bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of early postnatal nutrition on chronic kidney disease and arterial hypertension in adulthood: a narrative review
Authors: Juvet C. , Simeoni U. , Yzydorczyk C. , Siddeek B. , Armengaud J.-B. , Nardou K. , Juvet P. , Benahmed M. , Cachat F. , Chehade H.
Published: August 2018

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin–angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.
Quality of life of parents of mentally-ill children: a systematic review and meta-analysis
Authors: Dey M. , Paz Castro R. , Haug S. , Schaub M. P.
Published: August 2018

Aims

To examine the quality of life (QOL) of parents of children with a specific mental disorder (any age).

Methods

Relevant articles were searched using different databases. Articles were included that compared the QOL of parents with mentally-ill children to parents of healthy controls or norm values or provided the required data for this comparison. A meta-analysis was conducted to obtain an overall mean effect size estimate. Additional analyses were performed to assess publication bias and moderation.

Results

Twenty-six out of 10 548 articles met the pre-defined inclusion criteria. Most of these studies focused on attention-deficit/hyperactivity disorder or autism spectrum disorder, used clinical samples that mainly included males and young children and studied the QOL of mothers. The meta-analysis revealed that parents of mentally-ill children are experiencing a clinically relevant reduction in their QOL relative to parents of healthy children and norm values (g= −0.66).

Conclusions

The compromised QOL of parents of mentally-ill children needs to be considered and addressed by health professionals who are in contact with them. The paper provides insights into existing research gaps and suggests improvements for subsequent work.
Secure attachment style appears to compensate for the effect of prenatal maternal distress regarding difficult infant temperament development
Authors: Haselbeck Christin , Niederberger Uwe , Gubi-Kelm Silvia , Jahn Franziska , Dautwiz Friederike , Siniatchkin Michael
Published: August 2018

Abstract. Objective: Secure attachment style is a known protective factor regarding psychopathological development. The infant’s attachment style, which is developed during the first two years of life, is therefore considered a moderating factor on the association between prenatal maternal distress and child temperament development which has repeatedly been reported in previous studies. Method: In this longitudinal study on a new sample of 51 mother-child-dyads, reported maternal distress and maternal empathy were assessed during pregnancy. Infant temperament and motor development were assessed at 12 months, while additionally controlling for the infant’s attachment style as a postnatal factor. Results: Infants with secure attachment style whose mothers had experienced higher prenatal distress showed slightly better gross motor development at the age of 12 months. No association could be found between prenatal maternal distress and infant temperament. Conclusions: The results support the view that secure attachment style in children is a protective factor and softens the effects of prenatal maternal distress on difficult temperament development.
LGR5 regulates gastric adenocarcinoma cell proliferation and invasion via activating Wnt signaling pathway
Authors: Wang Xiangfei , Wang Xiumin , Liu Yang , Dong Yating , Wang Yanan , Kassab Muzaffer Ahmad , Fan Wufang , Yu Xiaochun , Wu Chen
Published: August 2018

LGR5 plays a critical role in tissue development and the maintenance of adult stem cells in gastrointestinal tract. However, the oncogenic role of LGR5 in the development of gastric adenocarcinoma remains elusive. Here, we show that LGR5 promotes gastric adenocarcinoma cell proliferation and metastasis. We find that knock down of LGR5 or suppression of Wnt signaling pathway by inhibitor C59 arrests gastric adenocarcinoma cell proliferation and invasion. Moreover, treatment of Wnt3a, the activator of Wnt signaling pathway, partially recovers the proliferation defect observed in LGR5 knockdown gastric adenocarcinoma cells. Moreover, LGR5 facilitates β-catenin nuclear accumulation, a surrogate marker of the activation of Wnt signaling pathway. In addition, C59 treatment suppresses transcription of Axin2 and TCF1, both of which are the target genes of β-catenin in gastric adenocarcinoma cells. Gastric adenocarcinoma cells with overexpressed LGR5 form a large quantity of visible actin filaments and pseudopods, suggesting that LGR5 significantly enhances the ability of cell movement, which might capacitate gastric adenocarcinoma cells with enhanced LGR5 expression to gain invasive and migratory properties. Taken together, our results show that LGR5 contributes to cell proliferation and invasion through the activation of Wnt/β-catenin-signaling pathway in gastric adenocarcinoma cells.
The detrimental effects of glucocorticoids exposure during pregnancy on offspring’s cardiac functions mediated by hypermethylation of bone morphogenetic protein-4
Authors: Peng Jieying , Zhou Yuhao , Zhang Zhiyu , Wang Zhiming , Gao Lingtong , Zhang Xiao , Fang Zhou , Li Guangyao , Chen Huaiyan , Yang Hongxing , Gao Lu
Published: August 2018

The intra-uterine and external environmental factors not only affect the early development of fetuses, their interaction with genesis will also substantially program the physiological functions of offspring throughout life. Synthetic glucocorticoid (GC) is widely used for the management of women at risk of preterm birth or undergone autoimmune diseases. However, excess GC might cause a number of chronic diseases in later life. In the present study, we set up a programming rat model by daily injection of dexamethasone (DEX) since 14.5 dpc until labor, and found that the cardiac functions were significantly compromised in the male offspring compared with that exposed to NS, especially after ischemia/reperfusion (I/R), due to the increased infarction and apoptosis of myocardium. Using MeDIP sequencing, we identified four genes involved in the cardiac muscle cell differentiation and development pathway exhibited increased methylation in their promoter regions, among which, bone morphogenetic protein-4 (BMP4) expression is coordinately decreased in myocardium from male mice prenatally exposed to DEX. The programming effect of DEX on cardiomyocytes apoptosis was found to be dependent on mitochondria dysfunction, whereas the breakdown of mitochondrial membrane potential (ΔΨm) and the decrease of ATP production from mitochondria caused by prenatal DEX exposure both can be restored by BMP4 predisposing on neonatal cardiomyocytes 24 h prior to I/R. Inversely consistent with ΔΨm and ATP production, the release of reactive oxygen species was dramatically elevated in cardiomyocytes, which was significantly inhibited in the presence of BMP4 prior to I/R. These findings suggested that the excess GC exposure during pregnancy increases the susceptibility of male offspring’s heart to “second strike”, due to the decrease of BMP4 expression caused by the hypermethylation on Bmp4 promoter and the absence of BMP4 protective effect in cardiomyocytes, making the addition of BMP4 a promising treatment for the congenital heart disease under such circumstances.
Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure
Authors: Huang Chenyang , Sun Haixiang , Wang Zhilong , Liu Yang , Cheng Xi , Liu Jingyu , Jiang Ruiwei , Zhang Xindong , Zhen Xin , Zhou Jidong , Chen Linjun , Ding Lijun , Yan Guijun , Jiang Yue
Published: August 2018

Recurrent implantation failure (RIF) caused by various etiological factors remains a challenge for fertility clinicians using assisted reproductive technology (ART) worldwide. Dysregulation of leukemia inhibitory factor (LIF) in the endometria of women with RIF is involved in impaired endometrial receptivity and embryo adhesion. However, the mechanism through which LIF expression is regulated in women with RIF is still poorly understood. Our previous study noted that the abnormally increased endometrial Krüppel-like factor 12 (KLF12) in RIF women led to impaired decidualization and embryo implantation. Here, we further found that KLF12 inhibited embryo adhesion in vivo and in vitro by repressing LIF expression. Mechanistically, KLF12 bound to conserved sites (CAGTGGG, −6771 to −6765 and −7115 to −7109) within the LIF promoter region and repressed LIF transcription directly. Exogenous LIF significantly reversed the KLF12-mediated repression of BeWo spheroid adhesion. KLF12 expression was reduced significantly in Ishikawa cells treated with progestogen, which was due to the activation of Akt signaling. These findings may provide novel potential therapeutic regimens for patients with RIF and disrupted endometrial receptivity.
A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Authors: Gettinger S. N. , Choi J. , Mani N. , Sanmamed M. F. , Datar I. , Sowell Ryan , Du Victor Y. , Kaftan E. , Goldberg S. , Dong W. , Zelterman D. , Politi K. , Kavathas P. , Kaech S. , Yu X. , Zhao H. , Schlessinger J. , Lifton R. , Rimm D. L. , Chen L. , Herbst R. S. , Schalper K. A.
Published: August 2018

The biological determinants of sensitivity and resistance to immune checkpoint blockers are not completely understood. To elucidate the role of intratumoral T-cells and their association with the tumor genomic landscape, we perform paired whole exome DNA sequencing and multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients treated with PD-1 axis blockers. QIF is used to simultaneously measure the level of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell proliferation (Ki-67 in CD3) and effector capacity (Granzyme-B in CD3). Elevated mutational load, candidate class-I neoantigens or intratumoral CD3 signal are significantly associated with favorable response to therapy. Additionally, a “dormant” TIL signature is associated with survival benefit in patients treated with immune checkpoint blockers characterized by elevated TILs with low activation and proliferation. We further demonstrate that dormant TILs can be reinvigorated upon PD-1 blockade in a patient-derived xenograft model.
Multiple timescales of normalized value coding underlie adaptive choice behavior
Authors: Zimmermann Jan , Glimcher Paul W. , Louie Kenway
Published: August 2018

Adaptation is a fundamental process crucial for the efficient coding of sensory information. Recent evidence suggests that similar coding principles operate in decision-related brain areas, where neural value coding adapts to recent reward history. However, the circuit mechanism for value adaptation is unknown, and the link between changes in adaptive value coding and choice behavior is unclear. Here we show that choice behavior in nonhuman primates varies with the statistics of recent rewards. Consistent with efficient coding theory, decision-making shows increased choice sensitivity in lower variance reward environments. Both the average adaptation effect and across-session variability are explained by a novel multiple timescale dynamical model of value representation implementing divisive normalization. The model predicts empirical variance-driven changes in behavior despite having no explicit knowledge of environmental statistics, suggesting that distributional characteristics can be captured by dynamic model architectures. These findings highlight the importance of treating decision-making as a dynamic process and the role of normalization as a unifying computation for contextual phenomena in choice.
Understanding the apparent fractional charge of protons in the aqueous electrochemical double layer
Authors: Chen Leanne D. , Bajdich Michal , Martirez J. Mark P. , Krauter Caroline M. , Gauthier Joseph A. , Carter Emily A. , Luntz Alan C. , Chan Karen , Nørskov Jens K.
Published: August 2018

A detailed atomic-scale description of the electrochemical interface is essential to the understanding of electrochemical energy transformations. In this work, we investigate the charge of solvated protons at the Pt(111) | H2O and Al(111) | H2O interfaces. Using semi-local density-functional theory as well as hybrid functionals and embedded correlated wavefunction methods as higher-level benchmarks, we show that the effective charge of a solvated proton in the electrochemical double layer or outer Helmholtz plane at all levels of theory is fractional, when the solvated proton and solvent band edges are aligned correctly with the Fermi level of the metal (EF). The observed fractional charge in the absence of frontier band misalignment arises from a significant overlap between the proton and the electron density from the metal surface, and results in an energetic difference between protons in bulk solution and those in the outer Helmholtz plane.
N2 activation on a molybdenum–titanium–sulfur cluster
Authors: Ohki Yasuhiro , Uchida Keisuke , Tada Mizuki , Cramer Roger E. , Ogura Takashi , Ohta Takehiro
Published: August 2018

The FeMo-cofactor of nitrogenase, a metal–sulfur cluster that contains eight transition metals, promotes the conversion of dinitrogen into ammonia when stored in the protein. Although various metal–sulfur clusters have been synthesized over the past decades, their use in the activation of N2 has remained challenging, and even the FeMo-cofactor extracted from nitrogenase is not able to reduce N2. Herein, we report the activation of N2 by a metal–sulfur cluster that contains molybdenum and titanium. An N2 moiety bridging two [Mo3S4Ti] cubes is converted into NH3 and N2H4 upon treatment with Brønsted acids in the presence of a reducing agent.
Long-term deep-supercooling of large-volume water and red cell suspensions via surface sealing with immiscible liquids
Authors: Huang Haishui , Yarmush Martin L. , Usta O. Berk
Published: August 2018

Supercooling of aqueous solutions is a fundamentally and practically important physical phenomenon with numerous applications in biopreservation and beyond. Under normal conditions, heterogeneous nucleation mechanisms critically prohibit the simultaneous long-term (> 1 week), large volume (> 1 ml), and low temperatures (< −10 °C) supercooling of aqueous solutions. Here, we report on the use of surface sealing of water by an oil phase to significantly diminish the primary heterogeneous nucleation at the water/air interface. We achieve deep supercooling (down to −20 °C) of large volumes of water (up to 100 ml) for long periods (up to 100 days) simultaneously via this approach. Since oils are mixtures of various hydrocarbons we also report on the use of pure alkanes and primary alcohols of various lengths to achieve the same. Furthermore, we demonstrate the utility of deep supercooling via preliminary studies on extended (100 days) preservation of human red blood cells.
Maximal viral information recovery from sequence data using VirMAP
Authors: Ajami Nadim J , Wong Matthew C. , Ross Matthew C. , Lloyd Richard E. , Petrosino Joseph F.
Published: August 2018

Accurate classification of the human virome is critical to a full understanding of the role viruses play in health and disease. This implies the need for sensitive, specific, and practical pipelines that return precise outputs while still enabling case-specific post hoc analysis. Viral taxonomic characterization from metagenomic data suffers from high background noise and signal crosstalk that confounds current methods. Here we develop VirMAP that overcomes these limitations using techniques that merge nucleotide and protein information to taxonomically classify viral reconstructions independent of genome coverage or read overlap. We validate VirMAP using published data sets and viral mock communities containing RNA and DNA viruses and bacteriophages. VirMAP offers opportunities to enhance metagenomic studies seeking to define virome-host interactions, improve biosurveillance capabilities, and strengthen molecular epidemiology reporting.
Lensfree OLEDs with over 50% external quantum efficiency via external scattering and horizontally oriented emitters
Authors: Song Jinouk , Kim Kwon-Hyeon , Kim Eunhye , Moon Chang-Ki , Kim Yun-Hi , Kim Jang-Joo , Yoo Seunghyup
Published: August 2018

High efficiency is important for successful deployment of any light sources. Continued efforts have recently made it possible to demonstrate organic light-emitting diodes with efficiency comparable to that of inorganic light-emitting diodes. However, such achievements were possible only with the help of a macroscopic lens or complex internal nanostructures, both of which undermine the key benefits of organic light-emitting diodes as an affordable planar light source. Here we present a systematic way to achieve organic light-emitting diodes with ultrahigh efficiency even only with an external scattering film, one of the simplest low-cost outcoupling structures. Through a global, multivariable analysis, we show that scattering with a high degree of forwardness has a potential to play a critical role in realizing ultimate efficiency. Combined with horizontally oriented emitters, organic light-emitting diodes equipped with particle-embedded films tailored for forward-intensive scattering achieve a maximum external quantum efficiency of 56%.
Capacitive neural network with neuro-transistors
Authors: Wang Zhongrui , Rao Mingyi , Han Jin-Woo , Zhang Jiaming , Lin Peng , Li Yunning , Li Can , Song Wenhao , Asapu Shiva , Midya Rivu , Zhuo Ye , Jiang Hao , Yoon Jung Ho , Upadhyay Navnidhi Kumar , Joshi Saumil , Hu Miao , Strachan John Paul , Barnell Mark , Wu Qing , Wu Huaqiang , Qiu Qinru , Williams R. Stanley , Xia Qiangfei , Yang J. Joshua
Published: August 2018

Experimental demonstration of resistive neural networks has been the recent focus of hardware implementation of neuromorphic computing. Capacitive neural networks, which call for novel building blocks, provide an alternative physical embodiment of neural networks featuring a lower static power and a better emulation of neural functionalities. Here, we develop neuro-transistors by integrating dynamic pseudo-memcapacitors as the gates of transistors to produce electronic analogs of the soma and axon of a neuron, with “leaky integrate-and-fire” dynamics augmented by a signal gain on the output. Paired with non-volatile pseudo-memcapacitive synapses, a Hebbian-like learning mechanism is implemented in a capacitive switching network, leading to the observed associative learning. A prototypical fully integrated capacitive neural network is built and used to classify inputs of signals.
Biology and genome of a newly discovered sibling species of Caenorhabditis elegans
Authors: Kanzaki Natsumi , Tsai Isheng J. , Tanaka Ryusei , Hunt Vicky L. , Liu Dang , Tsuyama Kenji , Maeda Yasunobu , Namai Satoshi , Kumagai Ryohei , Tracey Alan , Holroyd Nancy , Doyle Stephen R. , Woodruff Gavin C. , Murase Kazunori , Kitazume Hiromi , Chai Cynthia , Akagi Allison , Panda Oishika , Ke Huei-Mien , Schroeder Frank C. , Wang John , Berriman Matthew , Sternberg Paul W. , Sugimoto Asako , Kikuchi Taisei
Published: August 2018

A ‘sibling’ species of the model organism Caenorhabditis elegans has long been sought for use in comparative analyses that would enable deep evolutionary interpretations of biological phenomena. Here, we describe the first sibling species of C. elegans, C. inopinata n. sp., isolated from fig syconia in Okinawa, Japan. We investigate the morphology, developmental processes and behaviour of C. inopinata, which differ significantly from those of C. elegans. The 123-Mb C. inopinata genome was sequenced and assembled into six nuclear chromosomes, allowing delineation of Caenorhabditis genome evolution and revealing unique characteristics, such as highly expanded transposable elements that might have contributed to the genome evolution of C. inopinata. In addition, C. inopinata exhibits massive gene losses in chemoreceptor gene families, which could be correlated with its limited habitat area. We have developed genetic and molecular techniques for C. inopinata; thus C. inopinata provides an exciting new platform for comparative evolutionary studies.
Atomic engineering of high-density isolated Co atoms on graphene with proximal-atom controlled reaction selectivity
Authors: Yan Huan , Zhao Xiaoxu , Guo Na , Lyu Zhiyang , Du Yonghua , Xi Shibo , Guo Rui , Chen Cheng , Chen Zhongxin , Liu Wei , Yao Chuanhao , Li Jing , Pennycook Stephen J. , Chen Wei , Su Chenliang , Zhang Chun , Lu Jiong
Published: August 2018

Controllable synthesis of single atom catalysts (SACs) with high loading remains challenging due to the aggregation tendency of metal atoms as the surface coverage increases. Here we report the synthesis of graphene supported cobalt SACs (Co1/G) with a tuneable high loading by atomic layer deposition. Ozone treatment of the graphene support not only eliminates the undesirable ligands of the pre-deposited metal precursors, but also regenerates active sites for the precise tuning of the density of Co atoms. The Co1/G SACs also demonstrate exceptional activity and high selectivity for the hydrogenation of nitroarenes to produce azoxy aromatic compounds, attributable to the formation of a coordinatively unsaturated and positively charged catalytically active center (Co–O–C) arising from the proximal-atom induced partial depletion of the 3d Co orbitals. Our findings pave the way for the precise engineering of the metal loading in a variety of SACs for superior catalytic activities.
Publisher Correction: Bistable and photoswitchable states of matter
Authors: Worrell Brady T. , McBride Matthew K. , Lyon Gayla B. , Cox Lewis M. , Wang Chen , Mavila Sudheendran , Lim Chern-Hooi , Coley Hannah M. , Musgrave Charles B. , Ding Yifu , Bowman Christopher N.
Published: August 2018

The original version of this Article contained errors in Fig. 3. In Fig. 3a, the word ‘fluid’ in grey was incorrectly given as ‘solid’ in green, below that, ‘solid’ in green was previously ‘fluid’ in grey. Also, the label on the arrow incorrectly read ‘TMG (1 mol%) HABI-Cl (3 mol%) 455 nm, 1 min’; the correct version reads ‘TMG (1 mol%) HABI-O-n-oct (4 mol%) 455 nm, 4 min’. In the accompanying legend, the word ‘photobase’ was originally incorrectly given as ‘photoacid’. Additionally, in Fig. 3b, the label on the central image was ‘As is: solid’, rather than the correct ‘As is: fluid’. This has been corrected in both the PDF and HTML versions of the Article.
Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint
Authors: Boughey Judy C. , Alvarado Michael D. , Lancaster Rachael B. , Fraser Symmans W. , Mukhtar Rita , Wong Jasmine M. , Ewing Cheryl A. , Potter David A. , Tuttle Todd M. , Hieken Tina J. , Carter Jodi M. , Jakub James W. , Kaplan Henry G. , Buchanan Claire L. , Jaskowiak Nora T. , Sattar Husain A. , Mueller Jeffrey , Nanda Rita , Isaacs Claudine J. , Pohlmann Paula R. , Lynce Filipa , Tousimis Eleni A. , Zeck Jay C. , Lee M. Catherine , Lang Julie E. , Mhawech-Fauceglia Paulette , Rao Roshni , Taback Bret , Godellas Constantine , Chen Margaret , Kalinsky Kevin M. , Hibshoosh Hanina , Killelea Brigid , Sanft Tara , Hirst Gillian L. , Asare Smita , Matthews Jeffrey B. , Perlmutter Jane , Esserman Laura J. ,   and I-SPY 2 Investigators, Chien A. Jo , Forero-Torres Andres , Yee Douglas , Ellis Erin D. , Han Heather S. , Lu Janice , Wallace Anne M. , Albain Kathy S. , Elias Anthony D. , Clark Amy S. , Kemmer Kathleen
Published: August 2018

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease—the primary endpoint of many drug therapy trials in the neoadjuvant setting—is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.
Microgelation imparts emulsifying ability to surface-inactive polysaccharides—bottom-up vs top-down approaches
Authors: Ishii Toya , Matsumiya Kentaro , Aoshima Mai , Matsumura Yasuki
Published: August 2018

In order to impart emulsifying ability to gel-forming polysaccharides that have not been used as emulsifying agents, three kinds of polysaccharides, agar, curdlan, and gellan gum were converted to microgels by different gelation methods via the bottom-up and top-down approaches. We clearly demonstrated that agar and curdlan acquired the ability to emulsify an edible oil by microgel formation. Among the colloidal properties of microgel suspensions such as microstructure, particle size, zeta-potential, viscosity, and surface hydrophobicity, we pointed out the importance of particle size on the emulsifying ability of polysaccharide-based microgels. The creaming behavior of the microgel-stabilized emulsions depended on the polysaccharide types and microgel preparation methods. The emulsion stability against oil droplet coalescence was extremely high for agar and curdlan microgel-stabilized emulsions during storage in the static condition, whereas different stability was observed for both the emulsions, that is, the curdlan microgel-based ones were more resistant to dynamic forcible destabilization by centrifugation than the agar ones, which can be attributed to the surface hydrophobicity of the microgels.
AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by activating the NF-κB pathway and predicts poor outcome of the patients
Authors: Liu Jun-yan , Jiang Lei , Liu Jia-jia , He Tao , Cui You-hong , Qian Feng , Yu Pei-wu
Published: August 2018

Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. Recent studies have indicated that AEBP1 might function as a candidate oncogene and is overexpressed in several human malignancies. However, the role of AEBP1 in gastric cancer (GC) remains largely unknown. This study aimed to investigate the expression pattern, prognostic significance and biological function of AEBP1 in human gastric cancer and to explore the underlying mechanism. We found that both the mRNA and protein levels of AEBP1 were significantly increased in human GC tissues. Elevated AEBP1 expression was significantly correlated with poor overall survival in patients with both early-stage (Tumor, Node, Metastases (TNM) TNM I and II) and late-stage (TNM III and IV) GC. Silencing AEBP1 markedly suppressed the proliferation, migration, invasion, metastasis and epithelial-mesenchymal transition of GC cells. Moreover, we demonstrated that knockdown of AEBP1 in GC cells led to inhibition of the NF-κB pathway by hampering the degradation of IκBα. Thus, AEBP1 might be served as a promising prognostic indicator and a potential therapeutic target in human GC.
Genome-wide association study and genomic prediction using parental and breeding populations of Japanese pear (Pyrus pyrifolia Nakai)
Authors: Minamikawa Mai F. , Takada Norio , Terakami Shingo , Saito Toshihiro , Onogi Akio , Kajiya-Kanegae Hiromi , Hayashi Takeshi , Yamamoto Toshiya , Iwata Hiroyoshi
Published: August 2018

Breeding of fruit trees is hindered by their large size and long juvenile period. Genome-wide association study (GWAS) and genomic selection (GS) are promising methods for circumventing this hindrance, but preparing new large datasets for these methods may not always be practical. Here, we evaluated the potential of breeding populations evaluated routinely in breeding programs for GWAS and GS. We used a pear parental population of 86 varieties and breeding populations of 765 trees from 16 full-sib families, which were phenotyped for 18 traits and genotyped for 1,506 single nucleotide polymorphisms (SNPs). The power of GWAS and accuracy of genomic prediction were improved when we combined data from the breeding populations and the parental population. The accuracy of genomic prediction was improved further when full-sib data of the target family were available. The results suggest that phenotype data collected in breeding programs can be beneficial for GWAS and GS when they are combined with genome-wide marker data. The potential of GWAS and GS will be further extended if we can build a system for routine collection of the phenotype and marker genotype data for breeding populations.
Monitoring bone changes due to calcium, magnesium, and phosphorus loss in rat femurs using Quantitative Ultrasound
Authors: Fontes-Pereira Aldo , Rosa Paulo , Barboza Thiago , Matusin Daniel , Freire Aline Soares , Braz Bernardo Ferreira , Machado Christiano Bittencourt , von Krüger Marco Antônio , Souza Sergio Augusto Lopes de , Santelli Ricardo Erthal , Pereira Wagner Coelho de Albuquerque
Published: August 2018

Bone mineral density is an important parameter for the diagnosis of bone diseases, as well as for predicting fractures and treatment monitoring. Thus, the aim of the present study was to evaluate the potential of Quantitative Ultrasound (QUS) to monitor bone changes after calcium, phosphorus, and magnesium loss in rat femurs in vitro during a demineralization process. Four quantitative ultrasound parameters were estimated from bone surface echoes in eight femur diaphysis of rats. The echo signals were acquired during a decalcification process by Ethylenediaminetetraacetic Acid (EDTA). The results were compared to Quantitative Computed Tomography (QCT) and inductively coupled plasma optical emission spectrometry measurements for validation. Integrated Reflection Coefficient (IRC) reflection parameters and Frequency Slope of Reflection Transfer Function (FSRTF) during demineralization tended to decrease, while the backscattering parameter Apparent Integrated Backscatter (AIB) increased and Frequency Slope of Apparent Backscatter (FSAB) showed an oscillatory behavior with no defined trend. Results indicate a clear relation between demineralization and the corresponding decrease in the reflection parameters and increase in the scattering parameters. The trend analysis of the fall curve of the chemical elements showed a better relationship between IRC and QCT. It was possible to monitor bone changes after ions losses, through the QUS. Thus, it is an indication that the proposed protocol has potential to characterize bone tissue in animal models, providing consistent results towards standardization of bone characterization studies by QUS endorsing its use in humans.
Tissue metabolite profiles for the characterisation of paediatric cerebellar tumours
Authors: Bennett Christopher D. , Kohe Sarah E. , Gill Simrandip K. , Davies Nigel P. , Wilson Martin , Storer Lisa C. D. , Ritzmann Timothy , Paine Simon M. L. , Scott Ian S. , Nicklaus-Wollenteit Ina , Tennant Daniel A. , Grundy Richard G. , Peet Andrew C.
Published: August 2018

Paediatric brain tumors are becoming well characterized due to large genomic and epigenomic studies. Metabolomics is a powerful analytical approach aiding in the characterization of tumors. This study shows that common cerebellar tumors have metabolite profiles sufficiently different to build accurate, robust diagnostic classifiers, and that the metabolite profiles can be used to assess differences in metabolism between the tumors. Tissue metabolite profiles were obtained from cerebellar ependymoma (n = 18), medulloblastoma (n = 36), pilocytic astrocytoma (n = 24) and atypical teratoid/rhabdoid tumors (n = 5) samples using HR-MAS. Quantified metabolites accurately discriminated the tumors; classification accuracies were 94% for ependymoma and medulloblastoma and 92% for pilocytic astrocytoma. Using current intraoperative examination the diagnostic accuracy was 72% for ependymoma, 90% for medulloblastoma and 89% for pilocytic astrocytoma. Elevated myo-inositol was characteristic of ependymoma whilst high taurine, phosphocholine and glycine distinguished medulloblastoma. Glutamine, hypotaurine and N-acetylaspartate (NAA) were increased in pilocytic astrocytoma. High lipids, phosphocholine and glutathione were important for separating ATRTs from medulloblastomas. This study demonstrates the ability of metabolic profiling by HR-MAS on small biopsy tissue samples to characterize these tumors. Analysis of tissue metabolite profiles has advantages in terms of minimal tissue pre-processing, short data acquisition time giving the potential to be used as part of a rapid diagnostic work-up.
Time trends in stroke incidence and in prevalence of risk factors in Southern Germany, 1989 to 2008/09
Authors: Thiele Inke , Linseisen Jakob , Heier Margit , Holle Rolf , Kirchberger Inge , Peters Annette , Thorand Barbara , Meisinger Christa
Published: August 2018

In prior studies, stroke incidence has mainly shown either declining time trends or stable rates in high-income countries. Changes could partially be linked to trends in classic cardiovascular disease (CVD) risk factors. In the present study, we analyzed the incidence of stroke in parallel with the prevalence of CVD risk factors over time in a German population. Data from three independent population-based MONICA/KORA Augsburg surveys conducted in 1989/90 (S2), 1994/95 (S3), and 1999/2001 (S4) were used to calculate age-standardized incidence rates (IR) of first-ever stroke over eight years from each baseline survey. Furthermore, the age-standardized prevalence rates of CVD risk factors were analyzed for these surveys. Changes in IR or prevalence were considered significantly different if their 95% confidence intervals (CI) did not overlap. The age-standardized IR of stroke showed no significant time trend (S2: IR = 203.4 per 100,000 person-years; CI 176.4–233.4, S3: IR = 225.6; 197.1–257.0, S4: IR = 209.9; CI 182.4–240.3). In agreement, the prevalence of the CVD risk factors was quite stable over time, showing divergent, but mostly non-significant changes. However, due to the aging Western societies and the longer survival time of stroke patients, the total number of stroke patients in the population will increase even with a stable IR.
Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability
Authors: Mosqueira Alejo , Camino Pablo A. , Barrantes Francisco J.
Published: August 2018

