Arrhythmia Mechanism and Scaling Effect on the Spectral Properties of Electroanatomical Maps with Manifold Harmonics

[EN] Introduction: Spatial and temporal processing of intracardiac electrograms provides relevant information to support the arrhythmia ablation during electrophysio-logical studies. Current cardiac navigation systems (CNS) and electrocardiographic imaging (ECGI) build detailed 3-D electroanatomical maps (EAM), which represent the spatial anatomical distribution of bioelectrical features, such as activation time or voltage. Objective: We present a principled methodology for spectral analysis of both EAM geometry and bioelectrical feature in CNS or ECGI, including their spectral representation, cutoff frequency, or spatial sampling rate (SSR). Methods: Existing manifold harmonic techniques for spectral mesh analysis are adapted to account for a fourth dimension, corresponding to the EAM bioelectrical feature. Appropriate scaling is required to address different magnitudes and units. Results: With our approach, simulated and real EAM showed strong SSR dependence on both the arrhythmia mechanism and the cardiac anatomical shape. For instance, high frequencies increased significantly the SSR because of the "early-meets-late" in flutter EAM, compared with the sinus rhythm. Besides, higher frequency components were obtained for the left atrium (more complex anatomy) than for the right atrium in sinus rhythm. Conclusion: The proposed manifold harmonics methodology opens the field toward new signal processing tools for principled EAM spatiofeature analysis in CNS and ECGI, and to an improved knowledge on arrhythmia mechanisms.This work was partly supported by Spanish Research Projects TEC2013-48439-C4-1-R, TEC2016-75361-R, and TEC2016-75161-C2-1-4.Sanroman-Junquera, M.; Mora-Jimenez, I.; Garcia-Alberola, A.; Caamano, AJ.; Trénor Gomis, BA.; Rojo-Alvarez, JL. (2018). Arrhythmia Mechanism and Scaling Effect on the Spectral Properties of Electroanatomical Maps with Manifold Harmonics. IEEE Transactions on Biomedical Engineering (Online). 65(4):723-732. https://doi.org/10.1109/TBME.2017.2716189S72373265

Potential ecological and socio-economic effects of a novel megaherbivore introduction: the hippopotamus in Colombia

Introduced species can have strong ecological, social and economic effects on their non-native environment. Introductions of megafaunal species are rare and may contribute to rewilding efforts, but they may also have pronounced socio-ecological effects because of their scale of influence. A recent introduction of the hippopotamus Hippopotamus amphibius into Colombia is a novel introduction of a megaherbivore onto a new continent, and raises questions about the future dynamics of the socio-ecological system into which it has been introduced. Here we synthesize current knowledge about the Colombian hippopotamus population, review the literature on the species to predict potential ecological and socio-economic effects of this introduction, and make recommendations for future study. Hippopotamuses can have high population growth rates (7–11%) and, on the current trajectory, we predict there could be 400–800 individuals in Colombia by 2050. The hippopotamus is an ecosystem engineer that can have profound effects on terrestrial and aquatic environments and could therefore affect the native biodiversity of the Magdalena River basin. Hippopotamuses are also aggressive and may pose a threat to the many inhabitants of the region who rely upon the Magdalena River for their livelihoods, although the species could provide economic benefits through tourism. Further research is needed to quantify the current and future size and distribution of this hippopotamus population and to predict the likely ecological, social and economic effects. This knowledge must be balanced with consideration of social and cultural concerns to develop appropriate management strategies for this novel introduction

Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes

Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid β precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1, that bind the NFE2L2-regulated enhancer antioxidant response element (ARE). Using a script generated from the JASPAR's consensus ARE sequence, we identified 27 putative AREs in 16 autophagy-related genes. Twelve of these sequences were validated as NFE2L2 regulated AREs in 9 autophagy genes by additional ChIP assays and quantitative RT-PCR on human and mouse cells after NFE2L2 activation with sulforaphane. Mouse embryo fibroblasts of nfe2l2-knockout mice exhibited reduced expression of autophagy genes, which was rescued by an NFE2L2 expressing lentivirus, and impaired autophagy flux when exposed to hydrogen peroxide. NFE2L2-deficient mice co-expressing HsAPP(V717I) and HsMAPT(P301L), exhibited more intracellular aggregates of these proteins and reduced neuronal levels of SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5 and GABARAPL1. Also, colocalization of HsAPP(V717I) and HsMAPT(P301L) with the NFE2L2-regulated autophagy marker SQSTM1/p62 was reduced in the absence of NFE2L2. In AD patients, neurons expressing high levels of APP or MAPT also expressed SQSTM1/p62 and nuclear NFE2L2, suggesting their attempt to degrade intraneuronal aggregates through autophagy. This study shows that NFE2L2 modulates autophagy gene expression and suggests a new strategy to combat proteinopathies

