Comment on Curr Biol. 2021 Jul 26;31(14):3125-3131.e4.

Comment on Curr Biol. 2021 Jul 26;31(14):3168-3173.e4.

Comment on Curr Biol. 2021 Jul 26;31(14):3192-3198.e7.

Our social world has been transformed by the COVID-19 pandemic. Beyond the direct impact of the pandemic on physical health, the social distancing measures implemented worldwide to slow down disease transmission have dramatically impacted social interactions1,2. These measures, including orders to stay at home and to maintain a social distance of at least 2 meters, have been essential to limit the spread of the disease, but they have had severe costs for humans as social animals2. Right before and right after the adoption of the most stringent measures in Switzerland in Spring 2020, we were conducting a series of experiments to measure the representation of the so-called peripersonal space - the space immediately surrounding our body, where we normally interact with objects and other individuals3. We found that the introduction of social distancing measures led to a reduction in the extent of the peripersonal space and enhanced its segregation between individuals, as if the presence of others in close space would activate an implicit form of freezing response.

Comment in Curr Biol. 2021 Jul 26;31(14):R887-R888.

Andrew Hacket-Pain introduces the phenomenon known as 'masting', in which perennial plants show extraordinary variation in annual reproductive effort.

In any given perceptual task, the visual system selectively weighs or filters incoming information. The particular set of weights or filters form a kind of template, which reveals the regions or types of information that are particularly useful for a given perceptual decision.1,2 Unfortunately, sensory input is noisy and ever changing. To compensate for these fluctuations, the visual system could adopt a strategy of biasing the templates such that they reflect a temporal smoothing of input, which would be a form of serial dependence.3-5 Here, we demonstrate that perceptual templates are, in fact, altered by serial dependence. Using a simple orientation detection task and classification-image technique, we found that perceptual templates are systematically biased toward previously seen, task-irrelevant orientations. The results of an orientation discrimination task suggest that this shift in perceptual template derives from a change in the perceptual appearance of orientation. Our study reveals how serial dependence biases internal templates of orientation and suggests that the sensitivity of classification-image techniques in general could be improved by taking into account history-dependent fluctuations in templates.

At the early stage of cancer development, oncogenic mutations often cause multilayered epithelial structures. However, the underlying molecular mechanism still remains enigmatic. By performing a series of screenings targeting plasma membrane proteins, we have found that collagen XVII (COL17A1) and CD44 accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells. In addition, the expression of COL17A1 and CD44 is also regulated by cell density and upon apical cell extrusion. We further demonstrate that the expression of COL17A1 and CD44 is profoundly upregulated at the upper layers of multilayered, transformed epithelia in vitro and in vivo. The accumulated COL17A1 and CD44 suppress mitochondrial membrane potential and reactive oxygen species (ROS) production. The diminished intracellular ROS level then promotes resistance against ferroptosis-mediated cell death upon cell extrusion, thereby positively regulating the formation of multilayered structures. To further understand the functional role of COL17A1, we performed comprehensive metabolome analysis and compared intracellular metabolites between RasV12 and COL17A1-knockout RasV12 cells. The data imply that COL17A1 regulates the metabolic pathway from the GABA shunt to mitochondrial complex I through succinate, thereby suppressing the ROS production. Moreover, we demonstrate that CD44 regulates membrane accumulation of COL17A1 in multilayered structures. These results suggest that CD44 and COL17A1 are crucial regulators for the clonal expansion of transformed cells within multilayered epithelia, thus being potential targets for early diagnosis and preventive treatment for precancerous lesions.

Whales are now largely protected from direct harvest, leading to partial recoveries in many previously depleted species.1 However, most populations remain far below their historical abundances and incidental human impacts, especially vessel strikes and entanglement in fishing gear, are increasingly recognized as key threats.2 In addition, climate-driven changes to prey dynamics are impacting the seasonal foraging grounds of many baleen whales.2 In many cases these impacts result directly in mortality. But it is less clear how widespread and increasing sub-lethal impacts are affecting life history, individual fitness, and population viability. We evaluated changes in body lengths of North Atlantic right whales (NARW) using aerial photogrammetry measurements collected from crewed aircraft and remotely operated drones over a 20-year period (Figure 1). NARW have been monitored consistently since the 1980s and have been declining in abundance since 2011 due primarily to deaths associated with entanglements in active fishing gear and vessel strikes.3 High rates of sub-lethal injuries and individual-level information on age, size and observed entanglements make this an ideal population to evaluate the effects that these widespread stressors may have on individual fitness. We find that entanglements in fishing gear are associated with shorter whales, and that body lengths have been decreasing since 1981. Arrested growth may lead to reduced reproductive success4,5 and increased probability of lethal gear entanglements.6 These results show that sub-lethal stressors threaten the recoveries of vulnerable whale populations even in the absence of direct harvest.

Comment in Curr Biol. 2021 Jul 26;31(14):R896-R898.

