bluuebunny/crossref_metadata_2025 huggingface dataset:
Let's Talk about Stress: History of Stress Research
Authors: Robinson Alexandra M.
Published: February 2018

The reference to stress is ubiquitous in modern society, yet it is a relatively new field of research. The following article provides an overview of the history of stress research and its iterations over the last century. In this article, I provide an overview of the earliest stress research and theories introduced through physiology and medicine and eventually as a concept in psychology. I begin with an exploration of the research of biological stressors 1st explored by experimental physiologist Claude Bernard and eventually adopted as a foundational concept in stress research when Walter Cannon expanded on Bernard's work and identified homeostasis. The contributions of Hans Selye, considered the father of stress research; Sir William Osler; Yerkes and Dodson; and Richard Lazarus are also discussed. Finally, I discuss how, in the new millennium, research on psychological stress has expanded across disciplines ranging from physiology to medicine, chemistry, endocrinology, neurosciences, epidemiology, psychiatry, epigenetics, and psychology, reflecting the complexity of the construct both theoretically and biologically.
Novel rare variations in genes that regulate developmental change in N-methyl-d-aspartate receptor in patients with schizophrenia
Authors: Yoshikawa Akane , Nishimura Fumichika , Inai Aya , Eriguchi Yosuke , Nishioka Masaki , Takaya Atsuhiko , Tochigi Mamoru , Kawamura Yoshiya , Umekage Tadashi , Kato Kayoko , Sasaki Tsukasa , Kasai Kiyoto , Kakiuchi Chihiro
Published: February 2018

The mechanism underlying the vulnerability to developing schizophrenia (SCZ) during adolescence remains elusive. Hypofunction of N-methyl-d-aspartate receptors (NMDARs) has been implicated in the pathophysiology of SCZ. During development, the composition of synaptic NMDARs dramatically changes from NR2B-containing NMDARs to NR2A-containing NMDARs through the phosphorylation of NR2B S1480 or Y1472 by CDK5, CSNK2A1, and EphB2, which plays a pivotal role in the maturation of neural circuits. We hypothesized that the dysregulation of developmental change in NMDARs could be involved in the onset of SCZ. Using next-generation sequencing, we re-sequenced all the coding regions and splice sites of CDK5, CSNK2A1, and EphB2 in 474 patients with SCZ and 475 healthy controls. Variants on the database for human control subjects of Japanese origin were removed and all the nonsynonymous and nonsense variants were validated using Sanger sequencing. Four novel variants in CDK5 were observed in patients with SCZ but were not observed in controls. The total number of variants, however, was not significantly different between the SCZ and control groups (P=0.062). In silico analyses predicted P271T to be damaging. Further genetic research using a larger sample is required to examine whether CDK5 is involved in the pathophysiology of SCZ.
Testing frameworks for personalizing bipolar disorder
Authors: Cochran Amy L. , Schultz André , McInnis Melvin G. , Forger Daniel B.
Published: February 2018

The hallmark of bipolar disorder is a clinical course of recurrent manic and depressive symptoms of varying severity and duration. Mathematical modeling of bipolar disorder holds the promise of an ability to personalize diagnoses, to predict future mood episodes, to directly compare diverse datasets, and to link basic mechanisms to behavioral data. Several modeling frameworks have been proposed for bipolar disorder, which represent competing hypothesis about the basic framework of the disorder. Here, we test these hypotheses with self-report assessments of mania and depression symptoms from 178 bipolar patients followed prospectively for 4 or more years. Statistical analysis of the data did not support the hypotheses that mood arises from a rhythmic process or multiple stable states (e.g., mania or depression) or that manic and depressive symptoms are highly anti-correlated. Alternatively, it is shown that bipolar disorder could arise from an inability for mood to quickly return to normal when perturbed. This latter concept is embodied by an affective instability model that can be personalized to the clinical course of any individual with chronic disorders that have an affective component.
Ubiquitin-specific protease 4 promotes hepatocellular carcinoma progression via cyclophilin A stabilization and deubiquitination
Authors: Li Tianyi , Yan Bin , Ma Yang , Weng Junyong , Yang Shouwen , Zhao Nan , Wang Xiaoliang , Sun Xing
Published: February 2018

Ubiquitin-specific protease 4 (USP4) is a member of the deubiquitinating enzyme family, which plays an important role in human tumor diseases. However, the mechanisms by which USP4 facilitates tumor development, especially in hepatocellular carcinoma (HCC), remain unclear. Clinically, we found that USP4 is overexpressed in human HCC tissues compared with adjacent non-tumoral tissues and is significantly correlated with malignant phenotype characteristics, including tumor size, tumor number, differentiation, serum alpha-fetoprotein level, and vascular invasion. Moreover, Kaplan–Meier survival analysis showed a poor overall survival rate in patients with USP4-overexpressing tumors. Analyses of univariate and multivariate Cox proportional hazard models indicated that USP4 is a prognostic biomarker for poor outcome. Using in vitro and in vivo assays, we demonstrated that USP4 overexpression enhanced HCC cell growth, migration, and invasion. Mechanistically, cyclophilin A (CypA) was identified as an important molecule for USP4-mediated oncogenic activity in HCC. We observed that USP4 interacted with CypA and inhibited CypA degradation via deubiquitination in HCC cells. Subsequently, the USP4/CypA complex activated the MAPK signaling pathway and prevented CrkII phosphorylation. These data suggest that USP4 acts as a novel prognostic marker, offering potential therapeutic opportunities for HCC.
YAP triggers the Wnt/β-catenin signalling pathway and promotes enterocyte self-renewal, regeneration and tumorigenesis after DSS-induced injury
Authors: Deng Feihong , Peng Liang , Li Zhijun , Tan Gao , Liang Erbo , Chen Shengbo , Zhao Xinmei , Zhi Fachao
Published: February 2018

Impaired epithelial regeneration is a crucial pathophysiological feature of ulcerative colitis (UC). Yes-associated protein (YAP1) appears to control cell proliferation and differentiation. In this study, we sought to identify the roles of YAP in intestinal epithelial cell (IEC) self-renewal, regeneration and tumorigenesis. We first observed that YAP was significantly reduced in 62.5% (45/72) of human UC tissues and it was dramatically enhanced during epithelial regeneration in a murine colitis model. Using lentiviral infection, we established a YAP-overexpression (YAPWT) mouse model. We then found that after tissue injury, YAPWT mice had increased epithelial cell self-renewal capacity and drastically restored intestinal crypt structure. Strikingly, these mice were more susceptible to colitis-associated cancer (CAC) in chemically induced carcinoma. Mechanistically, YAP and β-catenin showed increased nuclear co-localization during regeneration after inflammation. Overexpressing YAP significantly improved IEC ‘wound-healing’ ability and increased the expression of both β-catenin and the transcriptional targets of Wnt signalling Lgr5 and cyclin D1, whereas silencing β-catenin in YAPWT cells attenuated this effect. Remarkably, we observed that YAP could directly interact with β-catenin in the nucleus and formed a transcriptional YAP/β-catenin/TCF4 complex; Lgr5 and cyclin D1 were confirmed to be the target genes of this complex. In contrast, cancer cell proliferation and tumour development were suppressed by the phospho-mimetic YAP mutant. In summary, nuclear YAP-driven IEC proliferation could control epithelial regeneration after inflammation and may serve as a potential therapeutic target in UC. However, excessive YAP activation promoted CAC development.
Boosting lithium storage in covalent organic framework via activation of 14-electron redox chemistry
Authors: Lei Zhendong , Yang Qinsi , Xu Yi , Guo Siyu , Sun Weiwei , Liu Hao , Lv Li-Ping , Zhang Yong , Wang Yong
Published: February 2018

Conjugated polymeric molecules have been heralded as promising electrode materials for the next-generation energy-storage technologies owing to their chemical flexibility at the molecular level, environmental benefit, and cost advantage. However, before any practical implementation takes place, the low capacity, poor structural stability, and sluggish ion/electron diffusion kinetics remain the obstacles that have to be overcome. Here, we report the synthesis of a few-layered two-dimensional covalent organic framework trapped by carbon nanotubes as the anode of lithium-ion batteries. Remarkably, upon activation, this organic electrode delivers a large reversible capacity of 1536 mAh g−1 and can sustain 500 cycles at 100 mA g−1. Aided by theoretical calculations and electrochemical probing of the electrochemical behavior at different stages of cycling, the storage mechanism is revealed to be governed by 14-electron redox chemistry for a covalent organic framework monomer with one lithium ion per C=N group and six lithium ions per benzene ring. This work may pave the way to the development of high-capacity electrodes for organic rechargeable batteries.
Self-assembly of emissive supramolecular rosettes with increasing complexity using multitopic terpyridine ligands
Authors: Yin Guang-Qiang , Wang Heng , Wang Xu-Qing , Song Bo , Chen Li-Jun , Wang Lei , Hao Xin-Qi , Yang Hai-Bo , Li Xiaopeng
Published: February 2018

Coordination-driven self-assembly has emerged as a powerful bottom-up approach to construct various supramolecular architectures with increasing complexity and functionality. Tetraphenylethylene (TPE) has been incorporated into metallo-supramolecules to build luminescent materials based on aggregation-induced emission. We herein report three generations of ligands with full conjugation of TPE with 2,2′:6′,2″-terpyridine (TPY) to construct emissive materials. Due to the bulky size of TPY substituents, the intramolecular rotations of ligands are partially restricted even in dilute solution, thus leading to emission in both solution and aggregation states. Furthermore, TPE-TPY ligands are assembled with Cd(II) to introduce additional restriction of intramolecular rotation and immobilize fluorophores into rosette-like metallo-supramolecules ranging from generation 1–3 (G1−G3). More importantly, the fluorescent behavior of TPE-TPY ligands is preserved in these rosettes, which display tunable emissive properties with respect to different generations, particularly, pure white-light emission for G2.
Efficient green light-emitting diodes based on quasi-two-dimensional composition and phase engineered perovskite with surface passivation
Authors: Yang Xiaolei , Zhang Xingwang , Deng Jinxiang , Chu Zema , Jiang Qi , Meng Junhua , Wang Pengyang , Zhang Liuqi , Yin Zhigang , You Jingbi
Published: February 2018

Perovskite light-emitting diodes (LEDs) are attracting great attention due to their efficient and narrow emission. Quasi-two-dimensional perovskites with Ruddlesden–Popper-type layered structures can enlarge exciton binding energy and confine charge carriers and are considered good candidate materials for efficient LEDs. However, these materials usually contain a mixture of phases and the phase impurity could cause low emission efficiency. In addition, converting three-dimensional into quasi-two-dimensional perovskite introduces more defects on the surface or at the grain boundaries due to the reduction of crystal sizes. Both factors limit the emission efficiency of LEDs. Here, firstly, through composition and phase engineering, optimal quasi-two-dimensional perovskites are selected. Secondly, surface passivation is carried out by coating organic small molecule trioctylphosphine oxide on the perovskite thin film surface. Accordingly, green LEDs based on quasi-two-dimensional perovskite reach a current efficiency of 62.4 cd A−1 and external quantum efficiency of 14.36%.
Genetic control of meristem arrest and life span in Arabidopsis by a FRUITFULL-APETALA2 pathway
Authors: Balanzà Vicente , Martínez-Fernández Irene , Sato Shusei , Yanofsky Martin F. , Kaufmann Kerstin , Angenent Gerco C. , Bemer Marian , Ferrándiz Cristina
Published: February 2018

Monocarpic plants have a single reproductive cycle in their lives, where life span is determined by the coordinated arrest of all meristems, or global proliferative arrest (GPA). The molecular bases for GPA and the signaling mechanisms involved are poorly understood, other than systemic cues from developing seeds of unknown nature. Here we uncover a genetic pathway regulating GPA in Arabidopsis that responds to age-dependent factors and acts in parallel to seed-derived signals. We show that FRUITFULL (FUL), a MADS-box gene involved in flowering and fruit development, has a key role in promoting meristem arrest, as GPA is delayed and fruit production is increased in ful mutants. FUL directly and negatively regulates APETALA2 expression in the shoot apical meristem and maintains the temporal expression of WUSCHEL which is an essential factor for meristem maintenance.
Observation of topological Uhlmann phases with superconducting qubits
Authors: Viyuela O. , Rivas A. , Gasparinetti S. , Wallraff A. , Filipp S. , Martin-Delgado M. A.
Published: February 2018

Topological insulators and superconductors at finite temperature can be characterized by the topological Uhlmann phase. However, a direct experimental measurement of this invariant has remained elusive in condensed matter systems. Here, we report a measurement of the topological Uhlmann phase for a topological insulator simulated by a system of entangled qubits in the IBM Quantum Experience platform. By making use of ancilla states, otherwise unobservable phases carrying topological information about the system become accessible, enabling the experimental determination of a complete phase diagram including environmental effects. We employ a state-independent measurement protocol which does not involve prior knowledge of the system state. The proposed measurement scheme is extensible to interacting particles and topological models with a large number of bands.
A comparative study of growth: different body weight trajectories in three species of the genus Eublepharis and their hybrids
Authors: Frynta Daniel , Jančúchová-Lásková Jitka , Frýdlová Petra , Landová Eva
Published: February 2018

An extensive research effort is devoted to the evolution of life-histories and processes underlying the variation in adult body weight; however, in this regard, some animal taxa remain neglected. Here we report rates and timing of growth recorded in two wild-derived populations of a model lizard species,Eublepharis macularius(M, W), other two related species, i.e.,E. angramainyu(A) andE. sp. (D), and their between-species hybrids. We detected clear differences among the examined species/populations, which can be interpreted in the terms of “fast – slow” continuum of life-history strategies. The mean asymptotic body size was the highest in A and further decreased in the following order: M, W, and D. In contrast, the growth rate showed an opposite pattern. Counter-intuitively, the largest species exhibited the slowest growth rates. The final body size was determined mainly by the inflexion point. This parameter reflecting the duration of exponential growth increased with mean asymptotic body size and easily overcompensated the effect of decreasing growth rates in larger species. Compared to the parental species, the F1and backcross hybrids exhibited intermediate values of growth parameters. Thus, except for the case of the F2hybrid of MxA, we failed to detect deleterious effects of hybridization in these animals with temperature sex determination.
Socio-ecological dynamics of Caribbean coral reef ecosystems and conservation opinion propagation
Authors: Thampi Vivek A. , Anand Madhur , Bauch Chris T.
Published: February 2018

The Caribbean coral reef ecosystem has experienced a long history of deterioration due to various stressors. For instance, over-fishing of parrotfish – an important grazer of macroalgae that can prevent destructive overgrowth of macroalgae – has threatened reef ecosystems in recent decades and stimulated conservation efforts such as the formation of marine protected areas. Here we develop a mathematical model of coupled socio-ecological interactions between reef dynamics and conservation opinion dynamics to better understand how natural and human factors interact individually and in combination to determine coral reef cover. We find that the coupling opinion and reef systems generates complex dynamics that are difficult to anticipate without use of a model. For instance, instead of converging to a stable state of constant coral cover and conservationist opinion, the system can oscillate between low and high live coral cover as human opinion oscillates in a boom-bust cycle between complacency and concern. Out of various possible parameter manipulations, we also find that raising awareness of coral reef endangerment best avoids counter-productive nonlinear feedbacks and always increases and stabilizes live coral reef cover. In conclusion, an improved understanding of coupled opinion-reef dynamics under anthrogenic stressors is possible using coupled socio-ecological models, and such models should be further researched.
Publisher Correction: Task-Correlated Cortical Asymmetry and Intra- and Inter-Hemispheric Separation
Authors: Cohen Yaniv , Wilson Donald A.
Published: February 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Phase contrast scanning transmission electron microscopy imaging of light and heavy atoms at the limit of contrast and resolution
Authors: Yücelen Emrah , Lazić Ivan , Bosch Eric G. T.
Published: February 2018

Using state of the art scanning transmission electron microscopy (STEM) it is nowadays possible to directly image single atomic columns at sub-Å resolution. In standard (high angle) annular dark field STEM ((HA)ADF-STEM), however, light elements are usually invisible when imaged together with heavier elements in one image. Here we demonstrate the capability of the recently introduced Integrated Differential Phase Contrast STEM (iDPC-STEM) technique to image both light and heavy atoms in a thin sample at sub-Å resolution. We use the technique to resolve both the Gallium and Nitrogen dumbbells in a GaN crystal in [$${\bf{10}}\bar{{\bf{1}}}{\bf{1}}$$
10

1
¯

1
] orientation, which each have a separation of only 63 pm. Reaching this ultimate resolution even for light elements is possible due to the fact that iDPC-STEM is a direct phase imaging technique that allows fine-tuning the microscope while imaging. Apart from this qualitative imaging result, we also demonstrate a quantitative match of ratios of the measured intensities with theoretical predictions based on simulations.
Repeated Measures of Blood and Breath Ammonia in Response to Control, Moderate and High Protein Dose in Healthy Men
Authors: Spacek Lisa A. , Strzepka Arthur , Saha Saurabh , Kotula Jonathan , Gelb Jeffrey , Guilmain Sarah , Risby Terence , Solga Steven F.
Published: February 2018

Ammonia physiology is important to numerous disease states including urea cycle disorders and hepatic encephalopathy. However, many unknowns persist regarding the ammonia response to common and potentially significant physiologic influences, such as food. Our aim was to evaluate the dynamic range of ammonia in response to an oral protein challenge in healthy participants. We measured blood and breath ammonia at baseline and every hour for 5.5 hours. Healthy men (N = 22, aged 18 to 24 years) consumed a 60 g protein shake (high dose); a subset of 10 consumed a 30 g protein shake (moderate dose) and 12 consumed an electrolyte drink containing 0 g protein (control). Change in blood ammonia over time varied by dose (p = 0.001). Difference in blood ammonia was significant for control versus high (p = 0.0004) and moderate versus high (p = 0.03). Change in breath ammonia over time varied by dose (p < 0.0001). Difference in breath ammonia was significant for control versus moderate (p = 0.03) and control versus high (p = 0.0003). Changes in blood and breath ammonia were detectable by fast, minimally-invasive (blood) or non-invasive (breath) point-of-care ammonia measurement methods. These pilot data may contribute to understanding normal ammonia metabolism. Novel measurement methods may aid research into genetic and metabolic ammonia disorders.
House dust mite and Cockroach specific Immunoglobulin E sensitization is associated with diabetes mellitus in the adult Korean population
Authors: Kim Mee Kyoung , Jeong Jee Sun , Han Kyungdo , Baek Ki Hyun , Song Ki-Ho , Kwon Hyuk-Sang
Published: February 2018

Immunoglobulin E (IgE) is known to activate mast cells. Prior studies have shown that mast cells contribute to diet-induced obesity and diabetes mellitus (DM). We aimed to determine whether adults with IgE sensitization were at risk of DM. We performed assays regarding serum total IgE and allergen-specific IgE levels against the house dust mite, the cockroach, and the dog on 1,528 adults randomly sampled from every age and gender group in various districts. The total and three allergen-specific IgE levels were positively correlated with fasting glucose level and insulin resistance. Subjects with increased levels of total IgE (>100 kU/L), compared to those without, had an odds ratio (OR) of 1.72 (95% confidence interval [95% CI], 1.17–2.54) for DM after adjusting for various covariates. Further controlling for previous allergic disease did not attenuate the association between total IgE level and DM. Subjects sensitized to the house dust mite (OR 1.63, 95% CI, 1.03–2.59) and the cockroach (OR 2.27, 95% CI, 1.40–3.66) were also at increased risk of DM. We found a strong positive association between IgE sensitization and DM in a general Korean population, suggesting that IgE may be an important independent risk factor for metabolic diseases in Koreans.
Genetic relatedness reveals total population size of white sharks in eastern Australia and New Zealand
Authors: Hillary R. M. , Bravington M. V. , Patterson T. A. , Grewe P. , Bradford R. , Feutry P. , Gunasekera R. , Peddemors V. , Werry J. , Francis M. P. , Duffy C. A. J. , Bruce B. D.
Published: February 2018

Conservation concerns exist for many sharks but robust estimates of abundance are often lacking. Improving population status is a performance measure for species under conservation or recovery plans, yet the lack of data permitting estimation of population size means the efficacy of management actions can be difficult to assess, and achieving the goal of removing species from conservation listing challenging. For potentially dangerous species, like the white shark, balancing conservation and public safety demands is politically and socially complex, often leading to vigorous debate about their population status. This increases the need for robust information to inform policy decisions. We developed a novel method for estimating the total abundance of white sharks in eastern Australia and New Zealand using the genetic-relatedness of juveniles and applying a close-kin mark-recapture framework and demographic model. Estimated numbers of adults are small (ca. 280–650), as is total population size (ca. 2,500–6,750). However, estimates of survival probability are high for adults (over 90%), and fairly high for juveniles (around 73%). This represents the first direct estimate of total white shark abundance and survival calculated from data across both the spatial and temporal life-history of the animal and provides a pathway to estimate population trend.
Internal noise sources limiting contrast sensitivity
Authors: Silvestre Daphné , Arleo Angelo , Allard Rémy
Published: February 2018

Contrast sensitivity varies substantially as a function of spatial frequency and luminance intensity. The variation as a function of luminance intensity is well known and characterized by three laws that can be attributed to the impact of three internal noise sources: early spontaneous neural activity limiting contrast sensitivity at low luminance intensities (i.e. early noise responsible for the linear law), probabilistic photon absorption at intermediate luminance intensities (i.e. photon noise responsible for de Vries-Rose law) and late spontaneous neural activity at high luminance intensities (i.e. late noise responsible for Weber’s law). The aim of this study was to characterize how the impact of these three internal noise sources vary with spatial frequency and determine which one is limiting contrast sensitivity as a function of luminance intensity and spatial frequency. To estimate the impact of the different internal noise sources, the current study used an external noise paradigm to factorize contrast sensitivity into equivalent input noise and calculation efficiency over a wide range of luminance intensities and spatial frequencies. The impact of early and late noise was found to drop linearly with spatial frequency, whereas the impact of photon noise rose with spatial frequency due to ocular factors.
Impact of Drinking Water Fluoride on Human Thyroid Hormones: A Case- Control Study
Authors: Kheradpisheh Zohreh , Mirzaei Masoud , Mahvi Amir Hossein , Mokhtari Mehdi , Azizi Reyhane , Fallahzadeh Hossein , Ehrampoush Mohammad Hassan
Published: February 2018

The elevated fluoride from drinking water impacts on T3, T4 and TSH hormones. The aim was study impacts of drinking water fluoride on T3, T4 and TSH hormones inYGA (Yazd Greater Area). In this case- control study 198 cases and 213 controls were selected. Fluoride was determined by the SPADNS Colorimetric Method. T3, T4 and TSH hormones tested in the Yazd central laboratory by RIA (Radio Immuno Assay) method. The average amount of TSH and T3 hormones based on the levels of fluoride in two concentration levels 0–0.29 and 0.3–0.5 (mg/L) was statistically significant (P = 0.001 for controls and P = 0.001 for cases). In multivariate regression logistic analysis, independent variable associated with Hypothyroidism were: gender (odds ratio: 2.5, CI 95%: 1.6–3.9), family history of thyroid disease (odds ratio: 2.7, CI 95%: 1.6–4.6), exercise (odds ratio: 5.34, CI 95%: 3.2–9), Diabetes (odds ratio: 3.7, CI 95%: 1.7–8), Hypertension (odds ratio: 3.2, CI 95%: 1.3–8.2), water consumption (odds ratio: 4, CI 95%: 1.2–14). It was found that fluoride has impacts on TSH, T3 hormones even in the standard concentration of less than 0.5 mg/L. Application of standard household water purification devices was recommended for hypothyroidism.
Hainan mantle plume produced late Cenozoic basaltic rocks in Thailand, Southeast Asia
Authors: Yan Quanshu , Shi Xuefa , Metcalfe Ian , Liu Shengfa , Xu Taoyu , Kornkanitnan Narumol , Sirichaiseth Thanyapat , Yuan Long , Zhang Ying , Zhang Hui
Published: February 2018

Intraplate volcanism initiated shortly after the cessation of Cenozoic seafloor spreading in the South China Sea (SCS) region, but the full extent of its influence on the Indochina block has not been well constrained. Here we present major and trace element data and Sr-Nd-Pb-Hf isotope ratios of late Cenozoic basaltic lavas from the Khorat plateau and some volcanic centers in the Paleozoic Sukhothai arc terrane in Thailand. These volcanic rocks are mainly trachybasalts and basaltic trachyandesites. Trace element patterns and Sr-Nd-Pb-Hf isotopic compositions show that these alkaline volcanic lavas exhibit oceanic island basalt (OIB)-like characteristics with enrichments in both large-ion lithophile elements (LILE) and high field strength elements (HFSEs). Their mantle source is a mixture between a depleted Indian MORB-type mantle and an enriched mantle type 2 (EMII). We suggest that the post-spreading intraplate volcanism in the SCS region was induced by a Hainan mantle plume which spread westwards to the Paleozoic Sukhothai arc terrane.
Accelerated invagination of vacuoles as a stress response in chronically heat-stressed yeasts
Authors: Ishii Ayane , Kawai Masahito , Noda Haruka , Kato Hiroyuki , Takeda Kohei , Asakawa Kotomi , Ichikawa Yoshinobu , Sasanami Tomohiro , Tanaka Keiji , Kimura Yoko
Published: February 2018

When exposed to sublethal high temperatures, budding yeast cells can survive for a period of time; however, a sufficient amount of ubiquitin is necessary for this survival. To understand the nature of the stress, we examined the morphological changes in yeast cells, focusing on the vacuoles. Changes in vacuolar morphology were notable, and ruffled vacuolar membranes, accelerated invaginations of vacuolar membranes, and vesicle-like formations were observed. These changes occurred in the absence of Atg1, Atg9 or Ivy1 but appeared to require endosomal sorting proteins, such as Vps23, Vps24 or Pep12. Furthermore, the serial sections of the vacuoles analysed using an electron microscopic analysis revealed that spherical invaginated structures were linked together in a vacuole. Because degradation of cell surface proteins is induced from heat stress, fusion of endosomal and vacuolar membranes might occur frequently in heat-stressed cells, and yeast cells might be able to cope with a rapid increase in vacuolar surface area by such invaginations.
Adverse drug events in Chinese pediatric inpatients and associated risk factors: a retrospective review using the Global Trigger Tool
Authors: Ji Huan-huan , Song Lin , Xiao Jian-wen , Guo Yu-xia , Wei Ping , Tang Ting-ting , Tian Xiao-jiang , Tang Xue-wen , Jia Yun-tao
Published: February 2018

Understanding the epidemiology and risk factors of adverse drug events (ADEs) in pediatric inpatient is essential if we are to prevent, reduce or ameliorate the harm experienced. The Global Trigger Tool (GTT) is a method of retrospective medical record review that measures harm in hospitalized children. We employed a three-stage retrospective chart review of random samples of 1800 pediatric inpatients discharged from January 2013 to December 2015. 31 kinds of pediatric-specific triggers were made based on the previous trigger tool studies developed for use in adult or pediatric. Positive predictive value (PPV) of individual triggers, as well as ADEs detection rates were calculated. Stepwise logistic regression was performed to investigate risk factors associated with ADEs. Of 1746 patients, detected in 221 patients (12.7%) with 247 ADEs. The PPV of the trigger tool was 13.3%. Of the 247 ADEs, 82.6% were identified as category E, 11.7% category F and 5.7% category H. The pediatric-focused trigger tool is a feasible and useful tool for detecting pediatric ADEs. Especially for patients who have had more drugs, more doses or more admissions which needs to be closely monitored as triggers to improve the safety.
Central Composite Design Optimization of Zinc Removal from Contaminated Soil, Using Citric Acid as Biodegradable Chelant
Authors: Asadzadeh Farrokh , Maleki-Kaklar Mahdi , Soiltanalinejad Nooshin , Shabani Farzin
Published: February 2018

Citric acid (CA) was evaluated in terms of its efficiency as a biodegradable chelating agent, in removing zinc (Zn) from heavily contaminated soil, using a soil washing process. To determine preliminary ranges of variables in the washing process, single factor experiments were carried out with different CA concentrations, pH levels and washing times. Optimization of batch washing conditions followed using a response surface methodology (RSM) based central composite design (CCD) approach. CCD predicted values and experimental results showed strong agreement, with an R2 value of 0.966. Maximum removal of 92.8% occurred with a CA concentration of 167.6 mM, pH of 4.43, and washing time of 30 min as optimal variable values. A leaching column experiment followed, to examine the efficiency of the optimum conditions established by the CCD model. A comparison of two soil washing techniques indicated that the removal efficiency rate of the column experiment (85.8%) closely matching that of the batch experiment (92.8%). The methodology supporting the research experimentation for optimizing Zn removal may be useful in the design of protocols for practical engineering soil decontamination applications
The yield difference between wild-type cotton and transgenic cotton that expresses IPT depends on when water-deficit stress is applied
Authors: Zhu Xunlu , Sun Li , Kuppu Sundaram , Hu Rongbin , Mishra Neelam , Smith Jennifer , Esmaeili Nardana , Herath Maheshika , Gore Michael A. , Payton Paxton , Shen Guoxin , Zhang Hong
Published: February 2018

Drought is the No. 1 factor that limits agricultural production in the world, thus, making crops more drought tolerant is a major goal in agriculture. Many genes with functions in abiotic stress tolerance were identified, and overexpression of these genes confers increased drought tolerance in transgenic plants. The isopentenyltransferase gene (IPT) that encodes a rate limiting enzyme in cytokinin biosynthesis is one of them. Interestingly, when IPT-transgenic cotton was field-tested at two different sites, Texas and Arizona, different results were obtained. To explain this phenomenon, reduced irrigation experiments with different timing in applying water deficit stress were conducted. It was found that the timing of water deficit stress is critical for IPT-transgenic cotton to display its yield advantage over control plants (i.e. wild-type and segregated non-transgenic plants). If water deficit stress occurs before flowering (vegetative phase), IPT-transgenic cotton would outperform control plants; however, if water deficit stress occurs at or after flowering (reproductive phase), there would not be a yield difference between IPT-transgenic and control cotton plants. This result suggests that an early induction of IPT expression (before first flowering) is needed in order to realize the benefits of IPT-expression in transgenic plants that face water-deficit stress later in development.
Multiparameter Analysis of Gas Transport Phenomena in Shale Gas Reservoirs: Apparent Permeability Characterization
Authors: Shen Yinghao , Pang Yu , Shen Ziqi , Tian Yuanyuan , Ge Hongkui
Published: February 2018

The large amount of nanoscale pores in shale results in the inability to apply Darcy’s law. Moreover, the gas adsorption of shale increases the complexity of pore size characterization and thus decreases the accuracy of flow regime estimation. In this study, an apparent permeability model, which describes the adsorptive gas flow behavior in shale by considering the effects of gas adsorption, stress dependence, and non-Darcy flow, is proposed. The pore size distribution, methane adsorption capacity, pore compressibility, and matrix permeability of the Barnett and Eagle Ford shales are measured in the laboratory to determine the critical parameters of gas transport phenomena. The slip coefficients, tortuosity, and surface diffusivity are predicted via the regression analysis of the permeability data. The results indicate that the apparent permeability model, which considers second-order gas slippage, Knudsen diffusion, and surface diffusion, could describe the gas flow behavior in the transition flow regime for nanoporous shale. Second-order gas slippage and surface diffusion play key roles in the gas flow in nanopores for Knudsen numbers ranging from 0.18 to 0.5. Therefore, the gas adsorption and non-Darcy flow effects, which involve gas slippage, Knudsen diffusion, and surface diffusion, are indispensable parameters of the permeability model for shale.
Soil salinity and matric potential interaction on water use, water use efficiency and yield response factor of bean and wheat
Authors: Khataar Mahnaz , Mohammadi Mohammad Hossien , Shabani Farzin
Published: February 2018

We studied the effects of soil matric potential and salinity on the water use (WU), water use efficiency (WUE) and yield response factor (Ky), for wheat (Triticum aestivum cv. Mahdavi) and bean (Phaseoulus vulgaris cv. COS16) in sandy loam and clay loam soils under greenhouse conditions. Results showed that aeration porosity is the predominant factor controlling WU, WUE, Ky and shoot biomass (Bs) at high soil water potentials. As matric potential was decreased, soil aeration improved, with Bs, WU and Ky reaching maximum value at −6 to −10 kPa, under all salinities. Wheat WUE remained almost unchanged by reduction of matric potential under low salinities (EC ≤ 8 dSm−1), but increased under higher salinities (EC ≥ 8 dSm−1), as did bean WUE at all salinities, as matric potential decreased to −33 kPa. Wheat WUE exceeds that of bean in both sandy loam and clay loam soils. WUE of both plants increased with higher shoot/root ratio and a high correlation coefficient exists between them. Results showed that salinity decreases all parameters, particularly at high potentials (h = −2 kPa), and amplifies the effects of waterlogging. Further, we observed a strong relationship between transpiration (T) and root respiration (Rr) for all experiments.
Flexible and Accurate Simulation of Radiation Cooling with FETD Method
Authors: Zhang Huan Huan , Sha Wei E. I. , Huang Zhi Xiang , Shi Guang Ming
Published: February 2018

Thermal management and simulation are becoming increasingly important in many areas of engineering applications. There are three cooling routes for thermal management, namely thermal conduction, thermal convection and thermal radiation, among which the first two approaches have been widely studied and applied, while the radiation cooling has not yet attracted much attention in terrestrial environment because it usually contributes less to the total amount of thermal dissipation. Thus the simulation method for radiation cooling was also seldom noticed. The traditional way to simulate the radiation cooling is to solve the thermal conduction equation with an approximate radiation boundary condition, which neglects the wavelength and angular dependence of the emissivity of the object surface. In this paper, we combine the heat conduction equation with a rigorous radiation boundary condition discretized by the finite-element time-domain method to simulate the radiation cooling accurately and flexibly. Numerical results are given to demonstrate the accuracy, flexibilities and potential applications of the proposed method. The proposed numerical model can provide a powerful tool to gain deep physical insight and optimize the physical design of radiation cooling.
Temporal downregulation of the polyubiquitin gene Ubb affects neuronal differentiation, but not maturation, in cells cultured in vitro
Authors: Jung Byung-Kwon , Park Chul-Woo , Ryu Kwon-Yul
Published: February 2018

Reduced levels of cellular ubiquitin (Ub) pools due to disruption of the polyubiquitin gene Ubb lead to dysregulation of neural stem cell (NSC) differentiation and impaired neuronal maturation in cells isolated from Ubb
−/−
mouse embryonic brains. However, it is currently unknown whether Ub is required for the specific stage of neuronal development or whether it plays a pleiotropic role throughout the process. To answer this question, we aimed to downregulate Ubb expression temporally during neuronal development, which could not be achieved in Ubb
−/−
cells. Therefore, we exploited lentivirus-mediated knockdown (KD) of Ubb at different stages of neuronal development, and investigated their phenotypes. Here, we report the outcome of Ubb KD on two independent culture days in vitro (DIV): DIV1 and DIV7. We observed that NSCs did not differentiate properly via Ubb KD on DIV1, but the maturation of already differentiated neurons was intact via Ubb KD on DIV7. Intriguingly, Ubb KD activated Notch signaling when it had been suppressed, but exerted no effect when it had already been activated. Therefore, our study suggests that Ub plays a pivotal role in NSC differentiation to suppress Notch signaling, but not in the subsequent maturation stages of neurons that had already been differentiated.
Identification of T helper (Th)1- and Th2-associated antigens of Cryptococcus neoformans in a murine model of pulmonary infection
Authors: Firacative Carolina , Gressler A. Elisabeth , Schubert Kristin , Schulze Bianca , Müller Uwe , Brombacher Frank , von Bergen Martin , Alber Gottfried
Published: February 2018

Cryptococcosis, caused by Cryptococcus neoformans, has been demonstrated to be controlled by T helper (Th)1 cells while Th2 cells are associated with fungal growth and dissemination. Although cryptococcal immunoreactive protein antigens were previously identified, their association with Th1 or Th2 immune responses was not provided. In mice, Th1-dependent IFN-γ induces the production of IgG2a, whereas the Th2 cytokine IL-4 stimulates the expression of IgG1 rendering each isotype an indicator of the underlying Th cell response. Therefore, we performed an immunoproteomic study that distinguishes Th1- and Th2-associated antigens by their reactivity with Th1-dependent IgG2a or Th2-dependent IgG1 antibodies in sera from C. neoformans-infected wild-type mice. We additionally analysed sera from Th2-prone IL-12-deficient and Th1-prone IL-4Rα-deficient mice extending the results found in wild-type mice. In total, ten, four, and three protein antigens associated with IgG1, IgG2a, or both isotypes, respectively, were identified. Th2-associated antigens represent promising candidates for development of immunotherapy regimens, whereas Th1-associated antigens may serve as candidates for vaccine development. In conclusion, this study points to intrinsic immunomodulatory effects of fungal antigens on the process of Th cell differentiation based on the identification of cryptococcal protein antigens specifically associated with Th1 or Th2 responses throughout mice of different genotypes.
Protein interactomes of protein phosphatase 2A B55 regulatory subunits reveal B55-mediated regulation of replication protein A under replication stress
Authors: Wang Feifei , Zhu Songli , Fisher Laura A. , Wang Weidong , Oakley Gregory G. , Li Chunling , Peng Aimin
Published: February 2018

The specific function of PP2A, a major serine/threonine phosphatase, is mediated by regulatory targeting subunits, such as members of the B55 family. Although implicated in cell division and other pathways, the specific substrates and functions of B55 targeting subunits are largely undefined. In this study we identified over 100 binding proteins of B55α and B55β in Xenopus egg extracts that are involved in metabolism, mitochondria function, molecular trafficking, cell division, cytoskeleton, DNA replication, DNA repair, and cell signaling. Among the B55α and B55β-associated proteins were numerous mitotic regulators, including many substrates of CDK1. Consistently, upregulation of B55α accelerated M-phase exit and inhibited M-phase entry. Moreover, specific substrates of CDK2, including factors of DNA replication and chromatin remodeling were identified within the interactomes of B55α and B55β, suggesting a role for these phosphatase subunits in DNA replication. In particular, we confirmed in human cells that B55α binds RPA and mediates the dephosphorylation of RPA2. The B55-RPA association is disrupted after replication stress, consistent with the induction of RPA2 phosphorylation. Thus, we report here a new mechanism that accounts for both how RPA phosphorylation is modulated by PP2A and how the phosphorylation of RPA2 is abruptly induced after replication stress.
Terawatt-scale optical half-cycle attosecond pulses
Authors: Xu Jiancai , Shen Baifei , Zhang Xiaomei , Shi Yin , Ji Liangliang , Zhang Lingang , Xu Tongjun , Wang Wenpeng , Zhao Xueyan , Xu Zhizhan
Published: February 2018

Extreme-ultravoilet (XUV) attosecond pulses with durations of a few tens of attosecond have been successfully applied for exploring ultrafast electron dynamics at the atomic scale. But their weak intensities limit the further application in demonstrating nonlinear responses of inner-shell electrons. Optical attosecond pulses will provide sufficient photon flux to initiate strong-field processes. Here we proposed a novel method to generate an ultra-intense isolated optical attosecond pulse through relativistic multi-cycle laser pulse interacting with a designed gas-foil target. The underdense gas target sharpens the multi-cycle laser pulse, producing a dense layer of relativistic electrons with a thickness of a few hundred nanometers. When the dense electron layer passes through an oblique foil, it emits single ultra-intense half-cycle attosecond pulse in the visible and ultraviolet spectral range. The emitted pulse has a peak intensity exceeding 1018 W/cm2 and full-width-half-maximum duration of 200 as. The peak power of this attosecond light source reaches 2 terawatt. The proposed method relaxes the single-cycle requirement on the driving pulse for isolated attosecond pulse generation and significantly boosts the peak power, thus it may open up the route to new experiments tracking the nonlinear response of inner-shell electrons as well as nonlinear attosecond phenomena investigation.
RNA-seq transcriptome analysis of breast cancer cell lines under shikonin treatment
Authors: Lin Kuo-Hua , Huang Ming-Yii , Cheng Wei-Chung , Wang Shu-Chi , Fang Shih-Hua , Tu Hung-Pin , Su Chia-Cheng , Hung Yung-Li , Liu Po-Len , Chen Chi-Shuo , Wang Yu-Ting , Li Chia-Yang
Published: February 2018

Shikonin is a naphthoquinone isolated from the dried root of Lithospermum erythrorhizon, an herb used in Chinese medicine. Although several studies have indicated that shikonin exhibits antitumor activity in breast cancer, the mechanism of action remains unclear. In the present study, we performed transcriptome analysis using RNA-seq and explored the mechanism of action of shikonin in regulating the growth of different types of breast cancer cells. The IC50 of shikonin on MCF-7, SKBR-3 and MDA-MB-231 cells were 10.3 μΜ, 15.0 μΜ, 15.0 μΜ respectively. Our results also demonstrated that shikonin arrests the progression of cell cycle and induces apoptosis in MDA-MB-231 cells. Using RNA-seq transcriptome analysis, we found 38 common genes that significantly express in different types of breast cancer cells under shikonin treatment. In particular, our results indicated that shikonin induces the expression of dual specificity phosphatase (DUSP)-1 and DUSP2 in both RNA and protein levels. In addition, shikonin also inhibits the phosphorylation of JNK and p38, the downstream signaling molecules of DUSP1 and DUSP2. Therefore, our results suggest that shikonin induces the expression of DUSP1 and DUSP2 which consequently switches off JNK and p38 MAPK pathways and causes cell cycle arrest and apoptosis in breast cancer cells.
Local raster image correlation spectroscopy generates high-resolution intracellular diffusion maps
Authors: Scipioni Lorenzo , Di Bona Melody , Vicidomini Giuseppe , Diaspro Alberto , Lanzanò Luca
Published: February 2018

Raster image correlation spectroscopy (RICS) is a powerful method for measuring molecular diffusion in live cells directly from images acquired on a laser scanning microscope. However, RICS only provides single average diffusion coefficients from regions with a lateral size on the order of few micrometers, which means that its spatial resolution is mainly limited to the cellular level. Here we introduce the local RICS (L-RICS), an easy-to-use tool that generates high resolution maps of diffusion coefficients from images acquired on a laser scanning microscope. As an application we show diffusion maps of a green fluorescent protein (GFP) within the nucleus and within the nucleolus of live cells at an effective spatial resolution of 500 nm. We find not only that diffusion in the nucleolus is slowed down compared to diffusion in the nucleoplasm, but also that diffusion in the nucleolus is highly heterogeneous.