A DNA-structured mathematical model of cell-cycle progression in cyclic hypoxia.

New experimental data have shown how the periodic exposure of cells to low oxygen levels (i.e., cyclic hypoxia) impacts their progress through the cell-cycle.

Replication catastrophe induced by cyclic hypoxia leads to increased APOBEC3B activity.

Tumor heterogeneity includes variable and fluctuating oxygen concentrations, which result in the accumulation of hypoxic regions in most solid tumors. Tumor hypoxia leads to increased therapy resistance and has been linked to genomic instability. Here, we tested the hypothesis that exposure to levels of hypoxia that cause replication stress could increase APOBEC activity and the accumulation of APOBEC-mediated mutations.

Cyclic Hypoxia: An Update on Its Characteristics, Methods to Measure It and Biological Implications in Cancer.

Regions of hypoxia occur in most if not all solid cancers. Although the presence of tumor hypoxia is a common occurrence, the levels of hypoxia and proportion of the tumor that are hypoxic vary significantly. Importantly, even within tumors, oxygen levels fluctuate due to changes in red blood cell flux, vascular remodeling and thermoregulation.

Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells.

The androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and metastasis. Thus, blocking AR activity and its downstream signaling constitutes a major strategy for PCa treatment. Here, we report on the potent anti-PCa activity of a small-molecule imidazoacridinone, C-1311.

A polarization-induced 2D hole gas in undoped gallium nitride quantum wells.

A high-conductivity two-dimensional (2D) hole gas, analogous to the ubiquitous 2D electron gas, is desirable in nitride semiconductors for wide-bandgap p-channel transistors. We report the observation of a polarization-induced high-density 2D hole gas in epitaxially grown gallium nitride on aluminium nitride and show that such hole gases can form without acceptor dopants. The measured high 2D hole gas densities of about 5 × 10 per square centimeters remain unchanged down to cryogenic temperatures and allow some of the lowest p-type sheet resistances among all wide-bandgap semiconductors.

A global Staphylococcus aureus proteome resource applied to the in vivo characterization of host-pathogen interactions.

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S.

Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry.

Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale.

An integrated transcriptomics-guided genome-wide promoter analysis and next-generation proteomics approach to mine factor(s) regulating cellular differentiation.

Differential next-generation-omics approaches aid in the visualization of biological processes and pave the way for divulging important events and/or interactions leading to a functional output at cellular or systems level. To this end, we undertook an integrated Nextgen transcriptomics and proteomics approach to divulge differential gene expression of infant and pubertal rat Sertoli cells (Sc).Unlike, pubertal Sc, infant Sc are immature and fail to support spermatogenesis.

Opening a SWATH Window on Posttranslational Modifications: Automated Pursuit of Modified Peptides.

Posttranslational modifications of proteins play an important role in biology. For example, phosphorylation is a key component in signal transduction in all three domains of life, and histones can be modified in such a variety of ways that a histone code for gene regulation has been proposed. Shotgun proteomics is commonly used to identify posttranslational modifications as well as chemical modifications from sample processing.

Automated Validation of Results and Removal of Fragment Ion Interferences in Targeted Analysis of Data-independent Acquisition Mass Spectrometry (MS) using SWATHProphet.

Proteomics by mass spectrometry technology is widely used for identifying and quantifying peptides and proteins. The breadth and sensitivity of peptide detection have been advanced by the advent of data-independent acquisition mass spectrometry. Analysis of such data, however, is challenging due to the complexity of fragment ion spectra that have contributions from multiple co-eluting precursor ions.

Coherence and decay of higher energy levels of a superconducting transmon qubit.

We present measurements of coherence and successive decay dynamics of higher energy levels of a superconducting transmon qubit. By applying consecutive π pulses for each sequential transition frequency, we excite the qubit from the ground state up to its fourth excited level and characterize the decay and coherence of each state. We find the decay to proceed mainly sequentially, with relaxation times in excess of 20  μs for all transitions.

Synthesis of maculalactone A and derivatives for environmental fate tracking studies.

