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1.
EMBO J ; 36(3): 334-345, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011581

RESUMO

Precise positioning of cells is crucial for metazoan development. Despite immense progress in the elucidation of the attractive cues of cell migration, the repulsive mechanisms that prevent the formation of secondary leading edges remain less investigated. Here, we demonstrate that Caenorhabditis elegans Hippo kinases promote cell migration along the anterior-posterior body axis via the inhibition of dorsal-ventral (DV) migration. Ectopic DV polarization was also demonstrated in gain-of-function mutant animals for C. elegans RhoG MIG-2. We identified serine 139 of MIG-2 as a novel conserved Hippo kinase phosphorylation site and demonstrated that purified Hippo kinases directly phosphorylate MIG-2S139 Live imaging analysis of genome-edited animals indicates that MIG-2S139 phosphorylation impedes actin assembly in migrating cells. Intriguingly, Hippo kinases are excluded from the leading edge in wild-type cells, while MIG-2 loss induces uniform distribution of Hippo kinases. We provide evidence that Hippo kinases inhibit RhoG activity locally and are in turn restricted to the cell body by RhoG-mediated polarization. Therefore, we propose that the Hippo-RhoG feedback regulation maintains cell polarity during directional cell motility.


Assuntos
Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/fisiologia , Movimento Celular , Polaridade Celular , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Actinas/metabolismo , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Retroalimentação Fisiológica , Fosforilação , Multimerização Proteica , Processamento de Proteína Pós-Traducional , Proteínas rac de Ligação ao GTP/metabolismo
2.
Science ; 382(6675): eadf8486, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38060664

RESUMO

The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed spatial transcriptomics of variable, diversity, and joining (VDJ) sequences (Spatial VDJ), a method that maps B cell and T cell receptor sequences in human tissue sections. Spatial VDJ captures lymphocyte clones that match canonical B and T cell distributions and amplifies clonal sequences confirmed by orthogonal methods. We found spatial congruency between paired receptor chains, developed a computational framework to predict receptor pairs, and linked the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity and lineage trajectories within their anatomical niche. Thus, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, providing a platform to harness clonal sequences for therapy.


Assuntos
Linfócitos B , Receptores de Células Precursoras de Linfócitos B , Receptores de Antígenos de Linfócitos T , Linfócitos T , Humanos , Linfócitos B/metabolismo , Células Clonais/metabolismo , Perfilação da Expressão Gênica/métodos , Receptores de Células Precursoras de Linfócitos B/genética , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/metabolismo
3.
Phys Rev E ; 104(3-1): 034420, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34654118

RESUMO

Anticipation is the phenomenon in which the response of a system is predictive of the stimulation. The encoding of stochastic light intensity (x) into spikes is investigated in an experiment with retinas from bullfrogs to understand the mechanism of anticipation of a retina. Partial information decomposition of the mutual information between the spike rates and the joint state {x,x[over ̇]} is found to be consistent with the encoding by the linear combination of x and x[over ̇] where x[over ̇] is the rate of change of x. This spike rate encoding form indicates that a retina is capable of anticipation based on the synergistic information generation between x and x[over ̇]. Our results suggest that illusions such as the anticipation studied here during retinal perception can originate from the recombination of information extracted in the retinal network.

4.
Cell Stem Cell ; 28(1): 63-78.e7, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33053374

RESUMO

Enormous amounts of essential intracellular events are crowdedly packed inside picoliter-sized cellular space. However, the significance of the physical properties of cells remains underappreciated because of a lack of evidence of how they affect cellular functionalities. Here, we show that volumetric compression regulates the growth of intestinal organoids by modifying intracellular crowding and elevating Wnt/ß-catenin signaling. Intracellular crowding varies upon stimulation by different types of extracellular physical/mechanical cues and leads to significant enhancement of Wnt/ß-catenin signaling by stabilizing the LRP6 signalosome. By enhancing intracellular crowding using osmotic and mechanical compression, we show that expansion of intestinal organoids was facilitated through elevated Wnt/ß-catenin signaling and greater intestinal stem cell (ISC) self-renewal. Our results provide an entry point for understanding how intracellular crowdedness functions as a physical regulator linking extracellular physical cues with intracellular signaling and potentially facilitate the design of engineering approaches for expansion of stem cells and organoids.


Assuntos
Organoides , beta Catenina , Autorrenovação Celular , Organoides/metabolismo , Células-Tronco/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
5.
Open Life Sci ; 15(1): 466-475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33817235

RESUMO

To determine the toxic effect of three imidazole ionic liquids (IILs) in terrestrial monocotyledonous and dicotyledonous plants, three IILs (1-butyl-3-methylimidazole tetrafluoroborate, 1-butyl-3-methylimidazole hexafluorophosphate, and butyl-3-methylimidazolium bi-[(trifluoromethyl)sulfonyl]imide) were investigated using rice and capsicum as target toxicity models. In hydroponic experiments, increasing the concentration of the IILs led to a decrease in the seed germination rate, a decrease in the reduced stem and root lengths, and an increase in the inhibition rate of the stem and root lengths; in addition, as the concentration increased, the reducing sugar content of rice and capsicum seedling leaves and roots first increased and then decreased, while permeability of the cell membranes of the stems and roots of the two plants also gradually increased. In terms of the effects on these indices in rice, the ranking of these three IIL anions was [TF2N]- > [PF6]- > [BF4]-; in terms of the effects on capsicum, the sequence was [BF4]- > [TF2N]- > [PF6]-. These findings provide a theoretical reference for the next step in the synthesis and the use of green ionic liquids.

6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(7): 615-7, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19961732

RESUMO

OBJECTIVE: To compare the value of dipyridamole (201)Tl Single photon emission computed tomography (SPECT) myocardial imaging and exercise myocardial (99)Tc(m)-MIBI SPECT imaging on diagnosing cardiac syndrome X. METHODS: Sixty-three patients with known cardiac syndrome X were divided into dipyridamole (201)Tl SPECT myocardial imaging group (group 1, n = 35) and exercise myocardial (99)Tc(m)-MIBI-SPECT imaging group (group 2, n = 28) and the diagnostic accuracy rates were compared. RESULTS: Thirty-one out of 35 cardiac syndrome X patients showed reverse redistribution in group 1 and the diagnostic accuracy rate was 89%. Positive test results were evidenced 24 out of 28 cardiac syndrome X patients in group 2 and the diagnostic accuracy rate was 87% (P > 0.05 vs. group 1). CONCLUSION: The diagnostic accuracy rates of these two myocardial imaging methods were satisfactory and comparable on detecting cardiac syndrome X.


Assuntos
Dipiridamol , Angina Microvascular/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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