Purification and identification of secernin, a novel cytosolic protein that regulates exocytosis in mast cells

After permeabilization with the pore-forming toxin streptolysin-O mast cells can be triggered to secrete by addition of both calcium and a GTP analogue. If stimulation is delayed after permeabilization, there is a progressive decrease in the extent of secretion upon stimulation, eventually leading to a complete loss of the secretory response. This loss of secretory response can be retarded by the addition of cytosol from other secretory tissues, demonstrating that the response is dependent on a number of cytosolic proteins. We have used this as the basis of a bioassay to purify Secernin 1, a novel 50-kDa cytosolic protein that appears to be involved in the regulation of exocytosis from peritoneal mast cells. Secernin 1 increases both the extent of secretion and increases the sensitivity of mast cells to stimulation with calcium

Addition-Deletion Networks

We study structural properties of growing networks where both addition and deletion of nodes are possible. Our model network evolves via two independent processes. With rate r, a node is added to the system and this node links to a randomly selected existing node. With rate 1, a randomly selected node is deleted, and its parent node inherits the links of its immediate descendants. We show that the in-component size distribution decays algebraically, c_k ~ k^{-beta}, as k-->infty. The exponent beta=2+1/(r-1) varies continuously with the addition rate r. Structural properties of the network including the height distribution, the diameter of the network, the average distance between two nodes, and the fraction of dangling nodes are also obtained analytically. Interestingly, the deletion process leads to a giant hub, a single node with a macroscopic degree whereas all other nodes have a microscopic degree.Comment: 8 pages, 5 figure

"Engaging with birth stories in pregnancy: a hermeneutic phenomenological study of women's experiences across two generations"

BACKGROUND: The birth story has been widely understood as a crucial source of knowledge about childbirth. What has not been reported is the effect that birth stories may have on primigravid women's understandings of birth. Findings are presented from a qualitative study exploring how two generations of women came to understand birth in the milieu of other's stories. The prior assumption was that birth stories must surely have a positive or negative influence on listeners, steering them towards either medical or midwifery-led models of care. METHODS: A Heideggerian hermeneutic phenomenological approach was used. Twenty UK participants were purposively selected and interviewed. Findings from the initial sample of 10 women who were pregnant in 2012 indicated that virtual media was a primary source of birth stories. This led to recruitment of a second sample of 10 women who gave birth in the 1970s-1980s, to determine whether they were more able to translate information into knowledge via stories told through personal contact and not through virtual technologies RESULTS: Findings revealed the experience of 'being-in-the-world' of birth and of stories in that world. From a Heideggerian perspective, the birth story was constructed through 'idle talk' (the taken for granted assumptions of things, which come into being through language). Both oral stories and those told through technology were described as the 'modern birth story'. The first theme 'Stories are difficult like that', examines the birth story as problematic and considers how stories shape meaning. The second 'It's a generational thing', considers how women from two generations came to understand what their experience might be. The third 'Birth in the twilight of certainty,' examines women's experience of Being in a system of birth as constructed, portrayed and sustained in the stories being shared. CONCLUSIONS: The women pregnant in 2012 framed their expectations in the language of choice, whilst the women who birthed in the 1970s-1980s framed their experience in the language of safety. For both, however, the world of birth was the same; saturated with, and only legitimised by the birth of a healthy baby. Rather than creating meaningful understanding, the 'idle talk' of birth made both cohorts fearful of leaving the relative comfort of the 'system', and of claiming an alternative birth

Self-reported management among people with rotator cuff related shoulder pain: An observational study.

Background Rotator cuff related shoulder pain is the most common cause of shoulder pain. Whilst guidelines recommend conservative management prior to imaging, injection or surgical management, recent findings suggest that patients experience management contrary to guideline recommendations. Objectives The aim of this study was to investigate self-reported management among people with rotator cuff related shoulder pain (RCRSP) and their beliefs towards management. Materials and methods Cross-sectional survey of people with RCRSP recruited when referred for imaging (n = 120). Electronic survey about demographic factors, management people had had (including imaging, injections, surgery, exercise, adjuncts), and beliefs about treatments. The frequency of various treatments was reported (separately for each cohort and traumatic onset) as well as the timing of interventions related to first-line care. Results Most people had tried exercise (99/120, 82.5%) but only one in five people reported exercise was helpful, and one in six reported it was unhelpful or made their symptoms worse. Approximately a third of the cohort reported not receiving activity modification advice (34.2%, 41/120), those that did received inconsistent information. People with both traumatic (imaging 31/43, 72.1%; injections 13/24, 54.2%, surgery 8/21, 38.1%) and atraumatic onset pain (imaging 43/77, 55.8%; injections 31/51, 60.8%, surgery 4/19, 21.1%) had similarly high rates of intervention prior to trialling conservative management. Patient beliefs in regards to management showed trends towards interventionalist care. Conclusion Patient reported management of RCRSP is often inconsistent with guideline recommended management

Dynorphin knockout reduces fat mass and increases weight loss during fasting in mice

Endogenous opioids, particularly dynorphins, have been implicated in regulation of energy balance, but it is not known how they mediate this in vivo. We investigated energy homeostasis in dynorphin knockout mice (Dyn -/- mice) and probed the interactions between dynorphins and the neuropeptide Y (NPY) system. Dyn-/- mice were no different from wild types with regards to body weight and basal and fasting-induced food intake, but fecal output was increased, suggesting decreased nutrient absorption, and they had significantly less white fat and lost more weight during a 24-h fast. The neuroendocrine and thermal responses to fasting were at least as pronounced in Dyn-/- as in wild types, and there was no stimulatory effect of dynorphin knockout on 24-h energy expenditure (kilocalories of heat produced) or physical activity. However, Dyn-/- mice showed increased circulating concentrations of 3,4-dihydroxyphenlacetic acid and 3,4-dihydroxyphenylglycol, suggesting increased activity of the sympathetic nervous system. The respiratory exchange ratio of male but not female Dyn-/- mice was reduced, demonstrating increased fat oxidation. Interestingly, expression of the orexigenic acting NPY in the hypothalamic arcuate nucleus was reduced in Dyn-/- mice. However, fasting-induced increases in pre-prodynorphin expression in the arcuate nucleus, the paraventricular nucleus, and the ventromedial hypothalamus but not the lateral hypothalamus were abolished by deletion of Y1 but not Y2 receptors. Therefore, ablation of dynorphins results in increases in fatty acid oxidation in male mice, reductions in adiposity, and increased weight loss during fasting, possibly via increases in sympathetic activity, decreases in intestinal nutrient absorption, and interactions with the NPYergic system

Generators for the hyperelliptic Torelli group and the kernel of the Burau representation at t = -1

We prove that the hyperelliptic Torelli group is generated by Dehn twists about separating curves that are preserved by the hyperelliptic involution. This verifies a conjecture of Hain. The hyperelliptic Torelli group can be identified with the kernel of the Burau representation evaluated at t = −1 and also the fundamental group of the branch locus of the period mapping, and so we obtain analogous generating sets for those. One application is that each component in Torelli space of the locus of hyperelliptic curves becomes simply connected when curves of compact type are added

Long and short paths in uniform random recursive dags

In a uniform random recursive k-dag, there is a root, 0, and each node in turn, from 1 to n, chooses k uniform random parents from among the nodes of smaller index. If S_n is the shortest path distance from node n to the root, then we determine the constant \sigma such that S_n/log(n) tends to \sigma in probability as n tends to infinity. We also show that max_{1 \le i \le n} S_i/log(n) tends to \sigma in probability.Comment: 16 page