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https://www.readbyqxmd.com/read/27925642/high-complication-rate-in-young-patients-with-high-energy-intertrochanteric-femoral-fractures
#1
Michael H Amini, John J Feldman, John C Weinlein
Although intertrochanteric femoral fractures in elderly patients are common injuries that have been studied extensively, little has been reported about high-energy intertrochanteric fractures in younger patients. This study examined the injury characteristics and outcomes of high-energy intertrochanteric fractures in patients younger than 65 years treated with either sliding hip screws (SHSs) or cephalomedullary nails (CMNs). A total of 37 patients younger than 65 years (mean age, 45 years) with high-energy intertrochanteric fractures and mean follow-up of 34 weeks were identified; 21 patients were treated with SHSs, and 16 patients were treated with CMNs...
December 7, 2016: Orthopedics
https://www.readbyqxmd.com/read/27919068/capturing-pairwise-and-multi-way-chromosomal-conformations-using-chromosomal-walks
#2
Pedro Olivares-Chauvet, Zohar Mukamel, Aviezer Lifshitz, Omer Schwartzman, Noa Oded Elkayam, Yaniv Lubling, Gintaras Deikus, Robert P Sebra, Amos Tanay
Chromosomes are folded into highly compacted structures to accommodate physical constraints within nuclei and to regulate access to genomic information. Recently, global mapping of pairwise contacts showed that loops anchoring topological domains (TADs) are highly conserved between cell types and species. Whether pairwise loops synergize to form higher-order structures is still unclear. Here we develop a conformation capture assay to study higher-order organization using chromosomal walks (C-walks) that link multiple genomic loci together into proximity chains in human and mouse cells...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27912890/persistence-of-123-i-mibg-prognostic-capability-in-relation-to-medical-therapy-in-heart-failure-from-the-admire-hf-trial
#3
Ileana L Piña, Peter Carson, JoAnn Lindenfeld, W Tad Archambault, Arnold F Jacobson
(123)I-mIBG imaging has been evaluated to assess sympathetic function and prognosis in heart failure (HF). However, the effect of combined HF medical therapies on (123)I-mIBG uptake and its prognostic significance has not been previously examined. This analysis examined the relation between the intensity of guideline-directed HF medical therapy and global (123)I-mIBG cardiac uptake in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) database. A second objective was to investigate whether this guideline-based therapy, measured by total medication doses, had the expected effect on outcome, that is, that patients with higher (123)I-mIBG cardiac uptake and more intensive medical therapy had the fewest outcome events...
October 31, 2016: American Journal of Cardiology
https://www.readbyqxmd.com/read/27907876/rational-design-and-synthesis-of-1-5-disubstituted-tetrazoles-as-potent-inhibitors-of-the-mdm2-p53-interaction
#4
Ewa Surmiak, Constantinos G Neochoritis, Bogdan Musielak, Aleksandra Twarda-Clapa, Katarzyna Kurpiewska, Grzegorz Dubin, Carlos Camacho, Tad A Holak, Alexander Dömling
Using the computational pharmacophore-based ANCHOR.QUERY platform a new scaffold was discovered. Potent compounds evolved inhibiting the protein-protein interaction p53-MDM2. An extensive SAR study was performed based on our four-point pharmacophore model, yielding derivatives with affinity to MDM2 in the nanomolar range. Their binding affinity with MDM2 was evaluated using both fluorescence polarization (FP) assay and 2D-NMR-HSQC experiments.
November 16, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27903487/disturbed-p53-mdm2-feedback-loop-contributes-to-thoracic-aortic-dissection-formation-and-may-be-a-result-of-trim-25-overexpression
#5
Bin Gong, Zhiwei Wang, Min Zhang, Zhipeng Hu, Zongli Ren, Zheng Tang, Wanli Jiang, Lianghao Cheng, Jun Huang, Wei Ren, Qingtao Wang
BACKGROUND: The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 feed-back loop in the formation of TAD, and one of a potential feed-back loop regulator, TRIM-25. METHODS: Surgical specimens of the aorta from TAD patients (n=10) and controls (n=10) were tested for α-smooth muscle actin (α-SMA),p53,murine double minute2(MDM2) and tripartite motif protein-25(TRIM-25) by western blot, immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) , respectively...
