Morphological Signatures Research Articles

IAMSAM: image-based analysis of molecular signatures using the Segment Anything Model.

Spatial transcriptomics is a cutting-edge technique that combines gene expression with spatial information, allowing researchers to study molecular patterns within tissue architecture. Here, we present IAMSAM, a user-friendly web-based tool for analyzing spatial transcriptomics data focusing on morphological features. IAMSAM accurately segments tissue images using the Segment Anything Model, allowing for the semi-automatic selection of regions of interest based on morphological signatures. Furthermore, IAMSAM provides downstream analysis, such as identifying differentially expressed genes, enrichment analysis, and cell type prediction within the selected regions. With its simple interface, IAMSAM empowers researchers to explore and interpret heterogeneous tissues in a streamlined manner.

Morphology, epidermal features and δ13C signature of Lopingian (late Permian) conifers

Morphology, epidermal features and δ13C signature of Lopingian (late Permian) conifers

Identifying signatures of the earliest benthic bulldozers in emergent subaerial conditions during the colonization of land by animals.

The colonization of land by animals was a milestone in the history of life. Approximately 100 million years before full terrestrialization, early animals sporadically traversed emergent subaerial substrates, leaving behind trace fossils recording their activities. However, identifying temporarily emergent environments and determining the affinities, motility and subaerial endurance of the trace-makers, and the timing and magnitude of their impacts on marginal-marine environments, are challenging. Here, we used semi-resolved computational fluid dynamics-discrete element method coupling to simulate trace formation on non-cohesive sediments in submerged and emergent subaerial conditions. This revealed instability-induced morphological signatures that allow us to identify the earliest terrestrial trace fossils. Quantitative metrics enable us to infer that the putative earliest terrestrial trace-makers were molluscs, and dimensional analysis suggests that their subaerial excursions could last at least 15 min. These organisms navigated emergent environments from the early Cambrian (stage 2), tens of millions of years earlier than arthropods. This quantitative paradigm provides new insights into the palaeobiology of the earliest subaerial bulldozers and highlights that mollusc-like animals were among the first ecosystem engineers to enter marginal-marine settings. They may thus have contributed to the establishment of marginal-marine biogeochemical cycles, laying the groundwork for subsequent terrestrialization by other animals.

Targeting Ferroptosis: Small-molecule Inducers as Novel Anticancer Agents.

Ferroptosis, a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation and reactive oxygen species (ROS) accumulation, is increasingly recognized for its role in cancer development and as a potential therapeutic target. This review consolidates insights into the molecular mechanisms underpinning ferroptosis and evaluates the therapeutic potential of small-molecule inducers, such as erastin, RSL3, sulfasalazine, and sorafenib, which selectively trigger ferroptosis in cancer cells. It highlights the distinct morphological and molecular signatures of ferroptosis, its complex interplay with iron, lipid, and amino acid metabolic pathways, and the resultant implications for cancer treatment strategies. Strategic manipulation of the ferroptosis pathway offers a groundbreaking approach to cancer treatment, potentially circumventing the resistance that cancers develop against traditional apoptosis-inducing agents. Furthermore, it also emphasizes the necessity of refining these small molecules for clinical application and exploring their synergistic potential when combined with current therapies to augment overall treatment efficacy and improve patient outcomes. Ferroptosis thus emerges as a promising avenue in the realm of cancer therapy. Moving forward, research endeavors should focus on a more nuanced understanding of the interconnections between ferroptosis and other cell death modalities. Additionally, comprehensive evaluations of the long-term safety and therapeutic indices of the involved compounds are imperative. Such investigations are poised to herald a transformative shift in the paradigm of oncology, paving the way for innovative and targeted interventions.

Astroblastoma: A molecularly defined entity, its clinico-radiological & pathological analysis of eight cases and review of literature

