Subcutaneous immunization with a novel immunogenic candidate (urease) confers protection against Brucella abortus and Brucella melitensis infections

Brucellosis is a world prevalent endemic illness that is transmitted from domestic animals to humans. Brucella spp. exploits urease for survival in the harsh conditions of stomach during the gastrointestinal infection. In this study, we examined the immune response and the protection elicited by using recombinant Brucella urease (rUrease) vaccination in BALB/c mice. The urease gene was cloned in pET28a and the resulting recombinant protein was employed as subunit vaccine. Recombinant protein was administered subcutaneously and intraperitoneally. Dosage reduction was observed with subcutaneous (SC) vaccination when compared with intraperitoneal (IP) vaccination. rUrease induced mixed Th1–Th2 immune responses with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay, splenocytes from IP and SC‐vaccinated mice displayed a strong recall proliferative response with high amounts of IL‐4, IL‐12 and IFN‐γ production. Vaccinated mice were challenged with virulent Brucella melitensis, B. abortus and B. suis. The SC vaccination route exhibited a higher degree of protection than IP vaccination (p value ≤ 0.05). Altogether, our results indicated that rUrease could be a useful antigen candidate for the development of subunit vaccines against brucellosis.     

Structure function interface with sequential shortening of basal and apical components of the myocardial band

Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30–85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18±3%, with endocardial exceeding epicardial shortening by 5±1%. Epicardial segment crystal displacement followed endocardial shortening by 82±23 ms in the anterior wall, and finished 92±33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation–contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed ‘isovolumetric relaxation’.     

In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated.     

Real-time ocular artifact suppression using recurrent neural network for electro-encephalogram based brain-computer interface

The paper presents an adaptive noise canceller (ANC) filter using an artificial neural network for real-time removal of electro-oculogram (EOG) interference from electro-encephalogram (EEG) signals. Conventional ANC filters are based on linear models of interference. Such linear models provide poorer prediction for biomedical signals. In this work, a recurrent neural network was employed for modelling the interference signals. The eye movement and eye blink artifacts were recorded by the placing of an electrode on the forehead above the left eye and an electrode on the left temple. The reference signal was then generated by the data collected from the forehead electrode being added to data recorded from the temple electrode. The reference signal was also contaminated by the EEG. To reduce the EEG interference, the reference signal was first low-pass filtered by a moving averaged filter and then applied to the ANC. Matlab Simulink was used for real-time data acquisition, filtering and ocular artifact suppression. Simulation results show the validity and effectiveness of the technique with different signal-to-noise ratios (SNRs) of the primary signal. On average, a significant improvement in SNR up to 27 dB was achieved with the recurrent neural network. The results from real data demonstrate that the proposed scheme removes ocular artifacts from contaminated EEG signals and is suitable for real-time and short-time EEG recordings.