CXCL12: role in neuroinflammation

CXCL12, also known as SDF-1 (stromal cell derived factor-1) is a small protein that belongs to the chemokine family, whose members have a crucial role in directing cell migration. CXCL12 has an essential role in neural and vascular development, hematopoiesis and in immunity. It acts through two receptors, CXCR4 and CXCR7. While the former is a classic G protein-coupled transmembrane chemokine receptor, the latter primarily function as a scavenger of CXCL12. CXCL12 has been considered as a standard pro-inflammatory molecule for a long time, as it attracts leukocytes to inflammatory sites and contributes to their activation. However, recent findings indicate that this chemokine has the opposite role in neuroinflammation. In this review, basic data about molecular and functional properties of CXCL12 are presented, while its role in CNS autoimmunity is addressed in details.     

Exercise-induced changes in redox status of elite karate athletes

Regular training has been claimed to increase the activity of antioxidant enzymes and, consequently, augments the resistance to oxidative stress; however, large volumes of training performed by elite sportsmen could lead to a chronic oxidative stress state. The aim of our study was to assess the oxidative status of elite athletes at the beginning of the preparatory and the beginning of the competition training phases, so that the influence of three months of programmed physical activity on redox status could be determined. The chronic effects of exercise on the redox state of the athletes were compared to the effects of a single bout of karate training. Thirty elite karate athletes, 16-30 years old, were subjected to maximal graded exercise test to estimate their aerobic capacity; blood sampling was also performed to measure levels of superoxide anion radical (O??), hydrogen peroxide (H?O?), superoxide dismutase activity (SOD) and catalase activity (CAT). The only significant change after the three-month training process was found in the significantly decreased CAT activity (X ± SE: 7.95 ± 0.13 U/g Hb × 103 in the preparatory period, 6.65 ± 0.28 U/g Hb × 103 in the competition stage; P < 0.01). After a single karate training session, there was statistically significant decrease of O??(X ± SE: 32.7 ± 4.9 nmol/ml in the preparatory period, 24.5 ± 2.5 nmol/ml in the competition stage; P < 0.05) and increase of H?O?(X ± SE: 11.8 ± 1.0 nmol/ml in the preparatory period, 14.2 ± 0.9 nmol/ml in the competition stage; P < 0.01), as well as significant CAT increase (X ± SE: 6.6 ± 0.6 U/g Hb × 103 in the preparatory period, 8.5 ± 0.5 U/g Hb × 103 in the competition stage; P < 0.05). Although the three-month training process induced, at the first sight, negative changes in the redox state, expressed through the decrease in CAT activity, adequate response of the antioxidant system of our athletes to acute exercise was preserved.     

Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis

The aim was to investigate different genotypes and haplotypes of methylenetetrahydrofolate reductase (MTHFR-677, -1298) and plasma concentration of total homocysteine (tHcy) in Macedonian patients with occlusive artery disease (OAD) and deep venous thrombosis (DVT). Investigated groups consists of 80 healthy, 74 patients with OAD, and 63 patients with DVT. Plasma tHcy was measured with Microplate Enzyme Immunoassay. Identification of MTHFR genotypes and haplotypes was done with CVD StripAssay. The probability level (P-value) was evaluated by the Student's t-test. Plasma concentration of tHcy in CC and CT genotypes of MTHFR C677T was significantly increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy in AC genotype of MTHFR A1298C was increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal:heterozygote (CC:AC), heterozygote:normal (CT:AA), and heterozygote:heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote:heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT.     

Mixed tetraoxanes containing the acetone subunit as antimalarials

Eleven new tetraoxanes possessing cholic acid-derived carrier and isopropylidene moiety were synthesized and were tested in vitro and in vivo. In vitro screening revealed that nine of them were more potent against CQ-resistant W2 than CQ-susceptible D6 strain and that two of them were equally or more potent than artemisinin and mefloquine against multi-drug resistant TM91C235 strain. Amine 8 cured all mice at the dose of 160mg/kg/day, while the anilide 9 exhibited MCD相似文献   

Translating Service Level Objectives to lower level policies for multi-tier services

Service providers and their customers agree on certain quality of service guarantees through Service Level Agreements (SLA). An SLA contains one or more Service Level Objectives (SLO)s that describe the agreed-upon quality requirements at the service level. Translating these SLOs into lower-level policies that can then be used for design and monitoring purposes is a difficult problem. Usually domain experts are involved in this translation that often necessitates application of domain knowledge to this problem. In this article, we propose an approach that combines performance modeling with regression analysis to solve this problem. We demonstrate that our approach is practical and that it can be applied to different n-tier services. Our experiments show that for a typical 3-tier e-commerce application in a virtualized environment, the SLA can be met while improving CPU utilization by up to 3 times.

Feedback Control of an Achiral Robotic Microswimmer

Magnetic microswimmers are useful for navigating and performing tasks at small scales.To demonstrate effective control over such microswimmers,we implemented feedback control of the three-bead achiral microswimmers in both simulation and experiment.The achiral microswimmers with the ability to swim in bulk fluid are controlled wirelessly using magnetic fields generated from electromagnetic coils.The achirality of the microswimmers introduces unknown handedness resulting in uncertainty in swimming direction.We use a combination of rotating and static magnetic fields generated from an approximate Helmholtz coil system to overcome such uncertainty.There are also movement uncertainties due to environmental factors such as unsteady flow conditions.A kinematic model based feedback controller was created based on data fitting of experimental data.However,the controller was unable to yield satisfactory performance due to uncertainties from environmental factors;i.e.,the time to reach target pose under adverse flow condition is too long.Following the implementation of an integral controller to control the microswimmers' swimming velocity,the microswimmers were able to reach the target in roughly half the time.Through simulation and experiments,we show that the feedback control law can move an achiral microswimmer from any initial conditions to a target pose.     

Fatigue compensation during FES using surface EMG

Muscle fatigue limits the effectiveness of FES when applied to regain functional movements in spinal cord injured (SCI) individuals. The stimulation intensity must be manually increased to provide more force output to compensate for the decreasing muscle force due to fatigue. An artificial neural network (ANN) system was designed to compensate for muscle fatigue during functional electrical stimulation (FES) by maintaining a constant joint angle. Surface electromyography signals (EMG) from electrically stimulated muscles were used to determine when to increase the stimulation intensity when the muscle’s output started to drop.

In two separate experiments on able-bodied subjects seated in hard back chairs, electrical stimulation was continuously applied to fatigue either the biceps (during elbow flexion) or the quadriceps muscle (during leg extension) while recording the surface EMG. An ANN system was created using processed surface EMG as the input, and a discrete fatigue compensation control signal, indicating when to increase the stimulation current, as the output. In order to provide training examples and test the systems’ performance, the stimulation current amplitude was manually increased to maintain constant joint angles. Manual stimulation amplitude increases were required upon observing a significant decrease in the joint angle. The goal of the ANN system was to generate fatigue compensation control signals in an attempt to maintain a constant joint angle.

On average, the systems could correctly predict 78.5% of the instances at which a stimulation increase was required to maintain the joint angle. The performance of these ANN systems demonstrates the feasibility of using surface EMG feedback in an FES control system.     

Respiratory sinus arrhythmia as a second order system

The presented study describes the influence of respiration on heart rate, under controlled respiration conditions. In addition, this study makes a comparison of a simple physical model, the spring-mass system, with the biophysics of respiration. It is possible to use the equations describing the behaviour of the respiratory system, under certain conditions, and analyse them in a way similar to the equations that describe the physical spring-mass system. The results of the heart rate and respiration measurements effected on 10 subjects at various respiration frequencies show us that the heart rate behaves as a second order system within the boundary conditions during a longer period of constant respiration. The results also show that the heart rate behaves as a second order system within the intermediate mode during short time intervals when there is no respiration.     

Oxidative stress and nitrite dynamics under maximal load in elite athletes: relation to sport type

Maximal workload in elite athletes induces increased generation of reactive oxygen/nitrogen species (RONS) and oxidative stress, but the dynamics of RONS production are not fully explored. The aim of our study was to examine the effects of long-term engagement in sports with different energy requirements (aerobic, anaerobic, and aerobic/anaerobic) on oxidative stress parameters during progressive exercise test. Concentrations of lactates, nitric oxide (NO) measured through stabile end product-nitrites (NO₂ ^?), superoxide anion radical (O₂ ^??), and thiobarbituric reactive substances (TBARS) as index of lipid peroxidation were determined in rest, after maximal workload, and at 4 and 10th min of recovery in blood plasma of top level competitors in rowing, cycling, and taekwondo. Results showed that sportmen had similar concentrations of lactates and O₂ ^?? in rest. Nitrite concentrations in rest were the lowest in taekwondo fighters, while rowers had the highest levels among examined groups. The order of magnitude for TBARS level in the rest was bicycling > taekwondo > rowing. During exercise at maximal intensity, the concentration of lactate significantly elevated to similar levels in all tested sportsmen and they were persistently elevated during recovery period of 4 and 10 min. There were no significant changes in O₂ ^??, nitrite, and TBARS levels neither at the maximum intensity of exercise nor during the recovery period comparing to the rest period in examined individuals. Our results showed that long term different training strategies establish different basal nitrites and lipid peroxidation levels in sportmen. However, progressive exercise does not influence basal nitrite and oxidative stress parameters level neither at maximal load nor during the first 10 min of recovery in sportmen studied.