Ribonucleoparticle-independent transport of proteins into mammalian microsomes

There are at least two different mechanisms for the transport of secretory proteins into the mammalian endoplasmic reticulum. Both mechanisms depend on the presence of a signal peptide on the respective precursor protein and involve a signal peptide receptor on the cis-side and signal peptidase on the trans-side of the membrane. Furthermore, both mechanisms involve a membrane component with a cytoplasmically exposed sulfhydryl. The decisive feature of the precursor protein with respect to which of the two mechanisms is used is the chain length of the polypeptide. The critical size seems to be around 70 amino acid residues (including the signal peptide). The one mechanism is used by precursor proteins larger than about 70 amino acid residues and involves two cytosolic ribonucleoparticles and their receptors on the microsomal surface. The other one is used by small precursor proteins and relies on the mature part within the precursor molecule and a cytosolic ATPase

Inflammation mitigation improves post-infarction functional recovery of the heart

Aim The in vitro evaluation of the cardiac functional effects of TNF-α antagonist administration in rats after isoproterenol induced myocardial infarction. Material and methods Myocardial infarction was reproduced using a proven model based on isoproterenol i/p administration in rats in 2 consecutive days in a similar dose, 150 mg/kg. In another group the animals after isoproterenol induced myocardial infarction (series IMI) have received daily TNF-α antagonist, a specific monoclonal antibody (ma-TNF-α) i/p in dose of 50 mg/kg during 8 days (series IMI+ma-TNF-α). In both series the animals were sacrificed after 10 days from the 1st injection and their isolated hearts ware perfused with Krebs solution according to Langendorff and Neely-Rovetto models. Results The most remarkable traits of left ventricle dysfunction in IMI in comparison to control were following: (1) diminution of cardiac output (CO), systolic pressure (SP) and +dP/dT max by respectively 28,7 and 34,7 and 23,3%; (2) negative inotropic effect to action of endothelin-1 manifested by decrease of SP and aortic jet during stimulation up to 13,9%; (3) increased cardiac arrhythmogenic activity in response to calcium overload; (4) increasing by 45,2% of ischemia induced contracture as well as decreasing by 37,5% of SP during reperfusion. The ma-TNF-α administration in post-infarction period led to noticeable benefits such as: significant enhancement of SP and CO respectively by 17,3 and 18,6% as well as positive inotropic effect developing to ET-1 action as well as significant increase of time regarding the appearance of ventricular extrasystole and ventricular tachyarrhythmia by respectively 12,9 and 11,7% as well as perceptible improvement of ischemia-reperfusion syndrome. Conclusion A sustained inflammation inhibition by ma-TNF-α administration in post-infarction period improves tangibly the cardiac functioning that proves the role of inflammatory response in myocardial infarction induced functional and structural myocardial remodeling and underlines the inflammation as a therapeutic target

Extracellular RNA – a new predictor and a supposable mechanism of in-stent restenosis

Department of Interventional Cardiology, Institute of Cardiology, Chisinau, the Republic of MoldovaBackground: The evaluation of new predictors of negative coronary remodeling after angioplasty remains an adequate approach of interventional cardiology in the diagnosis and prognosis of in-stent restenosis (ISR). Previously we have demonstrated on a murine model of atherosclerosis that extracellular RNA (eRNA) increases proportionally to vascular injury progression, and a first activation of the blood RNAase is changed by its steady quantitative decline, a reason that suggests a plausible role of eRNA in coronary neointima hyperplasia. Material and methods: This article is aimed at the study of eRNA amount in a tissue pattern of a stent with restenosis as well as its correlation with such inflammatory predictors as macrophage number and TNF-alpha expression. Using the techniques of confocal microscopy and immunohistochemistry we have first proved that eRNA level significantly increases in the coronary wall of segments with ISR (the specimens have been taken postmortem from 19 patients exposed to angioplasty). Results: The rise in the assay has been closely correlated to restenosis degree, and in muscular media it has been 2-4 times beyond the control range estimated in the adjacent coronary segment without negative vascular remodeling. In the restenosis zone eRNA has risen by about 130% from minimal to severe ISR. Moreover, its level has been found markedly increased earlier also comparatively to the control pattern: by 62% in moderate and 128% in severe ISR. A key disclosed evidence is that eRNA is positively correlated with TNF-alpha level (r = +0.88) and the number of macrophages (r = +0.84), whereas the last is notably enhanced depending on ISR progression. Conclusions: The obtained outcomes result in 2 opportunities: 1. eRNA may be a feasible predictor of negative coronary remodeling, facilitating the prognosis of ISR risk; 2. eRNA may be singled out as a factor involved in the pathogenesis of neointima formation and hyperplasia due to its relation to the inflammatory process

The extracellular matrix collagen in the coronary in-stent restenosis

Department of Interventional Cardiology, Institute of Cardiology, Chisinau, the Republic of MoldovaBackground: Extracellular matrix is underlined as an important factor regulating morphofunctional integrity of vascular wall, and is actively involved in vascular remodeling. Although collagen turnover activation is supported in mechanical artery injury, its character remains still unknown in the in-stent restenosis (ISR). The aim of this study is to evaluate the change of collagen type I and type III metabolism and metalloproteinase-2 (MMP2) expression in ISR. Material and methods: Using the confocal microscopy and immunochemistry techniques, the expression of collagen I and III, the markers of collagen I synthesis and degradation (PICP and CITP), as well as the expression of MMP2 and its tissue inhibitor (TIMMP2) have been assayed in the tissue pattern of ISR taken from 19 died patients. In 24 patients with ISR the markers of collagen I turnover were determined in blood also and compared with markers of 11 healthy persons. Results: The collagen I degradation is markedly increased in ISR and prevails over its synthesis while the collagen III degradation is enough preserved that led to collagen III/I ratio raising by 4-7 times already in minimal ISR. The CITP value is progressively increasing during restenosis exacerbation that is associated with a similar decline of PICP resulted consequently in a 7-10 fold elevation of the CITP/PICP ratio in muscular media of restenosis. Importantly to note that analogous changes of collagen type I turnover markers are established in blood in patients with ISR: PINP decreasing by 53.32% and CITP rise by 187.6%. The collagen I metabolism modification was accompanied by multiply MMP2 quantity increase and TIMPP2 diminution. Conclusions: 1. Extracellular matrix reorganization is a hallmark of the in-stent restenosis basically being exhibited by excessive collagen I degradation and preserved collagen III, splitting in conditions of MMP2/TIMMP2 ratio raising proportionally to ISR degree. 2. The shift of the circulating markers of collagen I turnover (PINP and CITP) is near to marker dynamics estimated in restenosis tissue that suggests their diagnostic and predictive role concerning ISR evolution

Diagnostic and prognostic value of neopterin and RNA-ase in patients with STEMI and NSTEMI

Background Neopterin and RNA-ase are markers of inflammation with low disclosed role in diagnosis and prognosis of either STEMI or NSTEMI, although inflammation is well documented as a leader pathogenic mechanism in these pathologies. Aim Evaluation of serum admission levels of neopterin and ARN-ase in pts with STEMI and NSTEMI and their prediction value concerning the risk of MACE in 1 year of follow up period. Material and methods The admission serum concentration of neopterin and ARN-ase was determined by ELISA in 94 pts with STEMI and 92 pts with NSTEMI which was compared with normal markers appreciated in 32 healthy persons. Likewise, the rate of MACE in both groups was estimated during 1 year of post-infarction period. Diagnostic worth and MACE prediction power of markers have been established using respectively ROC curve and odds ratio. Results In patients with STEMI the serum level of neopterin was significantly increased compared with normal index by 3,5 times (11,6±3,4 vs 3,3±1,4 nM/L), but RNA-ase was significantly decreased by 43,4% (24,1±3,2 vs 42,6±5,2 nM/ml). In pts with NSTEMI neopterin level was lesser than STEMI, but significantly elevated by 39% (4,6±2,5 vs 3,3±1,4 nM/L) vs normal marker. RNA-ase level didn't significantly differ from normal level. However, adjusted to diabetes mellitus established in 19 pts, RNA-ase significantly diminished (36,4±3,9 vs 42,6±5,2 nM/ml), and its diagnostic value of NSTEMI according to ROC was 69,6% (RNA-ase level indicates inversely inflammation response, such as it breaks down extracellular RNA which has proinflammatory ability). Both markers in pts with NSTEMI and diabetes mellitus demonstrated a diagnostic value of 77,6%. In pts with STEMI highest tertile level of neopterin and lowest tertile level of ARN-ase had 2,8fold (adds ratio=2,8; CI=1,98–4,62; p<0,05) and 2,3fold (adds ratio=2,3; CI=1,71–3,89; p<0,05) higher risk of MACE development. In pts with NSTEMI the combination of these markers (highest and lowest quartile levels) also had a significant prediction regarding MACE risk (adds ratio=2,1; CI=1,86–3,77; p=0,029). Conclusions 1. In STEMI both neopterin and RNA-ase could be as diagnostic markers, due to their significant change. In NSTEMI neopterin significantly elevated, but RNA-ase didn't shift from normal. In diabetic pts with NSTEMI, however, their combination demonstrated in ROC estimation a diagnostic value of 77,6%. 2. Prediction value of markers combination regarding MACE risk in pts with NSTEMI is significant and close to each marker in partly prediction of MACE for pts with STEMI. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Research Institute of Cardiology, Moldova Republic o

Early and late changes of multi-marker panel in patients with STEMI after angioplasty

Background: Post-infarction remodeling is strongly linked with collagen turnover which is influenced mostly by oxidative stress and inflammation, the last being, according to our previous data, triggered by early infiltrated neutrophils (24–48 h) followed by accumulation of macrophages M1 (72 h) and M2 (7–14 days). Aim: Evaluation of circulating markers of inflammation and oxidative stress in the different periods of 1 year follow up post-infarct evolution: first 2 weeks (each day), 1st month (synthesis of collagen type III), 3rd month (synthesis of collagen type I), 6 and 12 months. Material and methods: Study was performed in 47 patients (age range of 37–68 years) with STEMI exposed to angioplasty (<12 hours). Circulating levels of 28 markers were determined at admission, 1, 2, 3 ... 14 days, 1, 3, 6 and 12 months. Obtained results were compared with control value of markers determined in 17 apparently healthy persons and admission level (before PCI). Results: The earliest (first 24 h) significant change was inherent to MMP-8, whose double elevation (averagely from 3,1 up to 6,4 ng/ml) corresponded to period of neutrophil infiltration (24–48 h). Serum levels of IL-1, IL-6 have raised significantly since 48 h, followed by authentic increase of TNF-alpha, IL-8, CRPhs and phospholipase A2 since 72 h. Up to a period of 7 days these markers remained increased, but toward 14th day fell by 24–46% arguably due to macrophage M2 activation. This is consistent to dynamics of anti-inflammatory markers, IL-4 and IL-10 which decreased till 7th, elevated toward 14th day although remained below control. Inflammation boosting was associated by oxidative stress activation during 1st week manifested by malonic dialdehyde (MAD) rise and total antioxidant activity fall. To be noted that markers improvement till 3rd month was poor and a conspicuous dynamics began since 6th month with nearing to control level toward 12th month. However, at this time following markers significantly differed from control value: TNF-alpha (+29,6%), IL-4 (-31,7%), S-nitrosothiols (-17,8%), CRPhs exceeded 3,0 g/L (4,77±0,38) and MAD (+23,6%). Conclusions: (1). Dynamics of inflammation markers in patients with STEMI during first 14 days after angioplasty conclusive reflect chronologic accumulation of inflammatory cells in necrotic zone. (2). Maximal serum plateau of MMP-8, IL-1, IL-6, IL-6, TNF-alpha and CRPhs goes till 7th day of post-infarct evolution, associated with lowest IL-4 and IL-10. (3). Marker improvements begin since 3rd month with nearing to control toward 12th month, excepting IL-4, TNF-alpha, CRPhs and MAD indicating thus a late statement of inflammation dissemination

K-Space at TRECVID 2008

In this paper we describe K-Space’s participation in TRECVid 2008 in the interactive search task. For 2008 the K-Space group performed one of the largest interactive video information retrieval experiments conducted in a laboratory setting. We had three institutions participating in a multi-site multi-system experiment. In total 36 users participated, 12 each from Dublin City University (DCU, Ireland), University of Glasgow (GU, Scotland) and Centrum Wiskunde and Informatica (CWI, the Netherlands). Three user interfaces were developed, two from DCU which were also used in 2007 as well as an interface from GU. All interfaces leveraged the same search service. Using a latin squares arrangement, each user conducted 12 topics, leading in total to 6 runs per site, 18 in total. We officially submitted for evaluation 3 of these runs to NIST with an additional expert run using a 4th system. Our submitted runs performed around the median. In this paper we will present an overview of the search system utilized, the experimental setup and a preliminary analysis of our results

Layered gallium sulfide optical properties from monolayer to CVD crystalline thin films

Interest in layered van der Waals semiconductor gallium monosulfide (GaS) is growing rapidly because of its wide band gap value between those of two-dimensional transition metal dichalcogenides and of insulating layered materials such as hexagonal boron nitride. For the design of envisaged optoelectronic, photocatalytic and photonic applications of GaS, the knowledge of its dielectric function is fundamental. Here we present a combined theoretical and experimental investigation of the dielectric function of crystalline 2H-GaS from monolayer to bulk. Spectroscopic imaging ellipsometry with micron resolution measurements are corroborated by first principle calculations of the electronic structure and dielectric function. We further demonstrate and validate the applicability of the established dielectric function to the analysis of the optical response of c-axis oriented GaS layers grown by chemical vapor deposition (CVD). These optical results can guide the design of novel, to our knowledge, optoelectronic and photonic devices based on low-dimensional GaS.Horizon 2020 Framework Programme (No 899598 – PHEMTRONICS)

Interlaboratory study on Sb2S3 interplay between structure, dielectric function, and morphous-to-crystalline phase change for photonics

Antimony sulfide, Sb2S3, is interesting as the phase-change material for applications requiring high transmission from the visible to telecom wavelengths, with its band gap tunable from 2.2 to 1.6 eV, depending on the amorphous and crystalline phase. Here we present results from an interlaboratory study on the interplay between the structural change and resulting optical contrast during the amorphous-to-crystalline transformation triggered both thermally and optically. By statistical analysis of Raman and ellipsometric spectroscopic data, we have identified two regimes of crystallization, namely 250_C % T < 300_C, resulting in Type-I spherulitic crystallization yielding an optical contrast Dn _ 0.4, and 300 % T < 350 _ C, yielding Type-II crystallization bended spherulitic structure with different dielectric function and optical contrast Dn _ 0.2 below 1.5 eV. Based on our findings, applications of on-chip reconfigurable nanophotonic phase modulators and of a reconfigurable high-refractive-index core/phase-change shell nanoantenna are designed and proposed.The authors acknowledge the support from the European Union’s Horizon 2020 research and innovation program (No 899598 - PHEMTRONICS)