Ypt1/Rab1 regulates Hrr25/CK1δ kinase activity in ER-Golgi traffic and macroautophagy.

ER-derived COPII-coated vesicles are conventionally targeted to the Golgi. However, during cell stress these vesicles also become a membrane source for autophagosomes, distinct organelles that target cellular components for degradation. How the itinerary of COPII vesicles is coordinated on these pathways remains unknown. Phosphorylation of the COPII coat by casein kinase 1 (CK1), Hrr25, contributes to the directional delivery of ER-derived vesicles to the Golgi. CK1 family members are thought to be constitutively active kinases that are regulated through their subcellular localization. Instead, we show here that the Rab GTPase Ypt1/Rab1 binds and activates Hrr25/CK1δ to spatially regulate its kinase activity. Consistent with a role for COPII vesicles and Hrr25 in membrane traffic and autophagosome biogenesis, hrr25 mutants were defective in ER–Golgi traffic and macroautophagy. These studies are likely to serve as a paradigm for how CK1 kinases act in membrane traffic

NGC 1980 is not a foreground population of Orion : spectroscopic survey of young stars with low extinction in Orion A

We perform a spectroscopic survey of the foreground population in Orion A with MMT/Hectospec. We use these data, along with archival spectroscopic data and photometric data, to derive spectral types, extinction values, and masses for 691 stars. Using the Spitzer Space Telescope data, we characterize the disk properties of these sources. We identify 37 new transition disk (TD) objects, one globally depleted disk candidate, and 7 probable young debris disks. We discover an object with a mass less than 0.018-0.030 M⊙, which harbors a flaring disk. Using the Hα emission line, we characterize the accretion activity of the sources with disks, and confirm that fraction of accreting TDs is lower than that of optically thick disks (46±7% versus 73±9%, respectively). Using kinematic data from the Sloan Digital Sky Survey and APOGEE INfrared Spectroscopy of Young Nebulous Clusters program (IN-SYNC), we confirm that the foreground population shows similar kinematics to their local molecular clouds and other young stars in the same regions. Using the isochronal ages, we find that the foreground population has a median age around 1-2 Myr, which is similar to the one of other young stars in Orion A. Therefore, our results argue against the presence of a large and old foreground cluster in front of Orion A.PostprintPeer reviewe

Large-Scale Automatic Audiobook Creation

An audiobook can dramatically improve a work of literature's accessibility and improve reader engagement. However, audiobooks can take hundreds of hours of human effort to create, edit, and publish. In this work, we present a system that can automatically generate high-quality audiobooks from online e-books. In particular, we leverage recent advances in neural text-to-speech to create and release thousands of human-quality, open-license audiobooks from the Project Gutenberg e-book collection. Our method can identify the proper subset of e-book content to read for a wide collection of diversely structured books and can operate on hundreds of books in parallel. Our system allows users to customize an audiobook's speaking speed and style, emotional intonation, and can even match a desired voice using a small amount of sample audio. This work contributed over five thousand open-license audiobooks and an interactive demo that allows users to quickly create their own customized audiobooks. To listen to the audiobook collection visit \url{https://aka.ms/audiobook}

Spontaneously formed porous and composite materials

In recent years, a number of routes to porous materials have been developed which do not involve the use of pre-formed templates or structure-directing agents. These routes are usually spontaneous, meaning they are thermodynamically downhill. Kinetic control, deriving from slow diffusion of certain species in the solid state, allows metastable porous morphologies rather than dense materials to be obtained. While the porous structures so formed are random, the average architectural features can be well-defined, and the porosity is usually highly interconnected. The routes are applicable to a broad range of functional inorganic materials. Consequently, the porous architectures have uses in energy transduction and storage, chemical sensing, catalysis, and photoelectrochemistry. This is in addition to more straightforward uses deriving from the pore structure, such as in filtration, as a structural material, or as a cell-growth scaffold. In this feature article, some of the methods for the creation of porous materials are described, including shape-conserving routes that lead to hierarchical macro/mesoporous architectures. In some of the preparations, the resulting mesopores are aligned locally with certain crystallographic directions. The coupling between morphology and crystallography provides a macroscopic handle on nanoscale structure. Extension of these routes to create biphasic composite materials are also described

Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia

[EN] Background-Several metabolic conditions can cause the Brugada ECG pattern, also called Brugada phenotype (BrPh). We aimed to define the clinical characteristics and outcome of BrPh patients and elucidate the mechanisms underlying BrPh attributed to hyperkalemia. Methods and Results-We prospectively identified patients hospitalized with severe hyperkalemia and ECG diagnosis of BrPh and compared their clinical characteristics and outcome with patients with hyperkalemia but no BrPh ECG. Computer simulations investigated the roles of extracellular potassium increase, fibrosis at the right ventricular outflow tract, and epicardial/endocardial gradients in transient outward current. Over a 6-year period, 15 patients presented severe hyperkalemia with BrPh ECG that was transient and disappeared after normalization of their serum potassium. Most patients were admitted because of various severe medical conditions causing hyperkalemia. Six (40%) patients presented malignant arrhythmias and 6 died during admission. Multiple logistic regression analysis revealed that higher serum potassium levels (odds ratio, 15.8; 95% CI, 3.1-79; P=0.001) and male sex (odds ratio, 17; 95% CI, 1.05-286; P=0.045) were risk factors for developing BrPh ECG in patients with severe hyperkalemia. In simulations, hyperkalemia yielded BrPh by promoting delayed and heterogeneous right ventricular outflow tract activation attributed to elevation of resting potential, reduced availability of inward sodium channel conductance, and increased right ventricular outflow tract fibrosis. An elevated transient outward current gradient contributed to, but was not essential for, the BrPh phenotype. Conclusions-In patients with severe hyperkalemia, a BrPh ECG is associated with malignant arrhythmias and all-cause mortality secondary to resting potential depolarization, reduced sodium current availability, and fibrosis at the right ventricular outflow tract.This work was funded in part by the CIBERCV (Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares), Instituto de Salud Carlos III (PI14/00857, DTS16/0160, PI17/1059, PI01106), Spanish Ministry of Ecomomy (TEC2013-46067-R) and the ERDF (European Regional Development Fund).Rivera-Juárez, A.; Hernández-Romero, I.; Puertas, C.; Zhang-Wang, S.; Sánchez-Álamo, B.; Martins, R.; Figuera, C.... (2019). Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia. Journal of the American Heart Association. 8(3):1-15. https://doi.org/10.1161/JAHA.118.010115S11583Brugada, P., & Brugada, J. (1992). 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Nature Genetics, 45(9), 1044-1049. doi:10.1038/ng.2712Frustaci, A., Priori, S. G., Pieroni, M., Chimenti, C., Napolitano, C., Rivolta, I., … Russo, M. A. (2005). Cardiac Histological Substrate in Patients With Clinical Phenotype of Brugada Syndrome. Circulation, 112(24), 3680-3687. doi:10.1161/circulationaha.105.520999Corrado, D., Zorzi, A., Cerrone, M., Rigato, I., Mongillo, M., Bauce, B., & Delmar, M. (2016). Relationship Between Arrhythmogenic Right Ventricular Cardiomyopathy and Brugada Syndrome. Circulation: Arrhythmia and Electrophysiology, 9(4). doi:10.1161/circep.115.003631Coronel, R., Casini, S., Koopmann, T. T., Wilms-Schopman, F. J. G., Verkerk, A. O., de Groot, J. R., … de Bakker, J. M. T. (2005). Right Ventricular Fibrosis and Conduction Delay in a Patient With Clinical Signs of Brugada Syndrome. Circulation, 112(18), 2769-2777. doi:10.1161/circulationaha.105.532614Probst, V., Veltmann, C., Eckardt, L., Meregalli, P. G., Gaita, F., Tan, H. L., … Wilde, A. A. M. (2010). 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Journal of Molecular and Cellular Cardiology, 49(4), 543-553. doi:10.1016/j.yjmcc.2010.07.012Zhang, J., Sacher, F., Hoffmayer, K., O’Hara, T., Strom, M., Cuculich, P., … Rudy, Y. (2015). Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients. Circulation, 131(22), 1950-1959. doi:10.1161/circulationaha.114.013698Nademanee, K., Hocini, M., & Haïssaguerre, M. (2017). Epicardial substrate ablation for Brugada syndrome. Heart Rhythm, 14(3), 457-461. doi:10.1016/j.hrthm.2016.12.001Hoogendijk, M. G., Opthof, T., Postema, P. G., Wilde, A. A. M., de Bakker, J. M. T., & Coronel, R. (2010). The Brugada ECG Pattern. Circulation: Arrhythmia and Electrophysiology, 3(3), 283-290. doi:10.1161/circep.110.937029Hoogendijk, M. G., Potse, M., Linnenbank, A. C., Verkerk, A. O., den Ruijter, H. M., van Amersfoorth, S. C. M., … Coronel, R. (2010). Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch. Heart Rhythm, 7(2), 238-248. doi:10.1016/j.hrthm.2009.10.007Tsuneoka, H., Takagi, M., Murakoshi, N., Yamagishi, K., Yokoyama, Y., … Xu, D. (2016). Long‐Term Prognosis of Brugada‐Type ECG and ECG With Atypical ST‐Segment Elevation in the Right Precordial Leads Over 20 Years: Results From the Circulatory Risk in Communities Study (CIRCS). Journal of the American Heart Association, 5(8). doi:10.1161/jaha.115.002899Babai Bigi, M. A., Aslani, A., & Shahrzad, S. (2007). aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome. Heart Rhythm, 4(8), 1009-1012. doi:10.1016/j.hrthm.2007.04.017Van Oosterom, A. (2004). ECGSIM: an interactive tool for studying the genesis of QRST waveforms. Heart, 90(2), 165-168. doi:10.1136/hrt.2003.014662O’Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011). 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Towards Trustworthy Artificial Intelligence for Equitable Global Health

