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Journal: iScience


Domestication dramatically alters phenotypes across animal species. Standing variation among ancestral populations often drives phenotypic change during domestication, but some changes are caused by novel mutations. In dogs (Canis familiaris) specifically, it has been suggested that the ability to interpret social-communicative behavior expressed by humans originated post-domestication and this behavior is thus not expected to occur in wolves (Canis lupus). Here we report the observation of three 8-week-old wolf puppies spontaneously responding to social-communicative behaviors from an unfamiliar person by retrieving a ball. This behavioral expression in wolves has significant implications for our understanding and expectations of the genetic foundations of dog behavior. Importantly, our observations indicate that behavioral responses to human social-communicative cues are not unique to dogs. This suggests that, although probably rare, standing variation in the expression of human-directed behavior in ancestral populations could have been an important target for early selective pressures exerted during dog domestication.


Understanding why a transcription factor (TF) binds to a specific DNA element in the genome and whether that binding event affects transcriptional output remains a great challenge. In this study, we demonstrate that TF binding in the genome follows inversion symmetry (IS). In addition, the specific DNA elements where TFs bind in the genome are determined by internal IS within the DNA element. These DNA-binding rules quantitatively define how TFs select the appropriate regulatory targets from a large number of similar DNA elements in the genome to elicit specific transcriptional and cellular responses. Importantly, we also demonstrate that these DNA-binding rules extend to DNA elements that do not support transcriptional activity. That is, the DNA-binding rules are obeyed, but the retention time of the TF at these non-functional DNA elements is not long enough to initiate and/or maintain transcription. We further demonstrate that IS is universal within the genome. Thus, IS is the DNA code that TFs use to interact with the genome and dictates (in conjunction with known DNA sequence constraints) which of those interactions are functionally active.


Trees are commonly regarded as distinct entities, but the roots of many species fuse to form natural root grafts allowing the exchange of water, carbon, mineral nutrients, and microorganisms between individuals. Exploiting the phenomenon of leafless (photosynthetically inactive) tree remnants being kept alive by conspecifics, we show tight physiological coupling of a living kauri (Agathis australis) stump to conspecific neighbors. The trunk remnant displayed greatly reduced, inverted daily sap flow patterns compared with intact kauri trees. Its stem water potential showed strong diel variation with minima during daytime and maxima at night, coinciding with peak and minimal sap flow rates in neighbors, respectively. Sudden atmospherically driven changes in water relations in adjacent kauri trees were very rapidly and inversely mirrored in the living stump’s water status. Such intimate hydrological coupling suggests a “communal physiology” among (conspecific) trees with far-reaching implications for our understanding of forest functioning, particularly under water shortage.


Amphibians are known for their skin rich in glands containing toxins employed in passive chemical defense against predators, different from, for example, snakes that have active chemical defense, injecting their venom into the prey. Caecilians (Amphibia, Gymnophiona) are snake-shaped animals with fossorial habits, considered one of the least known vertebrate groups. We show here that amphibian caecilians, including species from the basal groups, besides having cutaneous poisonous glands as other amphibians do, possess specific glands at the base of the teeth that produce enzymes commonly found in venoms. Our analysis of the origin of these glands shows that they originate from the same tissue that gives rise to teeth, similar to the venom glands in reptiles. We speculate that caecilians might have independently developed mechanisms of production and injection of toxins early in their evolutionary history.


Natural and artificial flower pollination are critical processes in the life cycle of flowering plants. Declines in the number of global pollinator insects, the heavy labor of conducting artificial pollination manually, and the rising cost of pollen grains are considered to be significant worldwide problems. Here we show that chemically functionalized soap bubbles exhibit effective and convenient delivery of pollen grains to the targeted flowers thanks to their stickiness, softness, high flexibility, and enhancement of pollen activity. By exploring the physicochemical properties of functional soap bubbles, we could prepare mechanically stabilized soap bubbles capable of withstanding the windmills produced by robotic pollination. An unmanned aerial vehicle equipped with a soap bubble maker was autonomously controlled to pollinate flowers. Such technology of automatic intelligent robotic pollination with functional soft materials would lead to innovative agricultural systems that can tackle the global issues of pollination.


Using high-resolution diffusion magnetic resonance imaging (dMRI) and a suite of old and new staining techniques, the beginnings of a multi-scale connectome map of the squid brain is erected. The first of its kind for a cephalopod, this includes the confirmation of 281 known connections with the addition of 145 previously undescribed pathways. These and other features suggest a suite of functional attributes, including (1) retinotopic organization through the optic lobes and into other brain areas well beyond that previously recognized, (2) a level of complexity and sub-division in the basal lobe supporting ideas of convergence with the vertebrate basal ganglia, and (3) differential lobe-dependent growth rates that mirror complexity and transitions in ontogeny.


Although in recent years there has been an increased awareness of the widespread nature of biofluorescence in the marine environment, the diversity of the molecules responsible for this luminescent phenotype has been mostly limited to green fluorescent proteins (GFPs), GFP-like proteins, and fluorescent fatty acid-binding proteins (FABPs). In the present study, we describe a previously undescribed group of brominated tryptophan-kynurenine small molecule metabolites responsible for the green biofluorescence in two species of sharks and provide their structural, antimicrobial, and spectral characterization. Multi-scale fluorescence microscopy studies guided the discovery of metabolites that were differentially produced in fluorescent versus non-fluorescent skin, as well as the species-specific structural details of their unusual light-guiding denticles. Overall, this study provides the detailed description of a family of small molecules responsible for marine biofluorescence and opens new questions related to their roles in central nervous system signaling, resilience to microbial infections, and photoprotection.


GPRC5B recruitment of Src family kinases has been implicated in diet-induced insulin resistance. However, the mechanism of this action is not fully understood. Here, we report that GPRC5B-mediated phosphorylation of sphingomyelin synthase 2 (SMS2) by Fyn is a crucial step in the development of insulin resistance. Lipid-induced metabolic stress augments SMS2 phosphorylation by facilitating the interaction of GPRC5B and SMS2. SMS2 phosphorylation reduces its ubiquitination, and consequently increases SMS2 protein abundance. Although ceramide and diacylglycerol (DAG) have been known to be central mediators of lipid-induced insulin resistance, the accumulation of these lipids fails to impair insulin signaling in SMS2 knockout mouse embryonic fibroblasts (MEFs). Conversely, exogenous expression of a phosphomimetic SMS2 impairs insulin action in SMS2 knockout MEFs under metabolic stress conditions. We demonstrate that SMS2-generated DAG in sphingomyelin synthesis inhibits insulin signaling through JNK activation. Thus, GPRC5B links sphingolipid metabolism to diet-induced insulin resistance via SMS2-dependent DAG production.


SARM1, an NAD-utilizing enzyme, regulates axonal degeneration. We show that CZ-48, a cell-permeant mimetic of NMN, activated SARM1 in vitro and in cellulo to cyclize NAD and produce a Ca2+ messenger, cADPR, with similar efficiency as NMN. Knockout of NMN-adenylyltransferase elevated cellular NMN and activated SARM1 to produce cADPR, confirming NMN was its endogenous activator. Determinants for the activating effects and cell permeability of CZ-48 were identified. CZ-48 activated SARM1 via a conformational change of the auto-inhibitory domain and dimerization of its catalytic domain. SARM1 catalysis was similar to CD38, despite having no sequence similarity. Both catalyzed similar set of reactions, but SARM1 had much higher NAD-cyclizing activity, making it more efficient in elevating cADPR. CZ-48 acted selectively, activating SARM1 but inhibiting CD38. In SARM1-overexpressing cells, CZ-48 elevated cADPR, depleted NAD and ATP, and induced non-apoptotic death. CZ-48 is a specific modulator of SARM1 functions in cells.


Metal carbenes, divalent carbon species, are versatile intermediates that enable novel synthetic pathways. These species exhibit either electrophilic or nucleophilic character, depending on the carbene and metal fragments. Although the metal carbene reactivity is regulated by the metal, the umpolung of carbene reactivity by changing metal remains challenging. Here, we report a unique metal-induced de novo umpolung of carbene reactivity, wherein a carbene precursor can be transformed into either an electrophilic carbene or a nucleophilic carbenoid, depending on the metal promoters. Thus, a chemodivergent reaction of isatins and cyclopropenes is developed. Under the promotion of Zn2+ halides, a nucleophilic zinc carbenoid is formed and trapped by isatins to produce oxindole derivatives containing an alkenyl halide moiety. Using Rh2(esp)2 as a catalyst, the reaction delivers oxindoles carrying a dihydrofuran unit. This work provides a facile approach to harness the metal carbene reactivity and is critical for the development of diversity-oriented synthesis.