Schofieldwaddell5359

We also show that cell swelling induces programmed cell death within 3 h in a MSL10-dependent manner. Finally, we show that MSL10 is unable to potentiate cell swelling-induced death when phosphomimetic residues are introduced into its soluble N terminus. Thus, MSL10 functions as a phospho-regulated membrane-based sensor that connects the perception of cell swelling to a downstream signaling cascade and programmed cell death.Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte.Understanding the adaptive function of conspicuous coloration has been a major focus of evolutionary biology for much of the last century. Although considerable progress has been made in explaining how conspicuous coloration can be used in functions as diverse as sexual and social signaling, startling predators, and advertising toxicity [1], there remain a multitude of species that display conspicuous coloration that cannot be explained by existing theory. Here we detail a new "matador-like" divertive antipredator strategy based on conspicuous coloration in Trinidadian guppies (Poecilia reticulata). Guppies encountering predatory fish rapidly enhance the conspicuousness of their eyes by blackening their irises. By pitting biomimetic robotic guppies against real predatory fish, we show this conspicuous eye coloration diverts attacks away from the guppies' center of mass to their head. To determine the function of this seemingly counterintuitive behavior, we developed a method for simulating escape probabilities when live prey interact with ballistic attacking predators, and find this diversion effect significantly benefits black-eyed guppies because they evade capture by rapidly pivoting away from the predator once it has committed to its attack. Remarkably, this antipredator strategy reverses the commonly observed negative scaling relationship between prey size and evasive ability, with larger fish benefiting most from diverting predators. Taken together, our results introduce a new antipredator divertive strategy that may be widely used by conspicuously colored prey that rely on agility to escape their predators.Most bacterial species encompass strains with vastly different gene content. Strain diversity in microbial communities is therefore considered to be of functional importance. Yet little is known about the extent to which related microbial communities differ in diversity at this level and which underlying mechanisms may constrain and maintain strain-level diversity. Here, we used shotgun metagenomics to characterize and compare the gut microbiota of two honey bee species, Apis mellifera and Apis cerana, which diverged about 6 mya. Although the host species are colonized largely by the same bacterial 16S rRNA phylotypes, we find that their communities are host specific when analyzed with genomic resolution. Moreover, despite their similar ecology, A. mellifera displayed a much higher diversity of strains and functional gene content in the microbiota compared to A. cerana, both per colony and per individual bee. In particular, the gene repertoire for polysaccharide degradation was massively expanded in the microbiota of A. mellifera relative to A. cerana. Bee management practices, divergent ecological adaptation, or habitat size may have contributed to the observed differences in microbiota genomic diversity of these key pollinator species. Our results illustrate that the gut microbiota of closely related animal hosts can differ vastly in genomic diversity while displaying similar levels of diversity based on the 16S rRNA gene. Such differences are likely to have consequences for gut microbiota functioning and host-symbiont interactions, highlighting the need for metagenomic studies to understand the ecology and evolution of microbial communities.The regulation of proliferation is a primary function of Hedgehog (Hh) signaling in development. Hh signal transduction requires the primary cilium for several steps in the pathway [1-5]. Many cells only build a primary cilium upon cell cycle exit, in G0. In those proliferating cells that do make a cilium, it is a transient organelle, being assembled in G1 and disassembled sometime prior to mitosis [6-9]. Thus, the requirement for primary cilia presents a conundrum how are proliferative signals conveyed through an organelle that is present for only part of the cell cycle? Here, we investigate this question in a mouse medulloblastoma cell line, SMB55, that requires cilium-mediated Hh pathway activity for proliferation [10]. We show that SMB55 cells, and the primary cerebellar granule neuron precursors (GNPs) from which they derive, are often ciliated beyond G1 into S phase, and the presence of the cilium in SMB55 cells determines the periods of Hh pathway activity. Using live imaging over multiple cell cycles, we demonstrate that Hh pathway activity in either G1-S of the previous cell cycle or G1 of the cell cycle in which the decision is made is sufficient for cell cycle entry. We also show that cyclin D1 contributes to the persistent effects of pathway activity over multiple cell cycles. Together, our results reveal that, even though the signaling organelle itself is transient, Hh pathway control of proliferation is remarkably robust. check details Further, primary cilium transience may have implications for other Hh-mediated events in development.Dynamic integration of internal and external cues is essential for flexible, adaptive behavior. In C. elegans, biological sex and feeding state regulate expression of the food-associated chemoreceptor odr-10, contributing to plasticity in food detection and the decision between feeding and exploration. In adult hermaphrodites, odr-10 expression is high, but in well-fed adult males, odr-10 expression is low, promoting exploratory mate-searching behavior. Food-deprivation transiently activates male odr-10 expression, heightening food sensitivity and reducing food leaving. Here, we identify a neuroendocrine feedback loop that sex-specifically regulates odr-10 in response to food deprivation. In well-fed males, insulin-like (insulin/IGF-1 signaling [IIS]) and transforming growth factor β (TGF-β) signaling repress odr-10 expression. Upon food deprivation, odr-10 is directly activated by DAF-16/FoxO, the canonical C. elegans IIS effector. The TGF-β ligand DAF-7 likely acts upstream of IIS and links feeding to odr-10 only in males, due in part to the male-specific expression of daf-7 in ASJ. Surprisingly, these responses to food deprivation are not triggered by internal metabolic cues but rather by the loss of sensory signals associated with food. When males are starved in the presence of inedible food, they become nutritionally stressed, but odr-10 expression remains low and exploratory behavior is suppressed less than in starved control males. Food signals are detected by a small number of sensory neurons whose activity non-autonomously regulates daf-7 expression, IIS, and odr-10. Thus, adult C. elegans males employ a neuroendocrine feedback loop that integrates food detection and genetic sex to dynamically modulate chemoreceptor expression and influence the feeding-versus-exploration decision.The widespread reciprocal connectivity between the claustrum and the neocortex has stimulated numerous hypotheses regarding its function; all of these suggest that the claustrum acts as a hub that connects multiple cortical regions via dense reciprocal synaptic pathways. Although the connectivity between the anterior cingulate cortex (ACC) and the claustrum has been proposed as an important pathway for top-down cognitive control, little is known about the synaptic inputs that drive claustrum cells projecting to the ACC. Here, we used multi-neuron patch clamp recordings, retrograde and anterograde viral labeling, and optogenetics in mouse claustrum to investigate cortical inputs and outputs of ACC-projecting claustrum (CLA-ACC) neurons. Both ipsilateral and contralateral cortical regions were found to provide synaptic input to CLA-ACC neurons. These cortical regions were predominantly frontal and limbic regions and not primary sensorimotor regions. We show that CLA-ACC neurons receive monosynaptic input from the insular cortex, thereby revealing a potential claustrum substrate mediating the Salience Network. In contrast, sensorimotor cortical regions preferentially targeted non CLA-ACC claustrum neurons. Using dual retrograde labeling of claustrum projection neurons, we show selectivity also in the cortical targets of CLA-ACC neurons whereas CLA-ACC neurons co-projected mainly to other frontal regions, claustrum neurons projecting to primary sensorimotor cortices selectively targeted other sensorimotor regions. Our results show that both cortical inputs to and projections from CLA-ACC neurons are highly selective, suggesting an organization of cortico-claustral connectivity into functional modules that could be specialized for processing different types of information.To behave adaptively with sufficient flexibility, biological organisms must cognize beyond immediate reaction to a physically present stimulus. For this, humans use visual mental imagery [1, 2], the ability to conjure up a vivid internal experience from memory that stands in for the percept of the stimulus. Visually imagined contents subjectively mimic perceived contents, suggesting that imagery and perception share common neural mechanisms. Using multivariate pattern analysis on human electroencephalography (EEG) data, we compared the oscillatory time courses of mental imagery and perception of objects. We found that representations shared between imagery and perception emerged specifically in the alpha frequency band. These representations were present in posterior, but not anterior, electrodes, suggesting an origin in parieto-occipital cortex. Comparison of the shared representations to computational models using representational similarity analysis revealed a relationship to later layers of deep neural networks trained on object representations, but not auditory or semantic models, suggesting representations of complex visual features as the basis of commonality.