Artificial intelligence (AI) can potentially transform global health, but algorithmic bias can exacerbate social inequities and disparity. Trustworthy AI entails the intentional design to ensure equity and mitigate potential biases. To advance trustworthy AI in global health, we convened a workshop on Fairness in Machine Intelligence for Global Health (FairMI4GH). The event brought together a global mix of experts from various disciplines, community health practitioners, policymakers, and more. Topics covered included managing AI bias in socio-technical systems, AI's potential impacts on global health, and balancing data privacy with transparency. Panel discussions examined the cultural, political, and ethical dimensions of AI in global health. FairMI4GH aimed to stimulate dialogue, facilitate knowledge transfer, and spark innovative solutions. Drawing from NIST's AI Risk Management Framework, it provided suggestions for handling AI risks and biases. The need to mitigate data biases from the research design stage, adopt a human-centered approach, and advocate for AI transparency was recognized. Challenges such as updating legal frameworks, managing cross-border data sharing, and motivating developers to reduce bias were acknowledged. The event emphasized the necessity of diverse viewpoints and multi-dimensional dialogue for creating a fair and ethical AI framework for equitable global health.Comment: 7 page

Recent Ancestry of Kyasanur Forest Disease Virus

Clinicians in Asia should consider this disease when diagnosing acute febrile illnesses

A facile synthetic approach to nanostructured Li2S cathodes for rechargeable solid-state Li–S batteries

Li–S solid state batteries, employing Li2S as a pre-lithiated cathode, present a promising low cost, high capacity and safer alternative to their liquid electrolyte counterparts, where dissolution of intermediate polysulfide species can result in loss of active material and a subsequent decrease in ionic conductivity. A nanostructured Li2S material would afford greater flexibility in optimising the cathode composite for more harmonious electrode–electrolyte interactions, yet facile routes to such nanoscale materials are limited. Here, we report a facile and scalable microwave approach to directly synthesize nanostructured Li2S from a glyme solution containing lithium polysulfides. As-synthesized Li2S presents an ideal architecture for the construction of free-standing cathodes for all-solid-state Li–S batteries

X-ray absorption spectroscopy systematics at the tungsten L-edge

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, has been interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W<sup>0</sup>(PMe<sub>3</sub>)<sub>6</sub>], [W<sup>II</sup>Cl<sub>2</sub>(PMePh<sub>2</sub>)<sub>4</sub>], [W<sup>III</sup>Cl<sub>2</sub>(dppe)<sub>2</sub>][PF<sub>6</sub>] (dppe = 1,2-bis(diphenylphosphino)ethane), [W<sup>IV</sup>Cl<sub>4</sub>(PMePh<sub>2</sub>)<sub>2</sub>], [W<sup>V</sup>(NPh)Cl<sub>3</sub>(PMe<sub>3</sub>)<sub>2</sub>], and [W<sup>VI</sup>Cl<sub>6</sub>] correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio (EBR) of the L<sub>3,2</sub>-edges and the L<sub>1</sub> rising-edge energy with metal Z<sub>eff</sub>, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>] and [W<sup>IV</sup>(mdt)<sub>2</sub>(CN)<sub>2</sub>]<sup>2–</sup> (mdt<sup>2–</sup> = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W<sup>IV</sup> species. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: 1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Z<sub>eff</sub> in the species of interest; 2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS; 3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Z<sub>eff</sub> or, as in the case of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>], add other subtlety by modulating the redox level of other ligands in the coordination sphere

The plasticity of the mirror system: how reward learning modulates cortical motor simulation of others

Cortical motor simulation supports the understanding of others' actions and intentions. This mechanism is thought to rely on the mirror neuron system (MNS), a brain network that is active both during action execution and observation. Indirect evidence suggests that alpha/beta suppression, an electroencephalographic (EEG) index of MNS activity, is modulated by reward. In this study we aimed to test the plasticity of the MNS by directly investigating the link between alpha/beta suppression and reward. 40 individuals from a general population sample took part in an evaluative conditioning experiment, where different neutral faces were associated with high or low reward values. In the test phase, EEG was recorded while participants viewed videoclips of happy expressions made by the conditioned faces. Alpha/beta suppression (identified using event-related desynchronisation of specific independent components) in response to rewarding faces was found to be greater than for non-rewarding faces. This result provides a mechanistic insight into the plasticity of the MNS and, more generally, into the role of reward in modulating physiological responses linked to empathy