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Mucus is a slimy hydrogel that lines the mucosal surfaces in our body, including the intestines, stomach, eyes, lungs and urogenital tract. This glycoprotein-rich network is truly the jack of all trades. As a barrier, it lubricates surfaces, protects our cells from physical stress, and selectively allows the passage of nutrients while clearing out pathogens and debris. As a home to our microbiota, it supports a level of microbial diversity that is unattainable with most culture methods. As a reservoir of complex carbohydrate structures called glycans, it plays critical roles in controlling cell adhesion and signaling, and it alters the behavior and spatial distribution of microbes. On top of all this, mucus regulates the passage of sperm during fertilization, heals wounds, helps us smell, and prevents the stomach from digesting itself, to name just a few of its functions. Given these impressive features, it is no wonder that mucus crosses boundaries of species and kingdoms - mucus gels are made by organisms ranging from the simplest metazoans to corals, snails, fish, and frogs. It is also no surprise that mucus is exploited in everyday applications, including foods, cosmetics, and other products relevant to medicine and industry.

Interview with Andrew Sih, who studies the evolution and ecological impacts of behavior on population patterns at the University of California, Davis.

Comment in Curr Biol. 2021 Aug 9;31(15):R955-R957.

In the spinal cord, cerebrospinal fluid-contacting neurons (CSF-cNs) are GABAergic interoceptive sensory neurons that detect spinal curvature via a functional coupling with the Reissner fiber. This mechanosensory system has recently been found to be involved in spine morphogenesis and postural control but the underlying mechanisms are not fully understood. In zebrafish, CSF-cNs project an ascending and ipsilateral axon reaching two to six segments away. Rostralmost CSF-cNs send their axons ipsilaterally into the hindbrain, a brain region containing motor nuclei and reticulospinal neurons (RSNs), which send descending motor commands to spinal circuits. Until now, the synaptic connectivity of CSF-cNs has only been investigated in the spinal cord, where they synapse onto motor neurons and premotor excitatory interneurons. The identity of CSF-cN targets in the hindbrain and the behavioral relevance of these sensory projections from the spinal cord to the hindbrain are unknown. Here, we provide anatomical and molecular evidence that rostralmost CSF-cNs synapse onto the axons of large RSNs including Mauthner cells and V2a neurons. Functional anatomy and optogenetically assisted mapping reveal that rostral CSF-cNs also synapse onto the soma and dendrites of cranial motor neurons innervating hypobranchial muscles. During acousto-vestibular evoked escape responses, ablation of rostralmost CSF-cNs results in a weaker escape response with a decreased C-bend amplitude, lower speed, and deficient postural control. Our study demonstrates that spinal sensory feedback enhances speed and stabilizes posture, and reveals a novel spinal gating mechanism acting on the output of descending commands sent from the hindbrain to the spinal cord.

Comment in Curr Biol. 2021 Aug 9;31(15):R950-R952.

Mechanical stress influences cell- and tissue-scale processes across all kingdoms. It remains challenging to delineate how mechanical stress, originating at these different length scales, impacts cell and tissue form. We combine growth tracking of cells, quantitative image analysis, as well as molecular and mechanical perturbations to address this problem in pavement cells of Arabidopsis thaliana cotyledon tissue. We show that microtubule organization based on chemical signals and cell-shape-derived mechanical stress varies during early stages of pavement cell development and is mediated by the evolutionary conserved proteins, KATANIN and CLASP. However, we find that these proteins regulate microtubule organization in response to tissue-scale mechanical stress to different extents in the cotyledon epidermis. Our results further demonstrate that regulation of cotyledon form is uncoupled from the mechanical-stress-dependent control of pavement cell shape that relies on microtubule organization governed by subcellular mechanical stress.

Sleep is essential for a variety of plastic processes, including learning and memory. However, the consequences of insufficient sleep on circuit connectivity remain poorly understood. To better appreciate the effects of sleep loss on synaptic connectivity across a memory-encoding circuit, we examined changes in the distribution of synaptic markers in the Drosophila mushroom body (MB). Protein-trap tags for active zone components indicate that recent sleep time is inversely correlated with Bruchpilot (BRP) abundance in the MB lobes; sleep loss elevates BRP while sleep induction reduces BRP across the MB. Overnight sleep deprivation also elevated levels of dSyd-1 and Cacophony, but not other pre-synaptic proteins. Cell-type-specific genetic reporters show that MB-intrinsic Kenyon cells (KCs) exhibit increased pre-synaptic BRP throughout the axonal lobes after sleep deprivation; similar increases were not detected in projections from large interneurons or dopaminergic neurons that innervate the MB. These results indicate that pre-synaptic plasticity in KCs is responsible for elevated levels of BRP in the MB lobes of sleep-deprived flies. Because KCs provide synaptic inputs to several classes of post-synaptic partners, we next used a fluorescent reporter for synaptic contacts to test whether each class of KC output connections is scaled uniformly by sleep loss. The KC output synapses that we observed here can be divided into three classes: KCs to MB interneurons; KCs to dopaminergic neurons; and KCs to MB output neurons. No single class showed uniform scaling across each constituent member, indicating that different rules may govern plasticity during sleep loss across cell types.

It has long been known that some mouse and vole species have unusual sex chromosomes. A recent genome sequencing study advances understanding of a particularly puzzling vole system.

Comment on Curr Biol. 2021 Aug 9;31(15):3303-3314.e3.

Daniel Pederick and Liqun Luo introduce teneurins, evolutionarily conserved type II transmembrane proteins with functions in the nervous system.

Not much is known about how the dentate gyrus (DG) and hippocampal CA3 networks, critical for memory and spatial processing, malfunction in Alzheimer's disease (AD). While studies of associative memory deficits in AD have focused mainly on behavior, here, we directly measured neurophysiological network dysfunction. We asked what the pattern of deterioration of different networks is during disease progression. We investigated how the associative memory-processing capabilities in different hippocampal subfields are affected by familial AD (fAD) mutations leading to amyloid-β dyshomeostasis. Specifically, we focused on the DG and CA3, which are known to be involved in pattern completion and separation and are susceptible to pathological alterations in AD. To identify AD-related deficits in neural-ensemble dynamics, we recorded single-unit activity in wild-type (WT) and fAD model mice (APPSwe+PSEN1/ΔE9) in a novel tactile morph task, which utilizes the extremely developed somatosensory modality of mice. As expected from the sub-network regional specialization, we found that tactile changes induced lower rate map correlations in the DG than in CA3 of WT mice. This reflects DG pattern separation and CA3 pattern completion. In contrast, in fAD model mice, we observed pattern separation deficits in the DG and pattern completion deficits in CA3. This demonstration of region-dependent impairments in fAD model mice contributes to understanding of brain networks deterioration during fAD progression. Furthermore, it implies that the deterioration cannot be studied generally throughout the hippocampus but must be researched at a finer resolution of microcircuits. This opens novel systems-level approaches for analyzing AD-related neural network deficits.

Dopamine (DA) transmission is critical to motivation, movement, and emotion. Unlike glutamatergic and GABAergic synapses, the development of DA synapses is less understood. We show that bassoon (BSN) clusters along DA axons in the core of nucleus accumbens (NAcc) were increased in neonatal stages and reduced afterward, suggesting DA synapse elimination. Remarkably, DA neuron-specific ablating neuregulin 3 (NRG3), a protein whose levels correlate with BSN clusters, increased the clusters and impaired DA release and behaviors related to DA transmission. An unbiased screen of transmembrane proteins with the extracellular domain (ECD) of NRG3 identified Caspr3 (contactin associate-like protein 3) as a binding partner. Caspr3 was enriched in striatal medium spiny neurons (MSNs). NRG3 and Caspr3 interact in trans, which was blocked by Caspr3-ECD. Caspr3 null mice displayed phenotypes similar to those in DAT-Nrg3f/f mice in DA axonal BSN clusters and DA transmission. Finally, in vivo disruption of the NRG3-Caspr3 interaction increased BSN clusters. Together, these results demonstrate that DA synapse development is controlled by trans interaction between NRG3 in DA neurons and Caspr3 in MSNs, identifying a novel pair of cell adhesion molecules for brain circuit wiring.

Brain machine interfaces (BMIs) hold promise to restore impaired motor function and serve as powerful tools to study learned motor skill. While limb-based motor prosthetic systems have leveraged nonhuman primates as an important animal model,1-4 speech prostheses lack a similar animal model and are more limited in terms of neural interface technology, brain coverage, and behavioral study design.5-7 Songbirds are an attractive model for learned complex vocal behavior. Birdsong shares a number of unique similarities with human speech,8-10 and its study has yielded general insight into multiple mechanisms and circuits behind learning, execution, and maintenance of vocal motor skill.11-18 In addition, the biomechanics of song production bear similarity to those of humans and some nonhuman primates.19-23 Here, we demonstrate a vocal synthesizer for birdsong, realized by mapping neural population activity recorded from electrode arrays implanted in the premotor nucleus HVC onto low-dimensional compressed representations of song, using simple computational methods that are implementable in real time. Using a generative biomechanical model of the vocal organ (syrinx) as the low-dimensional target for these mappings allows for the synthesis of vocalizations that match the bird's own song. These results provide proof of concept that high-dimensional, complex natural behaviors can be directly synthesized from ongoing neural activity. This may inspire similar approaches to prosthetics in other species by exploiting knowledge of the peripheral systems and the temporal structure of their output.

Numerous hematophagous insects are attracted to ammonia, a volatile released in human sweat and breath.1-3 Low levels of ammonia also attract non-biting insects such as the genetic model organism Drosophila melanogaster and several species of agricultural pests.4,5 Two families of ligand-gated ion channels function as olfactory receptors in insects,6-10 and studies have linked ammonia sensitivity to a particular olfactory receptor in Drosophila.5,11,12 Given the widespread importance of ammonia to insect behavior, it is surprising that the genomes of most insects lack an ortholog of this gene.6 Here, we show that canonical olfactory receptors are not necessary for responses to ammonia in Drosophila. Instead, we demonstrate that a member of the ancient electrogenic ammonium transporter family, Amt, is likely a new type of olfactory receptor. We report two hitherto unidentified olfactory neuron populations that mediate neuronal and behavioral responses to ammonia in Drosophila. Their endogenous ammonia responses are lost in Amt mutant flies, and ectopic expression of either Drosophila or Anopheles Amt confers ammonia sensitivity. These results suggest that Amt is the first transporter known to function as an olfactory receptor in animals and that its function may be conserved across insect species.

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Many animals rely on taste to identify nutritious foods and to avoid the consumption of harmful substances. The tastes of macronutrients, as well as of non-caloric micronutrients such as sodium and calcium, contribute to the regulation of ingestive behavior1,2. Whether vitamins also affect feeding behavior through taste is less clear. Here, we show that the fly Drosophila melanogaster has a strong preference for consuming a vitamin-containing diet: both sexes show a preference for folic acid, whereas only females show a preference for riboflavin. Females show a preference with vitamin concentrations as low as ∼10 nM - at least 50,000-fold lower than the concentration needed for sucrose preference. This female vitamin preference requires inputs from external and internal taste organs, suggesting that post-ingestive signals, in the absence of gustatory input, are insufficient to actuate preferential consumption of vitamin-containing diets. Our studies demonstrate that vitamin perception is an important determinant of feeding behavior.

Comment in Curr Biol. 2021 Aug 9;31(15):R969-R971.

Macroautophagy (hereafter referred to as autophagy) is a conserved process that promotes cellular homeostasis through the degradation of cytosolic components, also known as cargo. During autophagy, cargo is sequestered into double-membrane vesicles called autophagosomes, which are predominantly transported in the retrograde direction to the perinuclear region to fuse with lysosomes, thus ensuring cargo degradation.1 The mechanisms regulating directional autophagosomal transport remain unclear. The ATG8 family of proteins associates with autophagosome membranes2 and plays key roles in autophagy, including the movement of autophagosomes. This is achieved via the association of ATG8 with adaptor proteins like FYCO1, involved in the anterograde transport of autophagosomes toward the cell periphery.1,3-5 We previously reported that phosphorylation of LC3B/ATG8 on threonine 50 (LC3B-T50) by the Hippo kinase STK4/MST1 is required for autophagy through unknown mechanisms.6 Here, we show that STK4-mediated phosphorylation of LC3B-T50 reduces the binding of FYCO1 to LC3B. In turn, impairment of LC3B-T50 phosphorylation decreases starvation-induced perinuclear positioning of autophagosomes as well as their colocalization with lysosomes. Moreover, a significantly higher number of LC3B-T50A-positive autophagosomes undergo aberrant anterograde movement to axonal tips in mammalian neurons and toward the periphery of mammalian cells. Our data support a role of a nutrient-sensitive STK4-LC3B-FYCO1 axis in the regulation of the directional transport of autophagosomes, a key step of the autophagy process, via the post-translational modification of LC3B.

Comment in Curr Biol. 2021 Aug 9;31(15):R957-R959.

Diatoms, an evolutionarily successful group of microalgae, display high levels of intraspecific genetic variability in natural populations. However, the contribution of various mechanisms generating such diversity is unknown. Here we estimated the genetic micro-diversity within a natural diatom population and mapped the genomic changes arising within clonally propagated diatom cell cultures. Through quantification of haplotype diversity by next-generation sequencing and amplicon re-sequencing of selected loci, we documented a rapid accumulation of multiple haplotypes accompanied by the appearance of novel protein variants in cell cultures initiated from a single founder cell. Comparison of the genomic changes between mother and daughter cells revealed copy number variation and copy-neutral loss of heterozygosity leading to the fixation of alleles within individual daughter cells. The loss of heterozygosity can be accomplished by recombination between homologous chromosomes. To test this hypothesis, we established an endogenous readout system and estimated that the frequency of interhomolog mitotic recombination was under standard growth conditions 4.2 events per 100 cell divisions. This frequency is increased under environmental stress conditions, including treatment with hydrogen peroxide and cadmium. These data demonstrate that copy number variation and mitotic recombination between homologous chromosomes underlie clonal variability in diatom populations. We discuss the potential adaptive evolutionary benefits of the plastic response in the interhomolog mitotic recombination rate, and we propose that this may have contributed to the ecological success of diatoms.

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Large terrestrial carnivores have undergone some of the largest population declines and range reductions of any species, which is of concern as they can have large effects on ecosystem dynamics and function.1-4 The jaguar (Panthera onca) is the apex predator throughout the majority of the Neotropics; however, its distribution has been reduced by >50% and it survives in increasingly isolated populations.5 Consequently, the range-wide management of the jaguar depends upon maintaining core populations connected through multi-national, transboundary cooperation, which requires understanding the movement ecology and space use of jaguars throughout their range.6-8 Using GPS telemetry data for 111 jaguars from 13 ecoregions within the four biomes that constitute the majority of jaguar habitat, we examined the landscape-level environmental and anthropogenic factors related to jaguar home range size and movement parameters. Home range size decreased with increasing net productivity and forest cover and increased with increasing road density. Speed decreased with increasing forest cover with no sexual differences, while males had more directional movements, but tortuosity in movements was not related to any landscape factors. We demonstrated a synergistic relationship between landscape-scale environmental and anthropogenic factors and jaguars' spatial needs, which has applications to the conservation strategy for the species throughout the Neotropics. Using large-scale collaboration, we overcame limitations from small sample sizes typical in large carnivore research to provide a mechanism to evaluate habitat quality for jaguars and an inferential modeling framework adaptable to the conservation of other large terrestrial carnivores.

The Triassic was a crucial period for the early evolution and diversification of insects, including Coleoptera1-3-the most diverse order of organisms on Earth. The study of Triassic beetles, however, relies almost exclusively on flattened fossils with limited character preservation. Using synchrotron microtomography, we investigated a fragmentary Upper Triassic coprolite, which contains a rich record of 3D-preserved minute beetle remains of Triamyxa coprolithica gen. et sp. nov. Some specimens are nearly complete, preserving delicate structures of the legs and antennae. Most of them are congruent morphologically, implying that they are conspecific. Phylogenetic analyses suggest that T. coprolithica is a member of Myxophaga, a small suborder of beetles with a sparse fossil record, and that it represents the only member of the extinct family Triamyxidae fam. nov. Our findings highlight that coprolites can contain insect remains, which are almost as well preserved as in amber. They are thus an important source of information for exploring insect evolution before the Cretaceous-Neogene "amber time window." Treated as food residues, insect remains preserved in coprolites also have important implications for the paleoecology of insectivores, in this case, likely the dinosauriform Silesaurus opolensis.

Comment in Curr Biol. 2021 Aug 9;31(15):R953-R954.

During primary growth, plant tissues increase their length, and as these tissues mature, they initiate secondary growth to increase thickness.1 It is not known what activates this transition to secondary growth. Cytokinins are key plant hormones regulating vascular development during both primary and secondary growth. During primary growth of Arabidopsis roots, cytokinins promote procambial cell proliferation2,3 and vascular patterning together with the hormone auxin.4-7 In the absence of cytokinins, secondary growth fails to initiate.8 Enhanced cytokinin levels, in turn, promote secondary growth.8,9 Despite the importance of cytokinins, little is known about the downstream signaling events in this process. Here, we show that cytokinins and a few downstream LATERAL ORGAN BOUNDARIES DOMAIN (LBD) family of transcription factors are rate-limiting components in activating and further promoting secondary growth in Arabidopsis roots. Cytokinins directly activate transcription of two homologous LBD genes, LBD3 and LBD4. Two other homologous LBDs, LBD1 and LBD11, are induced only after prolonged cytokinin treatment. Our genetic studies revealed a two-stage mechanism downstream of cytokinin signaling: while LBD3 and LBD4 regulate activation of secondary growth, LBD1, LBD3, LBD4, and LBD11 together promote further radial growth and maintenance of cambial stem cells. LBD overexpression promoted rapid cell growth followed by accelerated cell divisions, thus leading to enhanced secondary growth. Finally, we show that LBDs rapidly inhibit cytokinin signaling. Together, our data suggest that the cambium-promoting LBDs negatively feed back into cytokinin signaling to keep root secondary growth in balance.

The mechanisms coordinating action and perception over time are poorly understood. The sensory cortex needs to prepare for upcoming changes contingent on action, and this requires temporally precise communication that takes into account the variable delays between sensory and motor processing. Several theorists1,2 have proposed synchronization of the endogenous oscillatory activity observed in most regions of the brain3 as the basis for an efficient and flexible communication protocol between distal brain areas,2,4 a concept known as "communication through coherence." Synchronization of endogenous oscillations5,6 occurs after a salient sensory stimulus, such as a flash or a sound,7-11 and after a voluntary action,12-18 and this directly impacts perception, causing performance to oscillate rhythmically over time. Here we introduce a novel fMRI paradigm to probe the neural sources of oscillations, based on the concept of perturbative signals, which overcomes the low temporal resolution of BOLD signals. The assumption is that a synchronized endogenous rhythm will modulate cortical excitability rhythmically, which should be reflected in the BOLD responses to brief stimuli presented at different phases of the oscillation cycle. We record rhythmic oscillations of V1 BOLD synchronized by a simple voluntary action, in phase with behaviorally measured oscillations in visual sensitivity in the theta range. The functional connectivity between V1 and M1 also oscillates at the same rhythm. By demonstrating oscillatory temporal coupling between primary motor and sensory cortices, our results strongly implicate communication through coherence to achieve precise coordination and to encode sensory-motor timing.

The epidermis is a stratified epithelium in which structural and functional features are polarized across multiple cell layers. This type of polarity is essential for establishing the epidermal barrier, but how it is created and sustained is poorly understood. Previous work identified a role for the classic cadherin/filamentous-actin network in establishment of epidermal polarity. However, little is known about potential roles of the most prominent epidermal intercellular junction, the desmosome, in establishing epidermal polarity, in spite of the fact that desmosome constituents are patterned across the apical to basal cell layers. Here, we show that desmosomes and their associated intermediate filaments (IFs) are key regulators of mechanical polarization in epidermis, whereby basal and suprabasal cells experience different forces that drive layer-specific functions. Uncoupling desmosomes and IF or specific targeting of apical desmosomes through depletion of the superficial desmosomal cadherin, desmoglein 1, impedes basal stratification in an in vitro competition assay and suprabasal tight junction barrier functions in 3D reconstructed epidermis. Surprisingly, disengaging desmosomes from IF also accelerated the expression of differentiation markers, through precocious activation of the mechanosensitive transcriptional regulator serum response factor (SRF) and downstream activation of epidermal growth factor receptor family member ErbB2 by Src family kinase (SFK)-mediated phosphorylation. This Dsg1-SFK-ErbB2 axis also helps maintain tight junctions and barrier function later in differentiation. Together, these data demonstrate that the desmosome-IF network is a critical contributor to the cytoskeletal-adhesive machinery that supports the polarized function of the epidermis.

The hippocampus is essential for human memory.1 The protracted maturation of memory capacities from infancy through early childhood2-4 is thus often attributed to hippocampal immaturity.5-7 The hippocampus of human infants has been characterized in terms of anatomy,8,9 but its function has never been tested directly because of technical challenges.10,11 Here, we use recently developed methods for task-based fMRI in awake human infants12 to test the hypothesis that the infant hippocampus supports statistical learning.13-15 Hippocampal activity increased with exposure to visual sequences of objects when the temporal order contained regularities to be learned, compared to when the order was random. Despite the hippocampus doubling in anatomical volume across infancy, learning-related functional activity bore no relationship to age. This suggests that the hippocampus is recruited for statistical learning at the youngest ages in our sample, around 3 months. Within the hippocampus, statistical learning was clearer in anterior than posterior divisions. This is consistent with the theory that statistical learning occurs in the monosynaptic pathway,16 which is more strongly represented in the anterior hippocampus.17,18 The monosynaptic pathway develops earlier than the trisynaptic pathway, which is linked to episodic memory,19,20 raising the possibility that the infant hippocampus participates in statistical learning before it forms durable memories. Beyond the hippocampus, the medial prefrontal cortex showed statistical learning, consistent with its role in adult memory integration21 and generalization.22 These results suggest that the hippocampus supports the vital ability of infants to extract the structure of their environment through experience.

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Episodic memory is the memory for experienced events. A peak competence of episodic memory is the mental combination of events to infer commonalities. Inferring commonalities may proceed with and without consciousness of events. Yet what distinguishes conscious from unconscious inference? This question inspired nine experiments that featured strongly and weakly masked cartoon clips presented for unconscious and conscious inference. Each clip featured a scene with a visually impenetrable hiding place. Five animals crossed the scene one-by-one consecutively. One animal trajectory represented one event. The animals moved through the hiding place, where they might linger or not. The participants' task was to observe the animals' entrances and exits to maintain a mental record of which animals hid simultaneously. We manipulated information load to explore capacity limits. Memory of inferences was tested immediately, 3.5 or 6 min following encoding. The participants retrieved inferences well when encoding was conscious. When encoding was unconscious, the participants needed to respond intuitively. Only habitually intuitive decision makers exhibited a significant delayed retrieval of inferences drawn unconsciously. Their unconscious retrieval performance did not drop significantly with increasing information load, while conscious retrieval performance dropped significantly. A working memory network, including hippocampus, was activated during both conscious and unconscious inference and correlated with retrieval success. An episodic retrieval network, including hippocampus, was activated during both conscious and unconscious retrieval of inferences and correlated with retrieval success. Only conscious encoding/retrieval recruited additional brain regions outside these networks. Hence, levels of consciousness influenced the memories' behavioral impact, memory capacity, and the neural representational code.

Microtubules are polarized intracellular polymers that play key roles in the cell, including in transport, polarity, and cell division. Across eukaryotic cell types, microtubules adopt diverse intracellular organization to accommodate these distinct functions coordinated by specific cellular sites called microtubule-organizing centers (MTOCs). Over 50 years of research on MTOC biology has focused mainly on the centrosome; however, most differentiated cells employ non-centrosomal MTOCs (ncMTOCs) to organize their microtubules into diverse arrays, which are critical to cell function. To identify essential ncMTOC components, we developed the biotin ligase-based, proximity-labeling approach TurboID for use in C. elegans. We identified proteins proximal to the microtubule minus end protein PTRN-1/Patronin at the apical ncMTOC of intestinal epithelial cells, focusing on two conserved proteins: spectraplakin protein VAB-10B/MACF1 and WDR-62, a protein we identify as homologous to vertebrate primary microcephaly disease protein WDR62. VAB-10B and WDR-62 do not associate with the centrosome and instead specifically regulate non-centrosomal microtubules and the apical targeting of microtubule minus-end proteins. Depletion of VAB-10B resulted in microtubule mislocalization and delayed localization of a microtubule nucleation complex ɣ-tubulin ring complex (γ-TuRC), while loss of WDR-62 decreased the number of dynamic microtubules and abolished γ-TuRC localization. This regulation occurs downstream of cell polarity and in conjunction with actin. As this is the first report for non-centrosomal roles of WDR62 family proteins, we expand the basic cell biological roles of this important disease protein. Our studies identify essential ncMTOC components and suggest a division of labor where microtubule growth and localization are distinctly regulated.

Sour has been studied almost exclusively as an aversive taste modality. Yet recent work in Drosophila demonstrates that specific carboxylic acids are attractive at ecologically relevant concentrations. Here, we demonstrate that lactic acid is an appetitive and energetic tastant, which stimulates feeding through activation of sweet gustatory receptor neurons (GRNs). This activation displays distinct, mechanistically separable stimulus onset and removal phases. Ionotropic receptor 25a (IR25a) primarily mediates the onset response, which shows specificity for the lactate anion and drives feeding initiation through proboscis extension. Conversely, sweet gustatory receptors (Gr64a-f) mediate a non-specific removal response to low pH that primarily impacts ingestion. While mutations in either receptor family have marginal impacts on feeding, lactic acid attraction is completely abolished in combined mutants. Thus, specific components of lactic acid are detected through two classes of receptors to activate a single set of sensory neurons in physiologically distinct ways, ultimately leading to robust behavioral attraction.

CRISPR-associated proteins (Cas1 and Cas2) integrate foreign DNA at the "leader" end of CRISPR loci. Several CRISPR leader sequences are reported to contain a binding site for a DNA-bending protein called integration host factor (IHF). IHF-induced DNA bending kinks the leader of type I-E CRISPRs, recruiting an upstream sequence motif that helps dock Cas1-2 onto the first repeat of the CRISPR locus. To determine the prevalence of IHF-directed CRISPR adaptation, we analyzed 15,274 bacterial and archaeal CRISPR leaders. These experiments reveal multiple IHF binding sites and diverse upstream sequence motifs in a subset of the I-C, I-E, I-F, and II-C CRISPR leaders. We identify subtype-specific motifs and show that the phase of these motifs is critical for CRISPR adaptation. Collectively, this work clarifies the prevalence and mechanism(s) of IHF-dependent CRISPR adaptation and suggests that leader sequences and adaptation proteins may coevolve under the selective pressures of foreign genetic elements like plasmids or phages.

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Comment in Curr Biol. 2021 Aug 23;31(16):R1006-R1008.

Bees, ants, and wasps are well known to visually navigate when traveling between their nests and foraging sites. When leaving their nest, landmarks in the vicinity are memorized and used upon return to locate the nest entrance.1,2 The Neotropical nocturnal sweat bee Megalopta genalis navigates under the forest canopy at light intensities ten times dimmer than starlight.3 Despite these dim conditions, Megalopta is able to memorize visual landmarks around the nest entrance in the frontal visual field.4 Even though frontal landmarks can clearly be discerned by Megalopta, the visual feature of greatest contrast in the rainforest at night is actually the dark dorsal silhouette of the distant canopy against the brighter night sky. Several species of ants,5-10 as well as a subsocial shield bug,11 use bright open gaps in the canopy as dorsal landmarks to navigate home while walking. Here we show that Megalopta is also able to distinguish dorsal landmarks during homing, the first flying insect known with this capacity. Megalopta is able to discriminate between differently oriented dorsal black striped patterns, or an "artificial canopy" of black circles, and to use this information to locate its nest entrance. These results suggest that the local foliage patterns created by the canopy against the brighter sky could potentially provide the bee with reliable landmark information for navigation during foraging and homing at night. VIDEO ABSTRACT.

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Tortoises (land turtles) are familiar animals and are generally assumed to be strict herbivores. Their ecological roles are most obvious in giant tortoise species which, due to their size and local abundance, play major roles as keystone species and ecosystem engineers1-3. In the Galápagos and Seychelles islands these species are known to play major roles as the islands' largest herbivores, with exceptionally high biomass and consuming up to 11% of primary production1. In addition they act as ecosystem engineers, dispersing seeds, breaking vegetation and eroding rocks2. However, as slow-moving poikilotherms most people assume their behaviour to be simple. Here we present video evidence of a Seychelles giant tortoise (Aldabrachelys gigantea) attacking a tern chick and pursuing it along a log. Finally the tortoise killed the chick and was observed to eat it. Other tortoises in the same area have been seen making similar attacks, although those were not fully documented. We believe that the exceptional combination of a tree-nesting tern colony with a resident giant tortoise population has created conditions leading to systematic hunting of birds by several individual tortoises; an entirely novel behavioural strategy for any tortoise species. VIDEO ABSTRACT.

