bluuebunny/crossref_metadata_2025 huggingface dataset:
GP.04 Network connectivity following a single unprovoked seizure using 7 Tesla resting-state fMRI
Authors: Ikeda KM , Mirsattari SM , Khan AR , Johnsrude I , Burneo JG , Peters TM
Published: June 2017

Background: Predicting epilepsy following a first seizure is difficult. Network abnormalities are observed in patients with epilepsy using resting-state functional MRI (rs-fMRI), which worsen with duration of epilepsy. We use rs-fMRI to identify network abnormalities in patients after a first seizure that can be used as a biomarker to predict development of epilepsy. Methods: Patients after a single, unprovoked seizure and age/sex matched healthy controls underwent 7 Tesla structural and resting-state functional MRI. Data were analyzed using graph theory measures. Patients were followed for development of epilepsy. Results: Nine patients and nine control subjects were analyzed. There were no differences in baseline characteristics. No patients developed epilepsy (average follow-up 3 months). No differences between groups occurred on a whole-brain network level. At a 20% threshold, significant differences occurred in the default mode network (DMN). Patients demonstrated an increased local efficiency (p=0.02) and clustering coefficient (p=0.04), and decreased path length (p=0.02) and betweenness centrality (p=0.02). Conclusions: No whole-brain network changes occur after a single unprovoked seizure. No patient has developed epilepsy suggesting this group does not have network alterations after a single seizure. In the DMN, the alterations noted indicate increased segregation of network function.
A.06 Selective amygdalohippocampectomy in pediatric medically refractory temporal lobe epilepsy yields worse seizure outcomes
Authors: Elliott CA , Sinclair D , Broad A , Narvacan K , Steve T , Pugh J , Snyder T , Wheatley B
Published: June 2017

Background: Selective amygdalohippocampectomy (SAH) is a surgical option in well-selected cases of pediatric medically refractory temporal lobe epilepsy (TLE). The objective of this study was to compare the surgical outcome and the rate of reoperation for ongoing or recurrent seizures between SAH and anterior temporal lobectomy (ATL) in pediatric TLE. Methods: Retrospective review of 78 pediatric intractable TLE patients referred to the Comprehensive Epilepsy Program at our institution between 1988 and 2015 treated initially with either a trans-middle temporal gyrus SAH (19) or ATL (59). Patients underwent baseline long-term video electroencephalography and 1.5-Tesla MRI. Neuropsychological testing was performed preoperatively and 12-months postoperatively (including reoperations). Results: The mean follow-up was 64 months (range, 12-186 months). The average age at initial surgery was 10.6±5 years with an average delay of 5.7±4 years between seizure onset and surgery. Ultimately 78% were seizure-free (61/78) at most recent follow-up. Seizure freedom after initial surgical treatment was achieved in 81% of patients who underwent ATL (48 patients) versus 42% in SAH (8 patients; p<0.001). Of patients with ongoing disabling seizures following SAH, reoperation (ATL) was offered in 8 resulting in seizure freedom in 63%, without interval neuropsychological decline. Conclusions: SAH amongst well-selected pediatric TLE results in significantly worse seizure control compared with ATL.
B.01 Impact of work-hours and sleep on well-being and burnout for physicians-in-training: the prospective RATE Study
Authors: Mendelsohn D , Despot I , Gooderham PA , Singhal A , Redekop GJ , Toyota BD
Published: June 2017

Background: Wearable activity trackers are an innovative tool for measuring sleep and physical activity. The Resident Activity Tracker Evaluation (RATE) is a prospective observational study evaluating the impact of work-hours, sleep, and physical activity on resident well-being, burnout, and job satisfaction. Methods: Residents were recruited from: 1. general surgery and orthopedics (SURG), 2. internal medicine and neurology (MED) and 3. anesthesia and radiology (RCD). Groups 1 and 2 do not enforce on-call duration restrictions and group 3 had 12-hour restricted-call durations (RCD). Participants wore FitBit activity trackers for 14 days and completed four validated surveys assessing self-reported health, sleepiness, burnout, and job satisfaction. Results: Fifty-nine residents completed the study. 778 days of activity and 244 on-call periods were tracked. Surgical residents worked 24 more hours per week than non-surgical residents (84.3 vs 60.7). Surgical residents had 7 less hours of sleep per week and reported significantly higher Epworth Sleepiness scores. Nearly two-thirds of participants (61%) scored high burnout on the Maslach depersonalization subscore. Total steps per day and self-reported well-being, burnout, and job satisfaction were comparable between the groups. Conclusions: Despite a positive correlation between work-hours and sleepiness, burnout and well-being were similar among residents. Physical activity did not prevent burnout. These findings are relevant to work-hours policies.
P.005 Painful epileptic seizures involving the insula
Authors: Young G , Blume WT
Published: June 2017

Background: We have previously described painful epileptic seizures involving the primary and second somatosensory cortices. A recently encountered 24 year old man described left hemicorporial, painful seizures in association with a tumor involving the right insula. Methods: Case description with imaging and EEG. Results: The patient described frequent, sharp pains simultaneously involving the left face, upper and lower limbs and trunk that lasted from several seconds to a minute and were 10/10 in intensity. These markedly lessened in frequency but the severity of the pain persisted with a maintenance dose of 600 mg/day of carbamazepine. Neurological examination, including cortical sensation, was normal. MRI revealed a 3 cm rounded lesion deep to but immediately against the entire right insula but not extending cortically beyond the confines of the insula. EEGs have been unremarkable. The lesion has been stable for over 1 year. Conclusions: Insular seizures can produce brief, sharp, intense pain that involves the whole of the contralateral body simultaneously. This is in keeping with the insula as part of the pain matrix with connections with the thalamus. Stimulation of the posterior insula can produce hemicorporial pain without a march similar to that experienced by our patient.
Resonant three-dimensional nonlinear sloshing in a square-base basin. Part 4. Oblique forcing and linear viscous damping
Authors: Faltinsen Odd M. , Timokha Alexander N.
Published: June 2017

Faltinsenet al.(J. Fluid Mech., vol. 487, 2003, pp. 1–42) (henceforth, Part 1) examined an undamped nonlinear resonant steady-state sloshing in a square-base tank by developing an approximate (asymptotic) Narimanov–Moiseev-type multimodal theory. The focus was on longitudinal and diagonal harmonic tank excitations. Neglecting the linear viscous boundary-layer damping was justified for model tanks with breadths of the order of metres. However, nonlinear sloshing in clean tanks of smaller size (count in centimetres) may be affected by damping in finite depth conditions. Qualitative and quantitative properties of the damped resonant steady-state sloshing in a square-base tank are now studied by using the modal theory from Part 1 equipped with the linear damping terms. The tank harmonically oscillates along an arbitrary horizontal (oblique) direction. An analytical asymptotic steady-state undamped solution is derived and the corresponding response curves are analysed versus the forcing direction. When the tank width$=$breadth$=$ $L\sim 10$ cm, the surface tension effect on the free-surface dynamics can be neglected but the linear viscous damping should be included into the Narimanov–Moiseev nonlinear asymptotic modal theory. We analytically show that the steady-state damped sloshing possesses a series of distinguishing features so that, e.g. the square-like standing wave regime fully disappears and becomes replaced by swirling. Typical response curves of the damped steady-state resonant sloshing are studied for the liquid depth-to-width ratio exceeding 0.5. The computational results of the steady-state resonant response amplitudes are in a satisfactory agreement with observations and measurements by Ikedaet al.(J. Fluid Mech., vol. 700, 2012, pp. 304–328), which were conducted with a relatively small laboratory container.
Iconic enrichments: Signs vs. gestures
Authors: Schlenker Philippe
Published: May 2017

Semantic work on sign language iconicity suggests, as do Goldin-Meadow & Brentari (G-M&B) in their target article, that “sign should be compared with speech-plus-gesture, not speech alone” (sect. 7.1). One key question is whether speech-plus-gesture and sign-with-iconicity really display the same expressive resources. This need not be the case, because gestural enrichments are typically not at-issue, whereas iconic enrichments in sign language can often be at-issue. Future research should thus focus on the “projection” properties of different sorts of iconic enrichment in both modalities.
French pretensions
Authors: Davidson Keith
Published: May 2017

The ‘English’ have an ambiguous relationship with the language of their nearest neighbour, France. There is a history, ‘1066 and all that’. Christmas Day 2016 saw the 950th anniversary of the crowning at Westminster Abbey of the French Duke William of Normandy as King of England (not, please note, of ‘Britain’); William having defeated King Harold – and so the very last ‘English’ monarch – at the battle of Hastings. (The other ‘nations’ of these European off-shore islands have different trajectories.) Sooner or later the English at least would have to come to terms with French.
Study on the transmission characteristics of magnetic resonance wireless power transfer system
Authors: Wang Xiufang , Wang Yu , Liang Yilang , Fan Guangcheng , Nie Xinyi , Yan Zhongming , Xu Qingying
Published: June 2017

Magnetic coupling resonance wireless power transfer technology has attracted worldwide attention in recent years due to its mid-range, non-radiative, and high-efficiency power transfer. However, in regard to its practical applications, there are still some issues that need to be considered and studied with respect to coil design, such as coil structure, and parasitic parameter extraction. This paper investigated the characteristics of magnetic coupling resonance wireless power transfer systems with different coil structures, including circular coils and rectangular coils arranged in parallel. We calculated the magnetic field distributions and mutual inductances by subdividing the receiving coils and computing the magnetic flux density of each subdivision. The proposed analysis was validated by means of the finite element analysis and the experimental results. We investigated the effects of the coil's structure, and topological structures, on the power transfer efficiency. The results demonstrate that using circular coils in parallel is more advantageous than using rectangular coils.
Das Emotionstraining in der Schule
Authors: Nitkowski Dennis , Laakmann Mirjam , Petersen Rieke , Petermann Ulrike , Petermann Franz
Published: May 2017

Zusammenfassung. In der Forschung wird zunehmend die Bedeutung emotionaler Kompetenzen in der Entstehung und Aufrechterhaltung von depressiven Symptomen bei Jugendlichen herausgestellt, woraus Implikationen für Präventionsmaßnahmen resultieren. Das Emotionstraining in der Schule stellt ein schulbasiertes Präventionsprogramm für die Altersgruppe der 10- bis 13-Jährigen dar, das emotionale Kompetenzen fördert, um der Entwicklung einer depressiven oder Angstsymptomatik vorzubeugen. Ziel der Studie ist es, die Effektivität des Trainings in einem Wartekontrollgruppen-Design zu bestimmen. Eine Stichprobe von insgesamt 543 Schülerinnen und Schüler (Altersmittelwert = 11.46 Jahre; SD .69) nahmen an der Studie teil. Der Mangel an emotionalem Bewusstsein, die Abneigung gegen den Emotionsausdruck und das subjektive Wohlbefinden, welches als Gegenpol zur depressiven Symptomatik zu verstehen ist, wurden im Selbsturteil unmittelbar vor und nach dem Training erhoben. Gegenüber dem ersten Erhebungszeitpunkt zeigten sich nach Abschluss der Maßnahme keine Änderungen in den Merkmalsausprägungen. Im Rahmen einer Moderatorenanalyse konnten jedoch puffernde Effekte in der Trainingsgruppe belegt werden. In zukünftigen Studien muss der Wirkmechanismus hinter diesen Effekten weiter exploriert werden.
Sequential EMT-MET induces neuronal conversion through Sox2
Authors: He Songwei , Chen Jinlong , Zhang Yixin , Zhang Mengdan , Yang Xiao , Li Yuan , Sun Hao , Lin Lilong , Fan Ke , Liang Lining , Feng Chengqian , Wang Fuhui , Zhang Xiao , Guo Yiping , Pei Duanqing , Zheng Hui
Published: May 2017

Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial–mesenchymal transition (EMT) to late mesenchymal–epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ+ cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of Stat3 and Sox2, and the subsequent activation of neuron projection. Up-regulated Sox2 then induced MET and directed cells towards a neuronal fate at the late stage. Inhibiting either stage of this sequential EMT-MET impaired the conversion. In addition, Sox2 could replace sequential EMT-MET to induce a similar conversion within a high proliferation context, and its functions were confirmed with other neuronal conversion protocols and MEFs reprogramming. Therefore, the critical roles of the sequential EMT-MET were implicated in direct cell fate conversion in addition to reprogramming, embryonic development and cancer progression.
Non-interferometric photoacoustic remote sensing microscopy
Authors: Hajireza Parsin , Shi Wei , Bell Kevan , Paproski Robert J , Zemp Roger J
Published: June 2017

Elasto-optical refractive index modulation due to photoacoustic initial pressure transients produced significant reflection of a probe beam when the absorbing interface had an appreciable refractive index difference. This effect was harnessed in a new form of non-contact optical resolution photoacoustic microscopy called photoacoustic remote sensing microscopy. A non-interferometric system architecture with a low-coherence probe beam precludes detection of surface oscillations and other phase-modulation phenomenon. The probe beam was confocal with a scanned excitation beam to ensure detection of initial pressure-induced intensity reflections at the subsurface origin where pressures are largest. Phantom studies confirmed signal dependence on optical absorption, index contrast and excitation fluence. In vivo imaging of superficial microvasculature and melanoma tumors was demonstrated with ~2.7±0.5 μm lateral resolution.
CRISPR/Cas9 targeting events cause complex deletions and insertions at 17 sites in the mouse genome
Authors: Shin Ha Youn , Wang Chaochen , Lee Hye Kyung , Yoo Kyung Hyun , Zeng Xianke , Kuhns Tyler , Yang Chul Min , Mohr Teresa , Liu Chengyu , Hennighausen Lothar
Published: May 2017

Although CRISPR/Cas9 genome editing has provided numerous opportunities to interrogate the functional significance of any given genomic site, there is a paucity of data on the extent of molecular scars inflicted on the mouse genome. Here we interrogate the molecular consequences of CRISPR/Cas9-mediated deletions at 17 sites in four loci of the mouse genome. We sequence targeted sites in 632 founder mice and analyse 54 established lines. While the median deletion size using single sgRNAs is 9 bp, we also obtain large deletions of up to 600 bp. Furthermore, we show unreported asymmetric deletions and large insertions of middle repetitive sequences. Simultaneous targeting of distant loci results in the removal of the intervening sequences. Reliable deletion of juxtaposed sites is only achieved through two-step targeting. Our findings also demonstrate that an extended analysis of F1 genotypes is required to obtain conclusive information on the exact molecular consequences of targeting events.
Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data
Authors: Sinha Subarna , Thomas Daniel , Chan Steven , Gao Yang , Brunen Diede , Torabi Damoun , Reinisch Andreas , Hernandez David , Chan Andy , Rankin Erinn B. , Bernards Rene , Majeti Ravindra , Dill David L.
Published: May 2017

Two genes are synthetically lethal (SL) when defects in both are lethal to a cell but a single defect is non-lethal. SL partners of cancer mutations are of great interest as pharmacological targets; however, identifying them by cell line-based methods is challenging. Here we develop MiSL (Mining Synthetic Lethals), an algorithm that mines pan-cancer human primary tumour data to identify mutation-specific SL partners for specific cancers. We apply MiSL to 12 different cancers and predict 145,891 SL partners for 3,120 mutations, including known mutation-specific SL partners. Comparisons with functional screens show that MiSL predictions are enriched for SLs in multiple cancers. We extensively validate a SL interaction identified by MiSL between the IDH1 mutation and ACACA in leukaemia using gene targeting and patient-derived xenografts. Furthermore, we apply MiSL to pinpoint genetic biomarkers for drug sensitivity. These results demonstrate that MiSL can accelerate precision oncology by identifying mutation-specific targets and biomarkers.
R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein
Authors: Cloutier Philippe , Poitras Christian , Durand Mathieu , Hekmat Omid , Fiola-Masson Émilie , Bouchard Annie , Faubert Denis , Chabot Benoit , Coulombe Benoit
Published: May 2017

The R2TP/Prefoldin-like (R2TP/PFDL) complex has emerged as a cochaperone complex involved in the assembly of a number of critical protein complexes including snoRNPs, nuclear RNA polymerases and PIKK-containing complexes. Here we report on the use of multiple target affinity purification coupled to mass spectrometry to identify two additional complexes that interact with R2TP/PFDL: the TSC1–TSC2 complex and the U5 small nuclear ribonucleoprotein (snRNP). The interaction between R2TP/PFDL and the U5 snRNP is mostly mediated by the previously uncharacterized factor ZNHIT2. A more general function for the zinc-finger HIT domain in binding RUVBL2 is exposed. Disruption of ZNHIT2 and RUVBL2 expression impacts the protein composition of the U5 snRNP suggesting a function for these proteins in promoting the assembly of the ribonucleoprotein. A possible implication of R2TP/PFDL as a major effector of stress-, energy- and nutrient-sensing pathways that regulate anabolic processes through the regulation of its chaperoning activity is discussed.
Expression of CD226 is associated to but not required for NK cell education
Authors: Wagner Arnika K. , Kadri Nadir , Snäll Johanna , Brodin Petter , Gilfillan Susan , Colonna Marco , Bernhardt Günter , Höglund Petter , Kärre Klas , Chambers Benedict J.
Published: May 2017

DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice. DNAM-1 is expressed early during NK-cell development, precedes the expression of MHC-I-specific inhibitory receptors, and is modulated in an education-dependent fashion.Cd226−/−mice have missing self-responses and NK cells with a normal receptor repertoire. We propose a model in which NK-cell education prevents or delays downregulation of DNAM-1. This molecule endows educated NK cells with enhanced effector functions but is dispensable for education.
Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification
Authors: Dunne Philip D. , Alderdice Matthew , O'Reilly Paul G. , Roddy Aideen C. , McCorry Amy M. B. , Richman Susan , Maughan Tim , McDade Simon S. , Johnston Patrick G. , Longley Daniel B. , Kay Elaine , McArt Darragh G. , Lawler Mark
Published: May 2017

Stromal-derived intratumoural heterogeneity (ITH) has been shown to undermine molecular stratification of patients into appropriate prognostic/predictive subgroups. Here, using several clinically relevant colorectal cancer (CRC) gene expression signatures, we assessed the susceptibility of these signatures to the confounding effects of ITH using gene expression microarray data obtained from multiple tumour regions of a cohort of 24 patients, including central tumour, the tumour invasive front and lymph node metastasis. Sample clustering alongside correlative assessment revealed variation in the ability of each signature to cluster samples according to patient-of-origin rather than region-of-origin within the multi-region dataset. Signatures focused on cancer-cell intrinsic gene expression were found to produce more clinically useful, patient-centred classifiers, as exemplified by the CRC intrinsic signature (CRIS), which robustly clustered samples by patient-of-origin rather than region-of-origin. These findings highlight the potential of cancer-cell intrinsic signatures to reliably stratify CRC patients by minimising the confounding effects of stromal-derived ITH.
In vitro assembly of the Rous Sarcoma Virus capsid protein into hexamer tubes at physiological temperature
Authors: Jaballah Soumeya A. , Bailey Graham D. , Desfosses Ambroise , Hyun Jaekyung , Mitra Alok K. , Kingston Richard L.
Published: May 2017

During a proteolytically-driven maturation process, the orthoretroviral capsid protein (CA) assembles to form the convex shell that surrounds the viral genome. In some orthoretroviruses, including Rous Sarcoma Virus (RSV), CA carries a short and hydrophobic spacer peptide (SP) at its C-terminus early in the maturation process, which is progressively removed as maturation proceeds. In this work, we show that RSV CA assembles in vitro at near-physiological temperatures, forming hexamer tubes that effectively model the mature capsid surface. Tube assembly is strongly influenced by electrostatic effects, and is a nucleated process that remains thermodynamically favored at lower temperatures, but is effectively arrested by the large Gibbs energy barrier associated with nucleation. RSV CA tubes are multi-layered, being formed by nested and concentric tubes of capsid hexamers. However the spacer peptide acts as a layering determinant during tube assembly. If only a minor fraction of CA-SP is present, multi-layered tube formation is blocked, and single-layered tubes predominate. This likely prevents formation of biologically aberrant multi-layered capsids in the virion. The generation of single-layered hexamer tubes facilitated 3D helical image reconstruction from cryo-electron microscopy data, revealing the basic tube architecture.
Optimisation of a murine splenocyte mycobacterial growth inhibition assay using virulent Mycobacterium tuberculosis
Authors: Jensen Christina , Lindebo Holm Line , Svensson Erik , Aagaard Claus , Ruhwald Morten
Published: May 2017

In the absence of a validated correlate of protection or robust animal models for human tuberculosis, Mycobacterial growth inhibition assays (MGIAs) aim to assess vaccines ability to inhibit mycobacterial growth in-vitro. We optimised a reproducible murine splenocyte MGIA based on in-vitro infection with ﻿virulent Mycobacterium tuberculosis (M.tb) Erdman. We identified splenocyte viability as a problem in state-of-art MGIA protocols, which can be improved by simple changes in culture conditions (viability increase from 21% to 46% at last day of culture). The growth inhibitory potential in mice immunised with either BCG, H56:CAF01 or H56:CAF01 administered side-by-side with BCG was significantly better compared to placebo in all groups (0.3 log10 CFU [±0.2, p = 0.049], 0.5 [±0.2, p = 0.016] and 0.6 [±0.1, p = 0.0007], respectively) corresponding to the levels of in-vivo protection. Unexpectedly the CAF01 adjuvant control group also induced significant growth inhibition of 0.3 log10 CFU (±0.2, p = 0.047). Finally, we explored vaccine-associated T cell effector functions. Despite presence of high levels of vaccine-specific T cells, we found no increase in CD4+ T cell number or cytokine expression profile, nor a difference in cytokine levels in the supernatant after four days culture with or without M.tb. Spontaneous IFN-γ release correlated with growth inhibition levels (p = 0.02), however the cellular source was not found.
Genomic Selection in Commercial Perennial Crops: Applicability and Improvement in Oil Palm (Elaeis guineensis Jacq.)
Authors: Kwong Qi Bin , Ong Ai Ling , Teh Chee Keng , Chew Fook Tim , Tammi Martti , Mayes Sean , Kulaveerasingam Harikrishna , Yeoh Suat Hui , Harikrishna Jennifer Ann , Appleton David Ross
Published: May 2017

Genomic selection (GS) uses genome-wide markers to select individuals with the desired overall combination of breeding traits. A total of 1,218 individuals from a commercial population of Ulu Remis x AVROS (UR x AVROS) were genotyped using the OP200K array. The traits of interest included: shell-to-fruit ratio (S/F, %), mesocarp-to-fruit ratio (M/F, %), kernel-to-fruit ratio (K/F, %), fruit per bunch (F/B, %), oil per bunch (O/B, %) and oil per palm (O/P, kg/palm/year). Genomic heritabilities of these traits were estimated to be in the range of 0.40 to 0.80. GS methods assessed were RR-BLUP, Bayes A (BA), Cπ (BC), Lasso (BL) and Ridge Regression (BRR). All methods resulted in almost equal prediction accuracy. The accuracy achieved ranged from 0.40 to 0.70, correlating with the heritability of traits. By selecting the most important markers, RR-BLUP B has the potential to outperform other methods. The marker density for certain traits can be further reduced based on the linkage disequilibrium (LD). Together with in silico breeding, GS is now being used in oil palm breeding programs to hasten parental palm selection.
Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
Authors: da Silveira W. A. , Palma P. V. B. , Sicchieri R. D. , Villacis R. A. R. , Mandarano L. R. M. , Oliveira T. M. G. , Antonio H. M. R. , Andrade J. M. , Muglia V. F. , Rogatto S. R. , Theillet C. , du Manoir S. , Tiezzi D. G.
Published: May 2017

Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype. The second network is controlled by the SCML4, ZNF831, SP140 and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies.
Rumen Fluid Metabolomics Analysis Associated with Feed Efficiency on Crossbred Steers
Authors: Artegoitia Virginia M. , Foote Andrew P. , Lewis Ronald M. , Freetly Harvey C.
Published: May 2017

The rumen has a central role in the efficiency of digestion in ruminants. To identify potential differences in rumen function that lead to differences in average daily gain (ADG), rumen fluid metabolomic analysis by LC-MS and multivariate/univariate statistical analysis were used to identify differences in rumen metabolites. Individual feed intake and body-weight was measured on 144 steers during 105 d on a high concentrate ration. Eight steers with the greatest ADG and 8 steers with the least-ADG with dry matter intake near the population average were selected. Blood and rumen fluid was collected from the 16 steers 26 d before slaughter and at slaughter, respectively. As a result of the metabolomics analysis of rumen fluid, 33 metabolites differed between the ADG groups based on t-test, fold changes and partial least square discriminant analysis. These metabolites were primarily involved in linoleic and alpha-linolenic metabolism (impact-value 1.0 and 0.75, respectively; P < 0.05); both pathways were down-regulated in the greatest-ADG compared with least-ADG group. Ruminal biohydrogenation might be associated with the overall animal production. The fatty acids were quantified in rumen and plasma using targeted MS to validate and evaluate the simple combination of metabolites that effectively predict ADG.
Burkholderia pseudomallei in a lowland rice paddy: seasonal changes and influence of soil depth and physico-chemical properties
Authors: Manivanh L. , Pierret A. , Rattanavong S. , Kounnavongsa O. , Buisson Y. , Elliott I. , Maeght J. -L. , Xayyathip K. , Silisouk J. , Vongsouvath M. , Phetsouvanh R. , Newton P. N. , Lacombe G. , Ribolzi O. , Rochelle-Newall E. , Dance D. A. B.
Published: June 2017

Melioidosis, a severe infection with the environmental bacterium Burkholderia pseudomallei, is being recognised increasingly frequently. What determines its uneven distribution within endemic areas is poorly understood. We cultured soil from a rice field in Laos for B. pseudomallei at different depths on 4 occasions over a 13-month period. We also measured physical and chemical parameters in order to identify associated characteristics. Overall, 195 of 653 samples (29.7%) yielded B. pseudomallei. A higher prevalence of B. pseudomallei was found at soil depths greater than the 30 cm currently recommended for B. pseudomallei environmental sampling. B. pseudomallei was associated with a high soil water content and low total nitrogen, carbon and organic matter content. Our results suggested that a sampling grid of 25 five metre square quadrats (i.e. 25 × 25 m) should be sufficient to detect B. pseudomallei at a given location if samples are taken at a soil depth of at least 60 cm. However, culture of B. pseudomallei in environmental samples is difficult and liable to variation. Future studies should both rely on molecular approaches and address the micro-heterogeneity of soil when investigating physico-chemical associations with the presence of B. pseudomallei.
A Haptotaxis Assay for Neutrophils using Optical Patterning and a High-content Approach
Authors: Roy Joannie , Mazzaferri Javier , Filep János G. , Costantino Santiago
Published: May 2017

Neutrophil recruitment guided by chemotactic cues is a central event in host defense against infection and tissue injury. While the mechanisms underlying neutrophil chemotaxis have been extensively studied, these are just recently being addressed by using high-content approaches or surface-bound chemotactic gradients (haptotaxis)in vitro. Here, we report a haptotaxis assay, based on the classic under-agarose assay, which combines an optical patterning technique to generate surface-bound formyl peptide gradients as well as an automated imaging and analysis of a large number of migration trajectories. We show that human neutrophils migrate on covalently-bound formyl-peptide gradients, which influence the speed and frequency of neutrophil penetration under the agarose. Analysis revealed that neutrophils migrating on surface-bound patterns accumulate in the region of the highest peptide concentration, thereby mimickingin vivoevents. We propose the use of a chemotactic precision index, gyration tensors and neutrophil penetration rate for characterizing haptotaxis. This high-content assay provides a simple approach that can be applied for studying molecular mechanisms underlying haptotaxis on user-defined gradient shape.
Size and specimen-dependent strategy for x-ray micro-ct and tem correlative analysis of nervous system samples
Authors: Parlanti P. , Cappello V. , Brun F. , Tromba G. , Rigolio R. , Tonazzini I. , Cecchini M. , Piazza V. , Gemmi M.
Published: May 2017

Correlative approaches are a powerful tool in the investigation of biological samples, but require specific preparation procedures to maintain the strength of the employed methods. Here we report the optimization of the embedding protocol of nervous system samples for a correlative synchrotron X-ray computed microtomography (micro-CT) and transmission electron microscopy (TEM) approach. We demonstrate that it is possible to locate, with the micrometric resolution of micro-CT, specific volumes of interest for a further ultrastructural characterization to be performed with TEM. This approach can be applied to samples of different size and morphology up to several cm. Our optimized method represents an invaluable tool for investigating those pathologies in which microscopic alterations are localized in few confined regions, rather than diffused in entire tissues, organs or systems. We present a proof of concept of our method in a mouse model of Globoid Cells Leukodistrophy.
Estimation of the thermocapillary force and its applications to precise droplet control on a microfluidic chip
Authors: Won By June , Lee Wooyoung , Song Simon
Published: June 2017

Droplet control through the use of light-induced thermocapillary effects has recently garnered attention due to its non-intrusive and multifunctional nature. An important issue in droplet control is the estimation of the thermocapillary force. The purpose of the present study is to estimate the thermocapillary force and propose empirical equations between the force and simply measurable key parameters such as droplet diameter and power of heat source. In addition, we aim to shift the droplet trajectory and develop an on-demand droplet routing system based on the estimation of the thermocapillary force. We illuminated a continuous phase with a 532 nm laser beam to minimize possible damage or property changes to target molecules contained within droplets. A mixture of light-absorbing material and oleic acid was used for the continuous phase fluid, while deionized water (DI water) was used for the dispersed phase fluid. We proposed empirical equations to estimate the thermocapillary force, which was then applied to precise droplet shifting and routing. We found that the shifting distance was linearly proportional to the thermocapillary force, and that an on-demand droplet routing system resulted in a success rate greater than 95%.
Direct measurement of optical trapping force gradient on polystyrene microspheres using a carbon nanotube mechanical resonator
Authors: Yasuda Masaaki , Takei Kuniharu , Arie Takayuki , Akita Seiji
Published: May 2017

Optical tweezers based on optical radiation pressure are widely used to manipulate nanoscale to microscale particles. This study demonstrates direct measurement of the optical force gradient distribution acting on a polystyrene (PS) microsphere using a carbon nanotube (CNT) mechanical resonator, where a PS microsphere with 3 μm diameter is welded at the CNT tip using laser heating. With the CNT mechanical resonator with PS microsphere, we measured the distribution of optical force gradient with resolution near the thermal noise limit of 0.02 pN/μm in vacuum, in which condition enables us to high accuracy measurement using the CNT mechanical resonator because of reduced mechanical damping from surrounding fluid. The obtained force gradient and the force gradient distribution agree well with theoretical values calculated using Lorenz–Mie theory.
The dynamics of resting fluctuations in the brain: metastability and its dynamical cortical core
Authors: Deco Gustavo , Kringelbach Morten L. , Jirsa Viktor K. , Ritter Petra
Published: June 2017

In the human brain, spontaneous activity during resting state consists of rapid transitions between functional network states over time but the underlying mechanisms are not understood. We use connectome based computational brain network modeling to reveal fundamental principles of how the human brain generates large-scale activity observable by noninvasive neuroimaging. We used structural and functional neuroimaging data to construct whole- brain models. With this novel approach, we reveal that the human brain during resting state operates at maximum metastability, i.e. in a state of maximum network switching. In addition, we investigate cortical heterogeneity across areas. Optimization of the spectral characteristics of each local brain region revealed the dynamical cortical core of the human brain, which is driving the activity of the rest of the whole brain. Brain network modelling goes beyond correlational neuroimaging analysis and reveals non-trivial network mechanisms underlying non-invasive observations. Our novel findings significantly pertain to the important role of computational connectomics in understanding principles of brain function.
Spectral comb of highly chirped pulses generated via cascaded FWM of two frequency-shifted dissipative solitons
Authors: Podivilov Evgeniy V. , Kharenko Denis S. , Bednyakova Anastasia E. , Fedoruk Mikhail P. , Babin Sergey A.
Published: May 2017

Dissipative solitons generated in normal-dispersion mode-locked lasers are stable localized coherent structures with a mostly linear frequency modulation (chirp). The soliton energy in fiber lasers is limited by the Raman effect, but implementation of the intracavity feedback at the Stokes-shifted wavelength enables synchronous generation of a coherent Raman dissipative soliton. Here we demonstrate a new approach for generating chirped pulses at new wavelengths by mixing in a highly-nonlinear fiber of these two frequency-shifted dissipative solitons, as well as cascaded generation of their clones forming in the spectral domain a comb of highly chirped pulses. We observed up to eight equidistant components in the interval of more than 300 nm, which demonstrate compressibility from ~10 ps to ~300 fs. This approach, being different from traditional frequency combs, can inspire new developments in fundamental science and applications such as few-cycle/arbitrary-waveform pulse synthesis, comb spectroscopy, coherent communications and bio-imaging.
Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)
Authors: Kim Hee Young , Yoo Tae-Hyun , Hwang Yuri , Lee Ga Hye , Kim Bonah , Jang Jiyeon , Yu Hee Tae , Kim Min Chang , Cho Joo-Youn , Lee Chan Joo , Kim Hyeon Chang , Park Sungha , Lee Won-Woo
Published: June 2017

Progressive renal failure causes uremia-related immune dysfunction, which features a chronic inflammatory milieu. Given the central role of end-stage renal disease (ESRD)-related immune dysfunction in the pathogenesis of cardiovascular diseases (CVDs), much attention has been focused on how uremic toxins affect cellular immunity and the mechanisms underlying pathogenesis of atherosclerosis in ESRD patients. Here, we investigated the characteristics of monocytes and CD4+ T cells in ESRD patients and the immune responses induced by indoxyl sulfate (IS), a key uremic toxin, in order to explore the pathogenic effects of these cells on vascular endothelial cells. In ESRD patients, monocytes respond to IS through the aryl hydrocarbon receptor (AhR) and consequently produce increased levels of TNF-α. Upon stimulation with TNF-α, human vascular endothelial cells produce copious amounts of CX3CL1, a chemokine ligand of CX3CR1 that is highly expressed on CD4+CD28−T cells, the predominantly expanded cell type in ESRD patients. A migration assay showed that CD4+CD28− T cells were preferentially recruited by CX3CL1. Moreover, activated CD4+CD28− T cells exhibited cytotoxic capability allowing for the induction of apoptosis in HUVECs. Our findings suggest that in ESRD, IS-mediated immune dysfunction may cause vascular endothelial cell damage and thus, this toxin plays a pivotal role in the pathogenesis of CVD.
A novel network regularized matrix decomposition method to detect mutated cancer genes in tumour samples with inter-patient heterogeneity
Authors: Xi Jianing , Li Ao , Wang Minghui
Published: May 2017

Inter-patient heterogeneity is a major challenge for mutated cancer genes detection which is crucial to advance cancer diagnostics and therapeutics. To detect mutated cancer genes in heterogeneous tumour samples, a prominent strategy is to determine whether the genes are recurrently mutated in their interaction network context. However, recent studies show that some cancer genes in different perturbed pathways are mutated in different subsets of samples. Subsequently, these genes may not display significant mutational recurrence and thus remain undiscovered even in consideration of network information. We develop a novel method called mCGfinder to efficiently detect mutated cancer genes in tumour samples with inter-patient heterogeneity. Based on matrix decomposition framework incorporated with gene interaction network information, mCGfinder can successfully measure the significance of mutational recurrence of genes in a subset of samples. When applying mCGfinder on TCGA somatic mutation datasets of five types of cancers, we find that the genes detected by mCGfinder are significantly enriched for known cancer genes, and yield substantially smaller p-values than other existing methods. All the results demonstrate that mCGfinder is an efficient method in detecting mutated cancer genes.
An atypical phosphodiesterase capable of degrading haloalkyl phosphate diesters from Sphingobium sp. strain TCM1
Authors: Abe Katsumasa , Mukai Naoko , Morooka Yuka , Makino Takeshi , Oshima Kenji , Takahashi Shouji , Kera Yoshio
Published: May 2017