November 26, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27901235/use-of-miniplates-as-a-method-for-orthodontic-anchorage-a-case-report
#6
Fernando Gianzanti Peres, Luis Eduardo Marques Padovan, Leandro Eduardo Kluppel, Gustavo Calvalcanti Albuquerque, Paulo Cesar Ulson de Souza, Marcela Claudino
Introduction: Temporary anchorage devices (TADs) have been developed to be used as direct adjuncts in orthodontic treatment and have facilitated treatment of more complex orthodontic cases, including patients with dental impaction. Objectives: This clinical case reports the applicability of TADs in the orthodontic treatment of a patient with impacted mandibular second molars. Surgical and orthodontic procedures related to the use of miniplates were also discussed in this study...
September 2016: Dental Press Journal of Orthodontics
https://www.readbyqxmd.com/read/27899590/different%C3%A2-enhancer-classes-in-drosophila-bind-distinct-architectural-proteins-and-mediate-unique-chromatin-interactions-and-3d-architecture
#7
Caelin Cubeñas-Potts, M Jordan Rowley, Xiaowen Lyu, Ge Li, Elissa P Lei, Victor G Corces
Eukaryotic gene expression is regulated by enhancer-promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer-promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27894363/vector-species-richness-increases-haemorrhagic-disease-prevalence-through-functional-diversity-modulating-the-duration-of-seasonal-transmission-erratum
#8
Andrew W Park, Christopher A Cleveland, Tad A Dallas, Joseph L Corn
No abstract text is available yet for this article.
November 29, 2016: Parasitology
https://www.readbyqxmd.com/read/27893319/insight-into-the-machinery-that-oils-chromatin-dynamics
#9
Roni H G Wright, Narcis Fernandez-Fuentes, Baldomero Oliva, Miguel Beato
The packaging of genetic information in form of chromatin within the nucleus provides cells with the ability to store and protect massive amounts of information within a compact space. Storing information within chromatin allows selective access to specific DNA sequences by regulating the various levels of chromatin structure from nucleosomes, to chromatin fibers, loops and topological associating domains (TADs) using mechanisms that are being progressively unravelled. However, a relatively unexplored aspect is the energetic cost of changing the chromatin configuration to gain access to DNA information...
November 28, 2016: Nucleus
https://www.readbyqxmd.com/read/27889112/risk-factors-for-cut-out-of-double-lag-screw-fixation-in-proximal-femoral-fractures
#10
Kadir Buyukdogan, Omur Caglar, Samet Isik, Mazhar Tokgozoglu, Bulent Atilla
OBJECTIVE: We assessed factors associated with cut-out after internal fixation of proximal femoral fractures using double lag screw nails. DESIGN: Retrospective cohort study. SETTING: A university hospital. PATIENTS AND METHODS: Patients with non-pathological intertrochanteric femur fractures and a minumum 90days follow-up who underwent internal fixation with dual lag screw nails were included. Potential risk factors for lag screw cut-out investigated by our study were: age, gender, body mass index, comorbidities (American Society of Anesthesiologists [ASA] classification), type of fracture (AO/OTA classification), fracture stability, side, operation time, implant length, reduction quality, tip-apex distance (TAD), and lag screw configuration...
