Animations Are Dynamic, Effective Tools For Science Teaching: If You Just Follow The Rules!

Textbook companies are increasingly including larger numbers of animations as complementary resources for students and teachers. Are all animations useful as teaching tools? The answer is no. Animations can be useful for communicating dynamic events and processes but only when specific rules are followed. The authors review the important components of effective animations and their extensive, original research on the value of animations in learning and long-term memory retention. When the rules are applied, students can learn complex material more easily and retain more of what they have learned in short and long term memory than they can by viewing static textbook figures. Our results also indicate that learning from animations and graphics differs between males and females. Insight gained from student feedback is highlighted with some final comments on future research

Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium

The social amoebozoan Dictyostelium discoideum undergoes a developmental sequence wherein an extracellular matrix (ECM) sheath surrounds a group of differentiating cells. This sheath is comprised of proteins and carbohydrates, like the ECM of mammalian tissues. One of the characterized ECM proteins is the cysteine-rich, EGF-like (EGFL) repeat-containing, calmodulin (CaM)-binding protein (CaMBP) CyrA. The first EGFL repeat of CyrA increases the rate of random cell motility and cyclic AMP-mediated chemotaxis. Processing of full-length CyrA (~63 kDa) releases two major EGFL repeat-containing fragments (~45 kDa and ~40 kDa) in an event that is developmentally regulated. Evidence for an EGFL repeat receptor also exists and downstream intracellular signaling pathways involving CaM, Ras, protein kinase A and vinculin B phosphorylation have been characterized. In total, these results identify CyrA as a true matricellular protein comparable in function to tenascin C and other matricellular proteins from mammalian cells. Insight into the regulation and processing of CyrA has also been revealed. CyrA is the first identified extracellular CaMBP in this eukaryotic microbe. In keeping with this, extracellular CaM (extCaM) has been shown to be present in the ECM sheath where it binds to CyrA and inhibits its cleavage to release the 45 kDa and 40 kDa EGFL repeat-containing fragments. The presence of extCaM and its role in regulating a matricellular protein during morphogenesis extends our understanding of CaM-mediated signal transduction in eukaryotes

Rad53 homologue forkhead-associated kinase A (FhkA) and Ca2+-binding protein 4a (CBP4a) are nucleolar proteins that differentially redistribute during mitosis in Dictyostelium

Background During mitosis most nucleolar proteins redistribute to other locales providing an opportunity to study the relationship between nucleolar protein localization and function. Dictyostelium is a model organism for the study of several fundamental biological processes and human diseases but only two nucleolar proteins have been studied during mitosis: NumA1 and Snf12. Both of them are linked to the cell cycle. To acquire a better understanding of nucleolar protein localization and dynamics in Dictyostelium we studied the nucleolar localization of two additional proteins during mitosis: Snf12-linked forkhead-associated kinase A (FhkA), which is involved in the cell cycle, and Ca2+-binding protein 4a (CBP4a), which is a binding partner of NumA1. Methods Polyclonal antibodies were produced in-house. Cells were fixed and probed with either anti-FhkA or anti-CBP4a in order to determine cellular localization during interphase and throughout the stages of mitosis. Colocalization with DAPI nuclear stain allowed us to determine the location of the nucleus and nucleolus while colocalization with anti-α-tubulin allowed us to determine the cell cycle stage. Results Here we verify two novel nucleolar proteins, Rad53 homologue FhkA which localized around the edge of the nucleolus and CBP4a which was detected throughout the entire nucleolus. Treatment with the Ca2+ chelator BAPTA (5 mM) showed that the nucleolar localization of CBP4a is Ca2+-dependent. In response to actinomycin D (0.05 mg/mL) CBP4a disappeared from the nucleolus while FhkA protruded from the nucleus, eventually pinching off as cytoplasmic circles. FhkA and CBP4a redistributed differently during mitosis. FhkA redistributed throughout the entire cell and at the nuclear envelope region from prometaphase through telophase. In contrast, during prometaphase CBP4a relocated to many large, discrete “CBP4a islands” throughout the nucleoplasm. Two larger “CBP4a islands” were also detected specifically at the metaphase plate region. Conclusions FhkA and CBP4a represent the sixth and seventh nucleolar proteins that have been verified to date in Dictyostelium and the third and fourth studied during mitosis. The protein-specific distributions of all of these nucleolar proteins during interphase and mitosis provide unique insight into nucleolar protein dynamics in this model organism setting the stage for future work

Tissue Doppler imaging following paediatric cardiac surgery : early patterns of change and relationship to outcome

In this study, tissue Doppler imaging (TDI) was used to assess changes in ventricular function following repair of congenital heart defects. The relationship between TDI indices, myocardial injury and clinical outcome was explored. Forty-five children were studied; 35 withcardiac lesions and 10 controls. TDI was performed preoperatively, on admission to paediatric intensive care unit (PICU) and day 1. Regional myocardial Doppler signals were acquired from the right ventricle (RV), left ventricle (LV) and septum. TDI indices included: peak systolicvelocities, isovolumetric velocities (IVV) and isovolumetric acceleration (IVA). Preoperatively, bi-ventricular TDI velocities in the study groupwere reduced compared with normal controls. Postoperatively, RV velocities were significantly reduced and this persisted to day-1 (PreOp vs. PICU and day-1: 7.7+2.2 vs. 3.4+1.0, P < 0.0001 and 3.55+1.29, P < 0.0001). LV velocities initially declined but recovered towards baseline by day-1 (PreOp vs. PICU: 5.31+1.50 vs. 3.51+1.23, P < 0.0001). Isovolumetric parameters in all regions were reduced throughout the postoperative period. Troponin-I release correlated with longer X-clamp times (r=0.82, P < 0.0001) and reduced RV velocities (r=0.42, P=0.028). Reduced pre- and postoperative LV velocities correlated with longer ventilation (PreOp: r=0.54, P=0.002; PostOp: r=0.42, P=0.026). This study identified reduced postoperative RV velocities correlated with myocardial injury while reduced LV TDI correlated with longer postoperative ventilation

Calmodulin Binding Proteins and Alzheimer’s Disease

Abstract The small, calcium-sensor protein, calmodulin, is ubiquitously expressed and central to cell function in all cell types. Here the literature linking calmodulin to Alzheimer’s disease is reviewed. Several experimentally-verified calmodulin-binding proteins are involved in the formation of amyloid-β plaques including amyloid-β protein precursor, β-secretase, presenilin-1, and ADAM10. Many others possess potential calmodulin-binding domains that remain to be verified. Three calmodulin binding proteins are associated with the formation of neurofibrillary tangles: two kinases (CaMKII, CDK5) and one protein phosphatase (PP2B or calcineurin). Many of the genes recently identified by genome wide association studies and other studies encode proteins that contain putative calmodulin-binding domains but only a couple (e.g., APOE, BIN1) have been experimentally confirmed as calmodulin binding proteins. At least two receptors involved in calcium metabolism and linked to Alzheimer’s disease (mAchR; NMDAR) have also been identified as calmodulin-binding proteins. In addition to this, many proteins that are involved in other cellular events intimately associated with Alzheimer’s disease including calcium channel function, cholesterol metabolism, neuroinflammation, endocytosis, cell cycle events, and apoptosis have been tentatively or experimentally verified as calmodulin binding proteins. The use of calmodulin as a potential biomarker and as a therapeutic target is discussed

Simultaneous cardiac surgery with pulmonary resection: presentation of series and review of literature 1

Abstract Background: The issue of performing simultaneous pulmonary resection and cardiac surgery in patients with coexisting lung carcinoma and ischaemic heart disease remains controversial. We report our experience and review the literature. Methods: Thirteen patients (male ten, female three; mean age 65 years) underwent simultaneous cardiac surgery and pulmonary resection. Lung pathology consisted of primary lung carcinoma (n = 10), benign disease (n = 2) and carcinoid (n = 1). Lung resections included pneumonectomy (n = 3), lobectomy (n = 4), segmentectomy (n = 1) and local excision (n = 5). Cardiac procedures consisted of coronary artery bypass grafting (CABG) in 11, aortic valve replacement in one and mitral valve repair with CABG in one patient. In all but one case the lung resection was performed prior to heparinization and cardiopulmonary bypass (CPB). In two patients, with suitable coronary anatomy, myocardial revascularization without CPB was performed to reduce morbidity. Results: There was no hospital mortality. Postoperative blood loss and ventilation requirements were reduced in the patients who were operated on without CPB. Prolonged ventilatory support was required in two cases. All patients with benign pathology are alive. In the lung cancer group there have been five late deaths: disseminated metastatic disease (n = 3), anticoagulant related haemorrhage (n = 1) and broncho-pleural fistula (n = 1). Of the remaining five patients four are alive and disease free 7-23 months post-operatively; one patient has recurrent disease 40 months post-operatively. Conclusions: Simultaneous pulmonary resection and cardiac surgery is associated with acceptable operative morbidity and mortality. In patients with lung carcinoma long-term survival was determined by tumour stage. The avoidance of CPB may be advantageous by decreasing blood loss and ventilation requirements

How to design a complex behaviour change intervention: experiences from a nutrition-sensitive agriculture trial in rural India

Many public health interventions aim to promote healthful behaviours, with varying degrees of success. With a lack of existing empirical evidence on the optimal number or combination of behaviours to promote to achieve a given health outcome, a key challenge in intervention design lies in deciding what behaviours to prioritise, and how best to promote them. We describe how key behaviours were selected and promoted within a multisectoral nutrition-sensitive agriculture intervention that aimed to address maternal and child undernutrition in rural India. First, we formulated a Theory of Change, which outlined our hypothesised impact pathways. To do this, we used the following inputs: existing conceptual frameworks, published empirical evidence, a feasibility study, formative research and the intervention team’s local knowledge. Then, we selected specific behaviours to address within each impact pathway, based on our formative research, behaviour change models, local knowledge and community feedback. As the intervention progressed, we mapped each of the behaviours against our impact pathways and the transtheoretical model of behaviour change, to monitor the balance of behaviours across pathways and along stages of behaviour change. By collectively agreeing on definitions of complex concepts and hypothesised impact pathways, implementing partners were able to communicate clearly between each other and with intervention participants. Our intervention was iteratively informed by continuous review, by monitoring implementation against targets and by integrating community feedback. Impact and process evaluations will reveal whether these approaches are effective for improving maternal and child nutrition, and what the effects are on each hypothesised impact pathway

Late gadolinium enhancement and adverse outcomes in a contemporary cohort of adult survivors of tetralogy of Fallot

Objective: Myocardial fibrosis has been associated with poorer outcomes in tetralogy of Fallot, however only a handful of studies have assessed its significance in the current era. Our aim was to quantify the amount of late gadolinium enhancement in both the LV and RV in a contemporary cohort of adults with surgically repaired tetralogy of Fallot, and assess the relationship with adverse clinical outcomes. Design: Single centre cohort study Setting: National tertiary referral center Patients: One hundred fourteen patients with surgically repaired tetralogy of Fallot with median age 29.5 years (range 17.5-64.2). Prospective follow-up for mean 2.4 years (SD 1.29). Interventions: Cardiovascular magnetic resonance was performed, and late gadolinium enhancement mass was estimated for the LV using the 5-SD remote myocardium method, and for the RV using a segmental scoring system. Cohort characterization was determined through the use of a computerized database. Outcome measures: Survival analysis from time of scan to first adverse event, defined as an episode of atrial arrhythmia, sustained ventricular arrhythmia, hospitalization with heart failure, or implantable cardioverter-defibrillator insertion. Results: Eleven patients experienced an adverse outcome in the follow-up period, although there were no deaths. LV late gadolinium enhancement was associated with adverse outcomes in a univariate model (P = .027). However, when adjusted for age at scan the significant variables included NYHA class (P = .006), peak oxygen uptake (P = .028), number of prior sternotomies (P = .044), and higher indexed RV and LV end diastolic volumes (P = .002 and P < .001), but not RV or LV late gadolinium enhancement. Conclusions: Formal quantification of late gadolinium enhancement is not currently as helpful in ascertaining prognosis compared to other, more easily assessed parameters in a contemporary cohort of tetralogy of Fallot survivors, however assessment particularly of the LV holds promise for the future

Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are collectively the most frequent autosomal-recessive neurodegenerative disease of childhood, but the underlying cellular and molecular mechanisms remain unclear. Several lines of evidence have highlighted the important role that non-somatic compartments of neurons (axons and synapses) play in the instigation and progression of NCL pathogenesis. Here, we report a progressive breakdown of axons and synapses in the brains of two different mouse models of NCL: Ppt1−/− model of infantile NCL and Cln6nclf model of variant late-infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the two NCL models studied, 2 of the 15 proteins examined (VDAC1 and Pttg1) displayed robust and significant changes at pre/early-symptomatic time-points in both models. Our study demonstrates that synapses and axons are important early pathological targets in the NCLs and has identified two proteins, VDAC1 and Pttg1, with the potential for use as in vivo biomarkers of pre/early-symptomatic axonal and synaptic vulnerability in the NCLs

RIG-I contributes to the innate immune response after cerebral ischemia

BACKGROUND: Focal cerebral ischemia induces an inflammatory response that when exacerbated contributes to deleterious outcomes. The molecular basis regarding the regulation of the innate immune response after focal cerebral ischemia remains poorly understood. METHODS: In this study we examined the expression of retinoic acid-inducible gene (RIG)-like receptor-I (RIG-I) and its involvement in regulating inflammation after ischemia in the brain of rats subjected to middle cerebral artery occlusion (MCAO). In addition, we studied the regulation of RIG-I after oxygen glucose deprivation (OGD) in astrocytes in culture. RESULTS: In this study we show that in the hippocampus of rats, RIG-I and IFN-α are elevated after MCAO. Consistent with these results was an increased in RIG-I and IFN-α after OGD in astrocytes in culture. These data are consistent with immunohistochemical analysis of hippocampal sections, indicating that in GFAP-positive cells there was an increase in RIG-I after MCAO. In addition, in this study we have identified n-propyl gallate as an inhibitor of IFN-α signaling in astrocytes. CONCLUSION: Our findings suggest a role for RIG-I in contributing to the innate immune response after focal cerebral ischemia