Sphingobium sp. strain TCM1 can degrade tris(2-chloroethyl) phosphate (TCEP) to inorganic phosphate and 2-chloroethanol. A phosphotriesterase (PTE), phosphodiesterase (PDE) and phosphomonoesterase (PME) are believed to be involved in the degradation of TCEP. The PTE and PME that respectively catalyze the first and third steps of TCEP degradation in TCM1 have been identified. However, no information has been reported on a PDE catalyzing the second step. In this study, we identified, purified, and characterized a PDE capable of hydrolyzing haloalkyl phosphate diesters. The final preparation of the enzyme had a specific activity of 29 µmol min−1 mg−1 with bis(p-nitrophenyl) phosphate (BpNPP) as the substrate. It also possessed low PME activity with p-nitrophenyl phosphate (pNPP) as substrate. The catalytic efficiency (kcat/Km) with BpNPP was significantly higher than that with pNPP, indicating that the enzyme prefers the organophosphorus diester to the monoester. The enzyme degraded bis(2,3-dibromopropyl) phosphate, bis(1,3-dichloro-2-propyl) phosphate and bis(2-chloroethyl) phosphate, suggesting that it is involved in the metabolism of haloalkyl organophosphorus triesters. The primary structure of the PDE from TCM1 is distinct from those of typical PDE family members and the enzyme belongs to the polymerase and histidinol phosphatase superfamily.
Pre-RC Protein MCM7 depletion promotes mitotic exit by Inhibiting CDK1 activity
Authors: Zheng Dianpeng , Ye Sichao , Wang Xiuyun , Zhang Yongjun , Yan Daoyu , Cai Xiangsheng , Gao Weihong , Shan Hongbo , Gao Yang , Chen Juanjuan , Hu Zhiming , Li Hongwei , Li Jinlong
Published: May 2017

MCM7, a subunit of mini-chromosome maintenance proteins (MCM) complex, plays an important role in initiating DNA replication during the G1 phase and extending DNA strands during the S phase. Here, we demonstrated that MCM7 is not only sustained but maintains association with chromatin during M phase. Remarkably, MCM7 siRNA can accelerate mitotic exit. MCM7 depletion leads to CDK1 inactivation and promotes subsequent cohesin/RAD21 cleavage, which eventually leads to sister chromatin segregation. Moreover, MCM7 is co-localized with tubulin in the mitotic cells and MCM7 depletion results in aberrant mitosis. Our results indicate that MCM7 may exert certain functions on spindle formation to prevent cytokinesis during early mitosis by regulating CDK1 activity.
Effects of hydraulic retention time on adsorption behaviours of EPS in an A/O-MBR: biofouling study with QCM-D
Authors: Wang Xudong , Cheng Botao , Ji Cunrui , Zhou Miao , Wang Lei
Published: May 2017

Extra-cellular polymeric substances (EPS) are a major cause of membrane fouling in membrane bioreactors (MBRs). In this study, an anoxic–oxic membrane bioreactor (A/O-MBR) was run continuously for 98 days. The runs were divided into three stages according to hydraulic retention time (HRT) (11.8, 12.5 and 14.3 h, respectively). EPS were extracted from the reactor under the different HRTs. A quartz crystal microbalance with dissipation monitoring (QCM-D) and Fourier transform infrared (FT–IR) were used to study the adherence layer structures and the adsorption behaviours of EPS on the membrane surface. The results indicated that the removal rate of TN was more susceptible to HRT than NH3-N. The observations in the QCM-D suggested that at the lowest HRT (11.8 h), the structure of the adsorption layer is loose and soft and the fluidity was better than for HRTs of 12.5 or 14.3 h. It is likely one of the major reasons for the rapidly blocking of the membrane pores. Furthermore, the higher EPS adherence as analyzed in the QCM-D and EPS concentration could induce a higher osmotic pressure effect, leading to a rapid membrane-fouling rate.
Decision and coordination of low-carbon supply chain considering technological spillover and environmental awareness
Authors: Xu Lang , Wang Chuanxu , Li Hui
Published: June 2017

We focus on the impacts of technological spillovers and environmental awareness in a two-echelon supply chain with one-single supplier and one-single manufacturer to reduce carbon emission. In this supply chain, carbon abatement investment becomes one of key factors of cutting costs and improving profits, which is reducing production costs in the components and products—the investment from players in supply chain. On the basis of optimality theory, the centralized and decentralized models are respectively established to investigate the optimal decisions and profits. Further, setting the players’ profits of the decentralized scenario as the disagreement points, we propose a bargaining-coordination contract through revenue-cost sharing to enhance the performance. Finally, by theoretical comparison and numerical analysis, the results show that: (i) The optimal profits of players and supply chain improve as technological spillovers and environmental awareness increase, and the profits of them in the bargaining-coordination contract are higher than that in the decentralized scenario; (ii) Technological spillovers between the players amplify the impact of “free-ride” behavior, in which the supplier always incentives the manufacturer to improve carbon emission intensity, but the cooperation will achieves and the profits will improve only when technological spillovers and environmental awareness are great; (iii) The contract can effectively achieve coordinated supply chain, and improve carbon abatement investment.