ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis.

Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens to drive expression of the normally silent E26 transformation-specific (ETS) transcription factor ERG in prostate cells. Recent genomic landscape studies of such cancers have reported recurrent point mutations and focal deletions of another ETS member, the ETS2 repressor factor ERF. Here we show these ERF mutations cause decreased protein stability and mostly occur in tumours without ERG upregulation.

Lipid-polymer hybrid nanoparticle-mediated therapeutics delivery: advances and challenges.

With rapid advances in nanomedicine, lipid-polymer hybrid nanoparticles (LPHNPs) have emerged as promising nanocarriers for several biomedical applications, including therapeutics delivery and biomedical imaging. Significant research has been dedicated to biomimetic or targeting functionalization, as well as controlled and image-guided drug-release capabilities. Despite this research, the clinical translation of LPHNP-mediated therapeutics delivery has progressed incrementally.

Co-catalytic Effects of CoS on the Activity of the MoS Catalyst for Electrochemical Hydrogen Evolution.

MoS is a promising material to replace the Pt catalyst in the electrochemical hydrogen evolution reaction (HER). It is well known that the activity of the MoS catalyst in the HER is significantly promoted by doping cobalt atoms. Recently, the Co-Mo-S phase, in which cobalt atoms decorate the edge positions of the MoS slabs, has been identified as a co-catalytic phase in the Co-doped MoS (Co-MoS) with low Co content.

Analysis of healthy and tumour DNA methylation distributions in kidney-renal-clear-cell-carcinoma using Kullback-Leibler and Jensen-Shannon distance measures.

DNA methylation is an epigenetic phenomenon in which methyl groups get bonded to the cytosines of the DNA molecule altering the expression of the associated genes. Cancer is linked with hypo or hyper-methylation of specific genes as well as global changes in DNA methylation. In this study, the authors study the probability density function distribution of DNA methylation in various significant genes and across the genome in healthy and tumour samples.

Ultrasound as a Screening Tool for Central Venous Catheter Positioning and Exclusion of Pneumothorax.

Objectives: Although real-time ultrasound guidance during central venous catheter insertion has become a standard of care, postinsertion chest radiograph remains the gold standard to confirm central venous catheter tip position and rule out associated lung complications like pneumothorax. We hypothesize that a combination of transthoracic echocardiography and lung ultrasound is noninferior to chest radiograph when used to accurately assess central venous catheter positioning and screen for pneumothorax.

Setting: All operating rooms and surgical and trauma ICUs at the institution.

CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer.

CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine.

The p53 protein induces stable miRNAs that have the potential to modify subsequent p53 responses.

The p53 tumour suppressor is a transcription factor that can increase the expression of mRNAs and microRNAs (miRNAs). HT29-tsp53 cells expressing a temperature sensitive variant of p53 have provided a useful model to rapidly and reversibly control p53 activity. In this model, the majority of p53-responsive mRNAs were upregulated rapidly but they were short-lived leading to rapid decay of the p53 response at the restrictive temperature.

Efficient sortase-mediated N-terminal labeling of TEV protease cleaved recombinant proteins.

A major challenge in attaching fluorophores or other handles to proteins is the availability of a site-specific labeling strategy that provides stoichiometric modification without compromising protein integrity. We developed a simple approach that combines TEV protease cleavage, sortase modification and affinity purification to N-terminally label proteins. To achieve stoichiometrically-labeled protein, we included a short affinity tag in the fluorophore-containing peptide for post-labeling purification of the modified protein.

Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease.

Four-Dimensional Ultrafast Electron Microscopy: Insights into an Emerging Technique.

Four-dimensional ultrafast electron microscopy (4D-UEM) is a novel analytical technique that aims to fulfill the long-held dream of researchers to investigate materials at extremely short spatial and temporal resolutions by integrating the excellent spatial resolution of electron microscopes with the temporal resolution of ultrafast femtosecond laser-based spectroscopy. The ingenious use of pulsed photoelectrons to probe surfaces and volumes of materials enables time-resolved snapshots of the dynamics to be captured in a way hitherto impossible by other conventional techniques. The flexibility of 4D-UEM lies in the fact that it can be used in both the scanning (S-UEM) and transmission (UEM) modes depending upon the type of electron microscope involved.

Healing of Early Stage Fatigue Damage in Ionomer/Fe₃O₄ Nanoparticle Composites.

This work reports on the healing of early stage fatigue damage in ionomer/nano-particulate composites. A series of poly(ethylene--methacrylic acid) zinc ionomer/Fe₃O₄ nanoparticle composites with varying amounts of ionic clusters were developed and subjected to different levels of fatigue loading. The initiated damage was healed upon localized inductive heating of the embedded nanoparticles by exposure of the particulate composite to an alternating magnetic field.

Effect of the Dianhydride/Branched Diamine Ratio on the Architecture and Room Temperature Healing Behavior of Polyetherimides.

Traditional polyetherimides (PEIs) are commonly synthesized from an aromatic diamine and an aromatic dianhydride (e.g., 3,4'-oxidianiline (ODA) and 4,4'-oxidiphtalic anhydride (ODPA)) leading to the imide linkage and outstanding chemical, thermal and mechanical properties yet lacking any self-healing functionality.

Biophysical Evidence for Intrinsic Disorder in the C-terminal Tails of the Epidermal Growth Factor Receptor (EGFR) and HER3 Receptor Tyrosine Kinases.

The epidermal growth factor receptor (EGFR)/ErbB family of receptor tyrosine kinases includes oncogenes important in the progression of breast and other cancers, and they are targets for many drug development strategies. Each member of the ErbB family possesses a unique, structurally uncharacterized C-terminal tail that plays an important role in autophosphorylation and signal propagation. To determine whether these C-terminal tails are intrinsically disordered regions, we conducted a battery of biophysical experiments on the EGFR and HER3 tails.

Analysis of distribution of DNA methylation in kidney-renal-clear-cell-carcinoma specific genes using entropy.

DNA Methylation is an epigenetic phenomenon in which methyl groups are added to the cytosines, thereby altering the physio-chemical properties of the DNA region and influencing gene expression. Aberrant DNA methylation in a set of genes or across the genome results in many epigenetic diseases including cancer. In this paper, we use entropy to analyze the extent and distribution of DNA methylation in Tumor Suppressor Genes (TSG's) and Oncogenes related to a specific type of cancer (viz.

Lipid-based surface engineering of PLGA nanoparticles for drug and gene delivery applications.

The use of poly(lactic-co-glycolic acid) (PLGA)-based nanocarriers presents several major challenges, including their synthetic hydrophobic surface, low transfection efficiency, short circulation half-life, and nonspecific tissue distribution. Numerous engineering strategies have been employed to overcome these problems, with lipid-based surface functionalization of PLGA nanoparticles (NPs) showing promising results in the development of PLGA-based clinical nanomedicines. Surface engineering with different lipids enhances the target specificity of the carrier and improves its physicochemical properties as well as NP-cell associations, such as cellular membrane permeability, immune responses, and long circulation half-life in vivo.

[Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer.

Purpose: The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [Zr]trastuzumab in patients with HER2-positive breast cancer.

Procedures: Twelve women with HER2-positive breast cancer underwent [Zr]trastuzumab positron emission tomography (PET)/X-ray computed tomography (CT) twice within 7 days post-injection. Biodistribution data from whole-torso PET/CT images and organ time-activity curves were created using data from all patients.

Unsupervised detection of cancer driver mutations with parsimony-guided learning.

Methods are needed to reliably prioritize biologically active driver mutations over inactive passengers in high-throughput sequencing cancer data sets. We present ParsSNP, an unsupervised functional impact predictor that is guided by parsimony. ParsSNP uses an expectation-maximization framework to find mutations that explain tumor incidence broadly, without using predefined training labels that can introduce biases.

Insights into the anti-angiogenic properties of phosphaplatins.

Phosphaplatins are platinum-based antitumor compounds that, unlike other clinically utilized platinum drugs (i.e. cisplatin, carboplatin, and oxaliplatin), appear to target proteins rather than DNA.

Biofunctionalized nanoparticles: an emerging drug delivery platform for various disease treatments.

Biological barriers, such as phagocytosis and nonspecific distribution, are major factors limiting the clinical translation of nanomedicine. Biomimetic and bioengineering strategies have been used to overcome these challenges. In particular, natural cell membrane-based biofunctionalized nanoparticles (CMFNPs) have gained widespread attention owing to their cell surface mimetic characteristics and tailored nanomaterial features.

Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti-HER2 targeted therapies.

Background: Activating, nonamplification ERBB2 mutations (ERBB2mut) are not detected by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but are detected by DNA sequencing and may predict clinical responses to human epidermal growth factor receptor (HER2)-targeted therapy. The authors queried 5605 advanced/metastatic breast cancers (mBC) to uncover the frequency of ERBB2mut genomic alterations. Clinical responses to anti-HER2 therapeutics were identified.

Nanowires: Enhanced Optoelectronic Performance of a Passivated Nanowire-Based Device: Key Information from Real-Space Imaging Using 4D Electron Microscopy (Small 17/2016).

Selective mapping of surface charge carrier dynamics of InGaN nanowires before and after surface passivation with octadecylthiol (ODT) is reported by O. F. Mohammed and co-workers on page 2313, using scanning ultrafast electron microscopy.

Real-Space Visualization of Energy Loss and Carrier Diffusion in a Semiconductor Nanowire Array Using 4D Electron Microscopy.

A breakthrough in the development of 4D scanning ultrafast electron microscopy is described for real-time and space imaging of secondary electron energy loss and carrier diffusion on the surface of an array of nanowires as a model system, providing access to a territory that is beyond the reach of either static electron imaging or any time-resolved laser spectroscopy.