Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 1203

Publication Record

Connections

Identification and Characterization of Unique Neutralizing Antibodies to Mouse EGF Receptor.
Jae Huh W, Niitsu H, Carney B, McKinley ET, Houghton JL, Coffey RJ
(2020) Gastroenterology 158: 1500-1502
MeSH Terms: Animals, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Azoxymethane, Carcinogens, Cells, Cultured, Colonic Neoplasms, Dextran Sulfate, Disease Models, Animal, ErbB Receptors, Gastritis, Hypertrophic, Genes, Reporter, Hepatocytes, Humans, Mice, Mice, Transgenic, Primary Cell Culture
Added January 31, 2020
1 Communities
1 Members
0 Resources
17 MeSH Terms
Dynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states.
Hartley ND, Gaulden AD, Báldi R, Winters ND, Salimando GJ, Rosas-Vidal LE, Jameson A, Winder DG, Patel S
(2019) Nat Neurosci 22: 2000-2012
MeSH Terms: Animals, Basolateral Nuclear Complex, Central Amygdaloid Nucleus, Conditioning, Classical, Corticotropin-Releasing Hormone, Excitatory Postsynaptic Potentials, Extinction, Psychological, Fear, Freezing Reaction, Cataleptic, Glutamic Acid, Mice, Transgenic, Neural Pathways, Somatostatin
Show Abstract · Added March 3, 2020
Acquisition and extinction of learned fear responses utilize conserved but flexible neural circuits. Here we show that acquisition of conditioned freezing behavior is associated with dynamic remodeling of relative excitatory drive from the basolateral amygdala (BLA) away from corticotropin releasing factor-expressing (CRF) centrolateral amygdala neurons, and toward non-CRF (CRF) and somatostatin-expressing (SOM) neurons, while fear extinction training remodels this circuit back toward favoring CRF neurons. Importantly, BLA activity is required for this experience-dependent remodeling, while directed inhibition of the BLA-centrolateral amygdala circuit impairs both fear memory acquisition and extinction memory retrieval. Additionally, ectopic excitation of CRF neurons impairs fear memory acquisition and facilities extinction, whereas CRF neuron inhibition impairs extinction memory retrieval, supporting the notion that CRF neurons serve to inhibit learned freezing behavior. These data suggest that afferent-specific dynamic remodeling of relative excitatory drive to functionally distinct subcortical neuronal output populations represents an important mechanism underlying experience-dependent modification of behavioral selection.
0 Communities
1 Members
0 Resources
MeSH Terms
Inactivation of mTORC2 in macrophages is a signature of colorectal cancer that promotes tumorigenesis.
Katholnig K, Schütz B, Fritsch SD, Schörghofer D, Linke M, Sukhbaatar N, Matschinger JM, Unterleuthner D, Hirtl M, Lang M, Herac M, Spittler A, Bergthaler A, Schabbauer G, Bergmann M, Dolznig H, Hengstschläger M, Magnuson MA, Mikula M, Weichhart T
(2019) JCI Insight 4:
MeSH Terms: Animals, Carcinogenesis, Cell Line, Tumor, Cell Proliferation, Cells, Cultured, Colitis, Ulcerative, Colon, Colorectal Neoplasms, Dextran Sulfate, Disease Models, Animal, Female, Humans, Intestinal Mucosa, Kaplan-Meier Estimate, Macrophages, Male, Mechanistic Target of Rapamycin Complex 2, Mice, Mice, Transgenic, Morpholines, Osteopontin, Primary Cell Culture, Prognosis, Survival Rate
Show Abstract · Added November 6, 2019
The mechanistic target of rapamycin complex 2 (mTORC2) is a potentially novel and promising anticancer target due to its critical roles in proliferation, apoptosis, and metabolic reprogramming of cancer cells. However, the activity and function of mTORC2 in distinct cells within malignant tissue in vivo is insufficiently explored. Surprisingly, in primary human and mouse colorectal cancer (CRC) samples, mTORC2 signaling could not be detected in tumor cells. In contrast, only macrophages in tumor-adjacent areas showed mTORC2 activity, which was downregulated in stromal macrophages residing within human and mouse tumor tissues. Functionally, inhibition of mTORC2 by specific deletion of Rictor in macrophages stimulated tumorigenesis in a colitis-associated CRC mouse model. This phenotype was driven by a proinflammatory reprogramming of mTORC2-deficient macrophages that promoted colitis via the cytokine SPP1/osteopontin to stimulate tumor growth. In human CRC patients, high SPP1 levels and low mTORC2 activity in tumor-associated macrophages correlated with a worsened clinical prognosis. Treatment of mice with a second-generation mTOR inhibitor that inhibits mTORC2 and mTORC1 exacerbated experimental colorectal tumorigenesis in vivo. In conclusion, mTORC2 activity is confined to macrophages in CRC and limits tumorigenesis. These results suggest activation but not inhibition of mTORC2 as a therapeutic strategy for colitis-associated CRC.
1 Communities
1 Members
0 Resources
24 MeSH Terms
Heterosynaptic GABA Receptor Function within Feedforward Microcircuits Gates Glutamatergic Transmission in the Nucleus Accumbens Core.
Manz KM, Baxley AG, Zurawski Z, Hamm HE, Grueter BA
(2019) J Neurosci 39: 9277-9293
MeSH Terms: Animals, GABA-B Receptor Agonists, Glutamic Acid, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Nucleus Accumbens, Organ Culture Techniques, Receptors, GABA-B, Synapses, Synaptic Transmission
Show Abstract · Added March 24, 2020
Complex circuit interactions within the nucleus accumbens (NAc) facilitate goal-directed behavior. Medium spiny neurons (MSNs) mediate NAc output by projecting to functionally divergent brain regions, a property conferred, in part, by the differential projection patterns of D1- and D2 dopamine receptor-expressing MSNs. Glutamatergic afferents to the NAc direct MSN output by recruiting feedforward inhibitory microcircuits comprised of parvalbumin (PV)-expressing interneurons (INs). Furthermore, the GABA heteroreceptor (GABAR), a G-coupled G-protein-coupled receptor, is expressed at glutamatergic synapses throughout the mesolimbic network, yet its physiological context and synaptic mechanism within the NAc remains unknown. Here, we explored GABAR function at glutamatergic synapses within PV-IN-embedded microcircuits in the NAc core of male mice. We found that GABAR is expressed presynaptically and recruits a noncanonical signaling mechanism to reduce glutamatergic synaptic efficacy at D1(+) and D1(-) (putative D2) MSN subtypes. Furthermore, PV-INs, a robust source of neuronal GABA in the NAc, heterosynaptically target GABAR to selectively modulate glutamatergic transmission onto D1(+) MSNs. These findings elucidate a new mechanism of feedforward inhibition and refine mechanisms by which GABA heteroreceptors modulate mesolimbic circuit function. Glutamatergic transmission in the nucleus accumbens (NAc) critically contributes to goal-directed behaviors. However, intrinsic microcircuit mechanisms governing the integration of these synapses remain largely unknown. Here, we show that parvalbumin-expressing interneurons within feedforward microcircuits heterosynaptically target GABA heteroreceptors (GABAR) on glutamate terminals. Activation of presynaptically-expressed GABAR decreases glutamatergic synaptic strength by engaging a non-canonical signaling pathway that interferes with vesicular exocytotic release machinery. These findings offer mechanistic insight into the role of GABA heteroreceptors within reward circuitry, elucidate a novel arm to feedforward inhibitory networks, and inform the growing use of GABAR-selective pharmacotherapy for various motivational disorders, including addiction, major depressive disorder, and autism (Cousins et al., 2002; Kahn et al., 2009; Jacobson et al., 2018; Stoppel et al., 2018; Pisansky et al., 2019).
Copyright © 2019 the authors.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Identification of drug-specific public TCR driving severe cutaneous adverse reactions.
Pan RY, Chu MT, Wang CW, Lee YS, Lemonnier F, Michels AW, Schutte R, Ostrov DA, Chen CB, Phillips EJ, Mallal SA, Mockenhaupt M, Bellón T, Tassaneeyakul W, White KD, Roujeau JC, Chung WH, Hung SI
(2019) Nat Commun 10: 3569
MeSH Terms: Adoptive Transfer, Adult, Aged, Animals, Carbamazepine, Disease Models, Animal, Female, HLA-B15 Antigen, Humans, Male, Mice, Transgenic, Middle Aged, Receptor-CD3 Complex, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta, Severity of Illness Index, Skin, Stevens-Johnson Syndrome, T-Lymphocytes, Cytotoxic
Show Abstract · Added March 30, 2020
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αβTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
0 Communities
1 Members
0 Resources
MeSH Terms
Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing.
Saraswati S, Marrow SMW, Watch LA, Young PP
(2019) Nat Commun 10: 3027
MeSH Terms: Actins, Animals, Bone Marrow Transplantation, Calcium-Binding Proteins, Cell Differentiation, Disease Models, Animal, Fibroblasts, Fibrosis, Green Fluorescent Proteins, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myocardial Infarction, Myocardium, Neovascularization, Physiologic, S100 Calcium-Binding Protein A4, Transplantation Chimera, Wound Healing
Show Abstract · Added March 24, 2020
Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis along with physiological repair, making them a difficult therapeutic target. Although activated fibroblasts are phenotypically heterogeneous, they are not recognized as distinct functional entities. Using mice that express GFP under the FSP1 or αSMA promoter, we characterized two non-overlapping fibroblast subtypes from mouse hearts after myocardial infarction. Here, we report the identification of FSP1-GFP cells as a non-pericyte, non-hematopoietic fibroblast subpopulation with a predominant pro-angiogenic role, characterized by in vitro phenotypic/cellular/ultrastructural studies and in vivo granulation tissue formation assays combined with transcriptomics and proteomics. This work identifies a fibroblast subtype that is functionally distinct from the pro-fibrotic αSMA-expressing myofibroblast subtype. Our study has the potential to shift our focus towards viewing fibroblasts as molecularly and functionally heterogeneous and provides a paradigm to approach treatment for organ fibrosis.
0 Communities
1 Members
0 Resources
MeSH Terms
The Pdx1-Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet β-Cell Function.
Spaeth JM, Liu JH, Peters D, Guo M, Osipovich AB, Mohammadi F, Roy N, Bhushan A, Magnuson MA, Hebrok M, Wright CVE, Stein R
(2019) Diabetes 68: 1806-1818
MeSH Terms: Animals, Cell Proliferation, Chromatin Assembly and Disassembly, DNA Helicases, Gene Expression Regulation, Glucose Intolerance, Homeodomain Proteins, Insulin, Insulin-Secreting Cells, Mice, Mice, Transgenic, Nuclear Proteins, Pancreas, Trans-Activators, Transcription Factors
Show Abstract · Added June 28, 2019
Transcription factors positively and/or negatively impact gene expression by recruiting coregulatory factors, which interact through protein-protein binding. Here we demonstrate that mouse pancreas size and islet β-cell function are controlled by the ATP-dependent Swi/Snf chromatin remodeling coregulatory complex that physically associates with Pdx1, a diabetes-linked transcription factor essential to pancreatic morphogenesis and adult islet cell function and maintenance. Early embryonic deletion of just the Swi/Snf Brg1 ATPase subunit reduced multipotent pancreatic progenitor cell proliferation and resulted in pancreas hypoplasia. In contrast, removal of both Swi/Snf ATPase subunits, Brg1 and Brm, was necessary to compromise adult islet β-cell activity, which included whole-animal glucose intolerance, hyperglycemia, and impaired insulin secretion. Notably, lineage-tracing analysis revealed Swi/Snf-deficient β-cells lost the ability to produce the mRNAs for and other key metabolic genes without effecting the expression of many essential islet-enriched transcription factors. Swi/Snf was necessary for Pdx1 to bind to the gene enhancer, demonstrating the importance of this association in mediating chromatin accessibility. These results illustrate how fundamental the Pdx1:Swi/Snf coregulator complex is in the pancreas, and we discuss how disrupting their association could influence type 1 and type 2 diabetes susceptibility.
© 2019 by the American Diabetes Association.
1 Communities
3 Members
0 Resources
15 MeSH Terms
β-Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion.
Barella LF, Rossi M, Zhu L, Cui Y, Mei FC, Cheng X, Chen W, Gurevich VV, Wess J
(2019) J Clin Invest 129: 3732-3737
MeSH Terms: Animals, Genotype, Glyburide, Guanine Nucleotide Exchange Factors, Hypoglycemic Agents, Insulin Secretion, Insulin-Secreting Cells, Male, Mice, Mice, Knockout, Mice, Transgenic, Phenotype, Signal Transduction, Sulfonylurea Compounds, Tolbutamide, beta-Arrestin 1, beta-Arrestin 2
Show Abstract · Added March 18, 2020
Beta-arrestin-1 and -2 (Barr1 and Barr2, respectively) are intracellular signaling molecules that regulate many important metabolic functions. We previously demonstrated that mice lacking Barr2 selectively in pancreatic beta-cells showed pronounced metabolic impairments. Here we investigated whether Barr1 plays a similar role in regulating beta-cell function and whole body glucose homeostasis. Initially, we inactivated the Barr1 gene in beta-cells of adult mice (beta-barr1-KO mice). Beta-barr1-KO mice did not display any obvious phenotypes in a series of in vivo and in vitro metabolic tests. However, glibenclamide and tolbutamide, two widely used antidiabetic drugs of the sulfonylurea (SU) family, showed greatly reduced efficacy in stimulating insulin secretion in the KO mice in vivo and in perifused KO islets in vitro. Additional in vivo and in vitro studies demonstrated that Barr1 enhanced SU-stimulated insulin secretion by promoting SU-mediated activation of Epac2. Pull-down and co-immunoprecipitation experiments showed that Barr1 can directly interact with Epac2 and that SUs such as glibenclamide promote Barr1/Epac2 complex formation, triggering enhanced Rap1 signaling and insulin secretion. These findings suggest that strategies aimed at promoting Barr1 signaling in beta-cells may prove useful for the development of efficacious antidiabetic drugs.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Sex-Dependent Modulation of Anxiety and Fear by 5-HT Receptors in the Bed Nucleus of the Stria Terminalis.
Marcinkiewcz CA, Bierlein-De La Rosa G, Dorrier CE, McKnight M, DiBerto JF, Pati D, Gianessi CA, Hon OJ, Tipton G, McElligott ZA, Delpire E, Kash TL
(2019) ACS Chem Neurosci 10: 3154-3166
MeSH Terms: Animals, Anxiety, Behavior, Animal, Fear, Feeding Behavior, Female, Gene Knockdown Techniques, Male, Mice, Mice, Transgenic, Motor Activity, Neurons, Receptor, Serotonin, 5-HT1A, Septal Nuclei, Sex Factors
Show Abstract · Added June 28, 2019
Serotonin (5-hydroxytryptamine; 5-HT) coordinates behavioral responses to stress through a variety of presynaptic and postsynaptic receptors distributed across functionally diverse neuronal networks in the central nervous system. Efferent 5-HT projections from the dorsal raphe nucleus (DRN) to the bed nucleus of the stria terminalis (BNST) are generally thought to enhance anxiety and aversive learning by activating 5-HT receptor (5-HTR) signaling in the BNST, although an opposing role for postsynaptic 5-HT receptors has recently been suggested. In the present study, we sought to delineate a role for postsynaptic 5-HT receptors in the BNST in aversive behaviors using a conditional knockdown of the 5-HT receptor. Both males and females were tested to dissect out sex-specific effects. We found that male mice have significantly reduced fear memory recall relative to female mice and inactivation of 5-HT receptor in the BNST increases contextual fear conditioning in male mice so that they resemble the females. This coincided with an increase in neuronal excitability in males, suggesting that 5-HT receptor deletion may enhance contextual fear recall by disinhibiting fear memory circuits in the BNST. Interestingly, 5-HT receptor knockdown did not significantly alter anxiety-like behavior in male or female mice, which is in agreement with previous findings that anxiety and fear are modulated by dissociable circuits in the BNST. Overall, these results suggest that BNST 5-HT receptors do not significantly alter behavior under basal conditions, but can act as a molecular brake that buffer against excessive activation of aversive circuits in more threatening contexts.
1 Communities
1 Members
0 Resources
15 MeSH Terms
Disabling Gβγ-SNAP-25 interaction in gene-targeted mice results in enhancement of long-term potentiation at Schaffer collateral-CA1 synapses in the hippocampus.
Irfan M, Zurawski Z, Hamm HE, Bark C, Stanton PK
(2019) Neuroreport 30: 695-699
MeSH Terms: Animals, Excitatory Postsynaptic Potentials, Hippocampus, Long-Term Potentiation, Mice, Transgenic, Neuronal Plasticity, Synapses, Synaptic Transmission, Synaptosomal-Associated Protein 25, Temporal Lobe
Show Abstract · Added March 24, 2020
Three SNARE proteins, SNAP-25, syntaxin 1A, and VAMP2 or synaptobrevin 2, constitute the minimal functional machinery needed for the regulated secretion of neurotransmitters. Dynamic changes in the regulated release of neurotransmitters are associated with the induction of long-term plasticity at central synapses. In-vitro studies have validated the C-terminus of SNAP-25 as a target for inhibitory Gi/o-coupled G-protein coupled receptors at a number of synapses. The physiological consequences of the interaction between Gi/o proteins and SNAP-25 in the context of activity-dependent long-term synaptic plasticity are not well understood. Here, we report direct ex-vivo evidence of the involvement of the C-terminus of SNAP-25 in inducing long-term potentiation of synaptic strength at Schaffer collateral-CA1 synapses using a gene-targeted mouse model with truncated C-terminus (carboxyl terminus) of SNAP-25. It has been shown previously that truncation of the three extreme C-terminal residues in SNAP-25[INCREMENT]3 homozygote mice reduces its interaction with the inhibitory Gβγ subunits two-fold. In in-vitro hippocampal slices, we show that these SNAP-25[INCREMENT]3 mice express significantly larger magnitude of long-term potentiation at hippocampal Schaffer collateral-CA1 synapses.
0 Communities
1 Members
0 Resources
10 MeSH Terms