Abstract
Developing a single-phase self-rectifying memristor with the continuously tunable feature is structurally desirable and functionally adaptive to dynamic environmental stimuli variations, ...which is the pursuit of further smart memristors and neuromorphic computing. Herein, we report a van der Waals ferroelectric CuInP
2
S
6
as a single memristor with superior continuous modulation of current and self-rectifying to different bias stimuli (sweeping speed, direction, amplitude, etc.) and external mechanical load. The synergetic contribution of controllable Cu
+
ions migration and interfacial Schottky barrier is proposed to dynamically control the current flow and device performance. These outstanding sensitive features make this material possible for being superior candidate for future smart memristors with bidirectional operation mode and strong recognition to input faults and variations.
HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160)
cleaved to (gp120 and gp41)
, interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse ...viral and target-cell membranes. The gp120-coreceptor interaction has previously been proposed as the most crucial trigger for unleashing the fusogenic potential of gp41. Here we report a cryo-electron microscopy structure of a full-length gp120 in complex with soluble CD4 and unmodified human CCR5, at 3.9 Å resolution. The V3 loop of gp120 inserts into the chemokine-binding pocket formed by seven transmembrane helices of CCR5, and the N terminus of CCR5 contacts the CD4-induced bridging sheet of gp120. CCR5 induces no obvious allosteric changes in gp120 that can propagate to gp41; it does bring the Env trimer close to the target membrane. The N terminus of gp120, which is gripped by gp41 in the pre-fusion or CD4-bound Env, flips back in the CCR5-bound conformation and may irreversibly destabilize gp41 to initiate fusion. The coreceptor probably functions by stabilizing and anchoring the CD4-induced conformation of Env near the cell membrane. These results advance our understanding of HIV-1 entry into host cells and may guide the development of vaccines and therapeutic agents.
Many recent studies show that superconductivity not only exists in atomically thin monolayers but can exhibit enhanced properties such as a higher transition temperature and a stronger critical ...field. Nevertheless, besides being unstable in air, the weak tunability in these intrinsically metallic monolayers has limited the exploration of monolayer superconductivity, hindering their potential in electronic applications (e.g., superconductor-semiconductor hybrid devices). Here we show that using field effect gating, we can induce superconductivity in monolayer WS2 grown by chemical vapor deposition, a typical ambient-stable semiconducting transition metal dichalcogenide (TMD), and we are able to access a complete set of competing electronic phases over an unprecedented doping range from band insulator, superconductor, to a reentrant insulator at high doping. Throughout the superconducting dome, the Cooper pair spin is pinned by a strong internal spin-orbit interaction, making this material arguably the most resilient superconductor in the external magnetic field. The reentrant insulating state at positive high gating voltages is attributed to localization induced by the characteristically weak screening of the monolayer, providing insight into many dome-like superconducting phases observed in field-induced quasi-2D superconductors.
Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-electron ...microscopy structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase both the accessibility of its receptor binding domain and the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.
The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report the structure, ...function, and antigenicity of its full-length spike (S) trimer as well as those of the Gamma and Kappa variants, and compare their characteristics with the G614, Alpha, and Beta variants. Delta S can fuse membranes more efficiently at low levels of cellular receptor angiotensin converting enzyme 2 (ACE2), and its pseudotyped viruses infect target cells substantially faster than the other five variants, possibly accounting for its heightened transmissibility. Each variant shows different rearrangement of the antigenic surface of the amino-terminal domain of the S protein but only makes produces changes in the receptor binding domain (RBD), making the RBD a better target for therapeutic antibodies.
Abstract
Motivation
The large-scale multidimensional omics data in the Genomic Data Commons (GDC) provides opportunities to investigate the crosstalk among different RNA species and their regulatory ...mechanisms in cancers. Easy-to-use bioinformatics pipelines are needed to facilitate such studies.
Results
We have developed a user-friendly R/Bioconductor package, named GDCRNATools, for downloading, organizing and analyzing RNA data in GDC with an emphasis on deciphering the lncRNA-mRNA related competing endogenous RNAs regulatory network in cancers. Many widely used bioinformatics tools and databases are utilized in our package. Users can easily pack preferred downstream analysis pipelines or integrate their own pipelines into the workflow. Interactive shiny web apps built in GDCRNATools greatly improve visualization of results from the analysis.
Availability and implementation
GDCRNATools is an R/Bioconductor package that is freely available at Bioconductor (http://bioconductor.org/packages/devel/bioc/html/GDCRNATools.html). Detailed instructions, manual and example code are also available in Github (https://github.com/Jialab-UCR/GDCRNATools).
Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves ...as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based approach. The trimeric ACE2 variant has a binding affinity of ~60 pM for the spike protein of SARS‑CoV‑2 (compared with 77 nM for monomeric ACE2 and 12-22 nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin-angiotensin system are preserved. Moreover, the engineered ACE2 potently inhibits SARS‑CoV‑2 infection in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), bearing an unusually high number of mutations, has become a dominant strain in many countries within several ...weeks. We report here structural, functional, and antigenic properties of its full-length spike (S) protein with a native sequence in comparison with those of previously prevalent variants. Omicron S requires a substantially higher level of host receptor ACE2 for efficient membrane fusion than other variants, possibly explaining its unexpected cellular tropism. Mutations not only remodel the antigenic structure of the N-terminal domain of the S protein but also alter the surface of the receptor-binding domain in a way not seen in other variants, consistent with its remarkable resistance to neutralizing antibodies. These results suggest that Omicron S has acquired an extraordinary ability to evade host immunity by excessive mutations, which also compromise its fusogenic capability.
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•Omicron spike requires a high level of ACE2 for efficient membrane fusion•Mutations in Omicron remodel the antigenic surfaces of the spike trimer•Excessive mutations may have compromised fusogenic capability of Omicron spike
Zhang et al. report that SARS-CoV-2 Omicron variant has an unusually high number of mutations in its spike (S), which requires a high level of host receptor ACE2 for efficient membrane fusion, thereby compromising its fusogenic capability. Mutations remodel the S antigenic structure, causing remarkable resistance to neutralizing antibodies.
Similar to carbon, germanium exists in various structures such as three-dimensional crystalline germanium and germanene, a two-dimensional germanium atomic layer. Regarding the electronic properties, ...they are either semiconductors or Dirac semimetals. Here, we report a highly conductive metallic state in thermally annealed germanane (hydrogen-terminated germanene, GeH), which shows a resistivity of ∼10–7 Ω·m that is orders of magnitude lower than any other allotrope of germanium. By comparing the resistivity, Raman spectra, and thickness change measured by AFM, we suggest the highly conductive metallic state is associated with the dehydrogenation during heating, which likely transforms germanane thin flakes to multilayer germanene. In addition, weak antilocalization is observed, serving as solid evidence for strong spin–orbit interaction (SOI) in germanane/germanene. Our study opens a possible new route to investigate the electrical transport properties of germanane/germanene, and the large SOI might provide the essential ingredients to access their topological states predicted theoretically.
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