November 19, 2016: Injury
https://www.readbyqxmd.com/read/27869826/pan-cancer-analysis-of-somatic-copy-number-alterations-implicates-irs4-and-igf2-in-enhancer-hijacking
#11
Joachim Weischenfeldt, Taronish Dubash, Alexandros P Drainas, Balca R Mardin, Yuanyuan Chen, Adrian M Stütz, Sebastian M Waszak, Graziella Bosco, Ann Rita Halvorsen, Benjamin Raeder, Theocharis Efthymiopoulos, Serap Erkek, Christine Siegl, Hermann Brenner, Odd Terje Brustugun, Sebastian M Dieter, Paul A Northcott, Iver Petersen, Stefan M Pfister, Martin Schneider, Steinar K Solberg, Erik Thunissen, Wilko Weichert, Thomas Zichner, Roman Thomas, Martin Peifer, Aslaug Helland, Claudia R Ball, Martin Jechlinger, Rocio Sotillo, Hanno Glimm, Jan O Korbel
Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains unclear. Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT...
November 21, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27867070/the-shh-topological-domain-facilitates-the-action-of-remote-enhancers-by-reducing-the-effects-of-genomic-distances
#12
Orsolya Symmons, Leslie Pan, Silvia Remeseiro, Tugce Aktas, Felix Klein, Wolfgang Huber, François Spitz
Gene expression often requires interaction between promoters and distant enhancers, which occur within the context of highly organized topologically associating domains (TADs). Using a series of engineered chromosomal rearrangements at the Shh locus, we carried out an extensive fine-scale characterization of the factors that govern the long-range regulatory interactions controlling Shh expression. We show that Shh enhancers act pervasively, yet not uniformly, throughout the TAD. Importantly, changing intra-TAD distances had no impact on Shh expression...
December 5, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27864306/the-transactivation-domains-of-the-p53-protein
#13
Nitin Raj, Laura D Attardi
The p53 tumor suppressor is a transcriptional activator, with discrete domains that participate in sequence-specific DNA binding, tetramerization, and transcriptional activation. Mutagenesis and reporter studies have delineated two distinct activation domains (TADs) and specific hydrophobic residues within these TADs that are critical for their function. Knockin mice expressing p53 mutants with alterations in either or both of the two TADs have revealed that TAD1 is critical for responses to acute DNA damage, whereas both TAD1 and TAD2 participate in tumor suppression...
November 18, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27864032/%C3%AE-1a-adrenergic-receptor-antagonism-improves-erectile-and-cavernosal-responses-in-rats-with-cavernous-nerve-injury-and-enhances-neurogenic-responses-in-human-corpus-cavernosum-from-patients-with%C3%A2-erectile-dysfunction-secondary-to-radical-prostatectomy
#14
Juan I Martínez-Salamanca, José M La Fuente, Eduardo Martínez-Salamanca, Argentina Fernández, Augusto J Pepe-Cardoso, Nuno Louro, Joaquín Carballido, Javier Angulo
INTRODUCTION: Cavernous nerve injury (CNI) in rats and radical prostatectomy (RP) in men result in loss of nitrergic function and increased adrenergic-neurogenic contractions of cavernosal tissue. AIM: To evaluate the modulation of the α-adrenergic system as a strategy to relieve erectile dysfunction (ED) and functional cavernosal alterations induced by CNI. METHODS: A non-selective α-blocker (phentolamine 1 mg/kg daily), a selective α1A-blocker (silodosin [SILOD] 0...
December 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27860491/genomic-selection-in-dairy-cattle-the-usda-experience
#15
George R Wiggans, John B Cole, Suzanne M Hubbard, Tad S Sonstegard
Genomic selection has revolutionized dairy cattle breeding. Since 2000, assays have been developed to genotype large numbers of single-nucleotide polymorphisms (SNPs) at relatively low cost. The first commercial SNP genotyping chip was released with a set of 54,001 SNPs in December 2007. Over 15,000 genotypes were used to determine which SNPs should be used in genomic evaluation of US dairy cattle. Official USDA genomic evaluations were first released in January 2009 for Holsteins and Jerseys, in August 2009 for Brown Swiss, in April 2013 for Ayrshires, and in April 2016 for Guernseys...
November 16, 2016: Annual Review of Animal Biosciences
https://www.readbyqxmd.com/read/27854147/improving-the-developability-of-an-anti-epha2-single-chain-variable-fragment-for-nanoparticle-targeting
#16
Melissa L Geddie, Neeraj Kohli, Dmitri B Kirpotin, Maja Razlog, Yang Jiao, Tad Kornaga, Rachel Rennard, Lihui Xu, Birgit Schoerberl, James D Marks, Daryl C Drummond, Alexey A Lugovskoy
Antibody-targeted nanoparticles have great promise as anti-cancer drugs; however, substantial developmental challenges of antibody modules prevent many candidates from reaching the clinic. Here, we describe a robust strategy for developing an EphA2-targeting antibody fragment for immunoliposomal drug delivery. A highly bioactive single-chain variable fragment (scFv) was engineered to overcome developmental liabilities, including low thermostability and weak binding to affinity purification resins. Improved thermostability was achieved by modifying the framework of the scFv, and complementarity-determining region (CDR)-H2 was modified to increase binding to protein A resins...
November 17, 2016: MAbs
https://www.readbyqxmd.com/read/27833069/benefits-of-mobile-phone-technology-for-personal-environmental-monitoring
#17
David Donaire-Gonzalez, Antònia Valentín, Audrey de Nazelle, Albert Ambros, Glòria Carrasco-Turigas, Edmund Seto, Michael Jerrett, Mark J Nieuwenhuijsen
BACKGROUND: Tracking individuals in environmental epidemiological studies using novel mobile phone technologies can provide valuable information on geolocation and physical activity, which will improve our understanding of environmental exposures. OBJECTIVE: The objective of this study was to assess the performance of one of the least expensive mobile phones on the market to track people's travel-activity pattern. METHODS: Adults living and working in Barcelona (72/162 bicycle commuters) carried simultaneously a mobile phone and a Global Positioning System (GPS) tracker and filled in a travel-activity diary (TAD) for 1 week (N=162)...
November 10, 2016: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/27825926/the-interaction-mode-of-the-acidic-region-of-the-cell-cycle-transcription-factor-dp1-with-tfiih
#18
Masahiko Okuda, Keigo Araki, Kiyoshi Ohtani, Yoshifumi Nishimura
The heterodimeric transcription factor E2F1-DP1 plays crucial roles in coordinating gene expression during G1/S cell cycle progression. For transcriptional activation, the transactivation domain (TAD) of E2F1 is known to interact with the TATA-binding protein of TFIID and the p62 subunit of TFIIH. It is generally believed that DP1 facilitates E2F1 binding to target DNA and does not possess a TAD. Here, we show that an acidic region of DP1, whose function has remained elusive, binds to the plekstrin homology (PH) domain of p62 with higher affinity than that of E2F1 and contributes to transcriptional activation...
November 5, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27820858/saturation-mutagenesis-of-the-hiv-1-envelope-cd4-binding-loop-reveals-residues-controlling-distinct-trimer-conformations
#19
Maria Duenas-Decamp, Li Jiang, Daniel Bolon, Paul R Clapham
The conformation of HIV-1 envelope (Env) glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs) for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD) was investigated using a novel saturation mutagenesis approach...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27817996/patient-perceptions-of-the-direct-anterior-hip-arthroplasty
#20
William H Trousdale, Michael J Taunton, Tad M Mabry, Matthew P Abdel, Robert T Trousdale
BACKGROUND: The quest for less invasive surgical approaches for total hip arthroplasty (THA) has garnered much attention recently in the community, as well as media outlets. There are very little data demonstrating the actual differences in these approaches. We are unaware of any information documenting patients' perceptions of the direct anterior approach (DAA) for THA. The purpose of this study was to collect information regarding patients' perceptions of the DAA THA. METHODS: We surveyed 166 consecutive new patients being evaluated for hip osteoarthritis in our outpatient clinic...
October 13, 2016: Journal of Arthroplasty
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