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https://www.readbyqxmd.com/read/28630923/ribosome-rearrangements-at-the-onset-of-translational-bypassing
#1
Xabier Agirrezabala, Ekaterina Samatova, Mariia Klimova, Miguel Zamora, David Gil-Carton, Marina V Rodnina, Mikel Valle
Bypassing is a recoding event that leads to the translation of two distal open reading frames into a single polypeptide chain. We present the structure of a translating ribosome stalled at the bypassing take-off site of gene 60 of bacteriophage T4. The nascent peptide in the exit tunnel anchors the P-site peptidyl-tRNA(Gly) to the ribosome and locks an inactive conformation of the peptidyl transferase center (PTC). The mRNA forms a short dynamic hairpin in the decoding site. The ribosomal subunits adopt a rolling conformation in which the rotation of the small subunit around its long axis causes the opening of the A-site region...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630410/investigating-the-life-expectancy-and-proteolytic-degradation-of-engineered-skeletal-muscle-biological-machines
#2
Caroline Cvetkovic, Meghan C Ferrall-Fairbanks, Eunkyung Ko, Lauren Grant, Hyunjoon Kong, Manu O Platt, Rashid Bashir
A combination of techniques from 3D printing, tissue engineering and biomaterials has yielded a new class of engineered biological robots that could be reliably controlled via applied signals. These machines are powered by a muscle strip composed of differentiated skeletal myofibers in a matrix of natural proteins, including fibrin, that provide physical support and cues to the cells as an engineered basement membrane. However, maintaining consistent results becomes challenging when sustaining a living system in vitro...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630088/the-islet-resident-macrophage-is-in-an-inflammatory-state-and-senses-microbial-products-in-blood
#3
Stephen T Ferris, Pavel N Zakharov, Xiaoxiao Wan, Boris Calderon, Maxim N Artyomov, Emil R Unanue, Javier A Carrero
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of 3-wk-old non-obese diabetic (NOD), NOD.Rag1(-/-), and B6.g7 mice. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II at both the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them...
June 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28629775/8-oxo-7-8-dihydroguanine-friend-and-foe-epigenetic-like-regulator-versus-initiator-of-mutagenesis
#4
REVIEW
Aaron M Fleming, Cynthia J Burrows
A high flux of reactive oxygen species during oxidative stress results in oxidative modification of cellular components including DNA. Oxidative DNA "damage" to the heterocyclic bases is considered deleterious because polymerases may incorrectly read the modifications causing mutations. A prominent member in this class is the oxidized guanine base 8-oxo-7,8-dihydroguanine (OG) that is moderately mutagenic effecting G→T transversion mutations. Recent reports have identified that formation of OG in G-rich regulatory elements in the promoters of the VEGF, TNFα, and SIRT1 genes can increase transcription via activation of the base excision repair (BER) pathway...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28622731/navigating-tissue-chips-from-development-to-dissemination-a-pharmaceutical-industry-perspective
#5
Lorna Ewart, Kristin Fabre, Ananthsrinivas Chakilam, Yvonne Dragan, David B Duignan, Jeetu Eswaraka, Jinping Gan, Peggy Guzzie-Peck, Monicah Otieno, Claire G Jeong, Douglas A Keller, Sonia M de Morais, Jonathan A Phillips, William Proctor, Radhakrishna Sura, Terry Van Vleet, David Watson, Yvonne Will, Danilo Tagle, Brian Berridge
Tissue chips are poised to deliver a paradigm shift in drug discovery. By emulating human physiology, these chips have the potential to increase the predictive power of preclinical modeling, which in turn will move the pharmaceutical industry closer to its aspiration of clinically relevant and ultimately animal-free drug discovery. Despite the tremendous science and innovation invested in these tissue chips, significant challenges remain to be addressed to enable their routine adoption into the industrial laboratory...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28622175/predictors-prognosis-and-management-of-new-clinically-important-atrial-fibrillation-after-noncardiac-surgery-a-prospective-cohort-study
#6
Pablo Alonso-Coello, Deborah Cook, Shou Chun Xu, Alben Sigamani, Otavio Berwanger, Soori Sivakumaran, Homer Yang, Denis Xavier, Luz Ximena Martinez, Pedro Ibarra, Purnima Rao-Melacini, Janice Pogue, Kelly Zarnke, Pilar Paniagua, Jack Ostrander, Salim Yusuf, P J Devereaux
BACKGROUND: Despite the frequency of new clinically important atrial fibrillation (AF) after noncardiac surgery and its increased association with the risk of stroke at 30 days, there are limited data informing their prediction, association with outcomes, and management. METHODS: We used the data from the PeriOperative ISchemic Evaluation trial to determine, in patients undergoing noncardiac surgery, the association of new clinically important AF with 30-day outcomes, and to assess management of these patients...
July 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28619757/cdk4-6-inhibitors-sensitize-rb-positive-sarcoma-cells-to-wee1-kinase-inhibition-through-reversible-cell-cycle-arrest
#7
Ashleigh M Francis, Angela Alexander, Yanna Liu, Smruthi Vijayaraghavan, Kwang Hui Low, Dong Yang, Tuyen Bui, Neeta Somaiah, Vinod Ravi, Khandan Keyomarsi, Kelly K Hunt
Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28617487/organ-on-a-chip-devices-advance-to-market
#8
Boyang Zhang, Milica Radisic
To curb the high cost of drug development, there is an urgent need to develop more predictive tissue models using human cells to determine drug efficacy and safety in advance of clinical testing. Recent insights gained through fundamental biological studies have validated the importance of dynamic cell environments and cellular communication to the expression of high fidelity organ function. Building on this knowledge, emerging organ-on-a-chip technology is poised to fill the gaps in drug screening by offering predictive human tissue models with methods of sophisticated tissue assembly...
June 15, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28608597/perineal-techniques-during-the-second-stage-of-labour-for-reducing-perineal-trauma
#9
REVIEW
Vigdis Aasheim, Anne Britt Vika Nilsen, Liv Merete Reinar, Mirjam Lukasse
BACKGROUND: Most vaginal births are associated with trauma to the genital tract. The morbidity associated with perineal trauma can be significant, especially when it comes to third- and fourth-degree tears. Different interventions including perineal massage, warm or cold compresses, and perineal management techniques have been used to prevent trauma. This is an update of a Cochrane review that was first published in 2011. OBJECTIVES: To assess the effect of perineal techniques during the second stage of labour on the incidence and morbidity associated with perineal trauma...
June 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28607146/epigenetic-transcriptional-memory-of-gal-genes-depends-on-growth-in-glucose-and-the-tup1-transcription-factor-in-saccharomyces-cerevisiae
#10
Varun Sood, Ivelisse Cajigas, Agustina D'Urso, William H Light, Jason H Brickner
Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The GAL genes in Saccharomyces cerevisiae show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of GAL1, GAL10, GAL2 and GAL7 These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory...
June 12, 2017: Genetics
https://www.readbyqxmd.com/read/28606202/an-assessment-of-climate-change-impacts-on-los-angeles-california-usa-hospitals-wildfires-highest-priority
#11
Sabrina A Adelaine, Mizuki Sato, Yufang Jin, Hilary Godwin
Introduction Although many studies have delineated the variety and magnitude of impacts that climate change is likely to have on health, very little is known about how well hospitals are poised to respond to these impacts. Hypothesis/Problem The hypothesis is that most modern hospitals in urban areas in the United States need to augment their current disaster planning to include climate-related impacts. METHODS: Using Los Angeles County (California USA) as a case study, historical data for emergency department (ED) visits and projections for extreme-heat events were used to determine how much climate change is likely to increase ED visits by mid-century for each hospital...
June 13, 2017: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/28606143/effectiveness-of-reactive-case-detection-for-malaria-elimination-in-three-archetypical-transmission-settings-a-modelling-study
#12
Jaline Gerardin, Caitlin A Bever, Daniel Bridenbecker, Busiku Hamainza, Kafula Silumbe, John M Miller, Thomas P Eisele, Philip A Eckhoff, Edward A Wenger
BACKGROUND: Reactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages...
June 12, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28605593/simultaneous-drug-targeting-of-the-promoter-myc-g-quadruplex-and-bcl2-i-motif-in-diffuse-large-b-cell-lymphoma-delays-tumor-growth
#13
Samantha Kendrick, Andrea Muranyi, Vijay Gokhale, Laurence H Hurley, Lisa M Rimsza
Secondary DNA structures are uniquely poised as therapeutic targets due to their molecular switch function in turning gene expression on or off and scaffold-like properties for protein and small molecule interaction. Strategies to alter gene transcription through these structures thus far involve targeting single DNA conformations. Here we investigate the feasibility of simultaneously targeting different secondary DNA structures to modulate two key oncogenes, cellular-myelocytomatosis (MYC) and B-cell lymphoma gene-2 (BCL2), in diffuse large B-cell lymphoma (DLBCL)...
June 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28605376/anatomically-inspired-three-dimensional-micro-tissue-engineered-neural-networks-for-nervous-system-reconstruction-modulation-and-modeling
#14
Laura A Struzyna, Dayo O Adewole, Wisberty J Gordián-Vélez, Michael R Grovola, Justin C Burrell, Kritika S Katiyar, Dmitriy Petrov, James P Harris, D Kacy Cullen
Functional recovery rarely occurs following injury or disease-induced degeneration within the central nervous system (CNS) due to the inhibitory environment and the limited capacity for neurogenesis. We are developing a strategy to simultaneously address neuronal and axonal pathway loss within the damaged CNS. This manuscript presents the fabrication protocol for micro-tissue engineered neural networks (micro-TENNs), implantable constructs consisting of neurons and aligned axonal tracts spanning the extracellular matrix (ECM) lumen of a preformed hydrogel cylinder hundreds of microns in diameter that may extend centimeters in length...
May 31, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28605069/the-bacillus-subtilis-germinant-receptor-gera-triggers-premature-germination-in-response-to-morphological-defects-during-sporulation
#15
Fernando H Ramírez-Guadiana, Alexander J Meeske, Xindan Wang, Christopher D A Rodrigues, David Z Rudner
During sporulation in Bacillus subtilis, germinant receptors assemble in the inner membrane of the developing spore. In response to specific nutrients these receptors trigger germination and outgrowth. In a transposon-sequencing screen, we serendipitously discovered that loss of function mutations in the gerA receptor partially suppress the phenotypes of >25 sporulation mutants. Most of these mutants have modest defects in the assembly of the spore protective layers that are exacerbated in the presence of a functional GerA receptor...
June 12, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28603077/configuring-a-robust-nervous-system-with-fat-cadherins
#16
REVIEW
Evelyn C Avilés, Lisa V Goodrich
Atypical Fat cadherins represent a small but versatile group of signaling molecules that influence proliferation and tissue polarity. With huge extracellular domains and intracellular domains harboring many independent protein interaction sites, Fat cadherins are poised to translate local cell adhesion events into a variety of cell behaviors. The need for such global coordination is particularly prominent in the nervous system, where millions of morphologically diverse neurons are organized into functional networks...
June 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28594236/the-blood-of-my-veins-mercury-minamata-and-the-soul-of-japan
#17
Gerald F O'Malley
The methylmercury contamination of Minamata Bay during the WWII postwar period resulted in thousands of Japanese citizens suffering horrific neurological injury. Fear and miscommunication destroyed and changed family and social structure. In addition, the Minamata poisoning caused momentous changes in the civic discourse in Japan and was an instrumental event in the democratization of the country. This manuscript describes the effects that the environmental contamination and human poising had in the transition of Japan from a feudal society to a democratic one...
June 8, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28591578/plk1-activation-in-late-g2-sets-up-commitment-to-mitosis
#18
Lilia Gheghiani, Damarys Loew, Bérangère Lombard, Jörg Mansfeld, Olivier Gavet
Commitment to mitosis must be tightly coordinated with DNA replication to preserve genome integrity. While we have previously established that the timely activation of CyclinB1-Cdk1 in late G2 triggers mitotic entry, the upstream regulatory mechanisms remain unclear. Here, we report that Polo-like kinase 1 (Plk1) is required for entry into mitosis during an unperturbed cell cycle and is rapidly activated shortly before CyclinB1-Cdk1. We determine that Plk1 associates with the Cdc25C1 phosphatase and induces its phosphorylation before mitotic entry...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28578176/research-standardization-tools-pregnancy-measures-in-the-phenx-toolkit
#19
Ann Kinga Malinowski, Cande V Ananth, Patrick Catalano, Erin P Hines, Russell S Kirby, Mark A Klebanoff, John J Mulvihill, Hyagriv Simhan, Carol M Hamilton, Tabitha P Hendershot, Michael J Phillips, Lisa A Kilpatrick, Deborah R Maiese, Erin M Ramos, Rosalind J Wright, Siobhan M Dolan
Only through concerted and well-executed research endeavors can we gain the requisite knowledge to advance pregnancy care and positively impact maternal and newborn health. Yet the heterogeneity inherent in individual studies limits our ability to compare and synthesize study results, thus impeding the capacity to draw meaningful conclusions that can be trusted to inform clinical care. The PhenX Toolkit (http://www.phenxtoolkit.org), supported since 2007 by the National Institutes of Health, is a web-based catalog of standardized protocols for measuring phenotypes and exposures relevant for clinical research...
May 31, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28576981/stat1-represses-cytokine-producing-group-2-and-group-3-innate-lymphoid-cells-during-viral-infection
#20
Matthew T Stier, Kasia Goleniewska, Jacqueline Y Cephus, Dawn C Newcomb, Taylor P Sherrill, Kelli L Boyd, Melissa H Bloodworth, Martin L Moore, Kong Chen, Jay K Kolls, R Stokes Peebles
The appropriate orchestration of different arms of the immune response is critical during viral infection to promote efficient viral clearance while limiting immunopathology. However, the signals and mechanisms that guide this coordination are not fully understood. IFNs are produced at high levels during viral infection and have convergent signaling through STAT1. We hypothesized that STAT1 signaling during viral infection regulates the balance of innate lymphoid cells (ILC), a diverse class of lymphocytes that are poised to respond to environmental insults including viral infections with the potential for both antiviral or immunopathologic functions...
June 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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