Formation of I+III supercomplex rescues respiratory chain defects.

Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.

ProPr54 web server: predicting σ promoters and regulon with a hybrid convolutional and recurrent deep neural network.

σ serves as an unconventional sigma factor with a distinct mechanism of transcription initiation, which depends on the involvement of a transcription activator. This unique sigma factor σ is indispensable for orchestrating the transcription of genes crucial to nitrogen regulation, flagella biosynthesis, motility, chemotaxis and various other essential cellular processes. Currently, no comprehensive tools are available to determine σ promoters and regulon in bacterial genomes.

Potential Use of Plasma Rich in Growth Factors in Age-Related Macular Degeneration: Evidence from a Mouse Model.

: Age-related macular degeneration (AMD) is the leading cause of low vision and legal blindness in adults in developed countries. Wet AMD can be successfully treated using vascular endothelial growth factor (VEGF) inhibitors; however, dry AMD currently has no effective treatment. The purpose of this study is to analyze the efficacy of intraocular injection of plasma rich in growth factors (PRGF) in an AMD mouse model induced by intraperitoneal administration of sodium iodate.

Novel Eel Skin Fibroblast Cell Line: Bridging Adherent and Suspension Growth for Aquatic Applications Including Virus Susceptibility.

Suspension growth can greatly increase the cell density and yield of cell metabolites. To meet the requirements of aquatic industries, a culture model derived from skin was developed using the explant outgrowth and enzyme-digesting passaging methods. These cells were kept in vitro continuously for over 12 months and subcultured 68 times.

A novel isoform of Tensin1 promotes actin filament assembly for efficient erythroblast enucleation.

Mammalian red blood cells are generated via a terminal erythroid differentiation pathway culminating in cell polarization and enucleation. Actin filament polymerization is critical for enucleation, but the molecular regulatory mechanisms remain poorly understood. We utilized publicly available RNA-seq and proteomics datasets to mine for actin-binding proteins and actin-nucleation factors differentially expressed during human erythroid differentiation and discovered that a focal adhesion protein-Tensin-1-dramatically increases in expression late in differentiation.

Intellectual frameworks to understand complex biochemical systems at the origin of life.

Understanding the emergence of complex biochemical systems, such as protein translation, is a great challenge. Although synthetic approaches can provide insight into the potential early stages of life, they do not address the equally important question of why the complex systems of life would have evolved. In particular, the intricacies of the mechanisms governing the transfer of information from nucleic acid sequences to proteins make it difficult to imagine how coded protein synthesis could have emerged from a prebiotic soup.

Bioremediation of catecholic pollutants with novel oxygen-insensitive catechol 2,3-dioxygenase and its potential in biomonitoring of catechol in wastewater.

The oxygenases are essential in the bioremediation of xenobiotic pollutants. To overcome cultivability constraints, this study aims to identify new potential extradiol dioxygenases using the functional metagenomics approach. RW1-4CC, a novel catechol 2,3-dioxygenase, was isolated using functional metagenomics approach, expressed in a heterologous system, and characterized thoroughly using state-of-the-art techniques.

Influence of C/N ratio & double helical ribbon (DHR) impeller on microbial granulation in anaerobic co-digestion (AnCo-D) of industrial effluents.

The present study demonstrates the significance of the C/N ratio and double helical ribbon (DHR) impeller in the anaerobic co-digestion (AnCo-D) of sugar refining process (SRP) effluent and molasses-based distillery spent wash (DSW) for improved biogas production. Both SRP & DSW were mixed in different percentages to achieve an optimum C/N ratio. Further biomethane potential analysis of mixed feeds with different C/N ratios was performed.

Decoration of FeO-vitamin C nanoparticles on alginate-chitosan nanocomplex: Characterization, safety, bioacessibility boost and Iron Nanofortification in A2 goat milk gels.

In this study, an alginate-chitosan (AL-CS) nanocomplex decorated with vitamin C coated iron oxide nanoparticles (FeO-vit C NPs) was investigated as a novel nanoiron fortification agent. The FeO-vit C NPs decorated on AL-CS nanocomplex underwent comprehensive characterization, including zeta potential, fourier transform infrared spectroscopy, X-ray diffraction, and UV-vis spectroscopy. The transmission electron microscopy (TEM) analysis confirmed the decoration of FeO-vit C NPs on AL-CS nanocomplex.

Impact of increasingly complex cell culture conditions on the proteome of human periodontal ligament stem cells.

Aims: Human periodontal ligament stem cells (hPDLSCs) exhibit an enormous potential to regenerate periodontal tissue. However, their translatability to the clinical setting is constrained by technical difficulties in standardizing culture conditions. The aim was to assess complex culture conditions using a proteomic-based protocol to standardize multi-layer hPDLSC cultivation methodology.

A risk-based approach can guide safe cell line development and cell banking for scaled-up cultivated meat production.

For commercial viability, cultivated meats require scientifically informed approaches to identify and manage hazards and risks. Here we discuss food safety in the rapidly developing field of cultivated meat as it shifts from lab-based to commercial scales. We focus on what science-informed risk mitigation processes can be implemented from neighbouring fields.

Pivotal role of exogenous pyruvate in human natural killer cell metabolism.

Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription.

Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.

High-resolution cryo-EM using a common LaB 120-keV electron microscope equipped with a sub-200-keV direct electron detector.

