bluuebunny/crossref_metadata_2025 huggingface dataset:
A Global Perspective on Sulfur Oxide Controls in Coal-Fired Power Plants and Cardiovascular Disease
Authors: Lin Cheng-Kuan , Lin Ro-Ting , Chen Pi-Cheng , Wang Pu , De Marcellis-Warin Nathalie , Zigler Corwin , Christiani David C.
Published: February 2018

Sulfur oxides (SOx), particularly SO2 emitted by coal-fired power plants, produce long-term risks for cardiovascular disease (CVD). We estimated the relative risks of CVD and ischemic heart disease (IHD) attributable to SOx emission globally. National SOx reduction achieved by emissions control systems was defined as the average SOx reduction percentage weighted by generating capacities of individual plants in a country. We analyzed the relative risk of CVD incidence associated with national SOx reduction for 13,581 coal-fired power-generating units in 79 countries. A 10% decrease in SOx emission was associated with 0.28% (males; 95%CI = −0.39%~0.95%) and 1.69% (females; 95%CI = 0.99%~2.38%) lower CVD risk. The effects on IHD were > 2 times stronger among males than females (2.78%, 95%CI = 1.99%~3.57% vs. 1.18%, 95%CI = 0.19%~2.17%). Further, 1.43% (males) and 8.00% (females) of CVD cases were attributable to suboptimal SOx reduction. Thus, enhancing regulations on SOx emission control represents a target for national and international intervention to prevent CVD.
Csde1 binds transcripts involved in protein homeostasis and controls their expression in an erythroid cell line
Authors: Moore Kat S. , Yagci Nurcan , van Alphen Floris , Paolini Nahuel A. , Horos Rastislav , Held Ntsiki M. , Houtkooper Riekelt H. , van den Akker Emile , Meijer Alexander B. , ‘t Hoen Peter A. C. , von Lindern Marieke
Published: February 2018

Expression of the RNA-binding protein Csde1 (Cold shock domain protein e1) is strongly upregulated during erythropoiesis compared to other hematopoietic lineages. Csde1 expression is impaired in the severe congenital anemia Diamond Blackfan Anemia (DBA), and reduced expression of Csde1 in healthy erythroblasts impaired their proliferation and differentiation. To investigate the cellular pathways controlled by Csde1 in erythropoiesis, we identified the transcripts that physically associate with Csde1 in erythroid cells. These mainly encoded proteins involved in ribogenesis, mRNA translation and protein degradation, but also proteins associated with the mitochondrial respiratory chain and mitosis. Crispr/Cas9-mediated deletion of the first cold shock domain of Csde1 affected RNA expression and/or protein expression of Csde1-bound transcripts. For instance, protein expression of Pabpc1 was enhanced while Pabpc1 mRNA expression was reduced indicating more efficient translation of Pabpc1 followed by negative feedback on mRNA stability. Overall, the effect of reduced Csde1 function on mRNA stability and translation of Csde1-bound transcripts was modest. Clones with complete loss of Csde1, however, could not be generated. We suggest that Csde1 is involved in feed-back control in protein homeostasis and that it dampens stochastic changes in mRNA expression.
No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years
Authors: Mok Hoi Ping , Norton Nicholas J. , Hirst Jack C , Fun Axel , Bandara Mikaila , Wills Mark R. , Lever Andrew M. L.
Published: February 2018

The persistence of infected T cells harbouring intact HIV proviruses is the barrier to the eradication of HIV. This reservoir is stable over long periods of time despite antiretroviral therapy. There has been controversy on whether low level viral replication is occurring at sanctuary sites periodically reseeding infected cells into the latent reservoir to account its durability. To study viral evolution in a physiologically relevant population of latent viruses, we repeatedly performed virus outgrowth assays on a stably treated HIV positive patient over two years and sequenced the reactivated latent viruses. We sought evidence of increasing sequence pairwise distances with time as evidence of ongoing viral replication. 64 reactivatable latent viral sequences were obtained over 103 weeks. We did not observe an increase in genetic distance of the sequences with the time elapsed between sampling. No evolution could be discerned in these reactivatable latent viruses. Thus, in this patient, the contribution of low-level replication to the maintenance of the latent reservoir detectable in the blood compartment is limited.
The Importance of Phonons with Negative Phase Quotient in Disordered Solids
Authors: Seyf Hamid Reza , Lv Wei , Rohskopf Andrew , Henry Asegun
Published: February 2018

Current understanding of phonons is based on the phonon gas model (PGM), which is best rationalized for crystalline materials. However, most of the phonons/modes in disordered materials have a different character and thus may contribute to heat conduction in a fundamentally different way than is described by PGM. For the modes in crystals, which have sinusoidal character, one can separate the modes into two primary categories, namely acoustic and optical modes. However, for the modes in disordered materials, such designations may no longer rigorously apply. Nonetheless, the phase quotient (PQ) is a quantity that can be used to evaluate whether a mode more so shares a distinguishing property of acoustic vibrations manifested as a positive PQ, or a distinguishing property of an optical vibrations manifested as negative PQ. In thinking about this characteristic, there is essentially no intuition regarding the role of positive vs. negative PQ vibrational modes in disordered solids. Given this gap in understanding, herein we studied the respective contributions to thermal conductivity for several disordered solids as a function of PQ. The analysis sheds light on the importance of optical like/negative PQ modes in structurally/compositionally disordered solids, whereas in crystalline materials, the contributions of optical modes are usually small.
Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
Authors: Hernando Elsa , Capurro Valeria , Cossu Claudia , Fiore Michele , García-Valverde María , Soto-Cerrato Vanessa , Pérez-Tomás Ricardo , Moran Oscar , Zegarra-Moran Olga , Quesada Roberto
Published: February 2018

Anion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin and suppressed the characteristic high toxicity of the natural product. Their activity as anionophores in living cells was studied and chloride efflux and iodine influx from living cells mediated by these derivatives was demonstrated. These compounds were shown to permeabilize cellular membranes to halides with efficiencies close to the natural anion channel CFTR at doses that do not compromise cellular viability. Remarkably, optimal transport efficiency was measured in the presence of pH gradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These results support the viability of developing small molecule anionophores as anion channel protein surrogates with potential applications in the treatment of conditions such as Cystic Fibrosis derived from the malfunction of natural anion transport mechanisms.
Role of Precursor Carbides for Graphene Growth on Ni(111)
Authors: Rameshan Raffael , Vonk Vedran , Franz Dirk , Drnec Jakub , Penner Simon , Garhofer Andreas , Mittendorfer Florian , Stierle Andreas , Klötzer Bernhard
Published: February 2018

Surface X-ray Diffraction was used to study the transformation of a carbon-supersaturated carbidic precursor toward a complete single layer of graphene in the temperature region below 703 K without carbon supply from the gas phase. The excess carbon beyond the 0.45  monolayers of C atoms within a single Ni2C layer is accompanied by sharpened reflections of the |4772| superstructure, along with ring-like diffraction features resulting from non-coincidence rotated Ni2C-type domains. A dynamic Ni2C reordering process, accompanied by slow carbon loss to subsurface regions, is proposed to increase the Ni2C 2D carbide long-range order via ripening toward coherent domains, and to increase the local supersaturation of near-surface dissolved carbon required for spontaneous graphene nucleation and growth. Upon transformation, the intensities of the surface carbide reflections and of specific powder-like diffraction rings vanish. The associated change of the specular X-ray reflectivity allows to quantify a single, fully surface-covering layer of graphene (2 ML C) without diffraction contributions of rotated domains. The simultaneous presence of top-fcc and bridge-top configurations of graphene explains the crystal truncation rod data of the graphene-covered surface. Structure determination of the |4772| precursor surface-carbide using density functional theory is in perfect agreement with the experimentally derived X-ray structure factors.
Impact of erroneous meal insulin bolus with dual-hormone artificial pancreas using a simplified bolus strategy - A randomized controlled trial
Authors: Gingras Véronique , Smaoui Mohamed Raef , Cameli Charlotte , Messier Virginie , Ladouceur Martin , Legault Laurent , Rabasa-Lhoret Rémi
Published: February 2018

Postprandial glucose control remains challenging for patients with type 1 diabetes (T1D). A simplified meal bolus approach with a dual-hormone (insulin and glucagon) closed-loop system (DH-CLS) has been tested; yet, the impact of categorization errors with this strategy is unknown. The objective was to compare, in a randomized controlled inpatient trial, DH-CLS with the simplified meal bolus approach for two different meals properly categorized or overestimated. We tested, in patients with T1D, the simplified strategy with two standardized breakfasts (n = 10 per meal) adequately categorized or overestimated: (1) 75 g and (2) 45 g of carbohydrate. No difference was observed for percentage of time <4.0 mmol/L over a 4-hour post-meal period (primary outcome; median [IQR]: 0[0–0] vs. 0[0–0] for both comparisons, p = 0.47 and 0.31 for the 75 g and 45 g meals, respectively). Despite higher meal insulin boluses with overestimation for both meals (9.2 [8.2–9.6] vs. 8.1 [7.3–9.1] U and 8.4 [7.2–10.4] vs. 4.8 [3.7–5.6] U; p < 0.05), mean glycemia, percentage of time in target range and glucagon infusion did not differ. Additional scenarios were tested in silico with comparable results. These results suggest that the DH-CLS with a simplified meal bolus calculation is probably able to avoid hypoglycemia in the event of meal size misclassification.
Personalizing Androgen Suppression for Prostate Cancer Using Mathematical Modeling
Authors: Hirata Yoshito , Morino Kai , Akakura Koichiro , Higano Celestia S. , Aihara Kazuyuki
Published: February 2018

Using a dataset of 150 patients treated with intermittent androgen suppression (IAS) through a fixed treatment schedule, we retrospectively designed a personalized treatment schedule mathematically for each patient. We estimated 100 sets of parameter values for each patient by randomly resampling each patient’s time points to take into account the uncertainty for observations of prostate specific antigen (PSA). Then, we identified 3 types and classified patients accordingly: in type (i), the relapse, namely the divergence of PSA, can be prevented by IAS; in type (ii), the relapse can be delayed by IAS later than by continuous androgen suppression (CAS); in type (iii) IAS was not beneficial and therefore CAS would have been more appropriate in the long run. Moreover, we obtained a treatment schedule of hormone therapy by minimizing the PSA of 3 years later in the worst case scenario among the 100 parameter sets by searching exhaustively all over the possible treatment schedules. If the most frequent type among 100 sets was type (i), the maximal PSA tended to be kept less than 100 ng/ml longer in IAS than in CAS, while there was no statistical difference for the other cases. Thus, mathematically personalized IAS should be studied prospectively.
Mosquito community influences West Nile virus seroprevalence in wild birds: implications for the risk of spillover into human populations
Authors: Martínez-de la Puente Josué , Ferraguti Martina , Ruiz Santiago , Roiz David , Llorente Francisco , Pérez-Ramírez Elisa , Jiménez-Clavero Miguel Ángel , Soriguer Ramón , Figuerola Jordi
Published: February 2018

Mosquito community composition plays a central role in the transmission of zoonotic vector-borne pathogens. We evaluated how the mosquito community affects the seroprevalence of West Nile virus (WNV) in house sparrows along an urbanisation gradient in an area with the endemic circulation of this virus. We sampled 2544 birds and 340829 mosquitoes in 45 localities, analysed in 15 groups, each containing one urban, one rural and one natural area. WNV seroprevalence was evaluated using an epitope-blocking ELISA kit and a micro virus-neutralization test (VNT). The presence of WNV antibodies was confirmed in 1.96% and 0.67% of birds by ELISA and VNT, respectively. The VNT-seropositive birds were captured in rural and natural areas, but not in urban areas. Human population density was zero in all the localities where VNT-positive birds were captured, which potentially explains the low incidence of human WNV cases in the area. The prevalence of neutralizing antibodies against WNV was positively correlated with the abundance of the ornithophilic Culex perexiguus but negatively associated with the abundance of the mammophilic Ochlerotatus caspius and Anopheles atroparvus. These results suggest that the enzootic circulation of WNV in Spain occurs in areas with larger populations of Cx. perexiguus and low human population densities.
Africa-wide evaluation of host biomarkers in QuantiFERON supernatants for the diagnosis of pulmonary tuberculosis
Authors: Chegou Novel N. , Sutherland Jayne S. , Namuganga Anna-Ritah , Corstjens Paul LAM , Geluk Annemieke , Gebremichael Gebremedhin , Mendy Joseph , Malherbe Stephanus , Stanley Kim , van der Spuy Gian D. , Kriel Magdalena , Loxton Andre G. , Kriel Belinda , Simukonda Felanji , Bekele Yonas , Sheehama Jacob A. , Nelongo Josefina , van der Vyver Marieta , Gebrexabher Atsbeha , Hailu Habteyes , Esterhuyse Maria M. , Rosenkrands Ida , Aagard Claus , Kidd Martin , Kassa Desta , Mihret Adane , Howe Rawleigh , Cliff Jacqueline M. , Crampin Amelia C. , Mayanja-Kizza Harriet , Kaufmann Stefan H. E. , Dockrell Hazel M. , Ottenhoff Tom H. M. , Walzl Gerhard ,   AE-TBC consortium, McAnda Shirley P. , Owolabi Olumuyiwa , Sillah Abdou , Gindeh Awa , Donkor Simon , Togun Toyin , Ota Martin , Muzanye Grace , Nsereko Mary , Peters Pierre , Tjon Kon Fat Elisa M. , de Dood Claudia J. , Franken Kees , van der Ploeg-van Schip Jolien J. , Gebrezgeabher Atsbeha , Mesfin Getnet , Belay Yohannes , Alemayehu Yodit , Amberbir Alemayehu , Chilongo Femia , Houben Rein , Tessema Bamlak , Yamuah Lawrence , Amutenya Faustina N. , Monye Lidia , Iipinge Scholastica
Published: February 2018

We investigated host-derived biomarkers that were previously identified in QuantiFERON supernatants, in a large pan-African study. We recruited individuals presenting with symptoms of pulmonary TB at seven peripheral healthcare facilities in six African countries, prior to assessment for TB disease. We then evaluated the concentrations of 12 biomarkers in stored QuantiFERON supernatants using the Luminex platform. Based on laboratory, clinical and radiological findings and a pre-established algorithm, participants were classified as TB disease or other respiratory diseases(ORD). Of the 514 individuals included in the study, 179(34.8%) had TB disease, 274(51.5%) had ORD and 61(11.5%) had an uncertain diagnosis. A biosignature comprising unstimulated IFN-γ, MIP-1β, TGF-α and antigen-specific levels of TGF-α and VEGF, identified on a training sample set (n = 311), validated by diagnosing TB disease in the test set (n = 134) with an AUC of 0.81(95% CI, 0.76–0.86), corresponding to a sensitivity of 64.2%(95% CI, 49.7–76.5%) and specificity of 82.7%(95% CI, 72.4–89.9%). Host biomarkers detected in QuantiFERON supernatants can contribute to the diagnosis of active TB disease amongst people presenting with symptoms requiring investigation for TB disease, regardless of HIV status or ethnicity in Africa.
Impact of different ionization states of phosphorylated Serine-65 on ubiquitin structure and interactions
Authors: Kazansky Yaniv , Lai Ming-Yih , Singh Rajesh K. , Fushman David
Published: February 2018

The covalent attachment of ubiquitin (Ub) or Ub chains to cellular proteins is a versatile post-translational modification involved in a variety of eukaryotic cellular events. Recently, the post-translational modification of Ub itself by phosphorylation has emerged as an important component of the Ub-signaling system. Specifically, Ub phosphorylation at serine-65 was shown to activate parkin-mediated mitochondrial quality control. However, the impact of phosphorylation on Ub structure and interactions is poorly understood. Here we investigate the recently reported structural changes in Ub upon serine-65 phosphorylation, namely, the equilibrium between a native-like and a novel, alternate conformer of phosphorylated Ub (pUb). We show that this equilibrium is pH-dependent, and the two pUb conformers are linked to the different charge states of the phosphate group. We examined pUb binding to a known Ub-receptor and found that the alternate conformer is binding incompetent. Furthermore, serine-65 phosphorylation affects the conformational equilibrium of K48-linked Ub dimers. Lastly, our crystal structure of S65D Ub and NMR data indicate that phosphomimetic mutations do not adequately reproduce the salient features of pUb. Our results suggest that the pH-dependence of the conformations and binding properties of phosphorylated Ub and polyUb could provide an additional level of modulation in Ub-mediated signaling.
Electrically tunable perfect light absorbers as color filters and modulators
Authors: Mirshafieyan Seyed Sadreddin , Gregory Don A.
Published: February 2018

Methods for spectrally controlling light absorption in optoelectronic devices have attracted considerable attention in recent years. It is now well known that a Fabry-Perot nanocavity comprising thin semiconductor and metal films can be used to absorb light at selected wavelengths. The absorption wavelength is controlled by tailoring the thickness of the nanocavity and also by nanostructure patterning. However, the realization of dynamically tuning the absorption wavelength without changing the structural geometry remains a great challenge in optoelectronic device development. Here it is shown how an ultrathin n-type doped indium antimonide integrated into a subwavelength-thick optical nanocavity can result in an electrically tunable perfect light absorber in the visible and near infrared range. These absorbers require simple thin-film fabrication processes and are cost effective for large-area devices without resorting to sophisticated nanopatterning techniques. In the visible range, a 40 nm spectral shift can be attained by applying a reasonable bias voltage to effect the color change. It is also shown that these electrically tunable absorbers may be used as optical modulators in the infrared. The predicted (up to) 95.3% change in reflectance, transforming the device from perfectly absorbing to highly reflective, should make this technology attractive to the telecommunication (switching) industry.
Mediators of episodic memory decay across the adult life span
Authors: Cansino Selene , Torres-Trejo Frine , Estrada-Manilla Cinthya , Hernández-Ramos Evelia , Martínez-Galindo Joyce Graciela , Gómez-Fernández Tania , Ayala-Hernández Mariana , Ramírez-González María Dolores , Ruiz-Velasco Silvia
Published: February 2018

The ability to remember the details of our own experiences declines gradually as we get old. The reason for this decay has been attributed to several factors besides age, such as education, nutrient intake and health status. However, the influence of these factors has mainly been examined individually and rarely together. Here we identify those factors that jointly act as mediators of episodic memory decay across the adult life span. We examined source memory in a lifespan sample of 1557 healthy adults. A total of 70 physical, biological and lifestyle variables were measured and introduced into a structural equation model as potential mediators that intervene between age and source memory. Only 14 mediator variables reliably mediated source memory decay; notably, eight of these variables have an effect on the cardiovascular system. The model unequivocally highlights that the mediators that may impair cardiovascular functioning also impact brain resources involved in episodic memory. We identified the factors that are relevant to episodic memory decline when they interact together as occurs in real life.
Micronization potentiates curcumin’s anti-seizure effect and brings an important advance in epilepsy treatment
Authors: Bertoncello Kanandra Taisa , Aguiar Gean Pablo S. , Oliveira J. Vladimir , Siebel Anna Maria
Published: February 2018

Epilepsy is one of the most common neurological diseases, and current antiepileptic drugs fail to suppress seizure occurrence in around one third of epileptic patients. Curcumin is a phytochemical with promising effects on epilepsy treatment. However, its application has been hindered by its low bioavailability. In order to improve curcumin’s anti-seizure properties, increasing its bioavailability, here we proposed to micronize the compound through supercritical carbon dioxide processing, a suitable green chemistry technique to prepare and modify material properties. Here we investigated the anti-seizure potential of the classical antiepileptic drug valproate, curcumin in its natural state, and micronized curcumin in a PTZ-induced seizure model in zebrafish (Danio rerio). Concerning seizure development, valproate, curcumin and micronized curcumin showed protective effects, slowing seizure development both in larvae and adult animals. Nevertheless, considering the occurrence of the tonic-clonic seizure stage, only valproate and micronized curcumin reduced it, both in larvae and adult zebrafish, unlike non-processed curcumin. Our obtained results are very promising, since micronized curcumin showed effects that are similar to a classic antiepileptic drug, reducing seizure occurrence and slowing seizure progression.
Large uniaxial magnetostriction with sign inversion at the first order phase transition in the nanolaminated Mn2GaC MAX phase
Authors: Novoselova Iuliia P. , Petruhins Andrejs , Wiedwald Ulf , Ingason Árni Sigurdur , Hase Thomas , Magnus Fridrik , Kapaklis Vassilios , Palisaitis Justinas , Spasova Marina , Farle Michael , Rosen Johanna , Salikhov Ruslan
Published: February 2018

In 2013, a new class of inherently nanolaminated magnetic materials, the so called magnetic MAX phases, was discovered. Following predictive material stability calculations, the hexagonal Mn2GaC compound was synthesized as hetero-epitaxial films containing Mn as the exclusive M-element. Recent theoretical and experimental studies suggested a high magnetic ordering temperature and non-collinear antiferromagnetic (AFM) spin states as a result of competitive ferromagnetic and antiferromagnetic exchange interactions. In order to assess the potential for practical applications of Mn2GaC, we have studied the temperature-dependent magnetization, and the magnetoresistive, magnetostrictive as well as magnetocaloric properties of the compound. The material exhibits two magnetic phase transitions. The Néel temperature isTN ~ 507 K, at which the system changes from a collinear AFM state to the paramagnetic state. AtTt = 214 K the material undergoes a first order magnetic phase transition from AFM at higher temperature to a non-collinear AFM spin structure. Both states show large uniaxialc-axis magnetostriction of 450 ppm. Remarkably, the magnetostriction changes sign, being compressive (negative) aboveTtand tensile (positive) below theTt. The sign change of the magnetostriction is accompanied by a sign change in the magnetoresistance indicating a coupling among the spin, lattice and electrical transport properties.
Notch signaling regulates Hey2 expression in a spatiotemporal dependent manner during cardiac morphogenesis and trabecular specification
Authors: Miao Lianjie , Li Jingjing , Li Jun , Tian Xueying , Lu Yangyang , Hu Saiyang , Shieh David , Kanai Ryan , Zhou Bo-yang , Zhou Bin , Liu Jiandong , Firulli Anthony B. , Martin James F. , Singer Harold , Zhou Bin , Xin Hongbo , Wu Mingfu
Published: February 2018

Hey2 gene mutations in both humans and mice have been associated with multiple cardiac defects. However, the currently reported localization of Hey2 in the ventricular compact zone cannot explain the wide variety of cardiac defects. Furthermore, it was reported that, in contrast to other organs, Notch doesn’t regulate Hey2 in the heart. To determine the expression pattern and the regulation of Hey2, we used novel methods including RNAscope and a Hey2
CreERT2
knockin line to precisely determine the spatiotemporal expression pattern and level of Hey2 during cardiac development. We found that Hey2 is expressed in the endocardial cells of the atrioventricular canal and the outflow tract, as well as at the base of trabeculae, in addition to the reported expression in the ventricular compact myocardium. By disrupting several signaling pathways that regulate trabeculation and/or compaction, we found that, in contrast to previous reports, Notch signaling and Nrg1/ErbB2 regulate Hey2 expression level in myocardium and/or endocardium, but not its expression pattern: weak expression in trabecular myocardium and strong expression in compact myocardium. Instead, we found that FGF signaling regulates the expression pattern of Hey2 in the early myocardium, and regulates the expression level of Hey2 in a Notch1 dependent manner.
Long-Term Study of Heart Rate Variability Responses to Changes in the Solar and Geomagnetic Environment
Authors: Alabdulgader Abdullah , McCraty Rollin , Atkinson Michael , Dobyns York , Vainoras Alfonsas , Ragulskis Minvydas , Stolc Viktor
Published: February 2018

This long-term study examined relationships between solar and magnetic factors and the time course and lags of autonomic nervous system (ANS) responses to changes in solar and geomagnetic activity. Heart rate variability (HRV) was recorded for 72 consecutive hours each week over a five-month period in 16 participants in order to examine ANS responses during normal background environmental periods. HRV measures were correlated with solar and geomagnetic variables using multivariate linear regression analysis with Bonferroni corrections for multiple comparisons after removing circadian influences from both datasets. Overall, the study confirms that daily ANS activity responds to changes in geomagnetic and solar activity during periods of normal undisturbed activity and it is initiated at different times after the changes in the various environmental factors and persist over varying time periods. Increase in solar wind intensity was correlated with increases in heart rate, which we interpret as a biological stress response. Increase in cosmic rays, solar radio flux, and Schumann resonance power was all associated with increased HRV and parasympathetic activity. The findings support the hypothesis that energetic environmental phenomena affect psychophysical processes that can affect people in different ways depending on their sensitivity, health status and capacity for self-regulation.
Acidic organelles mediate TGF-β1-induced cellular fibrosis via (pro)renin receptor and vacuolar ATPase trafficking in human peritoneal mesothelial cells
Authors: Oba-Yabana Ikuko , Mori Takefumi , Takahashi Chika , Hirose Takuo , Ohsaki Yusuke , Kinugasa Satoshi , Muroya Yoshikazu , Sato Emiko , Nguyen Geneviève , Piedagnel Rémi , Ronco Pierre M. , Totsune Kazuhito , Ito Sadayoshi
Published: February 2018

TGF-β1, which can cause renal tubular injury through a vacuolar-type H+-ATPase (V-ATPase)-mediated pathway, is induced by the glucose degradation product methylglyoxal to yield peritoneal injury and fibrosis. The present study investigated the roles of V-ATPase and its accessory protein, the (pro)renin receptor, in peritoneal fibrosis during peritoneal dialysis. Rats daily administered 20 mM methylglyoxal intraperitoneally developed significant peritoneal fibrosis after 7 days with increased expression of TGF-β and V-ATPase, which was reduced by the inhibition of V-ATPase with co-administration of 100 mM bafilomycin A1. The (pro)renin receptor and V-ATPase were expressed in acidic organelles and cell membranes of human peritoneal mesothelial cells. TGF-β1 upregulated the expression of collagens, α-SMA, and EDA-fibronectin, together with ERK1/2 phosphorylation, which was reduced by inhibition of V-ATPase, (pro)renin receptor, or the MAPK pathway. Fibronectin and the soluble (pro)renin receptor were excreted from cells by acidic organelle trafficking in response to TGF-β1; this excretion was also suppressed by inhibition of V-ATPase. Soluble (pro)renin receptor concentrations in effluents of patients undergoing peritoneal dialysis were associated with the dialysate-to-plasma ratio of creatinine. Together, these results demonstrate a novel fibrosis mechanism through the (pro)renin receptor and V-ATPase in the acidic organelles of peritoneal mesothelial cells.
Evolution of enzymes with new specificity by high-throughput screening using DmpR-based genetic circuits and multiple flow cytometry rounds
Authors: Kwon Kil Koang , Lee Dae-Hee , Kim Su Jin , Choi Su-Lim , Rha Eugene , Yeom Soo-Jin , Subhadra Bindu , Lee Jinhyuk , Jeong Ki Jun , Lee Seung-Goo
Published: February 2018

