Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role

Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55^Gag), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55^Gag PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55^Gag to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle.     

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 μg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment.     

Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury

Neonatal arterial ischemic stroke is one of the more severe birth complications. The injury can result in extensive neurological damage and is robustly associated with later diagnoses of cerebral palsy (CP). An important part of efforts to develop new therapies include the on-going refinement and understanding of animal models that capture relevant clinical features of neonatal brain injury leading to CP. The potent vasoconstrictor peptide, Endothelin-1 (ET-1), has previously been utilised in animal models to reduce local blood flow to levels that mimic ischemic stroke. Our previous work in this area has shown that it is an effective and technically simple approach for modelling ischemic injury at very early neonatal ages, resulting in stable deficits in motor function. Here, we aimed to extend this model to also examine the impact on cognitive function. We show that focal delivery of ET-1 to the cortex of Sprague Dawley rats on postnatal day 0 (P0) resulted in impaired learning in a touchscreen-based test of visual discrimination and correlated with important clinical features of CP including damage to large white matter structures.     

Funktionspolymere-ein interdisziplinäres forschungsgebiet-

Functional polymers differ from structural polymers in various aspects. The most evident difference is their lack of visibility as they are mostly empolyed in surface applications, e.g. as crystal growth modifiers to inhibit encrustation in detergents, as hair setting agents, or as electro-conductive films. Additional important differences concerning the motivation for new developments, market aspects, and customer relationships are the subject of this paper. The development of technology and market competence in the field of functional polymers and the special problems of low-volume, high-performance chemicals are discussed in detail. The paper deals with examples of recent developments: Polyaramides for membranes, 3,4-polyethylenedioxythiophene as an electroconductive polymer, polyaspartic acid as a biodegradable polycarboxylate in detergents, highly crosslinked, insoluble vinylpyrrolidone/vinylimidazole copolymers for the removal of heavy metals from wine, and finally an insoluble, crosslinked polyvinylpyrrolidone-iodine complex for the sterile filtration of liquids. The outlook discusses the research challenges which remain before a full understanding of the structure/property relationships can be attained.     

Oxidative flavour deterioration of fish oil enriched milk

The oxidative deterioration of milk emulsions supplemented with 1.5 wt‐% fish oil was investigated by sensory evaluation and by determining the peroxide value and volatile oxidation products after cold storage. Two types of milk emulsions were produced, one with a highly unsaturated tuna oil (38 wt‐% of n‐3 fatty acids) and one with cod liver oil (26 wt‐% of n‐3 fatty acids). The effect of added calcium disodium ethylenediaminetetraacetate (EDTA) on oxidation was also investigated. Emulsions based on cod liver oil with a slightly elevated peroxide value (1.5 meq/kg) oxidised significantly faster than the tuna oil emulsions, having a lower initial peroxide value (0.1 meq/kg). In the tuna oil emulsions the fishy off‐flavour could not be detected throughout the storage period. Addition of 5—50 ppm EDTA significantly reduced the development of volatile oxidation products in the cod liver oil emulsions, indicating that metal chelation with EDTA could inhibit the decomposition of lipid hydroperoxides in these emulsions. This study showed that an oxidatively stable milk emulsion containing highly polyunsaturated tuna fish oil could be prepared without significant fishy off‐flavour development upon storage, provided that the initial peroxide value was sufficiently low.     

Time-of-flight studies on catalytic model reactions

Time-of-flight spectroscopy (TOF) and REMPI-TOF (resonance enhanced multi-photon ionization-TOF) were applied to measure the angular and translational energy distribution, as well as the internal state resolved energy distribution of desorption and reaction products on some model systems. Desorption of hydrogen and deuterium from clean and modified Pd(111) surfaces was studied, where the palladium sample was part of a permeation source. Water formation by reaction of oxygen with hydrogen on palladium was investigated by using different types of hydrogen supply: molecular H₂ exposure and atomic H exposure from the gas phase, as well as H exposure by permeating hydrogen. Vanadium oxide nanostructures on Pd(111) were prepared and the influence on D₂ desorption and D₂O production was investigated with the permeation technique. Additionally, deuterium desorption from sulfur and oxygen covered V(111) and V(100) surfaces was studied by TOF and REMPI-TOF spectroscopy. From the TOF spectra information concerning the reaction and desorption dynamics (activation barriers) could be gained.     

A numerical study of particle wall-deposition in a turbulent square duct flow

The deposition of dense solid particles in a downward, fully developed turbulent square duct flow at Re_τ = 360, based on the mean friction velocity and the duct width, is studied using large eddy simulations of the fluid flow. The fluid and the particulate phases are treated using Eulerian and Lagrangian approaches, respectively. A finite-volume based, second-order accurate fractional step scheme is used to integrate the incompressible form of the unsteady, three-dimensional, filtered Navier-Stokes equations on an 80 × 80 × 128 grid. A dynamic subgrid kinetic energy model is used to account for the unresolved scales. The Lagrangian particle equation of motion includes the drag, lift, and gravity forces and is integrated using the fourth-order accurate Runge-Kutta scheme. Two values of particle to fluid density ratio (ρ_p/ρ_f = 1000 and 8900) and five values of dimensionless particle diameter (d_p/δ × 10⁶ = 100, 250, 500, 1000 and 2000, δ is the duct width) are studied. Two particle number densities, consisting of 10⁵ and 1.5 × 10⁶ particles initially in the domain, are examined.Variations in the probability distribution function (PDF) of the particle deposition location with dimensionless particle response time, i.e. Stokes number, are presented. The deposition is seen to occur with greater probability near the center of the duct walls, than at the corners. The average streamwise and wall-normal deposition velocities of the particles increase with Stokes number, with their maxima occurring near the center of the duct wall. The computed deposition rates are compared to previously reported results for a circular pipe flow. It is observed that the deposition rates in a square duct are greater than those in a pipe flow, especially for the low Stokes number particles. Also, wall-deposition of the low Stokes number particles increases significantly by including the subgrid velocity fluctuations in computing the fluid forces on the particles. Two-way coupling and, to a greater extent, four-way coupling are seen to increase the deposition rates.     

Catalytic Combustion of Model Carbon Particles (CPs) over Pt/β-SiC Catalyst

Platinum catalyst supported on a medium surface area -SiC was successfully used for the catalytic combustion of model carbon particles and compared to a catalyst supported on a low surface area -SiC. The -SiC-based catalyst showed no deactivation as a function of cycling tests while a strong deactivation was observed on the -SiC-based catalyst. This deactivation was attributed to the progressive encapsulation of the platinum particles by a layer of silica which built up during the combustion cycle. These results render possible the use of Pt/-SiC catalyst as a diesel carbon particle catalytic filter with continuous regeneration.