150 million years ago, an animal no bigger than a herring gull soared above shallow lagoons in what is now Bavaria. It had obscenely long fingers on each hand, which anchored thin wings of skin, and long toothy jaws, perfectly suited to snatching squids and fishes from the warm waters. Our animal was probably doing just that before its untimely death. For one reason or another, the creature crashed into the water and sank to its anoxic depths, where it was eventually buried by layers of lime. The animal fossilised with sprawled arms and jaws agape - as if in shock and disbelief.

Bevil Conway introduces colors.

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Eye movements are an integral part of human visual perception. They allow us to have a small foveal region with exquisite acuity and at the same time a large visual field. For a long time, eye movements were regarded as machine-like behaviors in response to visual stimulation1, but over the past few decades it has been convincingly shown that expectations, intended actions, rewards and many other cognitive factors can have profound effects on the way we move our eyes2-4. In order to be useful, our oculomotor system must minimize delay with respect to the dynamic events in the visual scene. The ability to do so has been demonstrated in situations where we are in control of these events, for example when we are making a sandwich or tea5, and when we are active participants, for example when hitting a cricket ball6. But what about scenes with complex dynamics that we do not control or directly take part in, like a hockey game we are watching as a spectator? A semantic influence on gaze fixation location during viewing of tennis videos has been suggested before7. Here we use carefully annotated hockey videos to show that the brain is indeed able to exploit the semantic context of the game to anticipate the continuous motion of the puck, leading to eye movements that are fundamentally different than when following exactly the same motion without any context.

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Comment on Curr Biol. 2021 Aug 23;31(16):3648-3655.e9.

Erratum in Curr Biol. 2021 Aug 23;31(16):3705-3706.

The mitochondrion is an ancient endosymbiotic organelle that performs many essential functions in eukaryotic cells.1-3 Mitochondrial impairment often results in physiological defects or diseases.2-8 Since most mitochondrial genes have been copied into the nuclear genome during evolution,9 the regulatory and interaction mechanisms between the mitochondrial and nuclear genomes are very complex. Multiple mechanisms, including antioxidant, DNA repair, mitophagy, and mitochondrial biogenesis pathways, have been shown to monitor the quality and quantity of mitochondria.10-12 Nonetheless, it remains unclear if these pathways can be further modified to enhance mitochondrial stability. Previously, experimental evolution has been used to adapt cells to novel growth conditions. By analyzing the resulting evolved populations, insights have been gained into the underlying molecular mechanisms.13 Here, we experimentally evolved yeast cells under conditions that selected for efficient respiration while continuously assaulting the mitochondrial genome (mtDNA) with ethidium bromide (EtBr). We found that the ability to maintain functional mtDNA was enhanced in most of the evolved lines when challenged with mtDNA-damaging reagents. We identified mutations of the mitochondrial NADH dehydrogenase NDE1 in most of the evolved lines, but other pathways are also involved. Finally, we show that cells displaying enhanced mtDNA retention also exhibit a prolonged replicative lifespan. Our work reveals potential evolutionary trajectories by which cells can maintain functional mitochondria in response to mtDNA stress, as well as the physiological implications of such adaptations.

Comment in Curr Biol. 2021 Aug 23;31(16):R1003-R1006.

Erratum in Curr Biol. 2021 Aug 23;31(16):3703.

Comment in Curr Biol. 2021 Aug 23;31(16):R998-R1000.

Comment on Curr Biol. 2021 Aug 23;31(16):3621-3628.e4.

Interview with Ewelina Knapska, who studies the neurobiological basis of emotions at the Nencki Institute of Experimental Biology.

Prior experience is known to deeply influence new learning. A recent study describes a neural mechanism where initial sensory experience promotes the establishment of a competing and/or cooperative memory trace that shapes behavioral expression of subsequent learning.

Comment in Curr Biol. 2021 Aug 23;31(16):R993-R995.

Most new infectious diseases emerge when pathogens transfer from animals to humans.1,2 The suspected origin of the COVID pandemic in a wildlife wet market has resurfaced debates on the role of wildlife trade as a potential source of emerging zoonotic diseases.3-5 Yet there are no studies quantitatively assessing zoonotic disease risk associated with wildlife trade. Combining data on mammal species hosting zoonotic viruses and mammals known to be in current and future wildlife trade,6 we found that one-quarter (26.5%) of the mammals in wildlife trade harbor 75% of known zoonotic viruses, a level much higher than domesticated and non-traded mammals. The traded mammals also harbor distinct compositions of zoonotic viruses and different host reservoirs from non-traded and domesticated mammals. Furthermore, we highlight that primates, ungulates, carnivores, and bats represent significant zoonotic disease risks as they host 132 (58%) of 226 known zoonotic viruses in present wildlife trade, whereas species of bats, rodents, and marsupials represent significant zoonotic disease risks in future wildlife trade. Thus, the risk of carrying zoonotic diseases is not equal for all mammal species in wildlife trade. Overall, our findings strengthen the evidence that wildlife trade and zoonotic disease risks are strongly associated, and that mitigation measures should prioritize species with the highest risk of carrying zoonotic viruses. Curbing the sales of wildlife products and developing principles that support the sustainable and healthy trade of wildlife could be cost-effective investments given the potential risk and consequences of zoonotic outbreaks.

