Milk, meaning, and morality

Donated human milk’s status comes into question as it leaves the mother-child relationship and is reconfigured through practices and discursive structures that seek to stabilise it as a specific kind of object. Based on research conducted in Cape Town, South Africa, we examine the crucial role of technologies in aiding the milk’s transformation as milk moves from donors’ homes into the clinical setting where it is received by preterm, low-birth weight newborns. We show that the milk shifts back and forth between being a bodily fluid, food, and medicine in the course of this trajectory. Different techniques foreground milk’s diverse properties as a set of moral decisions converges around saving, securing, and sustaining life, and materialising relationships

Kynureninase: synthesis of substrate analogues and mechanistic studies

Kynureninase (EC.3.7.1.3) is an unusual pyridoxal 5'-phosphate (PLP) dependent enzyme which catalyses the beta-gamma hydrolytic cleavage of kynurenine to give anthranilic acid and alanine. The enzyme is a potential therapeutic target for controlling the levels of metabolites, quinolinic acid and kynurenic acid, that are important in a variety of neurodegenerative and inflammatory disorders, such as Alzheimer's disease, AIDS, Lyme disease and poliovirus. Studies have been carried out to elucidate the mechanism of the enzyme. A phosphinic acid analogue of kynurenine, designed as a putative transition state mimic for the reaction, has been prepared. This was found to be a competitive inhibitor, with a KI of 4.19 mM when its interaction with kynureninase, isolated from Pseudomonas fluorescens, was examined. The corresponding methyl phosphinate was also prepared. This was found to be a more potent inhibitor, with a KI of 0.88 mM. It is proposed that methylation of the acid removes a destabilising interaction between the negative charge of the ionised phosphinic acid and some group of the active site. A number of analogues of kynurenine were prepared in order to obtain information on the specificity of the enzyme and the interactions at the active site. A racemic mixture of desaminokynurenine was found to have a KI of 23.2 µM. Cyclohexyl and naphthyl amino acid derivatives prepared by the same method were found to be weak competitive inhibitors of the enzyme with KI values of 844 µM and 207 µM repectively. Desaminokynurenine was found to be a substrate with a rate of reaction twenty times slower than that of kynurenine. The naphthyl amino acid derivative was also found to be a substrate. The results suggested that interactions with the aromatic ring are important and that the naphthyl amino acid derivative may be too large for the active site. The synthesis of 25-[2-2H]-kynurenine is described using two different routes. Diacetylation / racemisation of racemic kynurenine in deuterium oxide followed by acylase catalysed resolution is the most direct route. The alternative is to prepare 2S-[2-2H]-tryptophan by a similar procedure and then to convert this to 2S-[2-2H]-kynurenine via ozonolysis. This compound has been used in isotope studies to gain an understanding of the mechanism of the enzyme catalysed reaction. The primary deuterium isotope effect, DV= 0.98 and D(V/K) = 3.6, showed that for the kynureninase catalysed reaction, alpha-H abstraction is partially rate limiting. A solvent isotope effect, DV= 4.4 and D(V/K) = 4.6 was also determined, showing that a proton transfer is also partially rate limiting

Responses of two marine top predators to an offshore wind farm

Quantifying the likely effects of offshore wind farms on wildlife is fundamental before permission for development can be granted by any Determining Authority. The effects on marine top predators from displacement from important habitat are key concerns during offshore wind farm construction and operation. In this respect, we present evidence for no significant displacement from a UK offshore wind farm for two broadly distributed species of conservation concern: common guillemot (Uria aalge) and harbor porpoise (Phocoena phocoena). Data were collected during boat-based line transect surveys across a 360 km2 study area that included the Robin Rigg offshore wind farm. Surveys were conducted over 10 years across the preconstruction, construction, and operational phases of the development. Changes in guillemot and harbor porpoise abundance and distribution in response to offshore wind farm construction and operation were estimated using generalized mixed models to test for evidence of displacement. Both common guillemot and harbor porpoise were present across the Robin Rigg study area throughout all three development phases. There was a significant reduction in relative harbor porpoise abundance both within and surrounding the Robin Rigg offshore wind farm during construction, but no significant difference was detected between the preconstruction and operational phases. Relative common guillemot abundance remained similar within the Robin Rigg offshore wind farm across all development phases. Offshore wind farms have the potential to negatively affect wildlife, but further evidence regarding the magnitude of effect is needed. The empirical data presented here for two marine top predators provide a valuable addition to the evidence base, allowing future decision making to be improved by reducing the uncertainty of displacement effects and increasing the accuracy of impact assessments

Assessment of Dietary Intake, Energy Status, and Factors Associated With RED-S in Vocational Female Ballet Students

