PP7 virus-like particle as a functional peptide carrying platform

Virus-like particles (VLPs) have attracted attention as therapeutic platforms for the delivery of peptide-based motifs for immunology, cell targeting, and drug delivery. The functional peptide sequences of interest are covalently attached to the VLP surface by either genetic fusion or bioconjugation techniques. Here, we report our initial exploration of the Leviviridae PP7 bacteriophage capsid as a platform for the genetically-programmed display of multiple peptide sequences of therapeutic and targeting interest. These peptides include short and long sequences that bind cell-surface EGF or transferrin receptors, as well as examples of other functional (Z-domain) and antigenic (OVA) peptides. The PP7 structure is far more tolerant than the closely related Q VLP to self-assembly of C- or N-terminally extended capsid proteins. Some of these constructs were able to form stable and homogeneous particles entirely from such proteins, thereby displaying exactly 180 copies of the functional peptide on the VLP surface, a property not shared by other Leviviridae-based platforms. Preliminary exploration of the chemical reactivity of the PP7 particle also shows it to be highly tolerant toward standard bioconjugation techniques. PP7 is therefore an excellent candidate for elaboration into useful diagnostic and therapeutic agents

Introducing new functions into (and onto) virus-like particles

Leviphage Qß and PP7 are well studied viruses that infect E. coli. They also provide highly stable and tailorable capsid protein structures that can be manipulated in a number of ways by the molecular biologist and chemist. We will describe our work with both particles, designed to give them new binding, shielding, and catalytic properties. This involves the expression of hybrid particles bearing catalytic protein domains on the inside or outside, the use of standard polymerization methods to grow organic polymers from the surface or into the interior of the particles, and the marriage of these particles with degradable hydrogel carriers Please click Additional Files below to see the full abstract

Syncytialization and prolonged exposure to palmitate impacts bewo respiration

Placental villous trophoblast mitochondrial respiratory function is critical for a successful pregnancy and environmental influences such as maternal obesity have been associated with respiratory impairment at term. More recently, a gestational high fat diet independent of maternal body composition, has been highlighted as a potential independent regulator of placental mitochondrial metabolism. The current study aimed to characterize the direct impact of a prolonged and isolated exposure to the dietary fatty acids Palmitate (PA) and Oleate (OA) upon placental cell mitochondrial respiratory function. BeWo cytotrophoblast (CT) and syncytiotrophoblast (SCT) cells were treated for 72 h with 100 μM PA, OA or PA+OA (P/O). Live-cell metabolic function was analyzed via the Seahorse XF Mito and Glycolysis Stress tests. Immunoblots and spectrophotometric activity assays were utilized to examine the protein expression and function of electron transport chain (ETC) complexes and key mitochondrial regulatory enzymes. Syncytialization of BeWo cells resulted reduced respiratory activity in conjunction with altered complex I and II activity and decreased pyruvate dehydrogenase (PDH) protein expression and activity. PA and P/O treatments were associated with increased basal and maximal respiratory activities in BeWo CT cells without alterations in protein expression or activity of individual ETC complexes and mitochondrial substrate regulators. The metabolic suppression in BeWo SCTs was consistent with that previously observed in primary human trophoblast cell cultures, while the observed increases in respiratory activity in PA-treated BeWo CTs may be indicative of an early timepoint of specific dietary saturated fat-mediated placental cell mitochondrial dysfunction

Accurate prediction of gene expression by integration of DNA sequence statistics with detailed modeling of transcription regulation

Gene regulation involves a hierarchy of events that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. The effects of DNA sequence on these processes have typically been studied based either on its quantitative connection with single-domain binding free energies or on empirical rules that combine different DNA motifs to predict gene expression trends on a genomic scale. The middle-point approach that quantitatively bridges these two extremes, however, remains largely unexplored. Here, we provide an integrated approach to accurately predict gene expression from statistical sequence information in combination with detailed biophysical modeling of transcription regulation by multidomain binding on multiple DNA sites. For the regulation of the prototypical lac operon, this approach predicts within 0.3-fold accuracy transcriptional activity over a 10,000-fold range from DNA sequence statistics for different intracellular conditions.Comment: 15 pages, 5 figure

Autonomous Control of Space Reactor Systems

Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are avilable to perform intelligent control functions that are necessary for both normal and abnormal operational conditions

Fibroblast growth factors 19 and 21 in acute liver damage

Currently there are very few pharmacological options available to treat acute liver injury. Because its natural exposure to noxious stimuli the liver has developed a strong endogenous hepatoprotective capacity. Indeed, experimental evidence exposed a variety of endogenous hepatic and systemic responses naturally activated to protect the hepatic parenchyma and to foster liver regeneration, therefore preserving individual’s survival. The fibroblast growth factor (FGF) family encompasses a range of polypeptides with important effects on cellular differentiation, growth survival and metabolic regulation in adult organisms. Among these FGFs, FGF19 and FGF21 are endocrine hormones that profoundly influence systemic metabolism but also exert important hepatoprotective activities. In this review, we revisit the biology of these factors and highlight their potential application for the clinical management of acute liver injur

Synchronous Periadriatic magmatism in the Western and Central Alps in the absence of slab breakoff

Periadriatic Alpine magmatism has long been attributed to slab breakoff after Adria-Europe continental collision, but this interpretation is challenged by geophysical data suggesting the existence of a continuous slab. Here, we shed light on this issue based on a comprehensive dataset of zircon U-Pb ages and Hf isotopic compositions from the main western Periadriatic intrusives (from Traversella to Adamello). Our zircon U-Pb data provide the first evidence of Eocene magmatism in the Western Alps (42-41 Ma in Traversella), and demonstrate that magmatism started synchronously in different segments of the Alpine belt, when subduction was still active. Zircon U-Pb ages define younging trends perpendicular to the strike of the European slab, suggesting a progressive Eocene-Oligocene slab steepening. We propose that slab steepening enhanced the corner flow. This process was more effective near the torn edge of the European slab, and triggered Periadriatic magmatism in the absence of slab breakoff

Measurements of J/psi Decays into 2(pi+pi-)eta and 3(pi+pi-)eta

Based on a sample of 5.8X 10^7 J/psi events taken with the BESII detector, the branching fractions of J/psi--> 2(pi+pi-)eta and J/psi-->3(pi+pi-)eta are measured for the first time to be (2.26+-0.08+-0.27)X10^{-3} and (7.24+-0.96+-1.11)X10^{-4}, respectively.Comment: 11 pages, 6 figure