Eukaryotic Research Articles

Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor

Myosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Motor activity control within the cell involves on/off switches, however, few examples are known of how myosins regulate speed or processivity and fine-tune their activity to a specific cellular task. Here, we describe a phosphorylation event for myosins of class VI (MYO6) in the motor domain, which accelerates its ATPase activity leading to a 4-fold increase in motor speed determined by actin-gliding assays, single molecule mechanics and stopped flow kinetics. We demonstrate that the serine/threonine kinase DYRK2 phosphorylates MYO6 at S267 in vitro. Single-molecule optical-tweezers studies at low load reveal that S267-phosphorylation results in faster nucleotide-exchange kinetics without change in the working stroke of the motor. The selective increase in stiffness of the acto-MYO6 complex when proceeding load-dependently into the nucleotide-free rigor state demonstrates that S267-phosphorylation turns MYO6 into a stronger motor. Finally, molecular dynamic simulations of the nucleotide-free motor reveal an alternative interaction network within insert-1 upon phosphorylation, suggesting a molecular mechanism, which regulates insert-1 positioning, turning the S267-phosphorylated MYO6 into a faster motor.

No observable non-thermal effect of microwave radiation on the growth of microtubules

Despite widespread public interest in the health impact of exposure to microwave radiation, studies of the influence of microwave radiation on biological samples are often inconclusive or contradictory. Here we examine the influence of microwave radiation of frequencies 3.5 GHz, 20 GHz and 29 GHz on the growth of microtubules, which are biological nanotubes that perform diverse functions in eukaryotic cells. Since microtubules are highly polar and can extend several micrometres in length, they are predicted to be sensitive to non-ionizing radiation. Moreover, it has been speculated that tubulin dimers within microtubules might rapidly toggle between different conformations, potentially participating in computational or other cooperative processes. Our data show that exposure to microwave radiation yields a microtubule growth curve that is distorted relative to control studies utilizing a homogeneous temperature jump. However, this apparent effect of non-ionizing radiation is reproduced by control experiments using an infrared laser or hot air to heat the sample and thereby mimic the thermal history of samples exposed to microwaves. As such, no non-thermal effects of microwave radiation on microtubule growth can be assigned. Our results highlight the need for appropriate control experiments in biophysical studies that may impact on the sphere of public interest.

Semisynthetic guanidino lipoglycopeptides with potent in vitro and in vivo antibacterial activity.

Gram-positive bacterial infections present a major clinical challenge, with methicillin- and vancomycin-resistant strains continuing to be a cause for concern. In recent years, semisynthetic vancomycin derivatives have been developed to overcome this problem as exemplified by the clinically used telavancin, which exhibits increased antibacterial potency but has also raised toxicity concerns. Thus, glycopeptide antibiotics with enhanced antibacterial activities and improved safety profiles are still necessary. We describe the development of a class of highly potent semisynthetic glycopeptide antibiotics, the guanidino lipoglycopeptides, which contain a positively charged guanidino moiety bearing a variable lipid group. These glycopeptides exhibited enhanced in vitro activity against a panel of Gram-positive bacteria including clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant strains, showed minimal toxicity toward eukaryotic cells, and had a low propensity for resistance selection. Mechanistically, guanidino lipoglycopeptides engaged with bacterial cell wall precursor lipid II with a higher binding affinity than vancomycin. Binding to both wild-type d-Ala-d-Ala lipid II and the vancomycin-resistant d-Ala-d-Lac variant was confirmed, providing insight into the enhanced activity of guanidino lipoglycopeptides against vancomycin-resistant isolates. The in vivo efficacy of guanidino lipoglycopeptide EVG7 was evaluated in a S. aureus murine thigh infection model and a 7-day sepsis survival study, both of which demonstrated superiority to vancomycin. Moreover, the minimal to mild kidney effects at supratherapeutic doses of EVG7 indicate an improved therapeutic safety profile compared with vancomycin. These findings position guanidino lipoglycopeptides as candidates for further development as antibacterial agents for the treatment of clinically relevant multidrug-resistant Gram-positive infections.

Assessing predictions on fitness effects of missense variants in HMBS in CAGI6.

This paper presents an evaluation of predictions submitted for the "HMBS" challenge, a component of the sixth round of the Critical Assessment of Genome Interpretation held in 2021. The challenge required participants to predict the effects of missense variants of the human HMBS gene on yeast growth. The HMBS enzyme, critical for the biosynthesis of heme in eukaryotic cells, is highly conserved among eukaryotes. Despite the application of a variety of algorithms and methods, the performance of predictors was relatively similar, with Kendall's tau correlation coefficients between predictions and experimental scores around 0.3 for a majority of submissions. Notably, the median correlation (≥ 0.34) observed among these predictors, especially the top predictions from different groups, was greater than the correlation observed between their predictions and the actual experimental results. Most predictors were moderately successful in distinguishing between deleterious and benign variants, as evidenced by an area under the receiver operating characteristic (ROC) curve (AUC) of approximately 0.7 respectively. Compared with the recent two rounds of CAGI competitions, we noticed more predictors outperformed the baseline predictor, which is solely based on the amino acid frequencies. Nevertheless, the overall accuracy of predictions is still far short of positive control, which is derived from experimental scores, indicating the necessity for considerable improvements in the field. The most inaccurately predicted variants in this round were associated with the insertion loop, which is absent in many orthologs, suggesting the predictors still heavily rely on the information from multiple sequence alignment.

Tributyltin induces apoptosis in mammalian cells invivo: a scoping review.

The present review aimed to evaluate the apoptotic effect of tributyltin (TBT) exposure on mammalian tissues and cells invivo. A search was conducted in specialized literature databases including Embase, Medline, Pubmed, Scholar Google, and Scopus for all manuscripts using the following keywords: "tributyltin", "apoptosis", "mammals", "mammalian cells', "eukaryotic cells", 'rodents', "rats", "mice" and "invivo" for all data published until September 2023. A total of 16 studies were included. The studies have demonstrated that TBT exposure induces apoptosis in cells from various mammalian organs or tissues invivo. TBT is capable to increase apoptotic cells, to activate proapoptotic proteins such as calpain, caspases, bax andbeclin-1 and to inhibit antiapoptotic protein bcl-2. Additionally, TBT alters the ratio of bcl-2/bax which favor apoptosis. Therefore, the activation of enzymes such as calpain induces apoptosis mediated by ERS and caspases through the intrinsic apoptosis pathway. This review has demonstrated that TBT exposure induces apoptosis in mammalian tissues and cells invivo.

D-Glutamate production by stressed Escherichia coli gives a clue for the hypothetical induction mechanism of the ALS disease

In the search for the origin of Amyotrophic Lateral Sclerosis disease (ALS), we hypothesized earlier (Monselise, 2019) that d-amino acids produced by stressed microbiome may serve as inducers of the disease development. Many examples of d-amino acid accumulation under various stress conditions were demonstrated in prokaryotic and eukaryotic cells. In this work, wild-type Escherichia coli, members of the digestive system, were subjected to carbon and nitrogen starvation stress. Using NMR and LC–MS techniques, we found for the first time that d-glutamate accumulated in the stressed bacteria but not in control cells. These results together with the existing knowledge, allow us to suggest a new insight into the pathway of ALS development: d-glutamate, produced by the stressed microbiome, induces neurobiochemical miscommunication setting on C1q of the complement system. Proving this insight may have great importance in preventive medicine of such MND modern-age diseases as ALS, Alzheimer, and Parkinson.

Anaplasma phagocytophilum effector EgeA facilitates infection by hijacking TANGO1 and SCFD1 from ER–Golgi exit sites to pathogen-occupied inclusions

The obligatory intracellular bacterium Anaplasma phagocytophilum causes human granulocytic anaplasmosis, an emerging zoonosis. Anaplasma has limited biosynthetic and metabolic capacities, yet it effectively replicates inside of inclusions/vacuoles of eukaryotic host cells. Here, we describe a unique Type IV secretion system (T4SS) effector, ER-Golgi exit site protein of Anaplasma (EgeA). In cells infected by Anaplasma, secreted native EgeA, EgeA-GFP, and the C-terminal half of EgeA (EgeA-C)-GFP localized to Anaplasma-containing inclusions. In uninfected cells, EgeA-C-GFP localized to cis-Golgi, whereas the N-terminal half of EgeA-GFP localized to the ER. Pull-down assays identified EgeA-GFP binding to a transmembrane protein in the ER, Transport and Golgi organization protein 1 (TANGO1). By yeast two-hybrid analysis, EgeA-C directly bound Sec1 family domain-containing protein 1 (SCFD1), a host protein of the cis-Golgi network that binds TANGO1 at ER-Golgi exit sites (ERES). Both TANGO1 and SCFD1 localized to the Anaplasma inclusion surface. Furthermore, knockdown of Anaplasma EgeA or either host TANGO1 or SCFD1 significantly reduced Anaplasma infection. TANGO1 and SCFD1 prevent ER congestion and stress by facilitating transport of bulky or unfolded proteins at ERES. A bulky cargo collagen and the ER-resident chaperon BiP were transported into Anaplasma inclusions, and several ER stress marker genes were not up-regulated in Anaplasma-infected cells. Furthermore, EgeA transfection reduced collagen overexpression-induced BiP upregulation. These results suggest that by binding to the two ERES proteins, EgeA redirects the cargo-adapted ERES to pathogen-occupied inclusions and reduces ERES congestion, which facilitates Anaplasma nutrient acquisition and reduces ER stress for Anaplasma survival and proliferation.

Structural and biophysical insights into the interactions of anisotropic gold nanoparticles with human telomeric G-quadruplex DNA: Spectroscopic and calorimetric approach

We are reporting curcumin-induced synthesis of anisotropic citrate capped Gold nanoparticles (ctGNPs). The techniques such as UV–visible spectroscopy, Raman spectroscopy, FT-IR, X-ray diffraction (XRD), and Transmission Electron Microscopy (TEM) were used to characterize the nanoparticles. The synthetic route shows the formation of an anisotropic gold nanostructure consisting of spherical, triangles, hexagonals, and a low-yield rod with an aspect ratio ranging from 4.2 to 8.5. Curcumin-derived ctGNPs shows stability at different physiological conditions and better biocompatibility. Synthesized nanoparticles are found non-toxic towards eukaryotic cells but more effective against the cancer cell lines HeLa and MCF-7. The interaction of these synthesized nanoparticles with human telomeric G-quadruplex (GQ) DNA was studied using different physiochemical methods. The spectroscopic studies show that synthesized nanoparticles have stronger binding affinity towards telomeric GQ as compared to ds DNA through Van der Waals and H-bonding interactions. Thermodynamic interpretation reveals that the formation of the complex between the telomeric GQ and ctGNPs are enthalpy driven and entropy unfavourable process, resulting in motion freezing and, eventually, AuNP aggregation. Thus, our study shows a new approach to understand the interaction of telomeric G-quadruplexes with gold nanoparticles generated via the green route.

Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease.

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues. Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC). Results: BNZ-NS exhibited particle size <500nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi. Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

Direct targeting of host microtubule and actin cytoskeletons by a chlamydial pathogenic effector protein.

To propagate within a eukaryotic cell, pathogenic bacteria hijack and remodulate host cell functions. The Gram-negative obligate intracellular Chlamydiaceae, which pose a serious threat to human and animal health, attach to host cells and inject effector proteins that reprogram host cell machineries. Members of the conserved chlamydial TarP family have been characterized as major, early effectors that bind to and remodel the host actin cytoskeleton. We now describe a new function for the Chlamydia pneumoniae TarP member CPn0572, namely the ability to bind and alter the microtubule cytoskeleton. Thus, CPn0572 is unique in being the only prokaryotic protein that directly modulates both dynamic cytoskeletons of a eukaryotic cell. Ectopically expressed GFP-CPn0572 associates in a dose-independent manner with either cytoskeleton singly or simultaneously. In vitro, CPn0572 binds directly to microtubules. Expression of a microtubule-only CPn0572 variant resulted in the formation of an aberrantly thick, stabilized microtubule network. Intriguingly, during infection, secreted CPn0572 also co-localized with altered microtubules, suggesting that this protein also affects microtubule dynamics during infection. Our analysis points to a crosstalk between actin and microtubule cytoskeletons via chlamydial CPn0572.

An Update on the Study of the Molecular Mechanisms Involved in Autophagy during Bacterial Pathogenesis

Autophagy is a unique catabolic process that degrades irrelevant or damaged components in eukaryotic cells to maintain homeostasis and eliminate infections from pathogenesis. Pathogenic bacteria have developed many autophagy manipulation techniques that affect host immune responses and intracellular bacterial pathogens have evolved to avoid xenophagy. However, reducing its effectiveness as an innate immune response has not yet been elucidated. Bacterial pathogens cause autophagy in infected cells as a cell-autonomous defense mechanism to eliminate the pathogen. However, harmful bacteria have learned to control autophagy and defeat host defenses. Intracellular bacteria can stimulate and control autophagy, while others inhibit it to prevent xenophagy and lysosomal breakdown. This review evaluates the putative functions for xenophagy in regulating bacterial infection, emphasizing that successful pathogens have evolved strategies to disrupt or exploit this defense, reducing its efficiency in innate immunity. Instead, animal models show that autophagy-associated proteins influence bacterial pathogenicity outside of xenophagy. We also examine the consequences of the complex interaction between autophagy and bacterial pathogens in light of current efforts to modify autophagy and develop host-directed therapeutics to fight bacterial infections. Therefore, effective pathogens have evolved to subvert or exploit xenophagy, although autophagy-associated proteins can influence bacterial pathogenicity outside of xenophagy. Finally, this review implies how the complex interaction between autophagy and bacterial pathogens affects host-directed therapy for bacterial pathogenesis.

Deciphering the genetic impact of signal peptide missense CTLA-4 polymorphism with rheumatoid arthritis in the Indian population: A case-control and in silico studies

Cytoplasmic T Lymphocyte Antigen-4 (CTLA-4) gene encodes for a glycoprotein, expressed on activated T-cells to transfer an inhibitory signal to control T-cell activation and proliferation. Techniques coupled with Real-time Polymerase Chain Reaction (PCR) and High-Resolution Melting Analysis (HRMA) were used to screen a missense signal peptide polymorphism (CTLA-4 + 49 A/G rs231775) in the Indian population to detect its association with Rheumatoid Arthritis (RA). Further, the resulting outcome was confirmed by Sanger’s sequencing technique, and genotype frequencies were calculated. In eukaryotic cells, the M domain of the Signal Recognition Particle (SRP-54) recognizes the N-terminal region of the Signal Peptide (SP) sequence. It directs the polypeptide chain into the Sec-61 translocon of the Endoplasmic Reticulum (ER) for further protein modification. As the Single Nucleotide Polymorphism (SNP) rs231775 lies in the signal peptide region of CTLA-4, an in-silico study was also performed to predict the mRNA stability and SP-SRP protein interaction. From the study, it was observed that the genotype frequency of rs231775 SNP G/G homozygous dominant was significantly higher in RA patients than G/A heterozygous dominant and A/A homozygous recessive conditions (Odd Ratio (OR) = 2.0862; 95 % Confidence Interval (C.I) = 1.2584 to 3.4584; Relative Risk (RR) = 1.8507; P = 0.0044). Moreover, the rs231775 SNP G allele frequency was higher than the control group G = 0.407 (40.7 %) vs 0.32 (32 %). In silico approaches of Protein-Protein docking and Molecular Dynamics (MD) simulation reveal CTLA-4 rs231775 SNP (G allele) has destabilized the SP-SRP protein complex, which may affect the translocation of CTLA-4 nascent polypeptide chains into the ER via activating Regulation of Aberrant Protein Production (RAPP) pathway.

Analysis of the partial sequencing of clbA, clbB and clbQ in Escherichia coli isolates that produce colibactin and multilocus sequence typing

Colibactin, is a cyclomodulin expressed from polyketide synthase (pk) genomic islands. These bacterial toxins interfere with the eukaryotic cell cycle and induce DNA damage. The aim of the present study was to investigate the prevalence of colibactin production among E. coli strains recovered from different infections, determine the similarity of clb nucleotide sequences, and identify genotype of isolates using multilocus sequence typing(MLST). This was a prospective, cross-sectional study conducted from January 2022 to February 2023. A total of 117 clinical isolates were obtained from various sample types collected from outpatients and inpatients recruited to the Department of Bacteriology Labs in different hospitals in Baghdad, Iraq. clbA/clbR, clbB and clbP/clbQ were detected via conventional PCR, and partial sequencing of amplicons was performed via Sanger sequencing. For select isolates, MLST genotyping was performed. The most common phylogenetic group was B2 (61/106; 57.54%). Among the E. coli strains, 27/106 (25.47%) were clb + ve, and the most common type was clbB (13/27; 48.14%). Analysis of the partial sequencing of clb among the strains revealed high molecular similarity. Genotyping of 37 selected E. coli strains via MLST revealed 28 different genotypes. There was a high prevalence of colibactin production in phylogroup B2, and it seems that the clb + ve strains had conserved molecular structures. There was high genetic diversity among the strains tested.

On the quaternary structure of human D-3-phosphoglycerate dehydrogenase.

D-3-phosphoglycerate dehydrogenase (PHGDH) catalyzes the NAD+-dependent conversion of D-3-phospho-glycerate to 3-phosphohydroxypyruvate, the first step in the phosphorylated pathway for L-serine (L-Ser) biosynthesis. L-Ser plays different relevant metabolic roles in eukaryotic cells: alterations in L-Ser metabolism have been linked to serious neurological disorders. The human PHGDH (hPHGDH), showing a homotetrameric state in solution, is made of four domains, among which there are two regulatory domains at the C-terminus: the aspartate kinase-chorismate mutase-tyrA prephenate dehydrogenase (ACT) and allosteric substrate-binding (ASB) domains. The structure of hPHGDH was solved only for a truncated, dimeric form harboring the N-terminal end containing the substrate and the cofactor binding domains. A model ensemble of the tetrameric hPHGDH was generated using AlphaFold coupled with molecular dynamics refinement. By analyzing the inter-subunit interactions at the tetrameric interface, the residues F418, L478, P479, R454, and Y495 were selected and their role was studied by the alanine-scanning mutagenesis approach. The F418A variant modifies the putative ASB, slightly alters the activity, the fraction of protein in the tetrameric state, and the protein stability; it seems relevant in dimers' recognition to yield the tetrameric oligomer. On the contrary, the R454A, L478A, P479A, and Y495A variants (ACT domain) determine a loss of the tetrameric assembly, resulting in low stability and misfolding, triggering the aggregation and hampering the activity. The predicted tetrameric interface seems mediated by residues at the ACT domain, and the tetramer formation seems crucial for proper folding of hPHGDH, which, in turn, is essential for both stability and functionality.

A dose-dependent bimodal switch by homologous Aux/IAA transcriptional repressors

Combinatorial interactions between different regulators diversify and enrich the chance of transcriptional regulation in eukaryotic cells. However, a dose-dependent functional switch of homologous transcriptional repressors has rarely been reported. Here, we show that SHY2, an Auxin/Indole-3-Acetic Acid (Aux/IAA) repressor, exhibits a dose-dependent bimodal role in auxin-sensitive root-hair growth and gene transcription in Arabidopsis, whereas other Aux/IAA homologs consistently repress the auxin responses. The corepressor (TOPLESS [TPL])-binding affinity of a bimodal Aux/IAA was lower than that of a consistently repressing Aux/IAA. The switch of a single amino-acid residue in the TPL-binding motif between the bimodal form and the consistently repressing form switched their TPL-binding affinity and transcriptional and biological roles in auxin responses. Based on these data, we propose a model whereby competition between homologous repressors with different corepressor-binding affinities could generate a bimodal output at the transcriptional and developmental levels.

A condensates-to-VPS41-associated phagic vacuoles conversion pathway controls autophagy degradation in plants.

Autophagy is a universal degradation system in eukaryotic cells. In plants, although autophagosome biogenesis has been extensively studied, the mechanism of how autophagosomes are transported to the vacuole for degradation remains largely unexplored. In this study, we demonstrated that upon autophagy induction, Arabidopsis homotypic fusion and protein sorting (HOPS) subunit VPS41 converts first from condensates to puncta, then to ring-like structures, termed VPS41-associated phagic vacuoles (VAPVs), which enclose autophagy-related gene (ATG)8s for vacuolar degradation. This process is initiated by ADP ribosylation factor (ARF)-like GTPases ARLA1s and occurs concurrently with autophagy progression through coupling with the synaptic-soluble N-ethylmaleimide-sensitive factor attachment protein rmleceptor (SNARE) proteins. Unlike in other eukaryotes, autophagy degradation in Arabidopsis is largely independent of the RAB7 pathway. By contrast, dysfunction in the condensates-to-VAPVs conversion process impairs autophagosome structure and disrupts their vacuolar transport, leading to a significant reduction in autophagic flux and plant survival rate. Our findings suggest that the conversion pathway might be an integral part of the autophagy program unique to plants.

The IGF2BP3/Notch/Jag1 pathway: A key regulator of hepatic stellate cell ferroptosis in liver fibrosis.

Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), which involves various epigenetic modifications. N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, influences numerous physiological and pathological processes. Nevertheless, the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader gene mediating m6A modifications, in liver fibrosis remains unclear. This study demonstrated that IGF2BP3 knockout reduces liver fibrosis by promoting HSC ferroptosis (FPT) and inactivating HSCs. Multi-omics analysis revealed that HSC-specific IGF2BP3 knockout decreased m6A content in Jagged1 (Jag1), a key component of the Notch signalling pathway. Furthermore, IGF2BP3 deficiency significantly reduced the expression of hairy and enhancer of split-1 (Hes1), a transcription factor in the Notch/Jag1 signalling pathway, with mRNA levels declining to 35%-62% and protein levels to 28%-35%. Additionally, it suppressed glutathione peroxidase 4 (GPX4) (decreased to approximately 31%-38%), a negative regulator of FPT, thereby facilitating HSC FPT progression and reducing profibrotic gene expression. These findings uncover a novel IGF2BP3/Notch/Jag1 signalling pathway involving HSC FPT, suggesting promising targets for ameliorating liver fibrosis. IGF2BP3 deficiency inactivates Jag1 signalling. IGF2BP3 deficiency-mediated m6A modifications promote HSC ferroptosis. IGF2BP3 inhibition facilitates ferroptosis in HSCs via the Hes1/GPX4 axis. IGF2BP3 deficiency inactivates Jag1/Notch1/3/Hes1 signalling pathway inactivation, leading to the decrease in GPX4, which contributes to HSC ferroptosis.

Dynamics of diversified A-to-I editing in Streptococcus pyogenes is governed by changes in mRNA stability.

Adenosine-to-inosine (A-to-I) RNA editing plays an important role in the post-transcriptional regulation of eukaryotic cell physiology. However, our understanding of the occurrence, function and regulation of A-to-I editing in bacteria remains limited. Bacterial mRNA editing is catalysed by the deaminase TadA, which was originally described to modify a single tRNA in Escherichia coli. Intriguingly, several bacterial species appear to perform A-to-I editing on more than one tRNA. Here, we provide evidence that in the human pathogen Streptococcus pyogenes, tRNA editing has expanded to an additional tRNA substrate. Using RNA sequencing, we identified more than 27 editing sites in the transcriptome of S.pyogenes SF370 and demonstrate that the adaptation of S.pyogenes TadA to a second tRNA substrate has also diversified the sequence context and recoding scope of mRNA editing. Based on the observation that editing is dynamically regulated in response to several infection-relevant stimuli, such as oxidative stress, we further investigated the underlying determinants of editing dynamics and identified mRNA stability as a key modulator of A-to-I editing. Overall, our findings reveal the presence and diversification of A-to-I editing in S.pyogenes and provide novel insights into the plasticity of the editome and its regulation in bacteria.

Mitosis: An expanded view of mitotic mechanisms that arose in evolution

Mitosis exhibits astonishing evolutionary plasticity, with dividing eukaryotic cells differing in the organization of the mitotic spindle and the extent of nuclear envelope breakdown. A new study suggests that a multinucleated lifestyle may favor the evolution of closed nuclear division.

An acridone based fluorescent dye for lipid droplet tracking and cancer diagnosis

Lipid droplets (LDs) are spherical organelles that localize in the cytosol of eukaryotic cells. Different proteins are embedded on the surface of LDs, so LDs play a vital role in the physiological activities of cells. The dysregulation of LDs is associated with various human diseases, such as diabetes and obesity. Therefore, it is essential to develop a fluorescent dye that labels LDs to detect and monitor illnesses. In this study, we developed the compound BDAA12C for staining LDs in cells. BDAA12C exhibits excellent LD specificity and low toxicity, enabling us to successfully stain and observe the fusion of LDs in A549 cancer cells. Furthermore, we also successfully distinguished A549 cancer cells and MRC-5 normal cells in a co-culture experiment and in normal and tumour tissues. Interestingly, we found different localizations of BDAA12C in well-fed and starved A549 cancer cells and consequently illustrated the transfer of fatty acids (FAs) from LDs to mitochondria to supply energy for β-oxidation upon starvation. Therefore, BDAA12C is a promising LD-targeted probe for cancer diagnosis and tracking lipid trafficking within cells.