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https://www.readbyqxmd.com/read/28734208/effect-of-mutation-on-a%C3%AE-1-42-heme-complex-in-aggregation-mechanism-alzheimer-s-disease
#1
Subramaniam Boopathi, Ponmalai Kolandaivel
Amyloid β (Aβ) peptide aggregation is one of the root causes for Alzheimer's disease. Recently, experimental studies show that three active binding sites (His6, His13 and His14) of Aβ peptides were bound with heme to form Aβ-Heme complex, which leads to inhibit the aggregation process. We apply molecular dynamic simulation to investigate the aggregation pathways of Aβ-Heme peptides. The above three binding sites were mutated by Glycine residue individually and generate three complex systems such as Aβ(His6Gly)-Heme, Aβ(His13Gly)-Heme and Aβ(His14Gly)-Heme...
July 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28734203/exenatide-mitigated-diet-induced-vascular-aging-and-atherosclerotic-plaque-growth-in-apoe-deficient-mice-under-chronic-stress
#2
Guang Yang, Yanna Lei, Aiko Inoue, Limei Piao, Lina Hu, Haiying Jiang, Takeshi Sasaki, Hongxian Wu, Wenhu Xu, Chenglin Yu, Guangxian Zhao, Shinyu Ogasawara, Kenji Okumura, Masafumi Kuzuya, Xian-Wu Cheng
BACKGROUND AND AIMS: Exposure to psychosocial stress is a risk factor for cardiovascular disorders. Because the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist prevents cardiovascular injury, we investigated the beneficial effects and mechanism of the GLP-1 analogue exenatide on stress-related vascular senescence and atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat (HF) diet. METHODS: ApoE(-/-) mice fed the HF diet were assigned to non-stressed and immobilized-stress groups for 12 weeks...
July 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#3
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28734138/ghrelin-plasma-concentration-does-not-covary-with-energy-demand-in-adult-laying-hens
#4
A Höhne, L Schrader, S Weigend, S Petow
The peptide hormone ghrelin is suggested to be involved in food intake regulation in young growing chicken. Whether ghrelin is involved in the regulation of energetic balance associated with laying performance in adult laying hens was studied by use of 4 chicken lines that differ in laying performance and phylogeny (4 lines; 16 hens per line). As housing conditions are also known to affect energy demand, half of the hens per line were housed in single cages and the other half of hens were maintained in a floor housing system...
June 29, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28732440/intravenous-injection-of-myelin-oligodendrocyte-glycoprotein-coated-plga-microparticles-have-tolerogenic-effects-in-experimental-autoimmune-encephalomyelitis
#5
Mehrdad Gholamzad, Masoumeh Ebtekar, Mehdi Shafiee Ardestani
The abnormal function of the T lymphocytes causes a range of autoimmune diseases, particularly multiple sclerosis; hence, several methods have been used to treat these disorders through the induction of antigen-specific tolerance in T cells. The present study aims to use a simple and low-cost method to produce poly (lactic-co-glycolic acid) (PLGA) nanoparticles for carrying antigens and inducing antigen-specific tolerance. In this study, PLGA nanoparticles were produced using the water/oil/water (W/O/W) method...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28732263/proteomic-analysis-of-naturally-occurring-boron-tolerant-plant-gypsophila-sphaerocephala-l-in-response-to-high-boron-concentration
#6
Huseyin Tombuloglu, Guzin Tombuloglu, Mehmet Serdal Sakcali, Ali Turkan, Khalid Rehman Hakeem, Hesham F Alharby, Shah Fahd, Waseem Mohammed Abdul
Gypsophila sphaerocephala is a naturally Boron (B) tolerant species that can grow around the B mining areas in Turkey, where the B concentration in soil reaches a lethal dose for plants (up to ∼8900mgkg(-1) (∼140mM). While its interesting survival capacity in extremely B containing soils, any molecular research has been conducted to understand its high tolerance mechanism yet. In the present study, we have performed a proteomic analysis of this plant to understand its high tolerance towards B-stress. Seedlings of G...
July 4, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28732245/interleukin-4-receptor-targeted-delivery-of-bcl-xl-sirna-sensitizes-tumors-to-chemotherapy-and-inhibits-tumor-growth
#7
Padmanaban Guruprasath, Jihoon Kim, Gowri Rangaswamy Gunassekaran, Lianhua Chi, Soyoun Kim, Rang-Woon Park, Sang-Hyun Kim, Moon-Chang Baek, Sang Mun Bae, Sang-Yeob Kim, Dong-Kyu Kim, In-Kyu Park, Won-Jong Kim, Byungheon Lee
IL-4 receptor (IL-4R) is commonly up-regulated on tumor cells, and interactions between the receptor and Interleukin-4 (IL-4) can induce the expression of anti-apoptotic proteins, including Bcl-xL. This contributes to tumor cell survival and their resistance to chemotherapy. In this study, we exploited IL-4R-targeted delivery of Bcl-xL siRNA to IL-4R-expressing tumor cells in order to sensitize them to chemotherapy. To target IL-4R, an IL-4R-binding peptide, IL4RPep-1, was attached to branched polyethyleneimine-superparamagnetic iron oxide nanoparticles (BPEI-SPION)...
July 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28732169/design-of-modular-peptide-surfactants-and-their-surface-activity
#8
Hao-Fei Wang, David Wibowo, Zhengzhong Shao, Anton Peter J Middelberg, Chun-Xia Zhao
Designed peptide surfactants offer a number of advanced properties over conventional petrochemical surfactants, including biocompatibility, sustainability, and tailorability of the chemical and physical properties through peptide design. Their biocompatibility and degradability make them attractive for various applications, particularly for food and pharmaceutical applications. In this work, two new peptide surfactants derived from an amphiphilic peptide surfactant (AM1) were designed (AM-S and C8-AM) to better understand links between structure, interfacial activity and emulsification...
July 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28732166/mel-n16-a-series-of-novel-endomorphin-analogs-with-good-analgesic-activity-and-a-favorable-side-effect-profile
#9
Xin Liu, Long Zhao, Yuan Wang, Jingjing Zhou, Dan Wang, Yixin Zhang, Xianghui Zhang, Zhaojuan Wang, Dongxu Yang, Lingyun Mou, Rui Wang
Opioid peptides are neuromodulators that bind to opioid receptors and reduce pain sensitivity. Endomorphins are one of the most active endogenous opioid peptides, and they have good affinity and selectivity toward the μ opioid receptor. However, their clinical usage is hindered by their inability to cross the blood-brain barrier, and their poor in vivo activity after peripheral injection. In order to overcome these defects, we have designed and synthesized a series of novel endomorphin analogs with multiple site modifications...
July 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28732135/synovial-immunophenotype-and-anti-citrullinated-protein-antibodies-in-ra-patients-relationship-to-treatment-response-and-radiological-prognosis
#10
Carl Orr, Aurelie Najm, Monika Biniecka, Trudy McGarry, Chin-Teck Ng, Francis Young, Ursula Fearon, Douglas J Veale
OBJECTIVE: Serum anti-citrullinated peptide antibodies (ACPA) may be present before development of rheumatoid arthritis (RA) and may predict more severe, erosive disease. This study examines synovial tissue immunophenotype according to ACPA status in RA patients, response to treatment and erosive status. METHODS: Consecutive RA patients were prospectively recruited and underwent clinical and serological assessment before and after treatment. Radiological assessment was performed at the time of clinical follow up...
