bluuebunny/crossref_metadata_2025 huggingface dataset:
Cover Crop Termination Treatment Impacts Weed Suppression Potential
Authors: Haramoto Erin R. , Pearce Robert
Published: January 2019

Weed management in tobacco (Nicotiana tabacumL.) is accomplished primarily with soil-residual herbicides, cultivation, and hand removal. Management practices that reduce weed emergence, like reduced tillage and cover crop mulches, may improve weed management efficacy. Depending on cover-cropping goals, growers face trade-offs in species selection and management priorities—producing weed-suppressive mulches may lead to transplanting difficulties and soil-residual herbicide interception. Managing more complex cover crop mixtures may result in different challenges. We established on-farm trials across 4 site-years to study impacts of cover crop composition [wheat (Triticum aestivumL.) monoculture or mixture], termination treatment (early or late chemical termination or removing aboveground biomass), and soil-residual herbicides on weed density and biomass. The cover crop mixture contained cereal rye (Secale cerealeL.), crimson clover (Trifolium incarnatumL.), and hairy vetch (Vicia villosaRoth.), with canola (Brassica napusL.) at 1 site-year. The mixture typically produced more biomass than monoculture wheat, although composition had few impacts on weed density or biomass. With residual herbicides, termination treatment had few impacts on weed density, suggesting that residues did not adversely affect herbicide efficacy. Without residual herbicides, early-season weed density was often higher following the late-terminated cover crop compared with other termination treatments, though midseason weed density was typically lower. When termination treatment affected final weed biomass, it was lower following late termination, with one exception—crop establishment was reduced at 1 site-year, leading to reduced weed–crop competition and greater weed biomass. Our results suggest that growers can use mixtures and, if well-timed to a rainfall event for incorporation, still effectively use soil-residual herbicides to maintain adequate weed control in tobacco regardless of how the cover crop is managed. Later termination, resulting in more residue, may lead to less weed biomass accumulation in the absence of herbicide use.
Bildungsunterschiede von Anfang an?
Authors: Hahn Inga , Schöps Katrin
Published: January 2019

Zusammenfassung. Die vorliegende Studie ging der Frage nach, inwiefern sich bereits bei Kindern im Alter von vier bis sechs Jahren migrationsbedingte Disparitäten in der naturwissenschaftlichen Kompetenz zeigen. Mit Daten des Nationalen Bildungspanels (National Educational Panel Study – NEPS) 1 wurde anhand von Regressionsmodellen untersucht, welche Struktur- und Prozessmerkmale einen Effekt auf die naturwissenschaftliche Kompetenz der Kinder haben. Besonderes Augenmerk wurde vor dem Hintergrund zunehmender Migrationsbewegungen und der Integration von Kindern mit Migrationshintergrund in unser Bildungssystem auf den häuslichen Sprachgebrauch und den rezeptiven Wortschatz in Deutsch, die Lernumgebungen und die soziale Herkunft der Kinder gelegt. Die Ergebnisse verdeutlichen, dass der rezeptive Wortschatz in Deutsch der wichtigste Prädiktor für die Ausprägung der naturwissenschaftlichen Kompetenz ist. Kinder mit Migrationshintergrund schnitten hinsichtlich ihrer Leistung im Naturwissenschaftstest signifikant schlechter ab als Gleichaltrige ohne Migrationshintergrund, was verdeutlicht, dass entsprechende migrationsbedingte Disparitäten bereits im Vorschulbereich existieren.
Interaktion von pädagogischen Fachkräften und Kindern in naturwissenschaftlichen Lerngelegenheiten im Kindergarten
Authors: Bürgermeister Anika , Große Gerlind , Leuchter Miriam , Studhalter Ueli , Saalbach Henrik
Published: January 2019

Zusammenfassung. Im Zusammenhang mit der Gestaltung von Lehr-Lerngelegenheiten im Vorschulbereich wird zunehmend die Bedeutung der Interaktionsqualität zwischen der pädagogischen Fachkraft (PFK) und den Kindern für das frühkindliche Lernen diskutiert. Mit der vorliegenden Studie wird die Interaktionsqualität im Rahmen einer naturwissenschaftlichen Lerngelegenheit in 34 schweizerischen Vorschulgruppen differenziert erfasst und sowohl qualitative (verbale Lernunterstützung der PFK) als auch quantitative Aspekte (Redeanteile der Kinder und PFK) und deren Effekt auf das inhaltliche Lernen der Kinder untersucht. Die Befunde zeigen, dass die Redeanteile zwischen PFK und Kindern ähnlich verteilt sind, die der PFK jedoch umfangreicher sind. Zudem belegen Ergebnisse aus Mehrebenenanalysen einen positiven Zusammenhang zwischen aktiver Beteiligung der Kinder in den Kleingruppengesprächen und dem naturwissenschaftlichen Lernen. Je mehr die PFK dabei das Vorwissen der Kinder aktiviert, desto größer ist dieser Effekt, sodass von einem Interaktionseffekt zwischen Lernunterstützung der PFK und aktiver Gesprächsbeteiligung der Kinder auf das Lernen ausgegangen wird. Die Befunde werden mit Blick auf die Gestaltung von Lehr-Lernprozessen im Kontext frühkindlicher naturwissenschaftlicher Bildung diskutiert.
Atmospheric Moisture Measurements Explain Increases in Tropical Rainfall Extremes
Authors: Roderick Thomas P. , Wasko Conrad , Sharma Ashish
Published: January 2019