Plants, as sessile organisms, gained the ability to sense and respond to biotic and abiotic stressors to survive severe changes in their environments. The change in our climate comes with extreme dry periods but also episodes of flooding. The latter stress condition causes anaerobiosis-triggered cytosolic acidosis and impairs plant function. The molecular mechanism that enables plant cells to sense acidity and convey this signal via membrane depolarization was previously unknown. Here, we show that acidosis-induced anion efflux from Arabidopsis (Arabidopsis thaliana) roots is dependent on the S-type anion channel AtSLAH3. Heterologous expression of SLAH3 in Xenopus oocytes revealed that the anion channel is directly activated by a small, physiological drop in cytosolic pH. Acidosis-triggered activation of SLAH3 is mediated by protonation of histidine 330 and 454. Super-resolution microscopy analysis showed that the increase in cellular proton concentration switches SLAH3 from an electrically silent channel dimer into its active monomeric form. Our results show that, upon acidification, protons directly switch SLAH3 to its open configuration, bypassing kinase-dependent activation. Moreover, under flooding conditions, the stress response of Arabidopsis wild-type (WT) plants was significantly higher compared to SLAH3 loss-of-function mutants. Our genetic evidence of SLAH3 pH sensor function may guide the development of crop varieties with improved stress tolerance.

The establishment of the symbiotic interaction between rhizobia and legumes involves the Nod factor signaling pathway. Nod factor recognition occurs through two plant receptors, NFR1 and NFR5. However, the signal transduction mechanisms downstream of NFR1-NFR5-mediated Nod factor perception remain largely unknown. Here, we report that a small guanosine triphosphatase (GTPase), GmROP9, and a guanine nucleotide exchange factor, GmGEF2, are involved in the soybean-rhizobium symbiosis. We show that GmNFR1α phosphorylates GmGEF2a at its N-terminal S86, which stimulates guanosine diphosphate (GDP)-to-GTP exchange to activate GmROP9 and that the active form of GmROP9 can associate with both GmNFR1α and GmNFR5α. We further show that a scaffold protein, GmRACK1, interacts with active GmROP9 and contributes to root nodule symbiosis. Collectively, our results highlight the symbiotic role of GmROP9-GmRACK1 and support the hypothesis that rhizobial signals promote the formation of a protein complex comprising GmNFR1, GmNFR5, GmROP9, and GmRACK1 for symbiotic signal transduction in soybean.

Comment in Nat Rev Microbiol. 2021 Sep;19(9):550.

Recent studies have drawn contrasting conclusions about the extent to which local-scale measures of biodiversity are declining and whether such patterns conflict with the global-scale declines that have attracted much attention.1 A key source of high-quality data for such analyses comes from longitudinal biodiversity studies, which sample a given taxon repeatedly over time at a specific location.2 There has been relatively little consideration of how habitat change might lead to biases in the sampling and continuity of biodiversity time series data, and the consequent potential for bias in the biodiversity trends that result. Here, based on analysis of standardized routes from the North American Breeding Bird Survey (3,014 routes sampled over 18 years),3 we demonstrate that major local habitat change is associated with an increase in the rate of survey cessations. We further show that routes that were continued despite major habitat changes show reduced diversity. By simulating potential rates of loss, we show that the underlying real trends in taxonomic, functional, and phylogenetic diversity can even reverse in sign if more than a quarter of diversity is lost from routes that ceased and are thus no longer included in surveys. Our analyses imply that biodiversity loss can be underestimated by biases introduced if continued sampling in longitudinal studies is influenced by local change. We argue that researchers and conservation practitioners should be aware of the potential for bias in such data and seek to use more robust methods to evaluate biodiversity trends and make conservation decisions.

Erratum in Curr Biol. 2021 Aug 23;31(16):3704.

Evolution on islands, together with the often extreme phenotypic changes associated with it, has attracted much interest from evolutionary biologists. However, measuring the rate of change of phenotypic traits of extinct animals can be challenging, in part due to the incompleteness of the fossil record. Here, we use combined molecular and fossil evidence to define the minimum and maximum rate of dwarfing in an extinct Mediterranean dwarf elephant from Puntali Cave (Sicily).1 Despite the challenges associated with recovering ancient DNA from warm climates,2 we successfully retrieved a mitogenome from a sample with an estimated age between 175,500 and 50,000 years. Our results suggest that this specific Sicilian elephant lineage evolved from one of the largest terrestrial mammals that ever lived3 to an island species weighing less than 20% of its original mass with an estimated mass reduction between 0.74 and 200.95 kg and height reduction between 0.15 and 41.49 mm per generation. We show that combining ancient DNA with paleontological and geochronological evidence can constrain the timing of phenotypic changes with greater accuracy than could be achieved using any source of evidence in isolation.

Comment in Curr Biol. 2021 Aug 23;31(16):R1012-R1014.