Analysis of low resolution mass spectra

Computer program determines gas constituents from measurements of mass/peak-height spectrum from residual gas analyzer. Applications of program include residual gas analysis for work in space environmental simulators, space environment contamination, and air pollution monitoring

Coordination of Substrate Binding and ATP Hydrolysis in Vps4-Mediated ESCRT-III Disassembly

Vps4 disassembly of ESCRT-III plays an important role in MVB sorting, viral budding, and cytokinesis. An in vitro system was developed to investigate this process. These studies revealed new insights into the mechanisms of Vps4 function

Mean field theory for global binding systematics

We review some possible improvements of mean field theory for application to nuclear binding systematics. Up to now, microscopic theory has been less successful than models starting from the liquid drop in describing accurately the global binding systematics. We believe that there are good prospects to develop a better global theory, using modern forms of energy density functionals and treating correlation energies systematically by the RPA.Comment: RevTex, 17 pages, 5 eps figures. To be published in Yadernaya Fizika, special edition for the 90th birthday of Professor A.B. Migda

Breast Cancer Exosome-like Microvesicles and Salivary Gland Cells Interplay Alters Salivary Gland Cell-Derived Exosome-like Microvesicles In Vitro

Saliva is a useful biofluid for the early detection of disease, but how distal tumors communicate with the oral cavity and create disease-specific salivary biomarkers remains unclear. Using an in vitro breast cancer model, we demonstrated that breast cancer-derived exosome-like microvesicles are capable of interacting with salivary gland cells, altering the composition of their secreted exosome-like microvesicles. We found that the salivary gland cells secreted exosome-like microvesicles encapsulating both protein and mRNA. We also showed that the interaction with breast cancer-derived exosome-like microvesicles communicated and activated the transcriptional machinery of the salivary gland cells. Thus, the interaction altered the composition of the salivary gland cell-derived exosome-like microvesicles on both the transcriptomically and proteomically

Let's agree to disagree on operative versus nonoperative (LADON) treatment for proximal humerus fractures: study protocol for an international multicenter prospective cohort study

BackgroundThe proximal humerus fracture is a common injury, but the optimal management is much debated. The decision for operative or nonoperative treatment is strongly influenced by patient specific factors, regional and cultural differences and the preference of the patient and treating surgeon. The aim of this study is to compare operative and nonoperative treatment of proximal humerus fractures for those patients for whom there is disagreement about optimal management.Methods and analysisThis protocol describes an international multicenter prospective cohort study, in which all patients of 18 years and older presenting within three weeks after injury with a radiographically diagnosed displaced proximal humerus fracture can be included. Based on patient characteristics and radiographic images several clinical experts advise on the preferred treatment option. In case of disagreement among the experts, the patient can be included in the study. The actual treatment that will be delivered is at the discretion of the treating physician. The primary outcome is the QuickDash score at 12 months. Propensity score matching will be used to control for potential confounding of the relation between treatment modality and QuickDash scores.DiscussionThe LADON study is an international multicenter prospective cohort study with a relatively new methodological study design. This study is a "natural experiment" meaning patients receive standard local treatment and surgeons perform standard local procedures, therefore high participation rates of patients and surgeons are expected. Patients are only included after expert panel evaluation, when there is proven disagreement between experts, which makes this a unique study design. Through this inclusion process, we create two comparable groups whom received different treatments and where expert disagree about the already initiated treatment. Since we are zooming in on this particular patient group, confounding will be largely mitigated. Internationally the treatment of proximal humerus fractures are still much debated and differs much per country and hospital. This observational study with a natural experiment design will create insight into which treatment modality is to be preferred for patients in whom there is disagreement about the optimal treatment strategy.Clinical epidemiolog

Characterization of Yeast Extracellular Vesicles: Evidence for the Participation of Different Pathways of Cellular Traffic in Vesicle Biogenesis

Background: Extracellular vesicles in yeast cells are involved in the molecular traffic across the cell wall. In yeast pathogens, these vesicles have been implicated in the transport of proteins, lipids, polysaccharide and pigments to the extracellular space. Cellular pathways required for the biogenesis of yeast extracellular vesicles are largely unknown. Methodology/Principal Findings: We characterized extracellular vesicle production in wild type (WT) and mutant strains of the model yeast Saccharomyces cerevisiae using transmission electron microscopy in combination with light scattering analysis, lipid extraction and proteomics. WT cells and mutants with defective expression of Sec4p, a secretory vesicleassociated Rab GTPase essential for Golgi-derived exocytosis, or Snf7p, which is involved in multivesicular body (MVB) formation, were analyzed in parallel. Bilayered vesicles with diameters at the 100–300 nm range were found in extracellular fractions from yeast cultures. Proteomic analysis of vesicular fractions from the cells aforementioned and additional mutants with defects in conventional secretion pathways (sec1-1, fusion of Golgi-derived exocytic vesicles with the plasm

The Nucleocapsid Region of HIV-1 Gag Cooperates with the PTAP and LYPXnL Late Domains to Recruit the Cellular Machinery Necessary for Viral Budding

HIV-1 release is mediated through two motifs in the p6 region of Gag, PTAP and LYPXnL, which recruit cellular proteins Tsg101 and Alix, respectively. The Nucleocapsid region of Gag (NC), which binds the Bro1 domain of Alix, also plays an important role in HIV-1 release, but the underlying mechanism remains unclear. Here we show that the first 202 residues of the Bro1 domain (Broi) are sufficient to bind Gag. Broi interferes with HIV-1 release in an NC–dependent manner and arrests viral budding at the plasma membrane. Similar interrupted budding structures are seen following over-expression of a fragment containing Bro1 with the adjacent V domain (Bro1-V). Although only Bro1-V contains binding determinants for CHMP4, both Broi and Bro1-V inhibited release via both the PTAP/Tsg101 and the LYPXnL/Alix pathways, suggesting that they interfere with a key step in HIV-1 release. Remarkably, we found that over-expression of Bro1 rescued the release of HIV-1 lacking both L domains. This rescue required the N-terminal region of the NC domain in Gag and the CHMP4 binding site in Bro1. Interestingly, release defects due to mutations in NC that prevented Bro1 mediated rescue of virus egress were rescued by providing a link to the ESCRT machinery via Nedd4.2s over-expression. Our data support a model in which NC cooperates with PTAP in the recruitment of cellular proteins necessary for its L domain activity and binds the Bro1–CHMP4 complex required for LYPXnL–mediated budding

The Sodium/Proton Exchanger NHE8 Regulates Late Endosomal Morphology and Function

The pH and lumenal environment of intracellular organelles is considered essential for protein sorting and trafficking through the cell. We provide the first evidence that a mammalian sodium (potassium)/proton exchanger, NHE8, plays a key role in the control of protein trafficking and endosome morphology

Genome-scale modeling of the protein secretory machinery in yeast

The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lacking. Here, we present the first genome-scale model for the yeast secretory machinery which captures the knowledge generated through more than 50 years of research. The model is based on the concept of a Protein Specific Information Matrix (PSIM: characterized by seven PTMs features). An algorithm was developed which mimics secretory machinery and assigns each secretory protein to a particular secretory class that determines the set of PTMs and transport steps specific to each protein. Protein abundances were integrated with the model in order to gain system level estimation of the metabolic demands associated with the processing of each specific protein as well as a quantitative estimation of the activity of each component of the secretory machinery