Elite ballet dancers are at risk of health issues associated with Relative Energy Deficiency in Sport (RED-S). This study determined the nutritional status, estimated energy status, and assessed factors related to RED-S in vocational female ballet students. Using a cross-sectional study design, we measured dietary intake (n=20; food diaries and 24hr dietary-recall) and energy expenditure (n=18; accelerometry) in vocational female ballet students (age: 18.1±1.1 years; body mass index: 19.0±1.6 kg·m2; body fat: 22.8±3.4 %) over 7 days, including 5 weekdays (with dance training) and 2 weekend days (without scheduled dance training). Furthermore, we assessed eating behaviours, menstrual function, risk of RED-S (questionnaires), and body composition (dual x-ray absorptiometry). Energy and macronutrient intakes of vocational ballet students were similar during weekdays and weekend days (P > 0.050), whereas total energy expenditure was greater on weekdays than weekend days (P < 0.010; 95% CI: 212, 379). Energy balance was lower on weekdays (-425±465 kcal·day-1) than weekend days (-6±506 kcal·day-1, P=0.015; 95% CI: -748, -92). Exercise energy expenditure was greater on weekdays (393±103 kcal·day-1) than weekend days (213±129 kcal·day-1;

Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

Oral Delivery of Nisin in Resistant Starch Based Matrices Alters the Gut Microbiota in Mice

peer-reviewedThere is a growing recognition of the role the gastrointestinal microbiota plays in health and disease. Ingested antimicrobial proteins and peptides have the potential to alter the gastrointestinal microbiota; particularly if protected from digestion. Nisin is an antimicrobial peptide that is used as a food preservative. This study examined the ability of nisin to affect the murine microbiota when fed to mice in two different starch based matrices; a starch dough comprising raw starch granules and a starch gel comprising starch that was gelatinized and retrograded. The effects of the two starch matrices by themselves on the microbiota were also examined. Following 16S rRNA compositional sequencing, beta diversity analysis highlighted a significant difference (p = 0.001, n = 10) in the murine microbiota between the four diet groups. The differences between the two nisin containing diets were mainly attributable to differences in the nisin release from the starch matrices while the differences between the carriers were mainly attributable to the type of resistant starch they possessed. Indeed, the differences in the relative abundance of several genera in the mice consuming the starch dough and starch gel diets, in particular Akkermansia, the relative abundance of which was 0.5 and 11.9%, respectively (p = 0.0002, n = 10), points to the potential value of resistance starch as a modulator of beneficial gut microbes. Intact nisin and nisin digestion products (in particular nisin fragment 22–31) were detected in the feces and the nisin was biologically active. However, despite a three-fold greater consumption of nisin in the group fed the nisin in starch dough diet, twice as much nisin was detected in the feces of the group which consumed the nisin in starch gel diet. In addition, the relative abundance of three times as many genera from the lower gastrointestinal tract (GIT) were significantly different (p < 0.001, n = 10) to the control for the group fed the nisin in starch gel diet, implying that the starch gel afforded a degree of protection from digestion to the nisin entrapped within it

High Efficiency Planar Geometry Germanium-on-silicon Single-photon Avalanche Diode Detectors

This paper presents the performance of 26 μm and 50 μm diameter planar Ge-on-Si single-photon avalanche diode (SPAD) detectors. The addition of germanium in these detectors extends the spectral range into the short-wave infrared (SWIR) region, beyond the capability of already well-established Si SPAD devices. There are several advantages for extending the spectral range into the SWIR region including: reduced eye-safety laser threshold, greater attainable ranges, and increased depth resolution in range finding applications, in addition to the enhanced capability to image through obscurants such as fog and smoke. The time correlated single-photon counting (TCSPC) technique has been utilized to observe record low dark count rates, below 100 kHz at a temperature of 125 K for up to a 6.6 % excess bias, for the 26 μm diameter devices. Under identical experimental conditions, in terms of excess bias and temperature, the 50 μm diameter device consistently demonstrates dark count rates a factor of 4 times greater than 26 μm diameter devices, indicating that the dark count rate is proportional to the device volume. Single-photon detection efficiencies of up to ~ 29 % were measured at a wavelength of 1310 nm at 125 K. Noise equivalent powers (NEP) down to 9.8 × 10-17 WHz-1/2 and jitters &lt; 160 ps are obtainable, both significantly lower than previous 100 μm diameter planar geometry devices, demonstrating the potential of these devices for highly sensitive and high-speed imaging in the SWIR

A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis

peer-reviewedCystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further

Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar)

BackgroundDense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array. ResultsSNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of &gt; 400 K putative SNPs. An Affymetrix Axiom&reg; myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex. ConclusionsThis manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection