bluuebunny/crossref_metadata_2025_split huggingface dataset:
Categorical improvement in functional impairment in depressed patients treated with desvenlafaxine
Authors: Soares Claudio N. , Zhang Min , Boucher Matthieu 
Published: November 2017

ObjectiveThis post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint.MethodsData were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0–3), moderate (4–6), and marked/extreme (7–10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression.ResultsGreater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (allp≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (allp&lt;0.0001).ConclusionsTreatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.
Structural basis for xenobiotic extrusion by eukaryotic MATE transporter
Authors: Miyauchi Hirotake , Moriyama Satomi , Kusakizako Tsukasa , Kumazaki Kaoru , Nakane Takanori , Yamashita Keitaro , Hirata Kunio , Dohmae Naoshi , Nishizawa Tomohiro , Ito Koichi , Miyaji Takaaki , Moriyama Yoshinori , Ishitani Ryuichiro , Nureki Osamu 
Published: November 2017

AbstractMulitidrug and toxic compound extrusion (MATE) family transporters export xenobiotics to maintain cellular homeostasis. The human MATE transporters mediate the excretion of xenobiotics and cationic clinical drugs, whereas some plant MATE transporters are responsible for aluminum tolerance and secondary metabolite transport. Here we report the crystal structure of the eukaryotic MATE transporter from Arabidopsis thaliana, at 2.6 Å resolution. The structure reveals that its carboxy-terminal lobe (C-lobe) contains an extensive hydrogen-bonding network with well-conserved acidic residues, and their importance is demonstrated by the structure-based mutational analysis. The structural and functional analyses suggest that the transport mechanism involves the structural change of transmembrane helix 7, induced by the formation of a hydrogen-bonding network upon the protonation of the conserved acidic residue in the C-lobe. Our findings provide insights into the transport mechanism of eukaryotic MATE transporters, which is important for the improvement of the pharmacokinetics of the clinical drugs.
3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry
Authors: Velez D. O. , Tsui B. , Goshia T. , Chute C. L. , Han A. , Carter H. , Fraley S. I. 
Published: November 2017

AbstractThe topographical organization of collagen within the tumor microenvironment has been implicated in modulating cancer cell migration and independently predicts progression to metastasis. Here, we show that collagen matrices with small pores and short fibers, but not Matrigel, trigger a conserved transcriptional response and subsequent motility switch in cancer cells resulting in the formation of multicellular network structures. The response is not mediated by hypoxia, matrix stiffness, or bulk matrix density, but rather by matrix architecture-induced β1-integrin upregulation. The transcriptional module associated with network formation is enriched for migration and vasculogenesis-associated genes that predict survival in patient data across nine distinct tumor types. Evidence of this gene module at the protein level is found in patient tumor slices displaying a vasculogenic mimicry (VM) phenotype. Our findings link a collagen-induced migration program to VM and suggest that this process may be broadly relevant to metastatic progression in solid human cancers.
mDia1 senses both force and torque during F-actin filament polymerization
Authors: Yu Miao , Yuan Xin , Lu Chen , Le Shimin , Kawamura Ryo , Efremov Artem K. , Zhao Zhihai , Kozlov Michael M. , Sheetz Michael , Bershadsky Alexander , Yan Jie 
Published: November 2017

AbstractFormins, an important family of force-bearing actin-polymerizing factors, function as homodimers that bind with the barbed end of actin filaments through a ring-like structure assembled from dimerized FH2 domains. It has been hypothesized that force applied to formin may facilitate transition of the FH2 ring from an inhibitory closed conformation to a permissive open conformation, speeding up actin polymerization. We confirm this hypothesis for mDia1 dependent actin polymerization by stretching a single-actin filament in the absence of profilin using magnetic tweezers, and observe that increasing force from 0.5 to 10 pN can drastically speed up the actin polymerization rate. Further, we find that this force-promoted actin polymerization requires torsionally unconstrained actin filament, suggesting that mDia1 also senses torque. As actin filaments are subject to complex mechanical constraints in living cells, these results provide important insights into how formin senses these mechanical constraints and regulates actin organization accordingly.
The HSF1–PARP13–PARP1 complex facilitates DNA repair and promotes mammary tumorigenesis
Authors: Fujimoto Mitsuaki , Takii Ryosuke , Takaki Eiichi , Katiyar Arpit , Nakato Ryuichiro , Shirahige Katsuhiko , Nakai Akira 
Published: November 2017

AbstractPoly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on DNA are poorly understood. Here, we show that heat shock transcription factor 1 (HSF1) recruits PARP1 through the scaffold protein PARP13. In response to DNA damage, activated and auto-poly-ADP-ribosylated PARP1 dissociates from HSF1–PARP13, and redistributes to DNA lesions and DNA damage-inducible gene loci. Histone deacetylase 1 maintains PARP1 in the ternary complex by inactivating PARP1 through deacetylation. Blocking ternary complex formation impairs redistribution of PARP1 during DNA damage, which reduces gene expression and DNA repair. Furthermore, ternary complex formation and PARP1 redistribution protect cells from DNA damage by promoting DNA repair, and support growth of BRCA1-null mammary tumors, which are sensitive to PARP inhibitors. Our findings identify HSF1 as a regulator of genome integrity and define this function as a guarding mechanism for a specific type of mammary tumorigenesis.
Surface plasmon induced direct detection of long wavelength photons
Authors: Tong Jinchao , Zhou Wei , Qu Yue , Xu Zhengji , Huang Zhiming , Zhang Dao Hua 
Published: November 2017

AbstractMillimeter and terahertz wave photodetectors have long been of great interest due to a wide range of applications, but they still face challenges in detection performance. Here, we propose a new strategy for the direct detection of millimeter and terahertz wave photons based on localized surface-plasmon-polariton (SPP)-induced non-equilibrium electrons in antenna-assisted subwavelength ohmic metal–semiconductor–metal (OMSM) structures. The subwavelength OMSM structure is used to convert the absorbed photons into localized SPPs, which then induce non-equilibrium electrons in the structure, while the antenna increases the number of photons coupled into the OMSM structure. When the structure is biased and illuminated, the unidirectional flow of the SPP-induced non-equilibrium electrons forms a photocurrent. The energy of the detected photons is determined by the structure rather than the band gap of the semiconductor. The detection scheme is confirmed by simulation and experimental results from the devices, made of gold and InSb, and a room temperature noise equivalent power (NEP) of 1.5 × 10−13 W Hz−1/2 is achieved.
The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis
Authors: Fusella Federica , Seclì Laura , Busso Elena , Krepelova Anna , Moiso Enrico , Rocca Stefania , Conti Laura , Annaratone Laura , Rubinetto Cristina , Mello-Grand Maurizia , Singh Vijay , Chiorino Giovanna , Silengo Lorenzo , Altruda Fiorella , Turco Emilia , Morotti Alessandro , Oliviero Salvatore , Castellano Isabella , Cavallo Federica , Provero Paolo , Tarone Guido , Brancaccio Mara 
Published: November 2017

AbstractNF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IκBα downregulation. High Morgana expression levels in cancer cells decrease recruitment of natural killer cells in the first phases of tumor growth and induce the expression of cytokines able to attract neutrophils in the primary tumor, as well as in the pre-metastatic lungs, fueling cancer metastasis. In accordance, high Morgana levels positively correlate with NF-κB target gene expression and poor prognosis in human patients.
Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila
Authors: Huang Chang , Yang Fu , Zhang Zhuqiang , Zhang Jing , Cai Gaihong , Li Lin , Zheng Yong , Chen She , Xi Rongwen , Zhu Bing 
Published: November 2017

AbstractAsh1 is a Trithorax group protein that possesses H3K36-specific histone methyltransferase activity, which antagonizes Polycomb silencing. Here we report the identification of two Ash1 complex subunits, Mrg15 and Nurf55. In vitro, Mrg15 stimulates the enzymatic activity of Ash1. In vivo, Mrg15 is recruited by Ash1 to their common targets, and Mrg15 reinforces Ash1 chromatin association and facilitates the proper deposition of H3K36me2. To dissect the functional role of Mrg15 in the context of the Ash1 complex, we identify an Ash1 point mutation (Ash1-R1288A) that displays a greatly attenuated interaction with Mrg15. Knock-in flies bearing this mutation display multiple homeotic transformation phenotypes, and these phenotypes are partially rescued by overexpressing the Mrg15-Nurf55 fusion protein, which stabilizes the association of Mrg15 with Ash1. In summary, Mrg15 is a subunit of the Ash1 complex, a stimulator of Ash1 enzymatic activity and a critical regulator of the TrxG protein function of Ash1 in Drosophila.
First-principles screening of structural properties of intermetallic compounds on martensitic transformation
Authors: Lee Joohwi , Ikeda Yuji , Tanaka Isao 
Published: November 2017

AbstractMartensitic transformation with good structural compatibility between parent and martensitic phases are required for shape memory alloys (SMAs) in terms of functional stability. In this study, first-principles-based materials screening is systematically performed to investigate the intermetallic compounds with the martensitic phases by focusing on energetic and dynamical stabilities as well as structural compatibility with the parent phase. The B2, D03, and L21crystal structures are considered as the parent phases, and the 2H and 6M structures are considered as the martensitic phases. In total, 3384 binary and 3243 ternary alloys with stoichiometric composition ratios are investigated. It is found that 187 alloys survive after the screening. Some of the surviving alloys are constituted by the chemical elements already widely used in SMAs, but other various metallic elements are also found in the surviving alloys. The energetic stability of the surviving alloys is further analyzed by comparison with the data in Materials Project Database (MPD) to examine the alloys whose martensitic structures may cause further phase separation or transition to the other structures.
Prioritising the application of genomic medicine
Authors: Doble Brett , Schofield Deborah J. , Roscioli Tony , Mattick John S. 
Published: November 2017

AbstractThe clinical translation of genomic sequencing is hampered by the limited information available to guide investment into those areas where genomics is well placed to deliver improved health and economic outcomes. To date, genomic medicine has achieved its greatest successes through applications to diseases that have a high genotype–phenotype correlation and high penetrance, with a near certainty that the individual will develop the condition in the presence of the genotype. It has been anticipated that genomics will play an important role in promoting population health by targeting at-risk individuals and reducing the incidence of highly prevalent, costly, complex diseases, with potential applications across screening, prevention, and treatment decisions. However, where primary or secondary prevention requires behavioural changes, there is currently very little evidence to support reduction in disease incidence. A better understanding of the relationship between genomic variation and complex diseases will be necessary before effective genomic risk identification and management of the risk of complex diseases in healthy individuals can be carried out in clinical practice. Our recommended approach is that priority for genomic testing should focus on diseases where there is strong genotype–phenotype correlation, high or certain penetrance, the effects of the disease are serious and near-term, there is the potential for prevention and/or treatment, and the net costs incurred are acceptable for the health gains achieved.
IGF-1-mediated PKM2/β-catenin/miR-152 regulatory circuit in breast cancer
Authors: Wen Yi-Yang , Liu Wei-Tao , Sun Hao-Ran , Ge Xin , Shi Zhu-Mei , Wang Min , Li Wei , Zhang Jian-Ying , Liu Ling-Zhi , Jiang Bing-Hua 
Published: November 2017

AbstractDysregulation of miRNAs is important in breast cancer initiation and malignant progression. Recently we showed that miR-152 downregulation is associated with breast cancer development, yet the underlying mechanism of miR-152 remains to be well elucidated. In this study, we identified β-catenin as a new direct target of miR-152. MiR-152 inhibited cell proliferation by targeting and inhibiting both β-catenin and PKM2 expression. We found that miR-152 expression sensitized the breast cancer cells to paclitaxel treatment by inhibiting β-catenin and PKM2 expression. Intriguingly, IGF-1 induced β-catenin and PKM2 expression and enhanced β-catenin and PKM2 interaction. Subsequently, IGF-1-induced β-catenin and PKM2 complex translocated into the nucleus, which in turn activated expression of miR-152. These results suggested a regulatory circuit between miR-152, β-catenin and PKM2 in breast cancer. By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with β-catenin and PKM2 levels in breast cancer tissues. Our findings provide new insights into a mechanism of miR-152 involved in β-catenin and PKM2 inhibition which would have clinical implication for the cancer development and new treatment option in the future.
Results of a 15-year systematic survey of commensal rodents in English dwellings
Authors: Lambert M. , Vial F. , Pietravalle S. , Cowan D. 
Published: November 2017

