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What are canonical pathways

Audrey Boulamery, Sophie Desplat-Jégo
Observed in many central nervous system diseases, neuroinflammation (NI) proceeds from peripheral immune cell infiltration into the parenchyma, from cytokine secretion and from oxidative stress. Astrocytes and microglia also get activated and proliferate. NI manifestations and consequences depend on its context and on the acute or chronic aspect of the disease. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 pathway has been involved in chronic human inflammatory pathologies such as neurodegenerative, autoimmune, or malignant diseases...
2017: Frontiers in Immunology
Elena Khanova, Raymond Wu, Wen Wang, Rui Yan, Yibu Chen, Samuel W French, Cristina Llorente, Stephanie Q Pan, Qihong Yang, Yuchang Li, Raul Lazaro, Charles Ansong, Richard D Smith, Ramon Bataller, Timothy Morgan, Bernd Schnabl, Hidekazu Tsukamoto
Alcoholic hepatitis (AH) continues to be a disease with high mortality and no efficacious medical treatment. Although severe AH is presented as acute on chronic liver failure, what underlies this transition from chronic alcoholic steatohepatitis (ASH) to AH, is largely unknown. To address this question, unbiased RNA-seq and proteomic analyses were performed on livers of the recently developed AH mouse model which exhibits the shift to AH from chronic ASH upon weekly alcohol binge, and these results are compared with gene expression profiling data from AH patients...
November 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Sarah Catherine Mills, Ramya Enganti, Albrecht G von Arnim
In most organisms gene expression over the course of the day is under the control of the circadian clock. The canonical clock operates as a gene expression circuit that is controlled at the level of transcription, and transcriptional control is also a major clock output. However, rhythmic transcription cannot explain all the observed rhythms in protein accumulation. Although it is clear that rhythmic gene expression also involves RNA processing and protein turnover, until two years ago little was known in any eukaryote about diel dynamics of mRNA translation into protein...
November 3, 2017: RNA Biology
Oksana O Piven, Cecilia L Winata
The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors...
January 1, 2017: Experimental Biology and Medicine
Wenjia Gu, Eric W Schmidt
Natural products are significant therapeutic agents and valuable drug leads. This is likely owing to their three-dimensional structural complexity, which enables them to form complex interactions with biological targets. Enzymes from natural product biosynthetic pathways show great potential to generate natural product-like compounds and libraries. Many challenges still remain in biosynthesis, such as how to rationally synthesize small molecules with novel structures and how to generate maximum chemical diversity...
October 17, 2017: Accounts of Chemical Research
Sun Wook Kim, Jonathan Ehrman, Mok-Ryeon Ahn, Jumpei Kondo, Andrea A Mancheno Lopez, Yun Sik Oh, Xander H Kim, Scott W Crawley, James R Goldenring, Matthew J Tyska, Erin C Rericha, Ken S Lau
Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen. We report that exposure to physiological levels of fluid shear stress leads to the formation of large vacuoles, containing extracellular contents within polarizing intestinal epithelial cell monolayers. These observations lead to two questions: how can cells lacking primary cilia transduce shear stress, and what molecular pathways support the formation of vacuoles that can exceed 80% of the cell volume? We find that shear forces are sensed by actin-rich microvilli that eventually generate the apical brush border, providing evidence that these structures possess mechanosensing ability...
November 1, 2017: Molecular Biology of the Cell
Rachel L Poole, Michael G Tordoff
Many people avidly consume foods and drinks containing caffeine, despite its bitter taste. Here, we review what is known about caffeine as a bitter taste stimulus. Topics include caffeine's action on the canonical bitter taste receptor pathway and caffeine's action on noncanonical receptor-dependent and -independent pathways in taste cells. Two conclusions are that (1) caffeine is a poor prototypical bitter taste stimulus because it acts on bitter taste receptor-independent pathways, and (2) caffeinated products most likely stimulate "taste" receptors in nongustatory cells...
