1,720,966 research outputs found
Seeing structure, losing sight: The case for morphological thinking in the age of integration
No full textIn the age of genomics, artificial intelligence (AI), and systems biology, morphology risks becoming an invisible discipline, present in the background, but often unacknowledged in its interpretative power. Biology, however, remains spatial, structured, and shaped. From subcellular compartments to complex organ systems, form continues to inform function. The ability to recognize, describe, and interpret structures across biological scales is a foundational scientific competence. Morphology is not merely descriptive; it is integrative. Morphological sciences bridge developmental, cellular, and evolutionary biology, revealing how gene activity, signaling dynamics, and mechanical forces influence biological architecture. Morphological thinking enables scientists to contextualize molecular processes within the spatial complexity of cells, tissues, and organs. Paradoxically, while technological tools for visualizing structures are expanding rapidly, the number of scientists trained in morphological reasoning is shrinking. If left unaddressed, this erosion threatens to undermine both the scientific depth and translational relevance of biological research. This commentary argues that rediscovering morphology is not a nostalgic act, but a necessary one. We must affirm morphological thinking as a core scientific competence, reframe educational practices to sustain spatial reasoning, and integrate morphology into the evolving world of AI-driven imaging and systems biology
Imaging Endocytosis Dynamics in Health and Disease
No full textEndocytosis is a critical process for cell growth and viability. It mediates nutrient uptake, guarantees plasma membrane homeostasis, and generates intracellular signaling cascades. Moreover, it plays an important role in dead cell clearance and defense against external microbes. Finally, endocytosis is an important cellular route for the delivery of nanomedicines for therapeutic treatments. Thus, it is not surprising that both environmental and genetic perturbation of endocytosis have been associated with several human conditions such as cancer, neurological disorders, and virus infections, among others. Over the last decades, a lot of research has been focused on developing advanced imaging methods to monitor endocytosis events with high resolution in living cells and tissues. These include fluorescence imaging, electron microscopy, and correlative and super-resolution microscopy. In this review, we outline the major endocytic pathways and briefly discuss how defects in the molecular machinery of these pathways lead to disease. We then discuss the current imaging methodologies used to study endocytosis in different contexts, highlighting strengths and weaknesses
Ultrastructural imaging reveals vascular remodeling in migraine patients
No full textMigraine is a neurological disorder and one of the most common pain conditions worldwide. Despite its prevalence, the basic biology and underlying mechanisms contributing to the development of migraine are still poorly understood. It is still unclear, for instance, whether the vasculature, both extra and intracranial, plays a significant role in the generation of migraine pain. Neuroimaging data, indeed, have reported conflicting results on blood vessels abnormalities like vasodilation, while functional studies suggest that vessels dysfunction may extend beyond vasodilation. Here we combined light and electron microscopy imaging to investigate the fine structure of superficial temporal (STA) and occipital arteries (OA) from patients that underwent minimally invasive surgery for migraine. Using optical microscopy, we observed that both STA and OA vessels showed marked endothelial thickening and internal elastic lamina fragmentation. In the muscular layer, we found profound shape changes of vascular smooth muscle cells (VSMCs), abundant extracellular matrix, and the presence of clear extracellular vacuoles. The electron microscopy analysis confirmed putative VSMCs infiltrated within the intima layer and revealed a consistent shifting of VSMCs from contractile to a synthetically active phenotype. We also report the presence of (i) abundant extracellular vacuoles filled with fine granular material and membranes, (ii) multilamellar structures, (iii) endosome-like organelles, and (iv) bona fide extracellular vesicles in the matrix space surrounding synthetically active cells. As both the endothelial layer and VSMCs coordinate a variety of vascular functions, these results suggest that a significant vascular remodeling is occurring in STA and OA of migraine patients. Thus, this phenomenon may represent an important target for future investigation designed toward the development of new therapeutic approaches
Morphologic Vascular Anomalies detected during Migraine Surgery
No full textAlthough there is increasing evidence of migraine headaches having extracranial origins, the exact mechanisms behind the pathogenesis of surgically treated migraines continue to be poorly investigated and described.
We studied the microscopic and ultrastructural characteristics of superficial temporal and occipital arteries in the auriculotemporal and great occipital trigger points of migraine patients to determine their possible role in migraine etiopathogenesis. Fifteen biopsies, 10 of superficial temporal artery and 5 from occipital arteries, were collected intraoperatively during migraine surgery and immediately processed for optical and ultramicroscopic analysis
We detected the following anomalies in all the specimens: a) endothelial damage with internal elastic lamina fragmentation and intimal thickening; b) marked irregularity in the shape and metachromasia of the Vascular Smooth Muscle Cells (VSMCs), separation of cells by abundant extracellular matrix and vacuoles. The electron microscopy analysis confirmed that presumed VSMCs infiltrated the intima layer revealing a consistent shift of VSMCs from contractile to synthetically active phenotypes, endosome-like organelles, multilamellar structures, abundant extracellular vacuoles filled with fine granular material and membranes, and extracellular vesicles in the matrix space surrounding synthetically active cells.
Our study revealed specific alterations in the vasculature at the neurovascular bundles of the temporal and occipital trigger sites. These findings are indicative of an active involvement of the arteries in the auriculo-temporal and great occipital trigger sites in evoking migraine
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Phosphorylation of Synapsin I by Cyclin-Dependent Kinase-5 Sets the Ratio between the Resting and Recycling Pools of Synaptic Vesicles at Hippocampal Synapses
No full textImaging of Endocytic Trafficking and Extracellular Vesicles Released Under Neratinib Treatment in ERBB2(+) Breast Cancer Cells
No full textBreast cancers (BCa) with ERBB2 amplification show rapid tumor growth, increased disease progression, and lower survival rate. Deregulated intracellular trafficking and extracellular vesicle (EVs) release are mechanisms that support cancer progression and resistance to treatments. Neratinib (NE) is a Food and Drug Administration–approved pan-ERBB inhibitor employed for the treatment of ERBB2(+) BCa that blocks signaling and causes survival inhibition. However, the effects of NE on ERBB2 internalization, its trafficking to multivesicular bodies (MVBs), and the release of EVs that originate from these organelles remain poorly studied. By confocal and electron microscopy, we observed that low nanomolar doses of NE induced a modest ERBB2 internalization along with an increase of clathrin-mediated endocytosis and of the CD63+ MVB compartment in SKBR-3 cells. Furthermore, we showed in the culture supernatant two distinct EV subsets, based on their size and ERBB2 positivity: small (30–100 nm) ERBB2(−) EVs and large (>100 nm) ERBB2(+) EVs. In particular, we found that NE increased the overall release of EVs, which displayed a reduced ERBB2 positivity compared with controls. Taken together, these results provide novel insight into the effects of NE on ERBB2(+) BCa cells that may lead to a reduction of ERBB2 potentially transferred to distant target cells by EVs
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
PHOSPHORYLATION OF SYNAPSIN I BY CYCLIN-DEPENDENT KINASE-5 REGULATES SYNAPTIC VESICLE SPATIAL DISTRIBUTION AND RECRUITMENT TO RECYCLING POOL AT HIPPOCAMPAL SYNAPSES.
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