Translational motion of neurotransmitter receptors is key for determining receptor number at the synapse and hence, synaptic efficacy. We combine live-cell STORM superresolution microscopy of nicotinic acetylcholine receptor (nAChR) with single-particle tracking, mean-squared displacement (MSD), turning angle, ergodicity, and clustering analyses to characterize the lateral motion of individual molecules and their collective behaviour. nAChR diffusion is highly heterogeneous: subdiffusive, Brownian and, less frequently, superdiffusive. At the single-track level, free walks are transiently interrupted by ms-long confinement sojourns occurring in nanodomains of ~36 nm radius. Cholesterol modulates the time and the area spent in confinement. Turning angle analysis reveals anticorrelated steps with time-lag dependence, in good agreement with the permeable fence model. At the ensemble level, nanocluster assembly occurs in second-long bursts separated by periods of cluster disassembly. Thus, millisecond-long confinement sojourns and second-long reversible nanoclustering with similar cholesterol sensitivities affect all trajectories; the proportion of the two regimes determines the resulting macroscopic motional mode and breadth of heterogeneity in the ensemble population.
Targeting Nucleotide Binding Domain of Multidrug Resistance-associated Protein-1 (MRP1) for the Reversal of Multi Drug Resistance in Cancer
Authors: Dhasmana Divya , Singh Ashutosh , Shukla Rohit , Tripathi Timir , Garg Neha
Published: August 2018

Multidrug resistance (MDR) is the major cause, by which cancer cells expel the drugs out, developing a challenge against the current chemotherapeutic drugs regime. This mechanism is attributed to the over expression of ABC transporters like MRP1 on the surface of cells. Since nucleotide binding domains (NBD) of ABC transporters are the site of ATP binding and hydrolysis, thereby in this study we have targeted NBD1 of MRP1using molecular docking and molecular dynamic simulations (MDS). The compounds present in the FDA approved library were docked against NBD1 of the human multidrug resistance associated protein 1 (PDB ID: 2CBZ). For the docking studies, Standard Precision and Extra Precision methods were employed. After the EP docking studies, ligands showed an extremely low docking score that was indicative of very high binding affinity of the ligands to the NBD. Apart from the low docking score, another short listing criterion in simulation studies was the interaction of incoming ligand with the desired conserved residues of NDB involved in ATP binding and hydrolysis. Based on these measures, potassium citrate (DB09125) and technetium Tc-99m medronate (DB09138) were chosen and subjected to 100 ns simulation studies. From the MDS study we concluded that between these two compounds, potassium citrate is a better candidate for targeting MRP1.
Circadian clock disruption by selective removal of endogenous carbon monoxide
Authors: Minegishi Saika , Sagami Ikuko , Negi Shigeru , Kano Koji , Kitagishi Hiroaki
Published: August 2018

Circadian rhythms are regulated by transcription-translation feedback loops (TTFL) of clock genes. Previous studies have demonstrated that core transcriptional factors, NPAS2 and CLOCK, in the TTFL can reversibly bind carbon monoxide (CO) in vitro. However, little is known about whether endogenous CO, which is continuously produced during a heme metabolic process, is involved in the circadian system. Here we show that selective removal of endogenous CO in mice considerably disrupts rhythmic expression of the clock genes. A highly selective CO scavenger, hemoCD1, which is a supramolecular complex of an iron(II)porphyrin with a per-O-methyl-β-cyclodextrin dimer, was used to remove endogenous CO in mice. Intraperitoneal administration of hemoCD1 to mice immediately reduced the amount of internal CO. The removal of CO promoted the bindings of NPAS2 and CLOCK to DNA (E-box) in the murine liver, resulting in up-regulation of the E-box-controlled clock genes (Per1, Per2, Cry1, Cry2, and Rev-erbα). Within 3 h after the administration, most hemoCD1 in mice was excreted in the urine, and heme oxygenase-1 (HO-1) was gradually induced in the liver. Increased endogenous CO production due to the overexpression of HO-1 caused dissociation of NPAS2 and CLOCK from E-box, which in turn induced down-regulation of the clock genes. The down-regulation continued over 12 h even after the internal CO level recovered to normal. The late down-regulation was ascribed to an inflammatory response caused by the endogenous CO reduction. The CO pseudo-knockdown experiments provided the clear evidence that endogenous CO contributes to regulation in the mammalian circadian clock.
Accelerated pharmaceutical protein development with integrated cell free expression, purification, and bioconjugation
Authors: Richardson Dominique , Itkonen Jaakko , Nievas Julia , Urtti Arto , Casteleijn Marco G.
Published: August 2018

The use of living cells for the synthesis of pharmaceutical proteins, though state-of-the-art, is hindered by its lengthy process comprising of many steps that may affect the protein’s stability and activity. We aimed to integrate protein expression, purification, and bioconjugation in small volumes coupled with cell free protein synthesis for the target protein, ciliary neurotrophic factor. Split-intein mediated capture by use of capture peptides onto a solid surface was efficient at 89–93%. Proof-of-principle of light triggered release was compared to affinity chromatography (His6 fusion tag coupled with Ni-NTA). The latter was more efficient, but more time consuming. Light triggered release was clearly demonstrated. Moreover, we transferred biotin from the capture peptide to the target protein without further purification steps. Finally, the target protein was released in a buffer-volume and composition of our choice, omitting the need for protein concentration or changing the buffer. Split-intein mediated capture, protein trans splicing followed by light triggered release, and bioconjugation for proteins synthesized in cell free systems might be performed in an integrated workflow resulting in the fast production of the target protein.
BCS thermal vacuum of fermionic superfluids and its perturbation theory
Authors: Hou Xu-Yang , Huang Ziwen , Guo Hao , He Yan , Chien Chih-Chun
Published: August 2018

The thermal field theory is applied to fermionic superfluids by doubling the degrees of freedom of the BCS theory. We construct the two-mode states and the corresponding Bogoliubov transformation to obtain the BCS thermal vacuum. The expectation values with respect to the BCS thermal vacuum produce the statistical average of the thermodynamic quantities. The BCS thermal vacuum allows a quantum-mechanical perturbation theory with the BCS theory serving as the unperturbed state. We evaluate the leading-order corrections to the order parameter and other physical quantities from the perturbation theory. A direct evaluation of the pairing correlation as a function of temperature shows the pseudogap phenomenon, where the pairing persists when the order parameter vanishes, emerges from the perturbation theory. The correspondence between the thermal vacuum and purification of the density matrix allows a unitary transformation, and we found the geometric phase associated with the transformation in the parameter space.
Resting-state alpha power is selectively associated with autistic traits reflecting behavioral rigidity
Authors: Carter Leno Virginia , Tomlinson Samuel B. , Chang Shou-An A. , Naples Adam J. , McPartland James C.
Published: August 2018

Previous research suggests that variation in at-rest neural activity correlates with specific domains of the ASD phenotype; however, few studies have linked patterns of brain activity with autistic trait expression in typically developing populations. The purpose of this study was to examine associations between resting-state electroencephalography (EEG) and three domains of the broader autism phenotype (social interest, rigidity, and pragmatic language) in typically developing individuals. High-density scalp EEG was recorded in thirty-seven typically developing adult participants (13 male, aged 18–52 years). The Broad Autism Phenotype Questionnaire (BAP-Q) was used to measure autistic trait expression. Absolute alpha power (8–13 Hz) was extracted from eyes-closed epochs using spectral decomposition techniques. Analyses revealed a specific positive association between scores on the BAP-Q Rigidity subscale and alpha power in the parietal scalp region. No significant associations were found between alpha power and the BAP-Q Aloofness or Pragmatic Language subscales. Furthermore, the association between EEG power and behavioral rigidity was specific to the alpha frequency band. This study demonstrates that specific traits within the broader autism phenotype are associated with dissociable patterns of at-rest neural activity.
Thermoelectric properties of SnSe nanowires with different diameters
Authors: Hernandez Jose A. , Ruiz Angel , Fonseca Luis F. , Pettes Michael T. , Jose-Yacaman Miguel , Benitez Alfredo
Published: August 2018

Tin selenide (SnSe) has been the subject of great attention in the last years due to its highly efficient thermoelectricity and its possibilities as a green material, free of Pb and Te. Here, we report for the first time a thermoelectricity and transport study of individual SnSe micro- and nano-wires with diameters in the range between 130 nm and 1.15 μm. X-ray diffraction and transmission electron microscopy analyses confirm an orthorhombic SnSe structure with Pnma (62) symmetry group and 1:1 Sn:Se atomic ratio. Electrical and thermal conductivity and the Seebeck coefficient were measured in each individual nanowire using a specialized suspended microdevice in the 150–370 K temperature range, yielding a thermal conductivity of 0.55 Wm−1 K−1 at room temperature and ZT ~ 0.156 at 370 K for the 130 nm diameter nanowire. The measured properties were correlated with electronic information obtained by model simulations and with phonon scattering analysis. The results confirm these structures as promising building blocks to develop efficient temperature sensors, refrigerators and thermoelectric energy converters. The thermoelectric response of the nanowires is compared with recent reports on crystalline, polycrystalline and layered bulk structures.
Single cell analysis reveals a biophysical aspect of collective cell-state transition in embryonic stem cell differentiation
Authors: Okamoto Kazuko , Germond Arno , Fujita Hideaki , Furusawa Chikara , Okada Yasushi , Watanabe Tomonobu M.
Published: August 2018

In the stem cell research field, the molecular regulatory network used to define cellular states has been extensively studied, however, the general driving force guiding the collective state dynamics remains to be identified from biophysical aspects. Here we monitored the time-development of the cell-state transition at the single-cell and colony levels, simultaneously, during the early differentiation process in mouse embryonic stem cells. Our quantitative analyses revealed that cellular heterogeneity was a result of spontaneous fluctuation of cellular state and cell-cell cooperativity. We considered that the cell state is like a ball fluctuating on a potential landscape, and found that the cooperativity affects the fluctuation. Importantly, the cooperativity temporarily decreased and increased in the intermediate state of cell differentiation, leading to cell-state transition in unison. This process can be explained using the mathematical equation of flashing-ratchet behaviour, which suggests that a general mechanism is driving the collective decision-making of stem cells.