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https://www.readbyqxmd.com/read/29345580/multi-potent-natural-scaffolds-targeting-amyloid-cascade-in-search-of-alzheimer-s-disease-therapeutics
#1
Sandipan Chakraborty
Alzheimer's disease (AD) once considered a rare disorder emerges as a major health concern in recent times. The disease pathogenesis is very complex and yet to be understood completely. However, "Amyloid Cascade" is the central event in disease pathogenesis. Several proteins of the amyloid cascade are currently being considered as potential targets for AD therapeutics discovery. Many potential compounds are in clinical trials, but till now there is no known cure for the disease. Recent years have witnessed remarkable research interest in search of novel concepts in drug designing for AD...
January 16, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29345285/the-epitranscriptome-m6a-writer-mettl3-promotes-chemo-and-radioresistance-in-pancreatic-cancer-cells
#2
Kosuke Taketo, Masamitsu Konno, Ayumu Asai, Jun Koseki, Masayasu Toratani, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii, Kazuhiko Ogawa
N6-methyladenosine (m6A) is the most abundant epitranscriptome modification in mammalian mRNA. Recent years have seen substantial progress in m6A epitranscriptomics, indicating its crucial roles in the initiation and progression of cancer through regulation of RNA stabilities, mRNA splicing, microRNA processing and mRNA translation. However, by what means m6A is dynamically regulated or written by enzymatic components represented by methyltransferase-like 3 (METTL3) and how m6A is significant for each of the numerous genes remain unclear...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29343974/identification-of-key-pathways-and-genes-in-tp53-mutation-acute-myeloid-leukemia-evidence-from-bioinformatics-analysis
#3
Rui Huang, Xiwen Liao, Qiaochuan Li
Background: Tumor protein p53 (TP53) mutations are not only a risk factor in acute myeloid leukemia (AML) but also a potential biomarker for individualized treatment options. This study aimed to investigate potential pathways and genes associated with TP53 mutations in adult de novo AML. Methods: An RNA sequencing dataset of adult de novo AML was downloaded from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified by edgeR of the R platform...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29342159/prediction-of-novel-target-genes-and-pathways-involved-in-bevacizumab-resistant-colorectal-cancer
#4
Precious Takondwa Makondi, Chia-Hwa Lee, Chien-Yu Huang, Chi-Ming Chu, Yu-Jia Chang, Po-Li Wei
Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs)...
2018: PloS One
https://www.readbyqxmd.com/read/29339733/role-of-macromolecular-crowding-on-the-intracellular-diffusion-of-dna-binding-proteins
#5
Pinki Dey, Arnab Bhattacherjee
Recent experiments suggest that cellular crowding facilitates the target search dynamics of proteins on DNA, the mechanism of which is not yet known. By using large scale computer simulations, we show that two competing factors, namely the width of the depletion layer that separates the crowder cloud from the DNA molecule and the degree of protein-crowder crosstalk, act in harmony to affect the target search dynamics of proteins. The impacts vary from nonspecific to specific target search regime. During a nonspecific search, dynamics of a protein is only minimally affected, whereas, a significantly different behaviour is observed when the protein starts forming a specific protein-DNA complex...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339380/negative-regulation-of-the-keap1-nrf2-pathway-by-a-p62-sqstm1-splicing-variant
#6
Shun Kageyama, Tetsuya Saito, Miki Obata, Ryo-Hei Koide, Yoshinobu Ichimura, Masaaki Komatsu
A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via multiple mechanisms, including gene expression, post-translational modifications such as ubiquitination and phosphorylation, and autophagic degradation of p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl database search and subsequent biochemical analyses in mice revealed the presence of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region (KIR), which is essential for the interaction with Keap1...
January 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29339344/analysis-and-evaluation-of-neuro-peptides-in-honey-bees-exposed-to-pesticides-in-field-conditions
#7
María Del Mar Gómez-Ramos, María José Gómez Ramos, María Martínez Galera, María Dolores Gil García, Amadeo R Fernández-Alba
During the last years, declines in honey bee colonies are being registered worldwide. Cholinergic pesticides and their extensive use have been correlated to the decline of pollinators and there is evidence that pesticides act as neuroendocrine disruptors affecting the metabolism of neuropeptides. However, there is a big absence of studies with quantitative results correlating the effect of pesticide exposure with changes on neuropeptides insects, and most of them are conducted under laboratory conditions, typically with individual active ingredients...
January 13, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29333542/acceleration-of-bursty-multiprotein-target-search-kinetics-on-dna-by-colocalisation
#8
Prathitha Kar, Andrey G Cherstvy, Ralf Metzler
Proteins are capable of locating specific targets on DNA by employing a facilitated diffusion process with intermittent 1D and 3D search steps. Gene colocalisation and coregulation-i.e. the spatial proximity of two communicating genes-is one factor capable of accelerating the target search process along the DNA. We perform Monte Carlo computer simulations and demonstrate the benefits of gene colocalisation for minimising the search time in a model DNA-protein system. We use a simple diffusion model to mimic the search for targets by proteins, produced initially in bursts of multiple proteins and performing the first-passage search on the DNA chain...
