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https://www.readbyqxmd.com/read/29161344/nuclear-localization-of-eif4g3-suggests-a-role-for-the-xy-body-in-translational-regulation-during-spermatogenesis-in-mice
#1
Jianjun Hu, Fengyun Sun, Mary Ann Handel
Eukaryotic translation initiation factor 4G (EIF4G) is an important scaffold protein in the translation initiation complex. In mice mutation of the Eif4g3 gene causes male infertility, with arrest of meiosis at the end of meiotic prophase. This study documents features of the developmental expression and sub-cellular localization of EIF4G3 that might contribute to its highly specific role in meiosis and spermatogenesis. Quite unexpectedly, EIF4G3 is located in the nucleus of spermatocytes, where it is highly enriched in the XY body, the chromatin domain formed by the transcriptionally inactive sex chromosomes...
November 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29160697/cascade-synthesis-of-3-functionalized-indoles-from-nitrones-and-their-conversion-to-cycloheptanone-fused-indoles
#2
Michelle A Kroc, Ami Prajapati, Donald J Wink, Laura L Anderson
A cascade reaction of N-aryl-α,β-unsaturated nitrones and electron-deficient allenes has been discovered that allows single-step access to 3-functionalized indoles that usually require pre-formation and alkylation of an indole precursor. The heterocycles prepared through the hydrogen-bond-donor catalyzed cascade reaction are poised to undergo a McMurry coupling to form previously synthetically elusive cycloheptanone-fused indoles. The scope of these transformations is discussed, as well as mechanistic experiments describing proposed intermediates of the cascade reaction, and an initial catalytic asymmetric example that generates a carbon stereocenter during the cascade process...
November 21, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29158839/characterization-of-cardiac-dynamics-in-an-acute-myocardial-infarction-model-by-four-dimensional-optoacoustic-and-magnetic-resonance-imaging
#3
Hsiao-Chun Amy Lin, Xosé Luís Déan-Ben, Ivana Ivankovic, Melanie A Kimm, Katja Kosanke, Helena Haas, Reinhard Meier, Fabian Lohöfer, Moritz Wildgruber, Daniel Razansky
Extraction of murine cardiac functional parameters on a beat-by-beat basis is limited with the existing imaging modalities due to insufficient three-dimensional temporal resolution. Faster volumetric imaging methods enabling in vivo characterization of functional parameters are poised to advance cardiovascular research and provide a better understanding of the mechanisms underlying cardiac diseases. We present a new approach based on analyzing contrast-enhanced optoacoustic (OA) images acquired at high volumetric frame rate without using cardiac gating or other approaches for motion correction...
2017: Theranostics
https://www.readbyqxmd.com/read/29158493/structural-and-spatial-chromatin-features-at-developmental-gene-loci-in-human-pluripotent-stem-cells
#4
Hiroki Ikeda, Masamitsu Sone, Shinya Yamanaka, Takuya Yamamoto
Higher-order chromatin organization controls transcriptional programs that govern cell properties and functions. In order for pluripotent stem cells (PSCs) to appropriately respond to differentiation signals, developmental gene loci should be structurally and spatially regulated to be readily available for immediate transcription, even though these genes are hardly expressed in PSCs. Here, we show that both chromatin interaction profiles and nuclear positions at developmental gene loci differ between human somatic cells and hPSCs, and that changes in the chromatin interactions are closely related to the nuclear repositioning...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29156422/syndecan-1-in-mechanosensing-of-nanotopological-cues-in-engineered-materials
#5
Victoria Le, Jason Lee, Somali Chaterji, Adrianne Spencer, Yen-Liang Liu, Peter Kim, Hsin-Chih Yeh, Deok-Ho Kim, Aaron B Baker
The cells of the vascular system are highly sensitive to biophysical cues from their local cellular microenvironment. To engineer improved materials for vascular devices and delivery of cell therapies, a key challenge is to understand the mechanisms that cells use to sense biophysical cues from their environment. Syndecans are heparan sulfate proteoglycans (HSPGs) that consist of a protein core modified with heparan sulfate glycosaminoglycan chains. Due to their presence on the cell surface and their interaction with cytoskeletal and focal adhesion associated molecules, cell surface proteoglycans are well poised to serve as mechanosensors of the cellular microenvironment...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29155379/women-break-an-engineering-barrier-while-other-engineering-disciplines-stumble-bme-represents-a-success-story-in-attracting-american-women-to-a-male-dominated-field
#6
Claudia Gutierrez, Meaghan Paulosky, Angeline Aguinaldo, Jackie Gerhart
While the field of engineering as a whole is largely male-dominated, biomedical engineering (BME) is one area poised to overturn this trend. Women in the United States were awarded only 20% of all engineering B.S. degrees in 2015; in BME, however, 40.9% of the degree recipients were women. This stands in stark contrast to the more traditional fields of mechanical and electrical engineering, where women were awarded just 13.2% and 12.5% of B.S. degrees, respectively. This trend toward more female participation in BME continues at both the M...
November 2017: IEEE Pulse
https://www.readbyqxmd.com/read/29155220/complement-components-as-promoters-of-immunological-tolerance-in-dendritic-cells
#7
REVIEW
Ana Luque, Inmaculada Serrano, Josep M Aran
Complement and dendritic cells (DCs) share many functional features that drive the outcome of immune-inflammatory processes. Both have a sentinel function, acting as danger sensors specialized for a rapid, comprehensive and selective action against potential threats without damaging the healthy host cells. But while complement has been considered as a "master alarm" system poised for direct pathogen killing, DCs are regarded as "master regulators" or orchestrators of a vast range of effector immune cells for an effective immune response against threatening insults...
November 16, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29154018/improving-patient-access-to-hepatitis-c-virus-treatment
#8
Milena M McLaughlin, Kevin T Marx, Colleen Terriff
OBJECTIVES: To discuss the current barriers to hepatitis C virus (HCV) treatment; to provide information and resources to assist health care providers with the prior authorization process; to provide resources for potential access to medications if a patient's third-party payer may not be an option; and to discuss the pharmacist's vital role as a patient advocate and considerations once medications are approved. SUMMARY: Access to HCV medications is often restricted by third-party payers...
November 16, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/29153504/pressure-dependent-chemical-shifts-in-the-r3-domain-of-talin-show-that-it-is-thermodynamically-poised-for-binding-to-either-vinculin-or-riam
#9
Nicola J Baxter, Thomas Zacharchenko, Igor L Barsukov, Mike P Williamson
Talin mediates attachment of the cell to the extracellular matrix. It is targeted by the Rap1 effector RIAM to focal adhesion sites and subsequently undergoes force-induced conformational opening to recruit the actin-interacting protein vinculin. The conformational switch involves the talin R3 domain, which binds RIAM when closed and vinculin when open. Here, we apply pressure to R3 and measure (1)H, (15)N, and (13)C chemical shift changes, which are fitted using a simple model, and indicate that R3 is only 50% closed: the closed form is a four-helix bundle, while in the open state helix 1 is twisted out...
November 10, 2017: Structure
https://www.readbyqxmd.com/read/29153196/metabolic-biomarkers-in-heart-failure
#10
REVIEW
Chonyang L Albert, W H Wilson Tang
Metabolomics is the study of small, organic molecules within biochemical pathways. With advancement of technology, nuclear magnetic resonance, gas chromatography, and mass spectrometry have allowed for the discovery and analysis of large databases of metabolites implicated in heart failure. Metabolomics also explores the patient and environment interactions and unlocks the link between environmental exposures and the development of cardiovascular disease. Although a relatively new field, metabolomics is poised to become a clinically impactful field that develops novel biomarkers and explores new therapeutic interventions in heart failure...
January 2018: Heart Failure Clinics
https://www.readbyqxmd.com/read/29152027/design-considerations-for-open-well-microfluidic-platforms-for-hypoxic-cell-studies
#11
Matthew B Byrne, Matthew T Leslie, Heeral S Patel, H Rex Gaskins, Paul J A Kenis
Regions of hypoxia are common in solid tumors and are associated with enhanced malignancy, metastasis, and chemo/radio resistance. Real-time hypoxic cellular experimentation is challenging due to the constant need for oxygen control. Most microfluidic platforms developed thus far for hypoxic cell studies are burdened by complex design parameters and are difficult to use for uninitiated investigators. However, open-well microfluidic platforms enable short and long term hypoxic cell studies with an ease of use workflow...
September 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/29139335/shprh-as-a-new-player-in-ribosomal-rna-transcription-and-its-potential-role-in-homeostasis-of-ribosomal-dna-repeats
#12
Deokjae Lee, Jun Hong Park, Shinseog Kim, Seon-Gyeong Lee, Kyungjae Myung
There are hundreds of copies of rDNA repeats in mammalian chromosomes and the ratio of active, poised, or inactive rDNA is regulated in epigenetic manners. Recent studies demonstrated that a post-DNA replication repair enzyme, SHPRH affects rRNA transcription by recognizing epigenetic markers on rDNA promoters and unveiled potential links between DNA repair and ribosome biogenesis (1) . This study suggests that SHPRH could be a link between mTOR-mediated epigenetic regulations and rRNA transcription, while concomitantly affecting genomic integrity...
