•Dynamic structural proteomic screens detect functional changes at high resolution•Detect enzyme activity, phosphorylation, and molecular interactions in situ•Generate new hypotheses increase proteomics coverage•Enabled discovery of a regulatory mechanism glucose uptake E. coli Biological processes are regulated by intermolecular chemical modifications that do not affect protein levels, thus es...

•Clonal multi-omics assesses daughters from one founder cell for different features•SIS-seq identifies the genes that control clonal fate•SIS-skew how perturbation affects fate•Bcor is identified as a novel regulator of dendritic subset development Despite advances in single-cell multi-omics, single stem or progenitor can only be tested once. We developed which clone act surrogates founder, the...

•IFNγ and attachment-independent growth promote IDO1 expression in PDAC cells•Metabolism of tryptophan by contributes one-carbons to the THF cycle•Tryptophan can substitute for serine as a one-carbon source•Serine glycine restriction enhances anti-tumor activity an inhibitor Cancer cells adapt their metabolism support elevated energetic anabolic demands proliferation. Folate-dependent is critic...

•Mitochondrial protein TARS2 interacts with lysosomal amino-acid-sensing machinery•Threonine modulates localization and activity of mTORC1 through TARS2•TARS2 binds inactive RagC elevates GTP loading RagA in response to threonine•TARS2 is required for threonine-dependent regulation the signaling pathway Mechanistic target rapamycin complex 1 (mTORC1) controls cell growth proliferation by sensin...

There is great therapeutic interest in manipulating (either enhancing or suppressing) G protein-coupled receptor (GPCR) signal transduction. However, most current strategies are limited to pharmacological activation or blockade of receptors. Human gene therapy, including both overexpression and antisense approaches, may allow manipulation of GPCR signaling at steps distal to receptors. To fully...

s | 35 administered at baseline, weeks 1, 2, 4, and week 8.The dose of desvenlafaxine was fixed (50mg/day) until week 4, after which it was flexible up to 100mg/day, based on response and tolerability. Results: Montgomery Asberg Depression Scale scores significantly decreased from baseline (M=23.61, SD=5.51) to end of treatment (M=12.29, SD=8.41), p<.0001. Severity of illness, as measured by th...

•The brain harbors distinct parenchymal and perivascular macrophages.•Binary split Cre transgenesis allows differential imaging translatome retrieval.•Cx3cr1ccre: Sall1ncre mice specifically target microglia.•Cx3cr1ccre: Lyve1ncre a subset of macrophages. The developmental molecular heterogeneity tissue macrophages is unravelling, as are their diverse contributions to physiology pathophysiology...

•Embryonic hypothalamic microglia are heterogeneous•A subpopulation of embryonic reside adjacent to NSCs•Maternal cold stress impacts signaling nearby NSCs in males•Exposure gestational leads disrupted social behaviors adulthood The interplay between neurons and as they integrate stressors regulate homeostasis is growing interest. We asked if the hypothalamus were likewise responsive and, so, w...

47 48 Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong 49 projections from somatosensory cortex. However the sensory representations encoded by 50 striatal projection neurons are not well understood. Here we characterized the 51 contribution of DLS to the encoding of vibrotactile information in rats by assessing 52 striatal responses to precise frequency stimu...

44 Current therapies for sarcomas are often inadequate. This study sought to 45 identify actionable gene targets by selective targeting of the molecular networks 46 that support sarcoma cell proliferation. Silencing of asparagine synthetase 47 (ASNS), an amidotransferase that converts aspartate into asparagine, produced 48 the strongest inhibitory effect on sarcoma growth in a functional genomi...