Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes

The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n-6 and 22:6n-3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women. Diester species predominated in all lipid classes measured. 20/54 Phosphatidylcholine (PtdCho) species were alkyl ester, 15/48 phosphatidylethanolamine (PtdEtn) species were alkyl ester, and 12/48 PtdEtn species were alkenyl ester. There were no significant differences between sexes in the proportions of alkyl PtdCho species. The proportion of alkyl ester PtdEtn species was greater in women than men, while the proportion of alkenyl ester PtdEtn species was greater in men than women. None of the phosphatidylinositol (PtdIns) or phosphatidylserine (PtdSer) molecular species contained ether-linked fatty acids. The proportion of PtdCho16:0_22:6, and the proportions of PtdEtn O-16:0_20:4 and PtdEtn O-18:2_20:4 were greater in women than men. There were no sex differences in PtdIns and PtdSer molecular species compositions. These findings show that plasma phospholipids can be modified by sex. Such differences in lipoprotein phospholipid composition could contribute to sexual dimorphism in patterns of health and disease.     

Ubiquitin C-Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor

The deubiquitinase (DUB) ubiquitin C-terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small-molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine-based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology.     

No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer’s Disease: A Randomised Controlled Trial

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer’s disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer’s disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.     

Fluorescent Amino Acid Initiated de novo Cyclic Peptides for the Label-Free Assessment of Cell Permeability**

The major obstacle in applying peptides to intracellular targets is their low inherent cell permeability. Standard approaches to attach a fluorophore (e. g. FITC, TAMRA) can change the physicochemical properties of the parent peptide and influence their ability to penetrate and localize in cells. We report a label-free strategy for evaluating the cell permeability of cyclic peptide leads. Fluorescent tryptophan analogues 4-cyanotryptophan (4CNW) and β-(1-azulenyl)-L-alanine (AzAla) were incorporated into in vitro translated macrocyclic peptides by initiator reprogramming. We then demonstrate these efficient blue fluorescent emitters are good tools for monitoring peptide penetration into cells.     

Homelessness and social control: a typology

Abstract

The use of ‘social control’ interventions in housing and welfare policy often courts intense controversy, and never more so than when attempts are made to bring about change in the conduct of street homeless people. To date, academic scrutiny has focused on the so-called ‘regulation’ or ‘criminalisation’ of rough sleepers occupying public space, but a range of ‘softer’ control mechanisms are also now in evidence within homelessness support services. This paper explicates the relationship between the distinct forms of social control that have been used in this field – force, coercion, bargaining, influence and tolerance – and compares the perspectives of policy makers, frontline practitioners and homeless people regarding the appropriateness of their deployment in England. It emphasizes that the use of every one of these modes of social control, and indeed the absence of such controls, raises moral and practical dilemmas, the nuance of which is often unacknowledged in academic accounts.     

Dynamic wavelet-based pilot allocation algorithm for OFDM-based cognitive radio systems

In a cognitive radio system, the goal is to make better use of the radio electric spectrum, allowing non-licensed users access to those currently unused electromagnetic bands assigned to licensed users (LUs). This can be achieved using OFDM, where the non-licensed users must select the temporarily available subcarriers and turn off those subcarriers used by LUs in order to avoid interference. Hence, only a subset of the subcarriers can be used for data or pilot tone transmission. To this end, some pilot allocation algorithms have been proposed for this dynamic scenario, but they are designed in such away that an equispaced pilot placement is respected (as much as possible) while minimizing the mean squared error of the channel estimate. Nevertheless, this equispaced placement can lead to the use of an increased number of pilots in order to achieve a good channel estimation. In this work, a new pilot allocation algorithm based on wavelet transform is presented. The proposed algorithm uses the discrete wavelet transform to analyze the previous channel state information, taking the knowledge of the available subcarriers into account to provide a suboptimal solution for the pilot positions. This solution leads to a non-equispaced pilot placement, which improves the channel estimation and consequently, the system performance. Likewise, the introduced algorithm allows a reduction of the number of necessary pilots, which aids in increasing the data rate. Finally, simulation results corroborate the effectiveness of the algorithm in dynamic channel scenarios.