Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.     

Rate of turnover of structural variants in the rDNA gene family of Drosophila melanogaster

A high degree of polymorphism for the length and copy number of rDNA spacers, in both the X and Y chromosome clusters, has been found in a wild population of Drosophila melanogaster. The genetic behaviour of rDNA structural variants in separate and mixed populations derived from isofemale lines suggest that they are not subject to strong selection and are stable for over 1,000 generations. The high structural variability suggests an evolutionary rapid process of turnover in the family which could partly explain widespread sequence homogeneity (concerted evolution) of rDNA within a species.     

Comparison of the responsiveness of isolated arteries and veins taken from the same dogs 17 days apart

Summary The present experiments demonstrate that isolated arteries and veins taken from the same dogs before and after an interval of 17 days show comparable responses to adrenergic nerve stimulation, exogenous norepinephrine and depolarizing solution. They provide an acceptable model for the in vitro study of chronic influences on canine vascular responsiveness.     

Choice-specific sequences in parietal cortex during a virtual-navigation decision task

The posterior parietal cortex (PPC) has an important role in many cognitive behaviours; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioural choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (<100 micrometres). During working memory decision tasks, the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits.     

Seed coat thickness in the evolution of angiosperms

The seed habit represents a remarkable evolutionary advance in plant sexual reproduction. Since the Paleozoic, seeds carry a seed coat that protects, nourishes and facilitates the dispersal of the fertilization product(s). The seed coat architecture evolved to adapt to different environments and reproductive strategies in part by modifying its thickness. Here, we review the great natural diversity observed in seed coat thickness among angiosperms and its molecular regulation in Arabidopsis.     

Bird song: superfast muscles control dove's trill

Bird songs frequently contain trilling sounds that demand extremely fast vocalization control. Here we show that doves control their syrinx, a vocal organ that is unique to birds, by using superfast muscles. These muscles, which are similar to those that operate highly specialist acoustic organs such as the rattle of the rattlesnake, are among the fastest vertebrate muscles known and could be much more widespread than previously thought if they are the principal muscle type used to control bird songs.