Plants display remarkable abilities to adjust growth and development to environmental conditions, such as the amount of available water. This developmental plasticity is apparent not only in root and shoot growth rates, but also in tissue patterning and cell morphology.1,2 We have previously shown that in response to limited water availability, Arabidopsis thaliana root displays changes in xylem morphology, mediated by the non-cell-autonomous action of abscisic acid, ABA.2 Here, we show, through analyses of ABA response reporters and tissue-specific suppression of ABA signaling, that xylem cells themselves act as primary signaling centers governing both xylem cell fate and xylem differentiation rate, revealing the cell-autonomous control of multiple aspects of xylem development by ABA. ABA rapidly activates the expression of genes encoding VASCULAR-RELATED NAC DOMAIN (VND) transcription factors. Molecular and genetic analyses revealed that the two ABA-mediated xylem developmental changes are regulated by distinct members of this transcription factor family, with VND2 and VND3 promoting differentiation rate of metaxylem cells, while VND7 promotes the conversion of metaxylem toward protoxylem morphology. This phenomenon shows how different aspects of developmental plasticity can be interlinked, yet genetically separable. Moreover, similarities in phenotypic and molecular responses to ABA in diverse species indicate evolutionary conservation of the ABA-xylem development regulatory network among eudicots. Hence, this study gives molecular insights into how environmental stress modifies plant vascular anatomy and has potential relevance for water use optimization and adaptation to drought conditions.

Comment in Curr Biol. 2021 Jul 26;31(14):R900-R901.

Comment in Curr Biol. 2021 Jul 26;31(14):R909-R912.

Comment in Curr Biol. 2021 Jul 26;31(14):R907-R909.

Comment on Curr Biol. 2021 Jul 26;31(14):3145-3152.e3.

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Comment on Curr Biol. 2020 Nov 16;30(22):4425-4431.e3. Curr Biol. 2021 Jul 26;31(14):R885-R887.

Comment in Curr Biol. 2021 Jul 26;31(14):R914-R917.

Comment in Curr Biol. 2021 Jul 26;31(14):R898-R900.

Mutations in Vps13D cause defects in autophagy, clearance of mitochondria, and human movement disorders. Here, we discover that Vps13D functions in a pathway downstream of Vmp1 and upstream of Marf/Mfn2. Like vps13d, vmp1 mutant cells exhibit defects in autophagy, mitochondrial size, and clearance. Through the relationship between vmp1 and vps13d, we reveal a novel role for Vps13D in the regulation of mitochondria and endoplasmic reticulum (ER) contact. Significantly, the function of Vps13D in mitochondria and ER contact is conserved between fly and human cells, including fibroblasts derived from patients suffering from VPS13D mutation-associated neurological symptoms. vps13d mutants have increased levels of Marf/MFN2, a regulator of mitochondrial fusion. Importantly, loss of marf/MFN2 suppresses vps13d mutant phenotypes, including mitochondria and ER contact. These findings indicate that Vps13d functions at a regulatory point between mitochondria and ER contact, mitochondrial fusion and autophagy, and help to explain how Vps13D contributes to disease.

One year into the global COVID-19 pandemic, the focus of attention has shifted to the emergence and spread of SARS-CoV-2 variants of concern (VOCs). After nearly a year of the pandemic with little evolutionary change affecting human health, several variants have now been shown to have substantial detrimental effects on transmission and severity of the virus. Public health officials, medical practitioners, scientists, and the broader community have since been scrambling to understand what these variants mean for diagnosis, treatment, and the control of the pandemic through nonpharmaceutical interventions and vaccines. Here we explore the evolutionary processes that are involved in the emergence of new variants, what we can expect in terms of the future emergence of VOCs, and what we can do to minimise their impact.

Comment on Curr Biol. 2021 Jul 26;31(14):3040-3052.e9.

Comment on Curr Biol. 2021 Jul 26;31(14):3053-3072.e5.

Interview with Christine Jacobs-Wagner, who studies the replication of bacterial cells at Stanford University.

Comment in Curr Biol. 2021 Jul 26;31(14):R902-R904.

In sexually reproducing animals, the oocyte contributes a large supply of RNAs that are essential to launch development upon fertilization. The mechanisms that regulate the composition of the maternal RNA contribution during oogenesis are unclear. Here, we show that a subset of RNAs expressed during the early stages of oogenesis is subjected to regulated degradation during oocyte specification. Failure to remove these RNAs results in oocyte dysfunction and death. We identify the RNA-degrading Super Killer complex and No-Go Decay factor Pelota as key regulators of oogenesis via targeted degradation of specific RNAs expressed in undifferentiated germ cells. These regulators target RNAs enriched for cytidine sequences that are bound by the polypyrimidine tract binding protein Half pint. Thus, RNA degradation helps orchestrate a germ cell-to-maternal transition that gives rise to the maternal contribution to the zygote.

Comment on Curr Biol. 2021 Jul 26;31(14):3098-3114.e7.

Comment on Curr Biol. 2021 Jul 26;31(14):3180-3184.e3.

Comment on Curr Biol. 2021 Jul 26;31(14):3137-3144.e11.

Comment in Curr Biol. 2021 Jul 26;31(14):R891-R893.

The motor control resolution of any animal behavior is limited to the minimal force step available when activating muscles, which is set by the number and size distribution of motor units (MUs) and muscle-specific force. Birdsong is an excellent model system for understanding acquisition and maintenance of complex fine motor skills, but we know surprisingly little about how the motor pool controlling the syrinx is organized and how MU recruitment drives changes in vocal output. Here we developed an experimental paradigm to measure MU size distribution using spatiotemporal imaging of intracellular calcium concentration in cross-sections of living intact syrinx muscles. We combined these measurements with muscle stress and an in vitro syrinx preparation to determine the control resolution of fundamental frequency (fo), a key vocal parameter, in zebra finches. We show that syringeal muscles have extremely small MUs, with 40%-50% innervating ≤3 and 13%-17% innervating a single muscle fiber. Combined with the lowest specific stress (5 mN/mm2) known to skeletal vertebrate muscle, small force steps by the major fo controlling muscle provide control of 50-mHz to 7.3-Hz steps per MU. We show that the song system has the highest motor control resolution possible in the vertebrate nervous system and suggest this evolved due to strong selection on fine gradation of vocal output. Furthermore, we propose that high-resolution motor control was a key feature contributing to the radiation of songbirds that allowed diversification of song and speciation by vocal space expansion.

Human cognition is believed to be unique in part because of early-emerging social skills for cooperative communication.1 Comparative studies show that at 2.5 years old, children reason about the physical world similarly to other great apes, yet already possess cognitive skills for cooperative communication far exceeding those in our closest primate relatives.2,3 A growing body of research indicates that domestic dogs exhibit functional similarities to human children in their sensitivity to cooperative-communicative acts. From early in development, dogs flexibly respond to diverse forms of cooperative gestures.4,5 Like human children, dogs are sensitive to ostensive signals marking gestures as communicative, as well as contextual factors needed for inferences about these communicative acts.6-8 However, key questions about potential biological bases for these abilities remain untested. To investigate their developmental and genetic origins, we tested 375 8-week-old dog puppies on a battery of social-cognitive measures. We hypothesized that if dogs' skills for cooperating with humans are biologically prepared, then they should emerge robustly in early development, not require extensive socialization or learning, and exhibit heritable variation. Puppies were highly skillful at using diverse human gestures, and we found no evidence that their performance required learning. Critically, over 40% of the variation in dogs' point-following abilities and attention to human faces was attributable to genetic factors. Our results suggest that these social skills in dogs emerge early in development and are under strong genetic control.

Integrins are transmembrane receptors that activate signal transduction pathways upon extracellular matrix binding. The integrin-mediated adhesive complex (IMAC) mediates various cell physiological processes. Although the IMAC was thought to be specific to animals, in the past ten years these complexes were discovered in other lineages of Obazoa, the group containing animals, fungi, and several microbial eukaryotes. Very recently, many genomes and transcriptomes from Amoebozoa (the eukaryotic supergroup sister to Obazoa), other obazoans, orphan protist lineages, and the eukaryotes' closest prokaryotic relatives, have become available. To increase the resolution of where and when IMAC proteins exist and have emerged, we surveyed these newly available genomes and transcriptomes for the presence of IMAC proteins. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought and that co-option of this apparently ancient protein complex was key to the emergence of animal-type multicellularity. The role of the IMACs in amoebozoans is unknown, but they play critical adhesive roles in at least some unicellular organisms.

Comment in Curr Biol. 2021 Jul 26;31(14):R893-R895.

Visual perception requires massive use of inference because the 3D structure of the world is not directly provided by the sensory input.1 Particularly challenging is anorthoscopic vision-when an object moves behind a narrow slit such that only a tiny fraction of it is visible at any instant. Impressively, human observers correctly recognize objects in slit-viewing conditions by early childhood,2,3 via temporal integration of the contours available in each sliver.4,5 But can this capability be acquired if one has been effectively blind throughout childhood? We studied 23 Ethiopian children which had bilateral early-onset cataracts-resulting in extremely poor vision in infancy-and surgically treated only years later. We tested their anorthoscopic vision, precisely because it requires a cascade of demanding visual inference processes to perceive veridical shape. Failure to perform the task may allow mapping specific bottlenecks for late visual recovery. The patients' visual acuity typically improved substantially within 6 months post-surgery. Still, at this stage many were unable to recover shape under slit-viewing conditions, although they could infer the direction of global motion. However, when retested later, almost all patients could judge shape in slit-conditions necessitating temporal integration. This acquired capability often transferred to novel stimuli, in similar slit-viewing conditions. Thus, learning was not limited to the specific visual features of the original shapes. These results indicate that plasticity of sophisticated visual inference routines is preserved well into adolescence, and vision restoration after prolonged early-onset blindness is feasible to a greater extent than previously thought.

Cadherins are essential adhesion proteins that regulate tissue cohesion and paracellular permeability by assembling dense adhesion plaques at cell-to-cell contacts. Adherens junctions are central to a wide range of tissue functions; identifying protein interactions that potentiate their assembly and regulation has been the focus of research for over 2 decades. Here, we present evidence for a new, unexpected mechanism of cadherin oligomerization on cells. Fully quantified spectral imaging fluorescence resonance energy transfer (FSI-FRET) and fluorescence intensity fluctuation (FIF) measurements directly demonstrate that E-cadherin forms constitutive lateral (cis) dimers at the plasma membrane. Results further show that binding of the cytosolic protein p120ctn binding to the intracellular region is required for constitutive E-cadherin dimerization. This finding differs from a model that attributes lateral (cis) cadherin oligomerization solely to extracellular domain interactions. The present, novel findings are further supported by studies of E-cadherin mutants that uncouple p120ctn binding or with cells in which p120ctn was knocked out using CRISPR-Cas9. Quantitative affinity measurements further demonstrate that uncoupling p120ctn binding reduces the cadherin trans binding affinity and cell adhesion. These findings transform the current model of cadherin assembly at cell surfaces and identify the core building blocks of cadherin-mediated intercellular adhesions. They also identify a new role for p120ctn and reconcile findings that implicate both the extracellular and intracellular cadherin domains in cadherin clustering and intercellular cohesion.

Temperature sensing is essential for the survival of living organisms. Some reptile embryos can reposition themselves within the egg to seek optimal temperatures, but the molecular sensors involved in this temperature detection remain unknown. Here, we show that such thermotaxic behavior is directly determined by the activation of two heat-sensitive ion channels of the turtle: the transient receptor potential ankyrin 1 (MrTRPA1) and transient receptor potential vanilloid-1 (MrTRPV1). These two TRP channels were found to exhibit distinctive distributions among turtle dorsal root ganglion (DRG) neurons. Additionally, our laser irradiation assays illustrated that the heat activation thresholds of MrTRPA1 and MrTRPV1 are consistent with the mild (28-33°C) and noxious (>33°C) heat determined by behavioral tests, respectively. Further pharmacological studies have demonstrated that ligand-induced intervention of MrTRPA1 or MrTRPV1 is sufficient to mimic heat stimuli or block temperature signaling, causing changes in embryo movement. These findings indicate that the initiation of thermotaxic response in turtle embryos relies on a delicate functional balance between the heat activation of MrTRPA1 and MrTRPV1. Our study reveals, for the first time, a unique molecular mechanism underlying thermal detection: the two TRP channels act as a physiological tandem to control the thermotaxic behavior of turtle embryos.

Comment in Curr Biol. 2021 Jul 26;31(14):R904-R906.

Comment in Curr Biol. 2021 Jul 26;31(14):R912-R914.

Few complete human genomes from the European Early Upper Palaeolithic (EUP) have been sequenced. Using novel sampling and DNA extraction approaches, we sequenced the genome of a woman from "Peştera Muierii," Romania who lived ∼34,000 years ago to 13.5× coverage. The genome shows similarities to modern-day Europeans, but she is not a direct ancestor. Although her cranium exhibits both modern human and Neanderthal features, the genome shows similar levels of Neanderthal admixture (∼3.1%) to most EUP humans but only half compared to the ∼40,000-year-old Peştera Oase 1. All EUP European hunter-gatherers display high genetic diversity, demonstrating that the severe loss of diversity occurred during and after the Last Glacial Maximum (LGM) rather than just during the out-of-Africa migration. The prevalence of genetic diseases is expected to increase with low diversity; however, pathogenic variant load was relatively constant from EUP to modern times, despite post-LGM hunter-gatherers having the lowest diversity ever observed among Europeans.

Comment on Curr Biol. 2021 Jul 26;31(14):3004-3016.e4.

Comment on Curr Biol. 2021 Jul 12;31(13):2757-2769.e6.

Comment on Curr Biol. 2021 Jul 12;31(13):2831-2843.e6.

Comment on Curr Biol. 2021 Jul 12;31(13):2955-2963.e4.

The primary cilium is an essential organizing center for signal transduction, and ciliary defects cause congenital disorders known collectively as ciliopathies.1-3 Primary cilia form by two pathways that are employed in a cell-type- and tissue-specific manner: an extracellular pathway in which the cilium grows out from the cell surface and an intracellular pathway in which the nascent cilium first forms inside the cell.4-8 After exposure to the external environment, cilia formed via the intracellular pathway may have distinct functional properties, as they often remain recessed within a ciliary pocket.9,10 However, the precise mechanism of intracellular ciliogenesis and its relatedness to extracellular ciliogenesis remain poorly understood. Here we show that Rab34, a poorly characterized GTPase recently linked to cilia,11-13 is a selective mediator of intracellular ciliogenesis. We find that Rab34 is required for formation of the ciliary vesicle at the mother centriole and that Rab34 marks the ciliary sheath, a unique sub-domain of assembling intracellular cilia. Rab34 activity is modulated by divergent residues within its GTPase domain, and ciliogenesis requires GTP binding and turnover by Rab34. Because Rab34 is found on assembly intermediates that are unique to intracellular ciliogenesis, we tested its role in the extracellular pathway used by polarized MDCK cells. Consistent with Rab34 acting specifically in the intracellular pathway, MDCK cells ciliate independently of Rab34 and its paralog Rab36. Together, these findings establish that different modes of ciliogenesis have distinct molecular requirements and reveal Rab34 as a new GTPase mediator of ciliary membrane biogenesis.

Organizational patterns can be shared across biological systems, and revealing the factors shaping common patterns can provide insight into fundamental biological mechanisms. The behavioral pattern that elements with more constituents tend to consist of shorter constituents (Menzerath's law [ML]) was described first in speech and language (e.g., words with more syllables consist of shorter syllables) and subsequently in music and animal communication. Menzerath's law is hypothesized to reflect efficiency in information transfer, but biases and constraints in motor production can also lead to this pattern. We investigated the evolutionary breadth of ML and the contribution of production mechanisms to ML in the songs of 15 songbird species. Negative relationships between the number and duration of constituents (e.g., syllables in phrases) were observed in all 15 species. However, negative relationships were also observed in null models in which constituents were randomly allocated into observed element durations, and the observed negative relationship for numerous species did not differ from the null model; consequently, ML in these species could simply reflect production constraints and not communicative efficiency. By contrast, ML was significantly different from the null model for more than half the cases, suggesting additional organizational rules are imposed onto birdsongs. Production mechanisms are also underscored by the finding that canaries and zebra finches reared without auditory experiences that guide vocal development produced songs with nearly identical ML patterning as typically reared birds. These analyses highlight the breadth with which production mechanisms contribute to this prevalent organizational pattern in behavior.

Comment in Curr Biol. 2022 Apr 25;32(8):R356-R357.

Air-based respiration limits the use of aquatic environments by ancestrally terrestrial animals. To overcome this challenge, diving arthropods have evolved to respire without resurfacing using air held between their cuticle and surrounding water.1-4 Inspired by natural history observations in Haiti (unpublished data) and Costa Rica,5,6 we conducted experiments documenting routine air-based underwater respiration in several distantly related semi-aquatic Anolis lizard species. Semi-aquatic anoles live along neotropical streams and frequently dive for refuge or food,7-12 remaining underwater for up to 18 min. While submerged, these lizards iteratively expire and re-inspire narial air bubbles-underwater "rebreathing." Rebreathed air is used in respiration, as the partial pressure of oxygen in the bubbles decreases with experimental submersion time in living anoles, but not in mechanical controls. Non-aquatic anoles occasionally rebreathe when submerged but exhibit more rudimentary rebreathing behaviors. Anole rebreathing is facilitated by a thin air layer (i.e., a "plastron," sensu Brocher13) supported by the animal's rugose skin upon submergence. We suggest that hydrophobic skin, which we observed in all sampled anoles,14,15 may have been exaptative, facilitating the repeated evolution of specialized rebreathing in species that regularly dive. Phylogenetic analyses strongly suggest that specialized rebreathing is adaptive for semi-aquatic habitat specialists. Air-based rebreathing may enhance dive performance by incorporating dead space air from the buccal cavity or plastron into the lungs, facilitating clearance of carbon dioxide, or allowing uptake of oxygen from surrounding water (i.e., a "physical gill" mechanism4,16).

Migration is common in marine animals,1-5 and use of the map-like information of Earth's magnetic field appears to play an important role.2,6-9 While sharks are iconic migrants10-12 and well known for their sensitivity to electromagnetic fields,13-20 whether this ability is used for navigation is unresolved.14,17,21,22 We conducted magnetic displacement experiments on wild-caught bonnetheads (Sphyrna tiburo) and show that magnetic map cues can elicit homeward orientation. We further show that use of a magnetic map to derive positional information may help explain aspects of the genetic structure of bonnethead populations in the northwest Atlantic.23-26 These results offer a compelling explanation for the puzzle of how migratory routes and population structure are maintained in marine environments, where few physical barriers limit movements of vagile species. VIDEO ABSTRACT.

Odor perception in non-humans is poorly understood. Here, we generated the most comprehensive mouse olfactory ethological atlas to date, consisting of behavioral responses to a diverse panel of 73 odorants, including 12 at multiple concentrations. These data revealed that mouse behavior is incredibly diverse and changes in response to odorant identity and concentration. Using only behavioral responses observed in other mice, we could predict which of two odorants was presented to a held-out mouse 82% of the time. Considering all 73 possible odorants, we could uniquely identify the target odorant from behavior on the first try 20% of the time and 46% within five attempts. Although mouse behavior is difficult to predict from human perception, they share three fundamental properties: first, odor valence parameters explained the highest variance of olfactory perception. Second, physicochemical properties of odorants can be used to predict the olfactory percept. Third, odorant concentration quantitatively and qualitatively impacts olfactory perception. These results increase our understanding of mouse olfactory behavior and how it compares to human odor perception and provide a template for future comparative studies of olfactory percepts among species.

Comment on Elife. 2021 May 20;10:

Comment on Curr Biol. 2021 Jul 12;31(13):2737-2746.e3.

Chance W. Riggins and Rita H. Mumm introduce the ancient amaranth genus, highlighting the ancient crop's controversial history and its contemporary use in improving food security.

In this My word, Joseph LeDoux explores what the emotional lives of other mammals might be like. He proposes that better understanding of the brain mechanisms of emotional consciousness in humans might shed light on the kinds of conscious capacities that might be possible in non-human primates and non-primate mammals, given the kinds of brains they possess.

Comment in Curr Biol. 2021 Jul 12;31(13):R850-R853.

Comment in Curr Biol. 2021 Jul 12;31(13):R853-R856.

