Dynamic changes of phosphatidylinositol and phosphatidylinositol 4-phosphate levels modulate H-ATPase and Na/H antiporter activities to maintain ion homeostasis in Arabidopsis under salt stress.

Plant metabolites are dynamically modified and distributed in response to environmental changes. However, it is poorly understood how metabolic change functions in plant stress responses. Maintaining ion homeostasis under salt stress requires coordinated activation of two types of central regulators: plasma membrane (PM) H-ATPase and Na/H antiporter.

Stereoselective Synthesis of -Decalin-Based Spirocarbocycles via Photocyclization of 1,2-Diketones.

Diastereoselective synthesis of the -decalin-based α-hydroxyl butanone spirocarbocycles bearing all-carbon quaternary stereogenic centers has been achieved via Norrish-Yang photocyclization of -decalin-substituted-2,3-butanediones using daylight. Density functional theory (DFT) calculations suggest that this diastereoselective reaction is affected by both substrate conformation and intramolecular hydrogen bonds. The developed chemistry could be applied to synthesizing the derivatives of the -decalin-based biologically important natural products.

Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA.

Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding.

A Synthetic Route to The Core Structure of (-)-Retigeranic Acid A.

Retigeranic acid A is a uniquely structured pentacyclic sesterterpene bearing eight stereogenic centers. We report a concise route to the core structure of (-)-retigeranic acid A. The stereochemistry of its six chiral centers and three quaternary carbon centers was well-controlled.

High-throughput Method for Detecting Siderophore Production by Rhizosphere Bacteria.

Siderophores, a key substance that microorganisms produce to obtain iron under iron-limited conditions, play an important role in regulating interactions between beneficial bacteria and pathogenic bacteria. A large number of bacteria were isolated from the rhizosphere, and we used the method presented here to assay the siderophore production by these rhizosphere bacteria. This method is a modified version of the universal chrome azurol S (CAS) assay that uses a 96-channel manual pipetting workstation.

Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination.

Histone acetylation is a key histone post-translational modification that shapes chromatin structure, dynamics, and function. Bromodomain (BRD) proteins, the readers of acetyl-lysines, are located in the center of the histone acetylation-signaling network. How they regulate DNA repair and genome stability remains poorly understood.

GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA.

In 2017, we released GEPIA (Gene Expression Profiling Interactive Analysis) webserver to facilitate the widely used analyses based on the bulk gene expression datasets in the TCGA and the GTEx projects, providing the biologists and clinicians with a handy tool to perform comprehensive and complex data mining tasks. Recently, the deconvolution tools have led to revolutionary trends to resolve bulk RNA datasets at cell type-level resolution, interrogating the characteristics of different cell types in cancer and controlled cohorts became an important strategy to investigate the biological questions. Thus, we present GEPIA2021, a standalone extension of GEPIA, allowing users to perform multiple interactive analysis based on the deconvolution results, including cell type-level proportion comparison, correlation analysis, differential expression, and survival analysis.

Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A.

Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing.

FACT interacts with Set3 HDAC and fine-tunes GAL1 transcription in response to environmental stimulation.

The histone chaperone facilitates chromatin transactions (FACT) functions in various DNA transactions. How FACT performs these multiple functions remains largely unknown. Here, we found, for the first time, that the N-terminal domain of its Spt16 subunit interacts with the Set3 histone deacetylase complex (Set3C) and that FACT and Set3C function in the same pathway to regulate gene expression in some settings.

Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex.

The abnormal amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington's disease (HD). At the protein level, this translates into the expansion of a polyglutamine (polyQ) stretch located at the HTT N terminus, which renders HTT aggregation prone by unknown mechanisms. Here we investigated the effects of polyQ expansion on HTT in a complex with its stabilizing interaction partner huntingtin-associated protein 40 (HAP40).

Rotational scan digital LAMP for accurate quantitation of nucleic acids.

Digital quantitation of nucleic acids is precise and sensitive because of its molecular-level resolution. However, only several quantitation formats are common, especially pertaining to how one obtains digital signals from multiple droplets. Here we present rotational scan digital loop-mediated amplification, termed RS-dLAMP.

Nonequilibrium Thermodynamics in Biochemical Systems and Its Application.

Living systems are open systems, where the laws of nonequilibrium thermodynamics play the important role. Therefore, studying living systems from a nonequilibrium thermodynamic aspect is interesting and useful. In this review, we briefly introduce the history and current development of nonequilibrium thermodynamics, especially that in biochemical systems.

Disentangling Intrinsic and Extrinsic Gene Expression Noise in Growing Cells.

Gene expression is a stochastic process. Despite the increase of protein numbers in growing cells, the protein concentrations are often found to be confined within small ranges throughout the cell cycle. Generally, the noise in protein concentration can be decomposed into an intrinsic and an extrinsic component, where the former vanishes for high expression levels.

Co-condensation between transcription factor and coactivator p300 modulates transcriptional bursting kinetics.

The coactivator p300/CREB-binding protein (CBP) regulates genes by facilitating the assembly of transcriptional machinery and by acetylating histones and other factors. However, it remains mostly unclear how both functions of p300 are dynamically coordinated during gene control. Here, we showed that p300 can orchestrate two functions through the formation of dynamic clusters with certain transcription factors (TFs), which is mediated by the interactions between a TF's transactivation domain (TAD) and the intrinsically disordered regions of p300.

The elevated transcription of ADAM19 by the oncohistone H2BE76K contributes to oncogenic properties in breast cancer.

The recent discovery of the cancer-associated E76K mutation in histone H2B (H2BE76-to-K) in several types of cancers revealed a new class of oncohistone. H2BE76K weakens the stability of histone octamers, alters gene expression, and promotes colony formation. However, the mechanism linking the H2BE76K mutation to cancer development remains largely unknown.

A benchmark and an algorithm for detecting germline transposon insertions and measuring de novo transposon insertion frequencies.

Transposons are genomic parasites, and their new insertions can cause instability and spur the evolution of their host genomes. Rapid accumulation of short-read whole-genome sequencing data provides a great opportunity for studying new transposon insertions and their impacts on the host genome. Although many algorithms are available for detecting transposon insertions, the task remains challenging and existing tools are not designed for identifying de novo insertions.

Automated multi-class classification of skin lesions through deep convolutional neural network with dermoscopic images.

As an analytic tool in medicine, deep learning has gained great attention and opened new ways for disease diagnosis. Recent studies validate the effectiveness of deep learning algorithms for binary classification of skin lesions (i.e.

Navigating the Pauson-Khand Reaction in Total Syntheses of Complex Natural Products.

"Total synthesis endeavors provide wonderful opportunities to discover and invent new synthetic reactions as a means to advance organic synthesis in general. Such discoveries and inventions can occur when the practitioner faces intransigent problems that cannot be solved by known methods and/or when method improvements are desired in terms of elegance, efficiency, cost-effectiveness, practicality, or environmental friendliness" (K. C.

Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.

β-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-β-lactamase 1 (NDM-1) is able to hydrolyze nearly all β-lactam antibiotics and even clinically used serine-β-lactamase inhibitors. The wide and rapid spreading of NDM-1 gene among pathogenic bacteria has attracted extensive attention, therefore high potency NDM-1 inhibitors are urgently needed.

Computational study on ratio-sensing in yeast galactose utilization pathway.

Metabolic networks undergo gene expression regulation in response to external nutrient signals. In microbes, the synthesis of enzymes that are used to transport and catabolize less preferred carbon sources is repressed in the presence of a preferred carbon source. For most microbes, glucose is a preferred carbon source, and it has long been believed that as long as glucose is present in the environment, the expression of genes related to the metabolism of alternative carbon sources is shut down, due to catabolite repression.

Total Synthesis of (+)-Haperforin G.

A concise chemical synthesis of (+)-haperforin G in 20 steps from commercially available starting materials is achieved with the integration of the Co-catalyzed intramolecular Pauson-Khand reaction for the stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position and the light-initiated photocatalysis for convergent and asymmetric cross-coupling of the unstabilized C(sp)-radical with an enone. The developed chemistry paves the way to synthesizing structurally diverse analogs of haperforin G ().

Protocol for Titrating Gene Expression Levels in Budding Yeast.

The biological phenotype is affected by the level of gene expression. Here, we provide a step-by-step protocol for precisely titrating and quantitatively observing the target gene expression level in budding yeast by manipulating its copy number in the genome. Using this method, we construct various strains with different gene copy numbers of the cell cycle inhibitor Whi5.

A novel microfluidic device integrating focus-separation speed reduction design and trap arrays for high-throughput capture of circulating tumor cells.

Isolation and analysis of circulating tumor cells (CTCs) from peripheral blood provides a potential way to detect and characterize cancer. Existing technologies to separate or capture CTCs from whole blood still have issues with sample throughput, separation efficiency or stable efficiency at different flow rates. Here, we proposed a new concept to capture rare CTCs from blood by integrating a triangular prism array-based capture apparatus with streamline-based focus-separation speed reduction design.

Regulating quantal size of neurotransmitter release through a GPCR voltage sensor.

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS.