Understanding Multicellularity: The Functional Organization of the Intercellular Space

The aim of this paper is to provide a theoretical framework to understand how multicellular systems realize functionally integrated physiological entities by organizing their intercellular space. From a perspective centered on physiology and integration, biological systems are often characterized as organized in such a way that they realize metabolic self-production and self-maintenance. The existence and activity of their components rely on the network they realize and on the continuous management of the exchange of matter and energy with their environment. One of the virtues of the organismic approach focused on organization is that it can provide an understanding of how biological systems are functionally integrated into coherent wholes. Organismic frameworks have been primarily developed by focusing on unicellular life. Multicellularity, however, presents additional challenges to our understanding of biological systems, related to how cells are capable to live together in higher-order entities, in such a way that some of their features and behaviors are constrained and controlled by the system they realize. Whereas most accounts of multicellularity focus on cell differentiation and increase in size as the main elements to understand biological systems at this level of organization, we argue that these factors are insufficient to provide an understanding of how cells are physically and functionally integrated in a coherent system. In this paper, we provide a new theoretical framework to understand multicellularity, capable to overcome these issues. Our thesis is that one of the fundamental theoretical principles to understand multicellularity, which is missing or underdeveloped in current accounts, is the functional organization of the intercellular space. In our view, the capability to be organized in space plays a central role in this context, as it enables (and allows to exploit all the implications of) cell differentiation and increase in size, and even specialized functions such as immunity. We argue that the extracellular matrix plays a crucial active role in this respect, as an evolutionary ancient and specific (non-cellular) control subsystem that contributes as a key actor to the functional specification of the multicellular space and to modulate cell fate and behavior. We also analyze how multicellular systems exert control upon internal movement and communication. Finally, we show how the organization of space is involved in some of the failures of multicellular organization, such as aging and cancer

Meta-Prior: Meta learning for Adaptive Inverse Problem Solvers

Deep neural networks have become a foundational tool for addressing imaging inverse problems. They are typically trained for a specific task, with a supervised loss to learn a mapping from the observations to the image to recover. However, real-world imaging challenges often lack ground truth data, rendering traditional supervised approaches ineffective. Moreover, for each new imaging task, a new model needs to be trained from scratch, wasting time and resources. To overcome these limitations, we introduce a novel approach based on meta-learning. Our method trains a meta-model on a diverse set of imaging tasks that allows the model to be efficiently fine-tuned for specific tasks with few fine-tuning steps. We show that the proposed method extends to the unsupervised setting, where no ground truth data is available. In its bilevel formulation, the outer level uses a supervised loss, that evaluates how well the fine-tuned model performs, while the inner loss can be either supervised or unsupervised, relying only on the measurement operator. This allows the meta-model to leverage a few ground truth samples for each task while being able to generalize to new imaging tasks. We show that in simple settings, this approach recovers the Bayes optimal estimator, illustrating the soundness of our approach. We also demonstrate our method's effectiveness on various tasks, including image processing and magnetic resonance imaging

3D sub-nanoscale imaging of unit cell doubling due to octahedral tilting and cation modulation in strained perovskite thin films

Determining the 3-dimensional crystallography of a material with sub-nanometre resolution is essential to understanding strain effects in epitaxial thin films. A new scanning transmission electron microscopy imaging technique is demonstrated that visualises the presence and strength of atomic movements leading to a period doubling of the unit cell along the beam direction, using the intensity in an extra Laue zone ring in the back focal plane recorded using a pixelated detector method. This method is used together with conventional atomic resolution imaging in the plane perpendicular to the beam direction to gain information about the 3D crystal structure in an epitaxial thin film of LaFeO3 sandwiched between a substrate of (111) SrTiO3 and a top layer of La0.7Sr0.3MnO3. It is found that a hitherto unreported structure of LaFeO3 is formed under the unusual combination of compressive strain and (111) growth, which is triclinic with a periodicity doubling from primitive perovskite along one of the three directions lying in the growth plane. This results from a combination of La-site modulation along the beam direction, and modulation of oxygen positions resulting from octahedral tilting. This transition to the period-doubled cell is suppressed near both the substrate and near the La0.7Sr0.3MnO3 top layer due to the clamping of the octahedral tilting by the absence of tilting in the substrate and due to an incompatible tilt pattern being present in the La0.7Sr0.3MnO3 layer. This work shows a rapid and easy way of scanning for such transitions in thin films or other systems where disorder-order transitions or domain structures may be present and does not require the use of atomic resolution imaging, and could be done on any scanning TEM instrument equipped with a suitable camera.Comment: Minor fixes, especially in reference

Structure and reactivity of small arteries in aging

Objective: Increased pulse pressure has been observed in aging subjects, but the impact on the structure and reactivity of small arteries has been scarcely evaluated. Methods: This study presents the modifications of vascular structure and function observed in female rats of 5, 18 and 32 months of age, and their relation to the prevailing hemodynamic status. Geometry and reactivity of perfused and pressurized basilar and mesenteric small arteries were analyzed in vitro using a video dimension analyzer. Results: Mean arterial pressure was similar in the three age groups, and only pulse pressure was increased in the oldest group. Media thickness and cross sectional area increased in basilar and mesenteric arteries of the oldest rats and these structural abnormalities were positively related to pulse pressure but not to mean, systolic or diastolic arterial pressure. Only minor changes of vascular reactivity were noted with age: there was a decreased contraction to angiotensin II in mesenteric arteries and an enhanced contraction to endothelin-1 in the basilar arteries. Conclusion: In conclusion, aging is associated with increased pulse pressure and hypertrophy of basilar and mesenteric resistance arteries, suggesting that this hemodynamic variable may influence cerebral and peripheral vascular structure in agin