July 21, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28732072/placental-peptides-metabolism-and-maternal-factors-as-predictors-of-risk-of-gestational-diabetes-in-pregnant-women-a-case-control-study
#11
Robert Amadu Ngala, Linda Ahenkorah Fondjo, Peter Gmagna, Frank Naku Ghartey, Martin Akilla Awe
BACKGROUND: Gestational diabetes is a risk factor for perinatal complications; include shoulder dystocia, birth injuries such as bone fractures and nerve palsies. It is associated with later development of type 2 diabetes, the risk of macrosomia and other long-term health effects of infants born to diabetic mothers. The study assesses placental peptides and maternal factors as potential predictors of gestational diabetes among pregnant women. MATERIAL AND METHODS: A total of 200 pregnant women were recruited for the study, 150 pregnant women without pre gestational diabetes including 50 women with low risk factors of diabetes as controls and 50 other pregnant women with pregestational diabetes as control...
2017: PloS One
https://www.readbyqxmd.com/read/28732052/protein-asparagine-deamidation-prediction-based-on-structures-with-machine-learning-methods
#12
Lei Jia, Yaxiong Sun
Chemical stability is a major concern in the development of protein therapeutics due to its impact on both efficacy and safety. Protein "hotspots" are amino acid residues that are subject to various chemical modifications, including deamidation, isomerization, glycosylation, oxidation etc. A more accurate prediction method for potential hotspot residues would allow their elimination or reduction as early as possible in the drug discovery process. In this work, we focus on prediction models for asparagine (Asn) deamidation...
2017: PloS One
https://www.readbyqxmd.com/read/28732041/understanding-russell-s-viper-venom-factor-v-activator-s-substrate-specificity-by-surface-plasmon-resonance-and-in-silico-studies
#13
Pradeep K Yadav, Christian B Antonyraj, Syed Ibrahim Basheer Ahamed, Sistla Srinivas
Blood coagulation factor V (FV) is activated either by Factor X or thrombin, cleaving at three different sites viz., Site I (Arg709-Ser710), site II (Arg1018-Thr1019), and site III (Arg1545-Ser1546). Russell's viper venom factor V activator (RVV-V) is a thrombin-like serine proteinase that activates FV with selective, single cleavage at site III. A long lasting effort is being pending in understanding the 'selective' binding specificity of the RVV-V towards site III. Here, we present the binding kinetic study of RVV-V with two designed peptides corresponding to the regions from site I (Gln699-Asn713) and site II (1008Lys-Pro1022), respectively, that include 15 amino acids...
2017: PloS One
https://www.readbyqxmd.com/read/28732021/in-vitro-comparison-of-213bi-and-177lu-radiation-for-peptide-receptor-radionuclide-therapy
#14
Ho Sze Chan, Erik de Blois, Alfred Morgenstern, Frank Bruchertseifer, Marion de Jong, Wouter Breeman, Mark Konijnenberg
BACKGROUND: Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET) nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE), 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28731783/identification-of-sppl2a-inhibitors-by-multiparametric-analysis-of-a-high-content-ultra-high-throughput-screen
#15
Xian Zhang, Marjo Götte, Yvonne Ibig-Rehm, Ansgar Schuffenhauer, Marion Kamke, Dan Beisner, Danilo Guerini, Daniela Siebert, Ghislain M C Bonamy, Daniela Gabriel, Ursula Bodendorf
The intramembrane protease signal peptide peptidase-like 2a (SPPL2a) is a potential drug target for the treatment of autoimmune diseases due to an essential role in B cells and dendritic cells. To screen a library of 1.4 million compounds for inhibitors of SPPL2a, we developed an imaging assay detecting nuclear translocation of the proteolytically released cytosolic substrate fragment. The state-of-the-art hit calling approach based on nuclear translocation resulted in numerous false-positive hits, mainly interrupting intracellular protein trafficking...
July 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28731688/the-%C3%AF-configuration-of-the-www-motif-of-a-short-trp-rich-peptide-is-critical-for-targeting-bacterial-membranes-disrupting-preformed-biofilms-and-killing-methicillin-resistant-staphylococcus-aureus
#16
D Zarena, Biswajit Mishra, Tamara Lushnikova, Fangyu Wang, Guangshun Wang
Tryptophan-rich peptides, being short and suitable for large-scale chemical synthesis, are attractive candidates for developing a new generation of antimicrobials to combat antibiotic-resistant bacteria (superbugs). Although there are numerous pictures for membrane-bound structure of a single tryptophan (W), how multiple Trp amino acids assemble themselves and interact with bacterial membranes are poorly understood. This communication presents the three-dimensional structure for an eight-residue Trp-rich peptide (WWWLRKIW-NH2 with 50% W) determined by the improved 2D NMR method, which includes the measurements of 13C and 15N chemical shifts at natural abundance...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28731675/sustained-release-of-a-peptide-based-matrix-metalloproteinase-2-inhibitor-to-attenuate-adverse-cardiac-remodeling-and-improve-cardiac-function-following-myocardial-infarction
#17
Zhaobo Fan, Minghuan Fu, Zhaobin Xu, Bo Zhang, Zhihong Li, Haichang Li, Xinyu Zhou, Xuanyou Liu, Yunyan Duan, Pei-Hui Lin, Pu Duann, Xiaoyun Xie, Jianjie Ma, Zhenguo Liu, Jianjun Guan
Following myocardial infarction (MI), degradation of extracellular matrix (ECM) by upregulated matrix metalloproteinases (MMPs) especially MMP-2 decreases tissue mechanical properties, leading to cardiac function deterioration. Attenuation of cardiac ECM degradation at the early stage of MI has the potential to preserve tissue mechanical properties, resulting in cardiac function increase. Yet the strategy for efficiently preventing cardiac ECM degradation remains to be established. Current preclinical approaches have shown limited efficacy due to low drug dosage allocated to the heart tissue, dose-limiting side effects, and cardiac fibrosis...
July 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28731449/cerebrospinal-fluid-neurogranin-as-a-biomarker-of-neurodegenerative-diseases-a-cross-sectional-study
#18
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Robert Nisticò, Roberto Floris, Francesco Garaci, Harald Hampel
We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35), FTD (n = 9), MCI (n = 41), cognitively HC (n = 23)]...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731447/chromatin-bound-oxidized-%C3%AE-synuclein-causes-strand-breaks-in-neuronal-genomes-in-in-vitro-models-of-parkinson-s-disease
#19
Velmarini Vasquez, Joy Mitra, Pavana M Hegde, Arvind Pandey, Shiladitya Sengupta, Sankar Mitra, K S Rao, Muralidhar L Hegde
Alpha-synuclein (α-Syn) overexpression and misfolding/aggregation in degenerating dopaminergic neurons have long been implicated in Parkinson's disease (PD). The neurotoxicity of α-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Although α-Syn is predominantly localized in presynaptic nerve terminals, a small fraction exists in neuronal nuclei. However, the functional and/or pathological role of nuclear α-Syn is unclear. Following up on our earlier report that α-Syn directly binds DNA in vitro, here we confirm the nuclear localization and chromatin association of α-Syn in neurons using proximity ligation and chromatin immunoprecipitation analysis...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731438/evidence-that-the-human-innate-immune-peptide-ll-37-may-be-a-binding-partner-of%C3%A2-amyloid-%C3%AE-and-inhibitor-of%C3%A2-fibril-assembly
#20
Ersilia De Lorenzi, Marcella Chiari, Raffaella Colombo, Marina Cretich, Laura Sola, Renzo Vanna, Paola Gagni, Federica Bisceglia, Carlo Morasso, Jennifer S Lin, Moonhee Lee, Patrick L McGeer, Annelise E Barron
BACKGROUND: Identifying physiologically relevant binding partners of amyloid-β (Aβ) that modulate in vivo fibril formation may yield new insights into Alzheimer's disease (AD) etiology. Human cathelicidin peptide, LL-37, is an innate immune effector and modulator, ubiquitous in human tissues and expressed in myriad cell types. OBJECTIVE: We present in vitro experimental evidence and discuss findings supporting a novel hypothesis that LL-37 binds to Aβ42 and can modulate Aβ fibril formation...
July 18, 2017: Journal of Alzheimer's Disease: JAD
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