by Lauren A. Green, Julia C. Nebiolo, Cody J. Smith

Microglia are central nervous system (CNS)-resident cells. Their ability to migrate outside of the CNS, however, is not understood. Using time-lapse imaging in an obstetrical brachial plexus injury (OBPI) model, we show that microglia squeeze through the spinal boundary and emigrate to peripheral spinal roots. Although both macrophages and microglia respond, microglia are the debris-clearing cell. Once outside the CNS, microglia re-enter the spinal cord in an altered state. These peripheral nervous system (PNS)-experienced microglia can travel to distal CNS areas from the injury site, including the brain, with debris. This emigration is balanced by two mechanisms—induced emigration via N-methyl-D-aspartate receptor (NMDA) dependence and restriction via contact-dependent cellular repulsion with macrophages. These discoveries open the possibility that microglia can migrate outside of their textbook-defined regions in disease states.

by Christian Flueck, Laura G. Drought, Andrew Jones, Avnish Patel, Abigail J. Perrin, Eloise M. Walker, Stephanie D. Nofal, Ambrosius P. Snijders, Michael J. Blackman, David A. Baker

Cyclic nucleotide signalling is a major regulator of malaria parasite differentiation. Phosphodiesterase (PDE) enzymes are known to control cyclic GMP (cGMP) levels in the parasite, but the mechanisms by which cyclic AMP (cAMP) is regulated remain enigmatic. Here, we demonstrate that Plasmodium falciparum phosphodiesterase β (PDEβ) hydrolyses both cAMP and cGMP and is essential for blood stage viability. Conditional gene disruption causes a profound reduction in invasion of erythrocytes and rapid death of those merozoites that invade. We show that this dual phenotype results from elevated cAMP levels and hyperactivation of the cAMP-dependent protein kinase (PKA). Phosphoproteomic analysis of PDEβ-null parasites reveals a >2-fold increase in phosphorylation at over 200 phosphosites, more than half of which conform to a PKA substrate consensus sequence. We conclude that PDEβ plays a critical role in governing correct temporal activation of PKA required for erythrocyte invasion, whilst suppressing untimely PKA activation during early intra-erythrocytic development.

by Samuel F. M. Hart, Hanbing Mi, Robin Green, Li Xie, Jose Mario Bello Pineda, Babak Momeni, Wenying Shou

Quantitative modeling is useful for predicting behaviors of a system and for rationally constructing or modifying the system. The predictive power of a model relies on accurate quantification of model parameters. Here, we illustrate challenges in parameter quantification and offer means to overcome these challenges, using a case example in which we quantitatively predict the growth rate of a cooperative community. Specifically, the community consists of two Saccharomyces cerevisiae strains, each engineered to release a metabolite required and consumed by its partner. The initial model, employing parameters measured in batch monocultures with zero or excess metabolite, failed to quantitatively predict experimental results. To resolve the model–experiment discrepancy, we chemically identified the correct exchanged metabolites, but this did not improve model performance. We then remeasured strain phenotypes in chemostats mimicking the metabolite-limited community environments, while mitigating or incorporating effects of rapid evolution. Almost all phenotypes we measured, including death rate, metabolite release rate, and the amount of metabolite consumed per cell birth, varied significantly with the metabolite environment. Once we used parameters measured in a range of community-like chemostat environments, prediction quantitatively agreed with experimental results. In summary, using a simplified community, we uncovered and devised means to resolve modeling challenges that are likely general to living systems.

by Mihailo Mirkovic, Leonardo G. Guilgur, Alexandra Tavares, Diogo Passagem-Santos, Raquel A. Oliveira

Studying aneuploidy during organism development has strong limitations because chronic mitotic perturbations used to generate aneuploidy usually result in lethality. We developed a genetic tool to induce aneuploidy in an acute and time-controlled manner during Drosophila development. This is achieved by reversible depletion of cohesin, a key molecule controlling mitotic fidelity. Larvae challenged with aneuploidy hatch into adults with severe motor defects shortening their life span. Neural stem cells, despite being aneuploid, display a delayed stress response and continue proliferating, resulting in the rapid appearance of chromosomal instability, a complex array of karyotypes, and cellular abnormalities. Notably, when other brain-cell lineages are forced to self-renew, aneuploidy-associated stress response is significantly delayed. Protecting only the developing brain from induced aneuploidy is sufficient to rescue motor defects and adult life span, suggesting that neural tissue is the most ill-equipped to deal with developmental aneuploidy.

The first test passenger has gone to the edge of space aboard Virgin Galactic’s Unity space plane, a key milestone in the firm’s quest to send paying customers to space

The first test passenger has gone to the edge of space aboard Virgin Galactic’s Unity space plane, a key milestone in the firm’s quest to send paying customers to space

The first test passenger has gone to the edge of space aboard Virgin Galactic’s Unity space plane, a key milestone in the firm’s quest to send paying customers to space

A complex probe of the foundations of quantum mechanics suggests that the nature of reality depends on who is looking – there are no objective facts we can agree on

A complex probe of the foundations of quantum mechanics suggests that the nature of reality depends on who is looking – there are no objective facts we can agree on

A complex probe of the foundations of quantum mechanics suggests that the nature of reality depends on who is looking – there are no objective facts we can agree on

When a star goes supernova it is usually destroyed in a powerful explosion, but four stars have survived to tell the tale and are running away fast

When a star goes supernova it is usually destroyed in a powerful explosion, but four stars have survived to tell the tale and are running away fast

When a star goes supernova it is usually destroyed in a powerful explosion, but four stars have survived to tell the tale and are running away fast

The mystery of why zebras have stripes has puzzled biologists for decades, and while we are closing in on the answer, the question isn’t settled yet

The mystery of why zebras have stripes has puzzled biologists for decades, and while we are closing in on the answer, the question isn’t settled yet

The mystery of why zebras have stripes has puzzled biologists for decades, and while we are closing in on the answer, the question isn’t settled yet

The congresswoman who sponsored the US Green New Deal suggested the plan won’t include any new money for nuclear power – that’s a mistake, says David Titley

The congresswoman who sponsored the US Green New Deal suggested the plan won’t include any new money for nuclear power – that’s a mistake, says David Titley

The congresswoman who sponsored the US Green New Deal suggested the plan won’t include any new money for nuclear power – that’s a mistake, says David Titley

A Japanese spacecraft has touched down on an asteroid and collected the first of three samples, raising hopes for the space mining industry