Epithelial colonies in vitro elongate through collective effects.

Epithelial tissues of the developing embryos elongate by different mechanisms, such as neighbor exchange, cell elongation, and oriented cell division. Since autonomous tissue self-organization is influenced by external cues such as morphogen gradients or neighboring tissues, it is difficult to distinguish intrinsic from directed tissue behavior. The mesoscopic processes leading to the different mechanisms remain elusive. Here, we study the spontaneous elongation behavior of spreading circular epithelial colonies in vitro. By quantifying deformation kinematics at multiple scales, we report that global elongation happens primarily due to cell elongations, and its direction correlates with the anisotropy of the average cell elongation. By imposing an external time-periodic stretch, the axis of this global symmetry breaking can be modified and elongation occurs primarily due to orientated neighbor exchange. These different behaviors are confirmed using a vertex model for collective cell behavior, providing a framework for understanding autonomous tissue elongation and its origins.

Development of motor control and behaviour in Asian elephants in the Kabini elephant population, southern India.

Although neonates of precocial mammals are capable of locomotory, sensory, nutritional, and thermoregulatory independence to some extent soon after birth, they attain their adult body mass more slowly than altricial mammals, allowing for an extended period of learning or perfecting skills to an adult-like degree. Asian elephants are precocial but are nutritionally dependent on the mother for at least two years and are long-lived and social. We wanted to examine the ontogeny of trunk motor control and various behaviours in Asian elephant calves and see whether the former develops faster than the latter since limb motor control is achieved soon after birth. We collected field data on trunk use, lateralisation, and behaviours from individually identified, free-ranging elephants in southern India and examined how they were affected by age and other factors. Unlike limb motor control, we found trunk motor skills and behaviours to develop gradually with age. Trunk lateralisation occurred very early on, was not highly dependent on trunk motor skills, and is probably not a developmental marker in Asian elephants. Adult-like behaviours that required low trunk usage emerged within 3 months, while some feeding behaviours emerged later. Calves spent less time resting and more time feeding as they grew, and their activity budgets resembled those of adults only after a year; hence, mother-offspring behavioural synchrony was low for young calves and increased with age. Behavioural development and trunk motor control in Asian elephants are both gradual processes, taking about a year to mature.

Photothermal therapies to improve immune checkpoint blockade for cancer.

Immune checkpoint blockade (ICB) comprising monoclonal antibodies (mAbs) against immune 'checkpoints', such as CTLA-4 and the PD1/PDL1 axis have dramatically improved clinical outcomes for patients with cancer. However, ICB by itself has failed to provide benefit in a wide range of solid tumors, where recurrence still occurs with high incidence. These poor response rates may be due to the therapeutic shortcomings of ICB; namely, a lack of cancer-specific cytotoxicity and ability to debulk tumors. To overcome these limitations, effective ICB therapy may require the combination with other complementary therapeutic platforms. Here, we propose that photothermal therapy (PTT) is an ideal therapeutic modality for combination with ICB because it can generate both tumor-specific cytotoxicity and immunogenicity. PTT elicits these specific effects because it is a localized thermal ablation technique that utilizes light-responsive nanoparticles activated by a wavelength-matched laser. While ICB immunotherapy alone improves cancer immunogenicity but does not generate robust antitumor cytotoxicity, nanoparticle-based PTT elicits targeted and controlled cytotoxicity but sub-optimal long-term immunogenicity. Thus, the two platforms offer complementary and potentially synergistic antitumor effects, which will be detailed in this review. We highlight three classes of nanoparticles used as agents of PTT (i.e., metallic inorganic nanoparticles, carbon-based nanoparticles and organic dyes), and illustrate the potential for nanoparticle-based PTT to potentiate the effects of ICB in preclinical models. Through this discussion, we aim to present PTT combined with ICB as a potent synergistic combination treatment for diverse cancer types currently refractory to ICB as well as PTT monotherapies.