bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractGiven 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

AbstractDiabetes 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

AbstractCOX-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

AbstractEpigenetic 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

AbstractAnaplastic 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

AbstractIn 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

AbstractAfter 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

AbstractCorpora 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

AbstractThe 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

AbstractGlobal 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

AbstractThis 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

AbstractThe 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

AbstractIncorporating 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

AbstractThyroid 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.