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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
#1
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/28637276/repetitive-element-transcripts-are-elevated-in-the-brain-of-c9orf72-als-ftld-patients
#2
Mercedes Prudencio, Patrick K Gonzales, Casey N Cook, Tania F Gendron, Lillian M Daughrity, Yuping Song, Mark T W Ebbert, Marka van Blitterswijk, Yong-Jie Zhang, Karen Jansen-West, Matthew C Baker, Michael DeTure, Rosa Rademakers, Kevin B Boylan, Dennis W Dickson, Leonard Petrucelli, Christopher D Link
Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analyzed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls...
June 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28637194/high-iron-supply-inhibits-the-synthesis-of-the-genotoxin-colibactin-by-pathogenic-escherichia-coli-through-a-non-canonical-fur-ryhb-mediated-pathway
#3
Sophie Tronnet, Christophe Garcie, Alexander O Brachmann, Jörn Piel, Eric Oswald, Patricia Martin
The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic Enterobacteria, and is associated with colon cancer development and acute systemic infections. The colibactin biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase ClbA. We recently evidenced that two master regulators of bacterial iron homeostasis, i.e. the ferric uptake regulator (Fur) and the small regulatory non-coding RNA RyhB, were involved in the regulation of the clbA transcription and of the colibactin production...
June 20, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28637116/neurosurgeon-or-spinal-surgeon-who-should-treat-cauda-equina-syndrome
#4
Christopher James Andrew Cowie, Jonathan Richard Ellenbogen
Suspected cauda equina syndrome (CES) requires urgent evaluation, investigation and treatment. Timing of cauda equina decompression is crucial, and delays in its management, leading to significant irreversible disability can be devastating for patient and surgeon alike. The standard of care in CES therefore needs to be clear and unambiguous. Todd and Dickson have written an excellent paper summarising the condition, and have outlined what they feel is the standard of care. We would ask the authors to clarify an important point...
March 2, 2017: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/28636958/protective-and-pathological-immunity-during-central-nervous-system-infections
#5
REVIEW
Robyn S Klein, Christopher A Hunter
The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636956/elicitation-of-robust-tier-2-neutralizing-antibody-responses-in-nonhuman-primates-by-hiv-envelope-trimer-immunization-using-optimized-approaches
#6
Matthias Pauthner, Colin Havenar-Daughton, Devin Sok, Joseph P Nkolola, Raiza Bastidas, Archana V Boopathy, Diane G Carnathan, Abishek Chandrashekar, Kimberly M Cirelli, Christopher A Cottrell, Alexey M Eroshkin, Javier Guenaga, Kirti Kaushik, Daniel W Kulp, Jinyan Liu, Laura E McCoy, Aaron L Oom, Gabriel Ozorowski, Kai W Post, Shailendra K Sharma, Jon M Steichen, Steven W de Taeye, Talar Tokatlian, Alba Torrents de la Peña, Salvatore T Butera, Celia C LaBranche, David C Montefiori, Guido Silvestri, Ian A Wilson, Darrell J Irvine, Rogier W Sanders, William R Schief, Andrew B Ward, Richard T Wyatt, Dan H Barouch, Shane Crotty, Dennis R Burton
The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636941/highly-aggressive-metastatic-melanoma-cells-unable-to-maintain-telomere-length
#7
Nikenza Viceconte, Marie-Sophie Dheur, Eva Majerova, Christophe E Pierreux, Jean-François Baurain, Nicolas van Baren, Anabelle Decottignies
Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636935/the-sensory-striatum-is-permanently-impaired-by-transient-developmental-deprivation
#8
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/28636911/direct-conversion-of-an-enzyme-from-native-like-to-amyloid-like-aggregates-within-inclusion-bodies
#9
Francesco Elia, Francesca Cantini, Fabrizio Chiti, Christopher Martin Dobson, Francesco Bemporad
The acylphosphatase from Sulfolobus solfataricus (Sso AcP) is a globular protein able to aggregate in vitro from a native-like conformational ensemble without the need for a transition across the major unfolding energy barrier. This process leads to the formation of assemblies in which the protein retains its native-like structure, which subsequently convert into amyloid-like aggregates. Here, we investigate the mechanism by which Sso AcP aggregates in vivo to form bacterial inclusion bodies after expression in E...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636886/sirt1-enzymatically-potentiates-1-25-dihydroxyvitamin-d3-signaling-via-vitamin-d-receptor-deacetylation
#10
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/28636870/adherence-to-and-acceptability-of-listerine-%C3%A2-mouthwash-as-a-potential-preventive-intervention-for-pharyngeal-gonorrhoea-among-men-who-have-sex-with-men-in-australia-a-longitudinal-study
#11
Vincent J Cornelisse, Christopher K Fairley, Sandra Walker, Tameka Young, David Lee, Marcus Y Chen, Catriona S Bradshaw, Eric P F Chow
We investigated whether men who have sex with men (MSM) would use mouthwash daily to prevent pharyngeal gonorrhoea. Ten MSM attending the Melbourne Sexual Health Centre were asked to use a Listerine(®) alcohol-containing mouthwash daily for 14 days in August 2015. Mouthwash was used at least once daily for 133 of 140 person-days (95% of days; 95% confidence interval 90-98%). All 10 men were willing to use mouthwash on a daily basis, and nine men were willing to use mouthwash after oral sex. This study showed that daily use of mouthwash is an acceptable intervention to prevent pharyngeal gonorrhoea in MSM...
October 2016: Sexual Health
https://www.readbyqxmd.com/read/28636869/association-between-sexual-mixing-and-genital-warts-in-heterosexual-men-in-australia-the-herd-protection-from-the-female-human-papillomavirus-vaccination-program
#12
Eric P F Chow, Christopher K Fairley
Australian-born women aged ≤32 years were eligible for the free female human papillomavirus (HPV) vaccination program introduced in 2007. A total of 1165 heterosexual couples attending the Melbourne Sexual Health Centre between 2011 and 2014 were included in this analysis. Findings showed the odds of having penile warts was 0.52-fold lower among men who had a female partner aged ≤32 years compared with men who had a female partners aged >32 years. This suggests men would have received herd protection from their female partners and hence they are at lower risk of acquiring genital warts...
October 2016: Sexual Health
https://www.readbyqxmd.com/read/28636867/assortative-sexual-mixing-patterns-in-male-female-and-male-male-partnerships-in-melbourne-australia-implications-for-hiv-and-sexually-transmissible-infection-transmission
#13
Eric P F Chow, Tim R H Read, Matthew G Law, Marcus Y Chen, Catriona S Bradshaw, Christopher K Fairley
BACKGROUND: Assortative mixing patterns have become a new and important focus in HIV/sexually transmissible infection (STI) research in recent years. There are very limited data on sexual mixing patterns, particularly in an Australian population. METHODS: Male-female and male-male partnerships attending the Melbourne Sexual Health Centre (MSHC) between 2011 and 2014 were included. Correlation of age between two individuals within a partnership was examined by using Spearman's rank correlation...
October 2016: Sexual Health
https://www.readbyqxmd.com/read/28636844/clonal-hematopoiesis-and-risk-of-atherosclerotic-cardiovascular-disease
#14
Siddhartha Jaiswal, Pradeep Natarajan, Alexander J Silver, Christopher J Gibson, Alexander G Bick, Eugenia Shvartz, Marie McConkey, Namrata Gupta, Stacey Gabriel, Diego Ardissino, Usman Baber, Roxana Mehran, Valentin Fuster, John Danesh, Philippe Frossard, Danish Saleheen, Olle Melander, Galina K Sukhova, Donna Neuberg, Peter Libby, Sekar Kathiresan, Benjamin L Ebert
Background Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. Methods We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls...
June 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636814/arsenic-compromises-both-p97-and-proteasome-functions
#15
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
https://www.readbyqxmd.com/read/28636798/a-ccpe-based-xenon-biosensor-for-magnetic-resonance-imaging-of-claudin-expressing-cells
#16
Anna Piontek, Christopher Witte, Honor May Rose, Miriam Eichner, Jonas Protze, Gerd Krause, Jörg Piontek, Leif Schröder
The majority of malignant tumors originate from epithelial cells, and many of them are characterized by an overexpression of claudins (Cldns) and their mislocalization out of tight junctions. We utilized the C-terminal claudin-binding domain of Clostridium perfringens enterotoxin (cCPE), with its high affinity to specific members of the claudin family, as the targeting unit for a claudin-sensitive cancer biosensor. To overcome the poor sensitivity of conventional relaxivity-based magnetic resonance imaging (MRI) contrast agents, we utilized the superior sensitivity of xenon Hyper-CEST biosensors...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28636753/stable-bromiranium-ions-with-weakly-coordinating-counterions-as-efficient-electrophilic-brominating-agents
#17
Christoph Ascheberg, Jonathan Bock, Florenz Buß, Christian Mück-Lichtenfeld, Constantin B Daniliuc, Klaus Bergander, Fabian Dielmann, Ulrich Hennecke
Electrophilic halogenating agents are an important class of reagents in chemical synthesis. Herein, we show that sterically demanding bromiranium ions with weakly coordinating counterions are highly reactive electrophilic brominating agents. Despite their high reactivity these reagents are stable, in one case even under ambient conditions and can be applied in electrophilic halogenations of alkenes as well as heteroatoms.
June 21, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28636740/initial-experience-of-a-hereditary-hemorrhagic-telangiectasia-center-of-excellence
#18
Christopher F Thompson, Jeffrey D Suh, Justin McWilliams, Gary Duckwiler, Marilene B Wang
Our objectives in reviewing the initial experience of a hereditary hemorrhagic telangiectasia center of excellence (HHT COE) were to better understand the interventions being performed in the comprehensive care of these patients and to present the early data as a reference for other tertiary centers considering starting an HHT COE. We conducted a retrospective review of consecutive patients referred to our newly developed HHT COE for evaluation and treatment between May 2010 and June 2013. Clinical presentation, otolaryngologic treatments, and other operative interventions were analyzed...
June 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28636729/massive-auricular-cutaneous-horn
#19
Christopher P Nyte
No abstract text is available yet for this article.
June 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28636665/monitoring-obesity-prevalence-in-the-united-states-through-bookmarking-activities-in-online-food-portals
#20
Christoph Trattner, Denis Parra, David Elsweiler
Studying the impact of food consumption on people's health is a serious matter for its implications on public policy, but it has traditionally been a slow process since it requires information gathered through expensive collection processes such as surveys, census and systematic reviews of research articles. We argue that this process could be supported and hastened using data collected via online social networks. In this work we investigate the relationships between the online traces left behind by users of a large US online food community and the prevalence of obesity in 47 states and 311 counties in the US...
2017: PloS One
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