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https://www.readbyqxmd.com/read/27933736/structural-insight-into-the-anti-prion-compound-inhibition-mechanism-of-native-prion-folding-over-misfolding
#1
Jiwon Choi, Rajiv Gandhi Govindaraj, Jae Wook Hyeon, Kyungro Lee, SongLing Ma, Su Yeon Kim, Jeongmin Lee, Kyoung Tai No
Transition of a physiological folded prion (PrP(C) ) into a pathogenic misfolded prion (PrP(S)(c) ) causes lethal neurodegenerative disorders and prion diseases. Anti-prion compounds have been developed to prevent this conversion; however, their mechanism of action remains unclear. Recently, we reported two anti-prion compounds, BMD29 and 35, identified by in silico and in vitro screening. In this study, we used extensive explicit-solvent molecular dynamics simulations to investigate ligand binding inhibition by anti-prion compounds in prion folding over misfolding behavior at acidic pH...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933717/mass-cytometry-analytical-approaches-reveal-cytokine-induced-changes-in-natural-killer-cells
#2
Elena Vendrame, Julia Fukuyama, Dara M Strauss-Albee, Susan Holmes, Catherine A Blish
BACKGROUND: Natural killer (NK) cells have antiviral and antitumor activity that could be harnessed for the treatment of infections and malignancies. To maintain cell viability and enhance antiviral and antitumor effects, NK cells are frequently treated with cytokines. Here we performed an extensive assessment of the effects of cytokines on the phenotype and function of human NK cells. METHODS: We used cytometry by time-of-flight (CyTOF) to evaluate NK cell repertoire changes after stimulation with interleukin (IL)-2, IL-15 or a combination of IL- 12/IL-15/IL-18...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933712/the-importance-of-mrna-structure-in-determining-the-pathogenicity-of-synonymous-and-non-synonymous-mutations-in-haemophilia
#3
N Hamasaki-Katagiri, B C Lin, J Simon, R C Hunt, T Schiller, E Russek-Cohen, A A Komar, H Bar, C Kimchi-Sarfaty
INTRODUCTION: Mutational analysis is commonly used to support the diagnosis and management of haemophilia. This has allowed for the generation of large mutation databases which provide unparalleled insight into genotype-phenotype relationships. Haemophilia is associated with inversions, deletions, insertions, nonsense and missense mutations. Both synonymous and non-synonymous mutations influence the base pairing of messenger RNA (mRNA), which can alter mRNA structure, cellular half-life and ribosome processivity/elongation...
December 9, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27933673/a-biophysical-and-computational-study-unraveling-the-molecular-interaction-mechanism-of-a-new-janus-kinase-inhibitor-tofacitinib-with-bovine-serum-albumin
#4
Ali Saber Abdelhameed, Saima Nusrat, Mohammad Rehan Ajmal, Syed Mohammad Zakariya, Masihuz Zaman, Rizwan Hasan Khan
The interaction of a recently certified kinase inhibitor Tofacitinib (TFB) with bovine serum albumin (BSA) has been studied, by spectroscopic and molecular docking studies. Spectrofluorimetric measurements at 3 different temperatures (288, 298, and 310 K) showed that TFB quench the intrinsic fluorescence of BSA upon forming a nonfluorescent complex. The intrinsic fluorescence data showed that TFB binds to BSA with binding constant (Kb ) of approximately 10(4) M(-1) , affirming a significant affinity of TFB with BSA...
December 9, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27933662/evidence-of-staphylococcus-aureus-deformation-proliferation-and-migration-in-canaliculi-of-live-cortical-bone-in-murine-models-of-osteomyelitis
#5
Karen L de Mesy Bentley, Ryan Trombetta, Kohei Nishitani, Sheila N Bello-Irizarry, Mark Ninomiya, Longze Zhang, Hung Li Chung, James L McGrath, John L Daiss, Hani A Awad, Stephen L Kates, Edward M Schwarz
While Staphylococcus aureus osteomyelitis is considered to be incurable, the major bacterial reservoir in live cortical bone has remained unknown. In addition to biofilm bacteria on necrotic tissue and implants, studies have implicated intracellular infection of osteoblasts and osteocytes as a mechanism of chronic osteomyelitis. Thus, we performed the first systematic transmission electron microscopy (TEM) studies to formally define major reservoirs of S. aureus in chronically infected mouse (Balb/c J) long bone tissue...
