Thermal hysteresis and seeding of twisted fibers formed by achiral discotic particles

In this paper, molecular dynamics simulations of simple disc-shaped particles are used to investigate the free self-assembly of defect-free fibers. Depending on the choice of particle shape and interaction strength, the formed fibers are reproducibly either straight or, for reasons of packing efficiency, spontaneously chiral. As they grow radially, increasing stresses cause chiral fibers to untwist either continuously or via morphological rearrangement. It is also found that, due to the kinetics of fiber initiation, the isotropic solution has to be significantly supercooled before aggregation takes place. As a result, the thermal hysteresis of one formed fiber extends to 13.9% of the formation temperature. In the presence of a three-thread seed cluster of 15 particles, however, monotonic fiber growth is observed 9.3% above the normal formation temperature. Thus, as in many experimental systems, it is the kinetic pathway, rather than the thermodynamic stability of the final assembly, that dominates the observed behavior

Alk2/ACVR1 and Alk3/BMPR1A Provide Essential Function for Bone Morphogenetic Protein–Induced Retinal AngiogenesisHighlights

OBJECTIVE: Increasing evidence suggests that bone morphogenetic protein (BMP) signaling regulates angiogenesis. Here, we aimed to define the function of BMP receptors in regulating early postnatal angiogenesis by analysis of inducible, endothelial-specific deletion of the BMP receptor components Bmpr2 (BMP type 2 receptor), Alk1 (activin receptor-like kinase 1), Alk2, and Alk3 in mouse retinal vessels. APPROACH AND RESULTS: Expression analysis of several BMP ligands showed that proangiogenic BMP ligands are highly expressed in postnatal retinas. Consistently, BMP receptors are also strongly expressed in retina with a distinct pattern. To assess the function of BMP signaling in retinal angiogenesis, we first generated mice carrying an endothelial-specific inducible deletion of Bmpr2. Postnatal deletion of Bmpr2 in endothelial cells substantially decreased the number of angiogenic sprouts at the vascular front and branch points behind the front, leading to attenuated radial expansion. To identify critical BMPR1s (BMP type 1 receptors) associated with BMPR2 in retinal angiogenesis, we generated endothelial-specific inducible deletion of 3 BMPR1s abundantly expressed in endothelial cells and analyzed the respective phenotypes. Among these, endothelial-specific deletion of either Alk2/acvr1 or Alk3/Bmpr1a caused a delay in radial expansion, reminiscent of vascular defects associated with postnatal endothelial-specific deletion of BMPR2, suggesting that ALK2/ACVR1 and ALK3/BMPR1A are likely to be the critical BMPR1s necessary for proangiogenic BMP signaling in retinal vessels. CONCLUSIONS: Our data identify BMP signaling mediated by coordination of ALK2/ACVR1, ALK3/BMPR1A, and BMPR2 as an essential proangiogenic cue for retinal vessels

Absolute Zero : Delivering the UK's climate Change Commitment with Incremental Changes to Today's Technologies