November 15, 2017: Transcription
https://www.readbyqxmd.com/read/29139289/tetraaza-14-and-octaaza-18-paracyclophane-synthesis-and-characterization-of-their-neutral-and-cationic-states
#13
Daisuke Sakamaki, Akihiro Ito, Yusuke Tsutsui, Shu Seki
Two kinds of aza[1n]paracyclophanes, tetraaza[14]paracyclophane (P4) and octaaza[18]paracyclophane (P8), were synthesized as the smallest and the largest monodisperse macrocyclic oligomers of polyaniline ever made. Herein we report the electronic nature of the cationic species of these two macrocycles with different ring size. By combining ESR spectroscopy and DFT calculations it was suggested that P4(·+) was classified as delocalized class III or poised on the class II/III borderline while P8(·+) was regarded as a localized class II mixed-valence system...
November 22, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29136283/population-pk-analyses-of-ubrogepant-mk-1602-a-cgrp-receptor-antagonist-enriching-in-clinic-plasma-pk-sampling-with-outpatient-dried-blood-spot-sampling
#14
Chi-Chung Li, Marissa Dockendorf, Ken Kowalski, Bei Yang, Yang Xu, Iris Xie, Huub Jan Kleijn, Rolien Bosch, Christopher Jones, Bob Thornton, Eugene E Marcantonio, Tiffini Voss, Kevin P Bateman, Prajakti A Kothare
Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late-stage trials for population pharmacokinetic (PK) modeling. We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. At the time of implementation, ubrogepant was entering phase 2 development. DBS was implemented to acquire PK information proximal to an acute migraine event to enable exposure-response modeling...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29134359/anxiety-depression-and-the-microbiome-a-role-for-gut-peptides
#15
REVIEW
Gilliard Lach, Harriet Schellekens, Timothy G Dinan, John F Cryan
The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling...
November 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29133290/cd137-4-1bb-costimulation-modifies-dna-methylation-in-cd8-t-cell-relevant-genes
#16
M Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Carmen Molina, Saray Garasa, Arantza Azpilicueta, Inaki Etxeberria, Alfonso R Sanchez-Paulete, Alan J Korman, Manel Esteller, Juan Sandoval, Ignacio Melero
CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA-methylation arrays were carried out on human peripheral blood CD8+ T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy. Several genes showed consistent methylation patterns in response to CD137 costimulation, which were confirmed by pyrosequencing in a series of healthy donors...
November 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29132976/investigations-into-the-carbonic-anhydrase-inhibition-of-cos-releasing-donor-core-motifs
#17
Andrea K Steiger, Yu Zhao, Won Jin Choi, Alder Crammond, McKinna R Tillotson, Michael D Pluth
Carbonyl sulfide (COS) releasing scaffolds are gaining popularity as hydrogen sulfide (H2S) donors through exploitation of the carbonic anhydrase (CA)-mediated hydrolysis of COS to H2S. The majority of compounds in this emerging class of donors undergo triggerable decomposition (often referred to as self-immolation) to release COS, and a handful of different COS-releasing structures have been reported. One benefit of this donation strategy is that numerous caged COS-containing core motifs are possible and are poised for development into self-immolative COS/H2S donors...
November 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29128695/insights-from-structures-of-cancer-relevant-pre-mrna-splicing-factors
#18
REVIEW
Clara L Kielkopf
Pre-mRNA splicing factors recognize consensus signals within preliminary transcripts, and as cogs of the spliceosome machine, orchestrate the excision and rejoining of pre-mRNA regions for gene expression. Large-scale sequencing has demonstrated that mutations in key genes encoding pre-mRNA splicing factors are common among myeloid neoplasms and also occur in a variety of other cancers. This revelation offers new therapeutic opportunities to target pre-mRNA splicing vulnerabilities in hematologic and other malignancies...
November 9, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29128351/drosophila-models-of-fop-provide-mechanistic-insight
#19
REVIEW
Viet Le, Edward Anderson, Takuya Akiyama, Kristi A Wharton
Fibrodysplasia ossificans progressiva (FOP) is a rare bone disease characterized by episodic events of heterotopic ossification (HO). All cases of FOP have been attributed to mutations in the ACVR1 gene that render the encoded BMP type I ALK2 receptor hypersensitive, resulting in the activation of BMP signaling, at inappropriate times in inappropriate locations. The episodic or sporadic nature of HO associated with FOP rests with the occurrence of specific 'triggers' that push the hypersensitive ALK2-FOP receptor into full signaling mode...
November 8, 2017: Bone
https://www.readbyqxmd.com/read/29121014/first-aav-gene-therapy-poised-for-landmark-approval
#20
Eric Smalley
No abstract text is available yet for this article.
November 9, 2017: Nature Biotechnology
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