145 results match your criteria cascade reminiscent

Ascorbate uptake enables tubular mitophagy to prevent septic AKI by PINK1-PARK2 axis.

Biochem Biophys Res Commun 2021 May 31;554:158-165. Epub 2021 Mar 31.

Department of Intensive Care Unit, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, PR China. Electronic address:

Ascorbate (Vitamin C) has been proposed as a promising therapeutic agent against sepsis in clinical trials, but there is little experimental evidence on its anti-septic efficacy. We report that Toll-like receptor 4 (TLR4) activation by LPS stimuli augments ascorbate uptake in murine and human tubular cells through upregulation of two ascorbate transporters SVCT-1 and -2 mediated by Fn14/SCF cascade. Ascorbate restriction, or knockout of SVCT-1 and -2, the circumstance reminiscent to blockade of ascorbate uptake, endows tubular cells more vulnerable to the LPS-inducible apoptosis, whereas exogenous administration of ascorbate overrides the ruin execution, for which the PINK1-PARK2, rather than BNIP3-NIX axis is required. Read More

View Article and Full-Text PDF

Microbiota-root-shoot-environment axis and stress tolerance in plants.

Curr Opin Plant Biol 2021 Mar 10;62:102028. Epub 2021 Mar 10.

Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany; Cluster of Excellence on Plant Sciences (CEPLAS), Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany. Electronic address:

Reminiscent to the microbiota-gut-brain axis described in animals, recent advances indicate that plants can take advantage of belowground microbial commensals to orchestrate aboveground stress responses. Integration of plant responses to microbial cues belowground and environmental cues aboveground emerges as a mechanism that promotes stress tolerance in plants. Using recent examples obtained from reductionist and community-level approaches, we discuss the extent to which perception of aboveground biotic and abiotic stresses can cascade along the shoot-root axis to sculpt root microbiota assembly and modulate the growth of root commensals that bolster aboveground stress tolerance. Read More

View Article and Full-Text PDF

Phase mechanics of colloidal gels: osmotic pressure drives non-equilibrium phase separation.

Soft Matter 2021 Apr 8;17(14):3784-3797. Epub 2021 Feb 8.

Department of Chemical Engineering, Stanford University, Stanford, CA, USA.

Although dense colloidal gels with interparticle bonds of order several kT are typically described as resulting from an arrest of phase separation, they continue to coarsen with age, owing to the dynamics of their temporary bonds. Here, k is Boltzmann's constant and T is the absolute temperature. Computational studies of gel aging reveal particle-scale dynamics reminiscent of condensation that suggests very slow but ongoing phase separation. Read More

View Article and Full-Text PDF

K63-linked ubiquitylation induces global sequestration of mitochondria.

Sci Rep 2020 12 18;10(1):22334. Epub 2020 Dec 18.

Department of Cell and Molecular Biology, Biomedicum, Karolinska Institutet, Solnavägen 9, 17177, Stockholm, Sweden.

Even though K63-linked polyubiquitin chains do not target proteins for proteasomal degradation, they play nevertheless a complementary protective role in maintaining protein homeostasis by directing malfunctioning proteins and organelles to inclusion bodies or autophagosomes. A paradigm for this process is the sequestration and autophagic degradation of dysfunctional mitochondria. Although studies have shown that K63-ubiquitylation of mitochondrial proteins by the ubiquitin ligase Parkin is important in this process, it is presently not clear if this modification also suffices to initiate this cascade of events. Read More

View Article and Full-Text PDF
December 2020

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response.

Front Immunol 2020 29;11:549319. Epub 2020 Oct 29.

Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.

Related interleukin-2, -15, and -15-like (IL-2, -15, and -15L) are ancient cytokines, with all three genes surviving in extant fish and some mammals. The present study is the first to identify IL-15L functions, namely in rainbow trout. In isolated trout splenocytes, and , purified recombinant IL-15L+IL-15Rα molecules induced expression of and homologs, which are markers of type 2 immunity. Read More

View Article and Full-Text PDF
October 2020

Period multiplication cascade at the order-by-disorder transition in uniaxial random field XY magnets.