Genetic circuit-based biosensors are useful in detecting target metabolites orin vivoenzymes using transcription factors (Tx) as a molecular switch to express reporter signals, such as cellular fluorescence and antibiotic resistance. Herein, a phenol-detecting Tx (DmpR) was employed as a critical tool for enzyme engineering, specifically for the rapid analysis of numerous mutants with multiple mutations at the active site of tryptophan-indole lyase (TIL, EC 4.1.99.1). Cellular fluorescence was monitored cell-by-cell using flow cytometry to detect the creation of phenolic compounds by a new tyrosine-phenol-lyase (TPL, EC 4.1.99.2). In the TIL scaffold, target amino acids near the indole ring (Asp137, Phe304, Val394, Ile396and His463) were mutated randomly to construct a large diversity of specificity variations. Collection of candidate positives by cell sorting using flow cytometry and subsequent shuffling of beneficial mutations identified a critical hit with four mutations (D137P, F304D, V394L, and I396R) in the TIL sequence. The variant displayed one-thirteenth the level of TPL activity, compared with native TPLs, and completely lost the original TIL activity. The findings demonstrate that hypersensitive, Tx-based biosensors could be useful critically to generate new activity from a related template, which would alleviate the current burden to high-throughput screening.
The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus
Authors: Thanadetsuntorn Chokchai , Ngamjanyaporn Pintip , Setthaudom Chavachol , Hodge Kenneth , Saengpiya Nisara , Pisitkun Prapaporn
Published: February 2018

Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in autoantibody production, immune complex deposition, and complement activation. The standard biomarkers such as anti-dsDNA and complements (C3 and C4) do not always correlate with active clinical SLE. The heterogeneity of SLE patients may require additional biomarkers to designate disease activity. Ninety SLE patients participated in this study. Evaluation of disease activity was achieved with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and modified SLEDAI-2K. The measured serum biomarkers were anti-dsDNA, C3, C4, ESR, interleukin-6 (IL-6), and circulating immune complexes (CIC). IL-6, ESR and CIC significantly increased in active clinical SLE. Complement, anti-dsDNA, ESR and CIC correlated with SLEDAI-2K while only anti-dsDNA, CIC, ESR and IL-6 correlated with modified SLEDAI-2K. A combination of biomarkers gave a higher odds ratio (OR) than any single biomarker. A combination of IL-6 or CIC exhibited the highest OR (OR = 7.27, 95%CI (1.99–26.63), p = 0.003) while either complement or anti-dsDNA showed a moderate odds ratio (OR = 3.14, 95%CI (1.16–8.48), p = 0.024) of predicting clinical active SLE. The combination of CIC and IL-6 strongly predicts active clinical SLE. CIC and IL-6 can be used in addition to standard biomarkers to determine SLE activity.
Evaluating the potential of endothelial cells derived from human induced pluripotent stem cells to form microvascular networks in 3D cultures
Authors: Bezenah Jonathan R. , Kong Yen P. , Putnam Andrew J.
Published: February 2018

A major translational challenge in the fields of therapeutic angiogenesis and regenerative medicine is the need to create functional microvasculature. The purpose of this study was to assess whether a potentially autologous endothelial cell (EC) source derived from human induced pluripotent stem cells (iPSC-ECs) can form the same robust, stable microvasculature as previously documented for other sources of ECs. We utilized a well-established in vitro assay, in which endothelial cell-coated (iPSC-EC or HUVEC) beads were co-embedded with fibroblasts in a 3D fibrin matrix to assess their ability to form stable microvessels. iPSC-ECs exhibited a five-fold reduction in capillary network formation compared to HUVECs. Increasing matrix density reduced sprouting, although this effect was attenuated by distributing the NHLFs throughout the matrix. Inhibition of both MMP- and plasmin-mediated fibrinolysis was required to completely block sprouting of both HUVECs and iPSC-ECs. Further analysis revealed MMP-9 expression and activity were significantly lower in iPSC-EC/NHLF co-cultures than in HUVEC/NHLF co-cultures at later time points, which may account for the observed deficiencies in angiogenic sprouting of the iPSC-ECs. Collectively, these findings suggest fundamental differences in EC phenotypes must be better understood to enable the promise and potential of iPSC-ECs for clinical translation to be realized.
The anti-mycobacterial activity of the cytochrome bcc inhibitor Q203 can be enhanced by small-molecule inhibition of cytochrome bd
Authors: Lu Ping , Asseri Amer H. , Kremer Martijn , Maaskant Janneke , Ummels Roy , Lill Holger , Bald Dirk
Published: February 2018

Mycobacterial energy metabolism currently attracts strong attention as new target space for development of anti-tuberculosis drugs. The imidazopyridine Q203 targets the cytochrome bcc complex of the respiratory chain, a key component in energy metabolism. Q203 blocks growth of Mycobacterium tuberculosis at nanomolar concentrations, however, it fails to actually kill the bacteria, which may limit the clinical applicability of this candidate drug. In this report we show that inhibition of cytochrome bd, a parallel branch of the mycobacterial respiratory chain, by aurachin D invoked bactericidal activity of Q203. In biochemical assays using inverted membrane vesicles from Mycobacterium tuberculosis and Mycobacterium smegmatis we found that inhibition of respiratory chain activity by Q203 was incomplete, but could be enhanced by inactivation of cytochrome bd, either by genetic knock-out or by inhibition with aurachin D. These results indicate that simultaneously targeting the cytochrome bcc and the cytochrome bd branch of the mycobacterial respiratory chain may turn out as effective strategy for combating M. tuberculosis.
Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study
Authors: Jabaudon Matthieu , Berthelin Pauline , Pranal Thibaut , Roszyk Laurence , Godet Thomas , Faure Jean-Sébastien , Chabanne Russell , Eisenmann Nathanael , Lautrette Alexandre , Belville Corinne , Blondonnet Raiko , Cayot Sophie , Gillart Thierry , Pascal Julien , Skrzypczak Yvan , Souweine Bertrand , Blanchon Loic , Sapin Vincent , Pereira Bruno , Constantin Jean-Michel
Published: February 2018

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.
Coordinated activation of a cluster of MMP genes in response to UVB radiation
Authors: Ujfaludi Zsuzsanna , Tuzesi Agota , Majoros Hajnalka , Rothler Balint , Pankotai Tibor , Boros Imre M.
Published: February 2018

Ultraviolet (UV) B radiation is a dangerous environmental stressor, which can lead to photoaging, inflammation, immune suppression and tumour formation. A recent report has shown the transcriptional activation of several skin-specific genes including matrix metalloproteases (MMPs) in response to UV irradiation. Here, we use a novel human keratinocyte model, HKerE6SFM, to demonstrate that UVB activates the transcription of most members of the 11q22.3 MMP gene cluster including MMP13, MMP12, MMP3, MMP1 and MMP10. Curiously, the expression of the well-characterized UVB-inducible MMP9, which is located outside of the cluster, remains unchanged. In accordance with the increased expression of the MMP gene cluster upon UVB irradiation, RNA polymerase II showed increased occupancy at their promoters following UVB irradiation. The results also demonstrate increased acetylated histone H3K9 levels at the promoters of the MMP13, MMP12, MMP3, MMP1 and MMP10 genes. These findings suggest a coordinated transcriptional activation of genes in the MMP cluster at 11q22.3 and that acetylation of histone H3 at lysine 9 has an important role in the UVB-dependent enhancement of transcription of MMP genes in this region.
Synthesis of light needles with tunable length and nearly constant irradiance
Authors: Martínez-Herrero Rosario , Maluenda David , Juvells Ignasi , Carnicer Artur
Published: February 2018

We introduce a new method for producing optical needles with tunable length and almost constant irradiance based on the evaluation of the on-axis power content of the light distribution at the focal area. According to theoretical considerations, we propose an adaptive modulating continuous function that presents a large derivative and a zero value jump at the entrance pupil of the focusing system. This distribution is displayed on liquid crystal devices using holographic techniques. In this way, a polarized input beam is shaped and subsequently focused using a high numerical aperture (NA) objective lens. As a result, needles with variable length and nearly constant irradiance are produced using conventional optics components. This procedure is experimentally demonstrated obtaining a 53λ-long and 0.8λ-wide needle.
Contemporary and historical oceanographic processes explain genetic connectivity in a Southwestern Atlantic coral
Authors: Peluso L. , Tascheri V. , Nunes F. L. D. , Castro C. B. , Pires D. O. , Zilberberg C.
Published: February 2018

Understanding connectivity patterns has implications for evolutionary and ecological processes, as well as for proper conservation strategies. This study examined population genetic structure and migration patterns of the coralMussismilia hispida, one of the main reef builders in the Southwestern Atlantic Ocean. For this, 15 sites were sampled along its entire distributional range employing 10 microsatelliteloci.M.hispidawas divided into five genetically differentiated populations by Structure analysis. Population structure and migration estimates are consistent with present-day oceanographic current patterns, zones of upwelling and historical sea-level changes. The Central Region and Oceanic Islands populations had the highest genetic diversity, were possibly the main sources of migrants for other populations and presented mutual migrant exchange. This mutual exchange and the high diversity of Oceanic Islands, a peripherical population, is highly interesting and unexpected, but can be explained if these sites acted as refugia in past low sea-level stance. This is the first connectivity study in the region using hyper-variable markers and a fine sampling scale along 3,500 km. These results enlighten the population dynamics of an important reef building species and shows how oceanographic processes may act as barriers to dispersal for marine species, providing valuable information for management strategies.
Dose and slice thickness evaluation with nMAG gel dosimeters in computed tomography
Authors: Chuang Chun-Chao , Wu Jay
Published: February 2018

Computed tomography (CT) has been widely used in clinical diagnosis. It is important to estimate radiation dose and perform image quality assurance procedures for CT scans. In this study, nMAG gel dosimeters were used to simultaneously measure the 300-mm weighted CT dose index (CTDI) and slice sensitivity profile (SSP) for multiple detector CT (MDCT). Magnetic resonance imaging (MRI) was performed on the irradiated gel to create R2‒dose response curves for the tube voltages of 120 and 140 kVp. The gel dosimeters were loaded in three home-made cylindrical phantoms to obtain CTDI100 and CTDI300. The full width at half maximum (FWHM) for 2, 5, 10, 14.4, and 38.4-mm slice thicknesses was measured and compared with the result obtained by radiochromic films. The difference in weighted CTDI100 obtained by the gel dosimeter and ionization chamber was less than 1%. The CTDI efficiency at 120 and 140 kVp was in the range of 80.1%–82.5%. The FWHM of SSP measured by the gel dosimeter matched very well with the nominal slice thickness. The use of nMAG gel dosimeters combined with the home-made cylindrical phantoms can provide 300-mm weighted CTDI and slice thickness information, showing potential for quality assurance and clinical applications in MDCT.
Evidence of thermophilisation and elevation-dependent warming during the Last Interglacial in the Italian Alps
Authors: Johnston V. E. , Borsato A. , Frisia S. , Spötl C. , Dublyansky Y. , Töchterle P. , Hellstrom J. C. , Bajo P. , Edwards R. L. , Cheng H.
Published: February 2018

Thermophilisation is the response of plants communities in mountainous areas to increasing temperatures, causing an upward migration of warm-adapted (thermophilic) species and consequently, the timberline. This greening, associated with warming, causes enhanced evapotranspiration that leads to intensification of the hydrological cycle, which is recorded by hydroclimate-sensitive archives, such as stalagmites and flowstones formed in caves. Understanding how hydroclimate manifests at high altitudes is important for predicting future water resources of many regions of Europe that rely on glaciers and snow accumulation. Using proxy data from three coeval speleothems (stalagmites and flowstone) from the Italian Alps, we reconstructed both the ecosystem and hydrological setting during the Last Interglacial (LIG); a warm period that may provide an analogue to a near-future climate scenario. Our speleothem proxy data, including calcite fabrics and the stable isotopes of calcite and fluid inclusions, indicate a +4.3 ± 1.6 °C temperature anomaly at ~2000 m a.s.l. for the peak LIG, with respect to present-day values (1961–1990). This anomaly is significantly higher than any low-altitude reconstructions for the LIG in Europe, implying elevation-dependent warming during the LIG. The enhanced warming at high altitudes must be accounted for when considering future climate adaption strategies in sensitive mountainous regions.
LC–MS/MS-based quantitative study of the acyl group- and site-selectivity of human sirtuins to acylated nucleosomes
Authors: Tanabe Kana , Liu Jiaan , Kato Daiki , Kurumizaka Hitoshi , Yamatsugu Kenzo , Kanai Motomu , Kawashima Shigehiro A.
Published: February 2018

Chromatin structure and gene expression are dynamically regulated by posttranslational modifications of histones. Recent advance in mass spectrometry has identified novel types of lysine acylations, such as butyrylation and malonylation, whose functions and regulations are likely different from those of acetylation. Sirtuins, nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, catalyze various deacylations. However, it is poorly understood how distinct sirtuins regulate the histone acylation states of nucleosomes that have many lysine residues. Here, we provide mass spectrometry-based quantitative information about the acyl group- and site-selectivity of all human sirtuins on acylated nucleosomes. The acyl group- and site-selectivity of each sirtuin is unique to its subtype. Sirt5 exclusively removes negatively-charged acyl groups, while Sirt1/2/3/6/7 preferentially remove hydrophobic acyl groups; Sirt1 and Sirt3 selectively remove acetyl group more than butyryl group, whereas Sirt2 and Sirt6 showed the opposite selectivity. Investigating site-selectivity for active sirtuins revealed acylated lysines on H4 tails to be poor substrates and acylated H3K18 to be a good substrate. Furthermore, we found Sirt7 to be a robust deacylase of H3K36/37, and its activity reliant on nucleosome-binding at its C-terminal basic region. All together, our quantitative dataset provides a useful resource in understanding chromatin regulations by histone acylations.
Effects of water flow on submerged macrophyte-biofilm systems in constructed wetlands
Authors: Han Bing , Zhang Songhe , Wang Peifang , Wang Chao
Published: February 2018

The effects of water flow on the leaf-biofilm interface ofVallisneria natansandHydrilla verticillatawere investigated using artificial plants as the control. Water flow inhibited the growth of two species of submerged macrophytes, reduced oxygen concentrations in plant leaves and changed oxygen profiles at the leaf-biofilm interface. The results from confocal laser scanning microscopy and multifractal analysis showed that water flow reduced biofilm thickness, changed biofilm topographic characterization and increased the percentages of single colony-like biofilm patches. A cluster analysis revealed that the bacterial compositions in biofilms were determined mainly by substrate types and were different from those in sediments. However, water flow increased the bacterial diversity in biofilms in terms of operational taxonomic unit numbers and Shannon Indices. Our results indicated that water flow can be used to regulate the biomass, distribution and bacterial diversities of epiphytic biofilms in constructed wetlands dominated by submerged macrophytes.