Astroblastoma, a unique entity of glial tumor, predominantly occur in young women with distinctive MN1 rearrangement, Given its limited documentation in existing literature, we report eight cases of astroblastoma, detailing their clinical, radiological, and histopathological characteristics along with molecular analysis. We conducted a retrospective analysis of our neuropathology archive database spanning the past 8 years. We included all cases that underwent Magnetic Resonance Imaging (MRI), surgical resection, histopathological examination, molecular testing, and follow-up. Histopathological examination involving immunohistochemistry and Fluorescence In Situ Hybridization (FISH) was carried out for all cases. All tumors were found to be located in the supratentorial region (cerebral hemisphere). The median age of the group was 35.1 years, with a female-to-male ratio of 1.6:1. The most common clinical presentation was headache. Morphologically, all tumors exhibited astroblastic features with pseudorosettes and perivascular hyalinization. Immunohistochemistry consistently revealed positivity for EMA and variable immunoreactivity for GFAP, OLIG2, and D2–40. Fluorescence In Situ Hybridization (FISH) analysis conducted for all cases showed MN1 rearrangement in 7 cases. The mean follow-up period was 45 months (ranging from 12 to 105 months). Radiotherapy was administered for high-grade and recurrent astroblastomas. All patients are currently alive and in good health.Astroblastomas are uncommon central nervous system (CNS) tumors with characteristics morphology and molecular signatures. They typically carry a favorable prognosis. High level suspicion is required for their diagnosis and molecular analysis is must to distinguish them from other morphological mimics.

Microglial and neuronal fates following inhibition of CSF-1R in synucleinopathy mouse model

Synucleinopathies are age-related neurological disorders characterized by the abnormal accumulation of α-synuclein (α-syn) in neuronal and non-neuronal cells. It has been proposed that microglial cells play an important role in synucleinopathy neuroinflammation, as well as homeostatically, such as in the clearance of α-syn aggregates in the brain. Here, we examined the effects of microglia on the pathogenesis of synucleinopathies by cell depletion in a mouse model of synucleinopathies. For this purpose, we treated non-transgenic (Non-tg) and α-synuclein transgenic (α-syn-tg) mice with pexidartinib (PLX3397), a tyrosine kinase inhibitor of colony-stimulating factor 1 receptor (CSF-1R). Neuropathological and immunoblot analysis confirmed that Iba-1 immunoreactive microglial cells were decreased by 95% following PLX3397 treatment in Non-tg and α-syn-tg mice. The level of total α-syn in the Triton X-insoluble fraction of brain homogenate was significantly decreased by microglial depletion in the α-syn-tg mice, while the level of Triton X-soluble human α-syn was not affected. Furthermore, the number of p-α-syn immunoreactive inclusions was reduced in α-syn-tg mice treated with PLX3397. Microglial depletion also ameliorated neuronal and synaptic degeneration in α-syn-tg mice, thereby resulted partially improving the motor behavioral deficit in α-syn-tg mice. Moreover, we demonstrated that microglia that survived post-PLX3397 treatment (PLX-resistant microglia) have lower expressions of CSF-1R, and microglial transcriptome analysis further elucidated that PLX-resistant microglia have unique morphology and transcriptomic signatures relative to vehicle-treated microglia of both genotypes; these include differences in definitive microglial functions such as their immune response, cell mobility, cell–cell communications, and regulation of neural homeostasis. Therefore, we suggest that microglia play a critical role in the pathogenesis of synucleinopathies, and that modulation of microglial status might be an effective therapeutic strategy for synucleinopathies.

Micro‐Ring Morphology of Ag7NCs and Light‐Induced Reversible Interconversion of FCC Ag14NCs via Cu2+ ions‐Mediated Particle‐Assisted Reversible Interconversion

AbstractDespite the remarkable progress made on intercluster conversion in atomically precise metal nanoclusters (MNCs) and their self‐organization to develop microscopic molecular architecture with well‐defined size and shape, achieving light‐induced reversible structural transformation and the development of micro‐ring self‐assembly in MNCs have, so far, remained elusive. The present investigation touches on these two long‐standing quests by showcasing a new route, light‐induced Particle‐Assisted Reversible Interconversion (PARI) for the reversible transformation from Face Centered Cubic (FCC) Ag14NCs to Ag7NCs. Our studies reveal that the lack of plasmonic silver nanoparticles (AgNPs) in the system results in the formation of Ag7NCs with metallic kernels having centrosymmetric crystal packing. The molecular self‐organization of Ag7NCs through various non‐covalent interactions such as C−H⋅⋅⋅O, C−H⋅⋅⋅H−C, and C−H⋅⋅⋅π leads to the formation of micro‐ring morphology, a unique molecular architecture in MNCs. The in situ generated AgNPs due to the acceleration of the reaction kinetics by Cu2+ ions facilitate the growth of Ag14NCs with FCC metallic kernel. These two structural units of AgNCs show light‐induced reversible structural transformation which is also associated with the reversible tuning of their spectroscopic and morphological signatures. This PARI‐guided interconversion strategy put forward a most appropriate example of a structure–property relationship in MNCs.