The Mitochondrial Contribution to Animal Performance, Adaptation, and Life-History Variation

We thank the National Science Foundation (grant IOS1738378 to W.R.H. and K.S.), SICB’s division of Comparative Physiology and Biochemistry and Comparative Endocrinology, the Company of Biologists, the Society of Experimental Biology, and the Canadian Society of Zoology for funding the symposium.  Peer reviewedPostprin

Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications

<p>Abstract</p> <p>Background</p> <p>Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity.</p> <p>Results</p> <p>We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells.</p> <p>Conclusions</p> <p>Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.</p

Spanish multicenter real – life registry of retrievable vena cava filters (REFiVeC)

Background The treatment of venous thromboembolic disease the treatment of choice is systemic anticoagulation. However, the interruption of the inferior vena cava with filters has been recommended when anticoagulation fails or there is a contraindication. Due to the rising inferior vena cava filter (IVCF) complications, physicians are encouraged to retrieve them when there is no longer recommended. In daily practice, it may be a difficult close follow-up of these patients. In this study, the primary objective was to evaluate the IVCF retrieval rate of all implanted filters in a Spanish registry. Secondary objectives were to analyze the causes of failed retrieval, procedure-related complications, and outcomes at a 12-month follow-up. Results Three hundred fifty-six vena cava filters were implanted in 355 patients. The types of filter were: Gunther Tulip (Cook Medical) 160 (44.9%), Optease (Cordis) 77 (21.6%), Celect (Cook Medical) 49 (13, 7%), Aegisy (Lifetech Scientific) 33 (9.2%), Option ELITE (Argon Medical devices) 16 (4.4%), Denali filter (BD Bard) 11 (3.08%), ALN filter (ALN) 10 (2.8%). Removal was achieved in 274/356 (76,9%). eighty-two (23,1%) IVCF were not retrieved due to the following: 41 (11,5%) patients required ongoing filtration, 24 IVCF (6,7%) patients died before retrieval, and 17 (4,7%) impossibility of retrieval because of a tilted and embedded filter apex. There were no major complications observed. Conclusions The global retrieval rate of IVCF was achieved in 76.9%, and the adjusted retrieval rate was of 94.15% with no major complications. IVCF tilting was associated with failure of filter removal in less than 5% of cases. This study demonstrates that the retrieval procedure of IVCF is controlled by the clinician and not by the interventional radiologist

PICALM modulates autophagy activity and tau accumulation.

Genome-wide association studies have identified several loci associated with Alzheimer's disease (AD), including proteins involved in endocytic trafficking such as PICALM/CALM (phosphatidylinositol binding clathrin assembly protein). It is unclear how these loci may contribute to AD pathology. Here we show that CALM modulates autophagy and alters clearance of tau, a protein which is a known autophagy substrate and which is causatively linked to AD, both in vitro and in vivo. Furthermore, altered CALM expression exacerbates tau-mediated toxicity in zebrafish transgenic models. CALM influences autophagy by regulating the endocytosis of SNAREs, such as VAMP2, VAMP3 and VAMP8, which have diverse effects on different stages of the autophagy pathway, from autophagosome formation to autophagosome degradation. This study suggests that the AD genetic risk factor CALM modulates autophagy, and this may affect disease in a number of ways including modulation of tau turnover.We are grateful for funding from a Wellcome Trust Principal Research Fellowship (D.C.R.), a Wellcome Trust/MRC Strategic Grant on Neurodegeneration (D.C.R., C.J.O’.K.), a Wellcome Trust Strategic Award to Cambridge Institute for Medical Research, Wellcome Trust Studentship (E.Z.), the Alzheimer’s disease Biomedical Research Unit and Addenbrooke’s Hospital, the Tau Consortium, a fellowship from University of Granada (A.L.R.), a V Foundation/Applebee’s Research Grant (D.S.W.) and NCI R01 CA 109281 (D.S.W.).This is the final published version. It is also available from Nature Publishing at http://www.nature.com/ncomms/2014/140922/ncomms5998/full/ncomms5998.html