Anthropogenic climate change is increasing extreme rainfall as a result of an increased water‐holding capacity of the atmosphere due to higher temperatures. However, observed rainfall‐temperature scaling relationships often differ from the theorized increases in moisture‐holding capacity. This discrepancy is most evident in the tropics, where higher surface temperatures show a marked decrease in extreme rainfall intensity despite observed increases in extreme rainfall. Here we use atmospheric moisture measurements from the National Aeronautics and Space Administration's Atmospheric Infrared Sounder with surface data to investigate the tropical rainfall‐temperature scaling relationship. We show rainfall intensity scales positively with integrated water vapor in all regions. Further, integrated water vapor does not consistently scale positively with surface air temperature and its dependence on background temperature offers a physical explanation for the apparent negative scaling. We conclude that the inconsistent relationship between surface air temperature and moisture is the reason for the “apparent” negative scaling consistently found in the tropics.
A Meteor Struck the Moon During the Total Lunar Eclipse
Authors: Cartier Kimberly
Published: January 2019

Telescopes around the world detected an impact event on the lunar surface just before totality on Monday. Amateur and professional astronomers are starting to coordinate data.
TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression
Authors: Hwang Jun-Ha , Kim A Rum , Kim Kyung Min , Il Park Jung , Oh Ho Taek , Moon Sung A , Byun Mi Ran , Jeong Hana , Kim Hyo Kyung , Yaffe Michael B. , Hwang Eun Sook , Hong Jeong-Ho
Published: January 2019

Insulin regulates blood glucose levels by binding its receptor and stimulating downstream proteins through the insulin receptor substrate (IRS). Impaired insulin signalling leads to metabolic syndrome, but the regulation of this process is not well understood. Here, we describe a novel insulin signalling regulatory pathway involving TAZ. TAZ upregulates IRS1 and stimulates Akt- and Glut4-mediated glucose uptake in muscle cells. Muscle-specific TAZ-knockout mice shows significantly decreased Irs1 expression and insulin sensitivity. Furthermore, TAZ is required for Wnt signalling-induced Irs1 expression, as observed by decreased Irs1 expression and insulin sensitivity in muscle-specific APC- and TAZ-double-knockout mice. TAZ physically interacts with c-Jun and Tead4 to induce Irs1 transcription. Finally, statin administration decreases TAZ, IRS1 level and insulin sensitivity. However, in myoblasts, the statin-mediated decrease in insulin sensitivity is counteracted by the expression of a constitutively active TAZ mutant. These results suggest that TAZ is a novel insulin signalling activator that increases insulin sensitivity and couples Hippo/Wnt signalling and insulin sensitivity.
Experience of adverse events with cerebral propofol testing in patients with drug resistant epilepsy
Authors: Szantroch Marta , Bala Aleksandra , Rysz Andrzej , Żyłkowski Jarosław , Marchel Andrzej
Published: January 2019

The aim of this study was to assess the type and frequency of adverse events during the Wada test conducted with propofol as an anaesthetic agent. In total, 122 patients with temporal lobe epilepsy underwent the Wada test with propofol between 2006 and 2016 as part of presurgical evaluation at the Department of Neurosurgery of the Medical University of Warsaw. The Wada test was conducted bilaterally on 118 patients (236 cases). In four cases, due to complications, the test was conducted only unilaterally, which resulted in a total of 240 cases. Those cases were further analysed for the presence of adverse events. In all cases, intracranial circulation angiography (via the transfemoral approach) was performed before memory and language testing. Of the 122 patients, adverse events were observed in 75 patients (61.4%). Serious complications were notably rare and observed only in two patients (1.6%): one patient had a carotid artery dissection, and the other had a pseudoaneurysm at the puncture site. Mild adverse events (e.g., shivers or pain of the eye) were highly common – we observed them in 71 patients (58%), but they were short-term and well-tolerated by the subjects. Two patients (1.6%) had a seizure during the Wada test. Most of the adverse events occurring during the Wada test with propofol were mild and short-lived. Considering a small risk of serious damage to health, this procedure can be perceived as a good method for assessing language and memory in a fraction of the epilepsy surgery candidates.
The time course of auditory looming cues in redirecting visuo-spatial attention
Authors: Glatz Christiane , Chuang Lewis L.
Published: January 2019

By orienting attention, auditory cues can improve the discrimination of spatially congruent visual targets. Looming sounds that increase in intensity are processed preferentially by the brain. Thus, we investigated whether auditory looming cues can orient visuo-spatial attention more effectively than static and receding sounds. Specifically, different auditory cues could redirect attention away from a continuous central visuo-motor tracking task to peripheral visual targets that appeared occasionally. To investigate the time course of crossmodal cuing, Experiment 1 presented visual targets at different time-points across a 500 ms auditory cue’s presentation. No benefits were found for simultaneous audio-visual cue-target presentation. The largest crossmodal benefit occurred at early cue-target asynchrony onsets (i.e., CTOA = 250 ms), regardless of auditory cue type, which diminished at CTOA = 500 ms for static and receding cues. However, auditory looming cues showed a late crossmodal cuing benefit at CTOA = 500 ms. Experiment 2 showed that this late auditory looming cue benefit was independent of the cue’s intensity when the visual target appeared. Thus, we conclude that the late crossmodal benefit throughout an auditory looming cue’s presentation is due to its increasing intensity profile. The neural basis for this benefit and its ecological implications are discussed.
Porous flower-like superstructures based on self-assembled colloidal quantum dots for sensing
Authors: Stepanidenko Evgeniia A. , Gromova Yulia A. , Kormilina Tatiana K. , Cherevkov Sergei A. , Kurshanov Danil A. , Dubavik Aliaksei , Baranov Mikhail A. , Medvedev Oleg S. , Fedorov Anatoly V. , Gun’ko Yurii K. , Ushakova Elena V. , Baranov Alexander V.
Published: January 2019

Quantum dots (QDs) have been envisaged as very promising materials for the development of advanced optical sensors. Here we report a new highly porous luminescent material based on colloidal QDs for potential applications in optical sensing devices. Bulk flower-like porous structures with sizes of hundreds of microns have been produced by slow destabilization of QD solution in the presence of a non-solvent vapor. The porous highly luminescent material was formed from CdSe QDs using the approach of non-solvent destabilization. This material demonstrated a 4-fold decrease in PL signal in the presence of the ammonia vapor. The relationship between the destabilization rate of QDs in solution and the resulting morphology of structural elements has been established. The proposed model of bulk porous flower-like nanostructured material fabrication can be applied to nanoparticles of different nature combining their unique properties. This research opens up a new approach to design novel multi-component composite materials enabling potential performance improvements of various photonic devices.
Precision of a Novel Craniofacial Surgical Navigation System Based on Augmented Reality Using an Occlusal Splint as a Registration Strategy
Authors: Jiang Taoran , Zhu Ming , Chai Gang , Li Qingfeng
Published: January 2019

The authors have developed a novel augmented reality (AR)-based navigation system (NS) for craniofacial surgery. In this study, the authors aimed to measure the precision of the system and further analyze the primary influencing factors of the precision. The drilling of holes into the mandibles of ten beagle dogs was performed under the AR-based NS, and the precision was analyzed by comparing the deviation between the preoperational plan and the surgical outcome. The AR-based NS was successfully applied to quickly and precisely drill holes in the mandibles. The mean positional deviation between the preoperative design and intraoperative navigation was 1.29 ± 0.70 mm for the entry points and 2.47 ± 0.66 mm for the end points, and the angular deviation was 1.32° ± 1.17°. The precision linearly decreased with the distance from the marker. In conclusion, the precision of this system could satisfy clinical requirements, and this system may serve as a helpful tool for improving the precision in craniofacial surgery.
The interplay between prematurity, maternal stress and children’s intelligence quotient at age 11: A longitudinal study
Authors: Turpin Hélène , Urben Sébastien , Ansermet François , Borghini Ayala , Murray Micah M. , Müller-Nix Carole
Published: January 2019

Very premature children (<33 weeks of gestational age (GA)) experience greater academic difficulties and have lower, though normal-range, intelligence quotients (IQs) versus their full-term peers. These differences are often attributed to GA or familial socio-economic status (SES). However, additional factors are increasingly recognized as likely contributors. Parental stress after a child’s premature birth can present as post-traumatic stress disorder (PTSD) symptoms and can in turn reinforce difficulties in parent-child interaction pattern. Following a longitudinal design, we studied the interplay between a premature child’s perinatal history and maternal PTSD symptoms on intelligence abilities assessed at 11 years of age. Thirty-three very preterm and 21 full-term mother-children dyads partook in the study. Children’s perinatal risk was evaluated at hospital discharge, maternal PTSD symptoms were assessed when the children were 18 months old, and children’s IQ was measured at 11 years old. IQ was significantly lower for preterm than full-term children, without reliable influences from perinatal risk scores. However, lower maternal PTSD symptoms predicted higher IQ in preterm children. This preliminary study highlights the importance detecting maternal PTSD symptoms after a preterm birth and suggests interventions should target reducing maternal PTSD symptoms during early childhood to enhance very preterm children’s intelligence development.
Deposition of calcium in an in vitro model of human breast tumour calcification reveals functional role for ALP activity, altered expression of osteogenic genes and dysregulation of the TRPM7 ion channel
Authors: O’Grady Shane , Morgan Maria P.
Published: January 2019

Microcalcifications are vital mammographic indicators contributing to the early detection of up to 50% of non-palpable tumours and may also be valuable as prognostic markers. However, the precise mechanism by which they form remains incompletely understood. Following development of an in vitro model using human breast cancer cells lines cultured with a combination of mineralisation-promoting reagents, analysis of calcium deposition, alkaline phosphatase (ALP) activity and changes in expression of key genes was used to monitor the calcification process. Two cell lines were identified as successfully mineralising in vitro, MDA-MB-231 and SKBR3. Mineralising cell lines displayed higher levels of ALP activity that was further increased by addition of mineralisation promoting media. qPCR analysis revealed changes in expression of both pro- (RUNX2) and anti- (MGP, ENPP1) mineralisation genes. Mineralisation was suppressed by chelation of intracellular Ca2+ and inhibition of TRPM7, demonstrating a functional role for the channel in formation of microcalcifications. Increased Mg2+ was also found to effectively reduce calcium deposition. These results expand the number of human breast cancer cell lines with a demonstrated in vitro mineralisation capability, provide further evidence for the role of an active, cellular process of microcalcification formation and demonstrate for the first time a role for TRPM7 mediated Ca2+ transport.
Peculiar optical properties of bilayer silicene under the influence of external electric and magnetic fields
Authors: Do Thi-Nga , Gumbs Godfrey , Shih Po-Hsin , Huang Danhong , Chiu Chih-Wei , Chen Chia-Yun , Lin Ming-Fa
Published: January 2019

