scholarly journals Increased Sociability in Mice Lacking Intergenic Dlx Enhancers

2021 ◽  
Vol 15 ◽  
Author(s):  
Siavash Fazel Darbandi ◽  
Crystal Esau ◽  
Cindy Lesage-Pelletier ◽  
Simon Monis ◽  
Luc Poitras ◽  
...  
Keyword(s):  
Mutant Mouse ◽  
Regulatory Elements ◽  
Gabaergic Interneuron ◽  
Learning Deficits ◽  
Forebrain Development ◽  
Human Genomes ◽  
And Migration ◽  
Fear Conditioning Test ◽  
Mouse Lines

The Dlx homeodomain transcription factors play important roles in the differentiation and migration of GABAergic interneuron precursors. The mouse and human genomes each have six Dlx genes organized into three convergently transcribed bigene clusters (Dlx1/2, Dlx3/4, and Dlx5/6) with cis-regulatory elements (CREs) located in the intergenic region of each cluster. Amongst these, the I56i and I12b enhancers from the Dlx1/2 and Dlx5/6 locus, respectively, are active in the developing forebrain. I56i is also a binding site for GTF2I, a transcription factor whose function is associated with increased sociability and Williams–Beuren syndrome. In determining the regulatory roles of these CREs on forebrain development, we have generated mutant mouse-lines where Dlx forebrain intergenic enhancers have been deleted (I56i(–/–), I12b(–/–)). Loss of Dlx intergenic enhancers impairs expression of Dlx genes as well as some of their downstream targets or associated genes including Gad2 and Evf2. The loss of the I56i enhancer resulted in a transient decrease in GABA+ cells in the developing forebrain. The intergenic enhancer mutants also demonstrate increased sociability and learning deficits in a fear conditioning test. Characterizing mice with mutated Dlx intergenic enhancers will help us to further enhance our understanding of the role of these Dlx genes in forebrain development.

scholarly journals Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration

2021 ◽  
Vol 14 ◽  
Author(s):  
Ashley McDonough ◽  
Gina E. Elsen ◽  
Ray M. Daza ◽  
Amelia R. Bachleda ◽  
Donald Pizzo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Specific Expression ◽  
Brush Cells ◽  
Knock Out ◽  
Unipolar Brush Cells ◽  
Human Cerebellum ◽  
And Migration ◽  
Rhombic Lip ◽  
Mouse Lines

Previous studies demonstrated specific expression of transcription factor Tbr2 in unipolar brush cells (UBCs) of the cerebellum during development and adulthood. To further study UBCs and the role of Tbr2 in their development we examined UBC morphology in transgenic mouse lines (reporter and lineage tracer) and also examined the effects of Tbr2 deficiency in Tbr2 (MGI: Eomes) conditional knock-out (cKO) mice. In Tbr2 reporter and lineage tracer cerebellum, UBCs exhibited more complex morphologies than previously reported including multiple dendrites, bifurcating dendrites, and up to four dendritic brushes. We propose that “dendritic brush cells” (DBCs) may be a more apt nomenclature. In Tbr2 cKO cerebellum, mature UBCs were completely absent. Migration of UBC precursors from rhombic lip to cerebellar cortex and other nuclei was impaired in Tbr2 cKO mice. Our results indicate that UBC migration and differentiation are sensitive to Tbr2 deficiency. To investigate whether UBCs develop similarly in humans as in rodents, we studied Tbr2 expression in mid-gestational human cerebellum. Remarkably, Tbr2+ UBC precursors migrate along the same pathways in humans as in rodent cerebellum and disperse to create the same “fountain-like” appearance characteristic of UBCs exiting the rhombic lip.

scholarly journals Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Ye ◽  
Dandan Fan ◽  
Weiwei Xiong ◽  
Min Li ◽  
Jian Yuan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Squamous Cell ◽  
Metastatic Lymph Node ◽  
Regulatory Elements ◽  
Cell Proliferation And Migration ◽  
Active Enhancer ◽  
Chemical Inhibitors ◽  
And Migration ◽  
Proliferation And Migration

AbstractThe role of cis-elements and their aberrations remains unclear in esophageal squamous cell carcinoma (ESCC, further abbreviated EC). Here we survey 28 H3K27ac-marked active enhancer profiles and 50 transcriptomes in primary EC, metastatic lymph node cancer (LNC), and adjacent normal (Nor) esophageal tissues. Thousands of gained or lost enhancers and hundreds of altered putative super-enhancers are identified in EC and LNC samples respectively relative to Nor, with a large number of common gained or lost enhancers. Moreover, these differential enhancers contribute to the transcriptomic aberrations in ECs and LNCs. We also reveal putative driver onco-transcription factors, depletion of which diminishes cell proliferation and migration. The administration of chemical inhibitors to suppress the predicted targets of gained super-enhances reveals HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Thus, our epigenomic profiling reveals a compendium of reprogrammed cis-regulatory elements during ESCC carcinogenesis and metastasis for uncovering promising targets for cancer treatment.

Credit constraints and Rural Migration: Evidence from Six Villages in Uttar Pradesh

2018 ◽  
Vol 15 (3) ◽  
pp. 389-398
Author(s):  
Ruchi Singh
Keyword(s):  
Credit Constraints ◽  
Uttar Pradesh ◽  
Binary Logistic Regression ◽  
Binary Logistic Regression Model ◽  
Male Migration ◽  
Rural Economies ◽  
And Migration ◽  
The Relationship ◽  
The Empirical Analysis

Rural economies in developing countries are often characterized by credit constraints. Although few attempts have been made to understand the trends and patterns of male out-migration from Uttar Pradesh (UP), there is dearth of literature on the linkage between credit accessibility and male migration in rural Uttar Pradesh. The present study tries to fill this gap. The objective of this study is to assess the role of credit accessibility in determining rural male migration. A primary survey of 370 households was conducted in six villages of Jaunpur district in Uttar Pradesh. Simple statistical tools and a binary logistic regression model were used for analyzing the data. The result of the empirical analysis shows that various sources of credit and accessibility to them play a very important role in male migration in rural Uttar Pradesh. The study also found that the relationship between credit constraints and migration varies across various social groups in UP.

Role of microenvironment on proliferation and migration of an SDHB silenced murine Pheochromocytoma cell line

2017 ◽  
Author(s):  
Serena Martinelli ◽  
Vanessa D'Antongiovanni ◽  
Susan Richter ◽  
Letizia Canu ◽  
Tonino Ercolino ◽  
...  
Keyword(s):  
Cell Line ◽  
Pheochromocytoma Cell ◽  
And Migration ◽  
Proliferation And Migration

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Lymphatic Invasion ◽  
Cancer Specific Survival ◽  
Candidate Target ◽  
Candidate Target Gene ◽  
And Migration

TRIM44 has oncogenic roles in various cancers. However, TRIM44 expression andits function in renal cell carcinoma (RCC) are still unknown. Here in this study, weinvestigated the clinical significance of TRIM44 and its biological function in RCC.TRIM44 overexpression was significantly associated with clinical M stage, histologictype (clear cell) and presence of lymphatic invasion (P = .047, P = .005, and P = .028,respectively). Moreover, TRIM44 overexpression was significantly associated withpoor prognosis in terms of cancer-specific survival (P = .019). Gain-of-function andloss-of-function studies using TRIM44 and siTRIM44 transfection showed thatTRIM44 promotes cell proliferation and cell migration in two RCC cell lines, Caki1and 769P. To further investigate the role of TRIM44 in RCC, we performed integratedmicroarray analysis in Caki1 and 769P cells and explored the data in the Oncominedatabase. Interestingly, FRK was identified as a promising candidate target gene ofTRIM44, which was downregulated in RCC compared with normal renal tissues. Wefound that cell proliferation was inhibited by TRIM44 knockdown and then recoveredby siFRK treatment. Taken together, the present study revealed the associationbetween high expression of TRIM44 and poor prognosis in

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

scholarly journals Global dynamics of international migration systems across South–South, North–North, and North–South flows, 1990–2015

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Diego F. Leal ◽  
Nicolas L. Harder
Keyword(s):  
International Migration ◽  
Network Effects ◽  
Global Dynamics ◽  
Core Set ◽  
Migration Dynamics ◽  
Key Drivers ◽  
Migration Flows ◽  
And Migration ◽  
Migration Systems

AbstractEvidence from 184 countries over the span of 25 years is gathered and analyzed to understand North–North, South–South, and North–South international migration flows. Conceptually, the analysis borrows from network theory and Migration Systems Theory (MST) to develop a model to characterize the structure and evolution of international migration flows. Methodologically, the Stochastic Actor-oriented Model of network dynamics is used to jointly model the three types of flows under analysis. Results show that endogenous network effects at the monadic, dyadic, and triadic levels of analysis are relevant to understand the emergence and evolution of migration flows. The findings also show that a core set of non-network covariates, suggested by MST as key drivers of migration flows, does not always explain migration dynamics in the systems under analysis in a consistent fashion; thus, suggesting the existence of important levels of heterogeneity inherent to these three types of flows. Finally, evidence related to the role of political instability and countries’ care deficits is also discussed as part of the analysis. Overall, the results highlight the importance of analyzing flows across the globe beyond typically studied migratory corridors (e.g., North–South flows) or regions (e.g., Europe).

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