Nat Commun 2020 Sep 16;11(1):4665. Epub 2020 Sep 16.

Department of Physics and Astronomy, Purdue University, West Lafayette, IN, 47907, USA.

Uniaxial random field disorder induces a spontaneous transverse magnetization in the XY model. Adding a rotating driving field, we find a critical point attached to the number of driving cycles needed to complete a limit cycle, the first discovery of this phenomenon in a magnetic system. Near the critical drive, time crystal behavior emerges, in which the period of the limit cycles becomes an integer n > 1 multiple of the driving period. Read More

View Article and Full-Text PDF
September 2020

Gut bacteria-derived peptidoglycan induces a metabolic syndrome-like phenotype via NF-κB-dependent insulin/PI3K signaling reduction in Drosophila renal system.

Sci Rep 2020 08 24;10(1):14097. Epub 2020 Aug 24.

Aix-Marseille Université, CNRS, IBDM, Marseille, France.

Although microbiome-host interactions are usual at steady state, gut microbiota dysbiosis can unbalance the physiological and behavioral parameters of the host, mostly via yet not understood mechanisms. Using the Drosophila model, we investigated the consequences of a gut chronic dysbiosis on the host physiology. Our results show that adult flies chronically infected with the non-pathogenic Erwinia carotorova caotovora bacteria displayed organ degeneration resembling wasting-like phenotypes reminiscent of Metabolic Syndrome associated pathologies. Read More

View Article and Full-Text PDF

Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder within the RASopathy Clinical Spectrum.

Am J Hum Genet 2020 09 27;107(3):499-513. Epub 2020 Jul 27.

Institute of Human Genetics, University Hospital Magdeburg, 39120 Magdeburg, Germany.

Signal transduction through the RAF-MEK-ERK pathway, the first described mitogen-associated protein kinase (MAPK) cascade, mediates multiple cellular processes and participates in early and late developmental programs. Aberrant signaling through this cascade contributes to oncogenesis and underlies the RASopathies, a family of cancer-prone disorders. Here, we report that de novo missense variants in MAPK1, encoding the mitogen-activated protein kinase 1 (i. Read More

View Article and Full-Text PDF
September 2020

Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19.

Pharmacotherapy 2020 08 27;40(8):843-856. Epub 2020 Jul 27.

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

A hyperinflammatory response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with coronavirus disease 2019 (COVID-19). Agents that inhibit components of the pro-inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the proinflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus-associated kinase (JAK)-inhibitor that interrupts the signaling of multiple cytokines implicated in COVID-19 immunopathology. Read More

View Article and Full-Text PDF

Intercellular Transmission of a Synthetic Bacterial Cytotoxic Prion-Like Protein in Mammalian Cells.

mBio 2020 04 14;11(2). Epub 2020 Apr 14.

Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain

RepA is a bacterial protein that builds intracellular amyloid oligomers acting as inhibitory complexes of plasmid DNA replication. When carrying a mutation enhancing its amyloidogenesis (A31V), the N-terminal domain (WH1) generates cytosolic amyloid particles that are inheritable within a bacterial lineage. Such amyloids trigger in bacteria a lethal cascade reminiscent of mitochondrial impairment in human cells affected by neurodegeneration. Read More

View Article and Full-Text PDF

Chemical signal cascading in a supramolecular network.

Chem Commun (Camb) 2020 Apr 3;56(26):3737-3740. Epub 2020 Mar 3.

CIQSO - Centre for Research in Sustainable Chemistry and Department of Chemistry, University of Huelva, Campus de El Carmen s/n, E-21071 Huelva, Spain.

A chemically-triggered signalling cascade between cucurbituril host-guest complexes by means of multi-step competitive displacement is demonstrated. The inter-complex communication of chemical information yields the release of bio-relevant cargo, reminiscent of cellular signalling pathways. Read More

View Article and Full-Text PDF

Channelization cascade in landscape evolution.

