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The persistent motility of individual constituents in microbial suspensions represents a prime example of the so-called active matter systems. Cells consume energy, exert forces and move, overall releasing the constraints of equilibrium statistical mechanics of passive elements and allowing for complex spatio-temporal patterns to emerge. Moreover, when subject to physico-chemical stimuli their collective behaviour often drives large-scale instabilities of a hydrodynamic nature, with implications for biomixing in natural environments and incipient industrial applications. In turn, our ability to exert external control of these driving stimuli could be used to govern the emerging patterns. Light, being easily manipulable and, at the same time, an important stimulus for a wide variety of microorganisms, is particularly well suited to this end. In this paper, we will discuss the current state, developments and some of the emerging advances in the fundamentals and applications of light-induced bioconvection with a focus on recent experimental realizations and modelling efforts. This article is part of the theme issue ‘Stokes at 200 (part 2)’.

Diatoms are one of the most abundant, diverse and ecologically relevant phytoplanktonic group, contributing enormously to global biogeochemical processes like the carbon and silica cycles. This large success has been partly attributed to the mechanical and optical properties of the silica shell (the frustule) that envelops their body. But since they lack motility it is difficult to conceive how they cope with the fast-fluctuating environment they live in and where distributions of resources are very heterogeneous and dynamical. This pinpoints an important but yet poorly understood feature of diatoms physiology: buoyancy regulation that helps them controlling their sinking speed and position in the water column. While buoyancy regulation by light and nutrients availability has been well studied, the effect of hydromechanical stress via fluid shear has been rather overlooked when considering diatoms dynamics. Here, we aim to start filling this gap by first presenting direct experimental evidences for buoyancy control in response to hydro-mechanical stress and then review recent theoretical models where simple couplings between local shear and buoyancy control always result in heterogeneous cell distributions, specific accumulation regions within complex flows and increased sedimentation times to the depths, features of direct ecological relevance. We conclude by suggesting future experiments aiming to unveil such coupling and therefore gain better understanding on the fate of these fascinating microorganisms in their natural habitat. This article is part of the theme issue ‘Stokes at 200 (part 2)’.

Phytoplankton are by definition autotrophic microorganisms that passively drift with fluid motion. Accordingly, the traditional view of a turbulence-homogenized phytoplankton distribution in the ocean, where cells randomly organize and interact, is deeply rooted in biological oceanography studies. However, increasing understanding of microscopic processes in the ocean is revealing a world of microscale patterns resulting from cell behaviors and fluid-cell interactions that challenges this vision. Autotrophic cells have developed active (i.e. flagella) and passive (i.e. morphological structures, vesicles) motility mechanisms that allow them different degrees of spatial control. Their complex interaction with the ocean physicochemical landscape commonly results in small-scale spatial heterogeneities and non-isotropic orientations that can strongly influence ecosystem level processes. Cell orientation, in particular, is fundamental for key biological functions such as sensing, metabolism, locomotion, chain formation or sexual reproduction. Moreover, preferential alignment of elongated cells can modulate the propagation of light through the ocean and is fundamental for accurate interpretation of remote sensing data. Innovative observational and experimental techniques (e.g. in situ holography, laser diffractometry, etc.) allowing the subtle analysis of cell-fluid interactions are revealing that, at the microscopic level, organisms present well defined orientation and interaction patterns under prevalent conditions in the sea. Thus, the interplay of biology, fluid dynamics, and optics may shape, by means of anisotropic cell distributions, pivotal cross-scale aspects of phytoplankton ecology.

The coordination of eukaryotic flagella is essential for many of the most basic processes of life (motility, sensing, and development), yet its emergence and regulation and its connection to locomotion are poorly understood. Previous studies show that the unicellular alga Chlamydomonas, widely regarded as an ideal system in which to study flagellar biology, swims forward by the synchronous action of its two flagella. Using high-speed imaging over long intervals, we found a richer behavior: A cell swimming in the dark stochastically switches between synchronous and asynchronous flagellar beating. Three-dimensional tracking shows that these regimes lead, respectively, to nearly straight swimming and to abrupt large reorientations, which yield a eukaryotic version of the \"run-and-tumble\" motion of peritrichously flagellated bacteria.

Diatoms are one of the most abundant, diverse and ecologically relevant phytoplanktonic group, contributing enormously to global biogeochemical processes like the carbon and silica cycles. This large success has been partly attributed to the mechanical and optical properties of the silica shell (the frustule) that envelops their body. But since they lack motility it is difficult to conceive how they cope with the fast-fluctuating environment they live in and where distributions of resources are very heterogeneous and dynamical. This pinpoints an important but yet poorly understood feature of diatoms physiology: buoyancy regulation that helps them controlling their sinking speed and position in the water column. While buoyancy regulation by light and nutrients availability has been well studied, the effect of hydromechanical stress via fluid shear has been rather overlooked when considering diatoms dynamics. Here, we aim to start filling this gap by first presenting direct experimental evidences for buoyancy control in response to hydro-mechanical stress and then review recent theoretical models where simple couplings between local shear and buoyancy control always result in heterogeneous cell distributions, specific accumulation regions within complex flows and increased sedimentation times to the depths, features of direct ecological relevance. We conclude by suggesting future experiments aiming to unveil such coupling and therefore gain better understanding on the fate of these fascinating microorganisms in their natural habitat. This article is part of the theme issue ‘Stokes at 200 (part 2)’.

The persistent motility of individual constituents in microbial suspensions represents a prime example of the so-called active matter systems. Cells consume energy, exert forces and move, overall releasing the constraints of equilibrium statistical mechanics of passive elements and allowing for complex spatio-temporal patterns to emerge. Moreover, when subject to physico-chemical stimuli their collective behaviour often drives large-scale instabilities of a hydrodynamic nature, with implications for biomixing in natural environments and incipient industrial applications. In turn, our ability to exert external control of these driving stimuli could be used to govern the emerging patterns. Light, being easily manipulable and, at the same time, an important stimulus for a wide variety of microorganisms, is particularly well suited to this end. In this paper, we will discuss the current state, developments and some of the emerging advances in the fundamentals and applications of light-induced bioconvection with a focus on recent experimental realizations and modelling efforts. This article is part of the theme issue ‘Stokes at 200 (part 2)’.

Spermatozoa of marine invertebrates are attracted to their conspecific female gamete by diffusive molecules, called chemoattractants, released from the egg in-vestments in a process known as chemotaxis. The information from the egg chemoat-tractant concentration field is decoded into intracellular Ca2+ concentration ([Ca2+]i) changes that regulate the internal motors that shape the flagellum as it beats. By studying sea urchin species-specific differences in sperm chemoattractant-receptor characteristics we show that receptor density constrains the steepness of the chemo-attractant concentration gradient detectable by spermatozoa. Through analyzing dif-ferent chemoattractant gradient forms, we demonstrate for the first time that Strongy-locentrotus purpuratus sperm are chemotactic and this response is consistent with frequency entrainment of two coupled physiological oscillators: i) the stimulus func-tion and ii) the [Ca2+]i changes. We demonstrate that the slope of the chemoattractant gradients provides the coupling force between both oscillators, arising as a funda-mental requirement for sperm chemotaxis.

We use the bailout embeddings of three-dimensional volume-preserving maps to study qualitatively the dy- namics of small spherical neutrally buoyant impurities suspended in a time-periodic incompressible fluid flow. The accumulation of impurities in tubular vortical structures, the detachment of particles from fluid trajectories near hyperbolic invariant lines, and the formation of nontrivial three-dimensional structures in the distribution of particles are predicted.

Research on relevant, carefully designed and controlled animal models is an indispensable part of biomedical science. But working with laboratory animals may have a negative impact on the researchers, technicians, veterinarians and support staff, who may experience a significant emotional cost of compassion fatigue and moral stress when performing their different roles in research. This \"cost of caring\" is mainly caused by the connection we form with the laboratory animals and the empathy we feel for them. The effects of this condition can manifest as mental, behavioral, and even physical changes, such as apathy, irritability, depression and isolation, that in extreme cases may lead to health deterioration and addictive behaviors. These effects may in turn negatively impact work morale, staff turnover and even animal welfare. The aim of this talk is to improve our understanding of the causes and symptoms of these conditions, and to provide suggestions and resources for addressing these issues, highlighting better ways to cope and mitigate them.

p53, which is encoded by the most frequently mutated gene in cancer, TP53, is an attractive target for novel cancer therapies. Despite major challenges associated with this approach, several compounds that either augment the activity of wild-type p53 or restore all, or some, of the wild-type functions to p53 mutants are currently being explored. In wild-type TP53 cancer cells, p53 function is often abrogated by overexpression of the negative regulator MDM2, and agents that disrupt p53–MDM2 binding can trigger a robust p53 response, albeit potentially with induction of p53 activity in non-malignant cells. In TP53-mutant cancer cells, compounds that promote the refolding of missense mutant p53 or the translational readthrough of nonsense mutant TP53 might elicit potent cell death. Some of these compounds have been, or are being, tested in clinical trials involving patients with various types of cancer. Nonetheless, no p53-targeting drug has so far been approved for clinical use. Advances in our understanding of p53 biology provide some clues as to the underlying reasons for the variable clinical activity of p53-restoring therapies seen thus far. In this Review, we discuss the intricate interactions between p53 and its cellular and microenvironmental contexts and factors that can influence p53’s activity. We also propose several strategies for improving the clinical efficacy of these agents through the complex perspective of p53 functionality.p53, encoded by TP53, the commonest mutated gene in cancer, is an appealing target for systemic anticancer therapies including those designed to restore p53 function. Thus far, and despite promising preclinical data and several clinical trials, no p53-restoring systemic therapy has been approved for therapeutic use. Despite this limited success, several research efforts are ongoing. In this Review, the authors summarize the role of p53 in cancer with a focus on the complexity of p53 function and how this relates to clinical attempts to restore at least some of these functions.