Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers

Metastases of osteosarcomas are heterogeneous. They may grow simultaneously with the primary tumor, during treatment or shortly after, or a long time after the end of the treatment. They occur mainly in lungs but also in bone and various soft tissues. They can have the same histology as the primary tumor or show a shift towards a different differentiation path. However, the metastatic capacities of osteosarcoma cells can be predicted by gene and microRNA signatures. Despite the identification of numerous metastasis-promoting/predicting factors, there is no efficient therapeutic strategy to reduce the number of patients developing a metastatic disease or to cure these metastatic patients, except surgery. Indeed, these patients are generally resistant to the classical chemo- and to immuno-therapy. Hence, the knowledge of specific mechanisms should be extended to reveal novel therapeutic approaches. Recent studies that used DNA and RNA sequencing technologies highlighted complex relations between primary and secondary tumors. The reported results also supported a hierarchical organization of the tumor cell clones, suggesting that cancer stem cells are involved. Because of their chemoresistance, their plasticity, and their ability to modulate the immune environment, the osteosarcoma stem cells could be important players in the metastatic process.

Neurons in the pigeon visual network discriminate between faces, scrambled faces, and sine grating images

Discriminating between object categories (e.g., conspecifics, food, potential predators) is a critical function of the primate and bird visual systems. We examined whether a similar hierarchical organization in the ventral stream that operates for processing faces in monkeys also exists in the avian visual system. We performed electrophysiological recordings from the pigeon Wulst of the thalamofugal pathway, in addition to the entopallium (ENTO) and mesopallium ventrolaterale (MVL) of the tectofugal pathway, while pigeons viewed images of faces, scrambled controls, and sine gratings. A greater proportion of MVL neurons fired to the stimuli, and linear discriminant analysis revealed that the population response of MVL neurons distinguished between the stimuli with greater capacity than ENTO and Wulst neurons. While MVL neurons displayed the greatest response selectivity, in contrast to the primate system no neurons were strongly face-selective and some responded best to the scrambled images. These findings suggest that MVL is primarily involved in processing the local features of images, much like the early visual cortex.

Cortical traveling waves reflect state-dependent hierarchical sequencing of local regions in the human connectome network

Recent human studies using electrocorticography have demonstrated that alpha and theta band oscillations form traveling waves on the cortical surface. According to neural synchronization theories, the cortical traveling waves may group local cortical regions and sequence them by phase synchronization; however these contributions have not yet been assessed. This study aimed to evaluate the functional contributions of traveling waves using connectome-based network modeling. In the simulation, we observed stable traveling waves on the entire cortical surface wherein the topographical pattern of these phases was substantially correlated with the empirically obtained resting-state networks, and local radial waves also appeared within the size of the empirical networks (< 50 mm). Importantly, individual regions in the entire network were instantaneously sequenced by their internal frequencies, and regions with higher intrinsic frequency were seen in the earlier phases of the traveling waves. Based on the communication-through-coherence theory, this phase configuration produced a hierarchical organization of each region by unidirectional communication between the arbitrarily paired regions. In conclusion, cortical traveling waves reflect the intrinsic frequency-dependent hierarchical sequencing of local regions, global traveling waves sequence the set of large-scale cortical networks, and local traveling waves sequence local regions within individual cortical networks.

Novel Cognitive Functions Arise at the Convergence of Macroscale Gradients

Functions in higher-order brain regions are the source of extensive debate. Although past trends have been to describe the brain—especially posterior cortical areas—in terms of a set of functional modules, a new emerging paradigm focuses on the integration of proximal functions. In this review, we synthesize emerging evidence that a variety of novel functions in the higher-order brain regions are due to convergence: convergence of macroscale gradients brings feature-rich representations into close proximity, presenting an opportunity for novel functions to arise. Using the TPJ as an example, we demonstrate that convergence is enabled via three properties of the brain: (1) hierarchical organization, (2) abstraction, and (3) equidistance. As gradients travel from primary sensory cortices to higher-order brain regions, information becomes abstracted and hierarchical, and eventually, gradients meet at a point maximally and equally distant from their sensory origins. This convergence, which produces multifaceted combinations, such as mentalizing another person's thought or projecting into a future space, parallels evolutionary and developmental characteristics in such regions, resulting in new cognitive and affective faculties.

Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning

Endothelial cell migration and proliferation are essential for the establishment of a hierarchical organization of blood vessels and optimal distribution of blood. However, how these cellular processes are quantitatively coordinated to drive vascular network morphogenesis remains unknown. Here, using the zebrafish vasculature as a model system, we demonstrate that the balanced distribution of endothelial cells as well as the resulting regularity of vessel caliber, is a result of cell migration from veins towards arteries and cell proliferation in veins. We identify the Wiskott-Aldrich Syndrome protein (WASp) as an important molecular regulator of this process and show that loss of coordinated migration from veins to arteries upon wasb depletion results in aberrant vessel morphology and the formation of persistent arteriovenous shunts. We demonstrate that WASp achieves its function through the coordination of junctional actin assembly and PECAM1 recruitment and provide evidence that this is conserved in human. Overall, we demonstrate that functional vascular patterning in the zebrafish trunk is established through differential cell migration regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations.

Efficient Coding in the Economics of Human Brain Connectomics

In systems neuroscience, most models posit that brain regions communicate information under constraints of efficiency. Yet, evidence for efficient communication in structural brain networks remains sparse. The principle of efficient coding proposes that the brain transmits maximal information in a metabolically economical or compressed form to improve future behavior. To determine how structural connectivity supports efficient coding, we develop a theory specifying minimum rates of message transmission between brain regions to achieve an expected fidelity, and we test five predictions from the theory based on random walk communication dynamics. In doing so, we introduce the metric of compression efficiency, which quantifies the trade-off between lossy compression and transmission fidelity in structural networks. In a large sample of youth (n = 1,042; age 8–23 years), we analyze structural networks derived from diffusion weighted imaging and metabolic expenditure operationalized using cerebral blood flow. We show that structural networks strike compression efficiency trade-offs consistent with theoretical predictions. We find that compression efficiency prioritizes fidelity with development, heightens when metabolic resources and myelination guide communication, explains advantages of hierarchical organization, links higher input fidelity to disproportionate areal expansion, and shows that hubs integrate information by lossy compression. Lastly, compression efficiency is predictive of behavior—beyond the conventional network efficiency metric—for cognitive domains including executive function, memory, complex reasoning, and social cognition. Our findings elucidate how macroscale connectivity supports efficient coding, and serve to foreground communication processes that utilize random walk dynamics constrained by network connectivity.

Internal state effects on behavioral shifts in freely behaving praying mantises (Tenodera sinensis)

How we interact with our environment largely depends on both the external cues presented by our surroundings and the internal state from within. Internal states are the ever-changing physiological conditions that communicate the immediate survival needs and motivate the animal to behaviorally fulfill them. Satiety level constitutes such a state, and therefore has a dynamic influence on the output behaviors of an animal. In predatory insects like the praying mantis, hunting tactics, grooming, and mating have been shown to change hierarchical organization of behaviors depending on satiety. Here, we analyze behavior sequences of freely hunting praying mantises (Tenodera sinensis) to explore potential differences in sequential patterning of behavior as a correlate of satiety. First, our data supports previous work that showed starved praying mantises were not just more often attentive to prey, but also more often attentive to further prey. This was indicated by the increased time fraction spent in attentive bouts such as prey monitoring, head turns (to track prey), translations (closing the distance to the prey), and more strike attempts. With increasing satiety, praying mantises showed reduced time in these behaviors and exhibited them primarily towards close-proximity prey. Furthermore, our data demonstrates that during states of starvation, the praying mantis exhibits a stereotyped pattern of behavior that is highly motivated by prey capture. As satiety increased, the sequenced behaviors became more variable, indicating a shift away from the necessity of prey capture to more fluid presentations of behavior assembly.

Science Forum: Building a community to engineer synthetic cells and organelles from the bottom-up

Employing concepts from physics, chemistry and bioengineering, 'learning-by-building' approaches are becoming increasingly popular in the life sciences, especially with researchers who are attempting to engineer cellular life from scratch. The SynCell2020/21 conference brought together researchers from different disciplines to highlight progress in this field, including areas where synthetic cells are having socioeconomic and technological impact. Conference participants also identified the challenges involved in designing, manipulating and creating synthetic cells with hierarchical organization and function. A key conclusion is the need to build an international and interdisciplinary research community through enhanced communication, resource-sharing, and educational initiatives.

Hierarchical cortical networks of “voice patches” for processing voices in human brain

Humans have an extraordinary ability to recognize and differentiate voices. It is yet unclear whether voices are uniquely processed in the human brain. To explore the underlying neural mechanisms of voice processing, we recorded electrocorticographic signals from intracranial electrodes in epilepsy patients while they listened to six different categories of voice and nonvoice sounds. Subregions in the temporal lobe exhibited preferences for distinct voice stimuli, which were defined as “voice patches.” Latency analyses suggested a dual hierarchical organization of the voice patches. We also found that voice patches were functionally connected under both task-engaged and resting states. Furthermore, the left motor areas were coactivated and correlated with the temporal voice patches during the sound-listening task. Taken together, this work reveals hierarchical cortical networks in the human brain for processing human voices.