scholarly journals A Gradient of Hippocampal Inputs to the Medial Mesocortex

2019 ◽  
Author(s):  
Emanuel Ferreira-Fernandes ◽  
Carolina Quintino ◽  
Miguel Remondes
Keyword(s):  
Retrosplenial Cortex ◽  
Anterior Cingulate ◽  
Stratum Radiatum ◽  
Inhibitory Input ◽  
Excitatory Synapses ◽  
Stratum Pyramidale ◽  
Bona Fide ◽  
Functional Circuitry

AbstractMemory-guided decisions depend on complex, finely tuned interactions between hippocampus and medial mesocortical regions anterior cingulate and retrosplenial cortices. The functional circuitry underlying these interactions is unclear. Using viral anatomical tracing,in vitroandin vivoelectrophysiology, and optogenetics, we show that such circuitry is characterized by a functional-anatomical gradient. While CG receives excitatory projections from dorsal-intermediate CA1 originated exclusively instratum pyramidale, retrosplenial cortex also receives inputs originating instratum radiatumandlacunosum-moleculare, including GAD+ neurons providing long-range GABAergic projections. Such hippocampal projections establishbona fidesynapses throughout cortical layers, with retrosplenial cortex densely targeted on its layer 3, around which it receives a combination of inhibitory and excitatory synapses. This gradient is reflected in the pattern of spontaneous oscillatory synchronicity found in the awake-behaving animal, compatible with the known functional similarity of hippocampus with retrosplenial cortex, which contrasts with the encoding of actions and “task-space” by cingulate cortex.HighlightsBoth MMC regions CG and RSC receive monosynaptic connections from the dorsal-intermediate CA1CG receives layer-sparse excitatory projections exclusively originated fromstratum piramidalewhereas RSC is targeted densely in superficial layers by a mixed excitatory and inhibitory input originating from all CA1strataCA1 monosynaptic projections correspond to active synapses onto distinct layers of the two MMC regionsDiverse synchrony between MMC and HIPP recordedin vivois consistent with the rostro-caudal diversity of direct HIPP-MMC connections

scholarly journals Vimentin in a cold-water fish, the rainbow trout: highly conserved primary structure but unique assembly properties

1996 ◽  
Vol 109 (3) ◽  
pp. 569-578 ◽  
Author(s):  
H. Herrmann ◽  
M.D. Munick ◽  
M. Brettel ◽  
B. Fouquet ◽  
J. Markl
Keyword(s):  
Rainbow Trout ◽  
Intermediate Filament ◽  
Cold Water ◽  
White Blood Cells ◽  
Cellular Functions ◽  
Filamentous Form ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Bona Fide

We have isolated from a rainbow trout (Oncorhynchus mykiss) spleen cDNA library a clone coding for vimentin. The deduced amino acid sequence reveals a high degree of identity with vimentin from carp (81%), frog (71%), chick and human (73% each). Large stretches in the central alpha-helical rod are identical within all four classes of vertebrates, but in 17 residues spread over the entire rod, the two fish differ distinctly from the tetrapod species. In addition, in the more diverged non-helical head domain, a nonapeptide motif previously shown to be important for regular filament formation is conserved. Recombinant trout vimentin assembles into bona fide filaments in vitro, with a temperature optimum between 18 and 24 degrees C. Above 27 degrees C, however, filament assembly is abruptly abolished and short filaments with thickened ends as well as structures without typical intermediate filament appearance are formed. This distinguishes its assembly properties significantly from amphibian, avian and mammalian vimentin. Also in vivo, after cDNA transfection into vimentin-free mammalian epithelial cells, trout vimentin does not form typical intermediate filament arrays at 37 degrees C. At 28 degrees C, and even more pronounced at 22 degrees C, the vimentin-positive material in the transfected cells is reorganized in the perinuclear region with a partial fibrillar appearance, but typical intermediate filament arrays are not formed. Together with immunoblotting and immunolocalization data from trout tissues, where vimentin is predominantly found in glial and white blood cells, we conclude that vimentin is indeed important in its filamentous form in fish and other vertebrates, possibly fulfilling cellular functions not directly evident in gene targeting experiments carried out in mice.

