Enhanced Nonradiative Charge Recombination in Microfiber-Based Bismuthene.

After the first report of a graphene-based passive mode-locking ultrafast fiber laser, two-dimensional materials as efficient saturable absorbers offer a new horizon in ultrafast fiber laser. However, the interactions on atomic scale between these two-dimensional materials and fiber and the fiber effect on the carrier dynamics have not been realized. To figure out the exact role of fiber and the carrier dynamics affected by the fiber substrate related to ultrafast photonics, bismuthene, a newly reported 2D quantum material used in a passive mode-locking fiber laser, deposited on α-quartz has been investigated. We surprisingly found that the α-quartz substrate can strongly accelerate the nonradiative electron-hole recombination of bismuthene in theory, and the transient absorption spectra of bismuthene on normal glass and α-quartz further verify the substrate effect on carrier dynamics of bismuthene. The discovery provides new thinking about substrate effect to regulate the performance of ultrafast mode-locking fiber lasers as well as ultrafast photonics.

Ependyma-expressed CCN1 restricts the size of the neural stem cell pool in the adult ventricular-subventricular zone.

Adult neural stem cells (NSCs) reside in specialized niches, which hold a balanced number of NSCs, their progeny, and other cells. How niche capacity is regulated to contain a specific number of NSCs remains unclear. Here, we show that ependyma-derived matricellular protein CCN1 (cellular communication network factor 1) negatively regulates niche capacity and NSC number in the adult ventricular-subventricular zone (V-SVZ). Adult ependyma-specific deletion of Ccn1 transiently enhanced NSC proliferation and reduced neuronal differentiation in mice, increasing the numbers of NSCs and NSC units. Although proliferation of NSCs and neurogenesis seen in Ccn1 knockout mice eventually returned to normal, the expanded NSC pool was maintained in the V-SVZ until old age. Inhibition of EGFR signaling prevented expansion of the NSC population observed in CCN1 deficient mice. Thus, ependyma-derived CCN1 restricts NSC expansion in the adult brain to maintain the proper niche capacity of the V-SVZ.

Ultrafast nonlinear optical response of layered violet phosphorus for femtosecond noise-like pulse generation.

As a new member of two-dimensional (2D) phosphorene, 2D layered violet phosphorus (VP) has unique optoelectronic properties and good environmental stability, showing its huge advantages in optoelectronic applications. In this paper, the ultrafast nonlinear optical (NLO) properties of layered VP nanosheets at 1 µm band were explored, which exhibit an obvious saturable absorption response with a modulation depth of ∼1.97%. Meanwhile, the fast and slow carrier lifetimes of VP nanosheets at 1µm band were also determined as 295.9 fs and 2.36 ps, respectively, which are much shorter than that of most reported 2D materials. The excellent saturable absorption response combined with ultrashort carrier lifetimes indicate the prospect of layered VP nanosheets as a fast saturable absorber (SA) for ultrafast laser modulation. Then we demonstrated a Yb-doped fiber laser based on the VP-deposited taper-shaped fiber (TSF) SA, which delivers stable Q-switched mode-locked (QSML) pulses, dual-wavelength mode-locked pulses and 404-fs noise-like pulses. This work fully demonstrates the great potential of 2D VP materials for 1 µm ultrashort laser pulse generation.

Diode-pumped Tm:YAP laser operating at 2.3†µm with enhanced performance through cascade lasing.

The laser diode (LD)-pumped Tm:YAP (a-cut, 3.5 at.%) laser generated a maximum ∼2.3 µm continuous wave (CW) laser output power of ∼3 W. The higher output power benefited from the positive effect of the cascade lasing (simultaneously operating on the 3H4 → 3H5 and 3F4 → 3H6 Tm3+ transition). It was the highest CW laser output power amongst the LD/Ti:Sapphire-CW-pumped ∼2.3 µm Tm3+-doped lasers reported so far. Under the cascade laser operation, the slope efficiency of the ∼2.3 µm laser emission versus the absorbed pump power increased from 13.0% to 21.4%.

Polarized spectral properties and 2.3†µm laser performance of the Tm:YVO4 crystal.

The polarized spectral properties and ∼2.3 µm high-power continuous-wave laser operation of Tm3+-doped yttrium orthovanadate crystal (Tm:YVO4) are reported. For the 3H4 → 3H5 transition, the stimulated-emission cross-section σSE is 1.01 × 10-20 cm2 at 2276 nm corresponding to a large emission bandwidth of 52 nm (for π-polarization). Pumped by a 794 nm laser diode, the 1.5 at.% Tm:YVO4 laser delivered 5.52 W at 2.29 µm with a slope efficiency of 19.9%, a laser threshold of 8.70 W, and a linear laser polarization (π). The Tm laser operated on the cascade scheme (on the 3H4 → 3H5 and 3F4 → 3H6 transitions) which was mainly responsible for the observed high laser slope efficiency. We also report on the first passively Q-switched Tm:YVO4 laser at 2.3 µm by employing porous nano-grained cuprous selenide (PNG-Cu2Se) as a saturable absorber. The shortest pulse duration and the highest single pulse energy amounted to 706 ns and 3.65 µJ, respectively, corresponding to a pulse repetition rate of 62.8 kHz.

Crystal growth, polarized spectral properties, and 2.3†µm laser performance of Tm:LuVO4 crystal.

We report on the Czochralski crystal growth, polarized optical spectroscopy, and the first continuous-wave laser operation of 1.5 at.% Tm:LuVO4 crystal on the 3H4 → 3H5 transition. The polarized absorption and stimulated-emission properties of Tm3+ ions in LuVO4 were revised and the crystal-field splitting of the Tm3+ multiplets was determined by low-temperature (12 K) spectroscopy. The maximum stimulated-emission cross-section for the 3H4 → 3H5 transition is 2.48 × 10-20 cm2 at 2363 nm for π-polarization corresponding to an emission bandwidth of 28 nm. Evidence of phonon-assisted emissions of Tm3+ ions above 2 µm is presented. The broadband emission properties of the Tm:LuVO4 crystal make it promising for ultrashort pulse generation. Additionally, pumped by a 796 nm fiber-coupled laser diode, the Tm:LuVO4 laser generated a Watt-level output power at 2279-2295 nm with a slope efficiency of 9.2% and linearly polarized emission (π-polarization).

Bosea beijingensis sp. nov., Telluria beijingensis sp. nov. and Agrococcus beijingensis sp. nov., isolated from baijiu mash.

The baijiu fermentation environment hosts a variety of micro-organisms, some of which still remain uncultured and uncharacterized. In this study, the isolation, cultivation and characterization of three novel aerobic bacterial strains are described. The cells of strain REN20T were Gram-negative, strictly aerobic, motile and grew at 26-37 °C, at pH 6.0-9.0 and in the presence of 0-5.0   % (w/v) NaCl. The cells of strain REN29T were Gram-negative, strictly aerobic, motile and grew at 15-30 °C, at pH 6.0-9.0 and in the presence of 0-10.0   % (w/v) NaCl. The cells of strain REN33T were Gram-positive, strictly aerobic, motile and grew at 15-37 °C, at pH 5.0-10.0 and in the presence of 0-7.0   % (w/v) NaCl. The digital DNA-DNA hybridization and average nucleotide identity by orthology values between type strains in related genera and REN20T (20.3-36.8 % and 79.8-89.9  %), REN29T (20.3-36.8  % and 74.5-88.5  %) and REN33T (22.6-48.6  % and 75.8-84.2  %) were below the standard cut-off criteria for the delineation of bacterial species, respectively. Based on polyphasic taxonomy analysis, we propose three new species, Bosea beijingensis sp. nov. (=REN20T=GDMCC 1.2894T=JCM 35118T), Telluria beijingensis sp. nov. (=REN29T=GDMCC 1.2896T=JCM 35119T) and Agrococcus beijingensis sp. nov. (=REN33T=GDMCC 1.2898T=JCM 35164T), which were recovered during cultivation and isolation from baijiu mash.

Establishing a protected area network in Xinlong with other effective area-based conservation measures.

Protected areas (PAs) are pivotal to biodiversity conservation, yet their efficacy is compromised by insufficient funding and management. So-called other effective area-based conservation measures (OECMs) present a paradigm shift and address PA limitations. Such measures can expand conservation areas, enhance connectivity, and improve the existing system. To assess the conservation status of biodiversity in Tibetan cultural areas in China, we investigated the spatial distribution of wildlife vulnerable to human disturbance (large- and medium-sized mammals and terrestrial birds) in Xinlong, a traditional Tibetan cultural area. In particular, we compared a PA (Xionglongxi Nature Reserve) and OECMs targeting species conservation. We also investigated the relationship of wildlife with human temporal and spatial activities. The OECMs complemented areas not covered by PA, especially in rich understory biodiversity regions. More species in OECMs tolerated human presence than species in the PA. Existing biodiversity reserves failed to cover areas of high conservation value in Tibet and offered limited protection capacity. Expanding PAs and identifying OECMs improved Xinlong's system by covering most biodiversity hotspots. Building on the tradition of wildlife conservation in Tibet, harnessing OECMs may be an effective means of augmenting biodiversity conservation capacity. We recommend further evaluation of OECMs effectiveness and coverage in Tibetan area as a way to enhance the current PA system.

自然保护地(protected areas, PAs)被认为是生物多样性保护的最重要且最有效的措施之一。然而, 由于资金不足和管理缺失等因素, 自然保护地体系的有效性被大幅度削弱。"其他有效的基于区域的保护措施(other effective area­based conservation measures, OECMs)"引起了基于区域的保护范式转变, 能够有效弥补PAs的不足。OECMs能够有效实现保护面积的扩大, 加强保护地之间的连通性, 完善现有保护地体系。基于此, 为进一步了解中国藏文化地区生物多样性的保护情况, 评估PAs和OECMs在物种保护上的差异。我们以中国新龙县为例, 调查了当地大中型哺乳动物和地栖鸟类这类容易受人为干扰的野生动物的空间分布和与人类互作的时空活动关系。结果表明, 在保护区无法覆盖的区域, OECMs能够提供有效的补充, 如林下区域的生物多样性保护。在OECMs范围内, 更多的物种能够在时空活动上容忍人类的存在, 尤其是猎物物种。在当前生物多样性优先保护区无法涵盖藏区高保护价值区域以及现有保护区保护能力有限的情况下, 藏区野生动物的保护需要采取更多针对性的措施。通过扩大保护区和确定OECMs区域, 能够覆盖新龙绝大部分生物多样性热点地区。鉴于藏区的野生动物保护传统, 借助OECMs的力量是完善和提高藏区生物多样性保护保护能力的有效手段。我们建议未来进一步评估藏区的OECMs的有效性及覆盖情况, 完善自然保护地体系。 基于其他有效的区域保护措施的中国新龙县保护地体系构建.

Mechanistic insights into central spindle assembly mediated by the centralspindlin complex.

The central spindle spatially and temporally regulates the formation of division plane during cytokinesis in animal cells. The heterotetrameric centralspindlin complex bundles microtubules to assemble the central spindle, the mechanism of which is poorly understood. Here, we determined the crystal structures of the molecular backbone of ZEN-4/CYK-4 centralspindlin from Caenorhabditis elegans, which revealed the detailed mechanism of complex formation. The molecular backbone of centralspindlin has the intrinsic propensity to undergo liquid-liquid phase separation. The condensation of centralspindlin requires two patches of basic residues at ZEN-4 and multiple acidic residues at the intrinsically disordered region of CYK-4, explaining the synergy of the two subunits for the function. These complementary charged residues were critical for the microtubule bundling activity of centralspindlin in vitro and for the assembly of the central spindle in vivo. Together, our findings provide insights into the mechanism of central spindle assembly mediated by centralspindlin through charge-driven macromolecular condensation.

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles.

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

Prefrontal GABAA(δ)R Promotes Fear Extinction through Enabling the Plastic Regulation of Neuronal Intrinsic Excitability.

Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABAA receptors (GABAARs). GABAARs consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, δ-subunit-containing GABAARs [GABAA(δ)Rs], had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAAR family. First, the fear extinction in individual mice was positively correlated with the level of GABAA(δ)R expression and function in their mPFC. Second, knockdown of GABAA(δ)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABAA(δ)R-deficient mice also showed fear extinction deficits, and re-expressing GABAA(δ)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABAA(δ)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABAA(δ)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABAA receptors in fear extinction through a route relying on nonsynaptic plasticity.SIGNIFICANCE STATEMENT The medial prefrontal cortex (mPFC) is one of the kernel brain regions engaged in fear extinction. Previous studies have repetitively shown that the GABAA receptor (GABAAR) family in this region act to suppress fear extinction. However, the roles of specific GABAAR subtypes in mPFC are largely unknown. We observed that the GABAAR-containing δ-subunit [GABAA(δ)R], a subtype of GABAARs exclusively situated in the extrasynaptic membrane and mediating the tonic neuronal inhibition, works oppositely to the whole GABAAR family and promotes (but does not suppress) fear extinction. More interestingly, in striking contrast to the synaptic GABAARs that suppress fear extinction by breaking the extinction-evoked plasticity of glutamatergic transmission, the GABAA(δ)R promotes fear extinction through enabling the plastic regulation of neuronal excitability in the infralimbic subregion of mPFC. Our findings thus reveal an unconventional role of GABAA(δ)R in promoting fear extinction through a route relying on nonsynaptic plasticity.