Micro-Ring Morphology of Ag7NCs and Light-Induced Reversible Interconversion of FCC Ag14NCs via Cu2+ ions-Mediated Particle-Assisted Reversible Interconversion.

Despite the remarkable progress made on intercluster conversion in atomically precise metal nanoclusters (MNCs) and their self-organization to develop microscopic molecular architecture with well-defined size and shape, achieving light-induced reversible structural transformation and the development of micro-ring self-assembly in MNCs have, so far, remained elusive. The present investigation touches on these two long-standing quests by showcasing a new route, light-induced Particle-Assisted Reversible Interconversion (PARI) for the reversible transformation from Face Centered Cubic (FCC) Ag14NCs to Ag7NCs. Our studies reveal that the lack of plasmonic silver nanoparticles (AgNPs) in the system results in the formation of Ag7NCs with metallic kernels having centrosymmetric crystal packing. The molecular self-organization of Ag7NCs through various non-covalent interactions such as C-H⋅⋅⋅O, C-H⋅⋅⋅H-C, and C-H⋅⋅⋅π leads to the formation of micro-ring morphology, a unique molecular architecture in MNCs. The in situ generated AgNPs due to the acceleration of the reaction kinetics by Cu2+ ions facilitate the growth of Ag14NCs with FCC metallic kernel. These two structural units of AgNCs show light-induced reversible structural transformation which is also associated with the reversible tuning of their spectroscopic and morphological signatures. This PARI-guided interconversion strategy put forward a most appropriate example of a structure-property relationship in MNCs.

Process mapping and anomaly detection in laser wire directed energy deposition additive manufacturing using in-situ imaging and process-aware machine learning

This work concerns the laser wire directed energy deposition (LW-DED) additive manufacturing process. The objectives were two-fold: (1) process mapping – demarcating the process states as a function of the processing parameters; and (2) process monitoring – detecting process anomalies (instabilities) using data acquired from an in-situ meltpool imaging sensor. The LW-DED process enables high-throughput, near-net shape manufacturing. Without rigorous parameter control, however, LW-DED often introduces defects due to stochastic process drifts. To enhance scalability and reliability, it is essential to understand how LW-DED parameters affect processing regimes, and detect deleterious process drifts. In this work, single-track experiments were conducted over 128 combinations of laser power, scanning velocity, and linear mass density. Four process states were observed via high-speed imaging and delineated as stable, dripping, stubbing, and incomplete melting regimes. Physically intuitive meltpool features were used to train simple machine learning models for classifying the process state into one of the four regimes. The approach was benchmarked against computationally intense, black-box deep machine learning models that directly use as-received meltpool images. Using only six intuitive meltpool morphology and intensity signatures, the approach classified the LW-DED process state with statistical fidelity approaching 90 % (F1-score) compared to F1-score 87 % for deep learning models.

MULTIMODAL NEURAL CORRELATES OF CHILDHOOD PSYCHOPATHOLOGY.

Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.

Evolution, development, and regeneration of tooth-like epithelial appendages in sharks

Sharks and their relatives are typically covered in highly specialized epithelial appendages embedded in the skin called dermal denticles; ancient tooth-like units (odontodes) composed of dentine and enamel-like tissues. These ‘skin teeth’ are remarkably similar to oral teeth of vertebrates and share comparable morphological and genetic signatures. Here we review the histological and morphological data from embryonic sharks to uncover characters that unite all tooth-like elements (odontodes), including teeth and skin denticles in sharks. In addition, we review the differences between the skin and oral odontodes that reflect their varied capacity for renewal. Our observations have begun to decipher the developmental and genetic shifts that separate these seemingly similar dental units, including elements of the regenerative nature in both oral teeth and the emerging skin denticles from the small-spotted catshark (Scyliorhinus canicula) and other chondrichthyan models. Ultimately, we ask what defines a tooth at both the molecular and morphological level. These insights aim to help us understand how nature makes, replaces and evolves a vast array of odontodes.

High-throughput analysis of dendrite and axonal arbors reveals transcriptomic correlates of neuroanatomy

Neuronal anatomy is central to the organization and function of brain cell types. However, anatomical variability within apparently homogeneous populations of cells can obscure such insights. Here, we report large-scale automation of neuronal morphology reconstruction and analysis on a dataset of 813 inhibitory neurons characterized using the Patch-seq method, which enables measurement of multiple properties from individual neurons, including local morphology and transcriptional signature. We demonstrate that these automated reconstructions can be used in the same manner as manual reconstructions to understand the relationship between some, but not all, cellular properties used to define cell types. We uncover gene expression correlates of laminar innervation on multiple transcriptomically defined neuronal subclasses and types. In particular, our results reveal correlates of the variability in Layer 1 (L1) axonal innervation in a transcriptomically defined subpopulation of Martinotti cells in the adult mouse neocortex.

Case report: Aggressive natural killer cell leukemia and refractory hemophagocytic lymphohistiocytosis in an adolescent

Aggressive natural killer cell leukemia (ANKL) is a rare, aggressive hematologic malignancy which often presents as fulminant Epstein-Barr virus (EBV)- driven hemophagocytic lymphohistiocytosis (HLH). ANKL lacks a distinct immunologic and morphologic signature, making early diagnosis particularly challenging. Here we present a case of ANKL in a patient presenting with EBV-HLH. After poor treatment response to the HLH-2004 protocol (etoposide and dexamethasone), bone marrow biopsy demonstrated an atypical CD3-/CD56+ natural killer (NK) cell population with diminished CD7 expression consistent with EBV+ ANKL. Asparaginase-based chemotherapy was initiated but his disease progressed and he died from multiorgan failure. This case highlights the diagnostic challenges of ANKL given the lack of standardized diagnostic criteria, the importance of considering T/NK cell malignancies in the differential diagnosis of EBV-HLH, and adds to the literature on this rare disease.

A Modeling Approach to Studying the Influence of Grafting on the Anatomical Features and SAUR Gene Expression in Watermelons

Grafting alters the genetic and anatomical features of plants. Although grafting has been widely applied in plant propagation, the underlying processes that govern the effects of the procedure are not fully understood. Samples were collected to study the long-term influence of grafting on the leaf-shoot morphology, leaf-shoot anatomy, and genetic signature of the grafted plants. Citrulus lanatus (Thunb.) Matsum. & Nakai (cv. Lady) was used as the scion, and Lagenaria siceraria (Molina) Standl (cv. Argentario) as a rootstock. In grafted plants, leaf blades and petioles were 20.92% and 12.82% longer, respectively, while the midrib collenchyma was 35.68% thicker, and the diameter of the vessel member was 11.17% larger than in ungrafted plants. In the stem, grafting affected the arrangement and number of vascular bundles (from 1 to 2 rings). The thickness of the epidermis decreased by 69.79%, and the size of the external fascicular phloem decreased by 23.56%. The diameter of the vessel member of the grafted plants increased by 28.94%. Eight out of ten evaluated primers met the requirements (stability in both watermelons and bottle gourd, tissue-specific). In the genetic tests, we examined whether this change in the gene expression pattern is due to the grafting and, if so, to what extent. Seven out of eight tested Small Auxin Up-Regulated RNA (SAUR) genes were expressed in the ungrafted and grafted C. lanatus lines in four cases; the expression increased by more than 10% after grafting. The morpho-anatomical changes and genetic variation reported in this study for grafted lines of C. lanatus contribute to the understanding of the underlying mechanisms of plant growth observations resulting from grafting.

Nanoscale characterization of Ediacaran microfossils from lower Doushantuo formation chert nodules

Microfossils identification, especially in very old rocks, is extremely challenging because morphological and chemical signatures of microfossils are subtle and inevitably altered with aging. Chert nodules from the Doushantuo Formation in the Yangtze Gorges area of South China have captured significant interest due to their remarkable preservation of Ediacaran microfossils. To understand the taphonomic processes leading to an exceptional preservation of microbes in these rocks, we studied the morphological and chemical features of microfossils within the lower Doushantuo Formation chert nodules down to atomic scales via advanced microscopy techniques. Our results align with previous studies, confirming that most microfossils there are preserved by silicification. Further analysis of a representative filamentous microfossil, Polytrichoides lineatus, reveals that both the cell wall (or extracellular sheath) and cytoplasm are preserved by loose aggregates of subrounded or irregular quartz grains, along with patchy organic residuals, which are distinctive from the closely packed and angular-shaped quartz grains in the non-fossil matrix of the chert nodule. The cell wall or extracellular sheath likely provided narrower spaces and more nucleation sites for silicification, resulting in smaller quartz grains (i.e., 115 ± 42 nm) compared to those formed in the cytoplasm (i.e., 1150 ± 258 nm). The permeation and precipitation of quartz grains within the cell wall or extracellular sheath could contribute to an exceptional preservation of subcellular structures. This study offers valuable insights into the preservation of microbes in the Doushantuo Formation chert nodules and even older siliceous sedimentary rocks.

