Iron Deposition following Chronic Myocardial Infarction as a Substrate for Cardiac Electrical Anomalies: Initial Findings in a Canine Model

Purpose: Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. Methods: Two groups of dogs (ex-vivo (n = 12) and in-vivo (n = 10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity () and conductivity (). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n = 5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs). Results: Compared to IRON- sections, IRON+ sections had higher, but no difference in. A linear relationship was found between iron content and (p1.5%)) with similar scar volumes (7.28%±1.02% (Iron (1.5%)), p = 0.51) but markedly different iron volumes (1.12%±0.64% (Iron (1.5%)), p = 0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. Conclusion: The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may evolve as an arrhythmogenic substrate in the post MI period

Development of Diagnostic SCAR Markers for Genomic DNA Amplifications in Breast Carcinoma by DNA Cloning of High-GC RAMP-PCR Fragments

Cancer is genetically heterogeneous regarding to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers, including DNA markers, is used in determining genomic instability, molecular subtype determination and disease prognosis, and estimating sensitivity to different drugs in clinical practice. In a previous study, we developed highly effective DNA markers using improved random amplified polymorphic DNA (RAPD) with high-GC primers, which is a valuable approach for the genetic authentication of medicinal plants. In this study, we applied this effective DNA marker technique to generate genetic fingerprints that detect genomic alterations in human breast cancer tissues and then developed sequence-characterized amplified region (SCAR) markers. Three SCAR markers (BC10-1, BC13-4 and BC31-2) had high levels of genomic DNA amplification in breast cancer. The PHKG2 and RNF40 genes are either overlapping or close to the sequences of SCAR marker BC13-4, while SCAR marker BC10-1 is in the intron and overlap the DPEP1 gene, suggesting that alterations in the expression of these genes could contribute to cancer progression. Screening of breast cancer cell lines showed that the mRNA expression levels for the PHKG2 and DPEP1 were lower in non-tumorigenic mammary epithelial cell MCF10A, but elevated in other cell lines. The DPEP1 mRNA level in invasive ductal carcinoma specimens was significantly higher than that of the adjacent normal tissues in women. Taken together, high-GC RAMP-PCR provides greater efficacy in measuring genomic DNA amplifications, deletion or copy number variations. Furthermore, SCAR markers BC10-1 and BC13-4 might be useful diagnostic markers for breast cancer carcinomas

Kinetics of Intramolecular Chemical Exchange by Initial Growth Rates of Spin Saturation Transfer Difference Experiments (SSTD NMR)

We report here the Initial Growth Rates SSTD NMR method, as a new powerful tool to obtain the kinetic parameters of intramolecular chemical exchange in challenging small organic and organometallic molecules

Understanding signaling cascades in melanoma

Understanding regulatory pathways involved in melanoma development and progression has advanced significantly in recent years. It is now appreciated that melanoma is the result of complex changes in multiple signaling pathways that affect growth control, metabolism, motility and the ability to escape cell death programs. Here we review the major signaling pathways currently known to be deregulated in melanoma with an implication to its development and progression. Among these pathways are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase (PI3Ks) and Akt which are constitutively activated in a significant number of melanoma tumors, in most cases due to genomic change. Other pathways discussed in this review include the [Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-beta pathways which are also activated in melanoma, although the underlying mechanism is not yet clear. As a paradigm for remodeled signaling pathways, melanoma also offers a unique opportunity for targeted drug development.Fil: Lopez Bergami, Pablo Roberto. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fitchmann, B. Sanford-burnham Medical Research Institute; Estados UnidosFil: Ronai, Ze´ev. Sanford-burnham Medical Research Institute; Estados Unido

High-precision multi-band measurements of the angular clustering of X-ray sources

In this paper we present the two-point angular correlation function of the X-ray source population of 1063 XMM-Newton observations at high Galactic latitudes, comprising up to ~30000 sources over a sky area of 125.5 sq. deg, in three energy bands: 0.5-2 (soft), 2-10 (hard), and 4.5-10 (ultrahard) keV. We have measured the angular clustering of our survey and find significant positive clustering signals in the soft and hard bands, and a marginal clustering detection in the ultrahard band. We find dependency of the clustering strength on the flux limit and no significant differences in the clustering properties between sources with high hardness ratios and those with low hardness ratios. Our results show that obscured and unobscured objects share similar clustering properties and therefore they both reside in similar environments, in agreement with the unified model of AGN. We deprojected the angular clustering parameters via Limber's equation to compute their typical spatial lengths. From that we have inferred the typical mass of the dark matter haloes in which AGN at redshifts of ~1 are embedded. The short AGN lifetimes derived suggest that AGN activity might be a transient phase that can be experienced several times by a large fraction of galaxies throughout their lives.Comment: 14 pages, 9 figures, accepted for publication in Astronomy and Astrophysic

Could the Recent Zika Epidemic Have Been Predicted?

Given knowledge at the time, the recent 2015–2016 zika virus (ZIKV) epidemic probably could not have been predicted. Without the prior knowledge of ZIKV being already present in South America, and given the lack of understanding of key epidemiologic processes and long-term records of ZIKV cases in the continent, the best related prediction could be carried out for the potential risk of a generic Aedes-borne disease epidemic. Here we use a recently published two-vector basic reproduction number model to assess the predictability of the conditions conducive to epidemics of diseases like zika, chikungunya, or dengue, transmitted by the independent or concurrent presence of Aedes aegypti and Aedes albopictus. We compare the potential risk of transmission forcing the model with the observed climate and with state-of-the-art operational forecasts from the North American Multi Model Ensemble (NMME), finding that the predictive skill of this new seasonal forecast system is highest for multiple countries in Latin America and the Caribbean during the December-February and March-May seasons, and slightly lower—but still of potential use to decision-makers—for the rest of the year. In particular, we find that above-normal suitable conditions for the occurrence of the zika epidemic at the beginning of 2015 could have been successfully predicted at least 1 month in advance for several zika hotspots, and in particular for Northeast Brazil: the heart of the epidemic. Nonetheless, the initiation and spread of an epidemic depends on the effect of multiple factors beyond climate conditions, and thus this type of approach must be considered as a guide and not as a formal predictive tool of vector-borne epidemics

Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate.

Compliance mismatch is a significant challenge to long-term patency in small-diameter bypass grafts because it causes intimal hyperplasia and ultimately graft occlusion. Current engineered grafts are typically stiff with high burst pressure but low compliance and low elastin expression. We postulated that engineering small arteries on elastomeric scaffolds under dynamic mechanical stimulation would result in strong and compliant arterial constructs. This study compares properties of engineered arterial constructs based on biodegradable polyester scaffolds composed of either rigid poly(lactide-co-glycolide) (PLGA) or elastomeric poly(glycerol sebacate) (PGS). Adult baboon arterial smooth muscle cells (SMCs) were cultured in vitro for 10 days in tubular, porous scaffolds. Scaffolds were significantly stronger after culture regardless of material, but the elastic modulus of PLGA constructs was an order of magnitude greater than that of porcine carotid arteries and PGS constructs. Deformation was elastic in PGS constructs and carotid arteries but plastic in PLGA constructs. Compliance of arteries and PGS constructs were equivalent at pressures tested. Altering scaffold material from PLGA to PGS significantly decreased collagen content and significantly increased insoluble elastin content in constructs without affecting soluble elastin concentration in the culture medium. PLGA constructs contained no appreciable insoluble elastin. This research demonstrates that: (1) substrate stiffness directly affects in vitro tissue development and mechanical properties; (2) rigid materials likely inhibit elastin incorporation into the extracellular matrix of engineered arterial tissues; and (3) grafts with physiologic compliance and significant elastin content can be engineered in vitro after only days of cell culture

An Evolutionary Sequence of Expanding Hydrogen Shells in Galaxy Discs

Large HI shells, with diameters of hundreds of pc and expansion velocities of 10-20kms-1 are well observed features of local gas rich galaxies. These shells could well be predicted as a result of the impact of OB associations on the ISM, but doubt has been cast on this scenario by the apparent absence of OB stars close to the centres of a large fraction of these shells in recent observations of the SMC. Using Fabry-Perot scanned Halpha emission line mapping of nearby galaxy discs we have detected, in all the HII regions where the observations yield sufficient angular resolution and S:N ratio, dominant Halpha shells with radii a few tens of pc, expanding at velocities of 50-100kms-1. We have applied a simple dynamically consistent framework in which we can extrapolate the properties of the observed Halpha shells to a few 10^7yr after the formation of the OB stars. The framework includes the dynamical inputs of both winds and SNe on the surrounding ISM. The results give quantitative statistical support to the hypothesis that the Halpha emitting shells are generic progenitors of the HI shells. During the time taken for an expanding shell to reach the size of a typical HI shell, the OB association may well lose its most luminous stars so the absence of such stars near the centres of many of the HI shells is well explained in this scenario.Comment: 8 pages, 4 figures, accepted for publication in Astronomy and Astrophysic

Lorenz-like systems and classical dynamical equations with memory forcing: a new point of view for singling out the origin of chaos

A novel view for the emergence of chaos in Lorenz-like systems is presented. For such purpose, the Lorenz problem is reformulated in a classical mechanical form and it turns out to be equivalent to the problem of a damped and forced one dimensional motion of a particle in a two-well potential, with a forcing term depending on the ``memory'' of the particle past motion. The dynamics of the original Lorenz system in the new particle phase space can then be rewritten in terms of an one-dimensional first-exit-time problem. The emergence of chaos turns out to be due to the discontinuous solutions of the transcendental equation ruling the time for the particle to cross the intermediate potential wall. The whole problem is tackled analytically deriving a piecewise linearized Lorenz-like system which preserves all the essential properties of the original model.Comment: 48 pages, 25 figure