PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors.

Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS.

Recoil Corrections to the Energy Levels of Hydrogenic Atoms.

We have completed the calculation of pure-recoil corrections of order (Zα)^{6} to Coulombic bound states of two spin-1/2 fermions without approximation in the particle masses. Our result applies to systems of arbitrary mass ratio such as muonium and positronium, as well as hydrogen and muonic hydrogen (with the neglect of proton structure effects). We have shown how the two-loop master integrals that occur in the relativistic region can be computed in analytic form and suggest that the same method can be applied to the three-loop integrals that would be present in a calculation of order (Zα)^{7} corrections.

Gut Microbiome Composition and Metabolic Capacity Differ by Secretor Status in Exclusively Breastfed Infants.

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (“secretors”), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme.

Identifying Interaction Partners of Yeast Protein Disulfide Isomerases Using a Small Thiol-Reactive Cross-Linker: Implications for Secretory Pathway Proteostasis.

Protein disulfide isomerases (PDIs) function in forming the correct disulfide bonds in client proteins, thereby aiding the folding of proteins that enter the secretory pathway. Recently, several PDIs have been identified as targets of organic electrophiles, yet the client proteins of specific PDIs remain largely undefined. Here, we report that PDIs expressed in are targets of divinyl sulfone (DVSF) and other thiol-reactive protein cross-linkers.

Calibration-free analysis of surface proteins on single extracellular vesicles enabled by DNA nanostructure.

Extracellular vesicles (EVs) are essential intercellular communicators that are of increasing interest as diagnostic biomarkers. Exploring their biological functions and clinical values, however, remains challenging due to their small sizes and high heterogeneity. Herein, we report an ultrasensitive method that employs target-initiated construction of DNA nanostructure to detect single EVs with an input as low as 100 vesicles/μL.

Mercury delays cerebellar development in a model songbird species, the zebra finch.

Mercury exposure can disrupt development of the cerebellum, part of the brain essential for coordination of movement through a complex environment, including flight. In precocial birds, such as fowl, the cerebellum develops embryonically, and the chick is capable of leaving the nest within hours of hatching. However, most birds, including all songbirds, are altricial, and spend weeks in the nest between hatching and fledging.

Asymmetrical Flow Field Flow Fractionation Coupled to Nanoparticle Tracking Analysis for Rapid Online Characterization of Nanomaterials.

Increasing applications of nanomaterials in consumer goods, industrial products, medical practices, etc., calls for the development of tools for rapid separation, quantification, and sizing of nanoparticles to ensure their safe and sustainable employment. While many techniques are available for characterization of pure, homogeneous nanomaterial preparations, particle sizing and counting remains difficult for heterogeneous mixtures that resulted from imperfect synthesis conditions, aggregation from product instability, or degradation during storage.

Physical and chemical template-blocking strategies in the exponential amplification reaction of circulating microRNAs.

The detection of circulating miRNA through isothermal amplification wields many attractive advantages over traditional methods, such as reverse transcription RT-qPCR. However, it is challenging to control the background signal produced in the absence of target, which severely hampers applications of such methods for detecting low abundance targets in complex biological samples. In the present work, we employed both the cobalt oxyhydroxide (CoOOH) nanoflakes and the chemical modification of hexanediol to block non-specific template elongation in exponential amplification reaction (EXPAR).

Learning Semisupervised Multilabel Fully Convolutional Network for Hierarchical Object Parsing.

This article presents a semisupervised multilabel fully convolutional network (FCN) for hierarchical object parsing of images. We consider each object part (e.g.

Rapid Enrichment and Detection of Extracellular Vesicles Enabled by CuS-Enclosed Microgels.

Extracellular vesicles (EVs) are cell-derived membranous vesicles that exist in nearly all biological fluids, including blood and urine; and carry a great number of cargo molecules such as protein, nucleic acids, and lipid. They may play important roles in cell-cell communication and modulation of pathological processes, which, however, are not yet well understood, calling for highly sensitive, specific, and rapid methods for EV detection and quantification in biological samples. Here, we report the CuS-enclosed microgels that not only help enrich EVs carrying specific protein markers from complex biomatrices, but also produce strong chemiluminescence (CL) to realize sensitive detection of the target EVs.

A DNA aptamer for binding and inhibition of DNA methyltransferase 1.

DNA methyltransferases (DNMTs) are enzymes responsible for establishing and maintaining DNA methylation in cells. DNMT inhibition is actively pursued in cancer treatment, dominantly through the formation of irreversible covalent complexes between small molecular compounds and DNMTs that suffers from low efficacy and high cytotoxicity, as well as no selectivity towards different DNMTs. Herein, we discover aptamers against the maintenance DNA methyltransferase, DNMT1, by coupling Asymmetrical Flow Field-Flow Fractionation (AF4) with Systematic Evolution of Ligands by EXponential enrichment (SELEX).

A Single Extracellular Vesicle (EV) Flow Cytometry Approach to Reveal EV Heterogeneity.

Extracellular vesicles (EVs) actively participate in intercellular communication and pathological processes. Studying the molecular signatures of EVs is key to reveal their biological functions and clinical values, which, however, is greatly hindered by their sub-100 nm dimensions, the low quantities of biomolecules each EV carries, and the large population heterogeneity. Now, single-EV flow cytometry analysis is introduced to realize single EV counting and phenotyping in a conventional flow cytometer for the first time, enabled by target-initiated engineering (TIE) of DNA nanostructures on each EV.

Highly Efficient Exosome Isolation and Protein Analysis by an Integrated Nanomaterial-Based Platform.

Exosomes play important roles in mediating intercellular communication and regulating a variety of biological processes, but clear understanding of their functions and biogenesis has not been achieved, due to the high technical difficulties involved in analysis of small vesicular structures that contain a high proportion of membrane structures. Herein, we designed a novel approach to integrate two nanomaterials carrying varied surface properties, the hydrophilic, macroporous graphene foam (GF) and the amphiphilic periodic mesoporous organosilica (PMO), for efficient exosome isolation from human serum and effective protein profiling. The high specific surface area of GF, after modification with the antibody against the exosomal protein marker, CD63, allowed highly specific isolation of exosomes from complex biological samples with high recovery.

Enhancement of the Intrinsic Peroxidase-Like Activity of Graphitic Carbon Nitride Nanosheets by ssDNAs and Its Application for Detection of Exosomes.

The present work investigates the capability of single-stranded DNA (ssDNA) in enhancing the intrinsic peroxidase-like activity of the g-CN nanosheets (NSs). We found that ssDNA adsorbed on g-CN NSs could improve the catalytic activity of the nanosheets. The maximum reaction rate of the HO-mediated TMB oxidation catalyzed by the ssDNA-NSs hybrid was at least 4 times faster than that obtained with unmodified NSs.

Rapid Enrichment and Sensitive Detection of Multiple Metal Ions Enabled by Macroporous Graphene Foam.

Nanomaterials have shown great promise in advancing biomedical and environmental analysis because of the unique properties originated from their ultrafine dimensions. In general, nanomaterials are separately applied to either enhance detection by producing strong signals upon target recognition or to specifically extract analytes taking advantage of their high specific surface area. Herein, we report a dual-functional nanomaterial-based platform that can simultaneously enrich and enable sensitive detection of multiple metal ions.

Photochemical Bionanoreactor for Efficient Visible-Light-Driven in Vitro Drug Metabolism.

In light of the significance of cytochrome P450 (CYP) catalyzed drug metabolism for drug development and toxicity screening, it is very important to imitate natural metabolic pathways accurately and efficiently in vitro. Herein, a novel and simple photochemical bionanoreactor has been constructed for efficient visible-light-driven in vitro drug metabolism based on eosin-Y-functionalized macroporous ordered silica foams (MOSF-EY). Because of the unique transfer of photoinduced electrons from photosensitizers to CYP heme domain, CYP catalyzed drug metabolism can be in vitro driven by the MOSF-EY nanoreactor under the irradiation of visible light.

Three-Photon-Annihilation Contributions to Positronium Energies at Order mα^{7}.

Positronium spectroscopy (n=1 hyperfine splitting, n=2 fine structure, and the 2S-1S interval) has reached a precision of order 1 MHz. Vigorous ongoing efforts to improve the experimental results motivate the calculation of the positronium energy levels at order mα^{7}. In this Letter, we present the result for a complete class of such contributions-those involving virtual annihilation of positronium to three photons in an intermediate state.

Potential role of cardiac chloride channels and transporters as novel therapeutic targets.

The heart and blood vessels express a range of anion currents (e.g. ICl.

Unidentified intralesional and intracellular coccoid microorganism discovered in the young man with a diffuse erosive gastroduodenitis and multiple superficial ulcerations.

A Helicobacter pylori-negative young Japanese man with dyspeptic symptoms suffered from a diffuse erosive gastroduodenitis and multiple superficial ulcerations. Histology and electron microscopic examinations on the biopsy specimens revealed the presence of multiple unidentified intralesional and intracellular coccoid microorganisms in the pathological gastroduodenal mucosa. Microaerophilic and anaerobic Gram-negative coccoid and filamentobacillary bacteria were cultured from the gastric aspirate.

Communicating with the coroner: how religion, culture, and family concerns may influence autopsy decision making.

Based on coronial data gathered in the state of Queensland in 2004, this article reviews how a change in legislation may have impacted autopsy decision making by coroners. More specifically, the authors evaluated whether the requirement that coronial autopsy orders specify the level of invasiveness of an autopsy to be performed by a pathologist was affected by the further requirement that coroners take into consideration a known religion, culture, and/or raised family concern before making such an order. Preliminary data reveal that the cultural status of the deceased did not affect coronial autopsy decision making.

Increasing the information available to coroners: the effect on autopsy decision-making.

This paper details research completed in 2007 which investigated autopsy decision-making in a death investigation. The data was gathered during the first year of operation in Queensland, Australia, of a new Coroners Act which changed the process of death investigation in three ways which are important to this paper. First, it required a greater amount of information to be gathered at the scene by police: this included a thorough investigation of the circumstances of the death, including statements from witnesses, friends and family, as well as evidence gathering at the scene.

The renaissance of Peiresc: Aubin-Louis Millin and the postrevolutionary republic of letters.

This essay argues for the emergence of a cultural and epistemological divide between amateur savants and members of the Royal Academy of the Sciences in late Old Regime and revolutionary France and suggests that the amateur ideal rose in significance even as intellectual activity came to be increasingly centralized in the postrevolutionary era. At the crux of the tensions between the amateur ideal and the professionalizing reality in the immediate postrevolutionary period stood Aubin-Louis Millin and his journal, the Magasin Encyclopédique. The essay examines, in particular, the revival in the pages of the Magasin Encyclopédique of interest in Nicolas-Claude Fabri de Peiresc, the seventeenth-century icon of an amateur ideal in which investigations in the natural sciences and scholarship were private, decentralized, often provincial activities.

The coronial system in Queensland: the effects of new legislation on decision-making.

The purpose of this article is to detail research completed in 2007 which investigated the way in which coroners made decisions in a death investigation, with a particular focus on their autopsy decision-making. The data were gathered during the first year of operation of a new Coroners Act in Queensland, Australia, which required a greater amount of information to be gathered at the scene by police, and this included a thorough investigation of the circumstances of the death, including statements from witnesses, friends and family, as well as evidence-gathering at the scene. This article addresses the outcomes of that increased information on coronial decision-making in three ways: first, whether or not the greater amount of information offered to coroners enabled them to be less reliant on full internal autopsies to establish cause of death; secondly whether certain factors were more influential in decision-making; and thirdly, whether the information gathered at the scene negates the need for full internal autopsies in many situations, irrespective of the decision-making by coroners.

Effects of crude aqueous medicinal plant extracts on growth and invasion of breast cancer cells.

Plants used in folklore medicine continue to be an important source of discovery and development of novel therapeutic agents. In the present study, we determined the effects of crude aqueous extracts of a panel of medicinal plants on the growth and invasion of cancer cells. Our results showed that extracts of L.