Maciasmadden3166

They also reveal the basis for variations in functional potency among wild-type motifs, and allow derivation of a quantitative matrix that predicts the strength of other candidate motif sequences. Finally, we find that variation in docking motif potency can advance or delay the time at which CDK substrate phosphorylation occurs, and thereby control the temporal ordering of cell cycle regulation. The overall results provide a general method for surveying viable docking motif sequences and quantifying their potency in vivo, and they reveal how variations in docking strength can tune the degree and timing of regulatory modifications.Mammalian sleep expression and regulation have historically been thought to reflect the activity of neurons. Changes in other brain cells (glia) across the sleep-wake cycle and their role in sleep regulation are comparatively unexplored. We show that sleep and wakefulness are accompanied by state-dependent changes in astroglial activity. Using a miniature microscope in freely behaving mice and a two-photon microscope in head-fixed, unanesthetized mice, we show that astroglial calcium signals are highest in wake and lowest in sleep and are most pronounced in astroglial processes. We also find that astroglial calcium signals during non-rapid eye movement sleep change in proportion to sleep need. In contrast to neurons, astrocytes become less synchronized during non-rapid eye movement sleep after sleep deprivation at the network and single-cell level. Finally, we show that conditionally reducing intracellular calcium in astrocytes impairs the homeostatic response to sleep deprivation. Thus, astroglial calcium activity changes dynamically across vigilance states, is proportional to sleep need, and is a component of the sleep homeostat.Although it is well established that fronto-parietal regions are active during action observation, whether they play a causal role in the ability to infer others' intentions from visual kinematics remains undetermined. In the experiments reported here, we combined offline continuous theta burst stimulation (cTBS) with computational modeling to reveal and causally probe single-trial computations in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Participants received cTBS over the left anterior IPL and the left IFG pars orbitalis in separate sessions before completing an intention discrimination task (discriminate intention of observed reach-to-grasp acts) or a kinematic discrimination task unrelated to intention (discriminate peak wrist height of the same acts). We targeted intention-sensitive regions whose fMRI activity, recorded when observing the same reach-to-grasp acts, could accurately discriminate intention. We found that transient disruption of activity of the left IPL, but not the IFG, impaired the observer's ability to attribute intention to action. Kinematic discrimination unrelated to intention, in contrast, was largely unaffected. Computational analyses of how encoding (mapping of intention to movement kinematics) and readout (mapping of kinematics to intention choices) intersect at the single-trial level revealed that IPL cTBS did not diminish the overall sensitivity of intention readout to movement kinematics. Rather, it selectively misaligned intention readout with respect to encoding, deteriorating mapping from informative kinematic features to intention choices. These results provide causal evidence of how the left anterior IPL computes mapping from kinematics to intentions.The basal ganglia are implicated in a range of perceptual functions [1], in addition to their well-known role in the regulation of movement [2]. One unifying explanation for these diverse roles is that the basal ganglia control the level of commitment to particular motor or cognitive outcomes based on the behavioral context [3, 4]. If this explanation is applicable to the allocation of visual spatial attention, then the involvement of basal ganglia circuits should incorporate the subject's expectations about the spatial location of upcoming events as well as the routing of visual signals that guide the response. From the viewpoint of signal detection theory, these changes in the level of commitment might correspond to shifts in the subject's decision criterion, one of two distinct components recently ascribed to visual selective attention [5]. We tested this idea using unilateral optogenetic activation of neurons in the dorsal striatum of mice during a visual spatial attention task [6], taking advantage of the ability to specifically target medium spiny neurons in the "direct" pathway associated with promoting responses [7, 8]. By comparing results across attention task conditions, we found that direct-pathway activation caused changes in performance determined by the spatial probability and location of the visual event. Moreover, across conditions with identical visual stimulation, activation shifted the decision criterion selectively when attention was directed to the contralateral visual field. These results demonstrate that activity through the basal ganglia may play an important and distinct role among the multifarious mechanisms that accomplish visual spatial attention.Domestication involves recent adaptation under strong human selection and rapid diversification and therefore constitutes a good model for studies of these processes. We studied the domestication of the emblematic white mold Penicillium camemberti, used for the maturation of soft cheeses, such as Camembert and Brie, about which surprisingly little was known, despite its economic and cultural importance. Whole-genome-based analyses of genetic relationships and diversity revealed that an ancient domestication event led to the emergence of the gray-green P. biforme mold used in cheese making, by divergence from the blue-green wild