Prokaryotes use repetitive genomic elements termed CRISPR (clustered regularly interspaced short palindromic repeats) to destroy invading genetic molecules. Although CRISPR systems have been widely ...used in DNA and RNA technology, certain adverse effects do occur. For example, constitutively active CRISPR systems may lead to a certain risk of off-target effects. Here, we introduce post-synthetic masking and chemical activation of guide RNA (gRNA) to controlling CRISPR systems. An RNA structure profiling probe (2-azidomethylnicotinic acid imidazolide) is used. Moreover, we accomplish conditional control of gene editing in live cells. This proof-of-concept study demonstrates promising potential of chemical activation of gRNAs as a versatile tool for chemical biology.
Dimethylsulfoniopropionate (DMSP) is a marine organosulfur compound with important roles in stress protection, marine biogeochemical cycling, chemical signalling and atmospheric chemistry. Diverse ...marine microorganisms catabolize DMSP via DMSP lyases to generate the climate‐cooling gas and info‐chemical dimethyl sulphide. Abundant marine heterotrophs of the Roseobacter group (MRG) are well known for their ability to catabolize DMSP via diverse DMSP lyases. Here, a new DMSP lyase DddU within the MRG strain Amylibacter cionae H‐12 and other related bacteria was identified. DddU is a cupin superfamily DMSP lyase like DddL, DddQ, DddW, DddK and DddY, but shares <15% amino acid sequence identity with these enzymes. Moreover, DddU proteins forms a distinct clade from these other cupin‐containing DMSP lyases. Structural prediction and mutational analyses suggested that a conserved tyrosine residue is the key catalytic amino acid residue in DddU. Bioinformatic analysis indicated that the dddU gene, mainly from Alphaproteobacteria, is widely distributed in the Atlantic, Pacific, Indian and polar oceans. For reference, dddU is less abundant than dddP, dddQ and dddK, but much more frequent than dddW, dddY and dddL in marine environments. This study broadens our knowledge on the diversity of DMSP lyases, and enhances our understanding of marine DMSP biotransformation.
Choose your poison: Chiral CdTe quantum dots (QDs) coated with L‐ or D‐glutathione (GSH) stabilizers exhibit differences in cytotoxicity although they have identical composition and size. D‐GSH‐QDs ...are less cytotoxic than L‐GSH‐QDs. The ability of QDs to induce cell death is correlated with their ability to induce autophagy, which is chirality‐dependent (see picture).
An unprecedented asymmetric allenylic alkylation of readily available imine esters, which was enabled by a synergistic Cu/Pd catalysis, has been developed. This dual catalytic system possesses good ...substrate compatibility, delivering a diverse array of nonproteinogenic α‐allenylic α‐mono‐ or α,α‐disubstituted α‐amino acids (α‐AAs) with high yields and generally excellent enantioselectivities. Furthermore, the scalability and practicability of the current synthetic protocol were proven by performing gram‐scale reactions and by the first catalytic asymmetric synthesis of naturally occurring (S)‐γ‐allenic α‐amino acid, respectively.
Synergy for asymmetry: An unprecedented asymmetric allenylic alkylation of readily available imine esters enabled by a synergistic Cu/Pd catalysis has been developed. This dual catalytic system possesses good substrate compatibility, delivering a diverse array of nonproteinogenic α‐allenylic α‐mono‐ or α,α‐disubstituted α‐amino acids with high yields and generally excellent enantioselectivities. Gram‐scale reactions were performed, and the synthetic protocol allowed for the first catalytic asymmetric synthesis of naturally occurring (S)‐γ‐allenic α‐amino acids.
The collagenases of Vibrio species, many of which are pathogens, have been regarded as an important virulence factor. However, there is little information on the structure and collagenolytic ...mechanism of Vibrio collagenase. Here, we report the crystal structure of the collagenase module (CM) of Vibrio collagenase VhaC and the conformation of VhaC in solution. Structural and biochemical analyses and molecular dynamics studies reveal that triple-helical collagen is initially recognized by the activator domain, followed by subsequent cleavage by the peptidase domain along with the closing movement of CM. This is different from the peptidolytic mode or the proposed collagenolysis of Clostridium collagenase. We propose a model for the integrated collagenolytic mechanism of VhaC, integrating the functions of VhaC accessory domains and its collagen degradation pattern. This study provides insight into the mechanism of bacterial collagenolysis and helps in structure-based drug design targeting of the Vibrio collagenase.
Uncovering the mechanisms of virus infection and assembly is crucial for preventing the spread of viruses and treating viral disease. The technique of single-virus tracking (SVT), also known as ...single-virus tracing, allows one to follow individual viruses at different parts of their life cycle and thereby provides dynamic insights into fundamental processes of viruses occurring in live cells. SVT is typically based on fluorescence imaging and reveals insights into previously unreported infection mechanisms. In this review article, we provide the readers a broad overview of the SVT technique. We first summarize recent advances in SVT, from the choice of fluorescent labels and labeling strategies to imaging implementation and analytical methodologies. We then describe representative applications in detail to elucidate how SVT serves as a valuable tool in virological research. Finally, we present our perspectives regarding the future possibilities and challenges of SVT.