Blood Pressure, Hypertension, and the Risk of Aortic Dissection Incidence and Mortality: Results From the J-SCH Study, the UK Biobank Study, and a Meta-Analysis of Cohort Studies.

BACKGROUND: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies on this topic have been published. We investigated the association between hypertension/elevated BP and AD in 2 cohorts and conducted a meta-analysis of published prospective studies, including these 2 studies. METHODS: We analyzed data from the J-SHC study (Japan-Specific Health Checkups) and UK Biobank, which prospectively followed up 534 378 and 502 424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks were calculated with random-effects models. A potential nonlinear dose-response relationship between BP and AD was tested with fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. RESULTS: In the J-SHC study and UK Biobank, there were 84 and 182 ADs during the 4- and 9-year follow-up, and the adjusted hazard ratios of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI, 1.78-4.04) in hypertensive individuals, 1.33 (95% CI, 1.05-1.68) and 1.27 (95% CI, 1.11-1.48) per 20-mm Hg increase in systolic BP (SBP), and 1.67 (95% CI, 1.40-2.00) and 1.66 (95% CI, 1.46-1.89) per 10-mm Hg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary relative risks were 3.07 (95% CI, 2.15-4.38, I2=76.7%, n=7 studies, 2818 ADs, 4 563 501 participants) for hypertension and 1.39 (95% CI, 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2 = 57.0%, n=3) per 20-mm Hg increase in SBP and per 10-mm Hg increase in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mm Hg and DBP >75 mm Hg. CONCLUSIONS: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

Protectin Conjugates in Tissue Regeneration 1 Inhibits Macrophage Pyroptosis by Restricting NLRP3 Inflammasome Assembly to Mitigate Sepsis via the cAMP-PKA Pathway.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.

Third-order optical nonlinearity and passively Q-switching operation with BiOCl nanosheets at 1.3†µm.

In this contribution, we measured the third-order nonlinear optical response of bismuth oxychloride (BiOCl) nanosheets with the open-aperture (OA) and the closed-aperture (CA) Z-scan techniques with a variable excitation intensity at 1.34 µm. The effective nonlinear absorption coefficient ßeff and the nonlinear refractive index n2 of the prepared BiOCl nanosheets with abundant oxygen vacancies were obtained under the excitation intensity. The third-order nonlinear optical susceptibility |χ(3)| was 1.64 × 10-9 esu. The nonlinear optical features of BiOCl enabled it as a superb saturable absorber for pulse laser generation. As a consequence, we demonstrated the first passively Q-switched Nd:GdVO4 laser with the BiOCl saturable absorber, producing a shortest pulse duration of 543 ns and a highest repetition rate of 227 kHz, leading to a maximum pulse energy of 74 nJ. Our findings show that BiOCl nanosheets with oxygen vacancies have large nonlinear optical sensitivities and can be exploited to generate optical pulses.

Diode-pumped efficient high-power cascade Tm:GdVO4 laser simultaneously operating at ∼2†µm and ∼2.3 µm.

The laser diode (LD)-pumped efficient high-power cascade Tm:GdVO4 laser simultaneously operating on the 3F4 → 3H6 (at ∼2 µm) and 3H4 → 3H5 (at ∼2.3 µm) Tm3+ transition was first reported in this paper. The cascade Tm:GdVO4 laser generated a maximum total continuous-wave (CW) laser output power of 8.42 W with a slope efficiency of 40%, out of which the maximum ∼2.3 µm CW laser output power was 2.88 W with a slope efficiency of 14%. To our knowledge, 2.88 W is the highest CW laser output power amongst the LD-CW-pumped ∼2.3 µm Tm3+-doped lasers reported so far.

