Organelle homeostasis requires ESCRTs.

The endosomal sorting complexes required for transport (ESCRT) catalyze membrane shape transformations throughout the cell. Canonical functions of the ESCRTs include endosomal multivesicular body biogenesis, enveloped virus budding, and abscission of daughter cell plasma membranes. The ESCRT machinery is also required for membranous organelle homeostasis generally, including by facilitating lipid transport at membrane contact sites, repairing membrane damage, driving lysosomal catabolism, and maintaining nuclear envelope integrity, among other roles.

Evaluating the relationship between news source sharing and political beliefs.

In an era marked by an abundance of news sources, access to information significantly influences public opinion. Notably, the bias of news sources often serves as an indicator of individuals' political leanings. This study explores this hypothesis by examining the news sharing behavior of politically active social media users, whose political ideologies were identified in a previous study.

Structure-function relationships in pure archaeal bipolar tetraether lipids.

Archaeal bipolar tetraether lipids (BTLs) are among the most unusual lipids occurring in nature because of their presumed ability to span the entire membrane to form a monolayer structure. It is believed that because of their unique structural organization and chemical stability, BTLs offer extraordinary adaptation to archaea to thrive in the most extreme milieus. BTLs have also received considerable attention for development of novel membrane-based materials.

Hsp47 promotes biogenesis of multi-subunit neuroreceptors in the endoplasmic reticulum.

Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: ), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric acid type A (GABA) receptors.

Novel RPTPγ and RPTPζ splice variants from mixed neuron-astrocyte hippocampal cultures as well as from the hippocampi of newborn and adult mice.

Receptor protein tyrosine phosphatases γ and ζ (RPTPγ and RPTPζ) are transmembrane signaling proteins with extracellular carbonic anhydrase-like domains that play vital roles in the development and functioning of the central nervous system (CNS) and are implicated in tumor suppression, neurodegeneration, and sensing of extracellular [CO] and [HCO ]. RPTPγ expresses throughout the body, whereas RPTPζ preferentially expresses in the CNS. Here, we investigate differential RPTPγ-RPTPζ expression in three sources derived from a wild-type laboratory strain of C57BL/6 mice: (a) mixed neuron-astrocyte hippocampal (HC) cultures 14 days post isolation from P0-P2 pups; (b) P0-P2 pup hippocampi; and (c) 9- to 12-week-old adult hippocampi.

Cardiolipin clustering promotes mitochondrial membrane dynamics.

Cardiolipin (CL) is a mitochondria-specific phospholipid that forms heterotypic interactions with membrane-shaping proteins and regulates the dynamic remodeling and function of mitochondria. However, the precise mechanisms through which CL influences mitochondrial morphology are not well understood. In this study, employing molecular dynamics (MD) simulations, we observed CL localize near the membrane-binding sites of the mitochondrial fusion protein Optic Atrophy 1 (OPA1).

Time-resolved cryogenic electron tomography for the study of transient cellular processes.

Cryogenic electron tomography (cryo-ET) is the highest resolution imaging technique applicable to the life sciences, enabling subnanometer visualization of specimens preserved in their near native states. The rapid plunge freezing process used to prepare samples lends itself to time-resolved studies, which researchers have pursued for in vitro samples for decades. Here, we focus on developing a freezing apparatus for time-resolved studies in situ.

Structural basis of TRPV1 modulation by endogenous bioactive lipids.

TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for deciphering lipid modulation, which is relevant to understanding how pro-algesic agents enhance channel activity in the setting of inflammatory pain. Identification of a pocket within the TRPV1 transmembrane core has provided initial clues as to how phosphoinositide lipids bind to and regulate the channel.

Too late for early intervention? The Healthy Ageing Service's mental health response.

Objectives: This paper describes the rationale for and development of an innovative mental health service for people aged over 65 years living in Northern and Eastern Melbourne, Victoria, Australia.

Conclusion: The Healthy Ageing Service (HAS) was established in July 2020 to provide care for people aged over 65 years experiencing mild-to-moderate mental health concerns. It embraces a prevention and early intervention model of care.

RNA structures and dynamics with Å resolution revealed by x-ray free-electron lasers.

RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free-electron laser sources to reveal the formation and ready identification of angstrom-scale features in structured and unstructured RNAs. Previously unrecognized structural signatures of RNA secondary and tertiary structures are identified through wide-angle solution scattering experiments.

Structural insights into functional properties of the oxidized form of cytochrome c oxidase.

Cytochrome c oxidase (CcO) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water and harnesses the chemical energy to translocate four protons across biological membranes. The turnover of the CcO reaction involves an oxidative phase, in which the reduced enzyme (R) is oxidized to the metastable O state, and a reductive phase, in which O is reduced back to the R state.

Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography.

Enzymes populate ensembles of structures with intrinsically different catalytic proficiencies that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL) to observe catalysis in a designed mutant (G150T) isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations and formation of the thioimidate catalytic intermediate selects for catalytically competent substates.

Structural mechanism of mitochondrial membrane remodelling by human OPA1.

Distinct morphologies of the mitochondrial network support divergent metabolic and regulatory processes that determine cell function and fate. The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane. Despite its fundamental importance, the molecular mechanisms by which OPA1 modulates mitochondrial morphology are unclear.

RNA structures and dynamics with Å resolution revealed by x-ray free electron lasers.

RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free electron laser sources to reveal the formation and ready identification of Å scale features in structured and unstructured RNAs. New structural signatures of RNA secondary and tertiary structures are identified through wide angle solution scattering experiments.

Structural basis of TRPV1 modulation by endogenous bioactive lipids.

TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for deciphering lipid modulation, which is relevant to understanding how pro-algesic agents enhance channel activity in the setting of inflammatory pain. Identification of a pocket within the TRPV1 transmembrane core has provided initial clues as to how phosphoinositide lipids bind to and regulate the channel.

Structural basis for functional properties of cytochrome oxidase.

Cytochrome oxidase (CO) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water and harnesses the chemical energy to translocate four protons across biological membranes, thereby establishing the proton gradient required for ATP synthesis. The full turnover of the CO reaction involves an oxidative phase, in which the reduced enzyme () is oxidized by molecular oxygen to the metastable oxidized state, and a reductive phase, in which is reduced back to the state.

Brominated lipid probes expose structural asymmetries in constricted membranes.

Lipids in biological membranes are thought to be functionally organized, but few experimental tools can probe nanoscale membrane structure. Using brominated lipids as contrast probes for cryo-EM and a model ESCRT-III membrane-remodeling system composed of human CHMP1B and IST1, we observed leaflet-level and protein-localized structural lipid patterns within highly constricted and thinned membrane nanotubes. These nanotubes differed markedly from protein-free, flat bilayers in leaflet thickness, lipid diffusion rates and lipid compositional and conformational asymmetries.

Distinguishing among HCO 3- , CO 3= , and H + as Substrates of Proteins That Appear To Be "Bicarbonate" Transporters.

Background: Differentiating among HCO 3- , CO 3= , and H + movements across membranes has long seemed impossible. We now seek to discriminate unambiguously among three alternate mechanisms: the inward flux of 2 HCO 3- (mechanism 1), the inward flux of 1 CO 3= (mechanism 2), and the CO 2 /HCO 3- -stimulated outward flux of 2 H + (mechanism 3).

Methods: As a test case, we use electrophysiology and heterologous expression in Xenopus oocytes to examine SLC4 family members that appear to transport "bicarbonate" ("HCO 3- ").

Development and Preliminary Evaluation of a Rapid Screening Tool for Detecting Borderline Personality Disorder in People Aged over 60 Years.

Objectives: Screening and diagnostic instruments for Borderline Personality Disorder (BPD) are not validated in people aged over 60. We report a pilot study examining the sensitivity and specificity of a de-novo screening instrument in older adults.

Methods: The BPD-OA screening tool incorporates DSM 5 and literature describing the expression of BPD in older adults.

Recombination between C and H to Form Acetylide (CH) Probes Nanoscale Interactions in Lipid Bilayers via Dynamic Secondary Ion Mass Spectrometry: Cholesterol and GM Clustering.

Although it is thought that there is lateral heterogeneity of lipid and protein components within biological membranes, probing this heterogeneity has proven challenging. The difficulty in such experiments is due to both the small length scale over which such heterogeneity can occur, and the significant perturbation resulting from fluorescent or spin labeling on the delicate interactions within bilayers. Atomic recombination during dynamic nanoscale secondary ion imaging mass spectrometry (NanoSIMS) is a non-perturbative method for examining nanoscale bilayer interactions.

XFEL serial crystallography reveals the room temperature structure of methyl-coenzyme M reductase.

Methyl-Coenzyme M Reductase (MCR) catalyzes the biosynthesis of methane in methanogenic archaea, using a catalytic Ni-centered Cofactor F430 in its active site. It also catalyzes the reverse reaction, that is, the anaerobic activation and oxidation, including the cleavage of the CH bond in methane. Because methanogenesis is the major source of methane on earth, understanding the reaction mechanism of this enzyme can have massive implications in global energy balances.

Carbonic anhydrase and soluble adenylate cyclase regulation of cystic fibrosis cellular phenotypes.

Several aspects of the cell biology of cystic fibrosis (CF) epithelial cells are altered including impaired lipid regulation, disrupted intracellular transport, and impaired microtubule regulation. It is unclear how the loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to these differences. It is hypothesized that the loss of CFTR function leads to altered regulation of carbonic anhydrase (CA) activity resulting in cellular phenotypic changes.

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding.

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding.