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Macrophage activation on "phagocytic synapse" arrays: Spacing of nanoclustered ligands directs TLR1/2 signaling with an intrinsic limit

The activation of Toll-like receptor heterodimer 1/2 (TLR1/2) by microbial components plays a critical role in host immune responses against pathogens. TLR1/2 signaling is sensitive to the chemical structure of ligands, but its dependence on the spatial distribution of ligands on microbial surfaces remains unexplored. Here, we reveal the quantitative...

Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders

Gut microbiome disturbances have been implicated in major depressive disorder (MDD). However, little is known about how the gut virome, microbiome, and fecal metabolome change, and how they interact in MDD. Here, using whole-genome shotgun metagenomic and untargeted metabolomic methods, we identified 3 bacteriophages, 47 bacterial species, and 50 fecal...

Rapid evolution of coordinated and collective movement in response to artificial selection

Collective motion occurs when individuals use social interaction rules to respond to the movements and positions of their neighbors. How readily these social decisions are shaped by selection remains unknown. Through artificial selection on fish (guppies, Poecilia reticulata) for increased group polarization, we demonstrate rapid evolution in how individuals...

A novel cardiomyogenic role for Isl1+ neural crest cells in the inflow tract

The degree to which populations of cardiac progenitors (CPCs) persist in the postnatal heart remains a controversial issue in cardiobiology. To address this question, we conducted a spatiotemporally resolved analysis of CPC deployment dynamics, tracking cells expressing the pan-CPC gene Isl1. Most CPCs undergo programmed silencing during early cardiogenesis...

BRAF inhibition protects against hearing loss in mice

Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a...

Context-specific control over the neural dynamics of temporal attention by the human cerebellum

Physiological methods have identified a number of signatures of temporal prediction, a core component of attention. While the underlying neural dynamics have been linked to activity within cortico-striatal networks, recent work has shown that the behavioral benefits of temporal prediction rely on the cerebellum. Here, we examine the involvement of the...

Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression

MicroRNAs (miRNAs) have been implicated in oxidative metabolism and brown/beige adipocyte identity. Here, we tested whether widespread changes in miRNA expression promoted by treatment with the small-molecule enoxacin cause browning and prevent obesity. Enoxacin mitigated diet-induced obesity in mice, and this was associated with increased energy expenditure....

Groundwater production from geothermal heating on early Mars and implication for early martian habitability

In explaining extensive evidence for past liquid water, the debate on whether Mars was primarily warm and wet or cold and arid 4 billion years (Ga) ago has continued for decades. The Sun’s luminosity was ~30% lower 4 Ga ago; thus, most martian climate models struggle to elevate the mean surface temperature past the melting point of water. Basal melting...

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all...

Potassium isotopic heterogeneity in subducting oceanic plates

Oceanic crust and sediments are the primary K sinks for seawater, and they deliver considerable amounts of K to the mantle via subduction. Historically, these crustal components were not studied for K isotopes because of the lack of analytical precision to differentiate terrestrial variations. Here, we report a high-precision dataset that reveals substantial...

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