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https://www.readbyqxmd.com/read/28637300/commercial-rodent-diets-differentially-regulate-autoimmune-glomerulonephritis-epigenetics-and-microbiota-in-mrl-lpr-mice
#1
Michael R Edwards, Rujuan Dai, Bettina Heid, Thomas E Cecere, Deena Khan, Qinghui Mu, Catharine Cowan, Xin M Luo, S Ansar Ahmed
The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone rich soy and alfalfa, Harlan 2018 isoflavone rich soy-based diet, or ResearchDiets Inc...
June 15, 2017: International Immunology
https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#2
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637217/experimental-support-that-natural-selection-has-shaped-the-latitudinal-distribution-of-mitochondrial-haplotypes-in-australian-drosophila-melanogaster
#3
M Florencia Camus, Jonci N Wolff, Carla M Sgrò, Damian K Dowling
Cellular metabolism is regulated by enzyme complexes within the mitochondrion, the function of which are sensitive to the prevailing temperature. Such thermal sensitivity, coupled with the observation that population frequencies of mitochondrial haplotypes tend to associate with latitude, altitude or climatic regions across species distributions, led to the hypothesis that thermal selection has played a role in shaping standing variation in the mitochondrial DNA (mtDNA) sequence. This hypothesis, however, remains controversial, and requires evidence that the distribution of haplotypes observed in nature corresponds with the capacity of these haplotypes to confer differences in thermal tolerance...
June 20, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28637198/multi-target-activity-of-hemidesmus-indicus-decoction-against-innovative-hiv-1-drug-targets-and-characterization-of-lupeol-mode-of-action
#4
Francesca Esposito, Manuela Mandrone, Claudia Del Vecchio, Ilaria Carli, Simona Distinto, Angela Corona, Mariacaterina Lianza, Dario Piano, Massimo Tacchini, Elias Maccioni, Filippo Cottiglia, Elisa Saccon, Ferruccio Poli, Cristina Parolin, Enzo Tramontano
Despite the availability of several anti-retrovirals there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors...
June 20, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28637181/crosstalk-between-histone-modifications-indicates-that-inhibition-of-arginine-methyltransferase-carm1-activity-reverses-hiv-latency
#5
Zheng Zhang, Bryan C Nikolai, Leah A Gates, Sung Yun Jung, Edward B Siwak, Bin He, Andrew P Rice, Bert W O'Malley, Qin Feng
In eukaryotic cells, the gene expression status is strictly controlled by epigenetic modifications on chromatin. The repressive status of chromatin largely contributes to HIV latency. Studies have shown that modification of histone H3K27 acts as a key molecular switch for activation or suppression of many cellular genes. In this study, we found that K27-acetylated histone H3 specifically recruited Super Elongation Complex (SEC), the transcriptional elongation complex essential for HIV-1 long terminal repeat (LTR)-mediated and general cellular transcription...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637104/-treatment-options-in-non-alcoholic-fatty-liver-disease
#6
REVIEW
Won Kim
The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10-20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28637102/-the-progression-of-liver-fibrosis-in-non-alcoholic-fatty-liver-disease
#7
REVIEW
Moon Young Kim
Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28637049/protecting-oligodendrocytes-by-targeting-non-glutamate-receptors-as-a-new-therapeutic-strategy-for-ischemic-stroke
#8
Pan Luo, Dong Liu, Lianjun Guo
Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons...
June 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28637023/cationic-liquid-crystalline-nanoparticles-for-the-delivery-of-synthetic-rnai-based-therapeutics
#9
Emanuela Gentile, Taro Oba, Jing Lin, Ruping Shao, Feng Meng, Xiaobo Cao, Heather Y Lin, Majidi Mourad, Apar Pataer, Veerabhadran Baladandayuthapani, Dong Cai, Jack A Roth, Lin Ji
RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short half-life, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636950/structural-evidence-of-quercetin-multi-target-bioactivity-a-reverse-virtual-screening-strategy
#10
Diego Carvalho, Margot Paulino, Fabio Polticelli, Florencia Arredondo, Robert J Williams, Juan A Abin-Carriquiry
The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways...
June 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28636946/ptbp2-controls-an-alternative-splicing-network-required-for-cell-communication-during-spermatogenesis
#11
Molly M Hannigan, Leah L Zagore, Donny D Licatalosi
Alternative splicing has essential roles in development. Remarkably, spermatogenic cells express more alternatively spliced RNAs compared to most whole tissues; however, regulation of these RNAs remains unclear. Here, we characterize the alternative splicing landscape during spermatogenesis and reveal an essential function for the RNA-binding protein Ptbp2 in this highly regulated developmental program. We found that Ptbp2 controls a network of genes involved in cell adhesion, migration, and polarity, suggesting that splicing regulation by Ptbp2 is critical for germ cell communication with Sertoli cells (multifunctional somatic cells necessary for spermatogenesis)...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636935/the-sensory-striatum-is-permanently-impaired-by-transient-developmental-deprivation
#12
Todd M Mowery, Kristina B Penikis, Stephen K Young, Christopher E Ferrer, Vibhakar C Kotak, Dan H Sanes
Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL), are commonly linked with processing deficits at or below the level of the auditory cortex (ACx). However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636931/p53-prohibits-propagation-of-chromosome-segregation-errors-that-produce-structural-aneuploidies
#13
Mar Soto, Jonne A Raaijmakers, Bjorn Bakker, Diana C J Spierings, Peter M Lansdorp, Floris Foijer, René H Medema
The presence of an abnormal karyotype has been shown to be profoundly detrimental at the cellular and organismal levels but is an overt hallmark of cancer. Aneuploidy can lead to p53 activation and thereby prevents proliferation, but the exact trigger for p53 activation has remained controversial. Here, we have used a system to induce aneuploidy in untransformed human cells to explore how cells deal with different segregation errors. We show that p53 is activated only in a subset of the cells with altered chromosome content...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636924/epithelial-folding-driven-by-apical-or-basal-lateral-modulation-geometric-features-mechanical-inference-and-boundary-effects
#14
Fu-Lai Wen, Yu-Chiun Wang, Tatsuo Shibata
During embryonic development, epithelial sheets fold into complex structures required for tissue and organ functions. Although substantial efforts have been devoted to identifying molecular mechanisms underlying epithelial folding, far less is understood about how forces deform individual cells to sculpt the overall sheet morphology. Here we describe a simple and general theoretical model for the autonomous folding of monolayered epithelial sheets. We show that active modulation of intracellular mechanics along the basal-lateral as well as the apical surfaces is capable of inducing fold formation in the absence of buckling instability...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636923/mechanosensitive-adhesion-explains-stepping-motility-in-amoeboid-cells
#15
Calina A Copos, Sam Walcott, Juan C Del Álamo, Effie Bastounis, Alex Mogilner, Robert D Guy
Cells employing amoeboid motility exhibit repetitive cycles of rapid expansion and contraction and apply coordinated traction forces to their environment. Although aspects of this process are well studied, it is unclear how the cell controls the coordination of cell length changes with adhesion to the surface. Here, we develop a simple model to mechanistically explain the emergence of periodic changes in length and spatiotemporal dynamics of traction forces measured in chemotaxing unicellular amoeba, Dictyostelium discoideum...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636919/monitoring-quantitative-ultrasound-parameter-changes-in-a-cell-pellet-model-of-cell-starvation
#16
Lauren A Wirtzfeld, Elizabeth S L Berndl, Gregory J Czarnota, Michael C Kolios
Although it has previously been shown that the spectral analysis of ultrasound backscatter data is sensitive to the cellular changes caused by apoptosis, the sensitivity of spectral analysis to oncosis or ischemic cell death had not previously been studied. Whereas many anticancer treatments induce apoptosis, others induce cell starvation, or oncosis. HT-29 colon adenocarcinoma cells were formed into pellets and covered in phosphate-buffered saline at room temperature for 56 h. The pellets were imaged every 8 h with high-frequency (55 MHz) ultrasound and the raw radio-frequency data processed...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636886/sirt1-enzymatically-potentiates-1-25-dihydroxyvitamin-d3-signaling-via-vitamin-d-receptor-deacetylation
#17
Marya S Sabir, Chengcheng Hu, Zainab Khan, Michael A Galligan, Christopher M Dussik, Sanchita Mallick, Angelika Dampf Stone, Shane F Batie, Elizabeth T Jacobs, G Kerr Whitfield, Mark R Haussler, Michael C Heck, Peter W Jurutka
The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1...
June 18, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28636880/behavioral-evidence-of-oxidative-stress-by-hematophagy-in-the-ocellar-system-of-rhodnius-prolixus-st%C3%A3-l-1859-red-eyed-mutants
#18
Carlos Alberto Vija Suarez, Mario Iván Ortiz, Jorge Molina
The photonegative response to light stimulation in Rhodnius prolixus (Reduviidae, Triatominae) is modulated by compound eyes and ocelli. Screening pigments in the visual system have been shown to protect the cellular structures from the oxidative stress damage produced by blood ingestion and light stimulation. Red-eyed mutants of Rhodnius prolixus lack screening pigments in their compound eyes and ocelli and are exposed to more oxidative stress. Experiments with Rhodnius prolixus and Triatoma infestans red-eyed mutants reared from the first nymphal stage show damage in the retinas of the compound eyes and a decrease in photonegative responses due to light stimulation...
June 18, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28636876/tissue-alignment-enhances-remodeling-potential-of-tendon-derived-cells-lessons-from-a-novel-microtissue-model-of-tendon-scarring
#19
Jasper Foolen, Stefania L Wunderli, Sandra Loerakker, Jess G Snedeker
Tendinopathy is a widespread and unresolved clinical challenge, in which associated pain and hampered mobility present a major cause for work-related disability. Tendinopathy associates with a change from a healthy tissue with aligned extracellular matrix (ECM) and highly polarized cells that are connected head-to-tail, towards a diseased tissue with a disorganized ECM and randomly distributed cells, scar-like features that are commonly attributed to poor innate regenerative capacity of the tissue. A fundamental clinical dilemma with this scarring process is whether treatment strategies should focus on healing the affected (disorganized) tissue or strengthen the remaining healthy (anisotropic) tissue...
June 18, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28636814/arsenic-compromises-both-p97-and-proteasome-functions
#20
Joseph Tillotson, Christopher J Zerio, Bryan Harder, Andrew Ambrose, Kevin S Jung, MinJin Kang, Donna D Zhang, Eli Chapman
Exposure to arsenic is a worldwide problem that affects more than 200 million people. The underlying mechanisms of arsenic toxicity have been difficult to ascertain due to arsenic's pleotropic effects. A number of recent investigations have shown arsenic can compromise protein quality control through the ubiquitin proteasome system (UPS) or the endoplasmic reticulum associated protein degradation (ERAD) pathway. In this report, a link between arsenic and protein quality control is reported. Biochemical and cellular data demonstrate a misregulation of the ATPase cycle of the ATPase associated with various cellular activities (AAA+) chaperone, p97...
June 21, 2017: Chemical Research in Toxicology
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