Abstract
The nearly 33 yr long-term radio light curve obtained with the Metsähovi Radio Observatory 14 m telescope at 37 GHz and the recent 12.7 yr
γ
-ray light curve of the blazar S5 0716+714 at ...0.1–300 GeV from the Fermi Large Area Telescope (Fermi-LAT) were analyzed by using the Lomb–Scargle periodogram and the weighted wavelet Z-transform techniques. In the radio light curve, we discovered a possible quasi-periodic oscillation (QPO) signal of about 352 ± 23 days at a confidence level of ∼3
σ
. We recalculated the periodicity and its significance in a chosen time range that has higher variability and denser sampling, and then found that the significance had increased to a confidence level of 99.996% (∼4.1
σ
). This QPO component was further confirmed by fitting a linear autoregressive integrated moving average model to the selected radio light curve. A possible QPO of 960 ± 80 days at a 99.35% level (∼2.7
σ
) was found in the
γ
-ray light curve, which generally agrees with the earlier QPO claims of S5 0716+714. This paper discusses possible mechanisms for this potential year-like QPO. One possibility is a pure geometrical scenario with blobs moving helically inside the jet. Another is a supermassive binary black hole involving a gravitational wave-driven regime. In the latter scenario, we derived a milliparsec separation in the binary system that undergoes coalescence within a century due to the emission of low-frequency gravitational waves.
Layered transition metal oxide (NaxTMO2), being one of the most promising cathode candidates for sodium‐ion batteries (SIBs), have attracted intensive interest because of their nontoxicity, high ...theoretical capacities, and easy manufacturability. However, their physical and electrochemical properties of water sensitivity, sluggish Na+ transport kinetics, and irreversible multiple‐phase translations hinder the practical application. Here, a concept of surface lattice‐matched engineering is proposed based on in situ spinel interfacial reconstruction to design a spinel coating P2/P3 heterostructure cathode material with enhanced air stability, rate, and cycle performance. The novel structure and its formation process are verified by transmission electron microscopy and in situ high‐temperature X‐ray diffraction. The electrode exhibits an excellent rate performance with the highly reversible phase transformation demonstrated by in situ charging/discharging X‐ray diffraction. Additionally, even after a rigorous water sensitivity test, the electrode materials still retain almost the same superior electrochemical performance as the fresh sample. The results show that the surface spinel phase can play a vital role in preventing the ingress of water molecules, improving transport kinetics, and enhancing structural integrity for NaxTMO2 cathodes. The concept of surface lattice‐matched engineering based on in situ spinel interfacial reconstruction will be helpful for designing new ultra‐stable cathode materials for high‐performance SIBs.
The formation process and function mechanism for inhibiting phase transformation and enhancing air stability of surface lattice‐matched engineering based on in situ spinel interfacial reconstruction are studied. This strategy of designing heterostructure with in situ interfacial reconstruction will inspire the exploitation of new chemistries and materials.
Photoacoustic molecular imaging is an emerging and promising diagnostic tool for heavy metal ions detection. Methylmercury (MeHg+) is one of the most potent neurotoxins, which damages the brain and ...nervous system of human beings through fish consumption. The development of a selective and sensitive method for MeHg+ detection is highly desirable. In this Communication, we develope a chemoselective photoacoustic sensor (LP‐hCy7) composed of the liposome (LP) and MeHg+‐responsive near‐infrared (NIR) cyanine dye (hCy7) for MeHg+ detection within living subjects, such as zebrafish and mouse. The as‐prepared LP‐hCy7 nanoprobe displays unique dual‐shift NIR absorbance peaks and produces a normalized turn‐on response after the reaction of MeHg+ and hCy7 through a mercury‐promoted cyclization reaction. The absorbance intensities of LP‐hCy7 nanoprobe at 690 and 860 nm are decreased and increased, respectively. The ratiometric photoacoustic signal (PA860/PA690) is noticeably increased in the presence of MeHg+. These findings not only provide a ratiometric photoacoustic molecular imaging probe for the detection of metal ions in vivo, but also provides a tool for spectroscopic photoacoustic molecular imaging.
A promising MeHg+ (methylmercury) detection strategy by ratiometric photoacoustic molecular imaging shows very high sensitivity and selectivity in living subjects, such as zebrafish and mouse. MeHg+ is one of the most potent neurotoxins and can damage the brain and nervous system of human beings through fish consumption. Therefore, the development of this visualization tool is highly desirable.
N
6
-Methyladenosine (m
6
A) is the most common posttranscriptional modification of RNA and plays critical roles in cancer pathogenesis. However, the biological function of long noncoding RNA ...(lncRNA) methylation remains unclear. As a demethylase, ALKBH5 (alkylation repair homolog protein 5) is involved in mediating methylation reversal. The purpose of this study was to investigate lncRNA m
6
A modification and its role in gastric cancer (GC). Bioinformatics predicted interactions of ALKBH5 with lncRNAs. Five methods were employed to assess the function of nuclear paraspeckle assembly transcript 1 (NEAT1), including gene silencing, RT-PCR, separation of nuclear and cytoplasmic fractions, scrape motility assays, and transwell migration assays. Then, m
6
A RNA immunoprecipitation and immunofluorescence were used to detect methylated NEAT1 in GC cells. Rescue assays were performed to define the relationship between NEAT1 and ALKBH5. NEAT1 is a potential binding lncRNA of ALKBH5. NEAT1 was overexpressed in GC cells and tissue. Additional experiments confirmed that knockdown of NEAT1 significantly repressed invasion and metastasis of GC cells. ALKBH5 affected the m
6
A level of NEAT1. The binding of ALKBH5 and NEAT1 influences the expression of EZH2 (a subunit of the polycomb repressive complex) and thus affects GC invasion and metastasis. Our findings indicate a novel mechanism by which ALKBH5 promotes GC invasion and metastasis by demethylating the lncRNA NEAT1. They may be potential therapeutic targets for GC.
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