We conduct a comprehensive investigation of the effect of an applied electric field on the optical and magneto-optical absorption spectra for AB-bt (bottom-top) bilayer silicene. The generalized tight-binding model in conjunction with the Kubo formula is efficiently employed in the numerical calculations. The electronic and optical properties are greatly diversified by the buckled lattice structure, stacking configuration, intralayer and interlayer hopping interactions, spin-orbital couplings, as well as the electric and magnetic fields ($${E}_{z}\hat{z}$$

E

z

z
ˆ

$$\& $$
&
$${B}_{z}\hat{z}$$

B

z

z
ˆ

). An electric field induces spin-split electronic states, a semiconductor-metal phase transitions and the Dirac cone formations in different valleys, leading to the special absorption features. The Ez-dependent low-lying Landau levels possess lower degeneracy, valley-created localization centers, peculiar distributions of quantum numbers, well-behaved and abnormal energy spectra in Bz-dependencies, and the absence of anti-crossing behavior. Consequently, the specific magneto-optical selection rules exist for diverse excitation categories under certain critical electric fields. The optical gaps are reduced as Ez is increased, but enhanced by Bz, in which the threshold channel might dramatically change in the former case. These characteristics are in sharp contrast with those for layered graphene.
Application of the Transcriptional Disease Signature (TDSs) to Screen Melanoma-Effective Compounds in a Small Fish Model
Authors: Lu Yuan , Boswell William , Boswell Mikki , Klotz Barbara , Kneitz Susanne , Regneri Janine , Savage Markita , Mendoza Cristina , Postlethwait John , Warren Wesley C. , Schartl Manfred , Walter Ronald B.
Published: January 2019

Cell culture and protein target-based compound screening strategies, though broadly utilized in selecting candidate compounds, often fail to eliminate candidate compounds with non-target effects and/or safety concerns until late in the drug developmental process. Phenotype screening using intact research animals is attractive because it can help identify small molecule candidate compounds that have a high probability of proceeding to clinical use. Most FDA approved, first-in-class small molecules were identified from phenotypic screening. However, phenotypic screening using rodent models is labor intensive, low-throughput, and very expensive. As a novel alternative for small molecule screening, we have been developing gene expression disease profiles, termed the Transcriptional Disease Signature (TDS), as readout of small molecule screens for therapeutic molecules. In this concept, compounds that can reverse, or otherwise affect known disease-associated gene expression patterns in whole animals may be rapidly identified for more detailed downstream direct testing of their efficacy and mode of action. To establish proof of concept for this screening strategy, we employed a transgenic strain of a small aquarium fish, medaka (Oryzias latipes), that overexpresses the malignant melanoma driver gene xmrk, a mutant egfr gene, that is driven by a pigment cell-specific mitf promoter. In this model, melanoma develops with 100% penetrance. Using the transgenic medaka malignant melanoma model, we established a screening system that employs the NanoString nCounter platform to quantify gene expression within custom sets of TDS gene targets that we had previously shown to exhibit differential transcription among xmrk-transgenic and wild-type medaka. Compound-modulated gene expression was identified using an internet-accessible custom-built data processing pipeline. The effect of a given drug on the entire TDS profile was estimated by comparing compound-modulated genes in the TDS using an activation Z-score and Kolmogorov-Smirnov statistics. TDS gene probes were designed that target common signaling pathways that include proliferation, development, toxicity, immune function, metabolism and detoxification. These pathways may be utilized to evaluate candidate compounds for potential favorable, or unfavorable, effects on melanoma-associated gene expression. Here we present the logistics of using medaka to screen compounds, as well as, the development of a user-friendly NanoString data analysis pipeline to support feasibility of this novel TDS drug-screening strategy.
Comparative prevalence of Oxalobacter formigenes in three human populations
Authors: PeBenito Amanda , Nazzal Lama , Wang Chan , Li Huilin , Jay Melanie , Noya-Alarcon Oscar , Contreras Monica , Lander Orlana , Leach Jeff , Dominguez-Bello Maria Gloria , Blaser Martin J.
Published: January 2019

There has been increasing interest in the human anaerobic colonic bacterium Oxalobacter formigenes because of its ability to metabolize oxalate, and its potential contribution to protection from calcium oxalate kidney stones. Prior studies examining the prevalence of this organism have focused on subjects in developed countries and on adults. Now using O. formigenes-specific PCR, we have compared the prevalence of these organisms among subjects in two remote areas in which modern medical practices have hardly been present with a USA group of mothers and their infants for the first three years of life. Among the Amerindians of the Yanomami-Sanema and Yekwana ethnic groups in Venezuela and the Hadza in Tanzania, O. formigenes was detected in 60–80% of the adult subjects, higher than found in adults from USA in this and prior studies. In young children, the prevalence was much lower in USA than in either tribal village. These data extend our understanding of the epidemiology of O. formigenes carriage, and are consistent with the hypothesis that the rising incidence of kidney stones is associated with the progressive loss of O. formigenes colonization in populations that have been highly impacted by modern medical practices.
Ascorbic acid encapsulated into negatively charged liposomes exhibits increased skin permeation, retention and enhances collagen synthesis by fibroblasts
Authors: Maione-Silva Lorena , de Castro Elisandra Gava , Nascimento Thais Leite , Cintra Emílio Ramos , Moreira Larissa Cleres , Cintra Bertilha Alves Santana , Valadares Marize Campos , Lima Eliana Martins
Published: January 2019

Ascorbic acid (AA) is widely used in cosmetic formulations due to its antioxidant property and ability to increase collagen synthesis. Here, we encapsulated AA in vesicles with different lipid compositions. Negative liposome charge favored AA skin retention, with accumulation of 37 ± 12 and 74 ± 23 μg/cm2 in the epidermis and dermis, respectively, after 6 hours. Drug flux was influenced by the formulation composition, and both the presence of cholesterol and the liposomes surface charge were able to increase the amount of AA crossing the skin. The formulation was stable for at least 30 days and promoted a 7-fold increase in flux compared to free AA. Additionally, liposomes were able to interact better with keratinocytes and fibroblasts membranes. In vitro efficacy studies demonstrated that associating AA to these liposomes resulted in increased effectiveness of type I collagen synthesis by fibroblasts and regeneration of UVA-induced damage in keratinocytes. Our results demonstrate the applicability of AA-negatively charged liposomes in promoting AA cutaneous permeation and increasing the retention and flux of this molecule in the skin. This formulation also increased AA stability and effectiveness, opening new perspectives for its application in view of reducing certain skin ageing outcomes.
Transient Second Harmonic Generation Induced by Single Cycle THz pulses in Ba0.8Sr0.2TiO3/MgO
Authors: Grishunin Kirill , Bilyk Vladislav , Sherstyuk Natalia , Mukhortov Vladimir , Ovchinnikov Andrey , Chefonov Oleg , Agranat Mikhail , Mishina Elena , Kimel Alexey V.
Published: January 2019

The ability to switch ferroics (magnets, ferroelectrics, multiferroics) between two stable bit states is the main principle of modern data storage technology. Due to many new ideas, originating from fundamental research during the last 50 years, this technology has developed in a breath-taking fashion. Ever increasing demands for faster and more energy efficient data storage strongly motivate fundamental studies of dynamics in ferroics triggered by ultrashort stimuli. It has been recently realized that nearly single cycle intense THz pulses and the phenomenon of the second harmonic generation are appealing tools for excitation and detection of poorly understood ultrafast dynamics of electric polarization in ferroelectrics at the picosecond timescale. Here we investigate picosecond dynamics of second harmonic from near-infrared pulse in ferroelectric heterostructure Ba0.8Sr0.2TiO3/MgO triggered by the electric field of a nearly single cycle intense THz pulse. The dynamics of the nonlinear optical signal is characterized by a step and oscillations at the frequency of about 1.67 THz. Although the observations can be mistakenly interpreted as oscillations of the electric polarization at the frequency of the soft mode and switching of the order parameter to another metastable state, here we show that the THz modulation of second harmonic generation in Ba0.8Sr0.2TiO3/MgO has a purely optical origin. The observation can be explained assuming that the THz pulse is a relativistically propagating inhomogeneity which induces center of symmetry breaking and linear birefringence. Our work reveals the role of propagation effects in interpretation of time-resolved non-linear optical experiments and thus it has important implications for experimental studies of ultrafast dynamics in ferroics.
Initiation of Pulmonary Fibrosis after Silica Inhalation in Rats is linked with Dysfunctional Shelterin Complex and DNA Damage Response
Authors: Shoeb Mohammad , Mustafa Gul M. , Joseph Pius , Umbright Christina , Kodali Vamsi , Roach Katherine A. , Meighan Terence , Roberts Jenny R. , Erdely Aaron , Antonini James M.
Published: January 2019

Occupational exposure to silica has been observed to cause pulmonary fibrosis and lung cancer through complex mechanisms. Telomeres, the nucleoprotein structures with repetitive (TTAGGG) sequences at the end of chromosomes, are a molecular “clock of life”, and alterations are associated with chronic disease. The shelterin complex (POT1, TRF1, TRF2, Tin2, Rap1, and POT1 and TPP1) plays an important role in maintaining telomere length and integrity, and any alteration in telomeres may activate DNA damage response (DDR) machinery resulting in telomere attrition. The goal of this study was to assess the effect of silica exposure on the regulation of the shelterin complex in an animal model. Male Fisher 344 rats were exposed by inhalation to Min-U-Sil 5 silica for 3, 6, or 12 wk at a concentration of 15 mg/m3 for 6 hr/d for 5 consecutive d/wk. Expression of shelterin complex genes was assessed in the lungs at 16 hr after the end of each exposure. Also, the relationship between increased DNA damage protein (γH2AX) and expression of silica-induced fibrotic marker, αSMA, was evaluated. Our findings reveal new information about the dysregulation of shelterin complex after silica inhalation in rats, and how this pathway may lead to the initiation of silica-induced pulmonary fibrosis.
Epithelial to Mesenchymal transition, eIF2α phosphorylation and Hsp70 expression enable greater tolerance in A549 cells to TiO2 over ZnO nanoparticles
Authors: Martin Ansie , Sarkar Angshuman
Published: January 2019

