1,661 results match your criteria reminiscent signaling


Long-access to cocaine self-administration dysregulates the glutamate synapse in the nucleus accumbens core of serotonin transporter knockout rats.

Br J Pharmacol 2021 Apr 20. Epub 2021 Apr 20.

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy.

Background And Purpose: It is well established that the nucleus accumbens (NAc) and glutamate play a critical role in the motivation to take drugs of abuse. We have previously demonstrated that rats with ablation of the serotonin transporter (SERT rats) show increased cocaine intake reminiscent of compulsivity.

Experimental Approach: By comparing SERT to SERT rats, we set out to explore whether SERT deletion influences glutamate neurotransmission under control conditions as well as after short access (ShA: 1 hr. Read More

View Article and Full-Text PDF

Mobile SAR signal N-hydroxypipecolic acid induces NPR1-dependent transcriptional reprogramming and immune priming.

Plant Physiol 2021 Apr 19. Epub 2021 Apr 19.

Institute for Molecular Ecophysiology of Plants, Department of Biology, Heinrich Heine University, Universitätsstraße 1, D-40225 Düsseldorf, Germany.

N-Hydroxypipecolic acid (NHP) accumulates in the plant foliage in response to a localized microbial attack and induces systemic acquired resistance (SAR) in distant leaf tissue. Previous studies indicated that pathogen inoculation of Arabidopsis (Arabidopsis thaliana) systemically activates SAR-related transcriptional reprogramming and a primed immune status in strict dependence of FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1), which mediates the endogenous biosynthesis of NHP. Here, we show that elevations of NHP by exogenous treatment are sufficient to induce a SAR-reminiscent transcriptional response that mobilizes key components of immune surveillance and signal transduction. Read More

View Article and Full-Text PDF

Structural Model for Recruitment of RIT1 to the LZTR1 E3 Ligase: Evidences from an Integrated Computational Approach.

J Chem Inf Model 2021 Apr 1;61(4):1875-1888. Epub 2021 Apr 1.

BIOGEM Istituto di Ricerche Genetiche "G. Salvatore", via Camporeale, Ariano Irpino 83031, Italy.

Leucine-zipper transcription regulator 1 (LZTR1) is a highly mutated tumor suppressor gene, involved in the pathogenesis of several cancer types and developmental disorders. In proteasomal degradation, it acts as an adaptor protein responsible for the recognition and recruitment of substrates to be ubiquitinated in Cullin3-RING ligase E3 (CRL3) machinery. LZTR1 belongs to the BTB-Kelch family, a multi-domain protein where the Kelch propeller plays as the substrate recognition region and for which no experimental structure has been solved. Read More

View Article and Full-Text PDF

HOXBLINC long non-coding RNA activation promotes leukemogenesis in NPM1-mutant acute myeloid leukemia.

Nat Commun 2021 03 29;12(1):1956. Epub 2021 Mar 29.

Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.

Nucleophosmin (NPM1) is the most commonly mutated gene in acute myeloid leukemia (AML) resulting in aberrant cytoplasmic translocation of the encoded nucleolar protein (NPM1c). NPM1c maintains a unique leukemic gene expression program, characterized by activation of HOXA/B clusters and MEIS1 oncogene to facilitate leukemogenesis. However, the mechanisms by which NPM1c controls such gene expression patterns to promote leukemogenesis remain largely unknown. Read More

View Article and Full-Text PDF

Insertion mutation in Tnfrsf11a causes a Paget's disease-like phenotype in heterozygous mice and osteopetrosis in homozygous mice.

J Bone Miner Res 2021 Mar 16. Epub 2021 Mar 16.

Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Early onset familial Paget's disease of bone (EoPDB), familial expansile osteolysis and expansile skeletal hyperphosphatasia are related disorders caused by insertion mutations in exon 1 of the TNFRSF11A gene which encodes receptor activator of nuclear factor kappa B (RANK) protein. To understand the mechanisms underlying these disorders, we developed a mouse model carrying the 75dup27 mutation which causes EoPDB. Mice heterozygous for the mutation (Tnfrsf11a ) developed a PDB-like disorder with focal osteolytic lesions in the hind limbs with increasing age. Read More

View Article and Full-Text PDF

The co-mutational spectrum determines the therapeutic response in murine FGFR2 fusion - driven cholangiocarcinoma.

Hepatology 2021 Mar 11. Epub 2021 Mar 11.

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Background & Aims: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and a highly lethal malignancy. Chemotherapeutic options are limited, but a considerable subset of patients harbors genetic lesions for which targeted agents exist. Fibroblast growth factor receptor 2 (FGFR2) fusions belong to the most frequent and therapeutically relevant alterations in ICC, and the first FGFR inhibitor was recently approved for the treatment of patients with progressed, fusion-positive ICC. Read More

View Article and Full-Text PDF

Sex-dependent role for EPHB2 in brain development and autism-associated behavior.

Neuropsychopharmacology 2021 Mar 1. Epub 2021 Mar 1.

Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.

Autism spectrum disorder (ASD) is characterized by impairments in social communication and interaction and restricted, repetitive behaviors. It is frequently associated with comorbidities, such as attention-deficit hyperactivity disorder, altered sensory sensitivity, and intellectual disability. A de novo nonsense mutation in EPHB2 (Q857X) was discovered in a female patient with ASD [13], revealing EPHB2 as a candidate ASD risk gene. Read More

View Article and Full-Text PDF

A transceptor-channel complex couples nitrate sensing to calcium signaling in Arabidopsis.

Mol Plant 2021 May 16;14(5):774-786. Epub 2021 Feb 16.

College of Life Sciences, Capital Normal University, Beijing 100048, China. Electronic address:

Nitrate-induced Ca signaling is crucial for the primary nitrate response in plants. However, the molecular mechanism underlying the generation of the nitrate-specific calcium signature remains unknown. We report here that a cyclic nucleotide-gated channel (CNGC) protein, CNGC15, and the nitrate transceptor (NRT1. Read More

View Article and Full-Text PDF

Alteration of oxidative-stress and related marker levels in mouse colonic tissues and fecal microbiota structures with chronic ethanol administration: Implications for the pathogenesis of ethanol-related colorectal cancer.

PLoS One 2021 12;16(2):e0246580. Epub 2021 Feb 12.

Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Japan.

Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on the colonic levels of oxidative stress and advance glycation end product (AGE) levels, as well as fecal microbiota structures, were examined in a mouse model. Chronic oral administration of ethanol in mice (1. Read More

View Article and Full-Text PDF
February 2021

Expression Level of Mature miR172 in Wild Type and -Silenced Plants of Is Sucrose-Dependent.

Int J Mol Sci 2021 Feb 1;22(3). Epub 2021 Feb 1.

Department of Plant Physiology, Institute of Biology, Humboldt-Universität zu Berlin, Philippstr. 13, Building 12, 10115 Berlin, Germany.

In potato plants, the phloem-mobile miR172 is involved in the sugar-dependent transmission of flower and tuber inducing signal transduction pathways and a clear link between solute transport and the induction of flowering and tuberization was demonstrated. The sucrose transporter StSUT4 seems to play an important role in the photoperiod-dependent triggering of both developmental processes, flowering and tuberization, and the phenotype of -inhibited potato plants is reminiscent to miR172 overexpressing plants. The first aim of this study was the determination of the level of miR172 in sink and source leaves of -silenced as well as -overexpressing plants in comparison to ssp. Read More

View Article and Full-Text PDF
February 2021

Unlocking mammalian regeneration through hypoxia inducible factor one alpha signaling.

Biomaterials 2021 Feb 9;269:120646. Epub 2021 Jan 9.

Department of Bioengineering and Materials Science and Engineering, University of California, Berkeley, CA, USA; Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Electronic address:

Historically, the field of regenerative medicine has aimed to heal damaged tissue through the use of biomaterials scaffolds or delivery of foreign progenitor cells. Despite 30 years of research, however, translation and commercialization of these techniques has been limited. To enable mammalian regeneration, a more practical approach may instead be to develop therapies that evoke endogenous processes reminiscent of those seen in innate regenerators. Read More

View Article and Full-Text PDF
February 2021

Interactions with Commensal and Pathogenic Bacteria Induce HIV-1 Latency in Macrophages through Altered Transcription Factor Recruitment to the LTR.

J Virol 2021 Jan 20. Epub 2021 Jan 20.

Department of Microbiology, Boston University School of Medicine, Boston, MA 02118

Macrophages are infected by HIV-1 and contribute to both viral spread and pathogenesis. Recent human and animal studies suggest that HIV-1-infected macrophages serve as a reservoir that contributes to HIV-1 persistence during anti-retroviral therapy. The ability of macrophages to serve as persistent viral reservoirs is likely influenced by the local tissue microenvironment, including interactions with pathogenic and commensal microbes. Read More

View Article and Full-Text PDF
January 2021

Engineering of a bona fide light-operated calcium channel.

Nat Commun 2021 01 11;12(1):164. Epub 2021 Jan 11.

Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.

The current optogenetic toolkit lacks a robust single-component Ca-selective ion channel tailored for remote control of Ca signaling in mammals. Existing tools are either derived from engineered channelrhodopsin variants without strict Ca selectivity or based on the stromal interaction molecule 1 (STIM1) that might crosstalk with other targets. Here, we describe the design of a light-operated Ca channel (designated LOCa) by inserting a plant-derived photosensory module into the intracellular loop of an engineered ORAI1 channel. Read More

View Article and Full-Text PDF
January 2021

Noncanonical Auxin Signaling.

Cold Spring Harb Perspect Biol 2021 May 3;13(5). Epub 2021 May 3.

Crop Genetics Department, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, United Kingdom.

Auxin influences all aspects of plant growth and development and exerts its function at scales ranging from the subcellular to the whole-organism level. A canonical mechanism for auxin signaling has been elucidated, which is based on derepression of downstream genes via ubiquitin-mediated degradation of transcriptional repressors. While the combinatorial nature of this canonical pathway provides great potential for specificity in the auxin response, alternative noncanonical signaling pathways required to mediate certain processes have been identified. Read More

View Article and Full-Text PDF

Dimeric Transmembrane Orientations of APP/C99 Regulate γ-Secretase Processing Line Impacting Signaling and Oligomerization.

iScience 2020 Dec 2;23(12):101887. Epub 2020 Dec 2.

Ludwig Cancer Research, Brussels 1200, Belgium.

Amyloid precursor protein (APP) cleavage by the β-secretase produces the C99 transmembrane (TM) protein, which contains three dimerization-inducing Gly-x-x-x-Gly motifs. We demonstrate that dimeric C99 TM orientations regulate the precise cleavage lines by γ-secretase. Of all possible dimeric orientations imposed by a coiled-coil to the C99 TM domain, the dimer containing the Gly-x-x-x-Gly motif in the interface promoted the Aβ processing line and APP intracellular domain-dependent gene transcription, including the induction of BACE1 mRNA, enhancing amyloidogenic processing and signaling. Read More

View Article and Full-Text PDF
December 2020

Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype.

Nat Commun 2020 12 18;11(1):6434. Epub 2020 Dec 18.

Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.

Glioblastoma frequently exhibits therapy-associated subtype transitions to mesenchymal phenotypes with adverse prognosis. Here, we perform multi-omic profiling of 60 glioblastoma primary tumours and use orthogonal analysis of chromatin and RNA-derived gene regulatory networks to identify 38 subtype master regulators, whose cell population-specific activities we further map in published single-cell RNA sequencing data. These analyses identify the oligodendrocyte precursor marker and chromatin modifier SOX10 as a master regulator in RTK I-subtype tumours. Read More

View Article and Full-Text PDF
December 2020

Prolyl isomerization controls activation kinetics of a cyclic nucleotide-gated ion channel.

Nat Commun 2020 12 16;11(1):6401. Epub 2020 Dec 16.

Weill Cornell Medicine, Department of Anesthesiology, 1300 York Avenue, New York, NY, 10065, USA.

SthK, a cyclic nucleotide-modulated ion channel from Spirochaeta thermophila, activates slowly upon cAMP increase. This is reminiscent of the slow, cAMP-induced activation reported for the hyperpolarization-activated and cyclic nucleotide-gated channel HCN2 in the family of so-called pacemaker channels. Here, we investigate slow cAMP-induced activation in purified SthK channels using stopped-flow assays, mutagenesis, enzymatic catalysis and inhibition assays revealing that the cis/trans conformation of a conserved proline in the cyclic nucleotide-binding domain determines the activation kinetics of SthK. Read More

View Article and Full-Text PDF
December 2020

The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary-like interactions at clone margins.

Sci Adv 2020 Dec 9;6(50). Epub 2020 Dec 9.

Department of Molecular and Cell Biology, 515 Weill Hall, University of California, Berkeley, Berkeley, CA 94720, USA.

During development, tissue-specific patterns of gene expression are established by transcription factors and then stably maintained via epigenetic mechanisms. Cancer cells often express genes that are inappropriate for that tissue or developmental stage. Here, we show that high activity levels of Yki, the Hippo pathway coactivator that causes overgrowth in imaginal discs, can also disrupt cell fates by altering expression of selector genes like () and (). Read More

View Article and Full-Text PDF
December 2020

The Non-structural Protein NSs of SFTSV Causes Cytokine Storm Through the Hyper-activation of NF-κB.

Mol Cell Biol 2020 Dec 7. Epub 2020 Dec 7.

Laboratory of Virus Immunology, Institute for Frontier Life and Medical Science, Kyoto University, Japan

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging highly pathogenic phlebovirus. The syndrome is characterized by the substantial production of inflammatory cytokines and chemokines, described as cytokine storm, which correlates with multi-organ failure and high mortality. SFSTV nonstructural (NSs) protein was suggested to mediate the pathogenesis by inhibiting antiviral interferon signaling in the host. Read More

View Article and Full-Text PDF
December 2020

Loss of cooperates with oncogenic to induce pancreatic cystic neoplasms.

Life Sci Alliance 2021 02 2;4(2). Epub 2020 Dec 2.

Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS, USA

Notch signaling exerts both oncogenic and tumor-suppressive functions in the pancreas. In this study, deletion of in conjunction with oncogenic expression in the mouse pancreas induced rapid development of acinar-to-ductal metaplasia and early stage pancreatic intraepithelial neoplasm; however, culminating in cystic neoplasms rather than ductal adenocarcinoma. Most cystic lesions in these mice were reminiscent of serous cystic neoplasm, and the rest resembled intraductal papillary mucinous neoplasm. Read More

View Article and Full-Text PDF
February 2021

Loss of Fbxw7 Impairs Development of and Induces Heterogeneous Tumor Formation in the Mouse Mammary Gland.

Cancer Res 2020 12 24;80(24):5515-5530. Epub 2020 Nov 24.

Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka Japan.

Fbxw7 is an F-box protein that contributes to regulation of cell proliferation and cell fate determination as well as to tumor suppression in various tissues. In this study, we generated mice with mammary gland-specific ablation of Fbxw7 ( mice) and found that most neonates born to mutant dams die soon after birth as a result of defective maternal lactation. The mammary gland of mutant dams was markedly atrophic and manifested both excessive cell proliferation and apoptosis in association with the accumulation of Notch1 and p63. Read More

View Article and Full-Text PDF
December 2020

Ionizing radiation results in a mixture of cellular outcomes including mitotic catastrophe, senescence, methuosis, and iron-dependent cell death.

Cell Death Dis 2020 11 23;11(11):1003. Epub 2020 Nov 23.

Unit of Molecular Signaling and Cell Death, VIB Center for Inflammation Research, Ghent, Belgium.

Radiotherapy is commonly used as a cytotoxic treatment of a wide variety of tumors. Interestingly, few case reports underlined its potential to induce immune-mediated abscopal effects, resulting in regression of metastases, distant from the irradiated site. These observations are rare, and apparently depend on the dose used, suggesting that dose-related cellular responses may be involved in the distant immunogenic responses. Read More

View Article and Full-Text PDF
November 2020

Luminescence imaging of leaf damage induced by lipid peroxidation products and its modulation by β-cyclocitral.

Physiol Plant 2021 Feb 1;171(2):246-259. Epub 2020 Dec 1.

Institute of Biosciences and Biotechnologies, CEA/Cadarache, Aix Marseille University, CEA, CNRS, BIAM, UMR7265, Saint-Paul-lez-Durance, France.

Lipid peroxidation is a primary event associated with oxidative stress in plants. This phenomenon secondarily generates bioactive and/or toxic compounds such as reactive carbonyl species (RCS), phytoprostanes, and phytofurans, as confirmed here in Arabidopsis plants exposed to photo-oxidative stress conditions. We analyzed the effects of exogenous applications of secondary lipid oxidation products on Arabidopsis plants by luminescence techniques. Read More

View Article and Full-Text PDF
February 2021

IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics.

Blood 2020 Nov 19. Epub 2020 Nov 19.

Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.

B-cell receptor (BCR) signaling is crucial for chronic lymphocytic leukemia (CLL) biology. IGLV3-21-expressing B-cells may acquire a single point mutation (R110) that triggers autonomous BCR signaling conferring aggressive behavior. Epigenetic studies have defined three CLL subtypes based on methylation signatures reminiscent of naïve-like (n-CLL), intermediate (i-CLL) and memory-like B-cells (m-CLL) with different biological features. Read More

View Article and Full-Text PDF
November 2020

Psychosis-Like Behavior and Hyperdopaminergic Dysregulation in Human α-Synuclein BAC Transgenic Rats.

Mov Disord 2021 03 17;36(3):716-728. Epub 2020 Nov 17.

Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece.

Background: Parkinson's disease psychosis is a prevalent yet underreported and understudied nonmotor manifestation of Parkinson's disease and, arguably, the most debilitating. It is unknown if α-synuclein plays a role in psychosis, and if so, this endophenotype may be crucial for elucidating the neurodegenerative process.

Objectives: We sought to dissect the underlying neurobiology of novelty-induced hyperactivity, reminiscent of psychosis-like behavior, in human α-synuclein BAC rats. Read More

View Article and Full-Text PDF

TBK1-Mediated DRP1 Targeting Confers Nucleic Acid Sensing to Reprogram Mitochondrial Dynamics and Physiology.

Mol Cell 2020 12 9;80(5):810-827.e7. Epub 2020 Nov 9.

MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:

Mitochondrial morphology shifts rapidly to manage cellular metabolism, organelle integrity, and cell fate. It remains unknown whether innate nucleic acid sensing, the central and general mechanisms of monitoring both microbial invasion and cellular damage, can reprogram and govern mitochondrial dynamics and function. Here, we unexpectedly observed that upon activation of RIG-I-like receptor (RLR)-MAVS signaling, TBK1 directly phosphorylated DRP1/DNM1L, which disabled DRP1, preventing its high-order oligomerization and mitochondrial fragmentation function. Read More

View Article and Full-Text PDF
December 2020

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits.

Proc Natl Acad Sci U S A 2020 11 3;117(46):28655-28666. Epub 2020 Nov 3.

Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030;

The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. Read More

View Article and Full-Text PDF
November 2020

Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia.

Neuron 2020 12 26;108(5):876-886.e4. Epub 2020 Oct 26.

F.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology and Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:

Myelination facilitates rapid axonal conduction, enabling efficient communication across different parts of the nervous system. Here we examined mechanisms controlling myelination after injury and during axon regeneration in the central nervous system (CNS). Previously, we discovered multiple molecular pathways and strategies that could promote robust axon regrowth after optic nerve injury. Read More

View Article and Full-Text PDF
December 2020

Gene silencing of extracellular matrix protein 1 (ECM1) results in phenotypic alterations of dermal fibroblasts reminiscent of clinical features of lichen sclerosus.

J Dermatol Sci 2020 Nov 25;100(2):99-109. Epub 2020 Jun 25.

Department of Dermatology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. Electronic address:

Background: Lichen sclerosus (LS) is an acquired inflammatory mucocutaneous disease affecting the anogenital area, characterized histologically by hyalinosis and thickened vessel walls in the dermis. The presence of serum autoantibodies against extracellular matrix protein 1 (ECM1) in LS patients may suggest its involvement in disease pathogenesis.

Objective: To examine if reduced ECM1 production by dermal fibroblasts contributes to the pathogenic features of LS. Read More

View Article and Full-Text PDF
November 2020

Cytotoxic T cells swarm by homotypic chemokine signalling.

Elife 2020 10 13;9. Epub 2020 Oct 13.

EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia.

Cytotoxic T lymphocytes (CTLs) are thought to arrive at target sites either via random search or following signals by other leukocytes. Here, we reveal independent emergent behaviour in CTL populations attacking tumour masses. Primary murine CTLs coordinate their migration in a process reminiscent of the swarming observed in neutrophils. Read More

View Article and Full-Text PDF
October 2020