A diverse proteome is present and enzymatically active in metabolite extracts.

Metabolite extraction is the critical first-step in metabolomics experiments, where it is generally regarded to inactivate and remove proteins. Here, arising from efforts to improve extraction conditions for polar metabolomics, we discover a proteomic landscape of over 1000 proteins within metabolite extracts. This is a ubiquitous feature across several common extraction and sample types.

deficiency modulates the stromal environment in the pretumorigenic rat mammary gland.

Background: Neurofibromin, coded by the tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1)-a tumor predisposition syndrome caused by a germline mutation-have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by which mutations lead to breast cancer tumorigenesis is not well understood.

Oocyte mitochondria link maternal environment to offspring phenotype.

During maturation oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies, frogs, and humans. This oocyte mitochondrial remodeling, which includes substantial changes in electron transport chain (ETC) subunit abundance, is regulated by maternal insulin signaling. Why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be an evolutionarily conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS).

p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs.

Malignant peripheral nerve sheath tumors (MPNSTs) are chemotherapy resistant sarcomas that are a leading cause of death in neurofibromatosis type 1 (NF1). Although NF1-related MPNSTs derive from neural crest cell origin, they also exhibit intratumoral heterogeneity. TP53 mutations are associated with significantly decreased survival in MPNSTs, however the mechanisms underlying TP53-mediated therapy responses are unclear in the context of NF1-deficiency.

Quasicontinuous Exhaust Scenario for a Fusion Reactor: The Renaissance of Small Edge Localized Modes.

Tokamak operational regimes with small edge localized modes (ELMs) could be a solution to the problem of large transient heat loads in fusion reactors. A ballooning mode near the last closed flux surface governed by the pressure gradient and the magnetic shear there has been proposed for small ELMs. In this Letter, we experimentally investigate several stabilizing effects near the last closed flux surface and present linear ideal simulations that indeed develop ballooninglike fluctuations there and connect them with nonlinear resistive simulations.

Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.

Autophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to Parkinson's disease by increasing α-synuclein levels, that in turn may promote aggregation of this protein. Here, we used two different genetic models-one heterozygous for a mutated form of the GBA protein (D409V), and the other heterozygous for an ATP13a2 loss-of-function mutation, to test whether these mutations exacerbate the spread of α-synuclein pathology following injection of α-synuclein preformed fibrils in the olfactory bulb of 12-week-old mice.

Excess dietary carbohydrate affects mitochondrial integrity as observed in brown adipose tissue.

Hyperglycemia affects over 400 million individuals worldwide. The detrimental health effects are well studied at the tissue level, but the in vivo effects at the organelle level are poorly understood. To establish such an in vivo model, we used mice lacking TXNIP, a negative regulator of glucose uptake.

Hexosylceramides and Glycerophosphatidylcholine GPC(36:1) Increase in Multi-Organ Dysfunction Syndrome Patients with Pediatric Intensive Care Unit Admission over 8-Day Hospitalization.

Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting the criteria for MODS were screened, consented ( = 24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO).

Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted "Shotgun" Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period, a Single-Center Observational Study.

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) ( = 24) are analyzed at three time-points and cross-referenced to sedation controls ( = 4) for a total of = 28.

Impact of Preanalytical Factors on the Measurement of Tumor Tissue Biomarkers Using Immunohistochemistry.

Analysis of formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemistry (IHC) is commonplace in clinical and research laboratories. However, reports suggest that IHC results can be compromised by biospecimen preanalytical factors. The National Cancer Institute's Biospecimen Preanalytical Variables Program conducted a systematic study to examine the potential effects of delay to fixation (DTF) and time in fixative (TIF) on IHC using 24 cancer biomarkers.

Chemical and Structural Changes in Corn Stover After Ensiling: Influence on Bioconversion.

Production of biofuels, bioproducts, and bioenergy requires a well-characterized, stable, and reasonably uniform biomass supply and well-established supply chains for shipping biomass from farm fields to biorefineries, while achieving year-round production targets. Preserving and stabilizing biomass feedstock during storage is a necessity for cost-effective and sustainable biofuel production. Ensiling is a common storage method used to preserve and even improve forage quality; however, the impact of ensiling on biomass physical and chemical properties that influence bioconversion processes has been variable.

Deficits in olfactory sensitivity in a mouse model of Parkinson's disease revealed by plethysmography of odor-evoked sniffing.

Hyposmia is evident in over 90% of Parkinson's disease (PD) patients. A characteristic of PD is intraneuronal deposits composed in part of α-synuclein fibrils. Based on the analysis of post-mortem PD patients, Braak and colleagues suggested that early in the disease α-synuclein pathology is present in the dorsal motor nucleus of the vagus, as well as the olfactory bulb and anterior olfactory nucleus, and then later affects other interconnected brain regions.

Adapting social conditioned place preference for use in young children.

Objective: Social-emotional processing is key to daily interactions and routines, yet a challenging construct to quantify. Measuring social and emotional processing in young children, children with language impairments, or non-verbal children, presents additional challenges. This study addresses a pressing need for tools to probe internal responses such as feelings, drives, and motivations that do not rely on intact language skills.

Kinome Profiling of NF1-Related MPNSTs in Response to Kinase Inhibition and Doxorubicin Reveals Therapeutic Vulnerabilities.

Neurofibromatosis Type 1 (NF1)-related Malignant Peripheral Nerve Sheath Tumors (MPNST) are highly resistant sarcomas that account for significant mortality. The mechanisms of therapy resistance are not well-understood in MPNSTs, particularly with respect to kinase inhibition strategies. In this study, we aimed to quantify the impact of both the genomic context and targeted therapy on MPNST resistance using reverse phase phosphoproteome array (RPPA) analysis.

Putative human myometrial and fibroid stem-like cells have mesenchymal stem cell and endometrial stromal cell properties.

Study Question: Can endometrial stromal stem/progenitor cell markers, SUSD2 and CD146/CD140b, enrich for human myometrial and fibroid stem/progenitor cells?

Summary Answer: SUSD2 enriches for myometrial and fibroid cells that have mesenchymal stem cell (MSC) characteristics and can also be induced to decidualise.

What Is Known Already: Mesenchymal stem-like cells have been separately characterised in the endometrial stroma and myometrium and may contribute to diseases in their respective tissues.

Study Design, Size, Duration: Normal myometrium, fibroids and endometrium were collected from hysterectomies with informed consent.

Assaying Sorghum for Fuel Production.

The publicly available NREL suite of laboratory analytical procedures (LAPs) provides researchers with the analytical tools to determine the composition of woody and herbaceous feedstocks. Feedstock characterization includes several steps: sample preparation, starch determination, moisture analysis, ashing, extraction, and hydrolysis. These steps provide information on specific compounds and classes of compounds such as ash, protein, moisture, extractives, sucrose, starch, glucan, xylan, galactan, arabinan, acetate and lignin.

Unified field studies of the algae testbed public-private partnership as the benchmark for algae agronomics.

National scale agronomic projections are an important input for assessing potential benefits of algae cultivation on the future of innovative agriculture. The Algae Testbed Public-Private Partnership was established with the goal of investigating open pond algae cultivation across different geographic, climatic, seasonal, and operational conditions while setting the benchmark for quality data collection, analysis, and dissemination. Identical algae cultivation systems and data analysis methodologies were established at testbed sites across the continental United States and Hawaii.

Helium line ratio spectroscopy for high spatiotemporal resolution plasma edge profile measurements at ASDEX Upgrade (invited).

The thermal helium beam edge diagnostic has recently been upgraded at the ASDEX Upgrade (AUG) tokamak experiment. Line ratio spectroscopy on neutral helium is a valuable tool for simultaneous determination of the electron temperature and density of plasmas. The diagnostic now offers a temporal resolution of 900 kHz with a spatial resolution of up to 3 mm at 32 lines of sight (LOS) simultaneously.

Label-Retaining, Putative Mesenchymal Stem Cells Contribute to Murine Myometrial Repair During Uterine Involution.

Uterine remodeling during pregnancy is a fundamental, dynamic process required for successful propagation of eutherian species. The uterus can increase in size up to 40-fold during pregnancy, which is largely attributed to expansion of the myometrium by hyperplasia and hypertrophy. After pregnancy, the uterus repairs the remodeled or "damaged" tissue during uterine involution (INV).

Presence of multiple Clostridium difficile strains at primary infection is associated with development of recurrent disease.

Recurrence of Clostridium difficile infection (CDI) places a major burden on the healthcare system. Previous studies have suggested that specific C. difficile strains, or ribotypes, are associated with severe disease and/or recurrence.

The buffering capacity of stems: genetic architecture of nonstructural carbohydrates in cultivated Asian rice, Oryza sativa.

Harnessing stem carbohydrate dynamics in grasses offers an opportunity to help meet future demands for plant-based food, fiber and fuel production, but requires a greater understanding of the genetic controls that govern the synthesis, interconversion and transport of such energy reserves. We map out a blueprint of the genetic architecture of rice (Oryza sativa) stem nonstructural carbohydrates (NSC) at two critical developmental time-points using a subpopulation-specific genome-wide association approach on two diverse germplasm panels followed by quantitative trait loci (QTL) mapping in a biparental population. Overall, 26 QTL are identified; three are detected in multiple panels and are associated with starch-at-maturity, sucrose-at-maturity and NSC-at-heading.

Fast piezoelectric valve offering controlled gas injection in magnetically confined fusion plasmas for diagnostic and fuelling purposes.

In magnetically confined fusion plasmas controlled gas injection is crucial for plasma fuelling as well as for various diagnostic applications such as active spectroscopy. We present a new, versatile system for the injection of collimated thermal gas beams into a vacuum chamber. This system consists of a gas pressure chamber, sealed by a custom made piezo valve towards a small capillary for gas injection.