some of their native residues are replaced with proline analogues and asymmetrical D-α,α-dialkyl glycines (two classes of noncanonical amino acids). Systematic substitutions of native Aib, Pro, Hyp, and Iva residues were performed to elucidate the folding properties of the modified peptaibols incorporating noncanonical residues...
October 16, 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29035044/nicotine-alters-the-gut-microbiome-and-metabolites-of-gut-brain-interactions-in-a-sex-specific-manner
#3
Liang Chi, Ridwan Mahbub, Bei Gao, Xiaoming Bian, Pengcheng Tu, Hongyu Ru, Kun Lu
As the primary active substance in tobacco, nicotine affects the activity of the central nervous system, and its effects are sex-dependent. There are complex interactions between the gut and brain, and the gut microbiome can influence neuronal activity and host behavior, with diverse chemical signaling being involved. However, it is unclear whether nicotine can affect the normal gut microbiome and associated chemical signaling of the gut-brain axis. Sex is an important factor that shapes the gut microbiome, but the role of sex in the interaction among nicotine, gut bacteria, and related metabolites remains unknown...
October 16, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29034879/induced-pluripotent-stem-cells-derived-from-an-autosomal-dominant-lateral-temporal-epilepsy-adlte-patient-carrying-s473l-mutation-in-leucine-rich-glioma-inactivated-1-lgi1
#4
Ghee Wan Tan, Takayuki Kondo, Nagahisa Murakami, Keiko Imamura, Takako Enami, Kayoko Tsukita, Ran Shibukawa, Misato Funayama, Riki Matsumoto, Akio Ikeda, Ryosuke Takahashi, Haruhisa Inoue
Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited epileptic syndrome, and it is associated with mutations of leucine-rich glioma inactivated 1 (LGI1) gene. The underlying mechanisms of ADLTE are still unknown, as human neurons are difficult to obtain as a research tool. Human induced pluripotent stem cells (iPSCs) allow the generation of patient-derived neuronal cells in a dish, and can be a promising tool to model ADLTE. Here, we report the establishment of human iPSCs from an ADLTE patient carrying LGI1 mutation (c...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29033963/convergent-evolution-of-pathogen-effectors-toward-reactive-oxygen-species-signaling-networks-in-plants
#5
REVIEW
Nam-Soo Jwa, Byung Kook Hwang
Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29032949/correction-of-hyperleucinemia-in-msud-patients-on-leucine-free-dietary-therapy
#6
Anna I Scott, Kristina Cusmano-Ozog, Gregory M Enns, Tina M Cowan
PURPOSE: Maple Syrup Urine Disease (MSUD) is a rare disorder of branched-chain amino acid catabolism associated with encephalopathy from accumulation of leucine. Leucine is closely monitored during normal growth and particularly during acute illness. As most hospitals do not have access to rapid plasma amino acid quantification, the initial management is often empirical. A model describing the reduction of plasma leucine in hyperleucinemic patients on leucine-free formula would help to guide management and optimize testing frequency...
October 5, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29032784/spent-culture-medium-analysis-from-individually-cultured-bovine-embryos-demonstrates-metabolomic-differences
#7
Kayla J Perkel, Pavneesh Madan
Spent culture medium can provide valuable information regarding the physiological state of a bovine preimplantation embryos through non-invasive analysis of the sum/depleted metabolite constituents. Metabolomics has become of great interest as an adjunct technique to morphological and cleavage-rate assessment, but more importantly, in improving our understanding of metabolism. In this study, in vitro produced bovine embryos developing at different rates were evaluated using proton nuclear magnetic resonance (1H NMR)...
October 16, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/29031723/inhibition-of-cholinergic-potentiation-of-insulin-secretion-from-pancreatic-islets-by-chronic-elevation-of-glucose-and-fatty-acids-protection-by-casein-kinase-2-inhibitor
#8
Nicolai M Doliba, Qin Liu, Changhong Li, Pan Chen, Chengyang Liu, Ali Naji, Franz M Matschinsky
OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031484/effects-of-leucine-enriched-essential-amino-acid-and-whey-protein-bolus-dosing-upon-skeletal-muscle-protein-synthesis-at-rest-and-after-exercise-in-older-women
#9
Daniel J Wilkinson, Syed S I Bukhari, Bethan E Phillips, Marie C Limb, Jessica Cegielski, Matthew S Brook, Debbie Rankin, William K Mitchell, Hisamine Kobayashi, John P Williams, Jonathan Lund, Paul L Greenhaff, Kenneth Smith, Philip J Atherton
BACKGROUND & AIMS: Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP). METHODS: Twenty-four older women (65 ± 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1...
September 23, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29031397/modulation-of-the-biomarkers-of-inflammation-and-oxidative-stress-by-ruminant-trans-fatty-acids-and-dairy-proteins-in-vascular-endothelial-cells-huvec
#10
Marine S Da Silva, Jean-François Bilodeau, Jessica Larose, Karine Greffard, Pierre Julien, Olivier Barbier, Iwona Rudkowska
This study aimed to determine whether dairy macronutrients alter markers of inflammation and oxidative stress in endothelial cells. Human endothelial cells (HUVEC) were treated with ruminant trans fatty acids (rTFA), either trans-vaccenic acid (tVA) or trans-palmitoleic acid (tPA), whey protein hydrolysate, leucine or combinations of rTFA and dairy protein compounds. Industrial TFA elaidic acid (EA) was also investigated and compared with rTFA. Inflammatory prostaglandins (PG) and F2-isoprostanes (F2-isoP) isomers, markers of oxidative stress, were assessed in cell supernatants by LC-MS/MS...
November 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/29029535/leucine-rich-alpha-2-glycoprotein-1-relevant-with-microvessel-density-is-an-independent-survival-prognostic-factor-for-stage-iii-colorectal-cancer-patients-a-retrospective-analysis
#11
De-Cong Sun, Yan Shi, Ling-Xiong Wang, Yao Lv, Quan-Li Han, Zhi-Kuan Wang, Guang-Hai Dai
BACKGROUND: Leucine-rich alpha-2-glycoprotein-1 (encoded by LRG1) has been shown to be involved in multiple cancer progression and angiogenesis. LRG1 has been shown to be one of the five plasma proteins that can be used for colorectal cancer (CRC) diagnosis. The objective of the current study was to explore relationship between LRG1 protein expression and microvessel density (MVD) in stage III CRC. METHODS: A single-center retrospective analysis of all stage III CRC who underwent surgery and adjuvant chemotherapy was carried out...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026998/acetolactate-synthase-alss-in-bacillus-licheniformis-wx-02-enzymatic-properties-and-efficient-functions-for-acetoin-butanediol-and-l-valine-biosynthesis
#12
Yanli Huo, Yangyang Zhan, Qin Wang, Shunyi Li, Shihui Yang, Christopher T Nomura, Changjun Wang, Shouwen Chen
Acetolactate synthase catalyzes two molecules of pyruvates to form α-acetolactate, which is further converted to acetoin and 2,3-butanediol. In this study, by heterologous expression in Escherichia coli, the enzymatic properties of acetolactate synthase (AlsS) from Bacillus licheniformis WX-02 were characterized. Its K m and k cat for pyruvate were 3.96 mM and 514/s, respectively. It has the optimal activity at pH 6.5, 37 °C and was feedback inhibited by L-valine, L-leucine and L-isoleucine. Furthermore, the alsS-deficient strain could not produce acetoin, 2,3-butanediol, and L-valine, while the complementary strain was able to restore these capacities...
October 11, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/29026156/metabolic-responses-of-eisenia-fetida-to-individual-pb-and-cd-contamination-in-two-types-of-soils
#13
Ronggui Tang, Changfeng Ding, Yibing Ma, Junsong Wang, Taolin Zhang, Xingxiang Wang
To characterize the potential toxicity of low Pb- and Cd-contaminated arable soils, earthworms were exposed to Pb contaminated ferrosol, cambosol or Cd contaminated ferrosol for two weeks. Polar metabolites of earthworms were detected by nuclear magnetic resonance. Data were then analyzed with principal component analysis followed by orthogonal signal correction-partial least squares-discriminant analysis and univariate analysis to determine possible mechanisms for the changes in metabolites. The survival rates, metal concentrations and bioaccumulation factor (BAF) of the earthworms were also measured and calculated as auxiliary data...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024560/enhanced-stem-cell-differentiation-and-immunopurification-of-genome-engineered-human-retinal-ganglion-cells
#14
Valentin M Sluch, Xitiz Chamling, Melissa M Liu, Cynthia A Berlinicke, Jie Cheng, Katherine L Mitchell, Derek S Welsbie, Donald J Zack
Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols are often lacking. Here, we describe the generation of clustered regularly-interspaced short palindromic repeats(CRISPR)-Cas9 engineered reporter knock-in embryonic stem cell lines in which tdTomato and a unique cell-surface protein, THY1...
October 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29023495/the-hnrnp-like-nab3-termination-factor-can-employ-heterologous-prion-like-domains-in-place-of-its-own-essential-low-complexity-domain
#15
Travis J Loya, Thomas W O'Rourke, Daniel Reines
Many RNA-binding proteins possess domains with a biased amino acid content. A common property of these low complexity domains (LCDs) is that they assemble into an ordered amyloid form, juxtaposing RNA recognition motifs in a subcellular compartment in which RNA metabolism is focused. Yeast Nab3 is one such protein that contains RNA-binding domains and a low complexity, glutamine/proline-rich, prion-like domain that can self-assemble. Nab3 also contains a region of structural homology to human hnRNP-C that resembles a leucine zipper which can oligomerize...
2017: PloS One
https://www.readbyqxmd.com/read/29023112/design-of-leucine-rich-repeat-kinase-2-lrrk2-inhibitors-using-a-crystallographic-surrogate-derived-from-checkpoint-kinase-1-chk1
#16
Douglas S Williamson, Garrick P Smith, Pamela Acheson-Dossang, Simon T Bedford, Victoria Chell, I-Jen Chen, Justus C A Daechsel, Zoe Daniels, Laurent David, Pawel Dokurno, Morten Hentzer, Martin C Herzig, Roderick E Hubbard, Jonathan D Moore, James B Murray, Samantha Newland, Stuart C Ray, Terry Shaw, Allan E Surgenor, Lindsey Terry, Kenneth Thirstrup, Yikang Wang, Kenneth V Christensen
Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson's disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed, expressed in insect cells infected with baculovirus, purified and crystallized. X-ray structures of the surrogates complexed with known LRRK2 inhibitors rationalized compound potency and selectivity. The CHK1 10-point mutant was preferred, following assessment of surrogate binding affinity with LRRK2 inhibitors...
October 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29022534/therapeutic-drug-monitoring-of-amlodipine-and-the-z-fhl-hhl-ratio-adherence-tools-in-patients-referred-for-apparent-treatment-resistant-hypertension
#17
E S W Jones, M Lesosky, M Blockman, S Castel, E H Decloedt, S L U Schwager, E D Sturrock, L Wiesner, B L Rayner
BACKGROUND: Non-adherence to antihypertensives is a cause of 'pseudo-treatment-resistant' hypertension. OBJECTIVE: To determine whether monitoring plasma amlodipine concentrations and inhibition of angiotensin-converting enzyme (ACE) can be adjunct adherence tools. METHODS: Patients with hypertension who were prescribed enalapril and amlodipine were enrolled. Blood pressures (BPs) were monitored and an adherence questionnaire was completed...
September 22, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/29021806/erecta-regulates-cell-elongation-by-activating-auxin-biosynthesis-in-arabidopsis-thaliana
#18
Xiaoya Qu, Zhong Zhao, Zhaoxia Tian
The ERECTA family genes, ERECTA (ER), ERECTA-LIKE1 (ERL1), and ERECTA-LIKE2 (ERL2), encode leucine-rich repeat receptor-like kinases in Arabidopsis thaliana. Knocking out these three genes can cause severe phenotypes, which indicates that they play significant roles in plant growth and development. However, the molecular mechanism within remains unclear. Here we show that the short hypocotyl phenotypes of er erl1 erl2 mutants are mainly due to the defects of cell elongation rather than the cell division. In contrast, in the ERECTA overexpression transgenic plants, the hypocotyl length is increased with elongated cells...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29019279/leucine-and-resistance-training-improve-hyperglycemia-white-adipose-tissue-loss-and-inflammatory-parameters-in-an-experimental-model-of-type-1-diabetes
#19
Henrique Quintas Teixeira Ribeiro, Audrey Yule Coqueiro, Vanessa Batista de Sousa Lima, Carlos Eduardo Carvalho Martins, Julio Tirapegui
BACKGROUND: Loss of white adipose tissue (WAT), associated with type 1 diabetes (DM1), contributes to increased chronic systemic inflammation. AIM: The aim of this study was to investigate the effects of leucine supplementation and resistance training (RT) in attenuating WAT loss and improving inflammatory parameters and glucose metabolism in DM1 rats. METHODS: Thirty-two male Wistar rats were distributed into four groups: DA (sedentary and supplemented with non-essential amino acids (NEAA)), DL (sedentary and supplemented with leucine), DTA (submitted to RT and supplemented with NEAA) and DTL (submitted to RT and supplemented with leucine)...
January 1, 2017: Nutrition and Health
https://www.readbyqxmd.com/read/29018805/insight-into-the-selectivity-of-the-g7-18nate-inhibitor-peptide-for-the-grb7-sh2-domain-target
#20
Gabrielle M Watson, William A H Lucas, Menachem J Gunzburg, Jacqueline A Wilce
Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7...
2017: Frontiers in Molecular Biosciences
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