Type II alveolar cells are highly robust in nature, yet susceptible to aerosolized nanoparticles (NPs). Dysfunction in these specialized cells, can often lead to emphysema, edema, and pulmonary inflammation. Long-time exposure can also lead to dangerous epigenetic modifications and cancer. Among the manufactured nanomaterials, metal oxide nanoparticles are widely encountered owing to their wide range of applications. Scores of published literatures affirm ZnO NPs are more toxic to human alveolar cells than TiO2. However, signalling cascades deducing differences in human alveolar responses to their exposure is not well documented. With A549 cells, we have demonstrated that epithelial to mesenchymal transition and an increased duration of phosphorylation of eIF2α are crucial mechanisms routing better tolerance to TiO2NP treatment over exposure to ZnO. The increased migratory capacity may help cells escape away from the zone of stress. Further, expression of chaperone such as Hsp70 is also enhanced during the same dose-time investigations. This is the first report of its kind. These novel findings could be successfully developed in the future to design relief strategies to alleviate metal oxide nanoparticle mediated stress.
Daclatasvir-based regimens in HCV cirrhosis: experience from the Italian early access program
Authors: Calvaruso Vincenza , Mazzarelli Chiara , Milazzo Laura , Badia Lorenzo , Pasulo Luisa , Guaraldi Giovanni , Lionetti Raffaella , Villa Erica , Borghi Vanni , Carrai Paola , Alberti Alfredo , Biolato Marco , Piai Guido , Persico Marcello , Santantonio Teresa , Felder Martina , Angelico Mario , Montalbano Marzia , Mancusi Rossella Letizia , Grieco Antonio , Angeli Elena , D’Offizi Gianpiero , Fagiuoli Stefano , Belli Luca , Verucchi Gabriella , Puoti Massimo , Craxì Antonio
Published: January 2019

We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n = 221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n = 54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p = 0.56 and 24.2% vs 11.4%, p = 0.13, respectively). SVR rate was significantly higher with the combination DCV + SOF compared with DCV + SIM or ASU (93.2% vs 63.0%, p < 0.0001). Bilirubin value (OR: 0.69, CI95%: 0.54–0.87, p = 0.002) and regimen containing SOF (OR: 9.99, CI95%: 4.09–24.40; p < 0.001) were independently related with SVR. Mean albumin and bilirubin values significantly improved between baseline and follow-up week 12. DCV-based antiviral therapy was well tolerated and resulted in a high SVR when combined with SOF either in pre-transplant and in OLT patients and in “difficult to treat” HCV genotypes. Regimens containing DCV in combination with NS3 protease inhibitors obtained suboptimal results.
Detailed characterization of the Arthrospira type species separating commercially grown taxa into the new genus Limnospira (Cyanobacteria)
Authors: Nowicka-Krawczyk Paulina , Mühlsteinová Radka , Hauer Tomáš
Published: January 2019

The genus Arthrospira has a long history of being used as a food source in different parts of the world. Its mass cultivation for production of food supplements and additives has contributed to a more detailed study of several species of this genus. In contrast, the type species of the genus (A. jenneri), has scarcely been studied. This work adopts a polyphasic approach to thoroughly investigate environmental samples of A. jenneri, whose persistent bloom was noticed in an urban reservoir in Poland, Central Europe. The obtained results were compared with strains designated as A. platensis, A. maxima, and A. fusiformis from several culture collections and other Arthrospira records from GenBank. The comparison has shown that A. jenneri differs from popular species that are massively utilized commercially with regard to its cell morphology, ultrastructure and ecology, as well as its 16S rRNA gene sequence. Based on our findings, we propose the establishment of a new genus, Limnospira, which currently encompasses three species including the massively produced L. (A.) fusiformis and L. (A.) maxima with the type species Limnospira fusiformis.
Surface Emitting, Tunable, Mid-Infrared Laser with High Output Power and Stable Output Beam
Authors: Slivken Steven , Wu Donghai , Razeghi Manijeh
Published: January 2019

A reflective outcoupler is demonstrated which can allow for stable surface emission from a quantum cascade laser and has potential for cost-effective wafer-scale manufacturing. This outcoupler is integrated with an amplified, electrically tunable laser architecture to demonstrate high power surface emission at a wavelength near 4.9 μm. Single mode peak power up to 6.7 W is demonstrated with >6 W available over a 90 cm−1 (215 nm) spectral range. A high quality output beam is realized with a simple, single-layer, anti-reflective coating. The beam shape and profile are shown to be independent of wavelength.
Arrestin-1 engineering facilitates complex stabilization with native rhodopsin
Authors: Haider Raphael S. , Wilhelm Florian , Rizk Aurélien , Mutt Eshita , Deupi Xavier , Peterhans Christian , Mühle Jonas , Berger Philipp , Schertler Gebhard F. X. , Standfuss Jörg , Ostermaier Martin K.
Published: January 2019

Arrestin-1 desensitizes the activated and phosphorylated photoreceptor rhodopsin by forming transient rhodopsin−arrestin-1 complexes that eventually decay to opsin, retinal and arrestin-1. Via a multi-dimensional screening setup, we identified and combined arrestin-1 mutants that form lasting complexes with light-activated and phosphorylated rhodopsin in harsh conditions, such as high ionic salt concentration. Two quadruple mutants, D303A + T304A + E341A + F375A and R171A + T304A + E341A + F375A share similar heterologous expression and thermo-stability levels with wild type (WT) arrestin-1, but are able to stabilize complexes with rhodopsin with more than seven times higher half-maximal inhibitory concentration (IC50) values for NaCl compared to the WT arrestin-1 protein. These quadruple mutants are also characterized by higher binding affinities to phosphorylated rhodopsin, light-activated rhodopsin and phosphorylated opsin, as compared with WT arrestin-1. Furthermore, the assessed arrestin-1 mutants are still specifically associating with phosphorylated or light-activated receptor states only, while binding to the inactive ground state of the receptor is not significantly altered. Additionally, we propose a novel functionality for R171 in stabilizing the inactive arrestin-1 conformation as well as the rhodopsin–arrestin-1 complex. The achieved stabilization of the active rhodopsin–arrestin-1 complex might be of great interest for future structure determination, antibody development studies as well as drug-screening efforts targeting G protein-coupled receptors (GPCRs).
High strength metallic wood from nanostructured nickel inverse opal materials
Authors: Pikul James H. , Özerinç Sezer , Liu Burigede , Zhang Runyu , Braun Paul V. , Deshpande Vikram S. , King William P.
Published: January 2019

This paper describes a nickel-based cellular material, which has the strength of titanium and the density of water. The material’s strength arises from size-dependent strengthening of load-bearing nickel struts whose diameter is as small as 17 nm and whose 8 GPa yield strength exceeds that of bulk nickel by up to 4X. The mechanical properties of this material can be controlled by varying the nanometer-scale geometry, with strength varying over the range 90–880 MPa, modulus varying over the range 14–116 GPa, and density varying over the range 880–14500 kg/m3. We refer to this material as a “metallic wood,” because it has the high mechanical strength and chemical stability of metal, as well as a density close to that of natural materials such as wood.
Delivery of mRNA to platelets using lipid nanoparticles
Authors: Novakowski S. , Jiang K. , Prakash G. , Kastrup C.
Published: January 2019

Platelets are natural delivery vehicles within the blood, carrying and releasing their contents at sites of vasculature damage. Investigating the biology of platelets, and modifying them for new therapeutic uses, is limited by a lack of methods for efficiently transfecting these cells. The ability of four different classes of lipid nanoparticles (LNPs) to deliver mRNA to platelets was compared using confocal microscopy, flow cytometry and quantitative PCR. The amount of mRNA delivered, mechanism of uptake, and extent of platelet activation depended on the LNP formulation and platelet storage conditions. Cationic LNPs (cLNPs) delivered mRNA to the largest percentage of platelets but induced platelet activation. Ionizable cationic LNPs (icLNPs) delivered mRNA to fewer platelets and did not induce activation. Furthermore, mRNA delivered using icLNPs and cLNPs was stable in resting platelets and was released in platelet microparticles under specific conditions. The results demonstrate that mRNA can be delivered to platelets using cLNPs and icLNPs without impairing platelet aggregation or spreading. Optimizing the LNP formulations used here may lead to a transfection agent for platelets that allows for de novo synthesis of exogenous proteins in the future.
TGF-β-SNAIL axis induces Müller glial-mesenchymal transition in the pathogenesis of idiopathic epiretinal membrane
Authors: Kanda Atsuhiro , Noda Kousuke , Hirose Ikuyo , Ishida Susumu
Published: January 2019

The epithelial-mesenchymal transition (EMT) is a key process in fibrogenic diseases where transdifferentiated myofibroblasts produce excessive amounts of extracellular matrix, resulting in organ dysfunction. Idiopathic epiretinal membrane (iERM) is a vision-threatening disorder characterized by fibrocellular proliferation and contraction on the central retina. Müller glial cells, which regulate retinal physiology and structure, are the major cellular components in the iERM tissue; however, the pathological role of this cell type remains incompletely understood. Here we revealed the involvement of Müller glial-mesenchymal transition (GMT), as an alternative to EMT, in the pathogenesis of iERM lacking epithelial contribution in nature. Of various pro-fibrotic cytokines, transforming growth factor (TGF)-β1 stimulation to human Müller glial cells exclusively increased mRNA and protein levels of several EMT-related molecular markers, together with the transcription factor SNAIL but not SLUG or TWIST. TGF-β1-stimulated Müller cells also exhibited EMT-related cell motility, while reducing the expression of glutamine synthetase (GS), a Müller glial marker. Notably, all of these TGF-β-induced EMT features were reversed bySNAI1knockdown in Müller cells. iERM patient specimens demonstrated co-immunolocalization of SNAIL with TGF-β1, GS, and smooth muscle protein 22. Our data implicated a critical role of the TGF-β-SNAIL axis in Müller GMT to promote iERM formation.
Legionella SBT applied directly to respiratory samples as a rapid molecular epidemiological tool
Authors: Quero Sara , Párraga-Niño Noemí , Sabria Miquel , Barrabeig Irene , Sala Maria Rosa , Jané Mireia , Mateu Lourdes , Sopena Nieves , Pedro-Botet Maria Luisa , Garcia-Nuñez Marian
Published: January 2019

Legionnaires’ disease (LD) is an atypical pneumonia caused by the inhalation of Legionella. The methods used for the diagnosis of LD are direct culture of respiratory samples and urinary antigen detection. However, the sensitivity of culture is low, and the urinary antigen test is specific only for L. pneumophila sg1. Moreover, as no isolates are obtained, epidemiological studies cannot be performed. The implementation of Nested-sequence-based typing (Nested-SBT) makes it possible to carry out epidemiological studies while also confirming LD, especially in cases caused by non-sg 1. Sixty-two respiratory samples from patients with Legionella clinically confirmed by positive urinary antigen tests were cultured and tested by Nested-SBT, following the European Study Group for Legionella Infections (ESGLI) protocol. Only 2/62 (3.2%) respiratory samples were culture-positive. Amplification and sequencing of Nested-SBT genes were successfully performed in 57/62 samples (91.9%). The seven target genes were characterised in 39/57 (68.4%) respiratory samples, and the complete sequence type (ST) was obtained. The mip gene was the most frequently amplified and sequenced. Nested-SBT is a useful method for epidemiological studies in culture-negative samples, achieving a 28.7-fold improvement over the results of culture studies and reducing the time needed to obtain molecular epidemiological results.
Experimental Demonstration on Quantum Sensitivity to Available Information in Decision Making
Authors: Lee Joong-Sung , Bang Jeongho , Lee Jinhyoung , Lee Kwang-Geol
Published: January 2019

We present an experimental illustration on the quantum sensitivity of decision making machinery. In the decision making process, we consider the role of available information, say hint, whether it influences the optimal choices. To the end, we consider a machinery method of decision making in a probabilistic way. Our main result shows that in decision making process our quantum machine is more highly sensitive than its classical counterpart to the hints we categorize into “good” and “poor”. This quantum feature originates from the quantum superposition involved in the decision making process. We also show that the quantum sensitivity persists before the quantum superposition is completely destroyed.
Gut microbiota-mediated Gene-Environment interaction in the TashT mouse model of Hirschsprung disease
Authors: Touré Aboubacrine Mahamane , Landry Mathieu , Souchkova Ouliana , Kembel Steven W. , Pilon Nicolas
Published: January 2019

Based on the bilateral relationship between the gut microbiota and formation/function of the enteric nervous system (ENS), we sought to determine whether antibiotics-induced dysbiosis might impact the expressivity of genetically-induced ENS abnormalities. To address this, we took advantage of the TashT mouse model of Hirschsprung disease, in which colonic aganglionosis and hypoganglionosis are both much more severe in males. These defects result into two male-biased colon motility phenotypes: either megacolon that is lethal around weaning age or chronic constipation in adults, the latter being also associated with an increased proportion of nitrergic neurons in the distal ENS. Induction of dysbiosis using a cocktail of broad-spectrum antibiotics specifically impacted the colonic ENS of TashTTg/Tg mice in a stage-dependent manner. It further decreased the neuronal density at post-weaning age and differentially modulated the otherwise increased proportion of nitrergic neurons, which appeared normalized around weaning age and further increased at post-weaning age. These changes delayed the development of megacolon around weaning age but led to premature onset of severe constipation later on. Finally, local inhibition of nitric oxide signaling improved motility and prevented death by megacolon. We thus conclude that exposure to antibiotics can negatively influence the expressivity of a genetically-induced enteric neuropathy.
Optimal composition of the poly(triarylamine)-based polymer composite to maximize photorefractive performance
Authors: Masumura Kento , Nakanishi Ikumi , Van Thi Khuat Khanh , Kinashi Kenji , Sakai Wataru , Tsutsumi Naoto
Published: January 2019

A holographic display system requires the external diffraction efficiency to be greater than 10% and four orders of magnitude of sensitivity for practical usage. To achieve such requirements, the photorefractive (PR) performance of PR composite based on poly[bis(2,4,6-trimethylpheneyl)amine] (PTAA) has been investigated. In the present report, the change of the content of PTAA as a photoconductive polymer, (2,4,6-trimethylphenyl)diphenylamine (TAA) as a photoconductive plasticizer, and second trap agent bathophenanthroline (BPhen) reasonably optimized the PR response time and external diffraction efficiency. High sensitivity of 1851 cm2 J−1 with response time of 494 μs and external diffraction efficiency of 23.9% were achieved at 532 nm and 60 V μm−1 by reducing the content of PTAA and increasing the contents of TAA and BPhen. Decreasing the amount of PTAA and increasing the contents of TAA and BPhen lowered the absorption coefficient, resulting in the high external diffraction efficiency. The narrower distribution of the electronic density of states (DOS) for PTAA/TAA (43.5/20 and 33.5/30) also contributed to the shorter PR response time of hundreds of microseconds.
Development of a peptide-siRNA nanocomplex targeting NF- κB for efficient cartilage delivery
Authors: Yan Huimin , Duan Xin , Pan Hua , Akk Antonina , Sandell Linda J. , Wickline Samuel A. , Rai Muhammad Farooq , Pham Christine T. N.
Published: January 2019

Delivery of therapeutic small interfering RNAs (siRNAs) in an effective dose to articular cartilage is very challenging as the cartilage dense extracellular matrix renders the chondrocytes inaccessible, even to intra-articular injections. Herein, we used a self-assembling peptidic nanoparticle (NP) platform featuring a cell penetrating peptide complexed to NF-κB p65 siRNA. We show that it efficiently and deeply penetrated human cartilage to deliver its siRNA cargo up to a depth of at least 700 μm. To simulate osteoarthritis in vitro, human articular cartilage explants were placed in culture and treated with IL-1β, a cytokine with known cartilage catabolic and pro-inflammatory effects. Exposure of peptide-siRNA NP to cartilage explants markedly suppressed p65 activation, an effect that persisted up to 3 weeks after an initial 48 h exposure to NP and in the presence of continuous IL-1β stimulation. Suppression of IL-1β-induced p65 activity attenuated chondrocyte apoptosis and maintained cartilage homeostasis. These findings confirm our previous in vivo studies in a murine model of post-traumatic osteoarthritis and suggest that the ability of peptide-siRNA NP to specifically modulate NF-κB pathway, a central regulator of the inflammatory responses in chondrocytes, may potentially mitigate the progression of cartilage degeneration.