Regulation of the Ras Signaling Network in C. Elegans Development

An EGF gradient induces the equipotent C. elegans vulval precursor cells (VPCs) to assume the 3˚-3˚-2˚-1˚-2˚-3˚ pattern of cell fates. EGF triggers the LET-60/Ras-LIN-45/Raf-MEK-2/MEK-MPK-1/ERK canonical MAP kinase cascade to induce 1˚ fate and synthesize of DSL ligands for the lateral Notch signal. In turn, LIN-12/Notch induces neighboring cells to become 2˚. In response to lower dose of EGF signal, LET-60/Ras switches effectors to use the RGL-1/RalGEF-RAL-1/Ral modulatory signaling cascade to promote 2˚ fate in support of LIN-12. The goals of this research are to define principles by which signaling networks function and to identify an effector cascade downstream of RAL-1. RAL-1 signals through EXOC-8/Exo84, an established Ral binding partner, GCK-2, a CNH domain-containing MAP4 Kinase, and PMK-1/p38 MAP kinase to promote 2˚ fate. We also show that RGL-1 plays opposing and genetically separable roles in VPC fate patterning. RGL-1 promotes 2˚ fate via canonical GEF-dependent activation of RAL-1 and 1˚ fate via a non-canonical GEF-independent activity. Our genetic epistasis experiments are consistent with RGL-1 functioning in the modulatory 1˚-promoting AGE-1/PI3-Kinase-PDK-1/PDK-AKT-1/Akt cascade. Animals without RGL-1 experience 15-fold higher rates of VPC patterning errors compared to the wild type. Yet VPC patterning in RGL-1 deletion mutants is not more sensitive to environmental perturbations. We propose that RGL-1 functions as a “Balanced Switch” that orchestrates opposing 1˚- and 2˚-promoting modulatory cascades to decrease developmental stochasticity. To investigate how LET-60/Ras switches effectors to promote different cell fates, we used CRISPR to tag endogenous LIN-45/Raf and RGL-1/RalGEF proteins. We found that they are recruited to different subcellular compartments during VPC induction. LIN-45 is recruited to the basolateral membrane in presumptive 1˚ cells. RGL-1 is recruited to the apical membrane in presumptive 2˚ cells, and this localization depends on functional LET-60. We hypothesize that RGL-1 apical localization in the VPCs is mediated by phosphorylation or scaffold proteins. Our studies delineate a novel Ral-dependent developmental signaling cascade, bifunctional RGL-1 as a “Balanced Switch”, and LET-60 effector segregation mechanism in vivo, thus providing critical insights for understanding Ras biology in cancer and development

Korea’s national approach to Open Science: present and possible future.

Open Science (OS) – an emerging global trend driven by advances in digital technologies and government's commitment to greater transparency and value for money of publicly funded research – is at its early stages, even in countries with high R&D expenditures, such as South Korea. This study provides a comprehensive overview and analysis of Korea's national OS approach, with a focus on exploring the current OS regulatory and technological environments it operates under, and uncovering its SWOT – strengths, weaknesses, opportunities and threats. It concludes that internal weaknesses, such as insufficient political will to promote OS, dominate other SWOT characteristics of Korea's national OS approach. Thus, the highest priority should be given to strategies attempting to minimise both internal weaknesses and external threats, such as reinforcing domestic Open Access publishing ecosystem to mitigate Korean researchers' dependency on large international commercial publishers

DRAINCLoG: Detecting Rogue Accounts with Illegally-obtained NFTs using Classifiers Learned on Graphs

As Non-Fungible Tokens (NFTs) continue to grow in popularity, NFT users have become targets of phishing attacks by cybercriminals, called \textit{NFT drainers}. Over the last year, \$100 million worth of NFTs were stolen by drainers, and their presence remains a serious threat to the NFT trading space. However, no work has yet comprehensively investigated the behaviors of drainers in the NFT ecosystem. In this paper, we present the first study on the trading behavior of NFT drainers and introduce the first dedicated NFT drainer detection system. We collect 127M NFT transaction data from the Ethereum blockchain and 1,135 drainer accounts from five sources for the year 2022. We find that drainers exhibit significantly different transactional and social contexts from those of regular users. With these insights, we design \textit{DRAINCLoG}, an automatic drainer detection system utilizing Graph Neural Networks. This system effectively captures the multifaceted web of interactions within the NFT space through two distinct graphs: the NFT-User graph for transaction contexts and the User graph for social contexts. Evaluations using real-world NFT transaction data underscore the robustness and precision of our model. Additionally, we analyze the security of \textit{DRAINCLoG} under a wide variety of evasion attacks.Comment: To appear in NDSS 202

Haemogenic endocardium contributes to transient definitive haematopoiesis.

Haematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial and haematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a haemogenic organ akin to the dorsal aorta. Here we examine the haemogenic activity of the developing endocardium. Mouse heart explants generate myeloid and erythroid colonies in the absence of circulation. Haemogenic activity arises from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and is transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, are expressed in and required for the haemogenic population of the endocardium. Together, these data suggest that a subset of endocardial/endothelial cells serve as a de novo source for transient definitive haematopoietic progenitors

Surface Geometry of C60 on Ag(111)

The geometry of adsorbed C60 influences its collective properties. We report the first dynamical low-energy electron diffraction study to determine the geometry of a C60 monolayer, Ag(111)-(23×23)30°-C60, and related density functional theory calculations. The stable monolayer has C60 molecules in vacancies that result from the displacement of surface atoms. C60 bonds with hexagons down, with their mirror planes parallel to that of the substrate. The results indicate that vacancy structures are the rule rather than the exception for C60 monolayers on close-packed metal surfaces. © 2009 The American Physical Society

Initiation and evolution of phase separation in heteroepitaxial InAlAs films

We have investigated the initiation and evolution of phase separation in heteroepitaxial InAlAs films. In misfit-free InAlAs layers, cross-sectional scanning tunneling microscopy (XSTM) reveals the presence of isotropic nanometer-sized clusters. For lattice-mismatched InAlAs layers with 1.2% misfit, quasiperiodic contrast modulations perpendicular to the growth direction are apparent. Interestingly, these lateral modulations are apparently initiated within the first few bilayers of film growth, and both the amplitude and wavelength of the modulations increase with film thickness. The saturation value of the modulation wavelength determined from XSTM coincides with the lateral superlattice period determined from (002) x-ray reciprocal space maps, suggesting that the lateral modulation wavelength represents a periodic composition variation. Together, these results suggest that phase separation in the heteroepitaxial InAlAs thin-film system is a misfit-driven kinetic process initiated by random compositional nonuniformities, which later develop into coupled compositional and surface morphological variations. © 2002 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69359/2/APPLAB-80-18-3292-1.pd

Mitophagy and the therapeutic clearance of damaged mitochondria for neuroprotection

Mitochondria are the foremost producers of the cellular energy currency ATP. They are also a significant source of reactive oxygen species and an important buffer of intracellular calcium. Mitochondrial retrograde signals regulate energy homeostasis and pro-survival elements whereas anterograde stimuli can trigger programmed cell death. Maintenance of a healthy, functional mitochondria network is therefore essential, and several mechanisms of mitochondrial quality control have been described. Mitochondrial dysfunction is linked to several neurodegenerative conditions including Parkinson, and Huntingdon diseases as well as Amyotrophic lateral sclerosis. Understanding the mechanisms governing mitochondrial quality control may reveal novel strategies for pharmacological intervention and disease therapy

Magnetic topological insulator MnBi6Te10 with zero-field ferromagnetic state and gapped Dirac surface states

Magnetic topological insulators (TIs) with nontrivial topological electronic structure and broken time-reversal symmetry exhibit various exotic topological quantum phenomena. The realization of such exotic phenomena at high temperature is one of central topics in this area. We reveal that MnBi6Te10 is a magnetic TI with an antiferromagnetic ground state below 10.8 K whose nontrivial topology is manifested by Dirac-like surface states. The ferromagnetic axion insulator state with Z4 = 2 emerges once spins polarized at field as low as 0.1 T, accompanied with saturated anomalous Hall resistivity up to 10 K. Such a ferromagnetic state is preserved even external field down to zero at 2 K. Theoretical calculations indicate that the few-layer ferromagnetic MnBi6Te10 is also topologically nontrivial with a non-zero Chern number. Angle-resolved photoemission spectroscopy experiments further reveal three types of Dirac surface states arising from different terminations on the cleavage surfaces, one of which has insulating behavior with an energy gap of ~ 28 meV at the Dirac point. These outstanding features suggest that MnBi6Te10 is a promising system to realize various topological quantum effects at zero field and high temperature.Comment: 18 pages, 4 figures and 1 tabl

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin