bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression
Authors: Strawbridge Rona J. , Ward Joey , Lyall Laura M. , Tunbridge Elizabeth M. , Cullen Breda , Graham Nicholas , Ferguson Amy , Johnston Keira J. A. , Lyall Donald M. , Mackay Daniel , Cavanagh Jonathan , Howard David M. , Adams Mark J. , Deary Ian , Escott-Price Valentina , O’Donovan Michael , McIntosh Andrew M. , Bailey Mark E. S. , Pell Jill P. , Harrison Paul J. , Smith Daniel J.
Published: September 2018

Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (n = 83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects.
SMRT-Cappable-seq reveals complex operon variants in bacteria
Authors: Yan Bo , Boitano Matthew , Clark Tyson A. , Ettwiller Laurence
Published: September 2018

Current methods for genome-wide analysis of gene expression require fragmentation of original transcripts into small fragments for short-read sequencing. In bacteria, the resulting fragmented information hides operon complexity. Additionally, in vivo processing of transcripts confounds the accurate identification of the 5′ and 3′ ends of operons. Here we develop a methodology called SMRT-Cappable-seq that combines the isolation of un-fragmented primary transcripts with single-molecule long read sequencing. Applied to E. coli, this technology results in an accurate definition of the transcriptome with 34% of known operons from RegulonDB being extended by at least one gene. Furthermore, 40% of transcription termination sites have read-through that alters the gene content of the operons. As a result, most of the bacterial genes are present in multiple operon variants reminiscent of eukaryotic splicing. By providing such granularity in the operon structure, this study represents an important resource for the study of prokaryotic gene network and regulation.
Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD
Authors: Schultz Mark L. , Krus Kelsey L. , Kaushik Susmita , Dang Derek , Chopra Ravi , Qi Ling , Shakkottai Vikram G. , Cuervo Ana Maria , Lieberman Andrew P.
Published: September 2018

Niemann–Pick type C disease is a fatal, progressive neurodegenerative disorder caused by loss-of-function mutations in NPC1, a multipass transmembrane glycoprotein essential for intracellular lipid trafficking. We sought to define the cellular machinery controlling degradation of the most common disease-causing mutant, I1061T NPC1. We show that this mutant is degraded, in part, by the proteasome following MARCH6-dependent ERAD. Unexpectedly, we demonstrate that I1061T NPC1 is also degraded by a recently described autophagic pathway called selective ER autophagy (ER-phagy). We establish the importance of ER-phagy both in vitro and in vivo, and identify I1061T as a misfolded endogenous substrate for this FAM134B-dependent process. Subcellular fractionation of I1061T Npc1 mouse tissues and analysis of human samples show alterations of key components of ER-phagy, including FAM134B. Our data establish that I1061T NPC1 is recognized in the ER and degraded by two different pathways that function in a complementary fashion to regulate protein turnover.
Efficient search of compositional space for hybrid organic–inorganic perovskites via Bayesian optimization
Authors: Herbol Henry C. , Hu Weici , Frazier Peter , Clancy Paulette , Poloczek Matthias
Published: September 2018

Accelerated searches, made possible by machine learning techniques, are of growing interest in materials discovery. A suitable case involves the solution processing of components that ultimately form thin films of solar cell materials known as hybrid organic–inorganic perovskites (HOIPs). The number of molecular species that combine in solution to form these films constitutes an overwhelmingly large “compositional” space (at times, exceeding 500,000 possible combinations). Selecting a HOIP with desirable characteristics involves choosing different cations, halides, and solvent blends from a diverse palette of options. An unguided search by experimental investigations or molecular simulations is prohibitively expensive. In this work, we propose a Bayesian optimization method that uses an application-specific kernel to overcome challenges where data is scarce, and in which the search space is given by binary variables indicating whether a constituent is present or not. We demonstrate that the proposed approach identifies HOIPs with the targeted maximum intermolecular binding energy between HOIP salt and solvent at considerably lower cost than previous state-of-the-art Bayesian optimization methodology and at a fraction of the time (less than 10%) needed to complete an exhaustive search. We find an optimal composition within 15 ± 10 iterations in a HOIP compositional space containing 72 combinations, and within 31 ± 9 iterations when considering mixed halides (240 combinations). Exhaustive quantum mechanical simulations of all possible combinations were used to validate the optimal prediction from a Bayesian optimization approach. This paper demonstrates the potential of the Bayesian optimization methodology reported here for new materials discovery.
Characterisation of pathogen-specific regions and novel effector candidates in Fusarium oxysporum f. sp. cepae
Authors: Armitage Andrew D. , Taylor Andrew , Sobczyk Maria K. , Baxter Laura , Greenfield Bethany P. J. , Bates Helen J. , Wilson Fiona , Jackson Alison C. , Ott Sascha , Harrison Richard J. , Clarkson John P.
Published: September 2018

