Recent Structural Models Research Articles

Spectator Exciton Effects in Nanocrystals III: Unveiling the Stimulated Emission Cross Section in Quantum Confined CsPbBr3 Nanocrystals.

Quantifying stimulated emission in semiconductor nanocrystals (NCs) remains challenging due to masking of its effects on pump-probe spectra by excited state absorption and ground state bleaching signals. The absence of this defining photophysical parameter in turn impedes assignment of band edge electronic structure in many of these important fluorophores. Here we employ a generally applicable 3-pulse ultrafast spectroscopic method coined the "Spectator Exciton" (SX) approach to measure stimulated-emission efficiency in quantum confined inorganic perovskite CsPbBr3 NCs, the band edge electronic structure of which is the subject of lively ongoing debate. Our results show that in 5-6 nm CsPbBr3 NCs, a single exciton bleaches more than half of the intense band edge absorption band, while the cross section for stimulated emission from the same state is nearly 6 times weaker. Discussion of these findings in light of several recent electronic structure models for this material proves them unable to simultaneously explain both measures, proving the importance of this new input to resolving this debate. Along with femtosecond time-resolved photoluminescence measurements on the same sample, SX results also verify that biexciton interaction energy is intensely attractive with a magnitude of ∼80 meV. In light of this observation, our previous suggestion that biexciton interaction is repulsive is reassigned to hot phonon induced slowdown of carrier relaxation leading to direct Auger recombination from an excited state. The mechanism behind the extreme slowing of carrier cooling after several stages of exciton recombination remains to be determined.

Quick-commerce: green initiatives on customer brand engagement

PurposeThe study examines quick-commerce (Q-commerce) green initiatives' (GI') impact on consumer brand engagement by mediating [perceived value (PV) and environmental concern (EC)] and moderating (brand attitude).Design/methodology/approachThe study gathered 458 surveys from recent Q-commerce shoppers, employing measurement and structural models alongside the PROCESS macro for data analysis.FindingsThe findings of the study indicate that (1) Q-commerce GI significantly affect PV, EC and directly impact customer brand engagement (CBE). The mediation analysis reveals that (2) PV positively influences EC and CBE; (3) EC has a favorable impact on CBE and (4) CBE positively affects brand attachment (Batta) and green-word of mouth (GWOM).Originality/valueThis study contributes to a deeper understanding of how Q-commerce's GI shape consumer brand engagement behavior. The insights provided can guide Q-commerce players and policymakers in the development and implementation of effective green practices.

Mechanistic implications of the ternary complex structural models for the photoenzyme protochlorophyllide oxidoreductase.

The photoenzyme protochlorophyllide oxidoreductase (POR) is an important enzyme for understanding biological H-transfer mechanisms. It uses light to catalyse the reduction of protochlorophyllide to chlorophyllide, a key step in chlorophyll biosynthesis. Although a wealth of spectroscopic data have provided crucial mechanistic insight, a structural rationale for POR photocatalysis has proved challenging and remains hotly debated. Recent structural models of the ternary enzyme-substrate complex, derived from crystal and electron microscopy data, show differences in the orientation of the protochlorophyllide substrate and the architecture of the POR active site, with significant implications for the catalytic mechanism. Here, we use a combination of computational and experimental approaches to investigate the compatibility of each structural model with the hypothesised reaction mechanisms and propose an alternative structural model for the cyanobacterial POR ternary complex. We show that a strictly conserved tyrosine, previously proposed to act as the proton donor in POR photocatalysis, is unlikely to be involved in this step of the reaction but is crucial for Pchlide binding. Instead, an active site cysteine is important for both hydride and proton transfer reactions in POR and is proposed to act as the proton donor, either directly or through a water-mediated network. Moreover, a conserved glutamine is important for Pchlide binding and ensuring efficient photochemistry by tuning its electronic properties, likely by interacting with the central Mg atom of the substrate. This optimal 'binding pose' for the POR ternary enzyme-substrate complex illustrates how light energy can be harnessed to facilitate enzyme catalysis by this unique enzyme.

Comparing dropout intentions of math students on trainee teacher courses versus bachelor of science courses using intensive longitudinal data

In the past, high dropout rates of university math students have been recurrently observed, causing psychological and economic costs for individuals and society. In this article, we draw on prospective, intensive longitudinal data (ILD) collected at a large German university to examine the effects of stable inter-individual differences (e.g., general math competencies) and intra-individual changes (e.g., motivational states) on the intention to drop out of math studies, an important precursor for actual dropout. Given the ongoing discussion on whether student teachers differ from other types of students in their characteristics (e.g., with respect to cognitive abilities), we were particularly interested in differences in dropout intentions between first-year math B.Sc. and B.Ed. students, who attend the same introductory lectures. Using recent residual dynamic structural equation modeling techniques (RDSEM) we find that dropout intentions of math students in their first semester depend on both baseline characteristics and motivational changeable states which occur during the course. Furthermore, it is shown that B.Sc. and B.Ed. students differ regarding their intra-individual effects and have different trajectories of dropout intentions over time such that they cannot be assumed to be a homogeneous group. The results suggest that the two groups require differential treatment concerning the prevention of early dropouts.

A novel germline hyperactivating JAK2 mutation L604F

Somatic JAK2 mutations are the main molecular cause of the vast majority of polycythemia vera (PV) cases. According to a recent structural model, the prevalent acquired V617F mutation improves the stability of the JAK2 dimer, thereby enhancing the constitutive JAK2 kinase activity. Germline JAK2 mutations usually do not largely alter JAK2 signaling, although they may modulate the impact of V617F. We found an unusual germline JAK2 mutation L604F in homozygous form in a young PV patient, along with a low allele burden JAK2 V617F mutation, and in her apparently healthy sister. Their father with a PV-like disease had L604F in a heterozygous state, without V617F. The functional consequences of JAK2 L604Fmutation were compared with those induced by V617F in two different in vitro model systems: (i) HEK293T cells were transfected with plasmids for exogenous JAK2-GFP expression, and (ii) endogenous JAK2 modifications were introduced into HeLa cells using CRISPR/Cas9. Both mutations significantly increased JAK2 constitutive activity in transfected HEK293T cells. In the second model, JAK2 modification resulted in reduced total JAK2 protein levels. An important difference was also detected: as described previously, the effect of V617F on JAK2 kinase activity was abrogated in the absence of the aromatic residue F595. In contrast, JAK2 hyperactivation by L604F was only partially inhibited by the F595 change to alanine. We propose that the L604F mutation increases the probability of spontaneous JAK2 dimer formation, which is physiologically mediated by F595. In addition, L604F may contribute to dimer stabilization similarly to V617F.

Redundant electrostatic interactions between GATOR1 and the Rag GTPase heterodimer drive efficient amino acid sensing in human cells

Cells need to coordinate nutrient availability with their growth and proliferation. In eukaryotic cells, this coordination is mediated by the mechanistic target of the rapamycin complex 1 (mTORC1) pathway. mTORC1 activation is regulated by two GTPase units, the Rag GTPase heterodimer and the Rheb GTPase. The RagA-RagC heterodimer controls the subcellular localization of mTORC1, and its nucleotide loading states are strictly controlled by upstream regulators including amino acid sensors. A critical negative regulator of the Rag GTPase heterodimer is GATOR1. In the absence of amino acids, GATOR1 stimulates GTP hydrolysis by the RagA subunit to turn off mTORC1 signaling. Despite the enzymatic specificity of GATOR1 to RagA, a recent cryo-EM structural model of the human GATOR1-Rag-Ragulator complex reveals an unexpected interface between Depdc5, a subunit of GATOR1, and RagC. Currently, there is no functional characterization of this interface, nor do we know its biological relevance. Here, combining structure-function analysis, enzymatic kinetic measurements, and cell-based signaling assays, we identified a critical electrostatic interaction between Depdc5 and RagC. This interaction is mediated by the positively charged Arg-1407 residue on Depdc5 and a patch of negatively charged residues on the lateral side of RagC. Abrogating this interaction impairs the GAP activity of GATOR1 and cellular response to amino acid withdrawal. Our results reveal how GATOR1 coordinates the nucleotide loading states of the Rag GTPase heterodimer, and thus precisely controls cellular behavior in the absence of amino acids.

Systematic mutagenesis of TFIIH subunit p52/Tfb2 identifies residues required for XPB/Ssl2 subunit function and genetic interactions with TFB6

TFIIH is an evolutionarily conserved complex that plays central roles in both RNA polymerase II (pol II) transcription and DNA repair. As an integral component of the pol II preinitiation complex, TFIIH regulates pol II enzyme activity in numerous ways. The TFIIH subunit XPB/Ssl2 is an ATP-dependent DNA translocase that stimulates promoter opening prior to transcription initiation. Crosslinking-mass spectrometry and cryo-EM results have shown a conserved interaction network involving XPB/Ssl2 and the C-terminal Hub region of the TFIIH p52/Tfb2 subunit, but the functional significance of specific residues is unclear. Here, we systematically mutagenized the HubA region of Tfb2 and screened for growth phenotypes in a TFB6 deletion background in Saccharomyces cerevisiae. We identified six lethal and 12 conditional mutants. Slow growth phenotypes of all but three conditional mutants were relieved in the presence of TFB6, thus identifying a functional interaction between Tfb2 HubA mutants and Tfb6, a protein that dissociates Ssl2 from TFIIH. Our biochemical analysis of Tfb2 mutants with severe growth phenotypes revealed defects in Ssl2 association, with similar results in human cells. Further characterization of these tfb2 mutant cells revealed defects in GAL gene induction, and reduced occupancy of TFIIH and pol II at GAL gene promoters, suggesting that functionally competent TFIIH is required for proper pol II recruitment to preinitiation complexes in vivo. Consistent with recent structural models of TFIIH, our results identify key residues in the p52/Tfb2 HubA domain that are required for stable incorporation of XPB/Ssl2 into TFIIH and for pol II transcription.

Extracellular Loops of the Treponema pallidum FadL Orthologs TP0856 and TP0858 Elicit IgG Antibodies and IgG+-Specific B-Cells in the Rabbit Model of Experimental Syphilis.

ABSTRACTThe resurgence of syphilis in the new millennium has called attention to the importance of a vaccine for global containment strategies. Studies with immune rabbit serum (IRS) indicate that a syphilis vaccine should elicit antibodies (Abs) that promote opsonophagocytosis of treponemes by activated macrophages. The availability of three-dimensional models for Treponema pallidum’s (Tp) repertoire of outer membrane proteins (OMPs) provides an architectural framework for identification of candidate vaccinogens with extracellular loops (ECLs) as the targets for protective Abs. Herein, we used Pyrococcus furiosus thioredoxin (PfTrx) as a scaffold to display Tp OMP ECLs to interrogate sera and peripheral blood mononuclear cells (PBMCs) from immune rabbits for ECL-specific Abs and B cells. We validated this approach using a PfTrx scaffold presenting ECL4 from BamA, a known opsonic target. Using scaffolds displaying ECLs of the FadL orthologs TP0856 and TP0858, we determined that ECL2 and ECL4 of both proteins are strongly antigenic. Comparison of ELISA and immunoblot results suggested that the PfTrx scaffolds present conformational and linear epitopes. We then used the FadL ECL2 and ECL4 PfTrx constructs as “hooks” to confirm the presence of ECL-specific B cells in PBMCs from immune rabbits. Our results pinpoint immunogenic ECLs of two newly discovered OMPs, while advancing the utility of the rabbit model for circumventing bottlenecks in vaccine development associated with large-scale production of folded OMPs. They also lay the groundwork for production of rabbit monoclonal Abs (MAbs) to characterize potentially protective ECL epitopes at the atomic level.

Trivial Excitation Energy Transfer to Carotenoids Is an Unlikely Mechanism for Non-photochemical Quenching in LHCII

Higher plants defend themselves from bursts of intense light via the mechanism of Non-Photochemical Quenching (NPQ). It involves the Photosystem II (PSII) antenna protein (LHCII) adopting a conformation that favors excitation quenching. In recent years several structural models have suggested that quenching proceeds via energy transfer to the optically forbidden and short-lived S1 states of a carotenoid. It was proposed that this pathway was controlled by subtle changes in the relative orientation of a small number of pigments. However, quantum chemical calculations of S1 properties are not trivial and therefore its energy, oscillator strength and lifetime are treated as rather loose parameters. Moreover, the models were based either on a single LHCII crystal structure or Molecular Dynamics (MD) trajectories about a single minimum. Here we try and address these limitations by parameterizing the vibronic structure and relaxation dynamics of lutein in terms of observable quantities, namely its linear absorption (LA), transient absorption (TA) and two-photon excitation (TPE) spectra. We also analyze a number of minima taken from an exhaustive meta-dynamical search of the LHCII free energy surface. We show that trivial, Coulomb-mediated energy transfer to S1 is an unlikely quenching mechanism, with pigment movements insufficiently pronounced to switch the system between quenched and unquenched states. Modulation of S1 energy level as a quenching switch is similarly unlikely. Moreover, the quenching predicted by previous models is possibly an artifact of quantum chemical over-estimation of S1 oscillator strength and the real mechanism likely involves short-range interaction and/or non-trivial inter-molecular states.

The seismic structure of the Antarctic upper mantle

Abstract The deployment of seismic stations and the development of ambient noise tomography as well as new analysis methods provide an opportunity for higher-resolution imaging of Antarctica. Here we review recent seismic structure models and describe their implications for the dynamics and history of the Antarctic upper mantle. Results show that most of East Antarctica is underlain by continental lithosphere to depths of approximately 200 km. The thickest lithosphere is found in a band 500–1000 km inboard from the Transantarctic Mountains, representing the continuation of cratonic lithosphere with Australian affinity beneath the ice. Dronning Maud Land and the Lambert Graben show much thinner lithosphere, consistent with Phanerozoic lithospheric disruption. The Transantarctic Mountains mark a sharp boundary between cratonic lithosphere and the warmer upper mantle of West Antarctica. In the southern Transantarctic Mountains, cratonic lithosphere has been replaced by warm asthenosphere, giving rise to Cenozoic volcanism and an elevated mountainous region. The Marie Byrd Land volcanic dome is underlain by slow seismic velocities extending through the transition zone, consistent with a mantle plume. Slow-velocity anomalies beneath the coast from the Amundsen Sea Embayment to the Antarctic Peninsula are likely to result from upwelling of warm asthenosphere during subduction of the Antarctic–Phoenix spreading centre.

Remodeling and activation mechanisms of outer arm dyneins revealed by cryo-EM.

Cilia are thin microtubule-based protrusions of eukaryotic cells. The swimming of ciliated protists and sperm cells is propelled by the beating of cilia. Cilia propagate the flow of mucus in the trachea and protect the human body from viral infections. The main force generators of ciliary beating are the outer dynein arms (ODAs) which attach to the doublet microtubules. The bending of cilia is driven by the ODAs' conformational changes caused by ATP hydrolysis. Here, we report the native ODA complex structure attaching to the doublet microtubule by cryo-electron microscopy. The structure reveals how the ODA complex is attached to the doublet microtubule via the docking complex in its native state. Combined with coarse-grained molecular dynamic simulations, we present a model of how the attachment of the ODA to the doublet microtubule induces remodeling and activation of the ODA complex.

Fully Coupled Nonlinear Aerothermoelastic Computational Model of a Plate in Hypersonic Flow

A recent structural model of a plate is extended to include a nonuniform temperature differential that varies in time using a modal expansion. The nonlinear structural plate model with first-order piston theory aerodynamics and cavity dynamics is coupled with the heat equation to form a single system of dynamical equations for the fluid-structural-thermal system. The heat flux from the boundary layer to the plate is modeled using the temperature reference method. A computational scheme is formulated by linearizing the heat flux in terms of two variables: the local aerodynamic downwash due to plate motion and the local wall temperature. The proposed linearization produces a local force equivalent for the pointwise heat flux and substantially simplifies the time-marching scheme of the coupled equations. The model is correlated with results from a recent supersonic wind-tunnel experiment conducted at Air Force Research Laboratory (AFRL). It is found that when a nonlinear response is expected in an experiment (for example, flutter that reaches limit cycle oscillation or a large static buckled deformation), the in-plane boundary stiffness should be measured before the wind-tunnel experiment to fully characterize the experimental model. The heat flux linearization error is quantified, and the modal convergence of the temperature differential is investigated.

Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel.

The transient receptor potential melastatin (TRPM) family belongs to the superfamily of TRP ion channels. It consists of eight family members that are involved in a plethora of cellular functions. TRPM2 is a homotetrameric Ca2+-permeable cation channel activated upon oxidative stress and is important, among others, for body heat control, immune cell activation and insulin secretion. Invertebrate TRPM2 proteins are channel enzymes; they hydrolyze the activating ligand, ADP-ribose, which is likely important for functional regulation. Since its cloning in 1998, the understanding of the biophysical properties of the channel has greatly advanced due to a vast number of structure–function studies. The physiological regulators of the channel have been identified and characterized in cell-free systems. In the wake of the recent structural biochemistry revolution, several TRPM2 cryo-EM structures have been published. These structures have helped to understand the general features of the channel, but at the same time have revealed unexplained mechanistic differences among channel orthologues. The present review aims at depicting the major research lines in TRPM2 structure-function. It discusses biophysical properties of the pore and the mode of action of direct channel effectors, and interprets these functional properties on the basis of recent three-dimensional structural models.

The Immediate Impact of Covid19 on Tourism Employment in Spain: Debunking the Myth of Job Precariousness?

