bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme Arsenic Bioaccumulation Factor Variability in Lake Titicaca, Bolivia
Authors: Sarret Géraldine , Guédron Stéphane , Acha Dario , Bureau Sarah , Arnaud-Godet Florent , Tisserand Delphine , Goni-Urriza Marisol , Gassie Claire , Duwig Céline , Proux Olivier , Aucour Anne-Marie 
Published: July 2019

AbstractLatin America, like other areas in the world, is faced with the problem of high arsenic (As) background in surface and groundwater, with impacts on human health. We studied As biogeochemical cycling by periphyton in Lake Titicaca and the mine-impacted Lake Uru Uru. As concentration was measured in water, sediment, totora plants (Schoenoplectus californicus) and periphyton growing on stems, and As speciation was determined by X-ray absorption spectroscopy in bulk and EDTA-extracted periphyton. Dissolved arsenic was between 5.0 and 15 μg L−1 in Lake Titicaca and reached 78.5 μg L−1 in Lake Uru Uru. As accumulation in periphyton was highly variable. We report the highest As bioaccumulation factors ever measured (BAFsperiphyton up to 245,000) in one zone of Lake Titicaca, with As present as As(V) and monomethyl-As (MMA(V)). Non-accumulating periphyton found in the other sites presented BAFsperiphyton between 1281 and 11,962, with As present as As(III), As(V) and arsenosugars. DNA analysis evidenced several taxa possibly related to this phenomenon. Further screening of bacterial and algal isolates would be necessary to identify the organism(s) responsible for As hyperaccumulation. Impacts on the ecosystem and human health appear limited, but such organisms or consortia would be of great interest for the treatment of As contaminated water.
Dose-dependent metabolite changes after ethanol intoxication in rat prefrontal cortex using in vivo magnetic resonance spectroscopy
Authors: Carton Louise , Auger Florent , Kyheng Maeva , Pétrault Maud , Durieux Nicolas , Allorge Delphine , Cottencin Olivier , Jardri Renaud , Bordet Régis , Rolland Benjamin 
Published: July 2019

AbstractEthanol disrupts the balance between the excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission systems. We aimed to assess how acute ethanol intoxication in rats affects the levels of GABA, glutamate and other cerebral metabolites after injection of two different doses of ethanol. One in vivo magnetic resonance spectrum of the prefrontal cortex region was acquired before and six spectra were acquired after intraperitoneal injections of saline or ethanol (1 g/kg or 2 g/kg). Brain kinetics after exposure to ethanol were compared to blood ethanol kinetics. GABA levels significantly decreased after injection of 1 g/kg but not 2 g/kg doses of ethanol. Choline levels, which serve as a marker of alterations in membrane composition, significantly decreased after injection of 2 g/kg but not 1 g/kg doses of ethanol. Acute ethanol intoxication appears to result in specific dose-dependent changes in the GABA level and choline level.
City-wide electronic health records reveal gender and age biases in administration of known drug–drug interactions
Authors: Brattig Correia Rion , de Araújo Kohler Luciana P. , Mattos Mauro M. , Rocha Luis M. 
Published: July 2019

AbstractThe occurrence of drug–drug-interactions (DDI) from multiple drug dispensations is a serious problem, both for individuals and health-care systems, since patients with complications due to DDI are likely to reenter the system at a costlier level. We present a large-scale longitudinal study (18 months) of the DDI phenomenon at the primary- and secondary-care level using electronic health records (EHR) from the city of Blumenau in Southern Brazil (pop. ≈340,000). We found that 181 distinct drug pairs known to interact were dispensed concomitantly to 12% of the patients in the city’s public health-care system. Further, 4% of the patients were dispensed drug pairs that are likely to result in major adverse drug reactions (ADR)—with costs estimated to be much larger than previously reported in smaller studies. The large-scale analysis reveals that women have a 60% increased risk of DDI as compared to men; the increase becomes 90% when considering only DDI known to lead to major ADR. Furthermore, DDI risk increases substantially with age; patients aged 70–79 years have a 34% risk of DDI when they are dispensed two or more drugs concomitantly. Interestingly, a statistical null model demonstrates that age- and female-specific risks from increased polypharmacy fail by far to explain the observed DDI risks in those populations, suggesting unknown social or biological causes. We also provide a network visualization of drugs and demographic factors that characterize the DDI phenomenon and demonstrate that accurate DDI prediction can be included in health care and public-health management, to reduce DDI-related ADR and costs.
Overexpression of long noncoding RNA HOXB-AS3 indicates an unfavorable prognosis and promotes tumorigenesis in epithelial ovarian cancer via Wnt/β-catenin signaling pathway
Authors: Zhuang Xiao-hong , liu Ying , Li Jin-ling 
Published: July 2019

Abstract
Long noncoding RNA HOXB cluster antisense RNA 3 (HOXB-AS3) has been reported to be dysregulated in several tumors. The present study mainly aims at the investigation in how HOXB-AS3 works in epithelial ovarian cancer (EOC) and to elucidate the mechanism involved. Initially, ‘GEPIA’ was mined to examine the differential expression levels and prognostic value of HOXB-AS3 in EOC patients. The expression of HOXB-AS3 in EOC cell lines and patient specimens was examined with quantitative RT-PCR. Simultaneously, the correlation of HOXB-AS3 expression with a variety of clinicopathological factors and patient survival was analyzed. MTT, colony formation and flow cytometry assays were performed to analyze the cell viability of EOC cells. Wound healing and Transwell assays were carried out to determine EOC cells’ capability of migrating and invading. The impact of HOXB-AS3 on EMT and Wnt/β-catenin signaling was explored with the approach of Western blot. We found that in both EOC cell lines and tissues, HOXB-AS3 expression was significantly up-regulated, and its high expression was an independent prognostic marker of poor outcome for EOC patients. In vitro loss-of-function assays revealed that HOXB-AS3 knockdown inhibited EOC cells proliferation, migration, invasion and EMT, and induced EOC cells’ apoptosis. Furthermore, we validated that down-regulated HOXB-AS3 attenuated the activity of Wnt/β-catenin signaling to suppress the invasion, migration and proliferation of EOC cells. To sum up, the present study came up with the conclusion that HOXB-AS3 acts as an oncogenic gene in EOC progression through HOXB-AS3-Wnt/β-catenin signaling regulation, providing a novel insight into EOC tumorigenesis.
Empagliflozin prevents cardiomyopathy via sGC-cGMP-PKG pathway in type 2 diabetes mice
Authors: Xue Mei , Li Ting , Wang Yue , Chang Yunpeng , Cheng Ying , Lu Yunhong , Liu Xiangyang , Xu Linxin , Li Xiaoyu , Yu Xiaochen , Sun Bei , Chen Liming 
Published: July 2019

Abstract
Cardiovascular complications contribute to the major mortality and morbidity in type 2 diabetes. Diabetic cardiomyopathy (DCM) is increasingly recognized as an important cause of heart failure. EMPA-REG OUTCOME trial has reported that empagliflozin, the sodium-glucose cotransporter 2 inhibitor, exerts cardiovascular benefits on diabetic population. However, the mechanism by which empagliflozin alleviates DCM still remains unclear. In the current study, we investigated the cardiac protective effects of empagliflozin on spontaneous type 2 diabetic db/db mice and its potential mechanism. Eight weeks of empagliflozin treatment (10 mg/kg/day) decreased body weight and blood glucose level, and increased urinary glucose excretion (UGE) in diabetic mice. Echocardiography revealed that both systolic and diastolic functions of db/db mice were also obviously improved by empagliflozin. Furthermore, empagliflozin-treated diabetic mice presented with amelioration of cardiac hypertrophy and fibrosis. In addition, diabetic hearts exhibited the deterioration of oxidative stress, apoptosis and pyroptosis, while these effects were significantly counteracted after empagliflozin treatment. Moreover, empagliflozin rescued diabetes-induced suppression of sGC (soluble guanylate cyclase enzyme)-cGMP (cyclic guanosine monophosphate)-PKG (cGMP-dependent protein kinase) pathway. However, when sGC-β expression of hearts was inhibited by transvascular delivery of small interfering RNA, cardiac dysfunction was aggravated and the advantages of empagliflozin were reversed through inhibiting sGC-cGMP-PKG pathway. Collectively, these findings indicate that empagliflozin improves cardiac function involving the inhibition of oxidative stress-induced injury via sGC-cGMP-PKG pathway and may be a promising therapeutic option for DCM.
Computerized Speechreading Training for Deaf Children: A Randomized Controlled Trial
Authors: Pimperton Hannah , Kyle Fiona , Hulme Charles , Harris Margaret , Beedie Indie , Ralph-Lewis Amelia , Worster Elizabeth , Rees Rachel , Donlan Chris , MacSweeney Mairéad 
Published: July 2019

Purpose
We developed and evaluated in a randomized controlled trial a computerized speechreading training program to determine (a) whether it is possible to train speechreading in deaf children and (b) whether speechreading training results in improvements in phonological and reading skills. Previous studies indicate a relationship between speechreading and reading skill and further suggest this relationship may be mediated by improved phonological representations. This is important since many deaf children find learning to read to be very challenging.

Method
Sixty-six deaf 5- to 7-year-olds were randomized into speechreading and maths training arms. Each training program was composed of a 10-min sessions a day, 4 days a week for 12 weeks. Children were assessed on a battery of language and literacy measures before training, immediately after training, and 3 months and 11 months after training.

Results
We found no significant benefits for participants who completed the speechreading training, compared to those who completed the maths training, on the speechreading primary outcome measure. However, significantly greater gains were observed in the speechreading training group on one of the secondary measures of speechreading. There was also some evidence of beneficial effects of the speechreading training on phonological representations; however, these effects were weaker. No benefits were seen to word reading.

Conclusions
Speechreading skill is trainable in deaf children. However, to support early reading, training may need to be longer or embedded in a broader literacy program. Nevertheless, a training tool that can improve speechreading is likely to be of great interest to professionals working with deaf children.

Supplemental Material

https://doi.org/10.23641/asha.8856356
Bifunctional reconfigurable metasurface for manipulating reflected waves in real‐time with broad tuning band
Authors: Liao Dashuang , Wang Haogang , Zhang Youfei , Qian Chao 
Published: July 2019

A bifunctional reconfigurable phase‐modulated metasurface for manipulating reflected waves is proposed. Each constituent element incorporates a varactor diode, and the reflection response of the unit cell can be tuned through feeding different bias voltages. Thus, the entire phase distribution of the metasurface is modulated to achieve different electromagnetic responses by controlling the active meta‐atoms. As the bias voltage changes from 0 to 19 V, the measured resonant frequency shifts from 6.5 to 8.7 GHz, resulting in a broad tuning band. Here, the functionalities of beam deflection and focusing are experimentally demonstrated at microwave frequencies, which can be switched in real‐time using a programmable voltage controller. The proposed metasurface provides a promising versatile platform for numerous applications, such as smart stealth missions and holograms.
Low‐profile transmitarray lens antenna of X‐band with one layer of substrate and metallic vias
Authors: Yu Shixing , Kou Na , Ding Zhao , Zhang Zhengping 
Published: July 2019

A low‐profile transmitarray lens design is presented at X‐band, which is composed of only one layer of substrate with thickness of 0.13 free‐space wavelengths. The transmitted unit cell utilises structure of two metallic layers and four via holes, broadening the transmitted phase shift range to more than 310° while transmission magnitude is within −3 dB under normal incidence. A prototype of the transmitarray lens with aperture size of 280 mm is designed, simulated and measured. Measurement and simulation results agree well with each other and gain of 23.9 dBi is obtained at 10 GHz; the proposed low‐profile transmitarray lens antenna could be applied to practical X‐band radar systems with low cost and convenience.
The bridge: a transient phenomenon of forming stellar multiples
Authors: Kuffmeier M. , Calcutt H. , Kristensen L. E. 
Published: July 2019

Context. Observations with modern instruments such as Herschel reveal that stars form clustered inside filamentary arms of ~1 pc length embedded in giant molecular clouds (GMCs). On smaller scales of ~1000 au, observations of IRAS 16293–2422, for example, show signs of filamentary “bridge” structures connecting young protostars to their birth environment.
Aims. We aim to find the origin of bridges associated with deeply embedded protostars by characterizing their connection to the filamentary structure present on GMC scales and to the formation of protostellar multiples.
Methods. Using the magnetohydrodynamical code RAMSES, we carried out zoom-in simulations of low-mass star formation starting from GMC scales. We analyzed the morphology and dynamics involved in the formation process of a triple system.
Results. Colliding flows of gas in the filamentary arms induce the formation of two protostellar companions at distances of ~1000 au from the primary. After their birth, the stellar companions quickly approach, at Δt ~ 10 kyr, and orbit the primary on eccentric orbits with separations of ~100 au. The colliding flows induce transient structures lasting for up to a few 10 kyr that connect two forming protostellar objects that are kinematically quiescent along the line-of-sight.
Conclusions. Colliding flows compress gas and trigger the formation of stellar companions via turbulent fragmentation. Our results suggest that protostellar companions initially form with a wide separation of ~1000 au. Smaller separations of a ≲ 100 au are a consequence of subsequent migration and capturing. Associated with the formation phase of the companion, the turbulent environment induces the formation of arc- and bridge-like structures. These bridges can become kinematically quiescent when the velocity components of the colliding flows eliminate each other. However, the gas in bridges still contributes to stellar accretion later. Our results demonstrate that bridge-like structures are a transient phenomenon of stellar multiple formation.
How do substitutability and effort asymmetry change resource management in coupled natural-human systems?
Authors: Oh Woi Sok , Muneepeerakul Rachata 
Published: July 2019

AbstractHumans require multiple natural resources for their wellbeing and assign different portions of their efforts to secure resources due to their limited time and energy. When one resource is scarce, it may be replaced with a substitute which may fully or partially cover the shortage. However, existing research of coupled natural-human systems (CNHS) usually focuses on a single resource and misses these aspects. To fill the gaps, we question: how would substitutability and effort asymmetry influence system responses, resource management, and sustainability? Building on an existing conceptual framework, we developed a CNHS model with two resources and infrastructures in a centralized governance structure. Model analysis showed that substitutability and effort asymmetry significantly influence policy flexibility, performance, and sustainability of the coupled system, thereby highlighting challenges and offering insights in governing systems with multiple resources.
Increased ER–mitochondria tethering promotes axon regeneration
Authors: Lee Soyeon , Wang Wei , Hwang Jinyeon , Namgung Uk , Min Kyung-Tai 
Published: July 2019

Significance
Small organelles such as endoplasmic reticulum (ER) and mitochondria play key roles in cellular functions and survival. Furthermore, physical tethering between ER–mitochondria allows communication between these 2 organelles, and proteins involved in the contact sites have been identified in various cells. However, physiological significances of ER–mitochondria contacts in axons are unknown. Here, we discover that Grp75 mRNA is locally translated in injured axonal tips. Up-regulation of Grp75 promotes ER–mitochondria tethering and enhances axon regeneration in vitro. Increased levels ofGrp75 in dorsal root ganglion neurons facilitates axon regeneration and functional recovery of animals with nerve injury. These results imply that overexpression of Grp75 may provide a therapeutic strategy to treat and enhance axonal regeneration following nerve injury.
Acute social isolation alters neurogenomic state in songbird forebrain
Authors: George Julia M. , Bell Zachary W. , Condliffe Daniel , Dohrer Kirstin , Abaurrea Teresa , Spencer Karen , Leitão Albertine , Gahr Manfred , Hurd Paul J. , Clayton David F. 
Published: July 2019

SignificanceOur results show that the experience of being alone has immediate consequences on brain gene activity. Clearly this is important for the human context, where loneliness (i.e., perceived social isolation) is a risk factor for psychological and neurodegenerative disorders. As the response occurs in brain areas involved in higher-order cognition and perception, these changes in gene activity may influence the ongoing processing of experience. Prior studies in humans have measured effects of social isolation in circulating leukocytes, but not in brain, and studies in mammalian models have typically focused on effects of much longer isolation periods (weeks or more). The results also bear on interpretation of animal experiments where short-term isolation is used to establish the baseline reference condition.
Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients
Authors: Artoni Pietro , Piffer Arianna , Vinci Viviana , LeBlanc Jocelyn , Nelson Charles A. , Hensch Takao K. , Fagiolini Michela 
Published: July 2019

Significance
Neurodevelopmental spectrum disorders such as autism (ASD) are typically diagnosed at an age beyond the heightened plasticity of the infant brain, when behavioral intervention would be most effective. Here, we show that mouse models of idiopathic or monogenic ASD share common alterations in arousal modulation that can be detected by machine learning early in life. In this transfer study across species and measures, we show that a neural network trained on mice can be refined by transfer learning to be useful for ASD patients, even when different proxies of arousal fluctuations are used (e.g., pupillometry or heart rate variation). This now offers a quantitative, noninvasive, and highly translational biomarker for the early detection of developmental disorders.
Human species-specific loss of CMP-
N
-acetylneuraminic acid hydroxylase enhances atherosclerosis via intrinsic and extrinsic mechanisms
Authors: Kawanishi Kunio , Dhar Chirag , Do Raymond , Varki Nissi , Gordts Philip L. S. M. , Varki Ajit 
Published: July 2019

Significance
Cardiovascular disease (CVD) events like heart attacks and strokes due to atherosclerotic narrowing of arteries are the commonest cause of worldwide deaths, but many first-time events occur in individuals without known risk factors. In contrast, such events are extremely rare in other animals despite some of the same risk factors. While environmental and behavioral factors likely contribute to the difference, we show here that a human-specific genetic mutation affecting cell-surface molecules called sialic acids may be one other factor. We also show that the same mutation can help explain the apparently human-specific increased risk of CVD events associated with red meat consumption. The humanized mouse systems we present could be explored as models for future studies of atherosclerosis.
Observation of methane filled hexagonal ice stable up to 150 GPa
Authors: Schaack Sofiane , Ranieri Umbertoluca , Depondt Philippe , Gaal Richard , Kuhs Werner F. , Gillet Philippe , Finocchi Fabio , Bove Livia E. 
Published: July 2019

Significance
Gas clathrates in which water cages enclose the guest gas molecules naturally form on our planet, for instance on ocean floors. Related methane hydrates are also expected to be present under very high pressures (10 to 200 GPa) in giant planetary interiors such as Uranus or Neptune. However, the stability of such structures at these pressures is currently debated. Joint Raman spectroscopy and ab initio simulations show the stability of a high-pressure methane hydrate phase up to at least 150 GPa, the highest pressure explored to date for such compounds. The structure of this phase and the complex transition mechanism from the known MH-III phase are detailed and shown to be in accordance with all known experimental observations.
A photostable fluorescent marker for the superresolution live imaging of the dynamic structure of the mitochondrial cristae
Authors: Wang Chenguang , Taki Masayasu , Sato Yoshikatsu , Tamura Yasushi , Yaginuma Hideyuki , Okada Yasushi , Yamaguchi Shigehiro 
Published: July 2019

Significance
Stimulated emission depletion (STED) microscopy is one of the most appealing tools to visualize nanoscale cellular structures and dynamics in living cells. However, its practical utility is significantly limited by the rapid photobleaching of fluorescent dyes under the ultrastrong depletion laser. In this context, superphotostable fluorescent probes, which enable repeated recording of the STED images, are crucial chemical tools to extend the application of STED microscopy in live-cell imaging. Herein, we report a developed fluorescent probe, MitoPB Yellow, which has the characters of outstanding photostability, long fluorescence lifetime, and mitochondrial inner membrane selectivity for staining. In combination with a time-gated-STED microscopy, the mitochondrial inner-membrane structures and dynamics can be impressively visualized in living cells.
Gid10 as an alternative N-recognin of the Pro/N-degron pathway
Authors: Melnykov Artem , Chen Shun-Jia , Varshavsky Alexander 
Published: July 2019

SignificanceIn eukaryotes, N-degron pathways comprise proteolytic systems whose unifying feature is their ability to recognize proteins containing N-terminal degradation signals called N-degrons, thereby causing degradation of these proteins. Gid4, a subunit of the GID ubiquitin ligase in the yeastSaccharomyces cerevisiae, is the recognition component (N-recognin) of the Pro/N-degron pathway. Gid4 targets proteins by recognizing their N-terminal Pro residues or a Pro at position 2. We identified an uncharacterized Gid4-like yeast protein, termed Gid10. A screen for N-terminal sequence motifs that can bind to Gid10 showed that substrate specificities of Gid10 and Gid4 overlap but are not identical. We also found that Gid10 can function as a specific N-recognin of the GID ubiquitin ligase and the Pro/N-degron pathway.