December 8, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27933579/oligomerization-and-chaperone-like-activity-of-drosophila-melanogaster-small-heat-shock-protein-dmhsp27-and-three-arginine-mutants-in-the-alpha-crystallin-domain
#6
Mohamed Taha Moutaoufik, Geneviève Morrow, Halim Maaroufi, Céline Férard, Stéphanie Finet, Robert M Tanguay
The small Hsp DmHsp27 from Drosophila melanogaster is one of the few small heat shock proteins (sHsps) found within the nucleus. We report that its dimerization is independent of disulfide bond formation and seems to rely on salt bridges. Unlike metazoan sHsps, DmHsp27 forms two populations of oligomers not in equilibrium. Mutations at highly conserved arginine residues in mammalian sHsps have been reported to be associated with protein conformational defects and intracellular aggregation. Independent mutation of three highly conserved arginines (R122, R131, and R135) to glycine in DmHsp27 results in only one population of higher molecular weight form...
December 8, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27933543/integrative-analysis-of-genetic-genomic-and-phenotypic-data-for-ethanol-behaviors-a-network-based-pipeline-for-identifying-mechanisms-and-potential-drug-targets
#7
James W Bogenpohl, Kristin M Mignogna, Maren L Smith, Michael F Miles
Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933531/using-baseline-transcriptional-connectomes-in-rat-to-identify-genetic-pathways-associated-with-predisposition-to-complex-traits
#8
Laura Saba, Paula Hoffman, Boris Tabakoff
Although rat is a critical model organism in preclinical medications development, its use in systems genetics studies remains sparse. The PhenoGen database and website contain detailed information on the qualitative and quantitative aspects of the rat brain, liver, heart, and brown adipose transcriptome. This database has been generated using the HXB/BXH recombinant inbred panel and is being expanded to a hybrid rat diversity panel that includes many common inbred strains as well. By using such a panel, the PhenoGen project has created a renewable and cumulative resource for the rat genomics community...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933490/alterations-in-the-cerebral-microvascular-proteome-expression-profile-after-transient-global-cerebral-ischemia-in-rat
#9
Stine Spray, Sara E Johansson, Alistair V G Edwards, Martin R Larsen, Aneta Radziwon-Balicka, Gro K Povlsen, Lars Edvinsson
This study aimed at obtaining an in-depth mapping of expressional changes of the cerebral microvasculature after transient global cerebral ischemia (GCI) and the impact on these GCI-induced expressional changes of post-GCI treatment with a mitogen-activated protein kinase kinase (MEK1/2) inhibitor. GCI was induced in male Wistar rats followed by treatment with either vehicle or the MEK1/2 inhibitor U0126 every 12 h post-GCI. Seventy-two hours after GCI or sham surgery, the cerebral microvasculature was isolated and the protein content analysed with state-of-the-art mass spectrometry...
December 8, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27933468/conditional-screening-for-ultra-high-dimensional-covariates-with-survival-outcomes
#10
Hyokyoung G Hong, Jian Kang, Yi Li
Identifying important biomarkers that are predictive for cancer patients' prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization...
December 8, 2016: Lifetime Data Analysis
https://www.readbyqxmd.com/read/27933379/the-role-of-receptor-like-protein-kinases-rlks-in-abiotic-stress-response-in-plants
#11
REVIEW
Yaoyao Ye, Yanfei Ding, Qiong Jiang, Feijuan Wang, Junwei Sun, Cheng Zhu
We review and introduce recent studies on RLK s involved in the abiotic stress response and provide insights into potential regulatory mechanisms for alleviating abiotic stress. Abiotic stresses are important factors affecting plant growth and development, resulting in crop production reduction and even plant death. To survive, plants utilize different mechanisms to respond and adapt to continuously changing environmental factors. Understanding of the molecular mechanisms of plant response to various stresses will aid in improving tolerance of plants to abiotic stress through genetic engineering, which would greatly promote the development of modern agriculture...
December 8, 2016: Plant Cell Reports
https://www.readbyqxmd.com/read/27933370/doxorubicin-induced-chronic-dilated-cardiomyopathy-the-apoptosis-hypothesis-revisited
#12
REVIEW
Cynthia Kankeu, Kylie Clarke, Egle Passante, Heinrich J Huber
The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10-20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation...
December 8, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27933291/endocytosis-and-physiology-insights-from-disabled-2-deficient-mice
#13
REVIEW
Wensi Tao, Robert Moore, Elizabeth R Smith, Xiang-Xi Xu
Disabled-2 (Dab2) is a clathrin and cargo binding endocytic adaptor protein, and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. A PTB/PID domain located in the N-terminus of Dab2 binds the NPXY motif(s) present at the cytoplasmic tails of certain transmembrane proteins/receptors. The membrane receptors reported to bind directly to Dab2 include LDL receptor and its family members LRP1 and LRP2 (megalin), growth factor receptors EGFR and FGFR, and the cell adhesion receptor beta1 integrin...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27933256/explaining-bioenergy-representations-of-jatropha-in-kenya-before-and-after-disappointing-results
#14
Carol Hunsberger
Proponents of Jatropha curcas portrayed the crop as a 'sustainable biofuel' that was less threatening to food security and forests than other energy crops, creating a reputation that helped jatropha projects to multiply quickly throughout the global South. However, many jatropha initiatives failed to thrive and ultimately collapsed. This paper investigates how actors involved with jatropha in Kenya explained their visions of bioenergy at two points in time. In 2009, when many activities were beginning, I interviewed small-scale farmers, NGO staff, researchers, donors, government officials and members of the private sector about their expectations of jatropha as an energy crop...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27933226/opposite-anisotropy-effects-of-singlet-and-triplet-exciton-diffusion-in-tetracene-crystal
#15
Xiaoyu Xie, Haibo Ma
We observe the diffusion anisotropy difference between singlet and triplet excitons in organic crystals; that is, singlet and triplet excitons may have completely different spatial direction preference for diffusion. This phenomenon can be ascribed to the distinct dependence of different excitonic couplings (Coulomb Förster vs. exchange Dexter) existing in singlet and triplet excitons on their intermolecular distance and intermolecular orientation. Such a discovery provides insights for understanding the fundamental photophysical process in a vast range of organic condensed-phase systems and optimizing the efficiency of organic optoelectronic materials...
June 2016: ChemistryOpen
https://www.readbyqxmd.com/read/27933223/epigenetic-editing-on-the-verge-of-reprogramming-gene-expression-at-will
#16
REVIEW
David Cano-Rodriguez, Marianne G Rots
Genome targeting has quickly developed as one of the most promising fields in science. By using programmable DNA-binding platforms and nucleases, scientists are now able to accurately edit the genome. These DNA-binding tools have recently also been applied to engineer the epigenome for gene expression modulation. Such epigenetic editing constructs have firmly demonstrated the causal role of epigenetics in instructing gene expression. Another focus of epigenome engineering is to understand the order of events of chromatin remodeling in gene expression regulation...
2016: Current Genetic Medicine Reports
https://www.readbyqxmd.com/read/27933213/molecular-pathology-of-cancer-how-to-communicate-with-disease
#17
REVIEW
Peter Birner, Gerald Prager, Berthold Streubel
: Recent technical advances have brought insights into the biology of cancer in human, establishing it as a disease driven by genetic mutations. Beside inherited family tumour syndromes caused by germline mutations, somatic genetic alterations occur early in tumourigenesis, which accumulate during the progression of the disease and its treatment. Based on these observations, medical oncology has started to enter an era of stratified medicine, where treatment selection is becoming tailored to drugable molecular pathways...
2016: ESMO Open
https://www.readbyqxmd.com/read/27933212/spontaneous-destructive-periodontitis-and-skeletal-bone-damage-in-transgenic-mice-carrying-a-human-shared-epitope-coding-hla-drb1-allele
#18
Prashasnika Gehlot, Sarah L Volk, Hector F Rios, Karl J Jepsen, Joseph Holoshitz
OBJECTIVE: Shared epitope (SE)-coding DRB1 alleles are associated with bone erosion in several diseases, including rheumatoid arthritis (RA) and periodontal disease (PD), but the underlying mechanism is unknown. We have recently identified the SE as an osteoclast-activating ligand. To better understand the biological effects of the SE in vivo, here we sought to determine whether it can facilitate spontaneous bone damage in naïve mice. METHODS: 3-month old naïve transgenic mice that carry the human SE-coding allele DRB1*04:01, or a SE-negative allele DRB1*04:02 were studied...
2016: RMD Open
https://www.readbyqxmd.com/read/27933112/osteoblast-and-stem-cell-response-to-nanoscale-topographies-a-review
#19
Nur Izzati Aminuddin, Roslina Ahmad, Sheikh Ali Akbar, Belinda Pingguan-Murphy
To understand how cells respond to the nanoscale extracellular environment in vivo, cells from various sources have been cultured on nanoscale patterns fabricated using bottom-up and top-down techniques. Human fetal osteoblasts (hFOBs) and stem cells are some of them and they are known to be overtly responsive to nanoscale topographies - allowing us to investigate the hows and whys of the response in vitro. Information gathered from these in vitro studies could be used to control the cells, i.e. make the stem cells differentiate or retain their characteristics without the use of medium supplements...
2016: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/27933109/functional-characterization-of-rare-foxp2-variants-in-neurodevelopmental-disorder
#20
Sara B Estruch, Sarah A Graham, Swathi M Chinnappa, Pelagia Deriziotis, Simon E Fisher
BACKGROUND: Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. METHODS: We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins...
2016: Journal of Neurodevelopmental Disorders
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