The bidirectional promoter of the divergently transcribed mouse Surf-1 and Surf-2 genes

1991 ◽  
Vol 11 (3) ◽  
pp. 1281-1294
Author(s):  
A C Lennard ◽  
M Fried
Keyword(s):  
Binding Site ◽  
Dimethyl Sulfate ◽  
Ribosomal Protein Gene ◽  
Bidirectional Promoter ◽  
Gene Promoters ◽  
Accurate Expression ◽  
Bona Fide ◽  
Efficient Expression

The ubiquitously expressed mouse Surf-1 and Surf-2 genes are divergently transcribed, and their heterogeneous start sites are separated by up to a maximum of only 73 bp. By using in vitro DNase I, dimethyl sulfate methylation, and gel retardation assays, we have identified five putative promoter control elements between and around the Surf-1 and Surf-2 start sites. The effects of each site on the regulation of Surf-1 and Surf-2 transcription have been studied in vivo, and four sites were found to be functional promoter elements. A novel binding site is required for efficient use of the intermediate but not the major start site of Surf-1. Three elements function in a bidirectional manner and are shared for efficient and accurate expression of both Surf-1 and Surf-2. One is an UEF (USF, MLTF) binding site which had a small effect on the use of the intermediate start sites of Surf-1 and also affected the major start sites of Surf-2. Another has sequence homology to the RPG alpha binding site associated with some ribosomal protein gene promoters and is required for efficient expression of the major but not intermediate start sites of Surf-1 and all start sites of Surf-2. The third, an RPG alpha-like site, is used for all start sites of both Surf-1 and Surf-2. Dissection of this cellular promoter region showed that different binding sites affect the use of different start sites and revealed a complex interaction between multiple elements that constitute a bona fide bidirectional promoter.

scholarly journals Synergy of NUP98-HOXA10 Fusion Gene and NrasG12D Mutation Preserves the Stemness of Hematopoietic Stem Cells on Culture Condition

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 951 ◽  
Author(s):  
Yong Dong ◽  
Chengxiang Xia ◽  
Qitong Weng ◽  
Tongjie Wang ◽  
Fangxiao Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Culture Condition ◽  
Fusion Gene ◽  
Nras Mutation ◽  
Hematopoietic Stem ◽  
Bona Fide

Natural hematopoietic stem cells (HSC) are susceptible and tend to lose stemness, differentiate, or die on culture condition in vitro, which adds technical challenge for maintaining bona fide HSC-like cells, if ever generated, in protocol screening from pluripotent stem cells. It remains largely unknown whether gene-editing of endogenous genes can genetically empower HSC to endure the culture stress and preserve stemness. In this study, we revealed that both NUP98-HOXA10HD fusion and endogenous Nras mutation modifications (NrasG12D) promoted the engraftment competitiveness of HSC. Furthermore, the synergy of these two genetic modifications endowed HSC with super competitiveness in vivo. Strikingly, single NAV-HSC successfully maintained its stemness and showed robust multi-lineage engraftments after undergoing the in vitro culture. Mechanistically, NUP98-HOXA10HD fusion and NrasG12D mutation distinctly altered multiple pathways involving the cell cycle, cell division, and DNA replication, and distinctly regulated stemness-related genes including Hoxa9, Prdm16, Hoxb4, Trim27, and Smarcc1 in the context of HSC. Thus, we develop a super-sensitive transgenic model reporting the existence of HSC at the single cell level on culture condition, which could be beneficial for protocol screening of bona fide HSC regeneration from pluripotent stem cells in vitro.

IL-17–producing invariant NKT cells in lymphoid organs are recent thymic emigrants identified by neuropilin-1 expression

Blood ◽  
2011 ◽  
Vol 118 (11) ◽  
pp. 2993-3002 ◽  
Author(s):  
Pierre Milpied ◽  
Bérangère Massot ◽  
Amédée Renand ◽  
Séverine Diem ◽  
André Herbelin ◽  
...  
Keyword(s):  
Cell Subset ◽  
Treg Cells ◽  
Lymphoid Organs ◽  
Inkt Cell ◽  
Inkt Cells ◽  
Invariant Nkt Cells ◽  
Neuropilin 1 ◽  
Bona Fide

Abstract Despite increasing knowledge on the mechanisms of invariant natural killer T (iNKT)–cell development in the thymus, the function of recent thymic emigrant (RTE) iNKT cells remains largely unexplored, principally because of a lack of bona fide markers to distinguish RTE from long-lived iNKT cells. Whether the recently described IL-17–producing iNKT cell subset is part of RTE has notably not been addressed. In the present study, we show that neuropilin-1 (Nrp-1), a transmembrane receptor mainly found on T-regulatory (Treg) cells in the murine immune system, is specifically expressed on RTE iNKT cells in naive mice. We used the Nrp-1 marker to discriminate RTE from mature iNKT cells and compare their functions. We show that RTE iNKT cells proliferate more than mature iNKT cells after in vitro activation; that, unlike mature iNKT cells, most RTE iNKT cells fail to rapidly produce IFN-γ and IL-4 after in vivo activation; and, most importantly, that IL-17–producing iNKT cells in lymphoid organs of naive mice are contained within the RTE iNKT cell pool. Our results establish an accurate marker of RTE iNKT cells and reveal that continuous thymic output is required for pro-inflammatory IL-17 secretion, a key function of adult iNKT cells.

Biochemical characterization of bona fide polycystin-1 in vitro and in vivo

2001 ◽  
Vol 38 (6) ◽  
pp. 1421-1429 ◽  
Author(s):  
Alessandra Boletta ◽  
Feng Qian ◽  
Luiz F. Onuchic ◽  
Alessandra Bragonzi ◽  
Marina Cortese ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Bona Fide

scholarly journals MEKK1 activates both IκB kinase α and IκB kinase β

1998 ◽  
Vol 95 (16) ◽  
pp. 9319-9324 ◽  
Author(s):  
Frank S. Lee ◽  
Robert T. Peters ◽  
Luan C. Dang ◽  
Tom Maniatis
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Mitogen Activated Protein Kinase ◽  
Site Specific ◽  
Iκb Kinase ◽  
Mitogen Activated Protein ◽  
Bona Fide ◽  
Factor Α

A critical step in the signal-induced activation of the transcription factor NF-κB is the site-specific phosphorylation of its inhibitor, IκB, that targets the latter for degradation by the ubiquitin–proteasome pathway. We have previously shown that mitogen-activated protein kinase/ERK kinase kinase 1 (MEKK1) can induce both this site-specific phosphorylation of IκBα at Ser-32 and Ser-36 in vivo and the activity of a high molecular weight IκB kinase complex in vitro. Subsequently, others have identified two proteins, IκB kinase α (IKK-α) and IκB kinase β (IKK-β), that are present in a tumor necrosis factor α-inducible, high molecular weight IκB kinase complex. These kinases are believed to directly phosphorylate IκB based on the examination of the kinase activities of IKK immunoprecipitates, but more rigorous proof of this has yet to be demonstrated. We show herein that recombinant IKK-α and IKK-β can, in fact, directly phosphorylate IκBα at Ser-32 and Ser-36, as well as homologous residues in IκBβ in vitro, and thus are bona fide IκB kinases. We also show that MEKK1 can induce the activation of both IKK-α and IKK-β in vivo. Finally, we show that IKK-α is present in the MEKK1-inducible, high molecular weight IκB kinase complex and treatment of this complex with MEKK1 induces phosphorylation of IKK-α in vitro. We conclude that IKK-α and IKK-β can mediate the NF-κB-inducing activity of MEKK1.

scholarly journals GABAergic and glycinergic inhibition modulate monaural auditory response properties in the avian superior olivary nucleus

2011 ◽  
Vol 105 (5) ◽  
pp. 2405-2420 ◽  
Author(s):  
W. L. Coleman ◽  
M. J. Fischl ◽  
S. R. Weimann ◽  
R. M. Burger
Keyword(s):  
Phase Locking ◽  
Auditory Brainstem ◽  
Inhibitory Input ◽  
Auditory Information ◽  
Low Frequencies ◽  
Response Properties ◽  
Glycinergic Inhibition ◽  
Olivary Nucleus

The superior olivary nucleus (SON) is the primary source of inhibition in the avian auditory brainstem. While much is known about the role of inhibition at the SON's target nuclei, little is known about how the SON itself processes auditory information or how inhibition modulates these properties. Additionally, the synaptic physiology of inhibitory inputs within the SON has not been described. We investigated these questions using in vivo and in vitro electrophysiological techniques in combination with immunohistochemistry in the chicken, an organism for which the auditory brainstem has otherwise been well characterized. We provide a thorough characterization of monaural response properties in the SON and the influence of inhibitory input in shaping these features. We found that the SON contains a heterogeneous mixture of response patterns to acoustic stimulation and that in most neurons these responses are modulated by both GABAergic and glycinergic inhibitory inputs. Interestingly, many SON neurons tuned to low frequencies have robust phase-locking capability and the precision of this phase locking is enhanced by inhibitory inputs. On the synaptic level, we found that evoked and spontaneous inhibitory postsynaptic currents (IPSCs) within the SON are also mediated by both GABAergic and glycinergic inhibition in all neurons tested. Analysis of spontaneous IPSCs suggests that most SON cells receive a mixture of both purely GABAergic terminals, as well as terminals from which GABA and glycine are coreleased. Evidence for glycinergic signaling within the SON is a novel result that has important implications for understanding inhibitory function in the auditory brainstem.