Morphological Signatures of Neurogenesis and Neuronal Migration in Hypothalamic Vasopressinergic Magnocellular Nuclei of the Adult Rat.

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5'-bromo-2'-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS's potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.

Emendation of Rhodomonas marina (Cryptophyceae): insights from morphology, molecular phylogeny and water-soluble pigment in an Arctic isolate

Rhodomonas (Cryptophyceae) and species assigned to this genus have undergone numerous taxonomic revisions. This also applies to R. marina studied here as it was originally assigned as a species of Cryptomonas and later considered a variation of R. baltica, the type species. Despite being described more than 130 years ago, R. marina still lacks a comprehensive characterization. Light and electron microscopy were employed to delineate a strain from western Greenland. The living cells were 18 μm long and 9 μm wide, elliptical in shape with a pointed to rounded posterior and truncated anterior in lateral view. Two sub-equal flagella emerged from a vestibulum, where also a furrow extended. In transmission electron microscopy, the furrow was associated with a tubular gullet and the pyrenoid embedded in a deeply lobed chloroplast. The chloroplast contained DNA in perforations and was surrounded by starch grains. A tubular nucleomorph was enclosed within the pyrenoid matrix. In scanning electron microscopy, the inner periplast consisted of rectangular plates with rounded edges and posteriorly these were replaced by a sheet-like structure. The water-soluble pigment was Crypto-Phycoerythrin type I (Cr-PE 545). A phylogenetic inference based on SSU rDNA confirmed the identity of strain S18 as a species of Rhodomonas as it clustered with congeners but also Rhinomonas, Storeatula, and Pyrenomonas. These genera formed a monophyletic clade separated from a diverse assemblage of other cryptophyte genera. To further explore the phylogeny of R. marina a concatenated phylogenetic analysis based on the SSU rDNA-ITS1-5.8S rDNA-ITS2- LSU rDNA region was performed but included only closely related species. The secondary structure of nuclear internal transcribed spacer 2 was predicted and compared to similar structures in related species. Using morphological and molecular signatures as diagnostic features the description of R. marina was emended.

Morphological and microchemical signatures of alluvial gold and electrum grains from the Tcholliré gold district, northern Cameroon: Insights to potential epithermal gold system in the area

Morphological and microchemical signatures of alluvial gold and electrum grains from the Tcholliré gold district, northern Cameroon: Insights to potential epithermal gold system in the area

Assemble-Disassemble-Reassemble Dynamics in Copper Nanocluster-Based Superstructures.

Assembling metal nanoclusters (MNCs) to form superstructures generates exciting photophysical properties distinct from those of their discrete precursors. Controlling the assembly process of MNCs and understanding the assembly-disassembly dynamics can have implications in achieving the reversible self-assembly of MNCs. The formation of self-assembled copper nanoclusters (CuNCs) as homogeneous superstructures and the underlying mechanisms governing such a process remain unexplored. Smart molecular imprinting of surface ligands can establish the forces necessary for the formation of such superstructures. Herein, we report highly luminescent, ordered superstructures of 4-phenylimidazole-2-thiol (4-PIT)-protected CuNCs with the help of l-ascorbic acid as a secondary ligand. Through a comprehensive spectroscopic analysis, we deciphered the mechanism of the self-assembly process, where the role of interligand H-bonding and C-H-π interactions was established. Notably, efficient reversibility of assembly-disassembly was demonstrated by re-establishing the interligand interactions and regenerating their photophysical and morphological signatures.

Molecular-Scale Visualization of Steric Effects of Ligand Binding to Reconstructed Au(111) Surfaces.

Direct imaging of single molecules at nanostructured interfaces is a grand challenge with potential to enable new, precise material architectures and technologies. Of particular interest are the structural morphology and spectroscopic signatures of the adsorbed molecule, where modern probes are only now being developed with the necessary spatial and energetic resolution to provide detailed information at the molecule-surface interface. Here, we directly characterize the adsorption of individual m-terphenyl isocyanide ligands on a reconstructed Au(111) surface through scanning tunneling microscopy and inelastic electron tunneling spectroscopy. The site-dependent steric pressure of the various surface features alters the vibrational fingerprints of the m-terphenyl isocyanides, which are characterized with single-molecule precision through joint experimental and theoretical approaches. This study provides molecular-level insights into the steric-pressure-enabled surface binding selectivity as well as its effect on the chemical properties of individual surface-binding ligands.