Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.     

Minimalist counting in sensor networks (Noise helps)

We propose a novel algorithm for counting N indistinguishable objects, called targets, by a collection of sensors. We adopt a minimalist scenario where sensors are unaware of the (non-empty) intersections of sensing regions, and so simple addition of all sensor counts inflates estimates of the total number of targets. The multiple counting in intersections must be accounted for, but with nothing more than the sensor counts, this is clearly impossible. However, noise is typically present in the target counting of many, if not most, applications. We make the key observation that if there is a (target-dependent) noise source affecting all sensors simultaneously, then it couples those with non-empty intersections. Exploitation of this coupling allows us to extract multiple-counting statistics from stochastic correlation patterns, and hence to compute accurate estimates of N via the classical inclusion–exclusion formula. Cumulants are the correlation measures of choice. Our analysis brings out and resolves certain technicalities that arise in our statistical counting algorithm. Examples are worked out to show the potential of the new algorithm. The paper concludes with a discussion of alternative models and open problems.     

Album: Two Editorials

Abstract

There is good reason to be curious about modern creative photography in England. There has been very little .... Robert M. Doty, Infinity     

Electrodeposition of copper into high aspect ratio PCB micro-via using megasonic agitation

This paper presents the use of micro-particle imaging velocimetry (micro-PIV) to analyse fluid flow and hence ion replenishment in PCB micro-via during the electroplating process. The cross section of a PCB via is fabricated in PMMA to allow optical access to the sample. Fluid flow within two 1:1 aspect ratio blind micro-vias, one with straight side walls and the other with tapered side walls were compared. Flow is also analysed in a 1:1 aspect ratio through via. Flow rates measured using micro-PIV are used to validate simulated flow models. The results show that there are increased flow rates within the blind via with tapered side walls. This goes some way to explaining the improved electroplating results obtained in industry when tapered vias are used. Initial experimental results using megasonic streaming to remove bubbles from blind micro-via and promote ion transportation within high aspect ratio PCB micro-via to enhance electrodeposition are also reported.     

Escherichia coli contamination of the river Thames in different seasons and weather conditions

Contamination of public water ways with sewage represents a serious environmental and health risk. We monitored pollution of the river Thames by enumerating the indicator organism Escherichia coli. Samples were taken from a site in central London near Waterloo Bridge in different seasons. E. coli were quantified using a membrane filtration method, and correlated with the tidal variations of the river and meteorological data on rainfall and temperature. More frequent and severe incidents of pollution occurred in the autumn. Heavy rainfall resulted in sharp peaks of E. coli contamination that implies a potential increase of numbers of pathogenic micro‐organisms. Sixty percent of all samples were found to be in excess of the accepted upper limit of pollution set by European Union (EU) legislation for bathing water. This study demonstrated that frequent sewage pollution of the Thames results in high numbers of E. coli and incidents of detectable levels of pathogenic bacteria demonstrating the need for regular monitoring of bacterial pollution.     

Eumelanin for nature‐inspired UV‐absorption enhancement of plastics

In the human body, the black‐brown biopigment eumelanin blocks harmful ultraviolet (UV) radiation. In the plastics industry, additives are often added to polymers to increase their UV‐absorption properties. We herein report an assessment of the biopigment eumelanin as a nature‐inspired additive for plastics to enhance their UV absorption. Since eumelanin is produced by natural sources and is nontoxic, it is an interesting candidate in the field of sustainable plastic additives. In this work, the eumelanin‐containing films of commercial ethylene–vinyl acetate copolymer, a plastic used for packaging applications, were obtained by melt compounding and compression molding. The biopigment dispersion in the films was improved by means of the melanin free acid treatment. It was observed that eumelanin amounts as low as 0.8 wt% caused an increase of the UV absorption, up to one order of magnitude in the UVA range. We also evaluated the effect of eumelanin on the thermal stability and photostability of the films: the biopigment proved to be double‐edged, working both as UV‐absorption enhancer and photo‐prooxidant, as thermogravimetric analysis and infrared spectroscopy revealed. © 2019 Society of Chemical Industry     

Discovery of Heterocyclic Nonacetamide Synaptic Vesicle Protein 2A (SV2A) Ligands with Single‐Digit Nanomolar Potency: Opening Avenues towards the First SV2A Positron Emission Tomography (PET) Ligands

The role of the synaptic vesicle protein 2A (SV2A) protein, target of the antiepileptic drug levetiracetam, is still mostly unknown. Considering its potential to provide in vivo functional insights into the role of SV2A in epileptic patients, the development of an SV2A positron emission tomography (PET) tracer has been undertaken. Using a 3D pharmacophore model based on close analogues of levetiracetam, we report the rationale design of three heterocyclic non‐acetamide lead compounds, UCB‐A, UCB‐H and UCB‐J, the first single‐digit nanomolar SV2A ligands with suitable properties for development as PET tracers.     

Pregnancy outcomes are not improved by administering gonadotropin-releasing hormone at initiation of a 5-day CIDR-Cosynch resynchronization protocol for lactating dairy cows

Using a 5-d controlled internal drug-release (CIDR)-Cosynch resynchronization protocol, the objective of this study was to determine the effect of the initial GnRH injection on pregnancy per artificial insemination (P/AI) to the second artificial insemination in lactating Holstein dairy cows. On 37 ± 3 d (mean ± standard deviation) after the first artificial insemination, and upon nonpregnancy diagnosis (d 0 of the experiment), lactating cows eligible for a second artificial insemination (n = 429) were enrolled in a 5-d CIDR-Cosynch protocol. On d 0, all cows received a CIDR insert and were assigned randomly to receive the initial GnRH injection (GnRH; n = 226) of the protocol or no-GnRH (n = 203). Blood samples were collected from a sub-group of cows (n = 184) on d 0 and analyzed for progesterone (P4) concentration. On d 5, CIDR inserts were removed, and all cows received 1 injection of PGF_2α. On d 6 and 7, cows were observed once daily by employees for tail-chalk removal, and cows detected in estrus on d 6 or 7 received artificial insemination that day (EDAI), and did not receive the final GnRH injection. The remaining cows not detected in estrus by d 8 received GnRH and timed artificial insemination (TAI). Pregnancy status was confirmed by transrectal palpation of uterine contents at 37 ± 3 d (mean ± standard deviation) after the second artificial insemination. Eliminating the initial GnRH injection had no effect on P/AI compared with cows receiving GnRH (27 vs. 21%), respectively. Similarly, method of insemination (EDAI vs. TAI) and its interaction with treatment had no effect on P/AI. Primiparous cows had greater P/AI than multiparous cows (31 vs. 21%). Mean P4 concentrations (n = 184) at the initiation of the protocol did not differ between treatments (4.51 ± 0.35 ng/mL no-GnRH vs. 3.96 ± 0.34 ng/mL of GnRH). When P4 concentrations were categorized as high (≥1 ng/mL) or low (<1 ng/mL), P/AI tended to be greater for high P4 concentrations (n = 136) compared with low (n = 48) P4 concentrations (26 vs. 16%, respectively). No differences were observed in the proportion of cows with high or low P4 between treatments. Collectively, these results provide evidence that eliminating the initial GnRH in a 5-d CIDR-Cosynch resynchronization protocol for lactating dairy cows did not reduce P/AI in this study.     

Analysis of sustainable materials used in ecovillages: Review of progress in BedZED and Masdar city

This paper explores reclaimed and recycled material used in ecovillages. The models discussed in this paper include BedZED in the United Kingdom and Masdar City in the Middle East. These two communities contain features characterized by the sustainable principles of the ecovillage concept by using non-traditional building materials. The creations of more ecovillages, along with the growth of current ecovillages, play an important role in positively solvening environmental and social problems. The sustainable materials used in the ecovillages also act as a model for communities wishing to implement sustainable development.