Structural basis for TIR domain-mediated innate immune signaling by Toll-like receptor adaptors TRIF and TRAM.

Innate immunity relies on Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns. The TIR (Toll/interleukin-1 receptor) domain-containing TLR adaptors TRIF (TIR domain-containing adaptor-inducing interferon-β) and TRAM (TRIF-related adaptor molecule) are essential for MyD88-independent TLR signaling. However, the structural basis of TRIF and TRAM TIR domain-based signaling remains unclear.

A decade of advances in human gut microbiome-derived biotherapeutics.

Microbiome science has evolved rapidly in the past decade, with high-profile publications suggesting that the gut microbiome is a causal determinant of human health. This has led to the emergence of microbiome-focused biotechnology companies and pharmaceutical company investment in the research and development of gut-derived therapeutics. Despite the early promise of this field, the first generation of microbiome-derived therapeutics (faecal microbiota products) have only recently been approved for clinical use.

Insights Into Phylogeny, Diversity and Functional Potential of Poseidoniales Viruses.

Viruses infecting archaea play significant ecological roles in marine ecosystems through host infection and lysis, yet they have remained an underexplored component of the virosphere. In this study, we recovered 451 archaeal viruses from a subtropical estuary, identifying 63 that are associated with the dominant marine order Poseidoniales (Marine Group II Archaea). Phylogenetic analyses of a subset of complete and nearly-complete viral genomes assigned these viruses to the order Magrovirales, a lineage of Poseidoniales viruses, and identified a novel group of viruses distinct from Magrovirales.

Isolation and Characterization of Antibodies Against Vascular Cell Adhesion Molecule-1 Reveals Putative Role for Ig-like Domains 2 and 3 in Cell-to-Cell Interaction.

The vascular cell adhesion molecule-1 (VCAM-1) plays an important role in inflammation, where it facilitates the recruitment of leukocytes to the inflamed area via leukocytes' VLA-4 and endothelial cells' VCAM-1 interaction. VCAM-1 expression is also upregulated in certain cancers. VCAM-1 has seven Ig-like domains, with domains 1 and 4 shown to be critical for VLA-4 binding.

Classical and Modern Models for Biofilm Studies: A Comprehensive Review.

Biofilms are structured microbial communities that adhere to various abiotic and biotic surfaces, where organisms are encased in an exo-polysaccharide matrix. Organisms within biofilms use various mechanisms that help them resist external challenges, such as antibiotics, rendering them more resistant to drugs. Therefore, researchers have attempted to develop suitable laboratory models to study the physical features of biofilms, their resistance mechanisms against antimicrobial agents, and their gene and protein expression profiles.

Steroids and steroid-like compounds alter the ion permeability of phospholipid bilayers distinct interactions with lipids and interfacial water.

Steroids are organic compounds found in all forms of biological life. Besides their structural roles in cell membranes, steroids act as signalling molecules in various physiological processes and are used to treat inflammatory conditions. It has been hypothesised that in addition to their well-characterised genomic and non-genomic pathways, steroids exert their biological or pharmacological activities an indirect, nonreceptor-mediated membrane mechanism caused by steroid-induced changes to the physicochemical properties of cell membranes.

β-Triketones from Leptospermum scoparium (mānuka) oil show potential as scabicides.

Background: Scabies is a debilitating and neglected infectious disease with limited effective treatment options and affecting millions of people worldwide, mainly in poor and overcrowded settings. Essential oils from Australasian Myrtaceae are known to have parasiticidal properties, often attributed to the presence of β-triketones, which are known inhibitors of the tyrosine catabolism pathway through inhibition of hydroxyphenylpyruvate dioxygenase (HPPD).

Purpose: In this study, essential oils from mānuka (Leptospermum scoparium) were evaluated in vitro for miticidal and ovicidal activities and their active β-triketone constituents (flavesone, leptospermone, and isoleptospermone) were identified.

Lysozyme-coated nanoparticles for active uptake and delivery of synthetic RNA and plasmid-encoded genes in plants.

Nanoparticle-mediated delivery of nucleic acids and proteins into intact plants has the potential to modify metabolic pathways and confer desirable traits in crops. Here we show that layered double hydroxide (LDH) nanosheets coated with lysozyme are actively taken up into the root tip, root hairs and lateral root junctions by endocytosis, and translocate via an active membrane trafficking pathway in plants. Lysozyme coating enhanced nanosheet uptake by (1) loosening the plant cell wall and (2) stimulating the expression of endocytosis and other membrane trafficking genes.

Isolation of a strain from an Eastern Gray Kangaroo.

Methanogenic archaea are a group of microorganisms found in the gastrointestinal tract of various herbivores and humans; however, the quantity (intensity) of methane emissions during feed digestion varies. Macropodids, such as the Eastern Gray Kangaroo (), are considered to be low methane-emitting animals, but their gut methanogenic archaea remain poorly characterized. Characterizing methanogens from animals with low methane emissions offers the potential to develop strategies and interventions that reduce methane emissions from livestock.

Impact of storage and extraction methods on peat soil microbiomes.

Recovered microbial community structure is known to be influenced by sample storage conditions and nucleic acid extraction methods, and the impact varies by sample type. Peat soils store a large portion of soil carbon and their microbiomes mediate climate feedbacks. Here, we tested three storage conditions and five extraction protocols on peat soils from three physicochemically distinct habitats in Stordalen Mire, Sweden, revealing significant methodological impacts on microbial (here, meaning bacteria and archaea) community structure.

Glycogenin is dispensable for normal liver glycogen metabolism and body glucose homeostasis.

Glycogen is a glucose-storage polysaccharide molecule present in animals, fungi and bacteria. The enzyme glycogenin can self-glycosylate, forming an oligosaccharide chain that primes glycogen synthesis. This priming role of glycogenin was first believed to be essential for glycogen synthesis, but glycogen was then found in the skeletal muscle, heart, liver and brain of glycogenin-knockout mice (Gyg KO), thereby showing that glycogen can be synthesized without glycogenin.

Assessing the predicted impact of single amino acid substitutions in calmodulin for CAGI6 challenges.

Recent thermodynamic and functional studies have been conducted to evaluate the impact of amino acid substitutions on Calmodulin (CaM). The Critical Assessment of Genome Interpretation (CAGI) data provider at University of Verona (Italy) measured the melting temperature (T) and the percentage of unfolding (%unfold) of a set of CaM variants (CaM challenge dataset). Thermodynamic measurements for the equilibrium unfolding of CaM were obtained by monitoring far-UV Circular Dichroism as a function of temperature.

Uncovering novel functions of the enigmatic, abundant, and active in a salt marsh ecosystem.

, particularly uncultured representatives, are one of the most abundant microbial groups in coastal salt marshes, dominating the belowground rhizosphere, where over half of plant biomass production occurs. However, this class generally remains poorly understood, particularly in a salt marsh context. Here, novel metagenome-assembled genomes (MAGs) were generated from the salt marsh rhizosphere representing , , JAAYZQ01, B4-G1, JAFGEY01, UCB3, and orders.

Therapeutic Potential of MCC950 in Restoring Autophagy and Cognitive Function in STZ-Induced Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is currently the seventh leading cause of death worldwide. In this study, we explored the critical role of autophagy in AD pathology using a streptozotocin (STZ)-induced AD model in Wistar rats. The experimental groups included sham, STZ-induced AD, and STZ + MCC950-treated animals.

The structural and functional analysis of mycobacteria cysteine desulfurase-loaded encapsulin.

Encapsulin nanocompartments loaded with dedicated cargo proteins via unique targeting peptides, play a key role in stress resistance, iron storage and natural product biosynthesis. Mmp1 and cysteine desulfurase (Enc-CD) have been identified as the most abundant representatives of family 2 encapsulin systems. However, the molecular assembly, catalytic mechanism, and physiological functions of the Mmp1 encapsulin system have not been studied in detail.

The Sweet Spirits of the Mineral Acids: Diethyl Ether, Ethyl Nitrite, and Chloroethane. Late Medieval-Early Modern Organic Chemistry.

The "sweet spirits" of sulfuric, nitric, and hydrochloric acids, viz. diethyl ether, ethyl nitrite, and chloroethane, have a history dating back to the late Middle Ages. The compound variously known as philosophorum spiritus vini, aqua Lulliana, Paracelsus' Schwefel süss, Cordus' dulce Vitrioli oleum, and Frobenius' æther is identical with diethyl ether.

Characterization of a novel SNP identified in Australian group A isolates derived from the M1 lineage.

Group A (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1 lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections. However, the basis for its evolutionary success is not yet fully understood.

A Heparan Sulfate Mimetic RAFT Copolymer Inhibits SARS-CoV-2 Infection and Ameliorates Viral-Induced Inflammation.

The high transmissibility and mutation ability of coronaviruses enable them to easily escape existing immune protection and also pose a challenge to existing antiviral drugs. Moreover, drugs only targeting viruses cannot always attenuate the "cytokine storm". Herein, a synthetic heparan sulfate (HS) mimetic, HMSA-06 is reported, that exhibited antiviral activities against both the SARS-CoV-2 prototype and Omicron strains by targeting viral entry and replication.

In search of herbistasis: COT-metsulfuron methyl displays rare herbistatic properties.

Weed management is an essential intervention for maintaining food security and protecting biodiversity but is heavily reliant on chemical control measures (, herbicides). Concerningly, only one herbicide has been developed with a new mode of action (MOA) since the 1980s. Therefore, alternative strategies for preventing weed growth need to be explored.

A new subgenus of hard ticks, Filippoviella n. subgen. (Acari: Ixodidae) comprising Ixodes trianguliceps Birula, 1895 and I. ghilarovi Filippova & Panova, 1988, parasites of small mammals in Europe and Asia.

We establish a new subgenus, Filippoviella n. subgen. (Acari: Ixodidae) based on two species formerly assigned to the subgenus Exopalpiger Schulze, 1935 in the genus Ixodes Latreille, 1795.

Identification of structural stability and fragility of mouse liver glycogen via label-free Raman spectroscopy coupled with convolutional neural network algorithm.

Glycogen structure is closely associated with its physiological functions. Previous studies confirmed that liver glycogen structure had two dominant states: mainly stable during the day and largely fragile at night. However, the diurnal change of glycogen structure is impaired, with dominant fragility in diseased conditions such as diabetes mellitus and liver fibrosis.

SiRCle (Signature Regulatory Clustering) model integration reveals mechanisms of phenotype regulation in renal cancer.

Background: Clear cell renal cell carcinoma (ccRCC) tumours develop and progress via complex remodelling of the kidney epigenome, transcriptome, proteome and metabolome. Given the subsequent tumour and inter-patient heterogeneity, drug-based treatments report limited success, calling for multi-omics studies to extract regulatory relationships, and ultimately, to develop targeted therapies. Yet, methods for multi-omics integration to reveal mechanisms of phenotype regulation are lacking.

Synthetic Access to l-Guluronic Acid via Fluorine-Directed C-5 Epimerization.

l-Guluronic acid is integral to the structures of alginates and to the pathogenesis of . The exploitation of this hexose in both existing and new contexts is, however, limited by its prohibitively high commercial cost. We report on a short and efficient synthetic route to an l-GulA building block from a simple d-mannose thioglycoside.