We have to cut our greenhouse gas emissions to zero by 2050: that's what climate scientists tell us, it's what social protesters are asking for and it's now the law in the UK. But we aren't on track. For twenty years we've been trying to solve the problem with new or breakthrough technologies that supply energy and allow industry to keep growing, so we don't have to change our lifestyles. But although some exciting new technology options are being developed, it will take a long time to deploy them, and they won't be operating at scale within thirty years. Meanwhile, our cars are getting heavier, we're flying more each year and we heat our homes to higher temperatures. We all know that this makes no sense, but it's difficult to start discussing how we really want to address climate change while we keep hoping that new technologies will take the problem away. In response, this report starts from today's technologies: if we really want to reach zero emissions in thirty years time, what does that involve? Most of what we most enjoy - spending time together as families or communities, leisure, sport, creativity - can continue and grow unhindered. We need to switch to using electricity as our only form of energy and if we continue today's impressive rates of growth in non-emitting generation, we'll only have to cut our use of energy to 60% of today's levels. We can achieve this with incremental changes to the way we use energy: we can drive smaller cars and take the train when possible, use efficient electric heat-pumps to keep warm and buy buildings, vehicles and equipment that are better designed and last much longer. The two big challenges we face with an all electric future are flying and shipping. Although there are lots of new ideas about electric planes, they won’t be operating at commercial scales within 30 years, so zero emissions means that for some period, we'll all stop using aeroplanes. Shipping is more challenging: although there are a few military ships run by nuclear reactors, we currently don’t have any large electric merchant ships, but we depend strongly on shipping for imported food and goods. In addition, obeying the law of our Climate Change Act requires that we stop doing anything that causes emissions regardless of its energy source. This requires that we stop eating beef and lamb - ruminants who release methane as they digest grass - and already many people have started to switch to more vegetarian diets. However the most difficult problem is cement: making cement releases emissions regardless of how it’s powered, there are currently no alternative options available at scale, and we don’t know how to install new renewables or make new energy efficient buildings without it. We need to discuss these challenges as a society. Making progress on climate change requires that the three key groups of players - government, businesses and individuals - work together, rather than waiting for the other two to act first. But until we face up to the fact that breakthrough technologies won’t arrive fast enough, we can’t even begin having the right discussion. Committing to zero emissions creates tremendous opportunities: there will be huge growth in the use and conversion of electricity for travel, warmth and in industry; growth in new zero emissions diets; growth in materials production, manufacturing and construction compatible with zero emissions; growth in leisure and domestic travel; growth in businesses that help us to use energy efficiently and to conserve the value in materials. Bringing about this change, and exploring the opportunities it creates requires three things to happen together: as individuals we need to be part of the process, exploring the changes in lifestyle we prefer in order to make zero emission a reality. Protest is no longer enough - we must together discuss the way we want the solution to develop; the government needs to treat this as a delivery challenge - just like we did with the London Olympics, ontime and on-budget; the emitting businesses that must close cannot be allowed to delay action, but meanwhile the authors of this report are funded by the government to work across industry to support the transition to growth compatible with zero emissions. Breakthrough technologies will be important in the future but we cannot depend on them to reach our zero emissions target in 2050. Instead this report sets an agenda for a long-overdue public conversation across the whole of UK society about how we really want to achieve Absolute Zero within thirty years

Endothelium-Derived Netrin-4 Supports Pancreatic Epithelial Cell Adhesion and Differentiation through Integrins α2β1 and α3β1

BACKGROUND: Netrins have been extensively studied in the developing central nervous system as pathfinding guidance cues, and more recently in non-neural tissues where they mediate cell adhesion, migration and differentiation. Netrin-4, a distant relative of Netrins 1-3, has been proposed to affect cell fate determination in developing epithelia, though receptors mediating these functions have yet to be identified. METHODOLOGY/PRINCIPAL FINDINGS: Using human embryonic pancreatic cells as a model of developing epithelium, here we report that Netrin-4 is abundantly expressed in vascular endothelial cells and pancreatic ductal cells, and supports epithelial cell adhesion through integrins α2β1 and α3β1. Interestingly, we find that Netrin-4 recognition by embryonic pancreatic cells through integrins α2β1 and α3β1 promotes insulin and glucagon gene expression. In addition, full genome microarray analysis revealed that fetal pancreatic cell adhesion to Netrin-4 causes a prominent down-regulation of cyclins and up-regulation of negative regulators of the cell cycle. Consistent with these results, a number of other genes whose activities have been linked to developmental decisions and/or cellular differentiation are up-regulated. CONCLUSIONS/SIGNIFICANCE: Given the recognized function of blood vessels in epithelial tissue morphogenesis, our results provide a mechanism by which endothelial-derived Netrin-4 may function as a pro-differentiation cue for adjacent developing pancreatic cell populations expressing adhesion receptors α2β1 and α3β1 integrins

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Limber Pine in the Central and Southern Rocky Mountains: Stand Conditions and Interactions with Blister Rust, Mistletoe, and Bark Beetles

Combined effects of the recent mountain pine beetle (Dendroctonus ponderosae) outbreak and white pine blister rust (caused by Cronartium ribicola) (WPBR) are causing extensive crown dieback and mortality in limber pine (Pinus flexilis) in the central and southern Rocky Mountains. Additional stressors such as climate change and limber pine dwarf mistletoe (Aceuthobium cyanocarpum) may significantly alter stand structure and biodiversity of these ecosystems. The objectives of this study were to: (1) assess site, stand, and tree health conditions in limber pine stands of northern Colorado, Wyoming, and southeastern Montana, (2) quantify impacts of WPBR, bark beetles, and dwarf mistletoe, and (3) determine biotic and abiotic factors that influence the occurrence and incidence of these damage agents. We assessed 22,700 limber pines on 508 plots in limber pine-dominated stands in twenty-five study areas in northern Colorado, Wyoming, and southeastern Montana. Average live limber pine density was 311 stems ha−1. Overall, 50% of limber pines were classified as healthy with over 50% of limber pine mortality attributed to bark beetle attacks. White pine blister rust damage was evident on over 60% of declining or dying limber pines. Blister rust was the primary damage agent, occurring on 73% of the plots and 26% of the trees. Bark beetle-caused mortality was found on 75% of plots and 18% of trees. Limber pine dwarf mistletoe was present on 29% of plots and 9% of trees. In study areas that were previously monitored, incidence of WPBR increased over 8–9 years by 6%, bark beetle-caused mortality by 17%, while dwarf mistletoe incidence remained the same. We used statistical modeling to determine meteorological, macro and micro site factors, and stand factors that influenced the occurrence and incidence of WPBR, bark beetles, and dwarf mistletoe on limber pines. Declines in health and rise in mortality due to bark beetles and WPBR has left some study areas with low limber pine basal area and stand density. These stands may be at risk for localized extirpation if the minimum viable population thresholds are not maintained and are identified as areas of concern for restoration and conservation efforts. Current condition status and long-term monitoring of limber pine is needed for land manager decision making and facilitation of restoration goals

Alk2/ACVR1 and Alk3/BMPR1A Provide Essential Function for Bone Morphogenetic Protein–Induced Retinal Angiogenesis

OBJECTIVE: Increasing evidence suggests that Bone Morphogenetic Protein (BMP) signaling regulates angiogenesis. Here, we aimed to define the function of BMP receptors in regulating early post-natal angiogenesis by analysis of inducible, endothelial specific deletion of the BMP receptor components Bmpr2, Alk1, Alk2 and Alk3 in mouse retinal vessels. APPROACH AND RESULTS: Expression analysis of several BMP ligands showed that pro-angiogenic BMP ligands are highly expressed in postnatal retinas. Consistently, BMP receptors are also strongly expressed in retina with a distinct pattern. To assess the function of BMP signaling in retinal angiogenesis, we first generated mice carrying an endothelial-specific inducible deletion of BMP Type 2 receptor (Bmpr2). Postnatal deletion of Bmpr2 in endothelial cells substantially decreased the number of angiogenic sprouts at the vascular front and branchpoints behind the front, leading to attenuated radial expansion. To identify critical BMPR1s associated with BMPR2 in retinal angiogenesis, we generated endothelial-specific inducible deletion of three BMPR1s abundantly expressed in endothelial cells and analyzed the respective phenotypes. Among these, endothelial specific deletion of either Alk2/acvr1 or Alk3/Bmpr1a caused a delay in radial expansion, reminiscent of vascular defects associated with postnatal endothelial specific deletion of BMPR2, suggesting that ALK2/ACVR1 and ALK3/BMPR1A are likely to be the critical BMPR1s necessary for pro-angiogenic BMP signaling in retinal vessels. CONCLUSIONS: Our data identify BMP signaling mediated by coordination of ALK2/ACVR1, ALK3/BMPR1A, and BMPR2 as an essential pro-angiogenic cue for retinal vessels