Proteolysis-free amoeboid migration of melanoma cells through crowded environments via bleb-driven worrying.

In crowded microenvironments, migrating cells must find or make a path. Amoeboid cells are thought to find a path by deforming their bodies to squeeze through tight spaces. Yet, some amoeboid cells seem to maintain a near-spherical morphology as they move.

Pituitary Adenoma Coexistent with Sellar Clear Cell Meningioma Unattached to the Dura: Case Report and Treatment Considerations.

Collision tumors involving the sella are rare. Intrasellar collision tumors are most commonly composed of a combination of pituitary adenomas and pituitary neuroendocrine tumors; however, collision tumors consisting of a pituitary adenoma and intrasellar meningioma are exceedingly rare. The authors present the case of a 47-year-old man who presented with progressive right eye vision loss.

Cellular harmonics for the morphology-invariant analysis of molecular organization at the cell surface.

The spatiotemporal organization of membrane-associated molecules is central to the regulation of cellular signals. Powerful new microscopy techniques enable the three-dimensional visualization of localization and activation of these molecules; however, the quantitative interpretation and comparison of molecular organization on the three-dimensional cell surface remains challenging because cells themselves vary greatly in morphology. Here we introduce u-signal3D, a framework to assess the spatial scales of molecular organization at the cell surface in a cell-morphology-invariant manner.

Surface-guided computing to analyze subcellular morphology and membrane-associated signals in 3D.

Signal transduction and cell function are governed by the spatiotemporal organization of membrane-associated molecules. Despite significant advances in visualizing molecular distributions by 3D light microscopy, cell biologists still have limited quantitative understanding of the processes implicated in the regulation of molecular signals at the whole cell scale. In particular, complex and transient cell surface morphologies challenge the complete sampling of cell geometry, membrane-associated molecular concentration and activity and the computing of meaningful parameters such as the cofluctuation between morphology and signals.

Surface-guided computing to analyze subcellular morphology and membrane-associated signals in 3D.

Signal transduction and cell function are governed by the spatiotemporal organization of membrane-associated molecules. Despite significant advances in visualizing molecular distributions by 3D light microscopy, cell biologists still have limited quantitative understanding of the processes implicated in the regulation of molecular signals at the whole cell scale. In particular, complex and transient cell surface morphologies challenge the complete sampling of cell geometry, membrane-associated molecular concentration and activity and the computing of meaningful parameters such as the cofluctuation between morphology and signals.

Blebs promote cell survival by assembling oncogenic signalling hubs.

Most human cells require anchorage for survival. Cell-substrate adhesion activates diverse signalling pathways, without which cells undergo anoikis-a form of programmed cell death. Acquisition of anoikis resistance is a pivotal step in cancer disease progression, as metastasizing cells often lose firm attachment to surrounding tissue.

Data science in cell imaging.

Cell imaging has entered the 'Big Data' era. New technologies in light microscopy and molecular biology have led to an explosion in high-content, dynamic and multidimensional imaging data. Similar to the 'omics' fields two decades ago, our current ability to process, visualize, integrate and mine this new generation of cell imaging data is becoming a critical bottleneck in advancing cell biology.

Actin-Membrane Release Initiates Cell Protrusions.

Despite the well-established role of actin polymerization as a driving mechanism for cell protrusion, upregulated actin polymerization alone does not initiate protrusions. Using a combination of theoretical modeling and quantitative live-cell imaging experiments, we show that local depletion of actin-membrane links is needed for protrusion initiation. Specifically, we show that the actin-membrane linker ezrin is depleted prior to protrusion onset and that perturbation of ezrin's affinity for actin modulates protrusion frequency and efficiency.

Low-Grade Gemistocytic Morphology in H3 G34R-Mutant Gliomas and Concurrent K27M Mutation: Clinicopathologic Findings.

Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations.

Light-sheet microscopy of cleared tissues with isotropic, subcellular resolution.

We present cleared-tissue axially swept light-sheet microscopy (ctASLM), which enables isotropic, subcellular resolution imaging with high optical sectioning capability and a large field of view over a broad range of immersion media. ctASLM can image live, expanded, and both aqueous and non-aqueous chemically cleared tissue preparations. Depending on the optical configuration, ctASLM provides up to 260 nm of axial resolution, a three to tenfold improvement over confocal and other reported cleared-tissue light-sheet microscopes.

Robust and automated detection of subcellular morphological motifs in 3D microscopy images.

Rapid developments in live-cell three-dimensional (3D) microscopy enable imaging of cell morphology and signaling with unprecedented detail. However, tools to systematically measure and visualize the intricate relationships between intracellular signaling, cytoskeletal organization and downstream cell morphological outputs do not exist. Here, we introduce u-shape3D, a computer graphics and machine-learning pipeline to probe molecular mechanisms underlying 3D cell morphogenesis and to test the intriguing possibility that morphogenesis itself affects intracellular signaling.

Nuclear positioning facilitates amoeboid migration along the path of least resistance.

During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell. Most mesenchymal and epithelial cells and some-but not all-cancer cells actively generate their migratory path using pericellular tissue proteolysis.

Preoperative and intraoperative perfusion magnetic resonance imaging in a RELA fusion-positive anaplastic ependymoma: A case report.

Background: Ependymomas are rare neuroepithelial tumors thought to arise from radial glial precursor cells lining the walls of the ventricles and central canal of the brain and spinal cord, respectively. Histopathological classification, according to World Health Organization criteria, has only recently defined the RELA-fusion positive ependymoma. These tumors may account for 70% of supratentorial ependymomas in children and represent an aggressive entity distinct from other ependymomas.

Varicella-Zoster Virus Infection and Osteomyelitis of the Skull.

Background: Varicella-zoster virus (VZV) is a common herpesvirus infection that can result in acute varicella/chickenpox, as well as delayed activation in herpes zoster/shingles. Ramsay-Hunt syndrome is a rare presentation of VZV reactivation, involving 1% of cases and resulting in lesion formation along the seventh cranial nerve distribution. We report the first case of a patient who presented with acute calvarial osteomyelitis after VZV reactivation and Propionibacterium acnes suprainfection.

Fatal Statin-Induced Rhabdomyolysis by Possible Interaction with Palbociclib.

A 60- to 65-year-old female on prior statin therapy was initiated on palbociclib and fulvestrant for the treatment of metastatic, hormone-receptor positive breast cancer. She subsequently developed sudden progressive muscle weakness that progressed to death within weeks. The patient noticed progressive proximal muscle weakness after two cycles of palbociclib, with no other medication changes in the interim.

-Intracellulare Complex (MAC) Producing a Periportal Pseudotumor in a Patient With HIV and a Normal CD4 Count.

intracellulare complex (MAC) is an opportunistic infection typically associated with profound immunosuppression, such as AIDS. The presentation of disseminated MAC can be subtle and mimic systemic symptoms associated with lymphoma; abdominal pseudotumor is an exceptionally rare presentation. In the era of highly active anti-retroviral therapy (HAART), opportunistic infections are increasingly rare, and secondary prophylaxis for MAC may be discontinued after adequate therapy and immune reconstitution.

Primary pituitary diffuse large B-cell lymphoma with somatotroph hyperplasia and acromegaly: case report.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and comprises approximately 30% of all lymphomas. Patients typically present with a nonpainful mass in the neck, groin, or abdomen associated with constitutional symptoms. In this report, however, the authors describe a rare case of a 61-year-old woman with hyperprolactinemia, hypothyroidism, and acromegaly (elevation of insulin-like growth factor-1 [IGF-1]) with elevated growth hormone-releasing hormone (GHRH) in whom an MRI demonstrated diffuse enlargement of the pituitary gland.

Machine learning based methodology to identify cell shape phenotypes associated with microenvironmental cues.

Cell morphology has been identified as a potential indicator of stem cell response to biomaterials. However, determination of cell shape phenotype in biomaterials is complicated by heterogeneous cell populations, microenvironment heterogeneity, and multi-parametric definitions of cell morphology. To associate cell morphology with cell-material interactions, we developed a shape phenotyping framework based on support vector machines.

Quantitative Multiscale Cell Imaging in Controlled 3D Microenvironments.

The microenvironment determines cell behavior, but the underlying molecular mechanisms are poorly understood because quantitative studies of cell signaling and behavior have been challenging due to insufficient spatial and/or temporal resolution and limitations on microenvironmental control. Here we introduce microenvironmental selective plane illumination microscopy (meSPIM) for imaging and quantification of intracellular signaling and submicrometer cellular structures as well as large-scale cell morphological and environmental features. We demonstrate the utility of this approach by showing that the mechanical properties of the microenvironment regulate the transition of melanoma cells from actin-driven protrusion to blebbing, and we present tools to quantify how cells manipulate individual collagen fibers.

Quantifying Modes of 3D Cell Migration.

Although it is widely appreciated that cells migrate in a variety of diverse environments in vivo, we are only now beginning to use experimental workflows that yield images with sufficient spatiotemporal resolution to study the molecular processes governing cell migration in 3D environments. Since cell migration is a dynamic process, it is usually studied via microscopy, but 3D movies of 3D processes are difficult to interpret by visual inspection. In this review, we discuss the technologies required to study the diversity of 3D cell migration modes with a focus on the visualization and computational analysis tools needed to study cell migration quantitatively at a level comparable to the analyses performed today on cells crawling on flat substrates.

BRCA2-positive spinal intramedullary ovarian metastatic disease: case report.

Background Context: Ovarian cancer is the fourth leading cause of cancer death in women, but advances in treatment have led to longer survival among these patients. Tied to these advances and increased survival, however, have been new patterns of metastatic spread.

Purpose: The authors discuss the management and surgical decision making in patients with intramedullary ovarian metastatic disease using a case illustration and relevant literature.

Asymmetric nanotopography biases cytoskeletal dynamics and promotes unidirectional cell guidance.

Many biological and physiological processes depend upon directed migration of cells, which is typically mediated by chemical or physical gradients or by signal relay. Here we show that cells can be guided in a single preferred direction based solely on local asymmetries in nano/microtopography on subcellular scales. These asymmetries can be repeated, and thereby provide directional guidance, over arbitrarily large areas.

Spatiotemporal relationships between the cell shape and the actomyosin cortex of periodically protruding cells.

We investigate the dynamics of cell shape and analyze the actin and myosin distributions of cells exhibiting cortical density traveling waves. These waves propagate by repeated cycles of cortical compression (folding) and dilation (unfolding) that lead to periodic protrusions (oscillations) of the cell boundary. The focus of our detailed analysis is the remarkable periodicity of this phenotype, in which both the overall shape transformation and distribution of actomyosin density are repeated from cycle to cycle even though the characteristics of the shape transformation vary significantly for different regions of the cell.

Geometry-Driven Polarity in Motile Amoeboid Cells.

Motile eukaryotic cells, such as leukocytes, cancer cells, and amoeba, typically move inside the narrow interstitial spacings of tissue or soil. While most of our knowledge of actin-driven eukaryotic motility was obtained from cells that move on planar open surfaces, recent work has demonstrated that confinement can lead to strongly altered motile behavior. Here, we report experimental evidence that motile amoeboid cells undergo a spontaneous symmetry breaking in confined interstitial spaces.

The interplay of cell-cell and cell-substrate adhesion in collective cell migration.

Collective cell migration often involves notable cell-cell and cell-substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell-substrate adhesion and cell-cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells (Dictyostelium discoideum), but significantly changes their ability to adhere to other cells.