Agilent Technologies

About: Agilent Technologies is a company organization based out in Santa Clara, California, United States. It is known for research contribution in the topics: Signal & Mass spectrometry. The organization has 7398 authors who have published 11518 publications receiving 262410 citations. The organization is also known as: Agilent Technologies, Inc..

An inhibitor of oxidative phosphorylation exploits cancer vulnerability.

Abstract: Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors.

Error Vector Magnitude as a Performance Measure for Advanced Modulation Formats

Abstract: We examine the relation between optical signal-to-noise ratio (OSNR), error vector magnitude (EVM), and bit-error ratio (BER). Theoretical results and numerical simulations are compared to measured values of OSNR, EVM, and BER. We conclude that the EVM is an appropriate metric for optical channels limited by additive white Gaussian noise. Results are supported by experiments with six modulation formats at symbol rates of 20 and 25 GBd generated by a software-defined transmitter.

Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming

Abstract: Current DNA methylation assays are limited in the flexibility and efficiency of characterizing a large number of genomic targets. We report a method to specifically capture an arbitrary subset of genomic targets for single-molecule bisulfite sequencing for digital quantification of DNA methylation at single-nucleotide resolution. A set of ~30,000 padlock probes was designed to assess methylation of ~66,000 CpG sites within 2,020 CpG islands on human chromosome 12, chromosome 20, and 34 selected regions. To investigate epigenetic differences associated with dedifferentiation, we compared methylation in three human fibroblast lines and eight human pluripotent stem cell lines. Chromosome-wide methylation patterns were similar among all lines studied, but cytosine methylation was slightly more prevalent in the pluripotent cells than in the fibroblasts. Induced pluripotent stem (iPS) cells appeared to display more methylation than embryonic stem cells. We found 288 regions methylated differently in fibroblasts and pluripotent cells. This targeted approach should be particularly useful for analyzing DNA methylation in large genomes.

Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry.

Abstract: Electron transfer dissociation (ETD) is a recently introduced mass spectrometric technique that provides a more comprehensive coverage of peptide sequences and posttranslational modifications. Here, we evaluated the use of ETD for a global phosphoproteome analysis. In all, we identified a total of 1,435 phosphorylation sites from human embryonic kidney 293T cells, of which 1,141 (≈80%) were not previously described. A detailed comparison of ETD and collision-induced dissociation (CID) modes showed that ETD identified 60% more phosphopeptides than CID, with an average of 40% more fragment ions that facilitated localization of phosphorylation sites. Although our data indicate that ETD is superior to CID for phosphorylation analysis, the two methods can be effectively combined in alternating ETD and CID modes for a more comprehensive analysis. Combining ETD and CID, from this single study, we were able to identify 80% of the known phosphorylation sites in >1,000 phosphorylated peptides analyzed. A hierarchical clustering of the identified phosphorylation sites allowed us to discover 15 phosphorylation motifs that have not been reported previously. Overall, ETD is an excellent method for localization of phosphorylation sites and should be an integral component of any strategy for comprehensive phosphorylation analysis.

Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing

Abstract: Although genetic information is stored in DNA, and faithfully copied into RNA, the cell can make the odd (and occasionally vitally important) change to the meaning of code during a process known as RNA editing. Thirteen edited genes are known in the nonrepetitive portion of the human genome, but the overall prevalence of RNA editing is unclear. Li et al. (p. [1210][1]), used an unbiased genome-wide approach to identify 239 sites (in 207 target genes), with stringent criteria for editing. The sites identified included 10 of the 13 known edited genes. Fourteen out of 18 randomly chosen sites were validated by sequencing, and these putatively edited genes were enriched for synapse, cell trafficking, and membrane functions. Furthermore, lowering the search stringency suggested that many more human genes may be edited at lower frequencies. [1]: /lookup/doi/10.1126/science.1170995