Modeling the roles of cohesotaxis, cell-intercalation, and tissue geometry in collective cell migration of Xenopus mesendoderm.

Collectively migrating Xenopus mesendoderm cells are arranged into leader and follower rows with distinct adhesive properties and protrusive behaviors. In vivo, leading row mesendoderm cells extend polarized protrusions and migrate along a fibronectin matrix assembled by blastocoel roof cells. Traction stresses generated at the leading row result in the pulling forward of attached follower row cells. Mesendoderm explants removed from embryos provide an experimentally tractable system for characterizing collective cell movements and behaviors, yet the cellular mechanisms responsible for this mode of migration remain elusive. We introduce an agent-based computational model of migrating mesendoderm in the Cellular-Potts computational framework to investigate the relative contributions of multiple parameters specific to the behaviors of leader and follower row cells. Sensitivity analyses identify cohesotaxis, tissue geometry, and cell intercalation as key parameters affecting the migration velocity of collectively migrating cells. The model predicts that cohesotaxis and tissue geometry in combination promote cooperative migration of leader cells resulting in increased migration velocity of the collective. Radial intercalation of cells towards the substrate is an additional mechanism to increase migratory speed of the tissue. Summary Statement: We present a novel Cellular-Potts model of collective cell migration to investigate the relative roles of cohesotaxis, tissue geometry, and cell intercalation on migration velocity of Xenopus mesendoderm.

3D mesenchymal cell migration is driven by anterior cellular contraction that generates an extracellular matrix prestrain.

We describe a cellular contractile mechanism employed by fibroblasts and mesenchymal cancer cells to migrate in 3D collagen gels. During 3D spreading, fibroblasts strongly deform the matrix. They protrude, polarize, and initiate migration in the direction of highest extracellular matrix (ECM) deformation (prestrain). This prestrain is maintained through anterior cellular contractions behind the leading edge prior to protrusion, coordinating a distinct 3D migration cycle that varies between cell types. Myosin IIA is required for strain polarization, generating anterior contractions, and maintaining prestrain for efficient directional cell migration. Local matrix severing disrupts the matrix prestrain, suppressing directional protrusion. We show that epithelial cancer and endothelial cells rarely demonstrate the sustained prestrain or anterior contractions. We propose that mesenchymal cells sense ECM stiffness in 3D and generate their own matrix prestrain. This requires myosin IIA to generate polarized periodic anterior contractions for maintaining a 3D migration cycle.

Starting Conversations toward Inclusion.

Communal discussions on anti-racism and inclusion are crucial to addressing the history of racism in scientific communities. Unfortunately, universities are not universally implementing these conversations. We provide a blueprint for initiating and executing student-led discussions to empower young scientists to take action toward making science more welcoming and inclusive.

Mounier-Kuhn Syndrome Mimicking Lymphangioleiomyomatosis.

We present the case of a man with Mounier-Kuhn syndrome (MKS), or tracheobronchomegaly, who was referred to the National Institutes of Health Clinical Research Center because of a potential diagnosis of lymphangioleiomyomatosis (LAM), a rare condition in men. The patient was evaluated using ongoing protocols and provided written informed consent. The case demonstrates the presence of chronic inflammation surrounding the dilated airways and histologic changes of the lung parenchyma with emphysematouslike disruption in areas adjacent to the dilated airways. This finding suggests that damage to the lung parenchyma is an ongoing phenomenon in MKS. Moreover, our analysis of CT images indicates similar abnormalities in areas remote from the dilated airways. Finally, because of increased anatomic dead space, calculation of lung diffusion capacity by the single-breath method yielded abnormally low values that required making a correction for the large anatomic dead space, which can be measured by the single-breath nitrogen washout test.

Doença de Ménière em criança / Ménière's disease in children

A Doença de Ménière foi descrita pela primeira vez por Prosper Ménière no século XIX e ainda nos dias atuais não existem explicações definitivas para a sua etiologia e para a sua fisiopatologia. A tétrade formada por esta doença é constituída de zumbido, vertigem, queda da acuidade auditiva e a sensação de plenitude aural. A faixa etária mais acometida pela doneça de Méniére corresponde à terceira e quinta décadas de vida, sendo de ocorrência pouco comum em crianças. Este relato tem como objetivo demonstrar que a doença de Ménière, mesmo sendo de baixa ocorrência em crianças, pode vir a acometer esta população e o otorrinolaringologista deve estar apto para o diagnóstico e tratamento. Neste relato de caso, uma criança de 11 anos apresentou, após um episódio de edema facial de causa indeterminada associado a sintomas cócleo-vestibilares, um quadro de Doença de Ménière após uma investigação mais minuciosa. O tratamento com drogas depressoras do labirinto e vasodilatadoras promoveram uma melhora sensível, dando fim à sintomatologia.