The Golgi apparatus functions as the central processing hub for proteins and lipids, orchestrating glycosylation, sorting, and secretion. Once viewed as a passive site of bulk enzyme recycling, the Golgi is now recognized as a highly dynamic, multimodular system in which intra-Golgi trafficking and glycan synthesis operate as tightly interdependent "Siamese twins." The classical cisternal maturation model, initially based on uniform COPI-mediated recycling, has evolved into the multimodular cisternal maturation (MCM) framework, revealing the coexistence of multiple, specialized recycling modules. Distinct sets of glycosyltransferases form coherent enzymatic modules, each maintained by dedicated retrograde pathways-some COPI-dependent, others COPI-independent-that ensure compartmental fidelity and enable differential regulation of glycan synthesis. These pathways are coordinated by adaptors, retainers, and lipid identity cues that collectively sustain Golgi polarity and adaptability to cellular and metabolic states. Disruption of this modular recycling logic leads to enzyme mislocalization, defective glycosylation, and disease, ranging from congenital disorders of glycosylation to oncogenic transformation. The transition from bulk to multimodular recycling thus redefines the Golgi as an integrated regulatory platform linking membrane trafficking to metabolic and signaling networks.

The collagen superfamily has evolved over nearly a billion years to produce a set of at least 28 proteins that are present in all vertebrates. Of these, the fibrillar collagens (Types I-III, V, XI, XIV, and XVII) comprise a diverse, fibrous structural polymer system that extensively invests and mechanically supports connective tissue. The chemistry, structure, and mechanics of single collagen molecules will be reviewed to provide insight into why collagen's triple helical motif is such an effective, efficient, and versatile structural building block. Review of the integration of molecular collagen into each successive length scale: fibrils, fibers, and tissues will show how the mechanical signature of each level in the hierarchy reflects the mechanical behavior of the smaller length scales from which it is composed. The remarkable structural and mechanical versatility of multiple whole connective tissues with completely different structural roles will demonstrate how each of them relies on collagen to perform their diverse mechanical functions. Finally, multiple themes that address more transcendent phenomena such as fibril diameter modulation, crosslinking, fatigue, and collagen mechanochemistry will be examined to provide a broader view of the field and open new directions for research.

In organelle biogenesis pathways, the Golgi apparatus plays a central role in synthesizing and distributing complex sphingolipids, glycerolipids, and cholesterol, which form the membranes of organelles. The concept of 'lipid flow' describes the circulation of lipids throughout the endomembrane system, mediated by vesicle-based carriers and lipid transfer proteins that directly transfer lipids at sites of organelle-organelle contact. The synthesis and trafficking of lipids are closely interconnected, as they undergo successive enzymatic transformations that begin in the endoplasmic reticulum and are completed in the Golgi apparatus before being distributed to other organelles. A phosphatidylinositol 4-phosphate signaling network that converges on the trans cisterna and trans Golgi network compartments regulates lipid flow to, though, and out of the Golgi apparatus, acting as a rheostat that tunes the rates and specificities of lipid trafficking by controlling phosphatidylinositol 4-phosphate levels in Golgi membranes. The integration of glycolipid and glycoprotein processing reactions within the Golgi with lipid sorting and trafficking pathways suggests that the Golgi apparatus serves as a lipid-based sorting station at the heart of organelle biogenesis pathways.

This work examined the integration of epigenetics and precision medicine in the management of various blood disorders, including anemias, antiphospholipid syndrome, hemochromatosis, hemophilia, leukemia, lymphoma, multiple myeloma, porphyria, thalassemia, thrombocytopenia, thrombocytosis, polycythemia, von Willebrand disease, and coagulopathy. It begins with an overview of key concepts and the significance of precision medicine in treating blood diseases, supported by current statistics. The role of noncoding RNAs (ncRNAs) is highlighted, detailing their mechanisms of action and clinical implications as potential biomarkers and therapeutic targets. Additionally, the chapter explores natural products used in personalized medicine, examining their sources, mechanisms, and successful case studies in blood disorders. A comprehensive review of recent clinical trials provides insights into the impact of innovative therapies and FDA approvals on treatment protocols, emphasizing the importance of combination therapies. Future directions address emerging research technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) and ethical considerations surrounding genetic testing and patient consent. The synthesis of findings underscores the contributions of epigenetics and precision medicine to blood disease treatment, advocating for interdisciplinary research and ongoing education to enhance patient care and outcomes.

The Golgi apparatus is a highly dynamic organelle and central to the regulation of a variety of cell processes. Here we review the relationship between the morphology and function of this organelle, especially to in relation to neuronal development and maintenance. The morphology of the Golgi organelle in neurons is unique as it is present as a Golgi ribbon in the cell body and also as dendritic Golgi elements, known as Golgi outposts, in the neuronal extensions. Many neurodegenerative diseases are associated with the loss of the Golgi ribbon structure and the appearance of dispersed and fragmented Golgi units in the cell body/soma. Here we summarise a key role of the Golgi to limit the proteolytic processing of amyloid precursor protein (APP) by secretases and protect healthy cells, and the perturbations of Golgi morphology arising from increased APP processing and amyloid β production in Alzheimer's disease, the most common of the neurodegenerative disease. The potential consequence of changes in the Golgi architecture and increase of amyloid β production on neuronal function is also considered.