Role of ESCRT component HD-PTP/PTPN23 in cancer

2017 ◽  
Vol 45 (3) ◽  
pp. 845-854 ◽  
Author(s):  
Marie-Claude Gingras ◽  
Jalal M. Kazan ◽  
Arnim Pause
Keyword(s):  
Plasma Membrane ◽  
Cancer Susceptibility ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Surface Receptors ◽  
Endosomal Sorting ◽  
Bona Fide

Sustained cellular signalling originated from the receptors located at the plasma membrane is widely associated with cancer susceptibility. Endosomal sorting and degradation of the cell surface receptors is therefore crucial to preventing chronic downstream signalling and tumorigenesis. Since the Endosomal Sorting Complexes Required for Transport (ESCRT) controls these processes, ESCRT components were proposed to act as tumour suppressor genes. However, the bona fide role of ESCRT components in tumorigenesis has not been clearly demonstrated. The ESCRT member HD-PTP/PTPN23 was recently identified as a novel haplo-insufficient tumour suppressor in vitro and in vivo, in mice and humans. In this mini-review, we outline the role of the ESCRT components in cancer and summarize the functions of HD-PTP/PTPN23 in tumorigenesis.

scholarly journals Cooperative Interaction between GATA-4 and GATA-6 Regulates Myocardial Gene Expression

1999 ◽  
Vol 19 (6) ◽  
pp. 4355-4365 ◽  
Author(s):  
Frédéric Charron ◽  
Pierre Paradis ◽  
Odile Bronchain ◽  
Georges Nemer ◽  
Mona Nemer
Keyword(s):  
Cooperative Interaction ◽  
Gata Factors ◽  
Cellular Processes ◽  
Two Factors ◽  
Bona Fide ◽  
Transcriptional Pathway ◽  
Combinatorial Interactions ◽  
Myocardial Gene Expression

ABSTRACT Two members of the GATA family of transcription factors, GATA-4 and GATA-6, are expressed in the developing and postnatal myocardium and are equally potent transactivators of several cardiac promoters. However, several in vitro and in vivo lines of evidence suggest distinct roles for the two factors in the heart. Since identification of the endogenous downstream targets of GATA factors would greatly help to elucidate their exact functions, we have developed an adenovirus-mediated antisense strategy to specifically inhibit GATA-4 and GATA-6 protein production in postnatal cardiomyocytes. Expression of several endogenous cardiac genes was significantly down-regulated in cells lacking GATA-4 or GATA-6, indicating that these factors are required for the maintenance of the cardiac genetic program. Interestingly, transcription of some genes like the α- and β-myosin heavy-chain (α- and β-MHC) genes was preferentially regulated by GATA-4 due, in part, to higher affinity of GATA-4 for their promoter GATA element. However, transcription of several other genes, including the atrial natriuretic factor and B-type natriuretic peptide (ANF and BNP) genes, was similarly down-regulated in cardiomyocytes lacking one or both GATA factors, suggesting that GATA-4 and GATA-6 could act through the same transcriptional pathway. Consistent with this, GATA-4 and GATA-6 were found to colocalize in postnatal cardiomyocytes and to interact functionally and physically to provide cooperative activation of the ANF and BNP promoters. The results identify for the first time bona fide in vivo targets for GATA-4 and GATA-6 in the myocardium. The data also show that GATA factors act in concert to regulate distinct subsets of genes, suggesting that combinatorial interactions among GATA factors may differentially control various cellular processes.

scholarly journals Metabotropic glutamate receptor signaling is required for NMDA receptor-dependent ocular dominance plasticity and LTD in visual cortex

2015 ◽  
Vol 112 (41) ◽  
pp. 12852-12857 ◽  
Author(s):  
Michael S. Sidorov ◽  
Eitan S. Kaplan ◽  
Emily K. Osterweil ◽  
Lothar Lindemann ◽  
Mark F. Bear
Keyword(s):  
Visual Cortex ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Ocular Dominance ◽  
Monocular Deprivation ◽  
Excitatory Synapses ◽  
Ocular Dominance Plasticity ◽  
Metabotropic Glutamate

A feature of early postnatal neocortical development is a transient peak in signaling via metabotropic glutamate receptor 5 (mGluR5). In visual cortex, this change coincides with increased sensitivity of excitatory synapses to monocular deprivation (MD). However, loss of visual responsiveness after MD occurs via mechanisms revealed by the study of long-term depression (LTD) of synaptic transmission, which in layer 4 is induced by acute activation of NMDA receptors (NMDARs) rather than mGluR5. Here we report that chronic postnatal down-regulation of mGluR5 signaling produces coordinated impairments in both NMDAR-dependent LTD in vitro and ocular dominance plasticity in vivo. The data suggest that ongoing mGluR5 signaling during a critical period of postnatal development establishes the biochemical conditions that are permissive for activity-dependent sculpting of excitatory synapses via the mechanism of NMDAR-dependent LTD.

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