Proc Natl Acad Sci U S A 2020 01 8;117(3):1375-1382. Epub 2020 Jan 8.

Department of Civil and Environmental Engineering, Princeton University, Princeton, NJ 08544;

The hierarchy of channel networks in landscapes displays features that are characteristic of nonequilibrium complex systems. Here we show that a sequence of increasingly complex ridge and valley networks is produced by a system of partial differential equations coupling landscape evolution dynamics with a specific catchment area equation. By means of a linear stability analysis we identify the critical conditions triggering channel formation and the emergence of characteristic valley spacing. Read More

View Article and Full-Text PDF
January 2020

Maternal Type-I interferon signaling adversely affects the microglia and the behavior of the offspring accompanied by increased sensitivity to stress.

Mol Psychiatry 2020 05 26;25(5):1050-1067. Epub 2019 Nov 26.

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Viral infection during pregnancy is often associated with neuropsychiatric conditions. In mice, exposure of pregnant dams to the viral mimetic poly(I:C), serves as a model that simulates such pathology in the offspring, through a process known as Maternal Immune Activation (MIA). To investigate the mechanism of such effect, we hypothesized that maternal upregulation of Type-I interferon (IFN-I), as part of the dam's antiviral response, might contribute to the damage imposed on the offspring. Read More

View Article and Full-Text PDF

Retrograde Regulation by the Viral Protein Kinase Epigenetically Sustains the Epstein-Barr Virus Latency-to-Lytic Switch To Augment Virus Production.

J Virol 2019 09 13;93(17). Epub 2019 Aug 13.

Division of Infectious Diseases, Department of Pediatrics, University of Florida, Gainesville, Florida, USA

Herpesviruses are ubiquitous, and infection by some, like Epstein-Barr virus (EBV), is nearly universal. To persist, EBV must periodically switch from a latent to a replicative/lytic phase. This productive phase is responsible for most herpesvirus-associated diseases. Read More

View Article and Full-Text PDF
September 2019

Circular IRE-type RNAs of the NR5A1 gene are formed in adrenocortical cells.

Biochem Biophys Res Commun 2019 04 8;512(1):1-6. Epub 2019 Mar 8.

Department of Endocrinology and Diabetes Mellitus, Faculty of Medicine, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-180, Japan; Department of Bioregulatory Science of Life-related Diseases, Faculty of Medicine, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-180, Japan. Electronic address:

The recently discovered circular RNAs (circRNAs) are mostly formed by back-splicing where the downstream 5' splice site splices to the upstream 3' splice site by conventional pre-mRNA splicing. These circRNAs regulate gene expression by acting as sponges for micro-RNAs or RNA-binding proteins. Here we show that the NR5A1 (previously called Ad4BP or SF-1) gene which is exclusively expressed in the adrenal cortex and steroidogenic tissue can form atypical circRNAs by unconventional splicing. Read More

View Article and Full-Text PDF

Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes.

PLoS One 2018 17;13(12):e0209150. Epub 2018 Dec 17.

Service d'Etude des Prions et Infections Atypiques (SEPIA), Institut François Jacob, CEA, Université Paris-Saclay, Fontenay-aux-Roses, France.

Human mini-brains (MB) are cerebral organoids that recapitulate in part the complexity of the human brain in a unique three-dimensional in vitro model, yielding discrete brain regions reminiscent of the cerebral cortex. Specific proteins linked to neurodegenerative disorders are physiologically expressed in MBs, such as APP-derived amyloids (Aβ), whose physiological and pathological roles and interactions with other proteins are not well established in humans. Here, we demonstrate that neuroectodermal organoids can be used to study the Aβ accumulation implicated in Alzheimer's disease (AD). Read More

View Article and Full-Text PDF

Insights into antitrypanosomal drug mode-of-action from cytology-based profiling.

PLoS Negl Trop Dis 2018 11 26;12(11):e0006980. Epub 2018 Nov 26.

Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom.

Chemotherapy continues to have a major impact on reducing the burden of disease caused by trypanosomatids. Unfortunately though, the mode-of-action (MoA) of antitrypanosomal drugs typically remains unclear or only partially characterised. This is the case for four of five current drugs used to treat Human African Trypanosomiasis (HAT); eflornithine is a specific inhibitor of ornithine decarboxylase. Read More

View Article and Full-Text PDF
November 2018

Glucose metabolism induced by Bmp signaling is essential for murine skeletal development.

Nat Commun 2018 11 16;9(1):4831. Epub 2018 Nov 16.

Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Much of the mammalian skeleton originates from a cartilage template eventually replaced by bone via endochondral ossification. Despite much knowledge about growth factors and nuclear proteins in skeletal development, little is understood about the role of metabolic regulation. Here we report that genetic deletion of the glucose transporter Glut1 (Slc2a1), either before or after the onset of chondrogenesis in the limb, severely impairs chondrocyte proliferation and hypertrophy, resulting in dramatic shortening of the limbs. Read More

View Article and Full-Text PDF
November 2018

Evolvability of Amyloidogenic Proteins in Human Brain.

J Alzheimers Dis 2018 ;62(1):73-83

Division of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.

Currently, the physiological roles of amyloidogenic proteins (APs) in human brain, such as amyloid-β and α-synuclein, are elusive. Given that many APs arose by gene duplication and have been resistant against the pressures of natural selection, APs may be associated with some functions that are advantageous for survival of offspring. Nonetheless, evolvability is the sole physiological quality of APs that has been characterized in microorganisms such as yeast. Read More

View Article and Full-Text PDF

Second messenger-mediated tactile response by a bacterial rotary motor.

Science 2017 10;358(6362):531-534

Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Switzerland.

When bacteria encounter surfaces, they respond with surface colonization and virulence induction. The mechanisms of bacterial mechanosensation and downstream signaling remain poorly understood. Here, we describe a tactile sensing cascade in in which the flagellar motor acts as sensor. Read More

View Article and Full-Text PDF
October 2017

Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon.

Nat Commun 2017 10 24;8(1):1120. Epub 2017 Oct 24.

Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YG, UK.

The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Read More

View Article and Full-Text PDF
October 2017

Fibroblast Growth Factor 2 as an Antifibrotic: Antagonism of Myofibroblast Differentiation and Suppression of Pro-Fibrotic Gene Expression.

Cytokine Growth Factor Rev 2017 Dec 23;38:49-58. Epub 2017 Sep 23.

Worcester Polytechnic Institute, Department of Biology and Biotechnology,100 Institute Road, Worcester, MA, 01609, United States. Electronic address:

Fibrosis is a pathological condition that is characterized by the replacement of dead or damaged tissue with a nonfunctional, mechanically aberrant scar, and fibrotic pathologies account for nearly half of all deaths worldwide. The causes of fibrosis differ somewhat from tissue to tissue and pathology to pathology, but in general some of the cellular and molecular mechanisms remain constant regardless of the specific pathology in question. One of the common mechanisms underlying fibroses is the paradigm of the activated fibroblast, termed the "myofibroblast," a differentiated mesenchymal cell with demonstrated contractile activity and a high rate of collagen deposition. Read More

View Article and Full-Text PDF
December 2017

Spectral imbalance in the inertial range dynamics of decaying rotating turbulence.

Phys Rev E 2017 Feb 24;95(2-1):023114. Epub 2017 Feb 24.

Department of Applied Mathematics, University of Leeds, Leeds LS2 9JT, United Kingdom.

Direct numerical simulations of homogeneous decaying turbulence with background rotation show the existence of a systematic and significant imbalance between the non-linear energy cascade to small scales and its dissipation. By starting the decay from a statistically stationary and weakly rotating turbulent state, where the dissipation and the energy flux are approximately equal, the data show a growing imbalance between the two until a maximum is reached when the dissipation is about twice the energy flux. This dichotomy of behaviors during decay is reminiscent of the nonequilibrium and the equilibrium regions previously reported for nonrotating turbulence [Valente and Vassilicos, Phys. Read More

View Article and Full-Text PDF
February 2017

Mitochondria, Cybrids, Aging, and Alzheimer's Disease.

