Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Partial Deletion of Chromosome 8 β-defensin Cluster Confers Sperm Dysfunction and Infertility in Male Mice

β-defensin peptides are a family of antimicrobial peptides present at mucosal surfaces, with the main site of expression under normal conditions in the male reproductive tract. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. We show here that homozygous deletion of a cluster of nine β-defensin genes (DefbΔ9) in the mouse results in male sterility. The sperm derived from the mutants have reduced motility and increased fragility. Epididymal sperm isolated from the cauda should require capacitation to induce the acrosome reaction but sperm from the mutants demonstrate precocious capacitation and increased spontaneous acrosome reaction compared to wild-types but have reduced ability to bind the zona pellucida of oocytes. Ultrastructural examination reveals a defect in microtubule structure of the axoneme with increased disintegration in mutant derived sperm present in the epididymis cauda region, but not in caput region or testes. Consistent with premature acrosome reaction, sperm from mutant animals have significantly increased intracellular calcium content. Thus we demonstrate in vivo that β-defensins are essential for successful sperm maturation, and their disruption leads to alteration in intracellular calcium, inappropriate spontaneous acrosome reaction and profound male infertility

Heterogeneous and rapid ice loss over the Patagonian Ice Fields revealed by CryoSat-2 swath radar altimetry

The Northern and Southern Patagonian Ice Fields (NPI and SPI) in South America are the largest bodies of ice in the Southern hemisphere outside of Antarctica and the largest contributors to eustatic sea level rise (SLR) in the world, per unit area. Here we exploit swath processed CryoSat-2 interferometric data to produce maps of surface elevation change at sub-kilometer spatial resolution over the Ice Fields for six glaciological years between April 2011 and March 2017. Mass balance is calculated independently for nine sub-regions, including six individual glaciers larger than 300 km². Overall, between 2011 and 2017 the Patagonian Ice Fields have lost mass at a combined rate of 21.29 ± 1.98 Gt a−¹, contributing 0.059 ± 0.005 mm a−¹ to SLR. We observe widespread thinning on the Ice Fields, particularly north of 49° S. However the pattern of surface elevation change is highly heterogeneous, partly reflecting the importance of dynamic processes on the Ice Fields. The Jorge Montt glacier (SPI), whose tidewater terminus is approaching floatation, retreated ~2.5 km during our study period and lost mass at the rate of 2.20 ± 0.38 Gt a−¹ (4.64 ± 0.80 mwe a−¹). In contrast with the general pattern of retreat and mass loss, Pio XI, the largest glacier in South America, is advancing and gaining mass at 0.67 ± 0.29 Gt a−¹ rate

TRPV6 and Cav1.3 Mediate Distal Small Intestine Calcium Absorption Before Weaning

BACKGROUND &amp; AIMS: Intestinal Ca2+ absorption early in life is vital to achieving optimal bone mineralization. The molecular details of intestinal Ca2+ absorption have been defined in adults after peak bone mass is obtained, but they are largely unexplored during development. We sought to delineate the molecular details of transcellular Ca2+ absorption during this critical period.METHODS: Expression of small intestinal and renal calcium transport genes was assessed by using quantitative polymerase chain reaction. Net calcium flux across small intestinal segments was measured in Ussing chambers, including after pharmacologic inhibition or genetic manipulation of TRPV6 or Cav1.3 calcium channels. Femurs were analyzed by using micro-computed tomography and histology.RESULTS: Net TRPV6-mediated Ca2+ flux across the duodenum was absent in pre-weaned (P14) mice but present after weaning. In contrast, we found significant transcellular Ca2+ absorption in the jejunum at 2 weeks but not 2 months of age. Net jejunal Ca2+ absorption observed at P14 was not present in either Trpv6 mutant (D541A) mice or Cav1.3 knockout mice. We observed significant nifedipine-sensitive transcellular absorption across the ileum at P14 but not 2 months. Cav1.3 knockout pups exhibited delayed bone mineral accrual, compensatory nifedipine-insensitive Ca2+ absorption in the ileum, and increased expression of renal Ca2+ reabsorption mediators at P14. Moreover, weaning pups at 2 weeks reduced jejunal and ileal Cav1.3 expression.CONCLUSIONS: We have detailed novel pathways contributing to transcellular Ca2+ transport across the distal small intestine of mice during development, highlighting the complexity of the multiple mechanisms involved in achieving a positive Ca2+ balance early in life.</p

Transient Receptor Potential Vanilloid 6 (TRPV6) Proteins Control the Extracellular Matrix Structure of the Placental Labyrinth

Calcium-selective transient receptor potential Vanilloid 6 (TRPV6) channels are expressed in fetal labyrinth trophoblasts as part of the feto–maternal barrier, necessary for sufficient calcium supply, embryo growth, and bone development during pregnancy. Recently, we have shown a less- compact labyrinth morphology of Trpv6-deficient placentae, and reduced Ca2+ uptake of primary trophoblasts upon functional deletion of TRPV6. Trpv6-/- trophoblasts show a distinct calcium-dependent phenotype. Deep proteomic profiling of wt and Trpv6-/- primary trophoblasts using label-free quantitative mass spectrometry leads to the identification of 2778 proteins. Among those, a group of proteases, including high-temperature requirement A serine peptidase 1 (HTRA1) and different granzymes are more abundantly expressed in Trpv6-/- trophoblast lysates, whereas the extracellular matrix protein fibronectin and the fibronectin-domain-containing protein 3A (FND3A) were markedly reduced. Trpv6-/- placenta lysates contain a higher intrinsic proteolytic activity increasing fibronectin degradation. Our results show that the extracellular matrix formation of the placental labyrinth depends on TRPV6; its deletion in trophoblasts correlates with the increased expression of proteases controlling the extracellular matrix in the labyrinth during pregnancy

Partnership through co-creation: lessons learnt at the University of Adelaide

This paper describes three exemplars of practice inspired by emerging evidence that student-staff partnerships have the potential to significantly enhance many areas of higher education. Students and academics at the University of Adelaide have successfully implemented this collaborative approach across a range of learning and teaching contexts. The Design Thinking Framework, developed by the Hasso Plattner Institute of Design at Stanford University, was utilised at a faculty, program, and course level to frame each of the exemplars, due to its implicit approach to creativity, collaborative development, and achievement of solutions. The iterative nature of the framework facilitated a review cycle for continuous improvement in each Students-as-Partners’ initiative. Analysing the outcomes of each exemplar has identified common hallmarks of successful partnership, and these indicators have the potential to contribute to the growing body of evidence that defines best practice in this pedagogy.Catherine Snelling, Beth R Loveys, Sophie Karanicolas, Nathan James Schofield, William Carlson-Jones, Joanne Weissgerber, Ruby Edmonds, and Jenny Ng

Registered Replication Report: A Large Multilab Cross-Cultural Conceptual Replication of Turri et al. (2015)

According to the justified true belief (JTB) account of knowledge, people can truly know something only if they have a belief that is both justified and true (i.e., knowledge is JTB). This account was challenged by Gettier, who argued that JTB does not explain knowledge attributions in certain situations, later called “Gettier-type cases,” wherein protagonists are justified in believing something to be true, but their belief was correct only because of luck. Laypeople may not attribute knowledge to protagonists with justified but only luckily true beliefs. Although some research has found evidence for these so-called Gettier intuitions, Turri et al. found no evidence that participants attributed knowledge in a counterfeit-object Gettier-type case differently than in a matched case of JTB. In a large-scale, cross-cultural conceptual replication of Turri and colleagues’ Experiment 1 (N = 4,724) using a within-participants design and three vignettes across 19 geopolitical regions, we did find evidence for Gettier intuitions; participants were 1.86 times more likely to attribute knowledge to protagonists in standard cases of JTB than to protagonists in Gettier-type cases. These results suggest that Gettier intuitions may be detectable across different scenarios and cultural contexts. However, the size of the Gettier intuition effect did vary by vignette, and the Turri et al. vignette produced the smallest effect, which was similar in size to that observed in the original study. Differences across vignettes suggest that epistemic intuitions may also depend on contextual factors unrelated to the criteria of knowledge, such as the characteristics of the protagonist being evaluated

The human penguin project: climate, social integration, and core body temperature

Social thermoregulation theory posits that modern human relationships are pleisiomorphically organized around body temperature regulation. In two studies (N = 1755) designed to test the principles from this theory, we used supervised machine learning to identify social and non-social factors that relate to core body temperature. This data-driven analysis found that complex social integration (CSI), defined as the number of high-contact roles one engages in, is a critical predictor of core body temperature. We further used a cross-validation approach to show that colder climates relate to higher levels of CSI, which in turn relates to higher CBT (when climates get colder). These results suggest that despite modern affordances for regulating body temperature, people still rely on social warmth to buffer their bodies against the cold.info:eu-repo/semantics/publishedVersio