Scientific Publications FROM Puerto Rico (Science Direct)

Multi-laboratory comparison of three commercially available Zika IgM enzyme-linked immunosorbent assays

Publication date: Available online 30 June 2018
Source:Journal of Virological Methods

Author(s): Alison Jane Basile, Christin Goodman, Kalanthe Horiuchi, Angela Sloan, Barbara W. Johnson, Olga Kosoy, Janeen Laven, Amanda J. Panella, Isabel Sheets, Freddy Medina, Emelissa J. Mendoza, Monica Epperson, Panagiotis Maniatis, Vera Semenova, Evelene Steward-Clark, Emily Wong, Brad J. Biggerstaff, Robert Lanciotti, Michael Drebot, David Safronetz, Jarad Schiffer







Low temperature magnetic and magnetocaloric studies in YCr0.85Mn0.15O3 ceramic

Publication date: Available online 30 June 2018
Source:Physica B: Condensed Matter

Author(s): Neeraj Panwar, Surendra Kumar, Indrani Coondoo, M. Vasundhara, Nitu Kumar

We have investigated low temperature magnetic and magnetocaloric properties of manganese (Mn) doped YCr0.85Mn0.15O3 (YCMO) polycrystalline compound, synthesized via solid state reaction route. The lattice volume was found to increase in comparison to that of pristine YCrO3 (YCO) compound. On the other hand, the paramagnetic-antiferromagnetic Néel temperature (T N  ∼ 132 K) was found to be lower than that for YCO ceramic. On cooling below T N , under field cooled (FC) mode with an applied magnetic field of 0.02 T, magnetization flipped the polarity from positive to negative at T comp = 62 K. Furthermore, the magnetization switching temperature, defined as compensation temperature, exhibited field dependency and decreased with increasing field. Besides, the magnetization reversal phenomenon disappeared under higher applied magnetic field values. For the first time, the magnetocaloric effect for this compound was measured near 36 K through the parameters like magnetic entropy change (−ΔS) = ∼0.186 J kg−1 K−1 and the relative cooling power (RCP) ∼ 6.65 J kg−1, under an applied field of 5 T.





Direct-Gap Semiconducting Tri-layer Silicene With 29% Photovoltaic Efficiency

Publication date: Available online 26 June 2018
Source:Nano Energy

Author(s): Jian Lv, Meiling Xu, Shiru Lin, Xuecheng Shao, Xinyu Zhang, Yanhui Liu, Yanchao Wang, Zhongfang Chen, Yanming Ma

Crystalline silicon is dominating the current solar cell market due to the significant efficiency improvement and cost reduction in last decades. However, its indirect band gap nature leads to inefficient visible-light absorption, which seriously impedes further performance enhancement in silicon-based photovoltaic devices. Thus, it is highly desirable to develop direct band gap silicon materials. Herein, by means of ab initio swarm-intelligence structure-searching method, we predicted a quasi-direct gap semiconducting tri-layer silicene structure consisting of alternating arrays of six-membered Si rings, which can be converted into a direct gap semiconductor of 0.86eV by applying a low tensile strain (~2.5%). Our calculations revealed that the photovoltaic efficiency of the tri-layer silicene reaches 29% at 1.0 μm, which is comparable to that of bulk GaAs with the highest conversion efficiency among thin-film solar cell absorbers.
Graphical abstract




Magnetic resonance imaging contrast enhancement in vitro and in vivo by octanuclear iron-oxo cluster-based agents

Publication date: September 2018
Source:Journal of Inorganic Biochemistry, Volume 186

Author(s): Soma Das, Kenia Parga, Indranil Chakraborty, Arthur D. Tinoco, Yamixa Delgado, Paola M. López, Lauren Fernández Vega, Yiannis Sanakis, Sukhen Ghosh, Jim Bankson, Jim Klostergaard, Ricardo González-Méndez, Raphael G. Raptis

A water-soluble octanuclear cluster, [Fe8], was studied with regard to its properties as a potential contrast enhancing agent in magnetic resonance imaging (MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse relaxivities r2 = 4.01, 10.09 and 15.83 mM s−1, respectively. A related hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57Fe-Mössbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r2 = 3.65 mM s−1 (1.3 T), 26.20 mM s−1 (7.2 T) and 52.18 mM s−1 (11.9 T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and its in vivo enhancement of T2-weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe8]-HA conjugate was i.v. injected to the tumor-bearing mouse, resulting in observable, heterogeneous signal change within the tumor, evident 15 min after injection and persisting for approximately 30 min. Both molecular [Fe8] and its HA-conjugate show a strong magnetic field dependence on r2, rendering them promising platforms for the further development of T2 MRI contrast agents in high and ultrahigh magnetic fields.
Graphical abstract




Framing the triple bottom line approach: Direct and mediation effects between economic, social and environmental elements

Publication date: Available online 26 June 2018
Source:Journal of Cleaner Production

Author(s): Göran Svensson, Carlos Ferro, Nils Høgevold, Carmen Padin, Juan Carlos Sosa Varela, Marko Sarstedt

Conflicting relationships between the economic, social and environmental elements of business sustainability, which are also referred to as the Triple Bottom Line (TBL), characterise today's business environment. While the TBL has recently attracted considerable research, not a single study has empirically tested the direct and indirect effects between the TBL elements. By addressing this gap in research, this study sheds light on the structural properties focusing on the direct effects and the indirect effect (i.e., mediation) between the TBL elements. The results of two cross-industrial studies in Norway and Spain indicate that the TBL's economic element has a direct effect on the environmental element, with the social element mediating this effect. The results reported here offer long-needed empirical insights into the interplay between the three TBL elements, which have important implications for research and practice.
Graphical abstract




Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America

Publication date: July 2018
Source:Clinical Microbiology and Infection, Volume 24, Issue 7

Author(s): J.L. Arredondo-García, S.R. Hadinegoro, H. Reynales, M.N. Chua, D.M. Rivera Medina, T. Chotpitayasunondh, N.H. Tran, C.C. Deseda, D.N. Wirawan, M. Cortés Supelano, C. Frago, E. Langevin, D. Coronel, T. Laot, A.P. Perroud, L. Sanchez, M. Bonaparte, K. Limkittikul, D. Chansinghakul, S. Gailhardou, F. Noriega, T.A. Wartel, A. Bouckenooghe, B. Zambrano

Objective Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. Methods The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. Results Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42–0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24–0.43). In vaccinated participants aged <9 years, particularly in those aged 2–5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60–1.03), with a higher protective effect in the 6–8 year olds than in the 2–5 year olds. Conclusions The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.





Electrostatic Tuning of a Potassium Channel in Electric Fish

Publication date: Available online 21 June 2018
Source:Current Biology

Author(s): Immani Swapna, Alfredo Ghezzi, Julia M. York, Michael R. Markham, D. Brent Halling, Ying Lu, Jason R. Gallant, Harold H. Zakon

Molecular variation contributes to the evolution of adaptive phenotypes, though it is often difficult to understand precisely how. The adaptively significant electric organ discharge behavior of weakly electric fish is the direct result of biophysical membrane properties set by ion channels. Here, we describe a voltage-gated potassium-channel gene in African electric fishes that is under positive selection and highly expressed in the electric organ. The channel produced by this gene shortens electric organ action potentials by activating quickly and at hyperpolarized membrane potentials. The source of these properties is a derived patch of negatively charged amino acids in an extracellular loop near the voltage sensor. We demonstrate that this negative patch acts by contributing to the global surface charge rather than by local interactions with specific amino acids in the channel’s extracellular face. We suggest a more widespread role for this loop in the evolutionary tuning of voltage-dependent channels.
Graphical abstract
Teaser In electric fish with ultra-brief discharges, Swapna et al. find a potassium channel that shortens action potentials by activating fast and close to resting potential. These properties derive from a patch of negative amino acids near the voltage sensor. Similarly placed charged amino acids may tune voltage sensitivity of channels more generally.



Dependence of leukocyte capture on instantaneous pulsatile flow

Publication date: Available online 15 June 2018
Source:Journal of Biomechanics

Author(s): Umberto Ciri, Rita Bhui, Jorge Bailon-Cuba, Heather N. Hayenga, Stefano Leonardi

Atherosclerosis, an artery disease, is currently the leading cause of death in the United States in both men and women. The first step in the development of atherosclerosis involves leukocyte adhesion to the arterial endothelium. It is broadly accepted that blood flow, more specifically wall shear stress (WSS), plays an important role in leukocyte capture and subsequent development of an atherosclerotic plaque. What is less known is how instantaneous WSS, which can vary by up to 5 Pa over one cardiac cycle, influences leukocyte capture. In this paper we use direct numerical simulations (DNS), performed using an in-house code, to illustrate that leukocyte capture is different whether as a function of instantaneous or time-averaged blood flow. Specifically, a stenotic plaque is modeled using a computational fluid dynamics (CFD) solver through fully three-dimensional Navier-Stokes equations and the immersed boundary method. Pulsatile triphasic inflow is used to simulate the cardiac cycle. The CFD is coupled with an agent-based leukocyte capture model to assess the impact of instantaneous hemodynamics on stenosis growth. The computed wall shear stress agrees well with the results obtained with a commercial software, as well as with theoretical results in the healthy region of the artery. The analysis emphasizes the importance of the instantaneous flow conditions in evaluating the leukocyte rate of capture. That is, the capture rate computed from mean flow field is generally underpredicted compared to the actual rate of capture. Thus, in order to obtain a reliable estimate, the flow unsteadiness during a cardiac cycle should be taken into account.





A new conceptual model for international franchising

Publication date: Available online 11 June 2018
Source:International Journal of Hospitality Management

Author(s): Alexander Rosado-Serrano, Justin Paul

International franchising has been widely studied from the franchisor perspective, as it relates to why and how firms decide to expand by viewing it as a uni-directional perspective. With the increased volume of international franchising businesses, theory development that considers multidimensional elements such as distance, trust and its effects on franchise relationship and the system’s performance is needed. The purpose of this paper is to develop a conceptual model on international franchising partnerships that integrates factors determining franchise formation, expansion and performance grounded in Relational Contracting Theory. The uniqueness of the proposed model is on its originality as a dynamic behavioral theoretical model to address the possibilities for value creation, performance improvement and minimizing failure probability in franchise systems which is important for managers as well as researchers.





Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer’s Disease

Publication date: 5 June 2018
Source:Cell Reports, Volume 23, Issue 10

Author(s): Andre M. Miranda, Mathieu Herman, Rong Cheng, Eden Nahmani, Geoffrey Barrett, Elizabeta Micevska, Gaelle Fontaine, Marie-Claude Potier, Elizabeth Head, Frederick A. Schmitt, Ira T. Lott, Ivonne Z. Jiménez-Velázquez, Stylianos E. Antonarakis, Gilbert Di Paolo, Joseph H. Lee, S. Abid Hussaini, Catherine Marquer

The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer’s disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD.
Graphical abstract
Teaser Miranda et al. combine human genetics, human brain samples, and behavior and electrophysiology in a transgenic mouse model to show that synaptojanin 1 levels regulate the function of place cells in the aging hippocampus. The results have implications for memory deficits in all types of Alzheimer’s disease.



An assessment of Landsat-8 atmospheric correction schemes and remote sensing reflectance products in coral reefs and coastal turbid waters

Publication date: 15 September 2018
Source:Remote Sensing of Environment, Volume 215

Author(s): Jianwei Wei, Zhongping Lee, Rodrigo Garcia, Laura Zoffoli, Roy A. Armstrong, Zhehai Shang, Patrick Sheldon, Robert F. Chen

The Operational Land Imager (OLI) onboard Landsat-8 satellite can provide remote sensing reflectance (R rs ) of aquatic environments with high spatial resolution (30 m), allowing for benthic habitat mapping and monitoring of bathymetry and water column optical properties. To facilitate these applications, accurate sensor-derived R rs is required. In this study, we assess atmospheric correction schemes, including NASA's NIR-SWIR approach, Acolite's NIR and SWIR approaches and the cloud-shadow approach. We provide the first comprehensive evaluation for Landsat-8 R rs retrievals in optically shallow coral reefs, along with an investigation of Landsat-8 R rs products in a temperate turbid embayment. The obtained Landsat-8 R rs data products are evaluated with concurrent in situ hyperspectral R rs measurements. Our analyses show that the NASA and the cloud-shadow approaches generated reliable R rs products across shallow coral reefs and optically deep waters. This evaluation suggests that high quality R rs products are achievable from the Landsat-8 satellite in optically shallow environments, which supports further application of Landsat-8 type measurements for coral reef studies.





