Limits to timescale dependence in erosion rates: Quantifying glacial and fluvial erosion across timescales.

Earth's topography and climate result from the competition between uplift and erosion, but it has been debated whether rivers or glaciers are more effective erosional agents. We present a global compilation of fluvial and glacial erosion rates alongside simple numerical experiments, which show that the "Sadler effect," wherein geological rates show an inverse relationship with measurement timescale, comprises three distinct effects: a measurement thickness bias, a bias of erosion and redeposition, and a bias introduced by not observing quiescent intervals. Furthermore, we find that, globally, average glacial erosion rates exceed fluvial erosion rates through time by an order of magnitude, and that this difference cannot be explained by Sadlerian biases or by variations in hillslope, precipitation, or latitude.

DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras.

Ligand-induced protein degradation has emerged as a compelling approach to promote the targeted elimination of proteins from cells by directing these proteins to the ubiquitin-proteasome machinery. So far, only a limited number of E3 ligases have been found to support ligand-induced protein degradation, reflecting a dearth of E3-binding compounds for proteolysis-targeting chimera (PROTAC) design. Here, we describe a functional screening strategy performed with a focused library of candidate electrophilic PROTACs to discover bifunctional compounds that degrade proteins in human cells by covalently engaging E3 ligases.

Erratum: Author Correction: High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity.

[This corrects the article DOI: 10.1038/s42003-019-0587-z.].

High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity.

Expression of human asparagine synthetase (ASNS) promotes metastatic progression and tumor cell invasiveness in colorectal and breast cancer, presumably by altering cellular levels of L-asparagine. Human ASNS is therefore emerging as a drug target for cancer therapy. Here we show that a slow-onset, tight binding inhibitor, which exhibits nanomolar affinity for human ASNS in vitro, exhibits excellent selectivity at 10 μM concentration in HCT-116 cell lysates with almost no off-target binding.

Acute effect of a supplemented milk drink on bone metabolism in healthy postmenopausal women is influenced by the metabolic syndrome.

Background: Dietary factors acutely influence the rate of bone resorption, as demonstrated by changes in serum bone resorption markers. Dietary calcium exerts its effect by reducing parathyroid hormone levels while other components induce gut incretin hormones both of which reduce bone resorption markers. The impact of dietary calcium on bone turnover when energy metabolism is modulated such as in metabolic syndrome has not been explored.