Browse Articles

Research on the controller of an active vibration isolation unit for underwater crushing operations

Mec1-mediated Atg9 phosphorylation regulates the PAS recruitment of Atg9 vesicles upon energy stress

Mec1 plays an essential role in both the DNA damage response and glucose starvation–induced autophagy. We recently reported that Mec1 regulates glucose starvation–induced autophagy through its direct binding to Atg13. However, the role of Mec1’s kinase activity in autophagy remains unclear. In this study, we demonstrate that the kinase activity of Mec1 is required for glucose starvation–induced autophagy by regulating the phagophore assembly site (PAS) recruitment of Atg9 vesicles. Mechanistic and functional analyses identified Atg9 as a direct phosphorylation substrate of Mec1, with phosphorylation occurring at the S35, T203, and T243 sites. Mutations at these sites reduce the association of Atg9 with Atg17, Atg23, and Atg27, thereby impairing the PAS recruitment of Atg9 vesicles. Notably, we found that the Mec1–Atg13 binding is a prerequisite for the phosphorylation of Atg9 by Mec1. Furthermore, Mec1-mediated phosphorylation of Atg9 is also crucial for the PAS recruitment of Atg9 vesicles in response to DNA damage. We thus propose that Mec1’s kinase activity regulates the PAS recruitment of Atg9 vesicles by phosphorylating Atg9 in response to energy stress and DNA damage.

Publisher Correction: A meta-analysis of bulk RNA-seq datasets identifies potential biomarkers and repurposable therapeutics against Alzheimer’s disease

An ear for an ear, but only if you are a deomyinid

Bioinformatics analysis of coronary microvascular dysfunction in rats based on single-cell RNA sequencing

Abscisic acid signaling gates salt-induced responses of plant roots

Soil salinity presents a dual challenge for plants, involving both osmotic and ionic stress. In response, plants deploy distinct yet interconnected mechanisms to cope with these facets of salinity stress. In this investigation, we observed a substantial overlap in the salt (NaCl)-induced transcriptional responses of Arabidopsis roots with those triggered by osmotic stress or the plant stress hormone abscisic acid (ABA), as anticipated. Notably, a specific cluster of genes responded uniquely to sodium (Na + ) ions and are not regulated by the known monovalent cation sensing mechanism MOCA1 . Surprisingly, expression of sodium-induced genes exhibited a negative correlation with the ABA response and preceded the activation of genes induced by the osmotic stress component of salt. Elevated exogenous ABA levels resulted in the complete abolition of sodium-induced responses. Consistently, the ABA insensitive snrk2.2/2.3 double mutant displayed prolonged sodium-induced gene expression, coupled with increased root cell damage and root swelling under high salinity conditions. Moreover, ABA biosynthesis and signaling mutants were unable to redirect root growth to avoid high sodium concentrations and had increased sodium accumulation in the shoot. In summary, our findings unveil an unexpected and pivotal role for ABA signaling in mitigating cellular damage induced by salinity stress and modulating sodium-induced responses in plant roots.

Assessment of heavy metals and microbial loads in Nile tilapia (Oreochromis niloticus) from different farms and rivers

Synergistic anion–π interactions in peptidomimetic polyethers

Anion–π interactions are crucial in various biological processes, such as enzyme catalysis and ion transport. Despite their significance, the exploitation of anion–π interactions in synthetic polymer systems remains underexplored. This study investigates anion–π interactions using chemically well-defined peptidomimetics guided by the composition of mussel foot proteins. Specifically, polyether-based polymers were designed utilizing two functional epoxide monomers—catechol acetonide glycidyl ether and 4,4-dimethyl-2-oxazoline glycidyl ether—to mimic the key amino acids 3,4-dihydroxyphenylalanine and aspartic acid, respectively. A surface forces apparatus was employed to study the anion–π interaction between the polymers, considering the effects of relative monomer composition and pH conditions. The maximum cohesion energy of 15.0 mJ/m 2 was observed at an equimolar monomer composition at pH 7. Incorporating a phenyl group instead of the catechol group and introducing competing anions confirmed the dominant role of anion–π interactions. This study highlights the significance of anion–π interactions, posing a high potential in the design and synthesis of functional materials.

Rapid antimicrobial susceptibility testing using carbon screen printed electrodes in a microfluidic device

Profile of Bik-Kwoon Tye

Visual perception of wind hazards using cycloidal scanning LiDAR system

QnAs with Jeremy J. Michalek and Corey D. Harper

ANGPTL3 regulates the peroxisomal translocation of SmarcAL1 in response to cell growth states

CO ₂ potentiates echinocandin efficacy during invasive candidiasis therapy via dephosphorylation of Hsp90 by Ptc2 in condensates

Carbon dioxide is a signaling cue critical for fungal pathogenesis. Ptc2, a type 2C protein phosphatase (PP2C), serves as a conserved CO 2 sensor in fungi. By combining phosphoproteomic and biochemical assays, we identified Hsp90 as a direct target of Ptc2 at host CO 2 concentrations and Ssb1 as a Ptc2 target protein regardless of CO 2 levels in Candida albicans , the most prevalent human fungal pathogen. Ptc2 forms reversible condensates at elevated CO 2 , which enables the recruitment of Hsp90, but not Ssb1, to condensates, allowing efficient dephosphorylation. This process confers an enhanced susceptibility to caspofungin in vitro and during in vivo infection therapy. Importantly, we demonstrate this phenomenon in non-albicans Candida species. Sequential passages of C. albicans in mice with caspofungin treatment readily induce in vivo drug tolerance, causing therapeutic failure. These evolved strains display increased resistance to caspofungin under host concentrations of CO 2 but remain susceptible in air. Collectively, our study reveals a profound impact of host concentrations of CO 2 on antifungal drug susceptibility and connects this phenotype to therapeutic outcomes and highlights condensate formation as an efficient means that enables selective recruitment of substrates for certain signaling events.

Quality control of hospitals and its effect on hospitalized fatality rate of COVID-19

Rapid restoration of potent neutralization activity against the latest Omicron variant JN.1 via AI rational design and antibody engineering

The rapid evolution of the viral genome has led to the continual generation of new variants of SARS-CoV-2. Developing antibody drugs with broad-spectrum and high efficiency is a long-term task. It is promising but challenging to develop therapeutic neutralizing antibodies (nAbs) through in vitro evolution based on antigen–antibody binding interactions. From an early B cell antibody repertoire, we isolated antibody 8G3 that retains its nonregressive neutralizing activity against Omicron BA.1 and various other strains in vitro. 8G3 protected ACE2 transgenic mice from BA.1 and WA1/2020 virus infection without adverse clinical manifestations and completely cleared viral load in the lungs. Similar to most IGHV3–53 antibodies, the binding sites of 8G3 and ACE2 largely overlap, enabling competition with ACE2 for binding to RBD. By comprehensively considering the binding free energy changes of the antigen–antibody complexes, the biological environment of their interactions, and the evolutionary direction of the antibodies, we were able to select 50 mutants. Among them, 11 were validated by experiments showing better neutralizing activities. Further, a combination of four mutations were identified in 8G3 that increased its neutralization potency against JN.1, the latest Omicron mutant, by approximately 1,500-fold, and one of the mutations led to an improvement in activity against multiple variants to a certain extent. Together, we established a procedure of rapid selection of neutralizing antibodies with potent SARS-CoV-2 neutralization activity. Our results provide a reference for engineering neutralizing antibodies against future SARS-CoV-2 variants and even other pandemic viruses.

The effects of perturbation intensities on backward slip-falls induced by a split-belt treadmill

Free-electron resonance transition radiation via Brewster randomness

Free-electron radiation, such as Cherenkov radiation and transition radiation, can generate light at arbitrary frequencies and is fundamental to diverse applications, ranging from electron microscopy, spectroscopy, lasers, to particle detectors. Generally, the features of free-electron radiation are stochastic when electrons interact with random media. Counterintuitively, here, we reveal a type of free-electron radiation that has both its intensity and directionality invariant to specific sorts of long-range structural randomness. Essentially, this invariance is enabled by the Brewster effect and the judiciously engineered phase coherence condition of emitted light, namely that the light induced by electron’s penetration through a layered aperiodic nanostructure is engineered to interfere constructively at the Brewster angle. As such, when each constituent layer with a random thickness fulfills this phase coherence condition, there is always the emergence of free-electron resonance transition radiation at the Brewster angle. At this resonant Brewster angle, we further find that the radiation intensity and directionality could be enhanced by orders of magnitude by readily increasing the interface number. The revealed resonance transition radiation via long-range Brewster randomness may offer a feasible route to explore more enticing photonic applications driven by free electrons, such as light sources at previously unreachable spectral regimes, optical frequency combs, particle detectors, and random lasers.

Performance analysis of palm tree microfibers in concrete

Ethylene-independent modulation of root development by ACC via downregulation of WOX5 and group I CLE peptide expression

In seed plants, the canonical role of 1-aminocyclopropane-1-carboxylic acid (ACC) is to serve as the precursor in the biosynthesis of the phytohormone ethylene, and indeed, ACC treatment is often used as a proxy for ethylene treatment. Increasing evidence suggests that ACC can also act independently of ethylene to regulate various aspects of plant growth and development. Here, we explore the effects of ACC on Arabidopsis thaliana root growth and the mechanisms by which it acts. ACC inhibits growth of the primary root in Arabidopsis seedlings when ethylene signaling is blocked, which becomes evident after 36 h of treatment with ACC. This reduced root growth is in part the result of suppressed cell proliferation in the root meristem resulting from altered expression of a key regulator of stem cell niche activity, WOX5. ACC also promotes lateral root (LR) development, in contrast to ethylene, which inhibits LR formation. Transcriptomic analysis of roots revealed no significant changes in gene expression after 45 min or 4 h of ACC treatment, but longer treatment times revealed a large number of differentially expressed genes, including the downregulation of the expression of a small group of phylogenetically related CLE peptides. Reduced expression of these group 1 CLEs in response to ACC leads to the activation of a transcription factor, LBD18, which promotes LR development. These results suggest that ACC acts to modulate multiple aspects of Arabidopsis root growth independently of ethylene via distinct transcriptional effects in the root meristem and LR precursor cells.