P. fuscoglaucum fungus. Another much more recent domestication event led to the generation of the P. camemberti clonal lineage as a sister group to P. biforme. Penicillium biforme displayed signs of phenotypic adaptation to cheese making relative to P. fuscoglaucum, in terms of whiter color, faster growth on cheese medium under cave conditions, lower amounts of toxin production, and greater ability to prevent the growth of other fungi. The P. camemberti lineage displayed even stronger signs of domestication for all these phenotypic features. We also identified two differentiated P. camemberti varieties, apparently associated with different kinds of cheeses and with contrasted phenotypic features in terms of color, growth, toxin production, and competitive ability. We have thus identified footprints of domestication in these fungi, with genetic differentiation between cheese and wild populations, bottlenecks, and specific phenotypic traits beneficial for cheese making. This study has not only fundamental implications for our understanding of domestication but can also have important effects on cheese making.Locating unpredictable but essential resources is a task that all mobile animals have to perform in order to survive and reproduce. Research on search strategies has focused largely on independent individuals [1-3], but many organisms display collective behaviors, including during group search and foraging [4-6]. One classical experimental search task, informing studies of navigation, memory, and learning, is the location of a reward in a confined, complex maze setting [7, 8]. Cathepsin B inhibitor Rats (Rattus norvegicus) have been paradigmatic in psychological and biological studies [9, 10], but despite rats being highly social [11, 12], their group search behavior has not been investigated. Here, we explore the decision making of rats searching individually, or in groups, for a reward in a complex maze environment. Using automated video tracking, we find that rats exhibit-even when alone-a partially systematic search, leading to a continuous increase in their chance of finding the reward because of increased attraction to unexplored regions. When searching together, however, synergistic group advantages arise through integration of individual exploratory and social behavior. The superior search performances result from a strategy that represents a hierarchy of influential preferences in response to social and asocial cues. Furthermore, we present a computational model to compare the essential factors that influence how collective search operates and to validate that the collective search strategy increases the search efficiency of individuals in groups. This strategy can serve as direct inspiration for designing computational search algorithms and systems, such as autonomous robot groups, to explore areas inaccessible to humans. VIDEO ABSTRACT.The origin of animals is one of the most intensely studied evolutionary events, and our understanding of this transition was greatly advanced by analyses of unicellular relatives of animals, which have shown many "animal-specific" genes actually arose in protistan ancestors long before the emergence of animals [1-3]. These genes have complex distributions, and the protists have diverse lifestyles, so understanding their evolutionary significance requires both a robust phylogeny of animal relatives and a detailed understanding of their biology [4, 5]. But discoveries of new animal-related lineages are rare and historically biased to bacteriovores and parasites. Here, we characterize the morphology and transcriptome content of a new animal-related lineage, predatory flagellate Tunicaraptor unikontum. Tunicaraptor is an extremely small (3-5 μm) and morphologically simple cell superficially resembling some fungal zoospores, but it survives by preying on other eukaryotes, possibly using a dedicated but transient "mouth," which is unique for unicellular opisthokonts. The Tunicaraptor transcriptome encodes a full complement of flagellar genes and the flagella-associated calcium channel, which is only common to predatory animal relatives and missing in microbial parasites and grazers. Tunicaraptor also encodes several major classes of animal cell adhesion molecules, as well as transcription factors and homologs of proteins involved in neurodevelopment that have not been found in other animal-related lineages. Phylogenomics, including Tunicaraptor, challenges the existing framework used to reconstruct the evolution of animal-specific genes and emphasizes that the diversity of animal-related lineages may be better understood only once the smaller, more inconspicuous animal-related lineages are better studied. VIDEO ABSTRACT.Locomotion requires energy, yet animals need to increase locomotion in order to find and consume food in energy-deprived states. While such energy homeostatic coordination suggests brain origin, whether the central melanocortin 4 receptor (Mc4r) system directly modulates locomotion through motor circuits is unknown. Here, we report that hypothalamic Pomc neurons in zebrafish and mice have long-range projections into spinal cord regions harboring Mc4r-expressing V2a interneurons, crucial components of the premotor networks. Furthermore, in zebrafish, Mc4r activation decreases the excitability of spinal V2a neurons as well as swimming and foraging, while systemic or V2a neuron-specific blockage of Mc4r promotes locomotion. In contrast, in mice, electrophysiological recordings revealed that two-thirds of V2a neurons in lamina X are excited by the Mc4r agonist α-MSH, and acute inhibition of Mc4r signaling reduces locomotor activity. In addition, we found other Mc4r neurons in spinal lamina X that are inhibited by α-MSH, which is in line with previous studies in rodents where Mc4r agonists reduced locomotor activity.