Optical absorption of bismuthene with a single vacancy: first-principle calculations.

The exceptional mechanical, electronic, topological, and optical properties, make bismuthene an ideal candidate for various applications in ultrafast saturation absorption and spintronics. Despite the extensive research efforts devoted to synthesizing this material, the introduction of defects, which can significantly affect its properties, remains a substantial obstacle. In this study, we investigate the transition dipole moment and joint density of states of bismuthene with/without single vacancy defect via energy band theory and interband transition theory. It is demonstrated that the existence of the single defect enhances the dipole transition and joint density of states at lower photon energies, ultimately resulting in an additional absorption peak in the absorption spectrum. Our results suggest that the manipulation of defects in bismuthene has enormous potential for improving the optoelectronic properties of this material.

Cascade lasing at ∼2†µm and ∼2.3†µm in a diode-pumped Tm:YVO4 laser.

We report on the cascade continuous-wave operation of a diode-pumped Tm:YVO4 laser on the 3F4 → 3H6 (at ∼2 µm) and 3H4 → 3H5 (at ∼2.3 µm) Tm3+ transitions. Pumped with a fiber-coupled spatially multimode 794 nm AlGaAs laser diode, the 1.5 at.% Tm:YVO4 laser yielded a maximum total output power of 6.09 W with a slope efficiency of 35.7% out of which the 3H4 → 3H5 laser emission corresponded to 1.15 W at 2291-2295 and 2362-2371 nm with a slope efficiency of 7.9% and a laser threshold of 6.25 W.

Six-watt diode-pumped Tm:GdVO4 laser at 2.29†µm.

A compact Tm:GdVO4 laser pumped by a 794 nm laser diode generated 6.09 W at 2.29 µm (3H4 → 3H5 Tm3+ transition) with a high slope efficiency of 30.8% and linear laser polarization (π). The polarized spectroscopic properties of Tm3+ in GdVO4 were also revised. The peak stimulated-emission cross section of Tm3+ is 2.97 × 10-20 cm2 at 2280 nm, corresponding to an emission bandwidth of 42 nm for π-polarized light.

An efficient model-free approach to interaction screening for high dimensional data.

An innovated model-free interaction screening procedure called the MCVIS is proposed for high dimensional data analysis. Specifically, we adopt the introduced MCV index for quantifying the importance of an interaction effect among predictors. Our proposed method is fully nonparametric and is capable of successfully selecting interactions even if the signal of parental main effects is weak. The MCVIS procedure has many distinctive features: (i) it can work with discrete, categorical and continuous covariates; (ii) it can deal with both categorical and continuous response, even handle the missing response; (iii) it is robust for heavy-tailed distributions, thus well accommodates heterogeneity typically caused by high dimensionality; (iv) it enjoys the sure screening and ranking consistency properties, therefore achieves dimension reduction without information loss. In another respect, computational feasibility is a top concern in high dimensional data analysis, by transforming our MCV into several variants, the MCVIS procedure is simple and fast to implement. Extensive numerical experiments and comparisons confirm the effectiveness and wide applicability of our MCVIS procedure. We further illustrate the proposed methodology by empirical study of two real datasets. Supplementary materials are available online.

Structure and regulation of human epithelial cell transforming 2 protein.

Epithelial cell transforming 2 (Ect2) protein activates Rho GTPases and controls cytokinesis and many other cellular processes. Dysregulation of Ect2 is associated with various cancers. Here, we report the crystal structure of human Ect2 and complementary mechanistic analyses. The data show the C-terminal PH domain of Ect2 folds back and blocks the canonical RhoA-binding site at the catalytic center of the DH domain, providing a mechanism of Ect2 autoinhibition. Ect2 is activated by binding of GTP-bound RhoA to the PH domain, which suggests an allosteric mechanism of Ect2 activation and a positive-feedback loop reinforcing RhoA signaling. This bimodal RhoA binding of Ect2 is unusual and was confirmed with Förster resonance energy transfer (FRET) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) analyses. Several recurrent cancer-associated mutations map to the catalytic and regulatory interfaces, and dysregulate Ect2 in vitro and in vivo. Together, our findings provide mechanistic insights into Ect2 regulation in normal cells and under disease conditions.