Reduction of cortical pulling at mitotic entry facilitates aster centration.

Equal cell division relies upon astral microtubule-based centering mechanisms, yet how the interplay between mitotic entry, cortical force generation and long astral microtubules leads to symmetric cell division is not resolved. We report that a cortically located sperm aster displaying long astral microtubules that penetrate the whole zygote does not undergo centration until mitotic entry. At mitotic entry, we find that microtubule-based cortical pulling is lost.

PML Nuclear bodies: the cancer connection and beyond.

Promyelocytic leukemia (PML) nuclear bodies, membrane-less organelles in the nucleus, play a crucial role in cellular homeostasis. These dynamic structures result from the assembly of scaffolding PML proteins and various partners. Recent crystal structure analyses revealed essential self-interacting domains, while liquid-liquid phase separation contributes to their formation.

Most axonal mitochondria in cortical pyramidal neurons lack mitochondrial DNA and consume ATP.

In neurons of the mammalian central nervous system (CNS), axonal mitochondria are thought to be indispensable for supplying ATP during energy-consuming processes such as neurotransmitter release. Here, we demonstrate using multiple, independent, and approaches that the majority (~80-90%) of axonal mitochondria in cortical pyramidal neurons (CPNs), lack mitochondrial DNA (mtDNA). Using dynamic, optical imaging analysis of genetically encoded sensors for mitochondrial matrix ATP and pH, we demonstrate that in axons of CPNs, but not in their dendrites, mitochondrial complex V (ATP synthase) functions in a reverse way, consuming ATP and protruding H out of the matrix to maintain mitochondrial membrane potential.

Mechanical Characterization of Murine Oocytes by Atomic Force Microscopy.

The quality of murine and human oocytes correlates to their mechanical properties, which are tightly regulated to reach the blastocyst stage after fertilization. Oocytes are nonadherent spherical cells with a diameter over 80 μm. Their mechanical properties have been studied in our lab and others using the micropipette aspiration technique, particularly to obtain the oocyte cortical tension.

Aberrant cortex contractions impact mammalian oocyte quality.

The cortex controls cell shape. In mouse oocytes, the cortex thickens in an Arp2/3-complex-dependent manner, ensuring chromosome positioning and segregation. Surprisingly, we identify that mouse oocytes lacking the Arp2/3 complex undergo cortical actin remodeling upon division, followed by cortical contractions that are unprecedented in mammalian oocytes.

A CTCF-dependent mechanism underlies the Hox timer: relation to a segmented body plan.

During gastrulation, Hox genes are activated in a time-sequence that follows the order of the genes along their clusters. This property, which is observed in all animals that develop following a progressive rostral-to-caudal morphogenesis, is associated with changes in the chromatin structure and epigenetic profiles of Hox clusters, suggesting a process at least partly based on sequential gene accessibility. Here, we discuss recent work on this issue, as well as a possible mechanism based on the surprising conservation in both the distribution and orientation of CTCF sites inside vertebrate Hox clusters.

Oxidative stress changes interactions between 2 bacterial species from competitive to facilitative.

Knowing how species interact within microbial communities is crucial to predicting and controlling community dynamics, but interactions can depend on environmental conditions. The stress-gradient hypothesis (SGH) predicts that species are more likely to facilitate each other in harsher environments. Even if the SGH gives some intuition, quantitative modeling of the context-dependency of interactions requires understanding the mechanisms behind the SGH.

Microglia maintain structural integrity during fetal brain morphogenesis.

Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display a large heterogeneity of cellular distribution and transcriptomic states, their functions remain poorly characterized. Here, we uncovered a role for MG in the maintenance of structural integrity at two fetal cortical boundaries.

Capturing Cytoskeleton-Based Agitation of The Mouse Oocyte Nucleus Across Spatial Scales.

A major challenge in understanding the causes of female infertility is to elucidate mechanisms governing the development of female germ cells, named oocytes. Their development is marked by cell growth and subsequent divisions, two critical phases that prepare the oocyte for fusion with sperm to initiate embryogenesis. During growth, oocytes reorganize their cytoplasm to position the nucleus at the cell center, an event predictive of successful oocyte development in mice and humans and, thus, their embryogenic potential.

Dynamic local mRNA localization and translation occurs during the postnatal molecular maturation of perivascular astrocytic processes.

Astrocytes are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain's blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts after birth and is essentially complete by postnatal day (P) 15.

Transcription-induced domains form the elementary constraining building blocks of bacterial chromosomes.