Maculalactone A (1) constitutes a promising antifouling agent, inhibiting the formation of biofilms in marine and freshwater systems. In this study, we developed a new route, based on a late-stage formation of the butenolide core, leading to the total synthesis of maculalactone A (three steps, overall yield of 45%) and delivering material on a gram scale. In addition, analogues of the title compound were assayed concerning their biological activity, utilizing Artemia franciscana and Thamnocephalus platyurus.

The effect of ligands on FePt-Fe3O4 core-shell magnetic nanoparticles.

FePt-Fe3O4 core-shell nanoparticles functionalized with 3,4-dihydroxyphenylacetic acid (DOPAC) and dimercaptosuccinic acid (DMSA) ligands were synthesized and characterized. We found that the DOPAC ligand enhances the magnetic properties of the FePt-Fe3O4 particles, in comparison with the DMSA ligand, which induces the oxidation of the shell layer that causes a significant reduction of the saturation magnetization. The synthesized magnetic nanoparticles were evaluated for applications in magnetic hyperthermia and magnetic resonance imaging contrast enhancement.

A repository of assays to quantify 10,000 human proteins by SWATH-MS.

Mass spectrometry is the method of choice for deep and reliable exploration of the (human) proteome. Targeted mass spectrometry reliably detects and quantifies pre-determined sets of proteins in a complex biological matrix and is used in studies that rely on the quantitatively accurate and reproducible measurement of proteins across multiple samples. It requires the one-time, a priori generation of a specific measurement assay for each targeted protein.

Nano-structured magnetic metamaterial with enhanced nonlinear properties.

Nano-structuring can significantly modify the properties of materials. We demonstrate that size-dependent modification of the spin-wave spectra in magnetic nano-particles can affect not only linear, but also nonlinear magnetic response. The discretization of the spectrum removes the frequency degeneracy between the main excitation mode of a nano-particle and the higher spin-wave modes, having the lowest magnetic damping, and reduces the strength of multi-magnon relaxation processes.

Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium.

Protein post-translational modifications (PTMs) represent important regulatory states that when combined have been hypothesized to act as molecular codes and to generate a functional diversity beyond genome and transcriptome. We systematically investigate the interplay of protein phosphorylation with other post-transcriptional regulatory mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae. Systematic perturbations by deletion of its only two protein kinases and its unique protein phosphatase identified not only the protein-specific effect on the phosphorylation network, but also a modulation of proteome abundance and lysine acetylation patterns, mostly in the absence of transcriptional changes.

Proteome organization in a genome-reduced bacterium.

The genome of Mycoplasma pneumoniae is among the smallest found in self-replicating organisms. To study the basic principles of bacterial proteome organization, we used tandem affinity purification-mass spectrometry (TAP-MS) in a proteome-wide screen. The analysis revealed 62 homomultimeric and 116 heteromultimeric soluble protein complexes, of which the majority are novel.

Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction.

Nanomagnetic materials offer exciting avenues for probing cell mechanics and activating mechanosensitive ion channels, as well as for advancing cancer therapies. Most experimental works so far have used superparamagnetic materials. This report describes a first approach based on interfacing cells with lithographically defined microdiscs that possess a spin-vortex ground state.

Interaction networks for systems biology.

Cellular functions are almost always the result of the coordinated action of several proteins, interacting in protein complexes, pathways or networks. Progress made in devising suitable tools for analysis of protein-protein interactions, have recently made it possible to chart interaction networks on a large-scale. The aim of this review is to provide a short overview of the most promising contributions of interaction networks to human biology, structural biology and human genetics.

Electronic reconstruction at SrMnO3-LaMnO3 superlattice interfaces.

We use resonant soft-x-ray scattering (RSXS) to study the electronic reconstruction at the interface between the Mott insulator LaMnO3 and the band insulator SrMnO3. Superlattices of these two insulators were shown previously to have both ferromagnetism and metallic tendencies [Koida, Phys. Rev.

Ligand effect on the growth and the digestion of Co nanocrystals.

The reaction product of cobalt carbonyl decomposition depends on the concentration of the oleic acid ligand. With a low concentration of ligand, nanocrystals nucleate and grow to large ferromagnetic particles through the process of Ostwald ripening and coalescence coarsening. With a high concentration of ligand, stable cluster complexes are formed.