bluuebunny/crossref_metadata_2025_split huggingface dataset:
UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras
Authors: Xu Zhiliang , Duan Fengsen , Lu Huiai , Abdulkadhim Dragh Maytham , Xia Yanzhi , Liang Huageng , Hong Ling 
Published: December 2018

AbstractUbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a key role in biosynthesis of vitamin K2 and coenzyme Q10 using geranylgeranyl diphosphate (GGPP). However, the mechanism by which UBIAD1 participates in tumorigenesis remains unknown. This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the proliferation of bladder cancer cells. In addition, GGPP was required to maintain the function of UBIAD1 in regulating the Ras/ERK signaling pathway. A Drosophila model was employed to confirm the function of UBIAD1/HEIX in vivo. The activation of Ras/ERK signaling at the plasma membrane induced melanotic masses in Drosophila larvae. Our study suggests that UBIAD1 serves as a tumor suppressor in cancer and tentatively reveals the underlying mechanism of melanotic mass formation in Drosophila.
LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA
Authors: Tang Jianming , Zhong Guangsheng , Zhang Haibo , Yu Bo , Wei Fangqiang , Luo Liming , kang Yao , Wu Jianhui , Jiang Jiaxiang , Li Yucheng , Wu Shuqiang , Jia Yongshi , Liang Xiaodong , Bi Aihong 
Published: December 2018

AbstactConventional therapies and novel molecular targeted therapies against breast cancer have gained great advances over the past two decades. However, poor prognosis and low survival rate are far from expectation for improvement, particularly in patients with triple negative breast cancer (TNBC). Here, we found that lncRNADANCRwas significantly overregulated in TNBC tissues and cell lines compared with normal breast tissues or other type of breast cancer. Knockdown ofDANCRsuppressed TNBC proliferation both in vitro and in vivo. Further study of underlying mechanisms demonstrated thatDANCRbound with RXRA and increased its serine 49/78 phosphorylation via GSK3β, resulting in activating PIK3CA transcription, and subsequently enhanced PI3K/AKT signaling and TNBC tumorigenesis. Taken together, Our findings identifiedDANCRas an pro-oncogene and uncoverd a new working pattern of lncRNA to mediate TNBC tumorigenesis, which may be a potential therapeutic target for improving treatment of TNBC.
Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation
Authors: Nakamura Yoshiyuki , Matsuzaka Takashi , Tahara-Hanaoka Satoko , Shibuya Kazuko , Shimano Hitoshi , Nakahashi-Oda Chigusa , Shibuya Akira 
Published: December 2018

AbstractMechanical damage on the skin not only affects barrier function but also induces various immune responses, which trigger or exacerbate skin inflammation. However, how mechanical damage-induced skin inflammation is regulated remains incompletely understood. Here, we show that keratinocytes express the long-chain fatty-acid elongase Elovl6. Mice deficient in Elovl6 showed higher levels of cis-vaccenic acid (CVA) in the epidermis and severe skin inflammation induced by mechanical damage due to tape stripping than did wild-type mice. CVA accelerated tape stripping-triggered keratinocyte death and release of danger-associated molecular patterns (DAMPs) such as high-mobility group box 1 protein (HMGB-1) and IL-1α, which induced production of proinflammatory cytokines and chemokines IL-1β and CXCL-1 by keratinocytes. Our results demonstrate that Elovl6 regulates mechanical damage—triggered keratinocyte death and the subsequent dermatitis.
A novel intragenic deletion in OPHN1 in a Japanese patient with Dandy-Walker malformation
Authors: Iida Aritoshi , Takeshita Eri , Kosugi Shunichi , Kamatani Yoichiro , Momozawa Yukihide , Kubo Michiaki , Nakagawa Eiji , Kurosawa Kenji , Inoue Ken , Goto Yu-ichi 
Published: December 2018

AbstractDandy-Walker malformation (DWM) is a rare congenital malformation defined by hypoplasia of the cerebellar vermis and cystic dilatation of the fourth ventricle. Oligophrenin-1 is mutated in X-linked intellectual disability with or without cerebellar hypoplasia. Here, we report a Japanese DWM patient carrying a novel intragenic 13.5-kb deletion in OPHN1 ranging from exon 11–15. This is the first report of an OPHN1 deletion in a Japanese patient with DWM.
Organic bromine compounds produced in sea ice in Antarctic winter
Authors: Abrahamsson Katarina , Granfors Anna , Ahnoff Martin , Cuevas Carlos A. , Saiz-Lopez Alfonso 
Published: December 2018

AbstractDuring polar springtime, active bromine drives ozone, a greenhouse gas, to near-zero levels. Bromine production and emission in the polar regions have so far been assumed to require sunlight. Here, we report measurements of bromocarbons in sea ice, snow, and air during the Antarctic winter that reveal an unexpected new source of organic bromine to the atmosphere during periods of no sunlight. The results show that Antarctic winter sea ice provides 10 times more bromocarbons to the atmosphere than Southern Ocean waters, and substantially more than summer sea ice. The inclusion of these measurements in a global climate model indicates that the emitted bromocarbons will disperse throughout the troposphere in the southern hemisphere and through photochemical degradation to bromine atoms, contribute ~ 10% to the tropospheric reactive bromine budget. Combined together, our results suggest that winter sea ice could potentially be an important source of atmospheric bromine with implications for atmospheric chemistry and climate at a hemispheric scale.
Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias
Authors: Chaudhury Shahzya , O’Connor Caitríona , Cañete Ana , Bittencourt-Silvestre Joana , Sarrou Evgenia , Prendergast Áine , Choi Jarny , Johnston Pamela , Wells Christine A. , Gibson Brenda , Keeshan Karen 
Published: December 2018

AbstractAcute myeloid leukaemia (AML) affects children and adults of all ages. AML remains one of the major causes of death in children with cancer and for children with AML relapse is the most common cause of death. Here, by modelling AML in vivo we demonstrate that AML is discriminated by the age of the cell of origin. Young cells give rise to myeloid, lymphoid or mixed phenotype acute leukaemia, whereas adult cells give rise exclusively to AML, with a shorter latency. Unlike adult, young AML cells do not remodel the bone marrow stroma. Transcriptional analysis distinguishes young AML by the upregulation of immune pathways. Analysis of human paediatric AML samples recapitulates a paediatric immune cell interaction gene signature, highlighting two genes, RGS10 and FAM26F as prognostically significant. This work advances our understanding of paediatric AML biology, and provides murine models that offer the potential for developing paediatric specific therapeutic strategies.
Transcriptomic meta-signatures identified in Anopheles gambiae populations reveal previously undetected insecticide resistance mechanisms
Authors: Ingham V. A. , Wagstaff S. , Ranson H. 
Published: December 2018

AbstractIncreasing insecticide resistance in malaria-transmitting vectors represents a public health threat, but underlying mechanisms are poorly understood. Here, a data integration approach is used to analyse transcriptomic data from comparisons of insecticide resistant and susceptible Anopheles populations from disparate geographical regions across the African continent. An unbiased, integrated analysis of this data confirms previously described resistance candidates but also identifies multiple novel genes involving alternative resistance mechanisms, including sequestration, and transcription factors regulating multiple downstream effector genes, which are validated by gene silencing. The integrated datasets can be interrogated with a bespoke Shiny R script, deployed as an interactive web-based application, that maps the expression of resistance candidates and identifies co-regulated transcripts that may give clues to the function of novel resistance-associated genes.
Microtubule asters anchored by FSD1 control axoneme assembly and ciliogenesis
Authors: Tu Hai-Qing , Qin Xuan-He , Liu Zhi-Bin , Song Zeng-Qing , Hu Huai-Bin , Zhang Yu-Cheng , Chang Yan , Wu Min , Huang Yan , Bai Yun-Feng , Wang Guang , Han Qiu-Ying , Li Ai-Ling , Zhou Tao , Liu Feng , Zhang Xue-Min , Li Hui-Yan 
Published: December 2018

AbstractDefective ciliogenesis causes human developmental diseases termed ciliopathies. Microtubule (MT) asters originating from centrosomes in mitosis ensure the fidelity of cell division by positioning the spindle apparatus. However, the function of microtubule asters in interphase remains largely unknown. Here, we reveal an essential role of MT asters in transition zone (TZ) assembly during ciliogenesis. We demonstrate that the centrosome protein FSD1, whose biological function is largely unknown, anchors MT asters to interphase centrosomes by binding to microtubules. FSD1 knockdown causes defective ciliogenesis and affects embryonic development in vertebrates. We further show that disruption of MT aster anchorage by depleting FSD1 or other known anchoring proteins delocalizes the TZ assembly factor Cep290 from centriolar satellites, and causes TZ assembly defects. Thus, our study establishes FSD1 as a MT aster anchorage protein and reveals an important function of MT asters anchored by FSD1 in TZ assembly during ciliogenesis.
Ultrahigh specificity in a network of computationally designed protein-interaction pairs
Authors: Netzer Ravit , Listov Dina , Lipsh Rosalie , Dym Orly , Albeck Shira , Knop Orli , Kleanthous Colin , Fleishman Sarel J. 
Published: December 2018

AbstractProtein networks in all organisms comprise homologous interacting pairs. In these networks, some proteins are specific, interacting with one or a few binding partners, whereas others are multispecific and bind a range of targets. We describe an algorithm that starts from an interacting pair and designs dozens of new pairs with diverse backbone conformations at the binding site as well as new binding orientations and sequences. Applied to a high-affinity bacterial pair, the algorithm results in 18 new ones, with cognate affinities from pico- to micromolar. Three pairs exhibit 3-5 orders of magnitude switch in specificity relative to the wild type, whereas others are multispecific, collectively forming a protein-interaction network. Crystallographic analysis confirms design accuracy, including in new backbones and polar interactions. Preorganized polar interaction networks are responsible for high specificity, thus defining design principles that can be applied to program synthetic cellular interaction networks of desired affinity and specificity.
Transcription factor DUO1 generated by neo-functionalization is associated with evolution of sperm differentiation in plants
Authors: Higo Asuka , Kawashima Tomokazu , Borg Michael , Zhao Mingmin , López-Vidriero Irene , Sakayama Hidetoshi , Montgomery Sean A. , Sekimoto Hiroyuki , Hackenberg Dieter , Shimamura Masaki , Nishiyama Tomoaki , Sakakibara Keiko , Tomita Yuki , Togawa Taisuke , Kunimoto Kan , Osakabe Akihisa , Suzuki Yutaka , Yamato Katsuyuki T. , Ishizaki Kimitsune , Nishihama Ryuichi , Kohchi Takayuki , Franco-Zorrilla José M. , Twell David , Berger Frédéric , Araki Takashi 
Published: December 2018

AbstractEvolutionary mechanisms underlying innovation of cell types have remained largely unclear. In multicellular eukaryotes, the evolutionary molecular origin of sperm differentiation is unknown in most lineages. Here, we report that in algal ancestors of land plants, changes in the DNA-binding domain of the ancestor of the MYB transcription factor DUO1 enabled the recognition of a new cis-regulatory element. This event led to the differentiation of motile sperm. After neo-functionalization, DUO1 acquired sperm lineage-specific expression in the common ancestor of land plants. Subsequently the downstream network of DUO1 was rewired leading to sperm with distinct morphologies. Conjugating green algae, a sister group of land plants, accumulated mutations in the DNA-binding domain of DUO1 and lost sperm differentiation. Our findings suggest that the emergence of DUO1 was the defining event in the evolution of sperm differentiation and the varied modes of sexual reproduction in the land plant lineage.
Bretschneider solution-induced alterations in the urine metabolome in cardiac surgery patients
Authors: Lee Cheng-Chia , Hsieh Ya-Ju , Chen Shao-Wei , Fu Shu-Hsuan , Hsu Chia-Wei , Wu Chih-Ching , Han Wei , Li Yunong , Huan Tao , Chang Yu-Sun , Yu Jau-Song , Li Liang , Chang Chih-Hsiang , Chen Yi-Ting 
Published: December 2018

AbstractThe development of Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution represented a major advancement in cardiac surgery, offering significant myocardial protection. However, metabolic changes induced by this additive in the whole body have not been systematically investigated. Using an untargeted mass spectrometry-based method to deeply explore the urine metabolome, we sought to provide a holistic and systematic view of metabolic perturbations occurred in patients receiving HTK. Prospective urine samples were collected from 100 patients who had undergone cardiac surgery, and metabolomic changes were profiled using a high-performance chemical isotope labeling liquid chromatography-mass spectrometry (LC-MS) method. A total of 14,642 peak pairs or metabolites were quantified using differential 13C-/12C-dansyl labeling LC-MS, which targets the amine/phenol submetabolome from urine specimens. We identified 223 metabolites that showed significant concentration change (fold change > 5) and assembled several potential metabolic pathway maps derived from these dysregulated metabolites. Our data indicated upregulated histidine metabolism with subsequently increased glutamine/glutamate metabolism, altered purine and pyrimidine metabolism, and enhanced vitamin B6 metabolism in patients receiving HTK. Our findings provide solid evidence that HTK solution causes significant perturbations in several metabolic pathways and establish a basis for further study of key mechanisms underlying its organ-protective or potential harmful effects.
Differential regulation of cysteine oxidative post-translational modifications in high and low aerobic capacity
Authors: Souza Rodrigo W. A. , Alves Christiano R. R. , Medeiros Alessandra , Rolim Natale , Silva Gustavo J. J. , Moreira José B. N. , Alves Marcia N. , Wohlwend Martin , Gebriel Mohammed , Hagen Lars , Sharma Animesh , Koch Lauren G. , Britton Steven L. , Slupphaug Geir , Wisløff Ulrik , Brum Patricia C. 
Published: December 2018

AbstractGiven the association between high aerobic capacity and the prevention of metabolic diseases, elucidating the mechanisms by which high aerobic capacity regulates whole-body metabolic homeostasis is a major research challenge. Oxidative post-translational modifications (Ox-PTMs) of proteins can regulate cellular homeostasis in skeletal and cardiac muscles, but the relationship between Ox-PTMs and intrinsic components of oxidative energy metabolism is still unclear. Here, we evaluated the Ox-PTM profile in cardiac and skeletal muscles of rats bred for low (LCR) and high (HCR) intrinsic aerobic capacity. Redox proteomics screening revealed different cysteine (Cys) Ox-PTM profile between HCR and LCR rats. HCR showed a higher number of oxidized Cys residues in skeletal muscle compared to LCR, while the opposite was observed in the heart. Most proteins with differentially oxidized Cys residues in the skeletal muscle are important regulators of oxidative metabolism. The most oxidized protein in the skeletal muscle of HCR rats was malate dehydrogenase (MDH1). HCR showed higher MDH1 activity compared to LCR in skeletal, but not cardiac muscle. These novel findings indicate a clear association between Cys Ox-PTMs and aerobic capacity, leading to novel insights into the role of Ox-PTMs as an essential signal to maintain metabolic homeostasis.
Fast adaptation of tropical diatoms to increased warming with trade-offs
Authors: Jin Peng , Agustí Susana 
Published: December 2018

AbstractOcean warming with climate change is forcing marine organisms to shift their distributions polewards and phenology. In warm tropical seas, evolutionary adaptation by local species to warming will be crucial to avoid predicted desertification and reduction in diversity. However, little is known about the adaptation of phytoplankton in warm seas. Across the ocean, diatomic microalgae are the main primary producers in cold waters; they also contribute to tropical communities where they play a necessary role in the biological pump. Here we show that four species of diatoms isolated from the tropical Red Sea adapted to warming conditions (30 °C) after 200–600 generations by using various thermal strategies. Two of the warming adapted species increased their optimal growth temperature (Topt) and maximum growth rate. The other two diatoms did not increase Topt and growth, but shifted from specialist to generalist increasing their maximum critical thermal limit. Our data show that tropical diatoms can adapt to warming, although trade offs on photosynthetic efficiency, high irradiance stress, and lower growth rate could alter their competitive fitness. Our findings suggest that adaptive responses to warming among phytoplankton could help to arrest the sharp decline in diversity resulting from climate change that is predicted for tropical waters.
Preferential attentional engagement drives attentional bias to snakes in Japanese macaques (Macaca fuscata) and humans (Homo sapiens)
Authors: Masataka Nobuo , Koda Hiroki , Atsumi Takeshi , Satoh Madoka , Lipp Ottmar V. 
Published: December 2018

AbstractIn humans, attentional biases have been shown to negative (dangerous animals, physical threat) and positive (high caloric food, alcohol) stimuli. However, it is not clear whether these attentional biases reflect on stimulus driven, bottom up, or goal driven, top down, attentional processes. Here we show that, like humans, Japanese macaques show an attentional bias to snakes in a dot probe task (Experiment 1). Moreover, this attentional bias reflects on bottom up driven, preferential engagement of attention by snake images (Experiment 2a), a finding that was replicated in a study that used the same methodology in humans (Experiment 2b). These results are consistent with the notion that attentional bias to snakes reflects on an evolutionarily old, stimulus driven threat detection mechanism which is found in both species.
Rafting behaviour of seabirds as a proxy to describe surface ocean currents in the Balearic Sea
Authors: Sánchez-Román A. , Gómez-Navarro L. , Fablet R. , Oro D. , Mason E. , Arcos J. M. , Ruiz S. , Pascual A. 
Published: December 2018

AbstractSpatio-temporal variability of surface geostrophic mesoscale currents in the Balearic Sea (western Mediterranean) is characterized from satellite altimetry in combination with in-situ velocity measurements collected, among others, by drifting buoys, gliders and high-frequency radar. Here, we explore the use of tracking data from living organisms in the Balearic Sea as an alternative way to acquire in-situ velocity measurements. Specifically, we use GPS-tracks of resting Scopoli’s shearwaters Calonectris diomedea, that act as passive drifters, and compare them with satellite-derived velocity patterns. Results suggest that animal-borne GPS data can be used to identify rafting behaviour outside of the breeding colonies and, furthermore, as a proxy to describe local sea surface currents. Four rafting patterns were identified according to the prevailing driving forces responsible for the observed trajectories. We find that 76% of the bird trajectories are associated with the combined effects of slippage and Ekman drift and/or surface drag; 59% are directly driven by the sea surface currents. Shearwaters are therefore likely to be passively transported by these driving forces while resting. The tracks are generally consistent with the mesoscale features observed in satellite data and identified with eddy-tracking software.
Clinical validation of smartphone-based activity tracking in peripheral artery disease patients
Authors: Ata Raheel , Gandhi Neil , Rasmussen Hannah , El-Gabalawy Osama , Gutierrez Santiago , Ahmad Alizeh , Suresh Siddharth , Ravi Roshini , Rothenberg Kara , Aalami Oliver 
Published: December 2018

AbstractPeripheral artery disease (PAD) is a vascular disease that leads to reduced blood flow to the limbs, often causing claudication symptoms that impair patients’ ability to walk. The distance walked during a 6-min walk test (6MWT) correlates well with patient claudication symptoms, so we developed the VascTrac iPhone app as a platform for monitoring PAD using a digital 6MWT. In this study, we evaluate the accuracy of the built-in iPhone distance and step-counting algorithms during 6MWTs. One hundred and fourteen (114) participants with PAD performed a supervised 6MWT using the VascTrac app while simultaneously wearing an ActiGraph GT9X Activity Monitor. Steps and distance-walked during the 6MWT were manually measured and used to assess the bias in the iPhone CMPedometer algorithms. The iPhone CMPedometer step algorithm underestimated steps with a bias of −7.2% ± 13.8% (mean ± SD) and had a mean percent difference with the Actigraph (Actigraph-iPhone) of 5.7% ± 20.5%. The iPhone CMPedometer distance algorithm overestimated distance with a bias of 43% ± 42% due to overestimation in stride length. Our correction factor improved distance estimation to 8% ± 32%. The Ankle-Brachial Index (ABI) correlated poorly with steps (R = 0.365) and distance (R = 0.413). Thus, in PAD patients, the iPhone’s built-in distance algorithm is unable to accurately measure distance, suggesting that custom algorithms are necessary for using iPhones as a platform for monitoring distance walked in PAD patients. Although the iPhone accurately measured steps, more research is necessary to establish step counting as a clinically meaningful metric for PAD.
The Role of Effortful Control in Stuttering Severity in Children: Replication Study
Authors: Kraft Shelly Jo , Lowther Emily , Beilby Janet 
Published: December 2018

Background
In 2014, Kraft et al. assessed the temperament, home environment, and significant life events of 69 North American children who stutter to examine the combined and compounded effects of these individualized factors on mediating overt stuttering severity. The temperament domain of effortful control was singularly found to be significantly predictive of stuttering severity.

Purpose
Because of the clinical significance of the initial study's findings, a replication study with a different, larger cohort of children who stutter was warranted to validate the reported outcomes.

Method

The current study assesses 98 children who stutter, ages 2;4 to 12;6 (years; months,
M
= 6;7), recruited from Perth, Australia.

Results

The results support the previous findings of
Kraft, Ambrose, and Chon (2014)
, with effortful control remaining the sole significant contributor to variability in stuttering severity, as rated by both parents and clinicians.

Conclusion
These cumulative and consistent outcomes support the need to develop targeted intervention strategies that specifically strengthen aspects of effortful control as a means to support positive therapeutic change in children who stutter.