The COVID-19 pandemic has impacted millions of people worldwide, and recent studies have shown that SARS-CoV-2 infection can lead to an Alzheimer's-like neuropathological and biomarker phenotype, as well as clinical symptoms of "brain fog". This raises an intriguing question: "How and where might the molecular pathways underlying SARS-CoV-2 infection and Alzheimer's disease (AD) converge?" One common feature of both SARS-CoV-2 infection and AD is the alteration of the endomembrane system, particularly the fragmentation of the Golgi apparatus. In this review article, we summarize the existing literature on SARS-CoV-2 infection biology and speculate about the potential mechanisms linking Golgi defects, SARS-CoV-2 infection, and neurodegeneration.

The osmium maceration method remains the only technique that enables direct three-dimensional (3D) visualization of subcellular structures via scanning electron microscopy (SEM), and it is particularly effective for resolving spatially complex organelles such as the Golgi apparatus. Here, we describe the 3D ultrastructure of the Golgi apparatus in various cell types, including epididymal epithelial principal cells, intestinal goblet cells, pituitary gonadotropes, and spinal ganglion cells, processed using the osmium maceration method. The overall morphology of the Golgi apparatus varied between cell types, exhibiting a range of configurations, including cup-shaped and spherical forms. Within the Golgi stacks, the cis-most cisterna and the trans-Golgi network displayed especially distinct structural characteristics. The cis-most cisterna typically appeared as a flat sheet with numerous fenestrations, a feature consistently observed across all four cell types. In contrast, the 3D organization of the trans-Golgi network, comprising tubules and/or plate-like membranes frequently interconnected to form elaborate architectures, varied according to the cell type. The morphological diversity of the Golgi apparatus in three dimensions likely reflects functional and structural specializations among different cell types.

The trans-Golgi network (TGN) has traditionally been considered the primary sorting hub for newly synthesized proteins, whereas recycling endosomes (REs) are recognized as intermediate stations for endocytosed materials before their return to the plasma membrane. However, over the past two decades, functional overlaps between the TGN and RE have become evident, with both playing roles in the exocytic and endocytic pathways. Recent studies have shown that REs can transition between two distinct states: Golgi-associated RE (GA-RE) and free-RE. Detachment and reattachment of REs to Golgi stacks are commonly observed. In plants, it has been established that there are two types of TGNs: Golgi-associated TGN and Golgi-independent TGN. The dynamics of REs in animal cells strongly resemble those in plant TGNs. Together with their molecular similarities, these findings suggest that REs may be equivalent to at least some parts of the TGN. Given that the TGN is now understood to be composed of distinct zones, REs could represent the trans-most zone of the TGN.GA-REs receive newly synthesized glycosylphosphatidylinositol-anchored proteins (GPI-APs) but not vesicular stomatitis virus G protein (VSV-G) from the trans-Golgi cisternae. Upon detachment from the Golgi stacks, free-REs serve as post-Golgi carriers for GPI-APs. Besides cargo sorting, the TGN/RE system may play a key role in regulating the spatial distribution of Golgi stacks within cells. We propose that the dynamic balance between the association and separation of Golgi stacks and TGNs/REs is crucial for determining the cell-wide arrangement of Golgi stacks, along with the organization of microtubules and the lateral-linking activity of Golgi stacks.

Intracellular transport is one of the most complex and debated topics in cell biology. Numerous models and their combinations have been proposed to explain experimental data on this process. This article describes our current understanding of the secretory pathway by analyzing different transport models. To identify the most realistic model, we identified observations that cannot be fully explained by the vesicular, diffusion, or cisterna maturation-progression models. The kiss-and-run model appears as the most powerful. From this perspective, vesicles at the ER exit sites are considered to be COPI-dependent. In cells with the central Golgi, the movement of carriers between the Golgi and peripheral structures occurs along microtubules via a bolus-like mechanism. In cells lacking microtubules, free ER-to-Golgi and Golgi-to-plasmalemma (or Golgi-to-endosome) carriers are extremely rare. Intra-Golgi transport relies heavily on temporary connections between cisternae, which subsequently break down. Cisternal perforations play a crucial role in this process. Cargo moves directionally through the Golgi stack, reaching the last two medial-cisternae and/or the trans-most cisterna, which function as the Golgi exit site. At this point, the dynamics of transport shifts from linear cargo movement to an exponential decay pattern. Post-Golgi carriers have to replace their own SNAREs with SNAREs that are able to facilitate their fusion with the plasmalemma.

Prion seed amplification assays, such as real-time quaking-induced conversion (RT-QuIC), are providing ultrasensitive, specific, and increasingly practical means of detecting prions and diagnosing prion diseases in humans and other animals. Widespread efforts have greatly increased the breadth of RT-QuIC applications for research, surveillance, and clinical purposes. Here, we summarize recent progress in several key areas in which RT-QuIC assays are being applied and further developed.