January 15, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29330773/mechanistic-regulation-of-epithelial-to-mesenchymal-transition-through-ras-signaling-pathway-and-therapeutic-implications-in-human-cancer
#9
REVIEW
Kiran Tripathi, Minal Garg
RAS effector signaling instead of being simple, unidirectional and linear cascade, is actually recognized as highly complex and dynamic signaling network. RAF-MEK-ERK cascade, being at the center of complex signaling network, links to multiple scaffold proteins through feed forward and feedback mechanisms and dynamically regulate tumor initiation and progression. Three isoforms of Ras harbor mutations in a cell and tissue specific manner. Besides mutations, their epigenetic silencing also attributes them to exhibit oncogenic activities...
January 12, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29330624/functional-transcriptomic-annotation-and-protein-protein-interaction-network-analysis-identify-nek2-birc5-and-top2a-as-potential-targets-in-obese-patients-with-luminal-a-breast-cancer
#10
Miriam Nuncia-Cantarero, Sandra Martinez-Canales, Fernando Andrés-Pretel, Gabriel Santpere, Alberto Ocaña, Eva Maria Galan-Moya
PURPOSE: Although obesity is a risk factor for breast cancer, little effort has been made in the identification of druggable molecular alterations in obese-breast cancer patients. Tumors are controlled by their surrounding microenvironment, in which the adipose tissue is a main component. In this work, we intended to describe molecular alterations at a transcriptomic and protein-protein interaction (PPI) level between obese and non-obese patients. METHODS AND RESULTS: Gene expression data of 269 primary breast tumors were compared between normal-weight (BMI < 25, n = 130) and obese (IMC > 30, n = 139) patients...
January 12, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29330299/effects-of-allelic-variations-in-the-human-myxovirus-resistance-protein-a-on-its-antiviral-activity
#11
Laura Graf, Alexej Dick, Franziska Sendker, Emanuel Barth, Manja Marz, Oliver Daumke, Georg Kochs
Only a minority of patients infected with seasonal influenza A viruses exhibits a severe or fatal outcome of infection, but the reasons for this inter-individual variability in influenza susceptibility are unclear. To gain further insights into the molecular mechanisms underlying this variability, we investigated naturally occurring allelic variations of the myxovirus resistance 1 (MX1) gene coding for the influenza restriction factor MxA. The interferon-induced dynamin-like GTPase consists of an N-terminal GTPase domain, a bundle signaling element, and a C-terminal stalk responsible for oligomerization and viral target recognition...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29330067/protein-complexes-as-psychiatric-and-neurological-drug-targets
#12
REVIEW
Akihiko S Kato, Jeffrey M Witkin
The need for improved medications for psychiatric and neurological disorders is clear. Difficulties in finding such drugs demands that all strategic means be utilized for their invention. The discovery of forebrain specific AMPA receptor antagonists, which selectively block the specific combinations of principal and auxiliary subunits present in forebrain regions but spare targets in the cerebellum, was recently disclosed. This discovery raised the possibility that other auxiliary protein systems could be utilized to help identify new medicines...
January 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29329271/transketolase-is-identified-as-a-target-of-herbicidal-substance-%C3%AE-terthienyl-by-proteomics
#13
Bin Zhao, Jingqian Huo, Ning Liu, Jinlin Zhang, Jingao Dong
α-terthienyl is a natural phytotoxin isolated originally from Flaveria bidentis (L.) Kuntze. The bioassay presented here shows the strong herbicidal activity of α-terthienyl on Digitaria sanguinalis, Arabidopsis thaliana and Chlamydomonas reinhardtii. The α-terthienyl-induced response of A. thaliana at the protein level was analyzed at different times. Changes in the protein expression profiles were analyzed by two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry (LC-MS/MS) mass spectrometry...
January 12, 2018: Toxins
https://www.readbyqxmd.com/read/29327814/systematic-evaluation-of-protein-sequence-filtering-algorithms-for-proteoform-identification-using-top-down-mass-spectrometry
#14
Qiang Kou, Si Wu, Xiaowen Liu
Complex proteoforms contain various primary structural alterations resulting from variations in genes, RNA, and proteins. Top-down mass spectrometry is commonly used for analyzing complex proteoforms because it provides whole sequence information of the proteoforms. Proteoform identification by top-down mass spectral database search is a challenging computational problem because the types and/or locations of some alterations in target proteoforms are in general unknown. Although spectral alignment and mass graph alignment algorithms have been proposed for identifying proteoforms with unknown alterations, they are extremely slow to align millions of spectra against tens of thousand protein sequences in high throughput proteome level analyses...
January 12, 2018: Proteomics
https://www.readbyqxmd.com/read/29321247/aberrant-regulation-of-autophagy-in-mammalian-diseases
#15
REVIEW
Wei Xie, Jun Zhou
Autophagy is a major cellular metabolic pathway that facilitates degradation of a subset of long-lived proteins and cytoplasmic organelles in eukaryotic cells. This pathway plays a vital role in preserving the cellular homeostasis of the cells themselves, in addition to maintaining the normal physiological state of cell renewal. Many stressors, such as starvation, ischaemia and oxidative stress can induce autophagy. In addition to its physiological roles, autophagy also occurs in a wide variety of pathological processes, including tumour progression, metabolic disorders, and neurodegenerative and lung diseases...
January 2018: Biology Letters
https://www.readbyqxmd.com/read/29319470/coupling-next-generation-sequencing-to-dominant-positive-screens-for-finding-antibiotic-cellular-targets-and-resistance-mechanisms-in-escherichia-coli
#16
Hélène Gingras, Bédis Dridi, Philippe Leprohon, Marc Ouellette
In order to expedite the discovery of genes coding for either drug targets or antibiotic resistance, we have developed a functional genomic strategy termed Plas-Seq. This technique involves coupling a multicopy suppressor library to next-generation sequencing. We generated an Escherichia coli plasmid genomic library that was transformed into E. coli. These transformants were selected step by step using 0.25× to 2× minimum inhibitory concentrations for ceftriaxone, gentamicin, levofloxacin, tetracycline or trimethoprim...
January 10, 2018: Microbial Genomics
https://www.readbyqxmd.com/read/29315602/comparison-of-two-docking-methods-for-peptide-protein-interactions
#17
Qiuying Yu, Fangyu Wang, Xiaofei Hu, Guangxu Xing, Ruiguang Deng, Junqing Guo, Anchun Cheng, Jing Wang, Junfang Hao, Dong Zhao, Man Teng, Gaiping Zhang
BACKGROUND: Based on the importance of peptides in regulatory interactions, peptide-protein docking has attracted many researchers' attention. Currently, a variety of methods specialized for molecular modeling of peptide-protein docking such as local search and global search are implemented. RESULTS: In this work, the interactions of eleven peptides and CSFV E2 protein were evaluated by GalaxyPepDock and FlexX/ SYBYL program, respectively. Then, the assessment scores of all the peptides were conducted a correlation analysis with their KD values...
January 9, 2018: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29311018/melanoma-associated-antigen-a11-reduces-erlotinib-and-afatinib-efficacy-in-head-and-neck-cancer
#18
Stefan Hartmann, Leonie Zwick, Katja Maurus, Andreas R Fuchs, Roman C Brands, Axel Seher, Alexander C Kübler, Urs D A Müller-Richter
Melanoma-associated antigen A (MAGE-A) proteins are members of the cancer/testis antigens (CTA), and the expression of these proteins is almost exclusively limited to malignant cells, making them an attractive treatment target. MAGE-A expression is correlated with poor overall survival in several cancers, including head and neck squamous cell carcinoma (HNSCC). Among others, MAGE-A11 was found to be associated with resistance to different antineoplastic and targeted compounds, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)...
December 24, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/29303709/cost-effectiveness-of-early-treatment-of-acpa-positive-rheumatoid-arthritis-patients-with-abatacept
#19
Aljoscha S Neubauer, Christof Minartz, Kirsten H Herrmann, Christoph G O Baerwald
OBJECTIVES: Studies have reported that the presence of elevated anti-citrullinated protein antibodies (ACPA)/RF levels, together with joint erosions, is associated with higher disease burden in terms of disability and mortality in rheumatoid arthritis (RA). Abatacept has been shown to be effective in this patient population with favourable comparative data against adalimumab. However, few studies have investigated the cost-effectiveness of abatacept in this population to similar treatments such as TNFs...
December 15, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29301499/coordinated-expression-and-genetic-polymorphisms-in-grainyhead-like-genes-in-human-non-melanoma-skin-cancers
#20
Agnieszka Kikulska, Tobias Rausch, Ewa Krzywinska, Magdalena Pawlak, Bartek Wilczynski, Vladimir Benes, Piotr Rutkowski, Tomasz Wilanowski
BACKGROUND: The Grainyhead-like (GRHL) transcription factors have been linked to many different types of cancer. However, no previous study has attempted to investigate potential correlations in expression of different GRHL genes in this context. Furthermore, there is very little information concerning damaging mutations and/or single nucleotide polymorphisms in GRHL genes that may be linked to cancer. METHODS: DNA and RNA were extracted from human non-melanoma skin cancers (NMSC) and adjacent normal tissues (n = 33 pairs of samples)...
January 4, 2018: BMC Cancer
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