Immunomodulatory Potential of Patchouli Alcohol Isolated from Pogostemon cablin (Blanco) Benth (Lamiaceae) in Mice

Purpose: To isolate and purify patchouli alcohol (PA), a tricyclic sesquiterpene constituent of Pogostemon cablin, and investigate its immunomodulatory potential in Kunming mice.Methods: PA was prepared from an ethanol aqueous extract of P. cablin by silica gel column chromatography, and further purified by crystallization using n-hexane. Purity was assessed by analytical gas chromatography (GC) and confirmation of chemical structure performed by Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). The effect of PA from Pogostemon cablin on immunological function was studied by macrophage phagocytosis, immune organ index, serum immunoglobulin level and delayed type  hypersensitivity (DTH) in mice that were administered orally doses of 20, 40 and 80 mg/kg.Results: The purity of PA was 99.3%. The oral administration of PA (40, or 80 mg/kg body weight) significantly increased the phagocytic index (p < 0.05), compared with prednisone acetate (PR) group. Administration of PA (80 mg/kg) boosted the production of circulating serum IgM (0.081 ± 0.010) and IgG (1.296 ± 0.120), while IgM and IgG in PR group was 0.069 ± 0.011 (p < 0.01) and 1.180 ± 0.070 (p < 0.01) respectively. However, PA (20 mg/kg) treatment elicited significant decrease in DTH induced by 2, 4-dinitro-chlorobenzene (DNCB) in mice (1.03 ± 0.40, p < 0.05), in comparison to DNCB-induced group (1.67 ± 0.84 mg).Conclusion: These results suggest that PA has significant immunomodulatory properties which probably act by activating mononuclear phagocytic system, augmenting humoral immune response while suppressing cellular immune response.Keywords: Patchouli alcohol, Pogostemon cablin, Immunomodulatory, Phagocytic index, Macrophag

Antifatigue Effect of Millettiae speciosae Champ (Leguminosae) Extract in Mice

Purpose: To evaluate whether Millettiae Speciosae Champ. (Leguminosae) can enhance exercise performance as well as ascertain if it a potential functional food material.Methods: The extract of Millettia speciosa Champ. (MSE) was orally administered to mice in 500, 1000, 2000 mg/kg doses to investigate its anti-fatigue effect in both forced swimming and climbing tests. Glycogen, triglyceride (TG), blood urea nitrogen (BUN) and creatine phosphokinase (CK) levels in plasma which can indicate alterations in energy utilization during exercise performance, were determined to analyze the operating exercise mechanisms.Results: The results showed that swimming time to exhaustion was longer in all treated groups (41.06 ± 1.92, 47.84 ± 1.60, 54.00 ± 2.45 min for 500, 10000 and 2000 mg/kg doses, respectively) than for control (19.45 ± 0.62 min, p < 0.05). The middle and high doses of MSE-treated groups significantly prolonged the climbing time compared with control (p < 0.05). Furthermore, MSE reduced the content of TG significantly by increasing fat utilization, delayed the accumulation of BUN and decreased the level of CK (p < 0.05). In addition, administration of MSE significantly protected the depletion of muscle glycogen when compared with control (p < 0.05).Conclusion: The results show for the first time that Millettia speciosa Champ. (Leguminosae) has significant anti-fatigue activity, and also suggest that it is a potential functional food material.Keywords: Radix millettiae speciosae, Anti-fatigue activity, Exercise performance, Serum urea nitrogen, Gastrocnemius muscle glycogen, Triglyceride, Functional foo

Estimating Dynamic Gait Stability Using Data from Non-aligned Inertial Sensors

Recently, two methods for quantifying the stability of a dynamical system have been applied to human locomotion: local stability (quantified by finite time maximum Lyapunov exponents, λs and λL) and orbital stability (quantified by maximum Floquet multipliers, MaxFm). In most studies published to date, data from optoelectronic measurement systems were used to calculate these measures. However, using wireless inertial sensors may be more practical as they are easier to use, also in ambulatory applications. While inertial sensors have been employed in some studies, it is unknown whether they lead to similar stability estimates as obtained with optoelectronic measurement systems. In the present study, we compared stability measures of human walking estimated from an optoelectronic measurement system with those calculated from an inertial sensor measurement system. Subjects walked on a treadmill at three different speeds while kinematics were recorded using both measurement systems. From the angular velocities and linear accelerations, λs, λL, and MaxFm were calculated. Both measurement systems showed the same effects of walking speed for all variables. Estimates from both measurement systems correlated high for λs and λL, (R > 0.85) but less strongly for MaxFm (R = 0.66). These results indicate that inertial sensors constitute a valid alternative for an optoelectronic measurement system when assessing dynamic stability in human locomotion, and may thus be used instead, which paves the way to studying gait stability during natural, everyday walking

A GMSK VHF-uplink/UHF-downlink transceiver for the CubeSat missions: Thermo-functional performance

© 2018, CEAS. Functional and thermal performance characteristics of a very high frequency/ultra high frequency (VHF/UHF) transceiver based on Gaussian minimum shift keying (GMSK) modulation are presented. The transceiver has been designed for CubeSats telemetry and commanding needs or low rate data download. The design is validated at 27 dBm, 30 dBm and 33 dBm transmitting powers over −20 ∘C to +51 ∘C. Under these thermal conditions, the transmitter spurious dynamic response shows little if any change and the average sensitivity of receiver at the 12 dB signal noise and distortion (SINAD) is −116.7 dBm at 140 MHz and −116.78 dBm at 149.98 MHz. The transmitter and receiver frequencies are stable and the current consumption as well the output RF levels are steady. The design has been verified against a simulation model which allows system tradeoff analysis. The measurements demonstrate the transceiver made with commercial grade parts has dependable performance at the low earth altitudes and orbital heating conditions

Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses

$\textit{Introduction}$ Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such neuroinflammation relates to other aspects of neuropathology (e.g., tau and amyloid pathology) as well as to structural and functional changes in the brain and symptoms (as assessed via MRI and clinical and neuropsychological assessment). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows $\textit{in vivo}$ imaging of inflammation, amyloid and tau deposition, together with neuropsychological profiling, magnetic resonance imaging (MRI) and peripheral biomarker analysis. \textit{Methods & analysis} Using PET imaging of the ligand [11C]PK11195 we will test for increased neuroinflammation $\textit{in vivo}$ in patients with Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late onset depression and mild cognitive impairment, when compared to healthy controls. We will assess whether areas of inflammatory change are associated with amyloid and tau deposition (assessed using $^{11}$C-labelled Pittsburgh Compound B ([$^{11}$C]PiB) and $^{18}$F-labelled AV-1451 respectively), as well as structural and functional connectivity changes found on MRI. Inflammatory biomarker analysis and immune-phenotyping of peripheral blood monocytes will determine the correlation between central (i.e., neural) and peripheral inflammation. Finally, we will examine whether neuroinflammatory changes seen on PET imaging are associated with global and domain specific cognitive impairments, or predict cognitive decline over 12 months. \textit{Ethics & dissemination} The study protocol was approved by the local ethics committee, East of England - Cambridge Central Research Ethics Committee (reference: 13/EE/0104). The study is also ARSAC approved as part of this process. Data will be disseminated by presentation at national and international conferences and by publication, predominantly in journals of neuroscience as well as clinical neurology and psychiatry. $\textit{Strengths}$ Multimodal deep phenotyping Comparisons between diseases as well as with controls Longitudinal neuropsychology data Comparison of central and peripheral inflammation $\textit{Weaknesses}$ Lack of longitudinal neuroimaging Not a prospective study, unable to assess causationThe study is funded by the UK National Institute of Health Research Cambridge Biomedical Research Unit in Dementia (Project 4 - RNAG/293). JBR is supported by the Wellcome Trust (103838). JPC is supported by the UK National Institute of Health Research Biomedical Research Centre at Cambridge. PVR is supported by the PSP Association

The identification of informative genes from multiple datasets with increasing complexity

Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

Accuracy and repeatability of wrist joint angles in boxing using an electromagnetic tracking system

© 2019, The Author(s). The hand-wrist region is reported as the most common injury site in boxing. Boxers are at risk due to the amount of wrist motions when impacting training equipment or their opponents, yet we know relatively little about these motions. This paper describes a new method for quantifying wrist motion in boxing using an electromagnetic tracking system. Surrogate testing procedure utilising a polyamide hand and forearm shape, and in vivo testing procedure utilising 29 elite boxers, were used to assess the accuracy and repeatability of the system. 2D kinematic analysis was used to calculate wrist angles using photogrammetry, whilst the data from the electromagnetic tracking system was processed with visual 3D software. The electromagnetic tracking system agreed with the video-based system (paired t tests) in both the surrogate ( 0.9). In the punch testing, for both repeated jab and hook shots, the electromagnetic tracking system showed good reliability (ICCs > 0.8) and substantial reliability (ICCs > 0.6) for flexion–extension and radial-ulnar deviation angles, respectively. The results indicate that wrist kinematics during punching activities can be measured using an electromagnetic tracking system

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease