Integrative epigenome and transcriptome analyses reveal transcriptional programs differentially regulated by ASCL1 and NEUROD1 in small cell lung cancer.

Small cell lung cancer (SCLC), an aggressive neuroendocrine carcinoma, has an extremely poor prognosis. ASCL1 and NEUROD1 are key regulators of neuroendocrine features, and previous studies have suggested that SCLC plasticity occurs during the transition from ASCL1-positive (SCLC-A) to NEUROD1-positive (SCLC-N) subtypes. In this study, we attempted to understand the transcriptional programs governed by ASCL1 and NEUROD1 to identify markers of SCLC plasticity.

CrypToth: Cryptic Pocket Detection through Mixed-Solvent Molecular Dynamics Simulations-Based Topological Data Analysis.

Some functional proteins undergo conformational changes to expose hidden binding sites when a binding molecule approaches their surface. Such binding sites are called cryptic sites and are important targets for drug discovery. However, it is still difficult to correctly predict cryptic sites.

Electrochemical Analysis and Inhibition Assay of Immune-Modulating Enzyme, Indoleamine 2,3-Dioxygenase.

An accurate and rapid analysis of human indoleamine 2,3-dioxygenase (hIDO) is crucial for the development of anticancer pharmaceuticals because of the role of hIDO in promoting tumoral immune escape. However, the conventional assay of hIDO is limited by interference from reductants, which are used to reduce the heme iron to begin the hIDO catalytic reaction. A direct electrochemical method was applied to drive the hIDO reaction.

Enzyme cycling method using hypoxanthine-guanine phosphoribosyltransferase: a highly sensitive assay for pyrophosphate.

We developed a novel enzyme cycling method using hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (EC 2.4.2.

Involvement of lncRNA MIR205HG in idiopathic pulmonary fibrosis and IL-33 regulation via Alu elements.

Idiopathic pulmonary fibrosis (IPF) causes remodeling of the distal lung. Pulmonary remodeling is histologically characterized by fibrosis, as well as appearance of basal cells; however, the involvement of basal cells in IPF remains unclear. Here, we focus on the long noncoding RNA MIR205HG, which is highly expressed in basal cells, using RNA sequencing.

Validation of machine learning-assisted screening of PKC ligands: PKC binding affinity and activation.

Protein kinase C (PKC) is a family of serine/threonine kinases, and PKC ligands have the potential to be therapeutic seeds for cancer, Alzheimer's disease, and human immunodeficiency virus infection. However, in addition to desired therapeutic effects, most PKC ligands also exhibit undesirable pro-inflammatory effects. The discovery of new scaffolds for PKC ligands is important for developing less inflammatory PKC ligands, such as bryostatins.

Advancements in lipid production research using the koji-mold and future outlook.

Research on enhancing the production of lipids, particularly polyunsaturated fatty acids that are considered important for health, has focused on improvement of metabolism as well as heterologous expression of biosynthetic genes in the oleaginous fungus . To date, the productivity and production yield of free fatty acids have been enhanced by 10-fold to 90-fold via improvements in metabolism and optimization of culture conditions. Moreover, the productivity of ester-type fatty acids present in triacylglycerols could be enhanced via metabolic improvement.

Diversification of single-cell growth dynamics under starvation influences subsequent reproduction in a clonal bacterial population.

Most of the microbes in nature infrequently receive nutrients and are thus in slow- or non-growing states. How quickly they can resume their growth upon an influx of new resources is crucial to occupy environmental niches. Isogenic microbial populations are known to harbor only a fraction of cells with rapid growth resumption, yet little is known about the physiological characteristics of those cells and their emergence in the population.

The Statistics of Parametrized Syncmers in a Simple Mutation Process Without Spurious Matches.

Often, bioinformatics uses summary sketches to analyze next-generation sequencing data, but most sketches are not well understood statistically. Under a simple mutation model, Blanca et al. analyzed complete sketches, that is, the complete set of unassembled -mers, from two closely related sequences.

The MTR4/hnRNPK complex surveils aberrant polyadenylated RNAs with multiple exons.

RNA surveillance systems degrade aberrant RNAs that result from defective transcriptional termination, splicing, and polyadenylation. Defective RNAs in the nucleus are recognized by RNA-binding proteins and MTR4, and are degraded by the RNA exosome complex. Here, we detect aberrant RNAs in MTR4-depleted cells using long-read direct RNA sequencing and 3' sequencing.

Landscape of evolutionary arms races between transposable elements and KRAB-ZFP family.

Transposable elements (TEs) are mobile parasitic sequences that have expanded within the host genome. It has been hypothesized that host organisms have expanded the Krüppel-associated box-containing zinc finger proteins (KRAB-ZFPs), which epigenetically suppress TEs, to counteract disorderly TE transpositions. This process is referred to as the evolutionary arms race.

Prediction of antibiotic resistance mechanisms using a protein language model.

Motivation: Antibiotic resistance has emerged as a major global health threat, with an increasing number of bacterial infections becoming difficult to treat. Predicting the underlying resistance mechanisms of antibiotic resistance genes (ARGs) is crucial for understanding and combating this problem. However, existing methods struggle to accurately predict resistance mechanisms for ARGs with low similarity to known sequences and lack sufficient interpretability of the prediction models.

Raman Hyperspectral Analysis of Microbial Colonies for Secondary Metabolites Screening.

Since the discovery of penicillin, a vast array of microbial antibiotics has been identified and applied in the medical field. Globally, the search for drug candidates microbial screening is ongoing. Traditional screening methods, however, are time-consuming and require labor-intensive sample processing, significantly reducing throughput.

Deviated binding of anti-HBV nucleoside analog E-CFCP-TP to the reverse transcriptase active site attenuates the effect of drug-resistant mutations.

While certain human hepatitis B virus-targeting nucleoside analogs (NAs) serve as crucial anti-HBV drugs, HBV yet remains to be a major global health threat. E-CFCP is a 4'-modified and fluoromethylenated NA that exhibits potent antiviral activity against both wild-type and drug-resistant HBVs but less potent against human immunodeficiency virus type-1 (HIV-1). Here, we show that HIV-1 with HBV-associated amino acid substitutions introduced into the RT's dNTP-binding site (N-site) is highly susceptible to E-CFCP.

The origin of esterase activity of Parkinson's disease causative factor DJ-1 implied by evolutionary trace analysis of its prokaryotic homolog HchA.

DJ-1, a causative gene for hereditary recessive Parkinsonism, is evolutionarily conserved across eukaryotes and prokaryotes. Structural analyses of DJ-1 and its homologs suggested the 106th Cys is a nucleophilic cysteine functioning as the catalytic center of hydratase or hydrolase activity. Indeed, DJ-1 and its homologs can convert highly electrophilic α-oxoaldehydes such as methylglyoxal into α-hydroxy acids as hydratase in vitro, and oxidation-dependent ester hydrolase (esterase) activity has also been reported for DJ-1.

VeloPro: A pipeline integrating Ribo-seq and AlphaFold deciphers association patterns between translation velocity and protein structure features.

VeloPro integrates Ribo-seq data and AlphaFold2-predicted 3D protein structure information for characterization of the association patterns between translation velocity and many protein structure features in prokaryotic and eukaryotic organisms across different taxonomical clades such as bacteria, fungi, protozoa, nematode, plants, insect, and mammals. We illustrated that association patterns between translation velocity and protein structure features differ across organisms, partially reflecting their taxonomical relationship.

Double knockout of two target genes via genome co-editing using a nitrate transporter gene and a putative thiamine transporter gene as selectable markers in .

Genome co-editing technology is effective in breeding filamentous fungi for applications in the fermentation industry, achieving site-directed mutagenesis, the status of non-genetically modified organisms (non-GMOs), and wild-type-like growth phenotype. Prior to this study, thiI gene was found as a selectable marker for such genome co-editing in the filamentous fungus Aspergillus oryzae, while it cannot be reused via marker recycling. Therefore, we aimed to identify another marker gene to knock out another target gene via genome co-editing in A.

Identification of a novel RNA transcript TISPL upregulated by stressors that stimulate ATF4.

Cells sense, respond, and adapt to environmental conditions that cause stress. In a previous study using HeLa cells, we isolated reporter cells responding to the endoplasmic reticulum (ER) stress inducers, thapsigargin and tunicamycin, using a highly sensitive promoter trap vector system. Splinkerette PCR and 5' rapid amplification of cDNA ends (5' RACE) identified a novel transcript that is upregulated by ER stress.

RaptGen-Assisted Generation of an RNA/DNA Hybrid Aptamer against SARS-CoV-2 Spike Protein.

Optimization of aptamers in length and chemistry is crucial for industrial applications. Here, we developed aptamers against the SARS-CoV-2 spike protein and achieved optimization with a deep-learning-based algorithm, RaptGen. We conducted a primer-less SELEX against the receptor binding domain (RBD) of the spike with an RNA/DNA hybrid library, and the resulting sequences were subjected to RaptGen analysis.

Gustatory Responsiveness of Honey Bees Colonized with a Defined or Conventional Gut Microbiota.

Gut microbes have many beneficial functions for host animals, such as food digestion and development of the immune system. An increasing number of studies report that gut bacteria also affect host neural function and behavior. The sucrose responsiveness of the western honey bee Apis mellifera, which harbors a characteristic gut microbiota, was recently reported to be increased by the presence of gut microbes.

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches.

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing.

Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms.

Deep generative design of RNA family sequences.

RNA engineering has immense potential to drive innovation in biotechnology and medicine. Despite its importance, a versatile platform for the automated design of functional RNA is still lacking. Here, we propose RNA family sequence generator (RfamGen), a deep generative model that designs RNA family sequences in a data-efficient manner by explicitly incorporating alignment and consensus secondary structure information.

Extensive antibody search with whole spectrum black-box optimization.

In designing functional biological sequences with machine learning, the activity predictor tends to be inaccurate due to shortage of data. Top ranked sequences are thus unlikely to contain effective ones. This paper proposes to take prediction stability into account to provide domain experts with a reasonable list of sequences to choose from.

Complete mitochondrial genome sequences of two ground crickets, and (Orthoptera: Grylloidea: trigonidiidae).

The authors sequenced the complete mitochondrial (mt) genomes of the band-legged ground cricket ( Matsumura, 1904) and a temperate form of the lawn ground cricket ( Walker, 1869), collected in Japan. The length of the mt genome sequences was 15,354 bp in and 16,063 bp in . Annotation of the mt genome sequences revealed 13 protein-coding genes, two rRNA genes, and 22 tRNA genes.

Atg15 is a vacuolar phospholipase that disintegrates organelle membranes.

Atg15 (autophagy-related 15) is a vacuolar phospholipase essential for the degradation of cytoplasm-to-vacuole targeting (Cvt) bodies and autophagic bodies, hereinafter referred to as intravacuolar/intralysosomal autophagic compartments (IACs), but it remains unknown if Atg15 directly disrupts IAC membranes. Here, we show that the recombinant Chaetomium thermophilum Atg15 lipase domain (CtAtg15(73-475)) possesses phospholipase activity. The activity of CtAtg15(73-475) was markedly elevated by limited digestion.