"Come i secchi nel pozzo". Scienza ed etica negli scritti contro la vivisezione delle femministe britanniche (1870-1910)

Il saggio ripercorre le riflessioni teoriche delle femministe britanniche su scienza ed etica in relazione al dibattito sulla vivisezion

A Comparison of the Chemical Evolutionary Histories of the Galactic Thin Disk and Thick Disk Stellar Populations

We have studied 23 long-lived G dwarfs that belong to the thin disk and thick disk stellar populations. Abundances have been derived for 24 elements: O, Na, Mg, Al, Si, Ca, Ti, Sc, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Y, Zr, Ba, La, Ce, Nd, and Eu. We find that the behavior of [alpha/Fe] and [Eu/Fe] vs. [Fe/H] are quite different for the two populations. As has long been known, the thin disk O, Mg, Si, Ca, and Ti ratios are enhanced relative to iron at the lowest metallicities, and decline toward solar values as [Fe/H] rises above -1.0. For the thick disk, the decline in [alpha/Fe] and [Eu/Fe] does not begin at [Fe/H] = -1.0, but at -0.4. Other elements share this behavior, including Sc, Co, and Zn, suggesting that at least in the chemical enrichment history of the thick disk, these elements were manufactured in similar-mass stars. Combining our results for the oldest and longest-lived stars with prior work, we find clear signs for an independent origin for the Galactic thick disk. (Abridged)Comment: 48 pages and 20 figures, accepted for publication in the Astronomical Journa

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer

We have identified a human homolog of the bacterial MutS and S. cerevisiae MSH proteins, called hMSH2. Expression of hMSH2 in E. coli causes a dominant mutator phenotype, suggesting that hMSH2, like other divergent MutS homologs, interferes with the normal bacterial mismatch repair pathway. hMSH2 maps to human chromosome 2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC). A T to C transition mutation has been detected in the -6 position of a splice acceptor site in sporadic colon tumors and in affected individuals of two small HNPCC kindreds. These data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene

Breakfast glycaemic index and exercise: combined effects on adolescents' cognition

The aim of the present study was to examine the combined effects of breakfast glycaemic index (GI) and a mid-morning bout of exercise on adolescents’ cognitive function. Participants were randomly allocated to a high or low GI breakfast group in a mixed research design, where each participant completed two experimental trials (exercise and resting). Forty-two adolescents (12.4±0.5 years old), undertook a bout of exercise (ten repeats of level one of the multi-stage fitness test; exercise trial) or continued to rest (resting trial) following consumption of either a high or low GI breakfast. A battery of cognitive function tests (visual search test, Stroop test and Sternberg paradigm) was completed 30 min before and 45 min following the exercise. Average heart rate during exercise was 170±15 beats.min-1. On the complex level of the Stroop test, response times improved across the morning following the low GI breakfast on both the exercise and resting trials, though the improvement was greatest on the exercise trial. However, response times only improved on the resting trial following the high GI breakfast (p = 0.012). On the 5 letter level of the Sternberg paradigm, response times improved across the morning following the low GI breakfast (regardless of exercise) and only on the exercise trial following the high GI breakfast (p = 0.019). The findings of the present study suggest that the combined effects of breakfast GI and exercise in adolescents depend upon the component of cognitive function examined. A low GI breakfast and mid-morning bout of exercise were individually beneficial for response times on the Sternberg paradigm, whereas they conferred additional benefits for response times on the Stroop test

Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs) in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE) in men with coronary artery disease.</p> <p>Methods</p> <p>We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction.</p> <p>Results</p> <p>All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E'), consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red), or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyl)lysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis.</p> <p>Conclusions</p> <p>Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the myocardial microvascular structure, or increased myocardial expression of Nε-(carboxymethyl)lysine or RAGE. These findings suggest that the increased myocardial fibrosis and AGE expression, cardiomyocyte hypertrophy, and altered microvasculature structure described in diabetic heart disease were a consequence, rather than an initiating cause, of cardiac dysfunction.</p

Women’s expectations and experiences of maternity care in NSW - what women highlight as most important

Background Although surveys have identified that women are generally highly satisfied with maternity care provision, those aspects of care that women highlight as most important for achieving satisfaction and a satisfactory maternity care experience have not been reported. The aim of this study was to investigate how women understand and experience their maternity care and to report which aspects of care women highlight as most important. Methods This large qualitative study explored women’s expectations and experiences of maternity care provision. In-depth semi-structured interviews were conducted with 53 women experiencing maternity care in a range of tertiary, regional, rural, remote hospitals and midwife-led practices in the state of New South Wales, Australia during 2011 to 2012. Included in the interview schedule was the question ‘What 3 aspects would you see as most important for delivery of maternity care?’ Descriptive analyses of entire transcripts and responses to the question on most important aspects of care were undertaken. Results Descriptive analyses of women’s responses identified 5 important aspects of care: woman-focused care, staff qualities, systems and facilities, family-focused care and continuity of care/information. First-time mothers were more likely to identify woman-focused care, staff qualities and continuity of care/information as important 3 aspects than multiparous mothers. Urban and regional mothers highlighted staff qualities as having greater importance for satisfaction with their care while rural and particularly remote women nominated systems and facilities as important. Conclusions Our study showed that women from a range of settings are more concerned with staff and relational issues than facilities. Differences in perceptions among primiparous versus multiparous women, at different stages of pregnancy and among women from rural and remote compared to urban settings highlight the need to include women with a diversity of experience when trying to understand the aspects of maternity care most important to women

Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity

Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity