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https://www.readbyqxmd.com/read/29775405/the-mouse-heart-attack-research-tool-mhart-1-0-database
#1
Kristine Y DeLeon-Pennell, Rugmani Padmanabhan Iyer, Yonggang Ma, Andriy Yabluchanskiy, Rogelio Zamilpa, Ying Ann Chiao, Presley Cannon, Courtney Cates, Elizabeth R Flynn, Ganesh V Halade, Lisandra E de Castro Bras, Merry L Lindsey
The generation of Big Data has enabled systems-level dissections into the mechanisms of cardiovascular pathology. Integration of genetic, proteomic, and pathophysiological variables across platforms and laboratories fosters discoveries through multidisciplinary investigations and minimizes unnecessary redundancy in research efforts. The Mouse Heart Attack Research Tool (mHART) consolidates a large dataset of over 10 years of experiments from a single laboratory for cardiovascular investigators to generate novel hypotheses and identify new predictive markers of progressive left ventricular remodeling following myocardial infarction (MI) in mice...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29774170/liquid-biopsy-of-vitreous-reveals-an-abundant-vesicle-population-consistent-with-the-size-and-morphology-of-exosomes
#2
Yuanjun Zhao, Sarah R Weber, Joshua Lease, Mariano Russo, Christopher A Siedlecki, Li-Chong Xu, Han Chen, Weiwei Wang, Michael Ford, Rafael Simó, Jeffrey M Sundstrom
Purpose: To investigate the molecular components of the vitreous in order to better understand retinal physiology and disease. Methods: Vitreous was acquired from patients undergoing vitrectomy for macular hole and/or epiretinal membrane, postmortem donors, and C57BL/6J mice. Unbiased proteomic analysis was performed via electrospray ionization tandem mass spectrometry (MS/MS). Gene ontology analysis was performed and results were confirmed with transmission electron microscopy, atomic force microscopy, and nanoparticle tracking analysis (NTA)...
May 2018: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/29772792/metabolic-regulation-of-hypoxia-inducible-transcription-factors-the-role-of-small-molecule-metabolites-and-iron
#3
REVIEW
Peter S J Bailey, James A Nathan
Hypoxia-inducible transcription factors (HIFs) facilitate cellular adaptations to low-oxygen environments. However, it is increasingly recognised that HIFs may be activated in response to metabolic stimuli, even when oxygen is present. Understanding the mechanisms for the crosstalk that exists between HIF signalling and metabolic pathways is therefore important. This review focuses on the metabolic regulation of HIFs by small molecule metabolites and iron, highlighting the latest studies that explore how tricarboxylic acid (TCA) cycle intermediates, 2-hydroxyglutarate (2-HG) and intracellular iron levels influence the HIF response through modulating the activity of prolyl hydroxylases (PHDs)...
May 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29772648/adhesion-in-physiological-benign-and-malignant-proliferative-states-of-the-endometrium-microenvironment-and-the-clinical-big-picture
#4
REVIEW
Emily J Rutherford, Arnold D K Hill, Ann M Hopkins
Although the developments in cellular and molecular biology over the last few decades have significantly advanced our understanding of the processes and players that regulate invasive disease, many areas of uncertainty remain. This review will discuss the contribution of dysregulated cell⁻cell and cell⁻matrix adhesion to the invasion in both benign and malignant contexts. Using the endometrium as an illustrative tissue that undergoes clinically significant invasion in both contexts, the adhesion considerations in the cells ("seed") and their microenvironment ("soil") will be discussed...
May 16, 2018: Cells
https://www.readbyqxmd.com/read/29772474/mitochondria-rich-cells-adjustments-and-ionic-balance-in-the-neotropical-fish-prochilodus-lineatus-exposed-to-titanium-dioxide-nanoparticles
#5
Talita L L Carmo, Vinícius C Azevedo, Priscila R Siqueira, Tiago D Galvão, Fabrício A Santos, Cláudia B R Martinez, Carlos R Appoloni, Marisa N Fernandes
Manufactured titanium dioxide nanoparticles (TiO2 -NP) have been intensely applied in numerous industrial products and may be a risk for aquatic systems as they are not completely removed from domestic and industrial wastes after water treatment. This study evaluated the osmo- and ionic balance, Na+ /K+ -ATPase, H+ -ATPase and carbonic anhydrase activities and the mitochondria-rich cells (MRC) in the gills and kidney of the Neotropical fish Prochilodus lineatus after 2 (acute) and 14 (subchronic) days of exposure to nominal 0, 1, 5, 10 and 50 mg L-1 TiO2 -NP...
May 9, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29772419/duality-of-estrogen-receptor-%C3%AE-action-in-cancer-progression
#6
REVIEW
T C Guillette, Thomas W Jackson, Scott M Belcher
The physiological actions of estrogens are primarily mediated by the nuclear hormone receptors estrogen receptor alpha (ERα) and beta (ERβ). Activities of these nuclear steroid hormone receptors in etiology and progression of many hormone-responsive cancers are well-established, yet the specific role of each receptor, and their various expressed isoforms, in estrogen-responsive cancers remains unclear. Recent advances in nuclear receptor profiling, characterization of expressed splice variants, and the availability of new experimental cancer models, has extended the understanding of the complex interplay between the differentially expressed nuclear estrogen receptors...
May 14, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29772073/julius-sachs-1868-the-father-of-plant-physiology
#7
Ulrich Kutschera, Karl J Niklas
The year 2018 marks the 150th anniversary of the first publication of Julius von Sachs' (1832-1897) Lehrbuch der Botanik (Textbook of Botany), which provided a comprehensive summary of what was then known about the plant sciences. Three years earlier, in 1865, Sachs produced the equally impressive Handbuch der Experimental-Physiologie der Pflanzen (Handbook of Experimental Plant Physiology), which summarized the state of knowledge in all aspects of the discipline known today as plant physiology. Both of these books provided numerous insights based on Sachs' seminal experiments...
May 17, 2018: American Journal of Botany
https://www.readbyqxmd.com/read/29772011/induction-of-influenza-specific-local-cd8-t-cells-in-the-respiratory-tract-after-aerosol-delivery-of-vaccine-antigen-or-virus-in-the-babraham-inbred-pig
#8
Katie Tungatt, Garry Dolton, Sophie B Morgan, Meriem Attaf, Anna Fuller, Thomas Whalley, Johanneke D Hemmink, Emily Porter, Barbara Szomolay, Maria Montoya, John A Hammond, John J Miles, David K Cole, Alain Townsend, Mick Bailey, Pierre J Rizkallah, Bryan Charleston, Elma Tchilian, Andrew K Sewell
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29771999/growth-medium-dependent-antimicrobial-activity-of-early-stage-mep-pathway-inhibitors
#9
Sara Sanders, David Bartee, Mackenzie J Harrison, Paul D Phillips, Andrew T Koppisch, Caren L Freel Meyers
The in vivo microenvironment of bacterial pathogens is often characterized by nutrient limitation. Consequently, conventional rich in vitro culture conditions used widely to evaluate antibacterial agents are often poorly predictive of in vivo activity, especially for agents targeting metabolic pathways. In one such pathway, the methylerythritol phosphate (MEP) pathway, which is essential for production of isoprenoids in bacterial pathogens, relatively little is known about the influence of growth environment on antibacterial properties of inhibitors targeting enzymes in this pathway...
2018: PloS One
https://www.readbyqxmd.com/read/29770487/inhibitory-effect-of-melatonin-on-necroptosis-via-repressing-the-ripk3-pgam5-cypd-mptp-pathway-attenuates-cardiac-microvascular-ischemia-reperfusion-injury
#10
Hao Zhou, Dandan Li, Pingjun Zhu, Qiang Ma, Toan Sam, Jin Wang, Shunying Hu, Yundai Chen, Yingmei Zhang
The molecular features of necroptosis in cardiac ischemia reperfusion (IR) injury have been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of melatonin acting on necroptosis in cardiac IR injury. This study was designed to determine the role of necroptosis in microvascular IR injury, and investigate the contribution of melatonin in repressing necroptosis and preventing IR-mediated endothelial system collapse. Our results demonstrated that Ripk3 was primarily activated by IR injury and consequently aggravated endothelial necroptosis, microvessel barrier dysfunction, capillary hyperpermeability, the inflammation response, microcirculatory vasospasms and microvascular perfusion defects...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29770299/regenerative-medicine-therapy-for-single-ventricle-congenital-heart-disease
#11
REVIEW
Chetan Ambastha, Gregory J Bittle, David Morales, Nathaniel Parchment, Progyaparamita Saha, Rachana Mishra, Sudhish Sharma, Alexander Vasilenko, Muthukumar Gunasekaran, Manal T Al-Suqi, Deqiang Li, Peixin Yang, Sunjay Kaushal
One of the most complex forms of congenital heart disease (CHD) involving single ventricle physiology is hypoplastic left heart syndrome (HLHS), characterized by underdevelopment of the left ventricle (LV), mitral and aortic valves, and narrowing of the ascending aorta. The underdeveloped LV is incapable of providing long-term systemic flow, and if left untreated, the condition is fatal. Current treatment for this condition consists of three consecutive staged palliative operations: the first is conducted within the first few weeks of birth, the second between 4 to 6 months, and the third and final surgery within the first 4 years...
April 2018: Translational Pediatrics
https://www.readbyqxmd.com/read/29770125/fgf23-actions-on-target-tissues-with-and-without-klotho
#12
REVIEW
Beatrice Richter, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone whose physiologic actions on target tissues are mediated by FGF receptors (FGFR) and klotho, which functions as a co-receptor that increases the binding affinity of FGF23 for FGFRs. By stimulating FGFR/klotho complexes in the kidney and parathyroid gland, FGF23 reduces renal phosphate uptake and secretion of parathyroid hormone, respectively, thereby acting as a key regulator of phosphate metabolism. Recently, it has been shown that FGF23 can also target cell types that lack klotho...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29769519/optical-functionalization-of-human-class-a-orphan-g-protein-coupled-receptors
#13
Maurizio Morri, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J Gerrard, Priscila P Hirschfeld, Jan Schwarz, Harald Janovjak
G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+ -, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29768917/how-native-and-non-native-cations-bind-and-modulate-the-properties-of-gtp-atp
#14
Todor Dudev, Cedric Grauffel, Shang-Te Danny Hsu, Carmay Lim
Adenosine triphosphate (ATP) and guanosine triphosphate (GTP) exist in physiological solution mostly bound to cations. Interestingly, their cellular Mg2+ -bound forms have been shown to bind Li+ , a first-line drug for bipolar disorder. However, solution structures of NTP/NDP (N = A or G) bound to Li+ and/or Mg2+ have not been solved, thus precluding knowledge of how the native Mg2+ -bound cofactor conformation changes upon binding non-native Li+ and/or switching its environment from aqueous solution to proteins...
May 16, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29768197/induction-of-nitric-oxide-metabolism-in-enterocytes-alleviates-colitis-and-inflammation-associated-colon-cancer
#15
Noa Stettner, Chava Rosen, Biana Bernshtein, Shiri Gur-Cohen, Julia Frug, Alon Silberman, Alona Sarver, Narin N Carmel-Neiderman, Raya Eilam, Inbal Biton, Meirav Pevsner-Fischer, Niv Zmora, Alexander Brandis, Keren Bahar Halpern, Ram Mazkereth, Diego di Bernardo, Nicola Brunetti-Pierri, Muralidhar H Premkumar, Gillian Dank, Sandesh C S Nagamani, Steffen Jung, Alon Harmelin, Ayelet Erez
Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768134/mtor-signalling-jack-of-all-trades
#16
Yassine El Hiani, Emmanuel E Egom, Xian-Ping Dong
The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that senses and integrates environmental information into cellular regulation and homeostasis. Accumulating evidence has suggested a master role of mTOR signaling in many fundamental aspects of cell biology and organismal development. mTOR deregulation is implicated in a broad range of pathological conditions, including diabetes, cancer, neurodegenerative diseases, myopathies, inflammatory, infectious and autoimmune conditions...
May 16, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29767973/discovery-of-orally-bioavailable-quinoline-based-aldehyde-dehydrogenase-1a1-aldh1a1-inhibitors-with-potent-cellular-activity
#17
Shyh-Ming Yang, Natalia J Martinez, Adam Yasgar, Carina Danchik, Catrine Johansson, Yuhong Wang, Bolormaa Baljinnyam, Amy Q Wang, Xin Xu, Pranav Shah, Dorian Cheff, Xinran S Wang, Jacob Roth, Madhu Lal-Nag, James Edward Dunford, Udo C T Oppermann, Vasilis Vasiliou, Anton Simeonov, Ajit Jadhav, David J Maloney
Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiological and toxicological functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g. ALDH1A1) are important biomarkers in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small molecule ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767378/dying-to-communicate-apoptotic-functions-of-eph-ephrin-proteins
#18
REVIEW
Mustapha Kandouz
The Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors constitute the largest family of receptor tyrosine kinases and interact with a group of ligands called Ephrins. An essential feature of the Eph receptors and Ephrin ligands is that both are membrane-bound and, upon cell-cell interaction, initiate a bidirectional signaling involving both the receptor (forward signaling) and the ligand (reverse signaling). They regulate a large set of pleiotropic functions in virtually every tissue and physiological system...
May 16, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29766782/role-of-oxidative-stress-in-diabetic-retinopathy-and-the-beneficial-effects-of-flavonoids
#19
Mohammad Shamsul Ola, Dalia Al-Dosari, Abdullah S Alhomida
Diabetic retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious changes through dysregulation of cellular physiology that damages both neuronal and vascular cells. Here in this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contributes to retinal pathology in diabetes...
May 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29765941/nano-and-micro-patterned-s-h-and-x-pdms-for-cell-based-applications-comparison-of-wettability-roughness-and-cell-derived-parameters
#20
Marina Scharin-Mehlmann, Aaron Häring, Mathias Rommel, Tobias Dirnecker, Oliver Friedrich, Lothar Frey, Daniel F Gilbert
Polydimethylsiloxane (PDMS) is a promising biomaterial for generating artificial extracellular matrix (ECM) like patterned topographies, yet its hydrophobic nature limits its applicability to cell-based approaches. Although plasma treatment can enhance the wettability of PDMS, the surface is known to recover its hydrophobicity within a few hours after exposure to air. To investigate the capability of a novel PDMS-type (X-PDMS) for in vitro based assessment of physiological cell properties, we designed and fabricated plane as well as nano- and micrometer-scaled pillar-patterned growth substrates using the elastomer types S-, H- and X-PDMS, which were fabricated from commercially available components...
2018: Frontiers in Bioengineering and Biotechnology
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