Prog Mol Biol Transl Sci 2017 1;146:259-302. Epub 2017 Feb 1.

University of Kansas Alzheimer's Disease Center, University of Kansas School of Medicine, Landon Center on Aging, Kansas City, KS, United States.

Mitochondrial and bioenergetic function change with advancing age and may drive aging phenotypes. Mitochondrial and bioenergetic changes are also documented in various age-related neurodegenerative diseases, including Alzheimer's disease (AD). In some instances AD mitochondrial and bioenergetic changes are reminiscent of those observed with advancing age but are greater in magnitude. Read More

View Article and Full-Text PDF
November 2017

Selective deletion of Pten in theca-interstitial cells leads to androgen excess and ovarian dysfunction in mice.

Mol Cell Endocrinol 2017 03 28;444:26-37. Epub 2017 Jan 28.

Department of OB/GYN & Women's Health, University of Louisville School of Medicine, Louisville, KY 40202, USA. Electronic address:

Theca cell-selective Pten mutation (tPtenMT) in mice resulted in increases in PDK1 and Akt phosphorylation, indicating an over-activation of PI3K signaling in the ovaries. These mice displayed elevated androgen levels, ovary enlargement, antral follicle accumulation, early fertility loss and increased expression of Lhcgr and genes that are crucial to androgenesis. These abnormalities were partially reversed by treatments of PI3K or Akt inhibitor. Read More

View Article and Full-Text PDF

Evolutionary aspects of the development of teeth and baleen in the bowhead whale.

J Anat 2017 Apr 10;230(4):549-566. Epub 2017 Jan 10.

Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, USA.

In utero, baleen whales initiate the development of several dozens of teeth in upper and lower jaws. These tooth germs reach the bell stage and are sometimes mineralized, but toward the end of prenatal life they are resorbed and no trace remains after birth. Around the time that the germs disappear, the keratinous baleen plates start to form in the upper jaw, and these form the food-collecting mechanism. Read More

View Article and Full-Text PDF

Proteomic analysis of the Rett syndrome experimental model mecp2 mutant zebrafish.

J Proteomics 2017 02 3;154:128-133. Epub 2017 Jan 3.

Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.

Rett syndrome (RTT) is a severe genetic disorder resulting from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Recently, a zebrafish carrying a mecp2-null mutation has been developed with the resulting phenotypes exhibiting defective sensory and thigmotactic responses, and abnormal motor behavior reminiscent of the human disease. Here, we performed a proteomic analysis to examine protein expression changes in mecp2-null vs. Read More

View Article and Full-Text PDF
February 2017

The onset of chaos in orbital pilot-wave dynamics.

Chaos 2016 Oct;26(10):103107

Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

We present the results of a numerical investigation of the emergence of chaos in the orbital dynamics of droplets walking on a vertically vibrating fluid bath and acted upon by one of the three different external forces, specifically, Coriolis, Coulomb, or linear spring forces. As the vibrational forcing of the bath is increased progressively, circular orbits destabilize into wobbling orbits and eventually chaotic trajectories. We demonstrate that the route to chaos depends on the form of the external force. Read More

View Article and Full-Text PDF
October 2016

Artificial Metalloenzymes Based on the Biotin-Streptavidin Technology: Challenges and Opportunities.

Acc Chem Res 2016 09 16;49(9):1711-21. Epub 2016 Aug 16.

Department of Chemistry, University of Basel , Spitalstrasse 51, CH-4056 Basel, Switzerland.

The biotin-streptavidin technology offers an attractive means to engineer artificial metalloenzymes (ArMs). Initiated over 50 years ago by Bayer and Wilchek, the biotin-(strept)avidin techonology relies on the exquisite supramolecular affinity of either avidin or streptavidin for biotin. This versatile tool, commonly referred to as "molecular velcro", allows nearly irreversible anchoring of biotinylated probes within a (strept)avidin host protein. Read More

View Article and Full-Text PDF
September 2016