A reference-quality assembly ofFusarium oxysporumf. sp.cepae(Foc), the causative agent of onion basal rot has been generated along with genomes of additional pathogenic and non-pathogenic isolates of onion. Phylogenetic analysis confirmed a single origin of the Foc pathogenic lineage. Genome alignments with otherF.oxysporumff. spp. and non pathogens revealed high levels of syntenic conservation of core chromosomes but little synteny between lineage specific (LS) chromosomes. Four LS contigs in Foc totaling 3.9 Mb were designated as pathogen-specific (PS). A two-fold increase in segmental duplication events was observed between LS regions of the genome compared to within core regions or from LS regions to the core. RNA-seq expression studies identified candidate effectors expressedin planta, consisting of both known effector homologs and novel candidates. FTF1 and a subset of other transcription factors implicated in regulation of effector expression were found to be expressedin planta.
A method of determining heated ancient nephrite jades in China
Authors: Bao Yi , Zhao Chaohong , Li Yuesheng , Yun Xuemei
Published: September 2018

Ancient jade is one of the most significant cultural relics in China. Despite the increasingly important role of heated jades in ancient jade study, there are still few in-depth material studies on heated jades for the time being, which results in limitations on archaeological research and conservation. In order to evaluate the appearance change of nephrite jades, we employ the heating simulation experiment to present these change under different heating temperature ranging from 100 °C to 1300 °C. In this study, a nondestructive identification method proposed is to help determine whether the ancient jades were heated before and what the approximate heating temperature was from 100 °C to 1300 °C though phase transformation, structure change and colour variation with several advanced characterization methods such as the X-ray diffraction (XRD), the thermo-gravimetric analyser (TGA), the ultraviolet-visible spectrophotometer (UV-Vis), the Fourier transform infrared spectroscopy (FTIR) and the scanning electron microscope (SEM). The hierarchy of colour (from ~500 °C) and structure (from ~800 °C) on heated jades in the jade research field were first proposed and discuss here. This method is considered useful and valuable in the study and protection of Chinese ancient jades.
Role of blood urea nitrogen in predicting the post-discharge prognosis in elderly patients with acute decompensated heart failure
Authors: Ren Xiaohong , Qu Wei , Zhang Lijuan , Liu Miao , Gao Xuling , Gao Yuting , Cheng Xiaodan , Xu Weiwei , Liu Youhong
Published: September 2018

Blood urea nitrogen (BUN) is a surrogate marker for neurohormonal activation, but the association between BUN and the post-discharge prognosis in elderly patients with acute decompensated heart failure (ADHF) is not well defined. We explored the association between BUN and post-discharge all-cause mortality in 652 elderly patients (73.9 ± 7.8 yr) with ADHF. All patients were followed for a mean duration of 32 months (12–69 months). BUN was analyzed both as a continuous variable and according to two categories: low BUN group (BUN < 15.35 mmol/L, N = 361) and high BUN group (BUN ≥ 15.35 mmol/L, N = 291). The risk of all-cause mortality increased by 1.6% per 1 mmol/L increase in BUN concentration when BUN was used as a continuous variable [hazard ratio (HR): 1.016, 95% confidence interval (CI): 1.006–1.026, p = 0.002]. BUN maintained an independent and significant positive correlation with all-cause mortality as a categorical variable (HR: 1.355, 95% CI: 1.023–1.794, p = 0.034 for the high BUN group). The BUN C-statistic for predicting all-cause mortality was 0.624 (95% CI: 0.585–0.661). The cut-off value for BUN was 15.35 mmol/L with sensitivity of 0.58 and specificity of 0.63. The prognostic performance of BUN was similar to brain natriuretic peptide (BNP) for predicting all-cause mortality (C-statistic: z = 0.044, p = 0.965). These results suggest that BUN is an independent predictor of post-discharge all-cause mortality in elderly patients with ADHF and its prognostic performance was similar to that of BNP.
Transferrin as a thermosensitizer in radiofrequency hyperthermia for cancer treatment
Authors: Chung Hea-Jong , Lee Heui-Kwan , Kwon Ki Beom , Kim Hyeon-Jin , Hong Seong-Tshool
Published: September 2018

One of the main characteristics of cancer tissues is poor development of neovascularization that results in a limited blood circulation. Because of this phenomenon, it is harder for cancer tissues to diffuse their elevated heat into other parts of the body. The scientific principle of radiofrequency hyperthermia relies on this quality of cancer tissues which with higher temperature becomes more apparent. Despite the obvious necessity to selectively heat the cancer tissue for radiofrequency hyperthermia, a proper thermosensitizer has not been developed until now. Here, we show that transferrin containing ferric ion could be an ideal thermosensitizer for the increased efficiency of radiofrequency hyperthermia. In our result, the ferric ion-enriched cancer tissues dramatically react with 13.56 MHz radiofrequency wave to cause cancer-selective dielectric temperature increment. The overall anticancer efficacy of a 13.56 MHz radiofrequency hyperthermia using transferrin as a thermosensitizer was much higher than the oncotherapeutic efficacy of paclitaxel, successfully eradicating cancer in a tumor-xenografted mouse experiment.
Super-silent FRET Sensor Enables Live Cell Imaging and Flow Cytometric Stratification of Intracellular Serine Protease Activity in Neutrophils
Authors: Craven Thomas H. , Avlonitis Nicolaos , McDonald Neil , Walton Tashfeen , Scholefield Emma , Akram Ahsan R. , Walsh Timothy S. , Haslett Chris , Bradley Mark , Dhaliwal Kevin
Published: September 2018

Serine proteases are released by neutrophils to act primarily as antimicrobial proteins but excessive and unbalanced serine protease activity results in serious host tissue damage. Here the synthesis of a novel chemical sensor based on a multi-branched fluorescence quencher is reported. It is super-silent, exhibiting no fluorescence until de-quenched by the exemplar serine protease human neutrophil elastase, rapidly enters human neutrophils, and is inhibited by serine protease inhibitors. This sensor allows live imaging of intracellular serine protease activity within human neutrophils and demonstrates that the unique combination of a multivalent scaffold combined with a FRET peptide represents a novel and efficient strategy to generate super-silent sensors that permit the visualisation of intracellular proteases and may enable point of care whole blood profiling of neutrophils.
Analyzing protein topology based on Laguerre tessellation of a pore-traversing water network
Authors: Esque Jérémy , Sansom Mark S. P. , Baaden Marc , Oguey Christophe
Published: September 2018

Given the tight relation between protein structure and function, we present a set of methods to analyze protein topology, implemented in the VLDP program, relying on Laguerre space partitions built from series of molecular dynamics snapshots. The Laguerre partition specifies inter-atomic contacts, formalized in graphs. The deduced properties are the existence and count of water aggregates, possible passage ways and constrictions, the structure, connectivity, stability and depth of the water network. As a test-case, the membrane protein FepA is investigated in its full environment, yielding a more precise description of the protein surface. Inside FepA, the solvent splits into isolated clusters and an intricate network connecting both sides of the lipid bilayer. The network is dynamic, connections set on and off, occasionally substantially relocating traversing paths. Subtle differences are detected between two forms of FepA, ligand-free and complexed with its natural iron carrier, the enterobactin. The complexed form has more constricted and more centered openings in the upper part whereas, in the lower part, constriction is released: two main channels between the plug and barrel lead directly to the periplasm. Reliability, precision and the variety of topological features are the main interest of the method.
Routine use of HbA1c amongst inpatients hospitalised with decompensated heart failure and the association of dysglycaemia with outcomes
Authors: Khoo K. , Lew J. , Neef P. , Kearney L. , Churilov L. , Robbins R. , Tan A. , Hachem M. , Owen-Jones L. , Lam Q. , Hart G. K. , Wilson A. , Sumithran P. , Johnson D. , Srivastava P. M. , Farouque O. , Burrell L. M. , Zajac J. D. , Ekinci E. I.
Published: September 2018

Diabetes is an independent risk factor for development of heart failure and has been associated with poor outcomes in these patients. The prevalence of diabetes continues to rise. Using routine HbA1c measurements on inpatients at a tertiary hospital, we aimed to investigate the prevalence of diabetes amongst patients hospitalised with decompensated heart failure and the association of dysglycaemia with hospital outcomes and mortality. 1191 heart failure admissions were identified and of these, 49% had diabetes (HbA1c ≥ 6.5%) and 34% had pre-diabetes (HbA1c 5.7–6.4%). Using a multivariable analysis adjusting for age, Charlson comorbidity score (excluding diabetes and age) and estimated glomerular filtration rate, diabetes was not associated with length of stay (LOS), Intensive Care Unit (ICU) admission or 28-day readmission. However, diabetes was associated with a lower risk of 6-month mortality. This finding was also supported using HbA1c as a continuous variable. The diabetes group were more likely to have diastolic dysfunction and to be on evidence-based cardiac medications. These observational data are hypothesis generating and possible explanations include that more diabetic patients were on medications that have proven mortality benefit or prevent cardiac remodelling, such as renin-angiotensin system antagonists, which may modulate the severity of heart failure and its consequences.
Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
Authors: Naftalin Claire M. , Verma Rupangi , Gurumurthy Meera , Hee Kim Hor , Lu Qingshu , Yeo Benjamin Chaik Meng , Tan Kin Hup , Lin Wenwei , Yu Buduo , Seng Kok Yong , Lee Lawrence Soon-U , Paton Nicholas I.
Published: September 2018

COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples withMycobacterium tuberculosisand estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA −0.10 ± 0.13ΔlogCFU versus −0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference −0.01, 95% CI −0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.
Ectopic expression of aPKC-mediated phosphorylation in p300 modulates hippocampal neurogenesis, CREB binding and fear memory differently with age
Authors: Syal Charvi , Seegobin Matthew , Sarma Sailendra Nath , Gouveia Ayden , Hsu Karolynn , Niibori Yosuke , He Ling , Wondisford Fredric E. , Frankland Paul W. , Wang Jing
Published: September 2018

Epigenetic modifications have become an emerging interface that links extrinsic signals to alterations of gene expression that determine cell identity and function. However, direct signaling that regulates epigenetic modifications is unknown. Our previous work demonstrated that phosphorylation of CBP at Ser 436 by atypical protein kinase C (aPKC) regulates age-dependent hippocampal neurogenesis and memory. p300, a close family member of CBP, lacks the aPKC-mediated phosphorylation found in CBP. Here, we use a phosphorylation-competent p300 (G442S) knock-in (KI) mouse model that ectopically expresses p300 phosphorylation in a homologous site to CBP Ser436, and assess its roles in modulating hippocampal neurogenesis, CREB binding ability, and fear memory. Young adult (3 months) p300G422S-KI mice exhibit enhanced hippocampal neurogenesis due to increased cell survival of newly-generated neurons, without alterations in CREB binding and contextual fear memory. On the other hand, mature adult (6 months) p300G422S-KI mice display reduced CREB binding, associated with impaired contextual fear memory without alterations in hippocampal neurogenesis. Additionally, we show that repulsive interaction between pS133-CREB and pS422-p300G422S may contribute to the reduced CREB binding to p300G422S. Together, these data suggest that a single phosphorylation change in p300 has the capability to modulate hippocampal neurogenesis, CREB binding, and associative fear memory.
An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures
Authors: Collord Grace , Tarpey Patrick , Kurbatova Natalja , Martincorena Inigo , Moran Sebastian , Castro Manuel , Nagy Tibor , Bignell Graham , Maura Francesco , Young Matthew D. , Berna Jorge , Tubio Jose M. C. , McMurran Chris E. , Young Adam M. H. , Sanders Mathijs , Noorani Imran , Price Stephen J. , Watts Colin , Leipnitz Elke , Kirsch Matthias , Schackert Gabriele , Pearson Danita , Devadass Abel , Ram Zvi , Collins V. Peter , Allinson Kieren , Jenkinson Michael D. , Zakaria Rasheed , Syed Khaja , Hanemann C. Oliver , Dunn Jemma , McDermott Michael W. , Kirollos Ramez W. , Vassiliou George S. , Esteller Manel , Behjati Sam , Brazma Alvis , Santarius Thomas , McDermott Ultan
Published: September 2018

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance.
Multisensory and Motor Representations in Rat Oral Somatosensory Cortex
Authors: Clemens Ann M. , Fernandez Delgado Yohami , Mehlman Max L. , Mishra Poonam , Brecht Michael
Published: September 2018

In mammals, a complex array of oral sensors assess the taste, temperature and haptic properties of food. Although the representation of taste has been extensively studied in the gustatory cortex, it is unclear how the somatosensory cortex encodes information about the properties of oral stimuli. Moreover, it is poorly understood how different oral sensory modalities are integrated and how sensory responses are translated into oral motor actions. To investigate whether oral somatosensory cortex processes food-related sensations and movements, we performed in vivo whole-cell recordings and motor mapping experiments in rats. Neurons in oral somatosensory cortex showed robust post-synaptic and sparse action potential responses to air puffs. Membrane potential showed that cold water evoked larger responses than room temperature or hot water. Most neurons showed no clear tuning of responses to bitter, sweet and neutral gustatory stimuli. Finally, motor mapping experiments with histological verification revealed an initiation of movements related to food consumption behavior, such as jaw opening and tongue protrusions. We conclude that somatosensory cortex: (i) provides a representation of the temperature of oral stimuli, (ii) does not systematically encode taste information and (iii) influences orofacial movements related to food consummatory behavior.
Candidate protein markers for radiation biodosimetry in the hematopoietically humanized mouse model
Authors: Lee Younghyun , Pujol Canadell Monica , Shuryak Igor , Perrier Jay R. , Taveras Maria , Patel Purvi , Koller Antonius , Smilenov Lubomir B. , Brenner David J. , Chen Emily I. , Turner Helen C.
Published: September 2018

After a radiological incident, there is an urgent need for fast and reliable bioassays to identify radiation-exposed individuals within the first week post exposure. This study aimed to identify candidate radiation-responsive protein biomarkers in human lymphocytes in vivo using humanized NOD scid gamma (Hu-NSG) mouse model. Three days after X-irradiation (0–2 Gy, 88 cGy/min), human CD45+ lymphocytes were collected from the Hu-NSG mouse spleen and quantitative changes in the proteome of the human lymphocytes were analysed by mass spectrometry. Forty-six proteins were differentially expressed in response to radiation exposure. FDXR, BAX, DDB2 and ACTN1 proteins were shown to have dose-dependent response with a fold change greater than 2. When these proteins were used to estimate radiation dose by linear regression, the combination of FDXR, ACTN1 and DDB2 showed the lowest mean absolute errors (≤0.13 Gy) and highest coefficients of determination (R2 = 0.96). Biomarker validation studies were performed in human lymphocytes 3 days after irradiation in vivo and in vitro. In conclusion, this is the first study to identify radiation-induced human protein signatures in vivo using the humanized mouse model and develop a protein panel which could be used for the rapid assessment of absorbed dose 3 days after radiation exposure.
Exploring the elusive composition of corpora amylacea of human brain
Authors: Augé Elisabet , Duran Jordi , Guinovart Joan J. , Pelegrí Carme , Vilaplana Jordi
Published: September 2018