June 1, 2017: Journal of Caffeine Research
José Carlos Del Río, Jorge Rencoret, Ana Gutiérrez, Hoon Kim, John Ralph
Lignin, the plant cell wall polymer that binds fibers together but makes processing difficult, is traditionally formed from three monomers, the so-called monolignols (p-coumaryl, coniferyl, and sinapyl alcohols). Recently, we discovered, in grass lignins, a phenolic monomer that falls outside the canonical lignin biosynthetic pathway, the flavone tricin. As we show here, palm fruit (macaúba [Acrocomia aculeata], carnauba [Copernicia prunifera], and coconut [Cocos nucifera]) endocarps contain lignin polymers derived in part from a previously unconsidered class of lignin monomers, the hydroxystilbenes, including the valuable compounds piceatannol and resveratrol...
August 2017: Plant Physiology
Carlos M Ferrario, Adam E Mullick
A collective century of discoveries establishes the importance of the renin angiotensin aldosterone system in maintaining blood pressure, fluid volume and electrolyte homeostasis via autocrine, paracrine and endocrine signaling. While research continues to yield new functions of angiotensin II and angiotensin-(1-7), the gap between basic research and clinical application of these new findings is widening. As data accumulates on the efficacy of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers as drugs of fundamental importance in the treatment of cardiovascular and renal disorders, it is becoming apparent that the achieved clinical benefits is suboptimal and surprisingly no different than what can be achieved with other therapeutic interventions...
November 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Stewart Shipp
Predictive coding theories of sensory brain function interpret the hierarchical construction of the cerebral cortex as a Bayesian, generative model capable of predicting the sensory data consistent with any given percept. Predictions are fed backward in the hierarchy and reciprocated by prediction error in the forward direction, acting to modify the representation of the outside world at increasing levels of abstraction, and so to optimize the nature of perception over a series of iterations. This accounts for many 'illusory' instances of perception where what is seen (heard, etc...
2016: Frontiers in Psychology
Nestor Gomez, Tatiana Erazo, Jose M Lizcano
ERK5, the last MAP kinase family member discovered, is activated by the upstream kinase MEK5 in response to growth factors and stress stimulation. MEK5-ERK5 pathway has been associated to different cellular processes, playing a crucial role in cell proliferation in normal and cancer cells by mechanisms that are both dependent and independent of its kinase activity. Thus, nuclear ERK5 activates transcription factors by either direct phosphorylation or acting as co-activator thanks to a unique transcriptional activation TAD domain located at its C-terminal tail...
2016: Frontiers in Cell and Developmental Biology
Fanny Ng, Bor Luen Tang
All eukaryotic cells secrete a range of proteins in a constitutive or regulated manner through the conventional or canonical exocytic/secretory pathway characterized by vesicular traffic from the endoplasmic reticulum, through the Golgi apparatus, and towards the plasma membrane. However, a number of proteins are secreted in an unconventional manner, which are insensitive to inhibitors of conventional exocytosis and use a route that bypasses the Golgi apparatus. These include cytosolic proteins such as fibroblast growth factor 2 (FGF2) and interleukin-1β (IL-1β), and membrane proteins that are known to also traverse to the plasma membrane by a conventional process of exocytosis, such as α integrin and the cystic fibrosis transmembrane conductor (CFTR)...
2016: Methods in Molecular Biology
Nils Knie, Felix Grewe, Simon Fischer, Volker Knoop
BACKGROUND: RNA editing by C-to-U conversions is nearly omnipresent in land plant chloroplasts and mitochondria, where it mainly serves to reconstitute conserved codon identities in the organelle mRNAs. Reverse U-to-C RNA editing in contrast appears to be restricted to hornworts, some lycophytes, and ferns (monilophytes). A well-resolved monilophyte phylogeny has recently emerged and now allows to trace the side-by-side evolution of both types of pyrimidine exchange editing in the two endosymbiotic organelles...
