The Actin Binding Domain of βI-Spectrin Regulates the Morphological and Functional Dynamics of Dendritic Spines

Actin microfilaments regulate the size, shape and mobility of dendritic spines and are in turn regulated by actin binding proteins and small GTPases. The βI isoform of spectrin, a protein that links the actin cytoskeleton to membrane proteins, is present in spines. To understand its function, we expressed its actin-binding domain (ABD) in CA1 pyramidal neurons in hippocampal slice cultures. The ABD of βI-spectrin bundled actin in principal dendrites and was concentrated in dendritic spines, where it significantly increased the size of the spine head. These effects were not observed after expression of homologous ABDs of utrophin, dystrophin, and α-actinin. Treatment of slice cultures with latrunculin-B significantly decreased spine head size and decreased actin-GFP fluorescence in cells expressing the ABD of α-actinin, but not the ABD of βI-spectrin, suggesting that its presence inhibits actin depolymerization. We also observed an increase in the area of GFP-tagged PSD-95 in the spine head and an increase in the amplitude of mEPSCs at spines expressing the ABD of βI-spectrin. The effects of the βI-spectrin ABD on spine size and mEPSC amplitude were mimicked by expressing wild-type Rac3, a small GTPase that co-immunoprecipitates specifically with βI-spectrin in extracts of cultured cortical neurons. Spine size was normal in cells co-expressing a dominant negative Rac3 construct with the βI-spectrin ABD. We suggest that βI-spectrin is a synaptic protein that can modulate both the morphological and functional dynamics of dendritic spines, perhaps via interaction with actin and Rac3

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Grain characteristics and composition of maize specialty hybrids

Improved nutritive and technological maize grain value is very important for its use in diets. In this work, the chemical composition and potential beneficial components, including total and soluble proteins, tryptophan, starch, sugars (sucrose and reducing sugars), and fibres were investigated in flour of eight specialty maize hybrids from Maize Research Institute Zemun Polje (ZP): two sweet, popping, red, white, waxy, yellow semiflint and yellow dent maize hybrids. In addition, digestibility of grain dry matter and viscosity of maize flour were determined. The highest nutritive value was recorded in sweet maize hybrids ZP 504su and ZP 531su which had the highest content of total protein, albumin, tryptophan, sugars and dietary fibres. Besides, low content of starch (55.32% and 54.59%, respectively) and lignin (0.39% and 0.45%) affected the highest dry matter digestibility (92.69% and 91.07%) of sweet maize flour. However, functional properties of ZP sweet hybrids were not satisfactory for food and industrial applications. In contrast, flour of ZP waxy maize hybrid was characterised by a clear and a high peak viscosity. All hybrids could be classified according to the sucrose content in three groups: a) > 4% (sweet and red hybrids-ZP 504su, ZP Rumenka), b) from 3 to 4% (waxy, standard dent and semi flint hybrids-ZP 704wx, ZP 434, ZP 633) and c) from 2 to 3% (sweet, white and popping maize hybrids-ZP 531su, ZP 74b, ZP 611k).á-Zein was the dominant protein fraction in all genotypes except the sweet maize hybrids, making 22.45% to 29.25% of the total protein content.La mejora en el valor nutritivo del maiz de grano es muy importante en las dietas. En este trabajo, se investigaron la composicion quimica y componentes potencialmente beneficiosos (proteinas totales y solubles, triptofano, almidon, azucares y fibras) en la harina de ocho hibridos de maiz de especialidad del Instituto de Investigacion del Maiz Zemun Polje (ZP): dos dulces, reventon, rojo, blanco, ceroso, amarillo semivitreo y amarillo dentado. Se determinaron, ademas, la digestibilidad de la materia seca del grano y la viscosidad de la harina. El valor nutritivo mas alto se registro en los hibridos dulces ZP 504su y ZP 531su, que presentaron el mayor contenido de proteinas totales, albumina, triptofano, azucares y fibras. Ademas, su bajo contenido de almidon (55,32% y 54,59%, respectivamente) y lignina (0,39% y 0,45%), afecto a la mayor digestibilidad de la materia seca (92,69% y 91,07%) de la harina de estos hibridos. Sin embargo, sus propiedades funcionales no fueron satisfactorias para la alimentacion y usos industriales. Por el contrario, la harina de maiz hibrido ZP ceroso se caracterizo por una alta viscosidad. Segun el contenido de sacarosa, los hibridos podrian ser clasificados en tres grupos: a) > 4% (ZP 504su, ZP Rumenka), b) 3-4% (ZP 704wx, ZP 434, ZP 633) y c) 2-3% (ZP 531su, ZP 74b, ZP 611k). La fraccion proteica dominante en todos los genotipos fue la �¿-zeina, excepto en los hibridos dulces, donde constituyen el 22,45-29,25% del contenido total de proteinas

Modified Method for Reliability Evaluation of Condensation Thermal Electric Power Plant

Abstract Present methods for forecasting and evaluation of thermal power plants reliability were based on appliance of statistics and probability calcu lation related to strength and in the same time lean ing on modern methods for deterministic project-constructive calculations of elements, subsystems and systems. Applying the advantages of modern directions in system reengineering and structural or RCM (Reliability Centered Maintenance) way of using the best methods in reliability analysis of complex systems, the block diagram of mod ified method for basis referential 300 MW block has been created. As a starting database, the results of research of basic configurations of thermal power p lants for solid fuel "Ug ljev ik" and "Gacko" with nominal referential power of 300 MW were used. For other facilities inside thermal power p lants witch no minal power differs fro m 300 MW, recalcu lation of reliability indicators has to be carried out. Whereat the simple emp irical relation in dependence of previously determined reliability indicator for 300 MW system is used so as the exponent determined on basis of statistical data processing from the exp loitation during the lifespan of the power plant. The method is of the iterative nature and is about to be terminated as the starting hypothesis related to matching of results of the forecasting and real exploitation results affirms. The research related for suggested modified method gave several relat ively new results which are presented inside the paper. The result represents the algorithm of modified method for evaluation of reliability of referential thermal power plant system and its modificat ion aiming to include thermal power plants of other nominal powers

The simultaneous role of an alveolus as flow mixer and flow feeder for the deposition of inhaled submicron particles

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps' dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus. © 2012 American Society of Mechanical Engineers

From state-of-the-art cell therapy to endogenous cardiac repair

Clinical heart failure prevention and contemporary therapy often involve breaking the vicious cycle of global haemodynamic consequences of myocardial decay. The lack of effective regenerative therapies results in a primary focus on preventing further deterioration of cardiac performance. The cellular transplantation hypothesis has been evaluated in many different preclinical models and a handful of important clinical trials. The primary expectation that cellular transplants will be embedded into failing myocardium and fuse with existing functioning cells appears unlikely. A multitude of cellular formulas, access routes and clinical surrogate endpoints for evaluation add to the complexity of cellular therapies. Several recent large clinical trials have provided insights into both the regenerative potential and clinical improvement from non-regenerative mechanisms. Initiating endogenous repair seems to be another meaningful alternative to recover structural integrity in myocardial injury. This option may be achieved using a transcoronary sinus catheter intervention, implying the understanding of basic principles in biology. With intermittent reduction of outflow in cardiac veins (PICSO), vascular cells appear to be activated and restart a programme similar to pathways in the developing heart. Structural regeneration may be possible without requiring exogenous agents, or a combination of both approaches may become clinical reality in the next decade

The simultaneous role of an alveolus as flow mixer and flow feeder for the deposition of inhaled submicron particles

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps' dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus