bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto–Kakizaki rats
Authors: Ouyang Xiaojun , Li Shiying , Tan Yan , Lin Lin , Yin Jieyun , Chen Jiande D. Z. 
Published: February 2019

Abstract
Background/Objective
Recently, intestinal electrical stimulation (IES) has been reported to result in weight loss; however, it is unclear whether it has a therapeutic potential for diabetes. The aim of the present study was to explore the potential hypoglycemic effects of IES and its possible mechanisms involving β cells in diabetic rats.

Subjects/Methods
Diabetic Goto–Kakizaki (GK) rats were chronically implanted with one pair of electrodes in the duodenum. The oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed with or without IES, and plasma glucagon-like peptide-1 (GLP-1) and insulin level were measured. In the other two OGTT sessions, rats were treated with either Exendin (9–39) (GLP-1 antagonist) or Exendin (9–39) plus IES to investigate the underlying mechanism involving GLP-1. Gastric emptying and small intestinal transit were also measured with or without IES. In a chronic study, GK rats were treated with IES or Sham-IES for 8 weeks. Blood glucose, plasma GLP-1 and insulin level, body weight, and food intake were measured. Pancreas weight, islet β-cell apoptosis, and proliferation were also analyzed.

Results
Acute IES reduced blood glucose level from 60 to 120 min during OGTT by 16–20% (all p < 0.05, vs. Sham-IES). GLP-1 antagonist significantly blocked the inhibitory effect of IES on hyperglycemia from 15 to 120 min (all p < 0.05). IES accelerated the small intestinal transit by 15% (p = 0.004). After 8 weeks of chronic stimulation, IES significantly reduced blood glucose (p < 0.05) and body weight (p = 0.02) and increased the plasma GLP-1 concentration (p < 0.05). Furthermore, we observed that chronic IES reduced pancreatic β-cell apoptosis (p = 0.045), but showed no effects on β-cell proliferation.

Conclusions
Our study firstly proved the hypoglycemic effect of IES in a rodent model of type 2 diabetes, possibly attributed to the increasing GLP-1 secretion and improvement in β-cell functions.
Defining the role of Parasutterella, a previously uncharacterized member of the core gut microbiota
Authors: Ju Tingting , Kong Ji Yoon , Stothard Paul , Willing Benjamin P 
Published: February 2019

Abstract
The genus of Parasutterella has been defined as a core component of the human and mouse gut microbiota, and has been correlated with various health outcomes. However, like most core microbes in the gastrointestinal tract (GIT), very little is known about the biology of Parasutterella and its role in intestinal ecology. In this study, Parasutterella was isolated from the mouse GIT and characterized in vitro and in vivo. Mouse, rat, and human Parasutterella isolates were all asaccharolytic and producers of succinate. The murine isolate stably colonized the mouse GIT without shifting bacterial composition. Notable changes in microbial-derived metabolites were aromatic amino acid, bilirubin, purine, and bile acid derivatives. The impacted bile acid profile was consistent with altered expression of ileal bile acid transporter genes and hepatic bile acid synthesis genes, supporting the potential role of Parasutterella in bile acid maintenance and cholesterol metabolism. The successful colonization of Parasutterella with a single environmental exposure to conventional adult mice demonstrates that it fills the ecological niche in the GIT and contributes to metabolic functionalities. This experiment provides the first indication of the role of Parasutterella in the GIT, beyond correlation, and provides insight into how it may contribute to host health.
Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model
Authors: van de Wijer Lisa , Garcia Lidiane P. , Hanswijk Sabrina I. , Rando Juliette , Middelman Anthonieke , ter Heine Rob , Mast Quirijn de , Martens Gerard J. M. , van der Ven André J. A. M. , Kolk Sharon M. , Schellekens Arnt F. A. , Homberg Judith R. 
Published: February 2019

AbstractEfavirenz is recommended as a preferred first-line drug for women of childbearing potential living with human immunodeficiency virus. Efavirenz is known for its central nervous system side effects, which are partly mediated by serotonergic actions. The neurotransmitter serotonin exerts neurotrophic effects during neurodevelopment and antenatal exposure to serotonergic agents has been linked to developmental delay. Although the teratogenic risks of efavirenz appear to be minimal, data on long-term developmental effects remain scarce. Here, we aimed to investigate the short- and long-term behavioral and neurodevelopmental effects of perinatal efavirenz exposure. We treated pregnant rats from gestation day 1 until postnatal day 7 with efavirenz (100 mg/kg) or vehicle. We measured behavioral outcomes in male offspring during the first 3 postnatal weeks, adolescence and adulthood, and conducted brain immunohistochemistry analyses after sacrifice. Perinatal efavirenz exposure resulted in reduced body weight and delayed reflex and motor development. During adulthood, we observed a decrease in the total number of cells and mature neurons in the motor cortex, as well as an increase in the number of Caspase-3-positive cells and serotonergic fibers. Together, our data show a developmental delay and persistent changes in the brain motor cortex of rats exposed to efavirenz perinatally. Because over 1 million children born annually are exposed to antiretroviral therapy, our findings underline the need for clinical studies on long-term neurodevelopmental outcomes of perinatal exposure to efavirenz.
p53 induces senescence through Lamin A/C stabilization-mediated nuclear deformation
Authors: Yoon Min-Ho , Kang So-mi , Lee Su-Jin , Woo Tae-Gyun , Oh Ah-Young , Park Soyoung , Ha Nam-Chul , Park Bum-Joon 
Published: February 2019

Abstractp53-mediated cellular senescence has been intensively investigated, because it is important for tumor suppressive function. In addition, p16/INK4A is well known to be critical for cellular senescence. However, detailed molecular mechanism or relevance between p53 and p16-mediated senescence has not been demonstrated yet. Here we show that p53 induces p16 through Lamin A/C stabilization via direct interaction. Stabilized Lamin A/C promotes degradation of BMI-1 and MEL-18 (Polycomb repressor complex 1, PRC1), which sequesters p16 promotor. Increased p53 can reduce BMI-1/MEL-18 and induce p16 expression via Lamin A/C. Elimination of Lamin A/C can abolish p53-induced p16 expression and BMI-1/MEL-18 reduction. As Lamin A/C expression is increased during cell differentiation, this mechanism seems to be very useful for selective induction of senescence in non-stem cells. Our results suggest that Lamin A/C-p53 network is important for p16/INK4A-mediated cellular senescence.
Necroptosis in primate luteolysis: a role for ceramide
Authors: Bagnjuk Konstantin , Stöckl Jan Bernd , Fröhlich Thomas , Arnold Georg Josef , Behr Rüdiger , Berg Ulrike , Berg Dieter , Kunz Lars , Bishop Cecily , Xu Jing , Mayerhofer Artur 
Published: February 2019

AbstractThe corpus luteum (CL) is a transient endocrine organ, yet molecular mechanisms resulting in its demise are not well known. The presence of phosphorylated mixed lineage kinase domain-like pseudokinase pMLKL(T357/S358) in human and nonhuman primate CL samples (Macaca mulatta and Callithrix jacchus) implied that necroptosis of luteal cells may be involved. In M. mulatta CL, pMLKL positive staining became detectable only from the mid-late luteal phase onwards, pointing to necroptosis during regression of the CL. Cell death, including necroptosis, was previously observed in cultures of human luteal granulosa cells (GCs), an apt model for the study of the human CL. To explore mechanisms of necroptotic cell death in GCs during culture, we performed a proteomic analysis. The levels of 50 proteins were significantly altered after 5 days of culture. Interconnectivity analysis and immunocytochemistry implicated specifically the ceramide salvage pathway to be enhanced. M. mulatta CL transcriptome analysis indicated in vivo relevance. Perturbing endogenous ceramide generation by fumonisin B1 (FB1) and addition of soluble ceramide (C2-CER) yielded opposite actions on viability of GCs and therefore supported the significance of the ceramide pathway. Morphological changes indicated necrotic cell death in the C2-CER treated group. Studies with the pan caspase blocker zVAD-fmk or the necroptosis blocker necrosulfonamid (NSA) further supported that C2-CER induced necroptosis. Our data pinpoint necroptosis in a physiological process, namely CL regression. This raises the possibility that the primate CL could be rescued by pharmacological inhibition of necroptosis or by interaction with ceramide metabolism.
MEK5/ERK5 activation regulates colon cancer stem-like cell properties
Authors: Pereira Diane M. , Gomes Sofia. E. , Borralho Pedro M. , Rodrigues Cecília M. P. 
Published: February 2019

AbstractColon cancer has been proposed to be sustained by a small subpopulation of stem-like cells with unique properties allowing them to survive conventional therapies and drive tumor recurrence. Identification of targetable signaling pathways contributing to malignant stem-like cell maintenance may therefore translate into new therapeutic strategies to overcome drug resistance. Here we demonstrated that MEK5/ERK5 signaling activation is associated with stem-like malignant phenotypes. Conversely, using a panel of cell line-derived three-dimensional models, we showed that ERK5 inhibition markedly suppresses the molecular and functional features of colon cancer stem-like cells. Particularly, pharmacological inhibition of ERK5 using XMD8-92 reduced the rate of primary and secondary sphere formation, the expression of pluripotency transcription factors SOX2, NANOG, and OCT4, and the proportion of tumor cells with increased ALDH activity. Notably, this was further associated with increased sensitivity to 5-fluorouracil-based chemotherapy. Mechanistically, ERK5 inhibition resulted in decreased IL-8 expression and NF-κB transcriptional activity, suggesting a possible ERK5/NF-κB/IL-8 signaling axis regulating stem-like cell malignancy. Taken together, our results provide proof of principle that ERK5-targeted inhibition may be a promising therapeutic approach to eliminate drug-resistant cancer stem-like cells and improve colon cancer treatment.
Significant contribution of subseafloor microparticles to the global manganese budget
Authors: Uramoto Go-Ichiro , Morono Yuki , Tomioka Naotaka , Wakaki Shigeyuki , Nakada Ryoichi , Wagai Rota , Uesugi Kentaro , Takeuchi Akihisa , Hoshino Masato , Suzuki Yoshio , Shiraishi Fumito , Mitsunobu Satoshi , Suga Hiroki , Takeichi Yasuo , Takahashi Yoshio , Inagaki Fumio 
Published: February 2019

AbstractFerromanganese minerals are widely distributed in subseafloor sediments and on the seafloor in oceanic abyssal plains. Assessing their input, formation and preservation is important for understanding the global marine manganese cycle and associated trace elements. However, the extent of ferromanganese minerals buried in subseafloor sediments remains unclear. Here we show that abundant (108–109 particles cm−3) micrometer-scale ferromanganese mineral particles (Mn-microparticles) are found in the oxic pelagic clays of the South Pacific Gyre (SPG) from the seafloor to the ~100 million-year-old sediments above the basement. Three-dimensional micro-texture, and major and trace element compositional analyses revealed that these Mn-microparticles consist of poorly crystalline ferromanganese oxides precipitating from bottom water. Based on our findings, we extrapolate that 1.5–8.8 × 1028 Mn-microparticles, accounting for 1.28–7.62 Tt of manganese, are globally present in oxic subseafloor sediments. This estimate is at least two orders of magnitude larger than the manganese budget for nodules and crusts on the seafloor. Subseafloor Mn-microparticles thus contribute significantly to the global manganese budget.
Revealing the role of lattice distortions in the hydrogen-induced metal-insulator transition of SmNiO3
Authors: Chen Jikun , Mao Wei , Ge Binghui , Wang Jiaou , Ke Xinyou , Wang Vei , Wang Yiping , Döbeli Max , Geng Wentong , Matsuzaki Hiroyuki , Shi Jian , Jiang Yong 
Published: February 2019

AbstractThe discovery of hydrogen-induced electronic phase transitions in strongly correlated materials such as rare-earth nickelates has opened up a new paradigm in regulating materials’ properties for both fundamental study and technological applications. However, the microscopic understanding of how protons and electrons behave in the phase transition is lacking, mainly due to the difficulty in the characterization of the hydrogen doping level. Here, we demonstrate the quantification and trajectory of hydrogen in strain-regulated SmNiO3 by using nuclear reaction analysis. Introducing 2.4% of elastic strain in SmNiO3 reduces the incorporated hydrogen concentration from ~1021 cm−3 to ~1020 cm−3. Unexpectedly, despite a lower hydrogen concentration, a more significant modification in resistivity is observed for tensile-strained SmNiO3, substantially different from the previous understanding. We argue that this transition is explained by an intermediate metastable state occurring in the transient diffusion process of hydrogen, despite the absence of hydrogen at the post-transition stage.
Flexible, transparent nanocellulose paper-based perovskite solar cells
Authors: Gao Lei , Chao Lingfeng , Hou Meihui , Liang Jin , Chen Yonghua , Yu Hai-Dong , Huang Wei 
Published: February 2019

AbstractRecently perovskite solar cells (PSCs), as photoelectric conversion devices, exhibit excellent power conversion efficiency (PCE) and low-processing cost, and have become one of the most promising devices to replace conventional silicon-based solar cells and address current pressing energy issues. Among them, the flexible PSCs are especially more widely applicable and may propel the rapid advancements of wearable electronics, causing a significant paradigm shift in consumer electronics. Current flexible PSCs use non-biodegradable petroleum-based polymer substrates, discarding of which will aggravate “white pollution”. Therefore, development of green, biodegradable and low-cost flexible substrates will provide a great alternative to flexible PSCs. Here we have developed transparent nanocellulose paper (NCP) with coating of acrylic resin as substrates to fabricate flexible PSCs, which are biodegradable and easily disposable. The PCE of these NCP-based PSCs reached 4.25%, while the power per weight (the ratio of power to device weight) was as high as 0.56 W g–1. The flexible PSCs also showed good stability, retaining >80% of original efficiency after 50 times of bending. The NCP-based substrates can also be applied to other electronic systems, which may prosper next-generation green flexible electronics.
Occurrence and public-perceived risk of endocrine disrupting compounds in drinking water
Authors: Wee Sze Yee , Aris Ahmad Zaharin 
Published: February 2019

AbstractAccess to safe water is a crucial factor in determining environmental sustainability, public health, and economic prosperity. Endocrine disrupting compounds (EDCs) are an environmental contaminant of growing concern, which undermine the safety of drinking water. The potential health issues of EDCs are not fully understood yet due to there being relatively scarce research on their exposure and associated risks via drinking water consumption. Because of ineffective drinking water supply systems and unknown risk perceptions of EDCs in drinking water, the role of perceived risks in ensuring access to safe drinking water remains unknown, contributing to the occurrence of such potential risks in the global water system. Integrating preventive measures with a multibarrier approach to safe drinking water is highly challenging because of the relatively low public awareness and political responsibility, as well as the nature and characteristics of EDCs themselves. In addition to reviewing the occurrence and public-perceived risks of EDCs in drinking water, this article focuses on building bases of knowledge and awareness for a better understanding of drinking water quality issues relative to the hazards surrounding EDCs from the perspectives of human exposure and health risk. A conceptual model illustrates the factors that potentially influence risk perception on drinking water quality in regard to not only EDCs but also other issues. Ensuring safe access to drinking water requires interventions that incorporate risk communication and governance, providing insights into political, economic, social, and environmental changes.
The role of defects in organic image sensors for green photodiode
Authors: Kim Seong Heon , lee Jooho , Cho Eunae , Lee Junho , Yun Dong-Jin , Lee Dongwook , Kim Yongsung , Ro Takkyun , Heo Chul-Joon , Lee Gae Hwang , Jin Yong Wan , Kim Sunghan , Park Kyung-Bae , Heo Sung 
Published: February 2019

AbstractControlling defect states in a buffer layer for organic photo devices is one of the vital factors which have great influence on the device performance. Defect states in silicon oxynitride (SiOxNy) buffer layer for organic photo devices can be controlled by introducing appropriate dopant materials. We performed ab initio simulations to identify the effect on doping SiOxNy with carbon (C), boron (B), and phosphorous (P) atoms. The results unveil that hole defects in the SiOxNy layer diminish with the phosphorous doping. Based on the simulation results, we fabricate the small molecule organic photodetector (OPD) including the phosphorous-doped SiOxNy buffer layer and the active film of blended naphthalene-based donor and C60 acceptor molecules, which shows excellent enhancement in the external quantum efficiency (EQE). The results of our charge-based deep level transient spectroscopy (Q-DLTS) measurements confirmed that the EQE enhancement originates from the decrease of the hole traps induced by the reduced hole defects. The method of controlling the defect states in SiOxNy buffer layers by the doping can be used to improve the performance in various organic photo devices.
Transcranial Current Stimulation During Sleep Facilitates Insight into Temporal Rules, but does not Consolidate Memories of Individual Sequential Experiences
Authors: Lerner Itamar , Ketz Nicholas A. , Jones Aaron P. , Bryant Natalie B. , Robert Bradley , Skorheim Steven W. , Hartholt Arno , Rizzo Albert S. , Gluck Mark A. , Clark Vincent P. , Pilly Praveen K. 
Published: February 2019

AbstractSlow-wave sleep (SWS) is known to contribute to memory consolidation, likely through the reactivation of previously encoded waking experiences. Contemporary studies demonstrate that when auditory or olfactory stimulation is administered during memory encoding and then reapplied during SWS, memory consolidation can be enhanced, an effect that is believed to rely on targeted memory reactivation (TMR) induced by the sensory stimulation. Here, we show that transcranial current stimulations (tCS) during sleep can also be used to induce TMR, resulting in the facilitation of high-level cognitive processes. Participants were exposed to repeating sequences in a realistic 3D immersive environment while being stimulated with particular tCS patterns. A subset of these tCS patterns was then reapplied during sleep stages N2 and SWS coupled to slow oscillations in a closed-loop manner. We found that in contrast to our initial hypothesis, performance for the sequences corresponding to the reapplied tCS patterns was no better than for other sequences that received stimulations only during wake or not at all. In contrast, we found that the more stimulations participants received overnight, the more likely they were to detect temporal regularities governing the learned sequences the following morning, with tCS-induced beta power modulations during sleep mediating this effect.
Critical roles for the phosphatidylinositide 3-kinase isoforms p110β and p110γ in thrombopoietin-mediated priming of platelet function
Authors: Moore Samantha F. , Smith Nina R. , Blair Thomas A. , Durrant Tom N. , Hers Ingeborg 
Published: February 2019

AbstractThrombopoietin (TPO) enhances platelet activation through activation of the tyrosine kinase; JAK2 and the lipid kinase phosphatidylinositide 3-kinase (PI3K). The aim of our study was to identify the PI3K isoforms involved in mediating the effect of TPO on platelet function and elucidate the underlying mechanism. We found that p110β plays an essential role in TPO-mediated (i) priming of protease-activated receptor (PAR)-mediated integrin αIIbβ3 activation and α-granule secretion, (ii) synergistic enhancement of PAR-mediated activation of the small GTPase RAP1, a regulator of integrin activation and (iii) phosphorylation of the PI3K effector Akt. More importantly, the synergistic effect of TPO on phosphorylation of extracellular-regulated kinase (ERK1/2) and thromboxane (TxA2) synthesis was dependent on both p110β and p110γ. p110β inhibition/deletion, or inhibition of p110γ, resulted in a partial reduction, whereas inhibiting both p110β and p110γ completely prevented the synergistic effect of TPO on ERK1/2 phosphorylation and TxA2 synthesis. The latter was ablated by inhibition of MEK, but not p38, confirming a role for ERK1/2 in regulating TPO-mediated increases in TxA2 synthesis. In conclusion, the synergistic effect of TPO on RAP1 and integrin activation is largely mediated by p110β, whereas p110β and p110γ contribute to the effect of TPO on ERK1/2 phosphorylation and TxA2 formation.
Learning the Dynamic Treatment Regimes from Medical Registry Data through Deep Q-network
Authors: Liu Ning , Liu Ying , Logan Brent , Xu Zhiyuan , Tang Jian , Wang Yanzhi 
Published: February 2019

AbstractThis paper presents the deep reinforcement learning (DRL) framework to estimate the optimal Dynamic Treatment Regimes from observational medical data. This framework is more flexible and adaptive for high dimensional action and state spaces than existing reinforcement learning methods to model real-life complexity in heterogeneous disease progression and treatment choices, with the goal of providing doctors and patients the data-driven personalized decision recommendations. The proposed DRL framework comprises (i) a supervised learning step to predict expert actions, and (ii) a deep reinforcement learning step to estimate the long-term value function of Dynamic Treatment Regimes. Both steps depend on deep neural networks. As a key motivational example, we have implemented the proposed framework on a data set from the Center for International Bone Marrow Transplant Research (CIBMTR) registry database, focusing on the sequence of prevention and treatments for acute and chronic graft versus host disease after transplantation. In the experimental results, we have demonstrated promising accuracy in predicting human experts’ decisions, as well as the high expected reward function in the DRL-based dynamic treatment regimes.