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.

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.

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.

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.

Structural plasticity of the coiled-coil interactions in human SFPQ.

The proteins SFPQ (splicing Factor Proline/Glutamine rich) and NONO (non-POU domain-containing octamer-binding protein) are mammalian members of the Drosophila Behaviour/Human Splicing (DBHS) protein family, which share 76% sequence identity in their conserved 320 amino acid DBHS domain. SFPQ and NONO are involved in all steps of post-transcriptional regulation and are primarily located in mammalian paraspeckles: liquid phase-separated, ribonucleoprotein sub-nuclear bodies templated by NEAT1 long non-coding RNA. A combination of structured and low-complexity regions provide polyvalent interaction interfaces that facilitate homo- and heterodimerisation, polymerisation, interactions with oligonucleotides, mRNA, long non-coding RNA, and liquid phase-separation, all of which have been implicated in cellular homeostasis and neurological diseases including neuroblastoma.

Protocol to study ex vivo T cell priming by conventional dendritic cells from the mouse spleen.

Conventional dendritic cells (cDC) are professional antigen-presenting cells able to prime naive T cells. Here, we present a protocol for ex vivo T cell priming by murine splenic cDC. We describe the steps of injecting fluorescently labeled antigens to mice, purifying antigen-bearing cDC, and priming antigen-specific T cells ex vivo.

Serial Paediatrics Omics Tracking in Myalgic Encephalomyelitis (SPOT-ME): protocol paper for a multidisciplinary, observational study of clinical and biological markers of paediatric myalgic encephalomyelitis/chronic fatigue syndrome in Australian adolescents aged 12-19 years.

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling condition that can affect adolescents during a vulnerable period of development. The underlying biological mechanisms for ME/CFS remain unclear and have rarely been investigated in the adolescent population, despite this period representing an age peak in the overall incidence. The primary objective of this is to provide a foundational set of biological data on adolescent ME/CFS patients.

A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.

The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase (PfTyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidine ribose sulfamate, ML901, as a potent reaction hijacking inhibitor of PfTyrRS. Here we examined the stage specificity of action of ML901, showing very good activity against the schizont stage, but lower trophozoite stage activity.

Relativistic EELS scattering cross-sections for microanalysis based on Dirac solutions.

The rich information of electron energy-loss spectroscopy (EELS) comes from the complex inelastic scattering process whereby fast electrons transfer energy and momentum to atoms, exciting bound electrons from their ground states to higher unoccupied states. To quantify EELS, the common practice is to compare the cross-sections integrated within an energy window or fit the observed spectrum with theoretical differential cross-sections calculated from a generalized oscillator strength (GOS) database with experimental parameters. The previous Hartree-Fock-based and DFT-based GOS are calculated from Schrödinger's solution of atomic orbitals, which does not include the full relativistic effects.

Overview of the super-resolution and advanced microscopy imaging session at the 21st IUPAB and the 62nd Biophysics Society of Japan joint congress.

Recent advancements in microscopic techniques have significantly progressed, with improvements in fundamental parameters such as resolution, as well as the emergence of novel imaging techniques for measuring cellular information. In this session, six invited speakers introduced recent advancements in super-resolution and advanced microscopy imaging, covering both the development of novel microscopy techniques and their biological applications.

A micro-costing study of mass-spectrometry based quantitative proteomics testing applied to the diagnostic pipeline of mitochondrial and other rare disorders.

Background: Mass spectrometry-based quantitative proteomics has a demonstrated utility in increasing the diagnostic yield of mitochondrial disorders (MDs) and other rare diseases. However, for this technology to be widely adopted in routine clinical practice, it is crucial to accurately estimate delivery costs. Resource use and unit costs required to undertake a proteomics test were measured and categorized into consumables, equipment, and labor.

Tandem Mass Spectrometry of Perfluorocarboxylate Anions: Fragmentation Induced by Reactive Species Formed From Microwave Excited Hydrogen and Water Plasmas.

Rationale: Polyfluoroalkyl substances (PFAS) like perfluorooctanoic acid have persistent environmental and physiological effects. This study investigates the degradation of CFCO (n = 1-7) with neutral radical fragmentation under oxygen attachment dissociation (OAD). Unique fragments absent from collision-induced dissociation (CID) are observed.

Discriminating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and comorbid conditions using metabolomics in UK Biobank.

Background: Diagnosing complex illnesses like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is complicated due to the diverse symptomology and presence of comorbid conditions. ME/CFS patients often present with multiple health issues, therefore, incorporating comorbidities into research can provide a more accurate understanding of the condition's symptomatology and severity, to better reflect real-life patient experiences.

Methods: We performed association studies and machine learning on 1194 ME/CFS individuals with blood plasma nuclear magnetic resonance (NMR) metabolomics profiles, and seven exclusive comorbid cohorts: hypertension (n = 13,559), depression (n = 2522), asthma (n = 6406), irritable bowel syndrome (n = 859), hay fever (n = 3025), hypothyroidism (n = 1226), migraine (n = 1551) and a non-diseased control group (n = 53,009).

Preclinical evaluation and automated synthesis of [Zr]ZrDFOSquaramide-girentuximab for diagnostic imaging of carbonic anhydrase IX positive tumours.

Background: Carbonic Anhydrase IX (CAIX) is a zinc metalloenzyme that is over-expressed in many cancers making it a valid target for targeted diagnostic imaging with Positron Emission Tomography (PET). The monoclonal antibody girentuximab binds to CAIX and when radiolabelled with positron-emitting zirconium-89 can be used for diagnostic PET imaging of CAIX positive tumours.

Results: Reaction of desferrioxamine squaramide ethyl ester with girentuximab allowed isolation of a conjugate with desferrioxamine squaramide (DFOSq) covalently attached to girentuximab through stable vinylogous amide linkages to give DFOSq-girentuximab.

Assessing the impact of bacterial blends, crosslinking enzyme and storage times on volatile and non-volatile compound production in fermented pea protein emulsion gels.

Pea protein is a promising ingredient for plant-based cheese production but has poor consumer acceptance due to intrinsic beany flavors. Fermentation could potentially decrease these off-flavors while also producing desirable cheese-like aromas. Pea protein emulsion gels were fermented using four different bacterial blends for 16 weeks with and without the crosslinking enzyme transglutaminase.

MLKL deficiency elevates testosterone production in male mice independently of necroptotic functions.

Mixed lineage kinase domain-like (MLKL) is a pseudokinase, best known for its role as the terminal effector of the necroptotic cell death pathway. MLKL-mediated necroptosis has long been linked to various age-related pathologies including neurodegeneration, atherosclerosis and male reproductive decline, however many of these attributions remain controversial. Here, we investigated the role of MLKL and necroptosis in the adult mouse testis: an organ divided into sperm-producing seminiferous tubules and the surrounding testosterone-producing interstitium.

Improved Three-Dimensional Reconstructions in Electron Ptychography through Defocus Series Measurements.

A detailed analysis of ptychography for three-dimensional (3D) phase reconstructions of thick specimens is performed. We introduce multi-focus ptychography, which incorporates a 4D-STEM defocus series to enhance the quality of 3D reconstructions along the beam direction through a higher overdetermination ratio. This method is compared with established multi-slice ptychography techniques, such as conventional ptychography, regularized ptychography, and multi-mode ptychography.