Transcription generates local topological and mechanical constraints on the DNA fiber, leading to the generation of supercoiled chromosome domains in bacteria. However, the global impact of transcription on chromosome organization remains elusive, as the scale of genes and operons in bacteria remains well below the resolution of chromosomal contact maps generated using Hi-C (~5-10 kb). Here we combined sub-kb Hi-C contact maps and chromosome engineering to visualize individual transcriptional units.

Synaptic plasticity through a naturalistic lens.

From the myriad of studies on neuronal plasticity, investigating its underlying molecular mechanisms up to its behavioral relevance, a very complex landscape has emerged. Recent efforts have been achieved toward more naturalistic investigations as an attempt to better capture the synaptic plasticity underpinning of learning and memory, which has been fostered by the development of electrophysiological and imaging tools. In this review, we examine these naturalistic investigations, by devoting a first part to synaptic plasticity rules issued from naturalistic -like activity patterns.

Evaluation of gliovascular functions of AQP4 readthrough isoforms.

Aquaporin-4 (AQP4) is a water channel protein that links the astrocytic endfeet to the blood-brain barrier (BBB) and regulates water and potassium homeostasis in the brain, as well as the glymphatic clearance of waste products that would otherwise potentiate neurological diseases. Recently, translational readthrough was shown to generate a C-terminally extended variant of AQP4, known as AQP4x, which preferentially localizes around the BBB through interaction with the scaffolding protein α-syntrophin, and loss of AQP4x disrupts waste clearance from the brain. To investigate the function of AQP4x, we generated a novel AQP4 mouse line (AllX) to increase relative levels of the readthrough variant above the ~15% of AQP4 in the brain of wild-type (WT) mice.

DNA supercoiling in bacteria: state of play and challenges from a viewpoint of physics based modeling.

DNA supercoiling is central to many fundamental processes of living organisms. Its average level along the chromosome and over time reflects the dynamic equilibrium of opposite activities of topoisomerases, which are required to relax mechanical stresses that are inevitably produced during DNA replication and gene transcription. Supercoiling affects all scales of the spatio-temporal organization of bacterial DNA, from the base pair to the large scale chromosome conformation.

Striatopallidal cannabinoid type-1 receptors mediate amphetamine-induced sensitization.

Repeated exposure to psychostimulants, such as amphetamine, causes a long-lasting enhancement in the behavioral responses to the drug, called behavioral sensitization. This phenomenon involves several neuronal systems and brain areas, among which the dorsal striatum plays a key role. The endocannabinoid system (ECS) has been proposed to participate in this effect, but the neuronal basis of this interaction has not been investigated.

Live-Imaging Centriole Amplification in Mouse Brain Multiciliated Cells.

Multiciliated cells (MCC) display on their apical surface hundreds of beating cilia that propel physiological fluids. They line brain ventricles where they propel the cerebrospinal liquid, airways where they clear mucus and pathogens and reproductive ducts where they concentrate the sperm in males or drive the egg along the oviducts in females. Motile cilia are nucleated from basal bodies which are modified centrioles.

Mapping and targeting of C1ql1-expressing cells in the mouse.

The C1Q complement protein C1QL1 is highly conserved in mammals where it is expressed in various tissues including the brain. This secreted protein interacts with Brain-specific Angiogenesis Inhibitor 3, BAI3/ADGRB3, and controls synapse formation and maintenance. C1ql1 is expressed in the inferior olivary neurons that send projections to cerebellar Purkinje cells, but its expression in the rest of the brain is less documented.

How Flexibility Can Enhance Catalysis.

Conformational changes are observed in many enzymes, but their role in catalysis is highly controversial. Here we present a theoretical model that illustrates how rigid catalysts can be fundamentally limited and how a conformational change induced by substrate binding can overcome this limitation, ultimately enabling barrier-free catalysis. The model is deliberately minimal, but the principle it illustrates is general and consistent with unique features of proteins as well as with previous informal proposals to explain the superiority of enzymes over other classes of catalysts.

Predicting the virulence of future emerging zoonotic viruses.

Would you rather kiss a platypus, a hedgehog, or a llama? According to a new study in this issue of PLOS Biology, the virulence of a zoonotic virus in humans depends on its reservoir host. Could physiology be the key to anticipating viral threats lethality?

Using Adhesive Micropatterns and AFM to Assess Cancer Cell Morphology and Mechanics.

The mechanical properties of living cells reflect their physiological and pathological state. In particular, cancer cells undergo cytoskeletal modifications that typically make them softer than healthy cells, a property that could be used as a diagnostic tool. However, this is challenging because cells are complex structures displaying a broad range of morphologies when cultured in standard 2D culture dishes.