Dynamic Edematous Response of the Human Heart to Myocardial Infarction Implications for Assessing Myocardial Area at Risk and Salvage

BACKGROUND: Clinical protocols aimed to characterize the post-myocardial infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized to take account of dynamic biological phenomena evolving early after the index ischemic event. Here, we evaluated the time course of edema reaction in patients with ST-segment-elevation MI by CMR and assessed its implications for myocardium-at-risk (MaR) quantification both in patients and in a large-animal model. METHODS: A total of 16 patients with anterior ST-segment-elevation MI successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR examinations were performed: patients with ST-segment-elevation MI were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were evaluated at all time points. In the experimental study, 20 pigs underwent 40-minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography during the index coronary occlusion. Generalized linear mixed models were used to take account of repeated measurements. RESULTS: In humans, T2 relaxation time in the ischemic myocardium declines significantly from early after reperfusion to 24 hours, and then increases up to day 4, reaching a plateau from which it decreases from day 7. Consequently, edema extent measured by T2-weighted short-tau triple inversion-recovery (CMR-MaR) varied with the timing of the CMR examination. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were similar to values measured by reference contrast-multidetector computed tomography. CONCLUSIONS: Post-MI edema in patients follows a bimodal pattern that affects CMR estimates of MaR. Dynamic changes in post-ST-segment-elevation MI edema highlight the need for standardization of CMR timing to retrospectively delineate MaR and quantify myocardial salvage. According to the present clinical and experimental data, a time window between days 4 and 7 post-MI seems a good compromise solution for standardization. Further studies are needed to study the effect of other factors on these variables.This study was partially supported by a competitive grant from the Spanish Society of Cardiology (Proyectos de Investigacion Traslacional en Cardiologia de la Sociedad Espanola de Cardiologia 2015, for the project Caracterizacion tiSUlar miocaRdica con resonancia magnetica en pacientes tras inFarto agudo de mioCardio con elevacioN de ST sometidos a angloplastia Coronaria primaria. Estudio SURF-CNIC), by a competitive grant from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria- and the European Regional Development Fund (ERDF/FEDER) (PI10/02268 and PI13/01979), the Spanish Ministry of economy, industry, and competitiveness (MEIC) and ERDF/FEDER SAF2013-49663-EXP. Dr Fernandez-Jimenez holds a FICNIC fellowship from the Fundacio Jesus Serra, the Fundacion Interhospitalaria de Investigacion Cardiovascular, and the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), and Dr Aguero is a FP7-PEOPLE-2013-ITN-Cardionext fellow. This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare, and is part of a bilateral research program between Hospital de Salamanca Cardiology Department and the CNIC. This research program is part of an institutional agreement between FIIS-Fundacion Jimenez Diaz and CNIC. The CNIC is supported by the MEIC and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505).S

Excitons in a Photosynthetic Light-Harvesting System: A Combined Molecular Dynamics/Quantum Chemistry and Polaron Model Study

The dynamics of pigment-pigment and pigment-protein interactions in light-harvesting complexes is studied with a novel approach which combines molecular dynamics (MD) simulations with quantum chemistry (QC) calculations. The MD simulations of an LH-II complex, solvated and embedded in a lipid bilayer at physiological conditions (with total system size of 87,055 atoms) revealed a pathway of a water molecule into the B800 binding site, as well as increased dimerization within the B850 BChl ring, as compared to the dimerization found for the crystal structure. The fluctuations of pigment (B850 BChl) excitation energies, as a function of time, were determined via ab initio QC calculations based on the geometries that emerged from the MD simulations. From the results of these calculations we constructed a time-dependent Hamiltonian of the B850 exciton system from which we determined the linear absorption spectrum. Finally, a polaron model is introduced to describe quantum mechanically both the excitonic and vibrational (phonon) degrees of freedom. The exciton-phonon coupling that enters into the polaron model, and the corresponding phonon spectral function are derived from the MD/QC simulations. It is demonstrated that, in the framework of the polaron model, the absorption spectrum of the B850 excitons can be calculated from the autocorrelation function of the excitation energies of individual BChls, which is readily available from the combined MD/QC simulations. The obtained result is in good agreement with the experimentally measured absorption spectrum.Comment: REVTeX3.1, 23 pages, 13 (EPS) figures included. A high quality PDF file of the paper is available at http://www.ks.uiuc.edu/Publications/Papers/PDF/DAMJ2001/DAMJ2001.pd