High-resolution cryo-electron microscopy (cryo-EM) requires costly 200- to 300-keV cryo-transmission electron microscopes (cryo-TEMs) with field emission gun (FEG) sources, stable columns, constant-powered lenses, autoloader, and direct electron detectors (DED). Recent advances in 100-keV imaging with the emergence of sub-200-keV optimized DED technology promises the development of more affordable cryo-TEMs. So far, 100-keV imaging has required microscopes with FEG sources.

Warfare under the waves: a review of bacteria-derived algaecidal natural products.

Covering: 1960s to 2024Harmful algal blooms pose a major threat to aquatic ecosystems and can impact human health. The frequency and intensity of these blooms has increased over recent decades, driven primarily by climate change and an increase in nutrient runoff. Algal blooms often produce toxins that contaminate water sources, disrupt fisheries, and harm human health.

Isolation and screening of wood-decaying fungi for lignocellulolytic enzyme production and bioremediation processes.

The growing demand for novel enzyme producers to meet industrial and environmental needs has driven interest in lignocellulose-degrading fungi. In this study, lignocellulolytic enzyme production capabilities of environmental fungal isolates collected from boreal coniferous and nemoral summer green deciduous forests were investigated, using Congo Red, ABTS, and Azure B as indicators of cellulolytic and ligninolytic enzyme productions. Through qualitative and quantitative assays, the study aimed to identify promising species for lignocellulose-degrading enzyme secretion and assess their potential for biotechnological applications.

The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities.

Cytokines are small proteins that are critical for controlling the growth and activity of hematopoietic cells by binding to cell surface receptors and transmitting signals across membranes. The β common (βc) cytokine receptor family, consisting of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 cytokine receptors, is an architype of the heterodimeric cytokine receptor systems. We now know that signaling by cytokine receptors is not always an "all or none" phenomenon.

Molecular intricacies of intrinsically disordered proteins and drought stress in plants.

Intrinsically Disordered Proteins (IDPs) and Intrinsically Disordered Regions (IDRs) are renowned for their dynamic structural characteristics and conformational adaptability, allowing them to assume diverse conformations in response to prevailing environmental conditions. This inherent flexibility facilitates their interactions with molecular targets, enabling them to engage in numerous cellular processes without any excessive energy consumption. This adaptability is instrumental in shaping cellular complexity and enhancing adaptability.

A Novel, Site-Specific N-Linked Glycosylation Model Provides Mechanistic Insights Into the Process-Condition Dependent Distinct Fab and Fc Glycosylation of an IgG1 Monoclonal Antibody Produced by CHO VRC01 Cells.

The CHO VRC01 cell line produces an anti-HIV IgG1 monoclonal antibody containing N-linked glycans on both the Fab (variable) and Fc (constant) regions. Site-specific glycan analysis was used to measure the complex effects of cell culture process conditions on Fab and Fc glycosylation. Experimental data revealed major differences in glycan fractions across the two sites.

Understanding the genetics of sex determination in insects and its relevance to genetic pest management.

Sex determination pathways regulate male and female-specific development and differentiation and offer potential targets for genetic pest management methods. Insect sex determination pathways are comprised of primary signals, relay genes and terminal genes. Primary signals of coleopteran, dipteran, hymenopteran and lepidopteran species are highly diverse and regulate the sex-specific splicing of relay genes based on the primary signal dosage, amino acid composition or the interaction with paternally inherited genes.

Membrane-embedded CdaA is required for efficient synthesis of second messenger cyclic di-AMP.

Cyclic di-adenylate monophosphate (cyclic di-AMP) is an important second messenger in microorganisms. Cyclic di-AMP regulates bacterial cell volume and turgor via control of potassium and compatible solute transport but is also involved in many other processes, including the activation of the metazoan innate immune response to bacterial infections. We compare the activity of full-length membrane-embedded CdaA, the enzyme that synthesizes cyclic di-AMP, with the water-soluble catalytic domain CdaA-DAC.

Efficient identification of genomic insertions and surrounding regions in two transgenic maize events using third-generation single-molecule nanopore sequencing technology.

The increasing development of new genetically modified organisms underscores the critical need for comprehensive safety assessments, emphasizing the significance of molecular evidence such as gene integration, copy numbers, and adjacent sequences. In this study, the maize nitrate-efficient utilization gene ZmNRT1.1 A was introduced into maize variety y822 using transgenic technology, producing transgenic maize events ND4401 and ND4403 with enhanced tolerance to low nitrogen stress.

The known unknowns of the Hsp90 chaperone.

Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases.

Soluble CD52 mediates immune suppression by human seminal fluid.

Seminal fluid provides for the carriage and nutrition of sperm, but also modulates immunity to prevent allo-rejection of sperm by the female. Immune suppression by seminal fluid has been associated with extracellular vesicles, originally termed prostasomes, which contain CD52, a glycosylated glycophosphoinositol-anchored peptide released from testicular epithelial cells. Previously, we reported that human T cell-derived CD52, bound to the danger-associated molecular pattern protein, high mobility group box 1 (HMGB1), suppresses T cell function via the inhibitory sialic acid-binding immunoglobulin-like lectin-10 (Siglec-10) receptor.

Analysis of mechanisms of the rabies virus P protein-nucleocapsid interaction using engineered N-protein peptides and potential applications in antivirals design.

The Phosphoprotein (P protein) of the rabies virus has multiple roles in virus replication. A critical function is to act as a cofactor in genome replication and mRNA production through binding via its N-terminal region to the L protein, the essential enzyme for mRNA and genome synthesis/processing, and via its C-terminal domain (P) to the N protein and viral RNA (N-RNA) ribonucleoprotein complex. The binding site of the P on the N protein is a disordered loop that is expected to be phosphorylated at Ser389.