Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Exploring the interpersonal consequences of adverse childhood experiences in college students

The Interpersonal Process Model of Intimacy characterizes intimacy as dyadic interpersonal interactions in which vulnerable behaviors are displayed and reinforced by suitable listeners. We posited that Adverse Childhood Experiences (ACEs) would foster avoidance of vulnerable speaker behaviors in dyadic exchanges, as seen in self-concealment, and that lower levels of ACEs would be associated with more self-disclosure. Correspondingly, we examined whether self-concealment and self-disclosure simultaneously mediated the relationship between ACEs and relationship closeness in college students. Results revealed that ACEs were significantly associated with more self-concealment only. After removing self-disclosure from the model, self-concealment mediated the relationship between ACEs and relationship closeness. Self-concealment mediated the relationship between ACEs and fear of intimacy. Together, the present investigation adds to existing literature by pointing to the interpersonal consequences of ACEs and a potential mechanism maintaining this relationship, and the potential for therapies targeting inflexible responding patterns to enhance functional intimacy-related repertoires

Towards a framework for critical citizenship education

Increasingly countries around the world are promoting forms of "critical" citizenship in the planned curricula of schools. However, the intended meaning behind this term varies markedly and can range from a set of creative and technical skills under the label "critical thinking" to a desire to encourage engagement, action and political emancipation, often labelled "critical pedagogy". This paper distinguishes these manifestations of the "critical" and, based on an analysis of the prevailing models of critical pedagogy and citizenship education, develops a conceptual framework for analysing and comparing the nature of critical citizenship

Comparison of Coincident Rayleigh-Scatter and Sodium Resonance Lidar Temperature Measurements from the Mesosphere-Lower-Thermosphere Region

There are relatively few instruments that have the capabilities to make near continuous measurements of the mesosphere-lower-thermosphere (MLT) region. Rayleigh scatter and resonance lidars, particularly sodium resonance lidar, have been the two dominant ground-based techniques for acquiring mesosphere and MLT vertical temperature profiles, respectively, for more than two decades. With these measurements, the dynamics (gravity waves, tides) and long-term temperature trends (upper atmosphere cooling) of the MLT region can be studied. The Utah State University (USU; 41.7º N, 111.8º W) campus hosts a unique upper atmospheric observatory which houses both a high-power, large-aperture Rayleigh lidar and a sodium resonance Doppler lidar. For the first time, we will present coordinated, night-time averaged temperatures, overlapping in observational range (80-110 km), from the two lidars. This overlap has been achieved through the relocation of the sodium lidar from Colorado State University to USU’s campus and through upgrades to the existing USU Rayleigh lidar which elevated its observational range from 45-90 km to 70-115 km. The comparison of the two sets of temperature measurements is important because the two lidar techniques derive temperature profiles using different scattering processes and analysis methods. Furthermore, previous climatological comparisons, between Rayleigh and sodium lidar, [Argall and Sica, 2007] have suggested that significant temperature differences can occur. This comparison aims to explore possible temperature effects from the differences in the two measurement techniques

The deep propagating gravity wave experiment (deepwave): an airborne and ground-based exploration of gravity wave propagation and effects from their sources throughout the lower and middle atmosphere

Abstract The Deep Propagating Gravity Wave Experiment (DEEPWAVE) was designed to quantify gravity wave (GW) dynamics and effects from orographic and other sources to regions of dissipation at high altitudes. The core DEEPWAVE field phase took place from May through July 2014 using a comprehensive suite of airborne and ground-based instruments providing measurements from Earth’s surface to ∼100 km. Austral winter was chosen to observe deep GW propagation to high altitudes. DEEPWAVE was based on South Island, New Zealand, to provide access to the New Zealand and Tasmanian “hotspots” of GW activity and additional GW sources over the Southern Ocean and Tasman Sea. To observe GWs up to ∼100 km, DEEPWAVE utilized three new instruments built specifically for the National Science Foundation (NSF)/National Center for Atmospheric Research (NCAR) Gulfstream V (GV): a Rayleigh lidar, a sodium resonance lidar, and an advanced mesosphere temperature mapper. These measurements were supplemented by in situ probes, dropsondes, and a microwave temperature profiler on the GV and by in situ probes and a Doppler lidar aboard the German DLR Falcon. Extensive ground-based instrumentation and radiosondes were deployed on South Island, Tasmania, and Southern Ocean islands. Deep orographic GWs were a primary target but multiple flights also observed deep GWs arising from deep convection, jet streams, and frontal systems. Highlights include the following: 1) strong orographic GW forcing accompanying strong cross-mountain flows, 2) strong high-altitude responses even when orographic forcing was weak, 3) large-scale GWs at high altitudes arising from jet stream sources, and 4) significant flight-level energy fluxes and often very large momentum fluxes at high altitudes.David C. Fritts, Ronald B. Smith, Michael J. Taylor, James D. Doyle, Stephen D. Eckermann, Andreas Dörnbrack, Markus Rapp, Bifffford P. Williams, P.-Dominique Pautet, Katrina Bossert, Neal R. Criddddle, Carolyn A. Reynolds, P. Alex Reinecke, Michael Uddddstrom, Michael J. Revell, Richard Turner, Bernd Kaifler, Johannes S. Wagner, Tyler Mixa, Christopher G. Kruse, Alison D. Nugent, Campbell D. Watson, Sonja Gisinger, Steven M. Smith, Ruth S. Lieberman, Brian Laughman, James J. Moore, William O. Brown, Julie A. Haggerty, Alison Rockwell, Gregory J. Stossmeister, Steven F. Williams, Gonzalo Hernandez, Damian J. Murphy, Andrew R. Klekociuk, Iain M. Reid, and Jun M

Affimer proteins for F-actin: novel affinity reagents that label F-actin in live and fixed cells

Imaging the actin cytoskeleton in cells uses a wide range of approaches. Typically, a fluorescent derivative of the small cyclic peptide phalloidin is used to image F-actin in fixed cells. Lifeact and F-tractin are popular for imaging the cytoskeleton in live cells. Here we characterised novel affinity reagents called Affimers that specifically bind to F-actin in vitro to determine if they are suitable alternatives as eGFP-fusion proteins, to label actin in live cells, or for labeling F-actin in fixed cells. In vitro experiments showed that 3 out of the 4 Affimers (Affimers 6, 14 and 24) tested bind tightly to purified F-actin, and appear to have overlapping binding sites. As eGFP-fusion proteins, the same 3 Affimers label F-actin in live cells. FRAP experiments suggest that eGFP-Affimer 6 behaves most similarly to F-tractin and Lifeact. However, it does not colocalize with mCherry-actin in dynamic ruffles, and may preferentially bind stable actin filaments. All 4 Affimers label F-actin in methanol fixed cells, while only Affimer 14 labels F-actin after paraformaldehyde fixation. eGFP-Affimer 6 has potential for use in selectively imaging the stable actin cytoskeleton in live cells, while all 4 Affimers are strong alternatives to phalloidin for labelling F-actin in fixed cells

Exploring metabolic responses of potato tissue induced by electric pulses

In this study, we investigated the metabolic responses of potato tissue induced by pulsed electric field (PEF). Potato tissue was subjected to field strengths ranging from 30 to 500 V/cm, with a single rectangular pulse of 10 μs, 100 μs, or 1 ms. Metabolic responses were monitored using isothermal calorimetry, changes on electrical resistance during the delivery of the pulse, as well as impedance measurements. Our results show that the metabolic response involves oxygen consuming pathways as well as other unidentified events that are shown to be insensitive to metabolic inhibitors such as KCN and sodium azide. The metabolic response is strongly dependent on pulsing conditions and is independent of the total permeabilization achieved by the pulse. Evidence shows that calorimetry is a simple and powerful method for exploring conditions for metabolic stimulation, providing information on metabolic responses that can not be obtained from electrical measurements. This study set the basis for further investigations on defense-related consequences of PEF-induced stress.Sparbanksstiftelsen Färs & Frosta (Sweden).Fundação para a Ciência e a Tecnologia (FCT).Lund University (Sweden).Department of Cell and Organism Biology; Department of Plant Biochemistry

Children’s rights online: challenges, dilemmas and emerging directions

In debates over internet governance, the interests of children figure unevenly, and only partial progress has been made in supporting children’s rights online globally. This chapter examines how the UN Convention on the Rights of the Child is helpful in mapping children’s rights to provision, protection and participation as they apply online as well as offline. However, challenges remain. First, opportunities and risks are positively linked, policy approaches are needed to resolve the potential conflict between protection on the one hand, and provision and participation on the other. Second, while parents may be relied on to some degree to balance their child’s rights and needs, the evidence suggests that a minority of parents are ill-equipped to manage this. Third, resolution is needed regarding the responsibility for implementing digital rights, since many governments prefer self-regulation in relation to internet governance. The chapter concludes by calling for a global governance body charged with ensuring the delivery of children’s rights

Referrals for proliferative diabetic retinopathy from two UK diabetic retinopathy screening services: a 10-year analysis of visual outcomes, requirement for vitrectomy, and mortality

\ua9 The Author(s) 2024. Background/objectives: To determine long-term outcomes of patients referred with proliferative diabetic retinopathy (PDR) from diabetic eye screening programmes (DESP) to tertiary care centres in the United Kingdom (UK). Methods: Retrospective multicentre study of patients referred from two DESPs in the UK over a 36-month period (2007–9) and followed-up for 10 years. Critical outcomes included severe vision loss (SVL) and the need for vitrectomy. Other outcomes assessed included moderate vision loss (MVL), and patient survival time. Univariate and multiple variable Cox proportional hazards regressions were used to analyse survival outcomes. Results: 212 eyes of 150 patients were referred with a diagnosis of PDR. 109 eyes of 72 patients were confirmed to have active PDR and included in the study. 61% of patients had low-risk PDR, while 39% exhibited high-risk features in at least one eye. Eight (7.3%) eyes developed SVL and 16 (14.7%) MVL during follow up. Vitrectomy was required in 24% (95% CI: 15 to 31%) of all PDR eyes and was most commonly performed for vitreous haemorrhage (65%). The 10-year survival in all PDR patients was 76% (95% CI: 63 to 85%) with the mean time to death for all deceased patients being 5.4 \ub1 3.6 years. On multivariable analysis, only age was found to have a significant association with the survival of patients with PDR. Conclusions: During the 10 year follow up SVL was uncommon, but MVL occurred in almost one-fifth of the eyes. Approximately 1 in 4 eyes required vitrectomy, highlighting its significance in patient management