Rethinking power and institutions in the shadows of neoliberalism

Publication date: Available online 31 May 2018
Source:World Development

Author(s): Prakash Kashwan, Lauren M. MacLean, Gustavo A. García-López

Despite the recognition that institutions matter for international development, the debates over institutional reforms tend to obscure the role of power. Neoliberal models of development are often promoted in terms of their technical merits and efficiency gains and rarely account for the multiple ways that social, economic and political power shape institutional design and institutional change. Even recent efforts to address power tend to conceptualize it too narrowly. This special issue seeks to rethink the role of power in institutional creation and change in the context of persistent neoliberalism. In the introduction, we synthesize the literature on the nature of power to develop a new conceptual framework – a power in institutions matrix – that highlights the multiple dimensions of power involved in institutional development and change. We argue that such a theoretically-informed mapping of power in institutions will enable scholars, practitioners, and citizen groups to go beyond the standard critiques in order to analyze the multifaceted effects of neoliberal institutional change. Our introduction draws on an extensive literature review as well as the special issue contributors who examine institutional change in a variety of policy sectors in Africa, South Asia, Latin America, and North America. We find that a range of diverse local, national and transnational actors, with disparate access to power, negotiate institutional changes from above and below through overt imposition of and resistance to new rules, influence of agendas, and promotion of discourses. Neoliberalism thus creates a new distributive politics. The special issue thus offers a theoretically-grounded approach for linking international and domestic power differences to the process of institutional change, with a specific focus on equity and sustainability. In a departure from the current literature’s focus on elite bargains, we showcase the efforts by less powerful groups to gain a foothold in decision-making processes.





An automatic method for screening clouds and cloud shadows in optical satellite image time series in cloudy regions

Publication date: 1 September 2018
Source:Remote Sensing of Environment, Volume 214

Author(s): Xiaolin Zhu, Eileen H. Helmer

Clouds and cloud shadows block land surface information in optical satellite images. Accurate detection of clouds and cloud shadows can help exclude these contaminated pixels in further applications. Existing cloud screening methods are challenged by cloudy regions where most of satellite images are contaminated by clouds. To solve this problem for landscapes where the typical frequency of cloud-free observations of a pixel is too small to use existing methods to mask clouds and shadows, this study presents a new Automatic Time-Series Analysis (ATSA) method to screen clouds and cloud shadows in multi-temporal optical images. ATSA has five main steps: (1) calculate cloud and shadow indices to highlight cloud and cloud shadow information; (2) obtain initial cloud mask by unsupervised classifiers; (3) refine initial cloud mask by analyzing time series of a cloud index; (4) predict the potential shadow mask using geometric relationships; and (5) refine the potential shadow mask by analyzing time series of a shadow index. Compared with existing methods, ATSA needs fewer predefined parameters, does not require a thermal infrared band, and is more suitable for areas with persistent clouds. The performance of ATSA was tested with Landsat-8 OLI images, Landsat-4 MSS images, and Sentinel-2 images in three sites. The results were compared with a popular method, Function of Mask (Fmask), which has been adopted by USGS to produce Landsat cloud masks. These tests show that ATSA and Fmask can get comparable cloud and shadow masks in some of the tested images. However, ATSA can consistently obtain high accuracy in all images, while Fmask has large omission or commission errors in some images. The quantitative accuracy was assessed using manual cloud masks of 15 images. The average cloud producer's accuracy of these 15 images is as high as 0.959 and the average shadow producer's accuracy reaches 0.901. Given that it can be applied to old satellite sensors and it is capable for cloudy regions, ATSA is a valuable supplement to the existing cloud screening methods.





Müller glial cells contribute to dim light vision in the spectacled caiman (Caiman crocodilus fuscus): Analysis of retinal light transmission

Publication date: August 2018
Source:Experimental Eye Research, Volume 173

Author(s): Silke Agte, Alexey Savvinov, Anett Karl, Astrid Zayas-Santiago, Elke Ulbricht, Vladimir I. Makarov, Andreas Reichenbach, Andreas Bringmann, Serguei N. Skatchkov

In this study, we show the capability of Müller glial cells to transport light through the inverted retina of reptiles, specifically the retina of the spectacled caimans. Thus, confirming that Müller cells of lower vertebrates also improve retinal light transmission. Confocal imaging of freshly isolated retinal wholemounts, that preserved the refractive index landscape of the tissue, indicated that the retina of the spectacled caiman is adapted for vision under dim light conditions. For light transmission experiments, we used a setup with two axially aligned objectives imaging the retina from both sides to project the light onto the inner (vitreal) surface and to detect the transmitted light behind the retina at the receptor layer. Simultaneously, a confocal microscope obtained images of the Müller cells embedded within the vital tissue. Projections of light onto several representative Müller cell trunks within the inner plexiform layer, i.e. (i) trunks with a straight orientation, (ii) trunks which are formed by the inner processes and (iii) trunks which get split into inner processes, were associated with increases in the intensity of the transmitted light. Projections of light onto the periphery of the Müller cell endfeet resulted in a lower intensity of transmitted light. In this way, retinal glial (Müller) cells support dim light vision by improving the signal-to-noise ratio which increases the sensitivity to light. The field of illuminated photoreceptors mainly include rods reflecting the rod dominance of the of tissue. A subpopulation of Müller cells with downstreaming cone cells led to a high-intensity illumination of the cones, while the surrounding rods were illuminated by light of lower intensity. Therefore, Müller cells that lie in front of cones may adapt the intensity of the transmitted light to the different sensitivities of cones and rods, presumably allowing a simultaneous vision with both receptor types under dim light conditions.





Porous Hexagonal Boron Oxide Monolayer with Robust Wide Band Gap: A Computational Study

Publication date: Available online 25 May 2018
Source:FlatChem

Author(s): Shiru Lin, Jinxing Gu, Haijun Zhang, Yu Wang, Zhongfang Chen

By means of density functional theory (DFT) computations, we designed porous hexagonal boron oxide (ph-BO) monolayer, which is purely planar, and has uniform pores in diameter of 6.27 Å. Its high binding energy, absence of imaginary phonon dispersions, and outstanding thermal stability suggest that it is possible to synthesize ph-BO monolayer experimentally. Interestingly, ph-BO is an indirect semiconductor with a rather wide band gap (5.23 eV) comparable to hexagonal boron nitride, and its band gap is rather robust against external strains. ph-BO is promising for many applications because of its exceptional electronic and optical properties, especially in the deep-UV range.
Graphical abstract




Which male and female characteristics influence the probability of extragroup paternities in rhesus macaques, Macaca mulatta?

Publication date: June 2018
Source:Animal Behaviour, Volume 140

Author(s): Angelina V. Ruiz-Lambides, Brigitte M. Weiß, Lars Kulik, Anja Widdig

Extragroup paternity (EGP) is found across a wide range of species and may entail reproductive benefits, but may also entail costs to both sexes. While population and group parameters affecting the degree of EGPs are relatively well established, less is known about the individual characteristics that make males and females engage in alternative reproductive tactics such as EGP. Applying a combination of long-term demographic and genetic data from the rhesus macaque population of Cayo Santiago (Puerto Rico, U.S.A.), we investigate which male and female characteristics influence the probability of EGP to better understand the circumstances that shape the distribution and occurrence of EGP. Our results show that, against our expectations, higher-ranking females were more likely to produce EGP offspring than lower-ranking females. The probability of producing extragroup offspring was not significantly related to female or male age, male tenure or previous reproductive success. Furthermore, genetic relatedness between the parents did not affect the production of extragroup offspring, but extragroup offspring were more frequently produced early rather than late in a given mating season. Altogether, our analysis suggests that individual attributes and seasonal aspects create different opportunities and preferences for engaging in EGP as an alternative reproductive tactic. The observed patterns of EGP in rhesus macaques appear to be consistent with female mate choice for genetic benefits, which needs to be confirmed in future studies.





Boosting sensitivity and suppressing artifacts via multi-acquisition in direct polarization NMR experiments with small flip-angle pulses

Publication date: Available online 24 May 2018
Source:Journal of Magnetic Resonance

Author(s): Riqiang Fu, Arturo J. Hernández-Maldonado

A small flip-angle pulse direct polarization is the simplest method commonly used to quantify various compositions in many materials applications. This method sacrifices the sensitivity per scan in exchange for rapid repeating of data acquisition for signal accumulation. In addition, the resulting spectrum often encounters artifacts from background signals from probe components and/or from acoustic rings leading to a distorted baseline, especially in low-γ nuclei and wideline NMR. In this work, a multi-acquisition scheme is proposed to boost the sensitivity per scan and at the same time effectively suppress these artifacts. Here, an adiabatic inversion pulse is first applied in order to bring the magnetization from the +z to –z axis and then a small flip-angle pulse excitation is used before the data acquisition. Right after the first acquisition, the adiabatic inversion pulse is applied again to flip the magnetization back to the +z axis. The second data acquisition takes place after another small flip-angle pulse excitation. The difference between the two consecutive acquisitions cancels out any artifacts, while the wanted signals are accumulated. This acquisition process can be repeated many times before going into next scan. Therefore, by acquiring the signals multiple times in a single scan the sensitivity is improved. A mixture sample of flufenamic acid and 3,5-difluorobenzoic acid and a titanium silicate sample have been used to demonstrate the advantages of this newly proposed method.
Graphical abstract




Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients with Familial Adenomatous Polyposis

Publication date: Available online 23 May 2018
Source:Gastroenterology

Author(s): Marcia Cruz-Correa, Linda M. Hylind, Jessica Hernandez Marrero, Marianna L. Zahurak, Tracy Murray-Stewart, Robert A. Casero, Elizabeth A. Montgomery, Christine Iacobuzio-Donahue, Lodewijk A. Brosens, G. Johan Offerhaus, Asad Umar, Luz M. Rodriguez, Francis M. Giardiello

Background & Aims Familial adenomatous polyposis is an autosomal dominant disorder characterized by development of hundreds of colorectal adenomas and eventually colorectal cancer. Oral administration of the spice curcumin has been followed by regression of polyps in patients with this disorder. We performed a double-blind, randomized trial to determine the safety and efficacy of curcumin in patients with familial adenomatous polyposis. Methods Our study comprised 44 patients with familial adenomatous polyposis (18 to 85 years old) who had either not undergone colectomy or had undergone colectomy with ileorectal anastomosis or ileal anal pouches and had 5 or more intestinal adenomatous polyps, enrolled in Puerto Rico or the United States from September 2011 through November 2016. Patients were randomly assigned (1:1) to groups given 100% pure curcumin (1500 mg orally, twice per day), or identical-appearing placebo capsules, for 12 months. The number and size of lower gastrointestinal tract polyps were evaluated every 4 months for 1 year. The primary outcome was the number of polyps in the curcumin and placebo groups at 12 months or at the time of withdrawal from the study according to the intention-to-treat principle. Results After 1 year of treatment the average rate of compliance was 83% in the curcumin group and 91% in the placebo group. After 12 weeks, there was no significant difference between the mean number of polyps in the placebo group (18.6; 95% CI, 9.3–27.8) vs the curcumin group (22.6; 95% CI, 12.1–33.1) (P=.58). We found no significant difference between mean polyp size in the curcumin group (2.3 mm; 95% CI, 1.8–2.8) vs the placebo group (2.1 mm; 95% CI, 1.5–2.7) (P=.76). Adverse events were few with no significant differences between the groups. Conclusions In a double-blind, randomized trial of patients with familial adenomatous polyposis, we found no difference in mean number or size of lower intestinal tract adenomas between groups of patients given 3000 mg/day curcumin vs placebo for 12 weeks. Clinicaltrials.gov no: NCT00641147





A-Kinase-Anchoring Protein (AKAP150) is expressed in astrocytes and upregulated in response to ischemia

Publication date: Available online 23 May 2018
Source:Neuroscience

Author(s): Aixa F. Rivera-Pagán, Miguel P. Méndez-González, David E. Rivera-Aponte, Christian J. Malpica-Nieves, Katya V. Melnik-Martínez, Astrid Zayas-Santiago, Gerónimo Maldonado-Martínez, Yaroslav M. Shuba, Serguei N. Skatchkov, Misty J. Eaton

A-kinase anchoring proteins, AKAPs, are scaffolding proteins that associate with kinases and phosphatases, and direct them to a specific submembrane site to coordinate signaling events. AKAP150, a rodent ortholog of human AKAP79, has been extensively studied in neurons, but very little is known about the localization and function of AKAP150 in astrocytes, the major cell type in brain. Thus, in this study, we assessed the localization of AKAP150 in astrocytes and elucidated its role during physiological and ischemic conditions. Herein, we demonstrate that AKAP150 is localized in astrocytes and is up-regulated during ischemia both in vitro and in vivo. Knock-down of AKAP150 by RNAi depolarizes the astrocytic membrane potential and substantially reduces by 80% the ability of astrocytes to take up extracellular potassium during ischemic conditions. Therefore, upregulation of AKAP150 during ischemia preserves potassium conductance and the associated hyperpolarized membrane potential of astrocytes; properties of astrocytes needed to maintain extracellular brain homeostasis. Taken together, these data suggest that AKAP150 may play a pivotal role in the neuroprotective mechanism of astrocytes during pathological conditions.





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