Proteomics: Concepts and applications in human medicine

Proteomics is the complete evaluation of the function and structure of proteins to understand an organism’s nature. Mass spectrometry is an essential tool that is used for profiling proteins in the cell. However, biomarker discovery remains the major challenge of proteomics because of their complexity and dynamicity. Therefore, combining the proteomics approach with genomics and bioinformatics will provide an understanding of the information of biological systems and their disease alteration. However, most studies have investigated a small part of the proteins in the blood. This review highlights the types of proteomics, the available proteomic techniques, and their applications in different research fields.     

Fair hop-by-hop interest rate control to mitigate congestion in named data networks

Cluster Computing - Data retrieval in Named Data Networking (NDN) is based on content names irrespective of their hosting location. The NDN architecture introduces original naming, forwarding and...     

Effect of surgery to implant motion and force sensors on vertical ground reaction forces in the ovine model

Activities of daily living (ADLs) generate complex, multidirectional forces in the anterior cruciate ligament (ACL). While calibration problems preclude direct measurement in patients, ACL forces can conceivably be measured in animals after technical challenges are overcome. For example, motion and force sensors can be implanted in the animal but investigators must determine the extent to which these sensors and surgery affect normal gait. Our objectives in this study were to determine (1) if surgically implanting knee motion sensors and an ACL force sensor significantly alter normal ovine gait and (2) how increasing gait speed and grade on a treadmill affect ovine gait before and after surgery. Ten skeletally mature, female sheep were used to test four hypotheses: (1) surgical implantation of sensors would significantly decrease average and peak vertical ground reaction forces (VGRFs) in the operated limb, (2) surgical implantation would significantly decrease single limb stance duration for the operated limb, (3) increasing treadmill speed would increase VGRFs pre- and post operatively, and (4) increasing treadmill grade would increase the hind limb VGRFs pre- and post operatively. An instrumented treadmill with two force plates was used to record fore and hind limb VGRFs during four combinations of two speeds (1.0 m/s and 1.3 m/s) and two grades (0 deg and 6 deg). Sensor implantation decreased average and peak VGRFs less than 10% and 20%, respectively, across all combinations of speed and grade. Sensor implantation significantly decreased the single limb stance duration in the operated hind limb during inclined walking at 1.3 m/s but had no effect on single limb stance duration in the operated limb during other activities. Increasing treadmill speed increased hind limb peak (but not average) VGRFs before surgery and peak VGRF only in the unoperated hind limb during level walking after surgery. Increasing treadmill grade (at 1 m/s) significantly increased hind limb average and peak VGRFs before surgery but increasing treadmill grade post op did not significantly affect any response measure. Since VGRF values exceeded 80% of presurgery levels, we conclude that animal gait post op is near normal. Thus, we can assume normal gait when conducting experiments following sensor implantation. Ultimately, we seek to measure ACL forces for ADLs to provide design criteria and evaluation benchmarks for traditional and tissue engineered ACL repairs and reconstructions.     

Serum Myeloperoxidase as a Biomarker of Asthma Severity Among Adults: A Case Control Study

Background:The contribution of neutrophils is still indistinct in the inflammatory response of bronchial asthma (BAs). Myeloperoxidase (MPO) is an enzyme released from the primary azurophilic granules of the neutrophils. The study aimed to evaluate the levels of serum MPO as a biomarker for the assessment of the level of asthma control. Methods:The study participants included 94 asthmatic patients and 86 healthy controls. The identification of asthma severity had assessed using the ''''Global Initiative for Asthma guidelines''''. Asthmatic adults had divided into three groups: Good (n= 22), partial (n= 30), and poor control (n= 44). Also, patients have been divided again into two groups (treated and untreated) for BAs.Results:The predicted FEV1% and the peak expiratory flow (PEF/L) of all participants had verified by spirometry. The mean patients’ age was 31.9±15.1 year, with a predominance of females. The mean asthma duration was 10.5±8.6 years. Mean spirometric parameters (FEV1 and PEF) were significantly lower among the patients (0.00). Significant higher MPO levels had observed among BAs patients (p-0.00). The MPO levels have not differed significantly with asthma levels and had significant differences with the history of treatment. There was a nonsignificant negative correlation between the mean MPO levels and the spirometry variables among the patients. ROC curves revealed a sensitivity, specificity, accuracy for MPO (80.9%, 72.1%, and 84.3%), respectively to predict asthmatic severity.Conclusion:There were significantly higher MPO levels compared to healthy controls. Levels of serum MPO had a non-significant positive correlation with levels of asthma control, but a negative non-significant correlation with spirometric results. Key Words: Asthma, And Neutrophils, FEV1, MPO, PEF     

Involvement of the synapse-specific zinc transporter ZnT3 in cadmium-induced hippocampal neurotoxicity

The present study examined the involvement of zinc (Zn)-transporters (ZnT3) in cadmium (Cd)-induced alterations of Zn homeostasis in rat hippocampal neurons. We treated primary rat hippocampal neurons for 24 or 48 hr with various concentrations of CdCl₂ (0, 0.5, 5, 10, 25, or 50 μM) and/or ZnCl ₂ (0, 10, 30, 50, 70, or 90 μM), using normal neuronal medium as control. By The CellTiter 96 ^® Aqueous One Solution Cell Proliferation Assay (MTS; Promega, Madison, WI) assay and immunohistochemistry for cell death markers, 10 and 25 μM of Cd were found to be noncytotoxic doses, and both 30 and 90 μM of Zn as the best concentrations for cell proliferation. We tested these selected doses. Cd, at concentrations of 10 or 25 μM (and depending on the absence or presence of Zn), decreased the percentage of surviving cells. Cd-induced neuronal death was either apoptotic or necrotic depending on dose, as indicated by 7-AAD and/or annexin V labeling. At the molecular level, Cd exposure induced a decrease in hippocampal brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) and Erk1/2 signaling, a significant downregulation of the expression of learning- and memory-related receptors and synaptic proteins such as the NMDAR NR2A subunit and PSD-95, as well as the expression of the synapse-specific vesicular Zn transporter ZnT3 in cultured hippocampal neurons. Zn supplementation, especially at the 30 μM concentration, led to partial or total protection against Cd neurotoxicity both with respect to the number of apoptotic cells and the expression of several genes. Interestingly, after knockdown of ZnT3 by small interfering RNA transfection, we did not find the restoration of the expression of this gene following Zn supplementation at 30 μM concentration. These data indicate the involvement of ZnT3 in the mechanism of Cd-induced hippocampal neurotoxicity.     

Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms might influence the cancer risk due to their antiproliferative, antiangiogenic, and apoptotic effects. The aim of this study was to explore the genetic association of VDR polymorphisms with lung cancer risk in Tunisian population. The genotype and haplotype frequencies of four VDR polymorphisms, FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were studied using polymerase chain reaction and restriction fragment length polymorphism analysis in 240 patients with lung cancer and 280 healthy controls. The distribution of genotype frequencies differed significantly between lung cancer subjects and controls (FokI P _adj  = 0.002; ApaI P _adj  = 0.013). Haplotype analyses revealed a significant association between G-A-C and A-C-T haplotypes and lung cancer risk (P _corr  = 0.0128, P _corr  = 0.008). When patients were stratified according to gender, age, and smoking, significant associations were detected with FokI and TaqI polymorphisms. We found a lack of association between BsmI, TaqI polymorphisms and lung cancer risk (P > 0.05). Only, the attributable proportion due to interaction and the synergic index for interaction between ApaI polymorphism and smoking were statistically significant (P _adj  = 0.74, 95 % CI = 0.38–1.20) and (P _adj  = 0.63, 95 % CI = 0.05–1.21), respectively. Both the additive interaction measures suggested the existence of a biological interaction between SNP ApaI, but not FokI, and smoking. The multiplicative interaction measure was not statistically significant (P > 0.05). This is the first study in Tunisia, which suggested that VDR FokI and ApaI polymorphisms might be risk factors for lung cancer development.     

Comparaison entre OSEM-3D et rétroprojection filtrée pour les images traitées par SISCOM dans l’épilepsie temporale

IntroductionWhen ictal and interictal brain SPECT are reconstructed with filtered backprojection (FBP), the noise level of subtraction images is frequently high and requires the use of thresholding methods. The aim of this study was to compare the subtraction images for cerebral SPECT reconstructed either with FBP or with a 3D iterative reconstruction method (OSEM-3D).Material and methodsAfter optimisation of the reconstruction parameters on phantom, the subtraction SPECT images, which were obtained with FBP or with OSEM-3D and coregistered with MRI images, were analyzed in 15 patients with refractory temporal epilepsy.ResultsOn phantom and with the constrain of high enough spatial resolution (full width at half of maximum for a punctual source less than or equal to 11 mm) were reached using: (i) a Butterworth filter with a cut-off frequency of 0.4 Nyquist at order 6 for FBP and (ii) five iterations, 16 subsets and a 9 mm gaussian filter for OSEM-3D. On the subtraction images, which were obtained with these optimal parameters, the temporal foci from patients were smaller with OSEM-3D than with FBP (11 ± 6 cm³ versus 17 ± 10 cm³, P = 0.02), mean voxel activities were equivalent between the two methods within temporal foci (6.30 ± 3.13 counts versus 6.34 ± 4.93 counts) but these activities were dramatically reduced by OSEM-3D within background regions (0.02 ± 0.02 counts versus 0.19 ± 0.12 counts, P < 0.001).ConclusionFor the ictal–interictal subtraction SPECT images, which are obtained in patients with refractory temporal epilepsy, the use of an optimized OSEM-3D method leads to dramatically reduce the volume of temporal foci, as well as the background noise level, two properties that are likely to facilitate the detection and localisation of epilepsy foci.