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1.
J Am Chem Soc ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832750

RESUMO

Dimerized quantum magnets are exotic crystalline materials where Bose-Einstein condensation of magnetic excitations can happen. However, known dimerized quantum magnets are limited to only a few oxides and halides. Here, we unveil 9 dimerized quantum magnets and 11 conventional antiferromagnets in ternary metal borides MTB4 (M = Sc, Y, La, Ce, Lu, Mg, Ca, and Al; T = V, Cr, Mn, Fe, Co, and Ni), where T atoms are arranged in structural dimers. Quantum magnetism in these compounds is dominated by strong antiferromagnetic (AFM) interactions between Cr (Cr and Mn for M = Mg and Ca) atoms within the dimers, with much weaker interactions between the dimers. These systems are proposed to be close to a quantum critical point between a disordered singlet spin-dimer phase, with a spin gap, and the ordered conventional Néel AFM phase. They greatly enrich the materials inventory that allows investigations of the spin-gap phase. Conventional antiferromagnetism in these compounds is dominated by ferromagnetic Mn (Fe for M = Mg and Ca) interactions within the dimers. The predicted stable and nonmagnetic (NM) YFeB4 phase is synthesized and characterized, providing a scarce candidate to study Fe dimers and Fe ladders in borides. The identified quantum, conventional, and NM systems provide a platform with abundant possibilities to tune the magnetic exchange coupling by doping and study the unconventional quantum phase transition and conventional magnetic transitions. This work opens new avenues for studying novel magnetism in borides arising from spin dimers and establishes a theoretical workflow for future searches for dimerized quantum magnets in other families of materials.

2.
J Cell Sci ; 134(7)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33758078

RESUMO

Centriole duplication is tightly controlled to maintain correct centriole number through the cell cycle. Key to this is the regulated degradation of PLK4, the master regulator of centriole duplication. Here, we show that the Rac1 guanine nucleotide exchange factor (GEF) Tiam1 localises to centrosomes during S-phase, where it is required for the maintenance of normal centriole number. Depletion of Tiam1 leads to an increase in centrosomal PLK4 and centriole overduplication, whereas overexpression of Tiam1 can restrict centriole overduplication. Ultimately, Tiam1 depletion leads to lagging chromosomes at anaphase and aneuploidy, which are potential drivers of malignant progression. The effects of Tiam1 depletion on centrosomal PLK4 levels and centriole overduplication can be rescued by re-expression of both wild-type Tiam1 and catalytically inactive (GEF*) Tiam1, but not by Tiam1 mutants unable to bind to the F-box protein ßTRCP (also known as F-box/WD repeat-containing protein 1A) implying that Tiam1 regulates PLK4 levels through promoting ßTRCP-mediated degradation independently of Rac1 activation.


Assuntos
Centríolos , Proteínas Serina-Treonina Quinases , Ciclo Celular , Proteínas de Ciclo Celular/genética , Centrossomo
3.
J Cell Sci ; 132(14)2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31289196

RESUMO

Oriented cell divisions are important for the formation of normal epithelial structures. Dlg1, a tumour suppressor, is required for mitotic spindle orientation in Drosophila epithelia and chick neuroepithelia, but how Dlg1 is localised to the membrane and its importance in mammalian epithelia are unknown. We show that Dlg1 is required in non-transformed mammalian epithelial cells for oriented cell divisions and normal lumen formation. We demonstrate that the MAGUK protein CASK, a membrane-associated scaffold, is the factor responsible for Dlg1 membrane localisation during spindle orientation, thereby identifying a new cellular function for CASK. Depletion of CASK leads to misoriented divisions in 3D, and to the formation of multilumen structures in cultured kidney and breast epithelial cells. Blocking the CASK-Dlg1 interaction with an interfering peptide, or by deletion of the CASK-interaction domain of Dlg1, disrupts spindle orientation and causes multilumen formation. We show that the CASK-Dlg1 interaction is important for localisation of the canonical LGN-NuMA complex known to be required for spindle orientation. These results establish the importance of the CASK-Dlg1 interaction in oriented cell division and epithelial integrity.This article has an associated First Person interview with the first author of the paper.


Assuntos
Proteína 1 Homóloga a Discs-Large/metabolismo , Epitélio/metabolismo , Guanilato Quinases/metabolismo , Mitose , Fuso Acromático/metabolismo , Animais , Membrana Celular/metabolismo , Cães , Células Madin Darby de Rim Canino , Mamíferos , Ligação Proteica
4.
Chem Mater ; 36(9): 4542-4552, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38764751

RESUMO

Tin-based semiconductors are highly desirable materials for energy applications due to their low toxicity and biocompatibility relative to analogous lead-based semiconductors. In particular, tin-based chalcohalides possess optoelectronic properties that are ideal for photovoltaic and photocatalytic applications. In addition, they are believed to benefit from increased stability compared with halide perovskites. However, to fully realize their potential, it is first necessary to better understand and predict the synthesis and phase evolution of these complex materials. Here, we describe a versatile solution-phase method for the preparation of the multinary tin chalcohalide semiconductors Sn2SbS2I3, Sn2BiS2I3, Sn2BiSI5, and Sn2SI2. We demonstrate how certain thiocyanate precursors are selective toward the synthesis of chalcohalides, thus preventing the formation of binary and other lower order impurities rather than the preferred multinary compositions. Critically, we utilized 119Sn ssNMR spectroscopy to further assess the phase purity of these materials. Further, we validate that the tin chalcohalides exhibit excellent water stability under ambient conditions, as well as remarkable resistance to heat over time compared to halide perovskites. Together, this work enables the isolation of lead-free, stable, direct band gap chalcohalide compositions that will help engineer more stable and biocompatible semiconductors and devices.

5.
Chem Commun (Camb) ; 58(55): 7622-7625, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35712888

RESUMO

A series of novel semiconductors AAe6Si12P20X (A = Na, K, Rb, Cs; Ae = Sr, Ba; X = Cl, Br, I) is reported. Their crystal structures feature a tetrahedral Si-P framework with large zeolite-like pores hosting two types of cations, monoatomic A+ and unprecedented octahedral X@Ae611+. Mixing of the A and Ba cations was detected by single crystal X-ray diffraction and confirmed by multinuclear solid state NMR. The reported compounds are highly stable semiconductors with a bandgap range from 1.4 to 2.0 eV.

6.
Small GTPases ; 7(3): 123-38, 2016 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-27104658

RESUMO

In vitro and in vivo studies and evidence from human tumors have long implicated Rho GTPase signaling in the formation and dissemination of a range of cancers. Recently next generation sequencing has identified direct mutations of Rho GTPases in human cancers. Moreover, the effects of ablating genes encoding Rho GTPases and their regulators in mouse models, or through pharmacological inhibition, strongly suggests that targeting Rho GTPase signaling could constitute an effective treatment. In this review we will explore the various ways in which Rho signaling can be deregulated in human cancers.


Assuntos
Neoplasias/enzimologia , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Variações do Número de Cópias de DNA , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteínas rho de Ligação ao GTP/antagonistas & inibidores , Proteínas rho de Ligação ao GTP/genética
7.
Exp Biol Med (Maywood) ; 240(1): 3-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25583953

RESUMO

The new cover of Experimental Biology and Medicine features the hermeneutic circle of biology, a concept we have adapted from the hermeneutic principle that one understands the whole only in terms of each part and the parts only in terms of the whole. Our hermeneutic circle summarizes the course of experimental biology through 2500 years of the achievements of reductionist research (understanding the parts), which culminates in our ability to rapidly sequence the genome. Rather than returning along the same path in a constructionist approach that simply builds upon this knowledge, but in reverse, an alternative is to close the circle with synthetic constructions that seek to integrate the full complexity of biological and physiological systems (understanding the whole), of which organs-on-chips are one example. This closing of the circle cannot be a comprehensively accurate representation of biology, but it can be a synthetic one that effectively defines particular biological subsystems. The illustration of the hermeneutic circle of biology is also intended to suggest both the multiple cycles that may be required to reach such a synthesis and the expansion of the circle in an outward spiral as knowledge increases. Our commentary explains the symbolism of the new cover in a philosophical and scientific discussion.


Assuntos
Biologia Molecular/tendências , Biologia de Sistemas/tendências , Animais , Humanos
8.
Nat Commun ; 6: 7437, 2015 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-26078008

RESUMO

Centrosome separation is critical for bipolar spindle formation and the accurate segregation of chromosomes during mammalian cell mitosis. Kinesin-5 (Eg5) is a microtubule motor essential for centrosome separation, and Tiam1 and its substrate Rac antagonize Eg5-dependent centrosome separation in early mitosis promoting efficient chromosome congression. Here we identify S1466 of Tiam1 as a novel Cdk1 site whose phosphorylation is required for the mitotic function of Tiam1. We find that this phosphorylation of Tiam1 is required for the activation of group I p21-activated kinases (Paks) on centrosomes in prophase. Further, we show that both Pak1 and Pak2 counteract centrosome separation in a kinase-dependent manner and demonstrate that they act downstream of Tiam1. We also show that depletion of Pak1/2 allows cells to escape monopolar arrest by Eg5 inhibition, highlighting the potential importance of this signalling pathway for the development of Eg5 inhibitors as cancer therapeutics.


Assuntos
Centrossomo/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Fuso Acromático/metabolismo , Animais , Proteína Quinase CDC2/metabolismo , Cães , Células HEK293 , Humanos , Cinesinas/metabolismo , Células Madin Darby de Rim Canino , Camundongos , Fosforilação , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Proteínas rac de Ligação ao GTP
9.
Nat Cell Biol ; 14(11): 1169-80, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23103911

RESUMO

Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify ß2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly ß2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that ß2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, ß2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that ß2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polarity.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas Associadas à Distrofina/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas de Membrana/metabolismo , Junções Íntimas/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Linhagem Celular , Polaridade Celular/efeitos dos fármacos , Cães , Doxiciclina/farmacologia , Proteínas Associadas à Distrofina/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Imuno-Histoquímica , Espectrometria de Massas , Proteínas de Membrana/genética , Microscopia de Fluorescência , Junções Íntimas/efeitos dos fármacos , Proteínas rac de Ligação ao GTP/genética
10.
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