June 21, 2016: BMC Evolutionary Biology
Valentin Roustan, Arpit Jain, Markus Teige, Ingo Ebersberger, Wolfram Weckwerth
AMPK and TOR protein kinases are the major control points of energy signaling in eukaryotic cells and organisms. They form the core of a complex regulatory network to co-ordinate metabolic activities in the cytosol with those in the mitochondria and plastids. Despite its relevance, it is still unclear when and how this regulatory pathway was formed during evolution, and to what extent its representations in the major eukaryotic lineages resemble each other. Here we have traced 153 essential proteins forming the human AMPK-TOR pathways across 412 species representing all three domains of life-prokaryotes (bacteria, archaea) and eukaryotes-and reconstructed their evolutionary history...
June 2016: Journal of Experimental Botany
Rodolfo Mattar Rosa, Juliana Almada Colucci, Rodrigo Yokota, Roseli Peres Moreira, Danielle Sanches Aragão, Amanda Aparecida Ribeiro, Danielle Yuri Arita, Ingrid Kazue Mizuno Watanabe, Zaira Palomino, Tatiana Sousa Cunha, Dulce Elena Casarini
Sepsis is an uncontrolled systemic inflammatory response against an infection and a major public health issue worldwide. This condition affects several organs, and, when caused by Gram-negative bacteria, kidneys are particularly damaged. Due to the importance of renin-angiotensin system (RAS) in regulating renal function, in the present study, we aimed to investigate the effects of endotoxemia over the renal RAS. Wistar rats were injected with Escherichia coli lipopolysaccharide (LPS) (4 mg/kg), mimicking the endotoxemia induced by Gram-negative bacteria...
September 1, 2016: American Journal of Physiology. Renal Physiology
Sibel Kucukyildirim, Hongan Long, Way Sung, Samuel F Miller, Thomas G Doak, Michael Lynch
Mycobacterium smegmatis is a bacterium that is naturally devoid of known postreplicative DNA mismatch repair (MMR) homologs, mutS and mutL, providing an opportunity to investigate how the mutation rate and spectrum has evolved in the absence of a highly conserved primary repair pathway. Mutation accumulation experiments of M. smegmatis yielded a base-substitution mutation rate of 5.27 × 10(-10) per site per generation, or 0.0036 per genome per generation, which is surprisingly similar to the mutation rate in MMR-functional unicellular organisms...
July 7, 2016: G3: Genes—Genomes—Genetics
Wei Huang, Qing Li, Mahmood Amiry-Moghaddam, Madoka Hokama, Sylvia H Sardi, Masashi Nagao, Matthew L Warman, Bjorn R Olsen
Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels...
2016: PloS One
Miguel A Gutiérrez-Monreal, Victor Treviño, Jorge E Moreno-Cuevas, Sean-Patrick Scott
Cancer cells have broken circadian clocks when compared to their normal tissue counterparts. Moreover, it has been shown in breast cancer that disruption of common circadian oscillations is associated with a more negative prognosis. Numerous studies, focused on canonical circadian genes in breast cancer cell lines, have suggested that there are no mRNA circadian-like oscillations. Nevertheless, cancer cell lines have not been extensively characterized and it is unknown to what extent the circadian oscillations are disrupted...
2016: Chronobiology International
Paul W Hamilton, Yu Sun, Jonathan J Henry
The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens...
April 2016: Experimental Eye Research
T Quintela, H Marcelino, M J Deery, R Feret, J Howard, K S Lilley, T Albuquerque, I Gonçalves, A C Duarte, C R A Santos
The choroid plexus (CP) epithelium is a unique structure in the brain that forms an interface between the peripheral blood and the cerebrospinal fluid (CSF), which is mostly produced by the CP itself. Because the CP transcriptome is regulated by the sex hormone background, the present study compared gene/protein expression profiles in the CP and CSF from male and female rats aiming to better understand sex-related differences in CP functions and brain physiology. We used data previously obtained by cDNA microarrays to compare the CP transcriptome between male and female rats, and complemented these data with the proteomic analysis of the CSF of castrated and sham-operated males and females...
January 2016: Journal of Neuroendocrinology
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