Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Antimicrobial peptides are a promising group of compounds used for the treatment of infections. In some cases, metal ions are essential to activate these molecules. Examples of metalloantibiotics are, for instance, bleomycin and dermcidin. This study is focused on three new pseudopeptides with potential biological activity. The coordination behavior of all ligands with Cu(II) and Ni(II) ions has been examined. Various analytical methods such as potentiometric titration, UV-Vis and CD spectroscopies, and mass spectrometry were used. All compounds are convenient chelators for metal ion-binding. Two of the ligands tested have histidine residues. Surprisingly, imidazole nitrogen is not involved in the coordination of the metal ion. The N-terminal amino group, Dab side chains, and amide nitrogen atoms of the peptide bonds coordinated Cu(II) and Ni(II) in all the complexes formed. The cytotoxicity of three pseudopeptides and their complexes was evaluated. Moreover, their other model allowed for assessing the attenuation of LPS-induced cytotoxicity and anti-inflammatory activities were also evaluated, the results of which revealed to be very promising.     

PD-L1 Inhibitors: Different Classes,Activities, and Mechanisms of Action

Targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) interaction has become an established strategy for cancer immunotherapy. Although hundreds of small-molecule, peptide, and peptidomimetic inhibitors have been proposed in recent years, only a limited number of drug candidates show good PD-1/PD-L1 blocking activity in cell-based assays. In this article, we compare representative molecules from different classes in terms of their PD-1/PD-L1 dissociation capacity measured by HTRF and in vitro bioactivity determined by the immune checkpoint blockade (ICB) co-culture assay. We point to recent discoveries that underscore important differences in the mechanisms of action of these molecules and also indicate one principal feature that needs to be considered, which is the eventual human PD-L1 specificity.     

The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus

VPS13 proteins are evolutionarily conserved. Mutations in the four human genes (VPS13A-D) encoding VPS13A-D proteins are linked to developmental or neurodegenerative diseases. The relationship between the specific localization of individual VPS13 proteins, their molecular functions, and the pathology of these diseases is unknown. Here we used a yeast model to establish the determinants of Vps13′s interaction with the membranes of Golgi apparatus. We analyzed the different phenotypes of the arf1-3 arf2Δ vps13∆ strain, with reduced activity of the Arf1 GTPase, the master regulator of Golgi function and entirely devoid of Vps13. Our analysis led us to propose that Vps13 and Arf1 proteins cooperate at the Golgi apparatus. We showed that Vps13 binds to the Arf1 GTPase through its C-terminal Pleckstrin homology (PH)-like domain. This domain also interacts with phosphoinositol 4,5-bisphosphate as it was bound to liposomes enriched with this lipid. The homologous domain of VPS13A exhibited the same behavior. Furthermore, a fusion of the PH-like domain of Vps13 to green fluorescent protein was localized to Golgi structures in an Arf1-dependent manner. These results suggest that the PH-like domains and Arf1 are determinants of the localization of VPS13 proteins to the Golgi apparatus in yeast and humans.     

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis

Background: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. Methods: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. Results: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. Conclusions: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.     

Using solution thermodynamics to describe the dispersion of rod-like solutes: application to dispersions of carbon nanotubes in organic solvents

We report a simple model describing the solubility of rods in solvents, expressing the final result explicitly in terms of the surface entropy and the enthalpy of mixing. This model can be combined with any expression for the mixing enthalpy depending on the requirements. For example, in one instance it predicts the dispersed concentration of rods to decrease exponentially with the Flory-Huggins parameter of the dispersion. Using a different enthalpy function, it predicts a Gaussian peak when concentration is plotted versus solvent surface energy. The model also suggests specific solvent-rod interactions to be important and shows the dispersed concentration to be very sensitive to ordering at the solvent-rod interface. We have used this model to describe experimental results for the concentration of dispersed nanotubes in various solvents. Qualitative agreement with these predictions is observed experimentally. However, we suggest that the fact that quantitative agreement is not found may be explained by solvent ordering at the nanotube surface.     

Representation of serial order in pigeons (Columba livia).

In Experiment 1, 2 groups of pigeons were trained to respond to either a 4-item (A→B→C→D) or 5-item (A→B→C→D→E) list. After learning their respective list, half of the subjects were trained on a positive pair with reinforcement provided when pairs were responded to in the order true to that of the original sequence (4-item: B→C; 5-item: B→D). The remaining subjects were trained on a negative pair with reinforcement provided for responding to the pairs in the order opposite to that learned in the original sequence (4-item: C→B; 5-item: D→B). Subjects in the positive pair condition learned their respective pair faster than did subjects in the negative pair condition. In Experiment 2, after reaching criterion on a 4-item list, subjects received 16 BC probe trials spread across 4 sessions of training. Subjects performed significantly above chance on the probe trials. The performance of our subjects in Experiments 1 and 2 demonstrates that, similar to monkeys, pigeons form a representation of the lists that they learn. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Method for Estimating the Potential Trading of Worked Water among Multiple Mines

In many parts of the world, mine production and expansion are increasingly limited by access to water. One solution is to consider a water market that would allow trading of mine site water (worked water) from wetter mines to drier mines. However, there is currently no policy support for such a market and it is likely that without government support via incentives, mines will continue to favour freshwater use because it is relatively inexpensive. Furthermore, mines have a high capacity to pay for the water they use, and freshwater creates few risks for production. The opportunity provided by water savings within a trading scheme could be viewed as a source of money to provide incentives for the transfer of worked water between mines. In this paper, we present a new method to trade water among mines based on a site water balance assessment utilising historical climate data, and apply this method to a demonstration region containing multiple coal mines. On average, 340 ML could be transferred per year to drier mines but there remains 11,440 ML per year of water demand unable to be met by trading. The direct monetary value of the worked water that could be transferred, derived from additional coal mining, would be significant. Irrigation may be an attractive option if available infrastructure can be used to trade the saved fresh water in existing markets, thereby providing indirect monetary value (i.e. external to coal production). Alternative uses of water savings may have considerable additional non-monetary value that directly affects the mining industry’s social license-to-operate and its security of long term water supply.     

Control Valve with a Constant Inner Authority Value

The aim of the article is to propose the method of designing double regulation control valves used in heating installations, allowing to obtain a constant value of the so-called inner authority and thus the constancy of the valve control characteristic, regardless of the pre-setting value set on the valve. The shape of the valve's regulation characteristics is one of the main factors determining the quality of the quantitative regulation, and thus the stability of the system's operation and overall operating costs. For this reason, the issue discussed in the article is important and can be applied in practical implementations of the valve sizing and the valve selection.The analysis was based on the relations binding the hydraulic resistances occurring inside the control valve, and the corresponding flow factors, using original author’s proposal.The experimental verification was performed on a special measuring stand prepared for this purpose, measuring the values of the medium volume flow at a constant differential pressure, and then the results were converted into values of the flow factor, used in the proposed mathematical model.The results confirm the thesis put forward and the proposed mathematical model. High convergence of the results of experimental verification with the proposed mathematical model was obtained.     

Improvement of hydrogen production by over-expression of a hydrogen-promoting protein gene in Enterobacter cloacae

The gene of a hydrogen-promoting protein (which we term HPP) from Enterobacter cloacae IIT-BT 08 was cloned and over-expressed in E. cloacae CICC10017 for the first time in this study, and the overall hydrogen yield was greatly improved using the recombinant strain. A recombinant plasmid containing the gene in-frame with Glutathione-S-Transferase (GST) gene was transformed into a hydrogen producing strain of E. cloacae CICC10017 to produce a GST-fusion protein. SDS-PAGE and western blot analysis confirm the successful expression of the GST-tagged protein. An in vitro assay of cell lysates indicates hydrogenase activity of the recombinant strain is 534.78 ± 18.51 ml/(g-DW·h), nearly 2-fold higher than the wild strain. The hydrogen yield of the recombinant strain is 2.55 ± 0.1 mol/mol-glucose, also 2-fold higher than the wild strain. The recombinant strain produces more acetate and butyrate during hydrogen fermentation, but less ethanol, due to the higher hydrogenase activity with the over-expression of the hydrogen-promoting protein. Together, the results demonstrate that successful expression of a single structural gene improves the overall yield of hydrogen by directing metabolic fluxes away from formation of products that compete for NADH.