Giant KASH proteins and ribosomes synergistically establish cytoplasmic biophysical properties .

Understanding how cells control their biophysical properties during development remains a fundamental challenge. While cytoplasmic macromolecular crowding affects multiple cellular processes in single cells, its regulation in living animals remains poorly understood. Using genetically encoded multimeric nanoparticles for rheology, we discovered that tissues maintain distinct cytoplasmic biophysical properties that differ from those observed across diverse systems, including bacteria, yeast species, and cultured mammalian cells.

The bioenergetics of nucleocytoplasmic transport.

How nucleocytoplasmic transport (NCT) rates change due to cellular physiology-mediated fluctuations in GTP availability remains unclear. In this issue, Scott et al. (https://doi.

Anchorage of H3K9-methylated heterochromatin to the nuclear periphery helps mediate P-cell nuclear migration though constricted spaces in .

Nuclei adjust their deformability while migrating through constrictions to enable structural changes and maintain nuclear integrity. The effect of heterochromatin anchored at the nucleoplasmic face of the inner nuclear membrane on nuclear morphology and deformability during nuclear migration through constricted spaces remains unclear. Here, we show that abolishing peripheral heterochromatin anchorage by eliminating CEC-4, a chromodomain protein that tethers H3K9-methylated chromatin to the nuclear periphery, disrupts constrained P-cell nuclear migration in larvae in the absence of the established LINC complex-dependent pathway.

FLN-2 functions in parallel to linker of nucleoskeleton and cytoskeleton complexes and CDC-42/actin pathways during P-cell nuclear migration through constricted spaces in Caenorhabditis elegans.

Nuclear migration through narrow constrictions is important for development, metastasis, and proinflammatory responses. Studies performed in tissue culture cells have implicated linker of nucleoskeleton and cytoskeleton (LINC) complexes, microtubule motors, the actin cytoskeleton, and nuclear envelope repair machinery as important mediators of nuclear movements through constricted spaces. However, little is understood about how these mechanisms operate to move nuclei in vivo.

Poxvirus A51R: A microtubule maestro and virulence virtuoso.

Seo et al. shed light on virus-host interactions as they reveal how poxvirus A51R stabilizes microtubules in infected cells, which impacts vaccinia virus virulence in mice by potentially inhibiting reactive-oxygen-species-dependent antiviral responses in macrophages.

The impact of coronavirus-19 vaccination on anti-nuclear cytoplasmic antibody vasculitis hospitalisations in a Sydney health network.

There have been reports of COVID-19 vaccination triggering anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but no robust studies have examined the link. This retrospective cohort study assessed the impact of COVID vaccination on the rate of denovo and relapsed AAV in a Sydney Local Health District from 2018 to 2022. Despite more than 95% of the population receiving vaccination, the case rate of AAV was stable.

Building and breaking mechanical bridges between the nucleus and cytoskeleton: Regulation of LINC complex assembly and disassembly.

The nucleus is physically coupled to the cytoskeleton through LINC complexes, macromolecular bridges composed of SUN and KASH proteins that span the nuclear envelope. LINC complexes are involved in a wide variety of critical cellular processes. For these processes to occur, cells regulate the composition, assembly, and disassembly of LINC complexes.

Actin and CDC-42 contribute to nuclear migration through constricted spaces in C. elegans.

Successful nuclear migration through constricted spaces between cells or in the extracellular matrix relies on the ability of the nucleus to deform. Little is known about how this takes place in vivo. We have studied confined nuclear migration in Caenorhabditis elegans larval P cells, which is mediated by the LINC complex to pull nuclei towards the minus ends of microtubules.

Caenorhabditis elegans models for striated muscle disorders caused by missense variants of human LMNA.

Striated muscle laminopathies caused by missense mutations in the nuclear lamin gene LMNA are characterized by cardiac dysfunction and often skeletal muscle defects. Attempts to predict which LMNA variants are pathogenic and to understand their physiological effects lag behind variant discovery. We created Caenorhabditis elegans models for striated muscle laminopathies by introducing pathogenic human LMNA variants and variants of unknown significance at conserved residues within the lmn-1 gene.

Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience.

Kidney transplantation in people living with HIV (PLWHIV) is occurring with increasing frequency. Limited international data suggest comparable patient and graft survival in kidney transplant recipients with and without HIV. All PLWHIV aged ≥18 years who received a kidney transplant between 2000 and 2020 were identified by retrospective data initially extracted from Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), with additional HIV-specific clinical data extracted from linked local health-care records.

FLN-2 functions in parallel to LINC complexes and Cdc42/actin pathways during P-cell nuclear migration through constricted spaces in .

Nuclear migration through narrow constrictions is important for development, metastasis, and pro-inflammatory responses. Studies performed in tissue culture cells have implicated LINC (linker of nucleoskeleton and cytoskeleton) complexes, microtubule motors, the actin cytoskeleton, and nuclear envelope repair machinery as important mediators of nuclear movements through constricted spaces. However, little is understood about how these mechanisms operate to move nuclei .

A humanized Caenorhabditis elegans model of hereditary spastic paraplegia-associated variants in KLC4.

Hereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified a variant in human kinesin light chain 4 (KLC4) that is suspected to be associated with autosomal-dominant HSP. How this and other variants relate to pathologies is unknown.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

Aims: The aim is to report the results of Australia's first uterus transplantation (UTx).

Methods: Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team.

A humanized model of Hereditary Spastic Paraplegia-associated variants in kinesin light chain KLC4.

Unlabelled: Hereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified a variant in human kinesin light chain that is suspected to be associated with autosomal dominant HSP. How this and other variants relate to pathologies is unknown.

The Role of Folate Deficiency as a Potential Risk Factor for Nontraumatic Anterior Spinal Artery Syndrome in an Adolescent Girl.

Nontraumatic anterior spinal artery syndrome (ASAS) is an extremely rare clinical condition in pediatric populations with a mostly unknown underlying etiology. Here we discuss the case of a previously healthy 14-year-old girl presenting with sudden onset acute flaccid paralysis to the emergency department. A spinal STIR/DWI MRI revealed hyperintensities extending from cervical vertebrae C3-6, consistent with the diagnosis of ASAS.

Synthesis and Reconstitution Using Mammalian Cell-Free Lysates Enables the Systematic Study of the Regulation of LINC Complex Assembly.

Understanding the structure and structure-function relationships of membrane proteins is a fundamental problem in biomedical research. Given the difficulties inherent to performing mechanistic biochemical and biophysical studies of membrane proteins , we previously developed a facile HeLa cell-based cell-free expression (CFE) system that enables the efficient reconstitution of full-length (FL) functional inner nuclear membrane Sad1/UNC-84 (SUN) proteins (i.e.

Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics.

The ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we conduct quantitative confocal imaging to show that the loss of A-type lamins tends to increase nuclear and cellular volume while the loss of B-type lamins behaves in the opposite manner.

Whole Exome Sequencing Identifies a Novel Homozygous Missense Mutation in the CSB Protein-Encoding Gene in a Taiwanese Boy with Cockayne Syndrome.

Background: Cockayne syndrome (CS) is a rare form of dwarfism that is characterized by progressive premature aging. CS is typically caused by mutations in the excision repair cross-complementing protein group 6 () gene that encodes the CS group B (CSB) protein. Using whole exome sequencing, we recently identified a novel homozygous missense mutation (Leu536Trp) in CSB in a Taiwanese boy with CS.

Cystatin C kidney functional reserve: a simple method to predict outcome in chronic kidney disease.

Background: Kidney functional reserve (KFR), the only clinical kidney stress test, is not routinely measured because the complexity of measurement has limited clinical application. We investigated the utility of plasma cystatin C (CysC) after oral protein loading (PL) to determine KFR in Stages 3 and 4 chronic kidney disease (CKD).

Methods: Following a 24-h low-protein diet, KFR was measured after oral protein by hourly plasma CysC and compared with simultaneous creatinine clearance (CrCl) and radionuclide 99technetium diethylenetriaminepentaacetatic acid (Tc-99m-DTPA) measured glomerular filtration rate (mGFR) measurement in an observational, single-centre cohort study of adults with CKD Stages 3 and 4.

Nesprin-2G tension fine-tunes Wnt/β-catenin signaling.

How LINC complexes mediate nuclear mechanotransduction remains unclear. In this issue, Déjardin, Carollo, et al. (2020.

Differentiating Luminal and Membrane-Associated Nuclear Envelope Proteins.

The nuclear envelope (NE) consists of two concentric nuclear membranes separated by the lumen, an ∼40-nm-wide fluid layer. NE proteins are implicated in important cellular processes ranging from gene expression to nuclear positioning. Although recent progress has been achieved in quantifying the assembly states of NE proteins in their native environment with fluorescence fluctuation spectroscopy, these studies raised questions regarding the association of NE proteins with nuclear membranes during the assembly process.

Function of Torsin AAA+ ATPases in Pseudorabies Virus Nuclear Egress.

Newly assembled herpesvirus nucleocapsids traverse the intact nuclear envelope by a vesicle-mediated nucleo-cytoplasmic transport for final virion maturation in the cytoplasm. For this, they bud at the inner nuclear membrane resulting in primary enveloped particles in the perinuclear space (PNS) followed by fusion of the primary envelope with the outer nuclear membrane (ONM). While the conserved viral nuclear egress complex orchestrates the first steps, effectors of fusion of the primary virion envelope with the ONM are still mostly enigmatic but might include cellular proteins like SUN2 or ESCRT-III components.

Identifying Heteroprotein Complexes in the Nuclear Envelope.

The nucleus is delineated by the nuclear envelope (NE), which is a double membrane barrier composed of the inner and outer nuclear membranes as well as a ∼40-nm wide lumen. In addition to its barrier function, the NE acts as a critical signaling node for a variety of cellular processes, which are mediated by protein complexes within this subcellular compartment. Although fluorescence fluctuation spectroscopy is a powerful tool for characterizing protein complexes in living cells, it was recently demonstrated that conventional fluorescence fluctuation spectroscopy methods are not suitable for applications in the NE because of the presence of slow nuclear membrane undulations.