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The adult murine heart has a sparse, phagocytically active macrophage population that expands through monocyte recruitment and adopts an 'M2' phenotype in response to Th2 immunologic challenge.
No full textTissue resident macrophages have vital homeostatic roles in many tissues but their roles are less well defined in the heart. The present study aimed to identify the density, polarisation status and distribution of macrophages in the healthy murine heart and to investigate their ability to respond to immune challenge. Histological analysis of hearts from CSF-1 receptor (csf1-GFP; MacGreen) and CX3CR1 (Cx3cr1(GFP/+)) reporter mice revealed a sparse population of GFP positive macrophages that were evenly distributed throughout the left and right ventricular free walls and septum. F4/80+CD11b+ cardiac macrophages, sorted from myocardial homogenates, were able to phagocytose fluorescent beads in vitro and expressed markers typical of both 'M1' (IL-1β, TNF and CCR2) and 'M2' activation (Ym1, Arg 1, RELMα and IL-10), suggesting no specific polarisation in healthy myocardium. Exposure to Th2 challenge by infection of mice with helminth parasites Schistosoma mansoni, or Heligmosomoides polygyrus, resulted in an increase in cardiac macrophage density, adoption of a stellate morphology and increased expression of Ym1, RELMα and CD206 (mannose receptor), indicative of 'M2' polarisation. This was dependent on recruitment of Ly6ChighCCR2+ monocytes and was accompanied by an increase in collagen content. In conclusion, in the healthy heart resident macrophages are relatively sparse and have a phagocytic role. Following Th2 challenge this population expands due to monocyte recruitment and adopts an 'M2' phenotype associated with increased tissue fibrosis
A Modular Synthesis of Multidentate S-, N- and O-Containing Meta- and Paracyclophanes
No full textThe development of a modular approach to macrocycle assembly has enabled the synthesis of a library of pyridine-based macrocyclic compds. possessing multiple donor sites where chirality was readily introduced from (R)-alanine or (S)-alanine, a representative amino acid. A facile, regioselective, nucleophilic ring opening of aziridines by dithiols enabled the synthesis of thioether-based linkers which on subsequent alkylation provided access to optically pure macrocycles. The synthesis of the target compds. was achieved by a reaction of (2S)-2-methyl-1-[(4-methylphenyl)sulfonyl]aziridine with 2,2'-(oxy)bis[ethanethiol], 2,2'-[1,2-ethanediylbis(oxy)]bis[ethanethiol], 1,3-benzenedimethanethiol. The title compds. thus formed included 3,17-dithia-6,14,23,24-tetraazatricyclo[17.3.1.18,12]tetracosa-1(23),8,10,12(24),19,21-hexaene derivs. and paracyclophane analogs
Selective removal of butanol from aqueous solution by pervaporation with a PIM-1 membrane and membrane aging
No full textIn this work, the selective removal of butanol from aqueous solution by pervaporation with a polymer of intrinsic microporosity (PIM-1) membrane was studied. The freshly cast and aged (370 days) PIM-1 membrane was used for pervaporation experiments at 50 °C. The aged PIM-1 membrane exhibited a decrease of permeability coefficient compared to the freshly cast membrane, from 9.0 × 10−5 to 1.1 × 10−5 mol m−1 kPa−1 h−1 for 1-butanol and from 3.2 × 10−5 to 2.2 × 10−6 mol m−1 kPa−1 h−1 for water, but simultaneously an increase of selectivity, from 2.8 to 5.1, for the separation process at 2 wt.% of butanol. The aging effect may be attributed to slow rearrangement of polymer chains, resulting in densification and reduction of accessible free volume. Renewed soaking of an aged membrane with methanol does not restore the original permeability. The selectivity of 1-butanol increases with higher 1-butanol concentration for fresh PIM membrane, however the opposite trend was observed for aged PIM-1 membrane
Antiobiotic resistence awareness:spreading the word, not the worry
No full textAntibiotic resistance and the emergence of multiple-resistant bacterial strains are a growing concern in UK clinics. Here, David Allison and Steven Hughes from the Manchester Pharmacy School at the University of Manchester, reflect on an interactive workshop aimed to educate students on issues surrounding antibiotic misuse, the importance of hand-washing and the role of pharmacists in public health deliver
Dynamic consent: a possible solution to improve patient confidence and trust in how electronic patient records are used in medical research.
No full textWith one million people treated every 36 hours, routinely collected UK National Health Service (NHS) health data has huge potential for medical research. Advances in data acquisition from electronic patient records (EPRs) means such data are increasingly digital and can be anonymised for research purposes. NHS England's care.data initiative recently sought to increase the amount and availability of such data. However, controversy and uncertainty following the care.data public awareness campaign led to a delay in rollout, indicating that the success of EPR data for medical research may be threatened by a loss of patient and public trust. The sharing of sensitive health care data can only be done through maintaining such trust in a constantly evolving ethicolegal and political landscape. We propose that a dynamic consent model, whereby patients can electronically control consent through time and receive information about the uses of their data, provides a transparent, flexible, and user-friendly means to maintain public trust. This could leverage the huge potential of the EPR for medical research and, ultimately, patient and societal benefit
Shifting sediment sources in the world's longest river: A strontium isotope record for the Holocene Nile
No full textThe Motherhood Pay Gap: A Review of the Issues, Theory and International Evidence
No full textExecutive summaryWhat is the motherhood pay gap?The motherhood pay gap measures the pay gap between mothers and non-mothers,the latter defined in most econometric studies as women without dependent children. Italso measures the pay gap between mothers and fathers. This is different from the genderpay gap, which measures the pay gap between all women and all men in the workforce.While there is a considerable international literature on the motherhood gap, differencesboth in methodologies and in how mothers, non-mothers and fathers are defined usingavailable data create difficulties in comparing estimates. Moreover, in many countries,the data are often unsuitable for analysis, typically because the questions posed insurveys make it difficult to establish the identity of a child’s mother or father(particularly in developing countries where the nuclear family is less common).Nevertheless, many studies draw on international harmonized pay and employment datawhich provide a useful basis for cross-country comparison, and others provideinformative trend analyses for single countries.Trends in the motherhood pay gapFrom the available data it appears that the unadjusted motherhood gap tends to belarger in developing countries than in developed countries. Globally, the motherhood gapincreases as the number of children a woman has increases; in many European countries,for example, having one child has only a small negative effect, but women with two andespecially three children experience a significant wage penalty. In developing countries,evidence suggests the gender of the child may matter as daughters may be more likelythan sons to help with household and caring tasks, thereby reducing the motherhood gap.Whether the wage penalty associated with motherhood is a one-off event or accumulatesover time also varies from one country to the next. For example, mothers who have astrong job attachment are found to experience a wage decrease immediately on return toemployment but soon catch up with non-mothers. In contrast, mothers taking longerleave periods experience a longer-lasting wage penalty. In short, while the existence of amotherhood gap seems universal, the magnitude and duration of the effect motherhoodhas on wages varies from country to country.Explanations for the motherhood pay gapThe main reasons for the motherhood pay gap can be located in one of threeanalytical frameworks – rationalist economics, sociological and comparativeinstitutionalist.The rationalist economics approach emphasizes the following factors: (1) reduced“human capital”, or knowledge, subsequent to labour market interruptions or reductionsin working time, and subsequent reduced commitment (since women are more likely toface employment interruptions, they are less inclined to seek out training or higher-paidpositions with more responsibility); and (2) employment in family-friendly jobs whichare lower-paying (after having children women often opt into part-time jobs, and mayhave little option but to accept jobs with less responsibility).vi Conditions of Work and Employment Series No. 57The sociological approach argues instead that: (1) some employers may build intotheir hiring and promotion decisions traditional stereotypical expectations of the burdensimposed by families on mothers’ time and energy; (2) the absence of child care and otherwork–family measures is a market failure (women are not promoted because investmentin child-care services, flexible working arrangements etc. is missing and vice versa); and(3) undervaluation of women’s work means that skill and experience in femaledominatedoccupations and workplaces tend to be rewarded unfairly.The comparative institutionalist approach emphasizes the following: (1) countriesprovide very different opportunities for mothers to access decent wages through specificpolicies to support care and work (e.g. child-care provision, maternity and paternityleave); (2) a country’s tax and benefit system exerts a strong influence on a mother’sstatus as economically dependent (on a spouse) or as an independent citizen; (3) the sizeof the motherhood wage penalty varies with the degree of inequality in a country’soverall wage structure; (4) the cultural and family context matters, especially in countrieswith less developed formal policy architectures; and (5) implementation gaps are a keyarea of concern, particularly in developing countries, where women work informally orunder precarious contracts in the formal sector which exclude them from statutoryprovisions related to leave, job protection and so on.How to address the motherhood pay gapThe magnitude of the motherhood pay gap and the relevance of some of the abovementionedexplanations depend on the constellation of work–family laws, policies andmeasures, labour market institutions, gender stereotypes and societal expectations inplace in a given country. Nonetheless, there are some general policy options which canbe used to address it: Job-protected parental leave of adequate duration and with income-related payfunded by social insurance or public funds for both women and men, withspecific provision for fathers. High accessibility of affordable and quality child-care services and flexibleworking arrangements for all workers. Tax and benefit rules which treat mothers as economically independent adults. Addressing the implementation gap in work−family and social policies. Preventing and eliminating discrimination based on maternity and familyresponsibilities and creating a family-friendly workplace cultureRight to regulated and flexible working hours, including the upgrading of part-timejobs and promoting access to them for women and men
Structural and nanomechanical effects of cholesterol in binary and ternary spin-coated single lipid bilayers in dry conditions
No full textUbiquitous Chromatin Opening Elements (UCOEs) effect on transgene position and expression stability in CHO cells following methotrexate (MTX) amplification.
No full textThe requirement for complex therapeutic proteins has resulted in mammalian cells, especially CHO cells, being the dominant host for recombinant protein manufacturing. In creating recombinant CHO cell lines, the expression vectors integrate into various parts of the genome leading to variable levels of expression and stability of protein production. This makes mammalian cell line development a long and laborious process. Therefore, with the intention to accelerate process development of recombinant protein production in CHO systems, UCOEs are utilized to diminish instability of production by maintaining an open chromatin surrounding in combination with MTX amplification. Chromosome painting and FISH analysis were performed to provide detailed molecular evaluation on the location of amplified genes and its relationship to the productivity and stability of the amplified cell lines. In summary, cell lines generated with vectors containing UCOEs retained stable GFP expression with MTX present (but instability was observed in the absence of MTX). UCOE cell lines displayed a higher frequency of integration into >1 chromosome than non-UCOE group. Cell populations were more homogenous in terms of transgene location at the end of Long-term culture (LTC). Overall our findings suggest variation in eGFP fluorescence may be attributed to changes in transgene integration profile over LTC