Primary cilia are sensory organelles present on most vertebrate cells and are critical for development and health. Ciliary dysfunction is associated with a large class of human pathologies collectively known as ciliopathies. These include cystic kidneys, blindness, obesity, skeletal malformations, and other organ anomalies. Using a proximity biotinylation with Ift27 as bait, we identified the small guanosine triphosphatase (GTPase) Rab34 as a ciliary protein. Rab34 localizes to the centrosomes near the mother centriole, the axoneme of developed cilia, and highly dynamic tubule structures in the centrosomal region. Rab34 is required for cilia formation in fibroblasts, where we find that Rab34 loss blocks ciliogenesis at an early step of ciliary vesicle formation. In inner medullary collecting duct (IMCD3) epithelial cells, the requirement is more complex, with Rab34 needed in cells grown at low density but becoming less important as cell density increases. Ciliogenesis can proceed by an internal pathway where cilia form in the cytoplasm before being displayed on the ciliary surface or cilia can assemble by an external pathway where the centriole docks on the plasma membrane before ciliary assembly. Fibroblasts are thought to use the internal pathway, although IMCD3 cells are thought to use the external pathway. However, we find that IMCD3 cells can use the internal assembly pathway and significant numbers of internally assembling cilia are observed in low-density cells. Together, our work indicates that Rab34 is required for internal assembly of cilia, but not for cilia built on the cell surface.

The action observation network (AON) includes a system of brain areas largely shared with action execution in both human and nonhuman primates. Yet temporal and tuning specificities of distinct areas and of physiologically identified neuronal classes in the encoding of self and others' action remain unknown. We recorded the activity of 355 single units from three crucial nodes of the AON, the anterior intraparietal area (AIP), and premotor areas F5 and F6, while monkeys performed a Go/No-Go grasping task and observed an experimenter performing it. At the system level, during task execution, F6 displays a prevalence of suppressed neurons and signals whether an action has to be performed, whereas AIP and F5 share a prevalence of facilitated neurons and remarkable target selectivity; during task observation, F5 stands out for its unique prevalence of facilitated neurons and its stronger and earlier modulation than AIP and F6. By applying unsupervised clustering of spike waveforms, we found distinct cell classes unevenly distributed across areas, with different firing properties and carrying specific visuomotor signals. Broadly spiking neurons exhibited a balanced amount of facilitated and suppressed activity during action execution and observation, whereas narrower spiking neurons showed more mutually facilitated responses during the execution of one's own and others' action, particularly in areas AIP and F5. Our findings elucidate the time course of activity and firing properties of neurons in the AON during one's own and others' action, from the system level of anatomically distinct areas to the local level of physiologically distinct cell classes.

Many aspects of bird migration are necessarily innate.1 However, the extent of deterministic genetic control, environmental influence, and individual decision making in the control of migration remains unclear.2-8 Globally, few cases of rapid and dramatic life-history changes resulting in novel migration strategies are known. An example is latitudinal trans-hemispheric breeding colonization, whereby a subpopulation suddenly begins breeding on its non-breeding range.9-13 These life-history reversals demand concomitant changes in the timing of migration, feather molt, and breeding if the population is to remain viable.13 Cliff swallows, Petrochelidon pyrrhonota, are long-distance migrants that breed in North America and spend the non-breeding season mostly in South America.14 However, in 2015, a small population switched hemispheres by breeding successfully in Argentina,9 over 8,000 km from the nearest potential source, after presumably failed attempts.15,16 This provided a unique chance to characterize the early mechanisms of change in migratory behavior and phenology and to assess the possibility of double breeding. We tracked cliff swallows with geolocators following their second and fourth breeding seasons in Argentina, documenting inverted seasonality, three new migratory patterns and non-breeding areas (North America, Mesoamerica, and South America), and a shift of molt phenology by approximately 6 months, all possibly arising within a single generation. These birds did not practice migratory double breeding, although some spent the boreal summer in the traditional breeding range. Our data show that fundamental phenological changes occurred very rapidly during colonization and that phenotypic plasticity can underlie profound changes in the life histories of migratory birds.

Most of the genetic, cellular, and biochemical diversity of life rests within single-celled organisms - the prokaryotes (bacteria and archaea) and microbial eukaryotes (protists). Very close interactions, or symbioses, between protists and prokaryotes are ubiquitous, ecologically significant, and date back at least two billion years ago to the origin of mitochondria. However, most of our knowledge about the evolution and functions of eukaryotic symbioses comes from the study of animal hosts, which represent only a small subset of eukaryotic diversity. Here, we take a broad view of bacterial and archaeal symbioses with protist hosts, focusing on their evolution, ecology, and cell biology, and also explore what functions (if any) the symbionts provide to their hosts. With the immense diversity of protist symbioses starting to come into focus, we can now begin to see how these systems will impact symbiosis theory more broadly.

Comment on Cell Metab. 2021 Jul 6;33(7):1322-1341.e13.

Comment on Curr Biol. 2021 Jul 12;31(13):2868-2880.e8.

Who eats whom?' is a fundamental question about the ecological roles and interactions of deep-sea organisms. However, the tools needed to analyze trophic relationships remain limited, especially with regard to studying meiofauna and small macrofauna in abyssal and hadal depths. We present results from indirect molecular analyses of the gut contents of abyssal and hadal Solenogastres (Mollusca, Aplacophora) of the Northwest Pacific. Our data revealed a high food specialization and a surprising diversity of food sources among these inconspicuous worm-shaped predators. We hypothesize that Hydrozoa forms the ancestral food source of Solenogastres, and that specialization on non-cnidarian prey (such as annelids, nemerteans, and bivalves) evolved independently along with modifications in the digestive tract. Despite being intuitively advantageous in the nutrient-limited deep sea, we found only one widespread generalist feeder (potentially associated with scavenging).