Corpora amylacea (CA) are polyglucosan bodies that accumulate in the human brain during ageing and are also present in large numbers in neurodegenerative conditions. Theories regarding the function of CA are regularly updated as new components are described. In previous work, we revealed the presence of some neo-epitopes in CA and the existence of some natural IgM antibodies directed against these neo-epitopes. We also noted that these neo-epitopes and IgMs were the cause of false staining in CA immunohistochemical studies, and disproved the proposed presence of β-amyloid peptides and tau protein in them. Here we extend the list of components erroneously attributed to CA. We show that, contrary to previous descriptions, CA do not contain GFAP, S100, AQP4, NeuN or class III β-tubulin, and we question the presence of other components. Nonetheless, we observe that CA contains ubiquitin and p62, both of them associated with processes of elimination of waste substances, and also glycogen synthase, an indispensable enzyme for polyglucosan formation. In summary, this study shows that it is imperative to continue reviewing previous studies about CA but, more importantly, it shows that the vision of CA as structures involved in protective or cleaning mechanisms remains the most consistent theory.
Co-overexpression of native phospholipid-biosynthetic genes plsX and plsC enhances lipid production in Synechocystis sp. PCC 6803
Authors: Towijit Umaporn , Songruk Nutchaya , Lindblad Peter , Incharoensakdi Aran , Jantaro Saowarath
Published: September 2018

The overexpression of native plsX and plsC genes involving in fatty acid/phospholipid synthesis first timely-reported the significantly enhanced lipid contents in Synechocystis sp. PCC 6803. Growth rate, intracellular pigment contents including chlorophyll a and carotenoids, and oxygen evolution rate of all overexpressing (OX) strains were normally similar as wild type. For fatty acid compositions, saturated fatty acid, in particular palmitic acid (16:0) was dominantly increased in OX strains whereas slight increases of unsaturated fatty acids were observed, specifically linoleic acid (18:2) and alpha-linolenic acid (18:3). The plsC/plsX-overexpressing (OX + XC) strain produced high lipid content of about 24.3%w/dcw under normal condition and was further enhanced up to 39.1%w/dcw by acetate induction. This OX + XC engineered strain was capable of decreasing phaA transcript level which related to poly-3-hydroxybutyrate (PHB) synthesis under acetate treatment. Moreover, the expression level of gene transcripts revealed that the plsX- and plsC/plsX-overexpression strains had also increased accA transcript amounts which involved in the irreversible carboxylation of acetyl-CoA to malonyl-CoA. Altogether, these overexpressing strains significantly augmented higher lipid contents when compared to wild type by partly overcoming the limitation of lipid production.
Distinct mental trainings differentially affect altruistically motivated, norm motivated, and self-reported prosocial behaviour
Authors: Böckler Anne , Tusche Anita , Schmidt Peter , Singer Tania
Published: September 2018

Global challenges such as climate change or the refugee crises emphasize the necessity of altruism and cooperation. In a large-scale 9-month intervention study, we investigated the malleability of prosociality by three distinct mental trainings cultivating attention, socio-affective, or socio-cognitive skills. We assessed numerous established measures of prosociality that capture three core facets: Altruistically motivated behaviours, norm motivated behaviours, and self-reported prosociality. Results of multiple time point confirmatory factor analyses support the validity and temporal stability of this model. Furthermore, linear mixed effects models reveal differential effects of mental trainings on the subcomponents of prosociality: Only training care and compassion effectively boosted altruistically motivated behaviour. No effects were revealed for norm-based behaviour. Self-reported prosociality increased withalltraining modules; this increase was, however, unrelated to changes in task-based measures of altruistic behaviour. These findings corroborate our motivation-based framework of prosociality, challenge economic views of fixed preferences by showing that socio-affective training boosts altruism, and inform policy makers and society about how to increase global cooperation.
Ballistic and Collisional Flow Contributions to Anti-Fourier Heat Transfer in Rarefied Cavity Flow
Authors: Akhlaghi Hassan , Roohi Ehsan , Stefanov Stefan
Published: September 2018

This paper investigates anti-Fourier heat transfer phenomenon in a rarefied gas confined within a lid-driven cavity using a novel flow decomposition technique in the direct simulation Monte Carlo (DSMC) method proposed by Stefanov and co-workers. An isothermal cavity with different degrees of flow rarefaction from near continuum to mid transition regimes was considered to investigate cold-to-hot heat transfer from ballistic/collision flow decomposition viewpoint. A new cold-to-hot heat transfer indicator in the form of a scalar product of normalized heat flow vector and normalized temperature gradient vector has been introduced for the overall, ballistic and collision parts of these vectors. Using the new indicator, contributions of ballistic and collision flow parts to temperature and heat flux components was investigated with a specific emphasis on the cold-to-hot heat transfer phenomenon. We demonstrated that both ballistic and collision flow parts contribute to the occurrence of cold-to-hot heat transfer. However, it was found out that considered separately both ballistic and collision parts of heat transfer, when related to corresponding ballistic and collision temperature fields, they are ever hot-to-cold for all degrees of flow rarefaction. Thus, cold-to-hot heat transfer is a result of a subtle interplay between ballistic and collision parts in the slip and transition Knudsen regimes.
High-throughput ovarian follicle counting by an innovative deep learning approach
Authors: Sonigo Charlotte , Jankowski Stéphane , Yoo Olivier , Trassard Olivier , Bousquet Nicolas , Grynberg Michael , Beau Isabelle , Binart Nadine
Published: September 2018

The evaluation of the number of mouse ovarian primordial follicles (PMF) can provide important information about ovarian function, regulation of folliculogenesis or the impact of chemotherapy on fertility. This counting, usually performed by specialized operators, is a tedious, time-consuming but indispensable procedure.The development and increasing use of deep machine learning algorithms promise to speed up and improve this process. Here, we present a new methodology of automatically detecting and counting PMF, using convolutional neural networks driven by labelled datasets and a sliding window algorithm to select test data. Trained from a database of 9 millions of images extracted from mouse ovaries, and tested over two ovaries (3 millions of images to classify and 2 000 follicles to detect), the algorithm processes the digitized histological slides of a completed ovary in less than one minute, dividing the usual processing time by a factor of about 30. It also outperforms the measurements made by a pathologist through optical detection. Its ability to correct label errors enables conducting an active learning process with the operator, improving the overall counting iteratively. These results could be suitable to adapt the methodology to the human ovarian follicles by transfer learning.
Highly Efficient Transfer of 7TM Membrane Protein from Native Membrane to Covalently Circularized Nanodisc
Authors: Yeh Vivien , Lee Tsung-Yen , Chen Chung-Wen , Kuo Pai-Chia , Shiue Jessie , Chu Li-Kang , Yu Tsyr-Yan
Published: September 2018

Incorporating membrane proteins into membrane mimicking systems is an essential process for biophysical studies and structure determination. Monodisperse lipid nanodiscs have been found to be a suitable tool, as they provide a near-native lipid bilayer environment. Recently, a covalently circularized nanodisc (cND) assembled with a membrane scaffold protein (MSP) in circular form, instead of conventional linear form, has emerged. Covalently circularized nanodiscs have been shown to have improved stability, however the optimal strategies for the incorporation of membrane proteins, as well as the physicochemical properties of the membrane protein embedded in the cND, have not been studied. Bacteriorhodopsin (bR) is a seven-transmembrane helix (7TM) membrane protein, and it forms a two dimensional crystal consisting of trimeric bR on the purple membrane of halophilic archea. Here it is reported that the bR trimer in its active form can be directly incorporated into a cND from its native purple membrane. Furthermore, the assembly conditions of the native purple membrane nanodisc (PMND) were optimized to achieve homogeneity and high yield using a high sodium chloride concentration. Additionally, the native PMND was demonstrated to have the ability to assemble over a range of different pHs, suggesting flexibility in the preparation conditions. The native PMND was then found to not only preserve the trimeric structure of bR and most of the native lipids in the PM, but also maintained the photocycle function of bR. This suggests a promising potential for assembling a cND with a 7TM membrane protein, extracted directly from its native membrane environment, while preserving the protein conformation and lipid composition.
Relationship between perioperative thyroid function and acute kidney injury after thyroidectomy
Authors: Joo Eun-Young , Kim Yeon Ju , Go Yonji , Song Jun-Gol
Published: September 2018

Thyroid dysfunction may alter kidney function via direct renal effects and systemic haemodynamic effects, but information on the effect of thyroid function on postoperative acute kidney injury (AKI) following thyroidectomy remains scarce. We reviewed the medical records of 486 patients who underwent thyroidectomy between January 2010 and December 2014. Thyroid function was evaluated based on the free thyroxine or thyroid stimulating hormone levels. The presence of postoperative AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI developed in 24 (4.9%) patients after thyroidectomy. There was no association between preoperative thyroid function and postoperative AKI. Patients with postoperative hypothyroidism showed a higher incidence of AKI than patients with normal thyroid function or hyperthyroidism (19.4%, 6.7%, and 0%, respectively; P = 0.044). Multivariable logistic regression analysis showed that male sex (OR, 4.45; 95% CI, 1.80–11.82; P = 0.002), preoperative use of beta-blockers (OR, 4.81; 95% CI, 1.24–16.50; P = 0.016), low preoperative serum albumin levels (OR, 0.29; 95% CI, 0.11–0.76; P = 0.011), and colloid administration (OR, 5.18; 95% CI, 1.42–18.15; P = 0.011) were associated with postoperative AKI. Our results showed that postoperative hypothyroidism might increase the incidence of AKI after thyroidectomy.
Genetic dissection of grain zinc concentration in spring wheat for mainstreaming biofortification in CIMMYT wheat breeding
Authors: Velu Govindan , Singh Ravi Prakash , Crespo-Herrera Leonardo , Juliana Philomin , Dreisigacker Susanne , Valluru Ravi , Stangoulis James , Sohu Virinder Singh , Mavi Gurvinder Singh , Mishra Vinod Kumar , Balasubramaniam Arun , Chatrath Ravish , Gupta Vikas , Singh Gyanendra Pratap , Joshi Arun Kumar
Published: September 2018

Wheat is an important staple that acts as a primary source of dietary energy, protein, and essential micronutrients such as iron (Fe) and zinc (Zn) for the world’s population. Approximately two billion people suffer from micronutrient deficiency, thus breeders have crossed high Zn progenitors such as synthetic hexaploid wheat, T. dicoccum, T. spelta, and landraces to generate wheat varieties with competitive yield and enhanced grain Zn that are being adopted by farmers in South Asia. Here we report a genome-wide association study (GWAS) using the wheat Illumina iSelect 90 K Infinitum SNP array to characterize grain Zn concentrations in 330 bread wheat lines. Grain Zn phenotype of this HarvestPlus Association Mapping (HPAM) panel was evaluated across a range of environments in India and Mexico. GWAS analysis revealed 39 marker-trait associations for grain Zn. Two larger effect QTL regions were found on chromosomes 2 and 7. Candidate genes (among them zinc finger motif of transcription-factors and metal-ion binding genes) were associated with the QTL. The linked markers and associated candidate genes identified in this study are being validated in new biparental mapping populations for marker-assisted breeding.
Solid-state random microlasers fabricated via femtosecond laser writing
Authors: Tomazio Nathália B. , Sciuti Lucas F. , de Almeida Gustavo F. B. , De Boni Leonardo , Mendonca Cleber R.
Published: September 2018

Here we demonstrate resonant random lasing in Rhodamine B-doped polymeric microstructures fabricated by means of femtosecond laser writing via two-photon polymerization. To the best of our knowledge, this is the first demonstration of random lasing action in on-chip microdevices. Their feedback mechanism relies on diffuse reflections at the structure sidewall surfaces, which is known as spatially localized feedback since the scattering centers lie over the edges of the gain medium. By exciting the structures with a pulsed laser at 532 nm, a multimode emission with randomly distributed narrow peaks was observed, in accordance with the random nature of the feedback mechanism. Interestingly, their lasing threshold was found to be on the order of tens of nanojoules, which is comparable to what had been achieved for usual microcavities, thereby demonstrating the potentiality of these devices as solid-state lasers for integrated optics applications.
Global sea level change signatures observed by GRACE satellite gravimetry
Authors: Jeon Taehwan , Seo Ki-Weon , Youm Kookhyoun , Chen Jianli , Wilson Clark R.
Published: September 2018

Ice mass loss on land results in sea level rise, but its rate varies regionally due to gravitational self-attraction effects. Observing regional sea level rates by ocean mass change using the Gravity Recovery and Climate Experiment (GRACE) gravity solutions is difficult due to GRACE’s spatial resolution (~a few hundred km) and other limitations. Here we estimate regional sea level mass change using GRACE data (without contributions from temperature and salinity variations) by addressing these limitations: restoring spatially spread and attenuated signals in post-processed GRACE data; constraining ocean mass distribution to conform to the changing geoid; and judging specific corrections applied to GRACE data including a new geocenter estimate. The estimated global sea level mass trend for 2003–2014 is 2.14 ± 0.12 mm/yr. Regional trends differ considerably among ocean basins, ranging from −0.5 mm/yr in the Arctic to about 2.4 mm/yr in the Indian and South Atlantic Oceans.
Bioengineering functional smooth muscle with spontaneous rhythmic contraction in vitro
Authors: Kobayashi Masae , Khalil Hassan A. , Lei Nan Ye , Wang Qianqian , Wang Ke , Wu Benjamin M. , Dunn James C. Y.
Published: September 2018

Oriented smooth muscle layers in the intestine contract rhythmically due to the action of interstitial cells of Cajal (ICC) that serve as pacemakers of the intestine. Disruption of ICC networks has been reported in various intestinal motility disorders, which limit the quality and expectancy of life. A significant challenge in intestinal smooth muscle engineering is the rapid loss of function in cultured ICC and smooth muscle cells (SMC). Here we demonstrate a novel approach to maintain the function of both ICC and SMC in vitro. Primary intestinal SMC mixtures cultured on feeder cells seeded electrospun poly(3-caprolactone) scaffolds exhibited rhythmic contractions with directionality for over 10 weeks in vitro. The simplicity of this system should allow for wide usage in research on intestinal motility disorders and tissue engineering, and may prove to be a versatile platform for generating other types of functional SMC in vitro.
New Optical Imaging Reporter-labeled Anaplastic Thyroid Cancer-Derived Extracellular Vesicles as a Platform for In Vivo Tumor Targeting in a Mouse Model
Authors: Gangadaran Prakash , Li Xiu Juan , Kalimuthu Senthil kumar , Min Oh Ji , Hong Chae Moon , Rajendran Ramya Lakshmi , Lee Ho Won , Zhu Liya , Baek Se Hwan , Jeong Shin Young , Lee Sang-Woo , Lee Jaetae , Ahn Byeong-Cheol
Published: September 2018

Extracellular vesicles (EVs), originating from multivesicular bodies by invagination of the endosomal membrane, are communication channels between distant cells. They are natural carriers of exogeneous cellular materials and have been exploited as drug delivery carriers in various diseases. Here, we found that tumor cell-derived EVs can be used as efficient targets in tumors by monitoring with an optical reporter system. Anaplastic thyroid cancer (CAL62) cell-derived EVs with Renilla luciferase (Rluc) were used to target CAL62 tumors in a mouse model. Optical imaging revealed that cancer cell-derived EVs (EV-CAL62/Rluc) targeted the original tumor (CAL62) in mice within 30 min after systemic injection. Furthermore, fluorescence imaging revealed that EV-CAL62/Rluc were internalized into CAL62 tumors in the mice. Ex vivo Optical imaging further confirmed the in vivo finding. Here, we successfully monitored the tumor targeting ability of tumor cell-derived EVs by optical imaging. Based on these results, tumor cell-derived EVs are highly effective natural carriers for drug delivery for cancer therapies.
Imaging and clinical data archive for head and neck squamous cell carcinoma patients treated with radiotherapy
Authors: Grossberg Aaron J. , Mohamed Abdallah S. R. , Elhalawani Hesham , Bennett William C. , Smith Kirk E. , Nolan Tracy S. , Williams Bowman , Chamchod Sasikarn , Heukelom Jolien , Kantor Michael E. , Browne Theodora , Hutcheson Katherine A. , Gunn G. Brandon , Garden Adam S. , Morrison William H. , Frank Steven J. , Rosenthal David I. , Freymann John B. , Fuller Clifton D.
Published: September 2018

Cross sectional imaging is essential for the patient-specific planning and delivery of radiotherapy, a primary determinant of head and neck cancer outcomes. Due to challenges ensuring data quality and patient de-identification, publicly available datasets including diagnostic and radiation treatment planning imaging are scarce. In this data descriptor, we detail the collection and processing of computed tomography based imaging in 215 patients with head and neck squamous cell carcinoma that were treated with radiotherapy. Using cross sectional imaging, we calculated total body skeletal muscle and adipose content before and after treatment. We detail techniques for validating the high quality of these data and describe the processes of data de-identification and transfer. All imaging data are subject- and date-matched to clinical data from each patient, including demographics, risk factors, grade, stage, recurrence, and survival. These data are a valuable resource for studying the association between patient-specific anatomic and metabolic features, treatment planning, and oncologic outcomes, and the first that allows for the integration of body composition as a risk factor or study outcome.
High resolution temperature data for ecological research and management on the Southern Ocean Islands
Authors: Leihy Rachel I. , Duffy Grant A. , Nortje Erika , Chown Steven L.
Published: September 2018

Southern Ocean Islands are globally significant conservation areas. Predicting how their terrestrial ecosystems will respond to current and forecast climate change is essential for their management and requires high-quality temperature data at fine spatial resolutions. Existing datasets are inadequate for this purpose. Remote-sensed land surface temperature (LST) observations, such as those collected by satellite-mounted spectroradiometers, can provide high-resolution, spatially-continuous data for isolated locations. These methods require a clear sightline to measure surface conditions, however, which can leave large data-gaps in temperature time series. Using a spatio-temporal gap-filling method applied to high-resolution (~1 km) LST observations for 20 Southern Ocean Islands, we compiled a complete monthly temperature dataset for a 15-year period (2001–2015). We validated results using in situ measurements of microclimate temperature. Gap-filled temperature observations described the thermal heterogeneity of the region better than existing climatology datasets, particularly for islands with steep elevational gradients and strong prevailing winds. This dataset will be especially useful for terrestrial ecologists, conservation biologists, and for developing island-specific management and mitigation strategies for environmental change.
Ratiometric red-emission fluorescence detection of Al3+in pure aqueous solution and live cells by a fluorescent peptidyl probe using aggregation-induced emission
Authors: Neupane Lok Nath , Mehta Pramod Kumar , Oh Semin , Park See-Hyoung , Lee Keun-Hyeung
Published: September 2018

A novel peptidyl probe using aggregation induced emission was proposed for the selective ratiometric detection of Al3+ions in pure aqueous solutions and live cells.
Conjugate addition from the excited state
Authors: Iyer Akila , Ahuja Sapna , Jockusch Steffen , Ugrinov Angel , Sivaguru Jayaraman
Published: September 2018

Conjugate addition occurs efficiently from excited hydrazide based acrylanilides under both UV and metal free visible light irradiations.
Triazole-bearing calixpyrroles: strong halide binding affinities through multiple N–H and C–H hydrogen bonds
Authors: Kim Hyeongcheol , Hong Kyeong-Im , Lee Jeong Heon , Kang Philjae , Choi Moon-Gun , Jang Woo-Dong
Published: September 2018

Triazole-bearing calixpyrroles (TCPs) were synthesized as artificial anion binding receptors.
Hydrogen bond directed aerobic oxidation of amines via photoredox catalysis
Authors: Wang Hongyu , Man Yunquan , Wang Kaiye , Wan Xiuyan , Tong Lili , Li Na , Tang Bo
Published: September 2018

An application of H-bonding interactions for directing the α-C–H oxidation of amines to amides and amino-ketones catalyzed by an organic photocatalyst with high yields and a wide substrate scope is reported.