ABSTRACT This note explores the immediate impact that the COVID-19 crisis has had on tourist and non-tourist employment in Spain as a result of the state of alarm and period of confinement decreed from March 14th. The employment and self-employment series drawn from the Social Security affiliation data corresponding to the period between January 2017 and April 2020 are examined using the classical Box–Jenkins method (ARIMA) and the more recent Bayesian Structural Time-Series Models.

TNNT2 mutations in the tropomyosin binding region of TNT1 disrupt its role in contractile inhibition and stimulate cardiac dysfunction

Muscle contraction is regulated by the movement of end-to-end-linked troponin-tropomyosin complexes over the thin filament surface, which uncovers or blocks myosin binding sites along F-actin. The N-terminal half of troponin T (TnT), TNT1, independently promotes tropomyosin-based, steric inhibition of acto-myosin associations, in vitro. Recent structural models additionally suggest TNT1 may restrain the uniform, regulatory translocation of tropomyosin. Therefore, TnT potentially contributes to striated muscle relaxation; however, the in vivo functional relevance and molecular basis of this noncanonical role remain unclear. Impaired relaxation is a hallmark of hypertrophic and restrictive cardiomyopathies (HCM and RCM). Investigating the effects of cardiomyopathy-causing mutations could help clarify TNT1's enigmatic inhibitory property. We tested the hypothesis that coupling of TNT1 with tropomyosin's end-to-end overlap region helps anchor tropomyosin to an inhibitory position on F-actin, where it deters myosin binding at rest, and that, correspondingly, cross-bridge cycling is defectively suppressed under diastolic/low Ca2+ conditions in the presence of HCM/RCM lesions. The impact of TNT1 mutations on Drosophila cardiac performance, rat myofibrillar and cardiomyocyte properties, and human TNT1's propensity to inhibit myosin-driven, F-actin-tropomyosin motility were evaluated. Our data collectively demonstrate that removing conserved, charged residues in TNT1's tropomyosin-binding domain impairs TnT's contribution to inhibitory tropomyosin positioning and relaxation. Thus, TNT1 may modulate acto-myosin activity by optimizing F-actin-tropomyosin interfacial contacts and by binding to actin, which restrict tropomyosin's movement to activating configurations. HCM/RCM mutations, therefore, highlight TNT1's essential role in contractile regulation by diminishing its tropomyosin-anchoring effects, potentially serving as the initial trigger of pathology in our animal models and humans.

The challenge of forming a fuzzy core in Jupiter

Recent structure models of Jupiter that match Juno gravity data suggest that the planet harbours an extended region in its deep interior that is enriched with heavy elements: a so-called dilute or fuzzy core. This finding raises the question of what possible formation pathways could have lead to such a structure. We modelled Jupiter’s formation and long-term evolution, starting at late-stage formation before runaway gas accretion. The formation scenarios we considered include both primordial composition gradients, as well as gradients that are built as proto-Jupiter rapidly acquires its gaseous envelope. We then followed Jupiter’s evolution as it cools down and contracts, with a particular focus on the energy and material transport in the interior. We find that none of the scenarios we consider lead to a fuzzy core that is compatible with interior structure models. In all the cases, most of Jupiter’s envelope becomes convective and fully mixed after a few million years at most. This is true even when we considered a case where the gas accretion leads to a cold planet, and large amounts of heavy elements are accreted. We therefore conclude that it is very challenging to explain Jupiter’s dilute core from standard formation models. We suggest that future works should consider more complex formation pathways as well as the modelling of additional physical processes that could lead to Jupiter’s current-state internal structure.

Jupiter’s heavy-element enrichment expected from formation models

Aims.The goal of this work is to investigate Jupiter’s growth by focusing on the amount of heavy elements accreted by the planet, and to compare this with recent structure models of Jupiter.Methods.Our model assumes an initial core growth dominated by pebble accretion, and a second growth phase that is characterised by a moderate accretion of both planetesimals and gas. The third phase is dominated by runaway gas accretion during which the planet becomes detached from the disc. The second and third phases were computed in detail, considering two different prescriptions for the planetesimal accretion and fits from hydrodynamical studies to compute the gas accretion in the detached phase.Results.In order for Jupiter to consist of ~20–40M⊕of heavy elements as suggested by structure models, we find that Jupiter’s formation location is preferably at an orbital distance of 1 ≲a≲ 10 au once the accretion of planetesimals dominates. We find that Jupiter could accrete between ~1 and ~15M⊕of heavy elements during runaway gas accretion, depending on the assumed initial surface density of planetesimals and the prescription used to estimate the heavy-element accretion during the final stage of the planetary formation. This would yield an envelope metallicity of ~0.5 to ~3 times solar. By computing the solid (heavy-element) accretion during the detached phase, we infer a planetary mass-metallicity (MP–MZ) relation ofMZ~MP2/5, when a gap in the planetesimal disc is created, and ofMZ~MP1/6without a planetesimal gap.Conclusions.Our hybrid pebble-planetesimal model can account for Jupiter’s bulk and atmospheric enrichment. The high bulk metallicity inferred for many giant exoplanets is difficult to explain from standard formation models. This might suggest a migration history for such highly enriched giant exoplanets and/or giant impacts after the disc’s dispersal.

Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.

F508del‐cystic fibrosis transmembrane conductance regulator (CFTR) is the major mutant responsible for cystic fibrosis (CF). ORKAMBI®, approved for patients bearing this mutant, contains lumacaftor (VX‐809) that partially corrects F508del‐CFTR's processing defect and ivacaftor (VX‐770) that potentiates its defective channel activity. Unfortunately, the clinical efficacy of ORKAMBI® is modest, highlighting the need to understand how the small molecules work so that superior compounds can be developed. Because, human CFTR (hCFTR) and zebrafish Cftr (zCftr) are structurally conserved as determined in recent cryo‐EM structural models, we hypothesized that the consequences of the major mutation and small molecule modulators would be similar for the two species of protein. As expected, like the F508del mutation in hCFTR, the homologous mutation in zCftr (F507del) is misprocessed, yet not as severely as the human mutant and this defect was restored by low‐temperature (27°C) culture conditions. After rescue to the cell surface, F507del‐zCftr exhibited regulated channel activity that was potentiated by ivacaftor. Surprisingly, lumacaftor failed to rescue misprocessing of the F507del‐zCftr at either 37 or 27°C suggesting that future comparative studies with F508del‐hCFTR would provide insight into its structure: function relationships. Interestingly, the robust rescue of F508del‐zCftr at 27°C and availability of methods for in vivo screening in zebrafish present the opportunity to define the cellular pathways underlying rescue.

Dissection of GTPase-activating proteins reveals functional asymmetry in the COPI coat of budding yeast

ABSTRACTThe Arf GTPase controls formation of the COPI vesicle coat. Recent structural models of COPI revealed the positioning of two Arf1 molecules in contrasting molecular environments. Each of these pockets for Arf1 is expected to also accommodate an Arf GTPase-activating protein (ArfGAP). Structural evidence and protein interactions observed between isolated domains indirectly suggest that each niche preferentially recruits one of the two ArfGAPs known to affect COPI, i.e. Gcs1/ArfGAP1 and Glo3/ArfGAP2/3, although only partial structures are available. The functional role of the unique non-catalytic domain of either ArfGAP has not been integrated into the current COPI structural model. Here, we delineate key differences in the consequences of triggering GTP hydrolysis through the activity of one versus the other ArfGAP. We demonstrate that Glo3/ArfGAP2/3 specifically triggers Arf1 GTP hydrolysis impinging on the stability of the COPI coat. We show that the Snf1 kinase complex, the yeast homologue of AMP-activated protein kinase (AMPK), phosphorylates the region of Glo3 that is crucial for this effect and, thereby, regulates its function in the COPI-vesicle cycle. Our results revise the model of ArfGAP function in the molecular context of COPI.This article has an associated First Person interview with the first author of the paper.

A global analysis of factors impacting the intensive and extensive margins of bilateral foreign direct investment

AbstractThis study investigates determinants of bilateral foreign direct investment (FDI) on both margins, the extensive margin (whether to invest) and the intensive margin (how much to invest), based on the recent structural gravity model for FDI developed by Anderson et al. (Trade and investment in the global economy. National Bureau of Economic Research, Cambridge, MA, 2017). I examine a global data set comprised of 110 countries over 9 years, 2004–12. Apart from conventional gravity variables, the source country's technology capital shows a significant and positive impact on both FDI margins. Bilateral investment treaties play a significant role only in determining the extensive margin. Results on FDI stocks and FDI flows can lead to different conclusions; thus, research should consult both types of data series to find which variables have robust effects. Furthermore, breaking down the sample by country development levels reveals that FDI from less‐developed countries (LDCs) is not affected by many common variables, and thus, there is a need to develop more theories and empirical work to investigate the FDI from LDCs in particular.