Comment in Curr Biol. 2021 Jul 12;31(13):R848-R850.

Comment in Curr Biol. 2021 Jul 12;31(13):R838-R840.

Comment in Curr Biol. 2021 Jul 12;31(13):R843-R845.

Comment in Curr Biol. 2021 Jul 12;31(13):R840-R842.

Dynamics of cell elongation and septation are key determinants of bacterial morphogenesis. These processes are intimately linked to peptidoglycan synthesis performed by macromolecular complexes called the elongasome and the divisome. In rod-shaped bacteria, cell elongation and septation, which are dissociated in time and space, have been well described. By contrast, in ovoid-shaped bacteria, the dynamics and relationships between these processes remain poorly understood because they are concomitant and confined to a nanometer-scale annular region at midcell. Here, we set up a metabolic peptidoglycan labeling approach using click chemistry to image peptidoglycan synthesis by single-molecule localization microscopy in the ovoid bacterium Streptococcus pneumoniae. Our nanoscale-resolution data reveal spatiotemporal features of peptidoglycan assembly and fate along the cell cycle and provide geometrical parameters that we used to construct a morphogenesis model of the ovoid cell. These analyses show that septal and peripheral peptidoglycan syntheses first occur within a single annular region that later separates in two concentric regions and that elongation persists after septation is completed. In addition, our data reveal that freshly synthesized peptidoglycan is remodeled all along the cell cycle. Altogether, our work provides evidence that septal peptidoglycan is synthesized from the beginning of the cell cycle and is constantly remodeled through cleavage and insertion of material at its periphery. The ovoid-cell morphogenesis would thus rely on the relative dynamics between peptidoglycan synthesis and cleavage rather than on the existence of two distinct successive phases of peripheral and septal synthesis.

Gregarines are an early-diverging lineage of apicomplexan parasites that hold many clues into the origin and evolution of the group, a remarkable transition from free-living phototrophic algae into obligate parasites of animals.1 Using single-cell transcriptomics targeting understudied lineages to complement available sequencing data, we characterized the mitochondrial metabolic repertoire across the tree of apicomplexans. In contrast to the large suite of proteins involved in aerobic respiration in well-studied parasites like Toxoplasma or Plasmodium,2 we find that gregarine trophozoites have significantly reduced energy metabolism: most lack respiratory complexes III and IV, and some lack the electron transport chains (ETCs) and tricarboxylic acid (TCA) cycle entirely. Phylogenomic analyses show that these reductions took place several times in parallel, resulting in a functional range from fully aerobic organelles to extremely reduced "mitosomes" restricted to Fe-S cluster biosynthesis. The mitochondrial genome has also been lost repeatedly: in species with severe functional reduction simply by gene loss but in one species with a complete ETC by relocating cox1 to the nuclear genome. Severe functional reduction of mitochondria is generally associated with structural reduction, resulting in small, nondescript mitochondrial-related organelles (MROs).3 By contrast, gregarines retain distinctive mitochondria with tubular cristae, even the most functionally reduced cases that also lack genes associated with cristae formation. Overall, the parallel, severe reduction of gregarine mitochondria expands the diversity of organisms that contain MROs and further emphasizes the role of parallel transitions in apicomplexan evolution.

Understanding how the brain represents the identity of complex objects is a central challenge of visual neuroscience. The principles governing object processing have been extensively studied in the macaque face patch system, a sub-network of inferotemporal (IT) cortex specialized for face processing. A previous study reported that single face patch neurons encode axes of a generative model called the "active appearance" model, which transforms 50D feature vectors separately representing facial shape and facial texture into facial images. However, a systematic investigation comparing this model to other computational models, especially convolutional neural network models that have shown success in explaining neural responses in the ventral visual stream, has been lacking. Here, we recorded responses of cells in the most anterior face patch anterior medial (AM) to a large set of real face images and compared a large number of models for explaining neural responses. We found that the active appearance model better explained responses than any other model except CORnet-Z, a feedforward deep neural network trained on general object classification to classify non-face images, whose performance it tied on some face image sets and exceeded on others. Surprisingly, deep neural networks trained specifically on facial identification did not explain neural responses well. A major reason is that units in the network, unlike neurons, are less modulated by face-related factors unrelated to facial identification, such as illumination.

Memory retrieval refers to the fundamental ability of organisms to make use of acquired, sometimes inconsistent, information about the world. Although memory acquisition has been studied extensively, the neurobiological mechanisms underlying memory retrieval remain largely unknown. Conditioned taste aversion (CTA) is a robust associative paradigm, through which animals can be trained to express aversion toward innately appetitive tastants. The anterior insula (aIC) is indispensable in the ability of mammals to retrieve associative information regarding tastants that have been previously linked with gastric malaise. Here, we show that CTA memory retrieval promotes cell-type-specific activation in the aIC. Using chemogenetic tools in the aIC, we found that CTA memory acquisition requires activation of excitatory neurons and inhibition of inhibitory neurons, whereas retrieval necessitates activation of both excitatory and inhibitory aIC circuits. CTA memory retrieval at the aIC activates parvalbumin (PV) interneurons and increases synaptic inhibition onto activated pyramidal neurons projecting to the basolateral amygdala (aIC-BLA). Unlike innately appetitive taste memory retrieval, CTA retrieval increases synaptic inhibition onto aIC-BLA-projecting neurons that is dependent on activity in aIC PV interneurons. PV aIC interneurons coordinate CTA memory retrieval and are necessary for its dominance when conflicting internal representations are encountered over time. The reinstatement of CTA memories following extinction is also dependent on activation of aIC PV interneurons, which increase the frequency of inhibition onto aIC-BLA-projecting neurons. This newly described interaction of PV and a subset of excitatory neurons can explain the coherency of aversive memory retrieval, an evolutionary pre-requisite for animal survival.

Organisms adapt to their environments by learning to approach states that predict rewards and avoid states associated with punishments. Knowledge about the affective value of states often relies on credit assignment (CA), whereby state values are updated on the basis of reward feedback. Remarkably, humans assign credit to states that are not observed but are instead inferred based on a cognitive map that represents structural knowledge of an environment. A pertinent example is authors attempting to infer the identity of anonymous reviewers to assign them credit or blame and, on this basis, inform future referee recommendations. Although inference is cognitively costly, it is unknown how it influences CA or how it is apportioned between hidden and observable states (for example, both anonymous and revealed reviewers). We addressed these questions in a task that provided choices between lotteries where each led to a unique pair of occasionally rewarding outcome states. On some trials, both states were observable (rendering inference nugatory), whereas on others, the identity of one of the states was concealed. Importantly, by exploiting knowledge of choice-state associations, subjects could infer the identity of this hidden state. We show that having to perform inference reduces state-value updates. Strikingly, and in violation of normative theories, this reduction in CA was selective for the observed outcome alone. These findings have implications for the operation of putative cognitive maps.

Comment on Curr Biol. 2021 Jul 12;31(13):2964-2971.e5.

Comment on Curr Biol. 2021 Jul 12;31(13):2857-2867.e4.

Interview with Larisa DeSantis, who uses fossil mammals to study ancient climate change and extinctions, with a view to understand past and present ecosystems, at Vanderbilt University.

The latitudinal gradient of increasing marine biodiversity from the poles to the tropics is one of the most conspicuous biological patterns in modern oceans.1-3 Low-latitude regions of the global ocean are often hotspots of animal biodiversity, yet they are set to be most critically affected by anthropogenic climate change.4 As ocean temperatures rise and deoxygenation proceeds in the coming centuries, the volume of aerobically viable habitat is predicted to decrease in these zones.5,6 In contrast to the slightly asymmetrical modern latitudinal biodiversity gradient,7 compilations of fossil occurrences indicate peaks in biodiversity may have existed much further away from the equator in the past, with transitions between climate states hypothesized to explain this trend.8-13 We combine a new compilation of fossil mollusc occurrences, paleotemperature proxies, and biogeographic data to reveal a non-monotonic relationship between temperature and diversity in the paleontological record over the last 145 million years. We derive a metabolic model that integrates the kinetic effects of temperature on biodiversity14 with the recently described Metabolic Index that calculates aerobic habitat availability based on the effect of temperature on hypoxia sensitivity.5,15,16 Although factors such as coastal habitat area and homeothermy are important,17,18 we find strong congruence between our metabolic model and our fossil and paleotemperature meta-analysis. We therefore suggest that the effects of ocean temperature on the aerobic scope of marine ectotherms is a primary driver of migrating biodiversity peaks through geologic time and will likely play a role in the restructuring of biodiversity under projected future climate scenarios.

Species is the fundamental taxonomic unit in biology and its delimitation has implications for conservation. In giraffe (Giraffa spp.), multiple taxonomic classifications have been proposed since the early 1900s.1 However, one species with nine subspecies has been generally accepted,2 likely due to limited in-depth assessments, subspecies hybridizing in captivity,3,4 and anecdotal reports of hybrids in the wild.5 Giraffe taxonomy received new attention after population genetic studies using traditional genetic markers suggested at least four species.6,7 This view has been met with controversy,8 setting the stage for debate.9,10 Genomics is significantly enhancing our understanding of biodiversity and speciation relative to traditional genetic approaches and thus has important implications for species delineation and conservation.11 We present a high-quality de novo genome assembly of the critically endangered Kordofan giraffe (G. camelopardalis antiquorum)12 and a comprehensive whole-genome analysis of 50 giraffe representing all traditionally recognized subspecies. Population structure and phylogenomic analyses support four separately evolving giraffe lineages, which diverged 230-370 ka ago. These lineages underwent distinct demographic histories and show different levels of heterozygosity and inbreeding. Our results strengthen previous findings of limited gene flow and admixture among putative giraffe species6,7,9 and establish a genomic foundation for recognizing four species and seven subspecies, the latter of which should be considered as evolutionary significant units. Achieving a consensus over the number of species and subspecies in giraffe is essential for adequately assessing their threat level and will improve conservation efforts for these iconic taxa.

Comment in Curr Biol. 2021 Jul 12;31(13):R845-R848.