Inefficient physiological transitions are known to cause metabolic disorders. Therefore, investigating mechanisms that constitute molecular switches in a central metabolic organ like the liver becomes crucial. Specifically, upstream mechanisms that control temporal engagement of transcription factors, which are essential to mediate physiological fed–fast–refed transitions are less understood. SIRT1, a NAD+-dependent deacetylase, is pivotal in regulating hepatic gene expression and has emerged as a key therapeutic target. Despite this, if/how nutrient inputs regulate SIRT1 interactions, stability, and therefore downstream functions are still unknown. Here, we establish nutrient-dependent O-GlcNAcylation of SIRT1, within its N-terminal domain, as a crucial determinant of hepatic functions. Our findings demonstrate that during a fasted-to-refed transition, glycosylation of SIRT1 modulates its interactions with various transcription factors and a nodal cytosolic kinase involved in insulin signaling. Moreover, sustained glycosylation in the fed state causes nuclear exclusion and cytosolic ubiquitin-mediated degradation of SIRT1. This mechanism exerts spatiotemporal control over SIRT1 functions by constituting a previously unknown molecular relay. Of note, loss of SIRT1 glycosylation discomposed these interactions resulting in aberrant gene expression, mitochondrial dysfunctions, and enhanced hepatic gluconeogenesis. Expression of nonglycosylatable SIRT1 in the liver abrogated metabolic flexibility, resulting in systemic insulin resistance, hyperglycemia, and hepatic inflammation, highlighting the physiological costs associated with its overactivation. Conversely, our study also reveals that hyperglycosylation of SIRT1 is associated with aging and high-fat–induced obesity. Thus, we establish that nutrient-dependent glycosylation of SIRT1 is essential to gate its functions and maintain physiological fitness.

The standard state-dependent Heisenberg-Robertson uncertainly-relation lower bound fails to capture the quintessential incompatibility of observables as the bound can be zero for some states. To remedy this problem, we establish a class of tight (i.e., inequalities are saturated) variance-based sum-uncertainty relations derived from the Lie algebraic properties of observables and show that our lower bounds depend only on the irreducible representation assumed carried by the Hilbert space of state of the system. We illustrate our result for the cases of the Weyl-Heisenberg algebra, special unitary algebras up to rank 4, and any semisimple compact algebra. We also prove the usefulness of our results by extending a known variance-based entanglement detection criterion.For ∆w 2 signifying the variance of measurement outcomes for the observable w, Heisenberg's uncertainty relation for position x and momentum p iswhere [x, p] = i1, and 1 is the identity operator. Eq. (1) fortuitously has a constant lower bound due to the appealing algebraic properties of the commutator of x and p. Robertson's generalization to ∆A 2 ∆B 2 ≥ | [A, B] | 2 /4 for arbitrary observables A and B more generally has a state-dependent lower bound [1], and so fails to capture the intrinsic incompatibility of noncommuting observables [2,3]. This cannot be amended as the underlying product of uncertainties is null whenever one of the uncertainties is null, an observation that provided impetus for the emergence of uncertainty relations [4-9] that eschew variance in favor of entropy. Properly assessing uncertainty is important for foundational quantum mechanics [10][11][12] and for quantum information and communication [13][14][15][16]; variance is closer than entropy for practical quantum mechanics, a driving motivation behind research into sum-uncertainty relations (SURs), which deliver state-independent lower bounds [17][18][19][20][21][22][23][24][25]. Here we discuss SURs by showing connections with the algebras of observables, with examples of the Weyl-Heisenberg wh, special unitary su(n) and su(1, 1) and generally semi-simple compact algebras thereby extending the range to applications of SURs in areas such as [26,27] and quantum information [28] where u(n) or su(n) symmetries are prevalent.Indeed, single-photon multi-path quantum optical interferometry provides a convenient way to realize SU (n) symmetry [29][30][31][32] with the experimental signature obtained via sampling photodetection of the photon emerging from each of the n output ports, both by direct detection and by adding special post-processing interferometers at the output followed by photodetection. Photodetection sampling statistics obtained in these ways yield uncertainties from estimates second-order cumulants for the distributions and, through this process, our uncer-(a) (b) FIG. 1: Sum of variances is a measure of total uncertainty. Given a (green) box with the uncertainties as edges, the sum of variances is the squared length of the (red) diagonal. [Here 30000 (blue) points ...

Understanding kinetic control of biological processes is as important as identifying components that constitute pathways. Insulin signaling is central for almost all metazoans, and its perturbations are associated with various developmental disorders, metabolic diseases, and aging. While temporal phosphorylation changes and kinetic constants have provided some insights, constant or variable parameters that establish and maintain signal topology are poorly understood. Here, we report kinetic parameters that encode insulin concentration and nutrient-dependent flow of information using iterative experimental and mathematical simulation-based approaches. Our results illustrate how dynamics of distinct phosphorylation events collectively contribute to selective kinetic gating of signals and maximum connectivity of the signaling cascade under normo-insulinemic but not hyper-insulinemic states. In addition to identifying parameters that provide predictive value for maintaining the balance between metabolic and growth-factor arms, we posit a kinetic basis for the emergence of insulin resistance. Given that pulsatile insulin secretion during a fasted state precedes a fed response, our findings reveal rewiring of insulin signaling akin to memory and anticipation, which was hitherto unknown. Striking disparate temporal behavior of key phosphorylation events that destroy the topology under hyper-insulinemic states underscores the importance of unraveling regulatory components that act as bandwidth filters. In conclusion, besides providing fundamental insights, our study will help in identifying therapeutic strategies that conserve coupling between metabolic and growth-factor arms, which is lost in diseases and conditions of hyper-insulinemia.

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It is shown that polarized light can be polarization squeezed only if it exhibits sub-Poissonian statistics with the Mandel's Q factor less than -1/2.In classical optics, Stokes parameters are used to denote the polarization state [1,2]. For light beam travelling along the 3-direction, the Stokes parameters S 0,1,2,3 are defined by and lead to the uncertainty relations,