Stevenson Stentoft (heliumwoman2)

The Arg/N-degron pathway targets proteins for degradation by recognizing their N-terminal or internal degrons. Our previous work produced double-knockout (2-KO) HEK293T human cell lines that lacked the functionally overlapping UBR1 and UBR2 E3 ubiquitin ligases of the Arg/N-degron pathway. Here, we studied these cells in conjunction with RNA-sequencing, mass spectrometry (MS), and split-ubiquitin binding assays. 1) Some mRNAs, such as those encoding lactate transporter MCT2 and β-adrenergic receptor ADRB2, are strongly (∼20-fold) up-regulated in 2-KO cells, whereas other mRNAs, including those encoding MAGEA6 (a regulator of ubiquitin ligases) and LCP1 (an actin-binding protein), are completely repressed in 2-KO cells, in contrast to wild-type cells. 2) Glucocorticoid receptor (GR), an immunity-modulating transcription factor (TF), is up-regulated in 2-KO cells and also physically binds to UBR1, strongly suggesting that GR is a physiological substrate of the Arg/N-degron pathway. 3) PREP1, another TF, was also found to bind to UBR1. 4) MS-based analyses identified ∼160 proteins whose levels were increased or decreased by more than 2-fold in 2-KO cells. For example, the homeodomain TF DACH1 and the neurofilament subunits NF-L (NFEL) and NF-M (NFEM) were expressed in wild-type cells but were virtually absent in 2-KO cells. 5) The disappearance of some proteins in 2-KO cells took place despite up-regulation of their mRNAs, strongly suggesting that the Arg/N-degron pathway can also modulate translation of specific mRNAs. In sum, this multifunctional proteolytic system has emerged as a regulator of mammalian gene expression, in part through conditional targeting of TFs that include ATF3, GR, and PREP1.Neuronal population responses to sensory stimuli are remarkably flexible. The responses of neurons in visual cortex have heterogeneous dependence on stimulus properties (e.g., contrast), processes that affect all stages of visual processing (e.g., adaptation), and cognitive processes (e.g., attention or task switching). Understanding whether these processes affect similar neuronal populations and whether they have similar effects on entire populations can provide insight into whether they utilize analogous mechanisms. In particular, it has recently been demonstrated that attention has low rank effects on the covariability of populations of visual neurons, which impacts perception and strongly constrains mechanistic models. We hypothesized that measuring changes in population covariability associated with other sensory and cognitive processes could clarify whether they utilize similar mechanisms or computations. Our experimental design included measurements in multiple visual areas using four distinct sensory and cognitive processes. We found that contrast, adaptation, attention, and task switching affect the variability of responses of populations of neurons in primate visual cortex in a similarly low rank way. These results suggest that a given circuit may use similar mechanisms to perform many forms of modulation and likely reflects a general principle that applies to a wide range of brain areas and sensory, cognitive, and motor processes.Animals that move through complex habitats must frequently contend with obstacles in their path. AMG900 Humans and other highly cognitive vertebrates avoid collisions by perceiving the relationship between the layout of their surroundings and the properties of their own body profile and action capacity. It is unknown whether insects, which have much smaller brains, possess such abilities. We used bumblebees, which vary widely in body size and regularly forage in dense vegetation, to investigate whether flying insects consider their own size when interacting with their surroundings. Bumblebees trained to fly in a tunnel were sporadically presented with an obstructing wall containing a gap that varied in width. Bees successfully flew through narrow gaps, even those that were much smaller than the