Rat heart fatty acid-binding protein is highly homologous to the murine adipocyte 422 protein and the P2 protein of peripheral nerve myelin

The rat heart contains an abundant cytosolic protein which binds long chain fatty acids. We have determined its primary structure by Edman degradation of peptides generated from chymotryptic, tryptic, and elastase digestions. This polypeptide (Mr = 14,992) contains 134 amino acids and has a blocked (acetylated) NH2 terminus. The sequence of rat heart fatty acid-binding protein (FABP) is remarkably similar to the murine adipocyte 422 protein and the P2 protein of peripheral nerve myelin. Computer-assisted alignment of heart FABP and 422 revealed that 82 of 132 comparable residues are identical (62%). There are 77 identities out of 131 possible matches between this protein and the human myelin P2 protein (59%). Similar comparisons demonstrate that heart FABP has significant homology to several other proteins which bind hydrophobic ligands. The rank of order of similarity to heart FABP is: 422 greater than myelin P2 greater than cellular retinoic acid-binding protein greater than cellular retinol-binding protein II greater than cellular retinol-binding protein greater than intestinal FABP greater than liver FABP. These eight sequences form a family of paralogous homologues. Heart FABP has a region of internal homology involving tandemly arrayed oligopeptides spanning residues 71-100 and 101-131. This feature is not found in the 422 and P2 sequences. The endogenous ligands bound by the 422, P2, and heart FABP sequences have not been defined. Interpretation of the biological significance of their structural similarities and differences will require information about their ligand specificities and affinities.     

Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain

Background  

Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator.     

A new formula for predicting the position of severe arterial stenosis

Noninvasive location of an occlusion or a severe stenosis in the arterial system is of a great interest for surgical interventions. Here, we present a new method to determine the location of arterial 99% stenosis in the arterial (sub) system. The method requires a measurement of propagation constant and the instantaneous flow rate or velocity at two sites of an arterial tree. The method was successfully tested using Womersley’s oscillatory flow theory and the data obtained by a simulation of Fluid structure interaction (FSI). The effect of noise has been investigated to simulate experimental conditions. The results demonstrate that location of 99% severe stenosis could be accurately obtained. The spatial resolution was approximately a few centimeters and the differences between exact and computed values didn’t exceed 13%. However, the identifications of stenotic sites decreased with the distance. Further investigation of the developed method in vivo and in vitro is required.     

Interactions with lectins indicate differences in the carbohydrate composition of the membrane-bound enzymes acetylcholinesterase and 5′-nucleotidase in different cell types

We have examined the interactions of the membrane-bound enzymes, 5′-nucleotidase and acetylcholinesterase from bovine tissues with lectins and shown that glycosylation contributes significantly to the polymorphism of these enzymes, in a tissue-specific manner.Lectins which bind 5′-nucleotidase also inhibit its catalytic activity to various degrees. We found different specificities with 5′-nucleotidases from various cell types: for example lymphocyte 5′-nucleotidase did not interact with wheat germ agglutinin, in contrast with 5′-nucleotidases from hepatocyte and caudate nucleus membranes. Treatment with glycohydrolases, α-d-mannosidase     

A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression

AimThe lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68⁺ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68⁺ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68⁺ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression.MethodsCD80, CD86 and PD-L1 expression by CD68⁺ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry.ResultsThe count of CD68⁺ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68⁺CD80⁺ cells and CD68⁺PD-L1⁺ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68⁺CD80⁺ cells was higher than that of CD68⁺CD86⁺ and CD68⁺PD-L1⁺ cells. In addition, the frequencies of CD68⁺CD80⁺ and CD68⁺CD86⁺ cells were higher in the lobular areas than the portal areas.ConclusionsOur results show that CD68⁺ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection.     

Biodegradation Kinetics of Four Substituted Chlorobenzoic Acids by Enterobacter aerogenes

Enterobacter aerogenes is generally found in soil, sewage plants, and human gastrointestinal tract. Thus, this study was conducted to evaluate the ability of Enterobacter aerogenes to degrade four chlorobenzoic acid compounds (2-chlorobenzoic acid (2-CBA), 3-chlorobenzoic acid (3-CBA), 4-chlorobenzoic acid (4-CBA), and 3,4-dichlorobenzoic acid (3,4-dCBA)) in minimal salt medium. Enterobacter aerogenes was partially able to degrade and dechlorinate these CBAs at concentration of 3.5 mM within 72 h of incubation. According to Haldane single-substrate model, the values of maximum predicted growth rate (μ_max), half saturation constant (K _s), and inhibition constant (K _i) fell in the range of 0.2–0.8 h^?1, 8–41 mM, and 5–53 mM, respectively. Based on the estimated values of both α, a growth-associated constant, and β, a non–growth-associated constant, the production of chloride was predominantly growth associated, since negligible values of the β were determined. Haldane model gave a good prediction of the CBA substrate utilization and degradation, and was in a very good agreement with the experimental data. Because of the capability of Enterobacter aerogenes to utilize these aromatic compounds as carbon and energy sources, this microorganism can be a valuable and promising candidate for use in the biotreatment of wastewater and soil samples contaminated with mixtures of chlorobenzoates.     

Malat-1-PRC2-EZH1 interaction supports adaptive oxidative stress dependent epigenome remodeling in skeletal myotubes

PRC2-mediated epigenetic function involves the interaction with long non-coding RNAs (lncRNAs). Although the identity of some of these RNAs has been elucidated in the context of developmental programs, their counterparts in postmitotic adult tissue homeostasis remain uncharacterized. To this aim, we used terminally differentiated postmitotic skeletal muscle cells in which oxidative stress induces the dynamic activation of PRC2-Ezh1 through Embryonic Ectoderm Develpment (EED) shuttling to the nucleus. We identify lncRNA Malat-1 as a necessary partner for PRC2-Ezh1-dependent response to oxidative stress. We show that in this pathway, PRC2-EZH1 dynamic assembly, and in turn stress induced skeletal muscle targeted genes repression, depends specifically on Malat-1. Our study reports about PRC2–RNA interactions in the physiological context of adaptive oxidative stress response and identifies the first lncRNA involved in PRC2-Ezh1 function.Subject terms: Gene silencing, Long non-coding RNAs