AbstractPopulation trends for commensal rodents are the subject of interest and speculation but accurate data are rarely available. Here we report data from a 15-year systematic survey of rats and mice in English dwellings and present national-level estimates of prevalence for 1996–2010. We found evidence for peaks in prevalence of mice inside and rats around dwellings in 2002 and 2008. Models containing twelve variables relating to the dwelling and local area explained some but not all of the variation in prevalence. Older dwellings, those in rural areas, those with litter, drainage faults and pets or other animals outdoors tended to have higher levels of rodent prevalence. Regional differences were found but there were no seasonal trends apart from lower prevalence of mice during summer. Rodent prevalence was generally higher in rented (compared to owner-occupied) dwellings, although apparently not due to reduced tendency to carry out rodent control. The percentage of households having taken some form of action against active rodent problems varied according to prevalence at the national level, and therefore appropriate data on number of rodent control treatments carried out each year could likely act as a useful index of household rodent prevalence.
Whole Exome Sequencing reveals new candidate genes in host genomic susceptibility to Respiratory Syncytial Virus Disease
Authors: Salas Antonio , Pardo-Seco Jacobo , Cebey-López Miriam , Gómez-Carballa Alberto , Obando-Pacheco Pablo , Rivero-Calle Irene , Currás-Tuala María-José , Amigo Jorge , Gómez-Rial José , Martinón-Torres Federico ,   GENDRES network, Justicia-Grande Antonio , Morillo Beatriz , Redondo-Collazo Lorenzo , Rodríguez-Tenreiro Carmen , Barral-Arca Ruth , Pischedda Sara , Peña-Guitián José , Curros Novo Carmen , Puente-Puig Miriam , Leis-Trabazo Rosaura , Martinón-Torres Nazareth , Martinón-Sánchez José María , Fraga-Rodríguez Máximo Francisco , Antúnez José Ramón , Bernaola-Iturbe Enrique , Moreno-Galarraga Laura , Álvarez Jorge , González-López Teresa , Suarez-Vázquez Delfina , Vázquez Vázquez Ángela , Rey-García Susana , Giménez-Sánchez Francisco , Forte Miguel Sánchez , Calvo-Rey Cristina , García-García María Luz , Oulego-Erroz Ignacio , Naranjo Vivas David , Lapeña Santiago , Alonso-Quintela Paula , Martínez-Sáenz de Jubera Jorge , Garrido-García Estibaliz , Calvo Monge Cristina , Oñate-Vergara Eider , de la Cruz Moreno Jesús , Martínez-Padilla Maria del Carmen , Baca-Cots Manuel , Moreno-Pérez David , Beatriz-Reyes Susana , León-León María Cruz 
Published: November 2017

AbstractRespiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) geneOR13C5as the best candidate variant (P-value = 1.16 × 10−12; OR = 5.56). Genetic variants at HLA genes (HLA-DQA1,HLA-DPB1), and in the mucin 4 gene (MUC4) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR geneOR8U1/OR8U8, the taste receptorTAS2R19, and another mucin gene (MUC6). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.
An organic fluorophore-nanodiamond hybrid sensor for photostable imaging and orthogonal, on-demand biosensing
Authors: Purdey Malcolm S. , Capon Patrick K. , Pullen Benjamin J. , Reineck Philipp , Schwarz Nisha , Psaltis Peter J. , Nicholls Stephen J. , Gibson Brant C. , Abell Andrew D. 
Published: November 2017

AbstractOrganic fluorescent probes are widely used to detect key biomolecules; however, they often lack the photostability required for extended intracellular imaging. Here we report a new hybrid nanomaterial (peroxynanosensor, PNS), consisting of an organic fluorescent probe bound to a nanodiamond, that overcomes this limitation to allow concurrent and extended cell-based imaging of the nanodiamond and ratiometric detection of hydrogen peroxide. Far-red fluorescence of the nanodiamond offers continuous monitoring without photobleaching, while the green fluorescence of the organic fluorescent probe attached to the nanodiamond surface detects hydrogen peroxide on demand. PNS detects basal production of hydrogen peroxide within M1 polarised macrophages and does not affect macrophage growth during prolonged co-incubation. This nanosensor can be used for extended bio-imaging not previously possible with an organic fluorescent probe, and is spectrally compatible with both Hoechst 33342 and MitoTracker Orange stains for hyperspectral imaging.
Dual-Mode Manipulating Multicenter Photoluminescence in a Single-Phased Ba9Lu2Si6O24:Bi3+, Eu3+ Phosphor to Realize White Light/Tunable Emissions
Authors: Guo Yue , Park Sung Heum , Choi Byung Chun , Jeong Jung Hyun , Kim Jung Hwan 
Published: November 2017

AbstractA Bi3+ and Eu3+ ion co-doped Ba9Lu2Si6O24 single-phased phosphor was synthesized successfully via a conventional high-temperature solid-state reaction. X-ray diffraction, crystal structure analysis, diffuse reflectance and luminescent spectra, quantum efficiency measurements, and thermal stability analysis were applied to investigate the phase, structure, luminescent and thermal stability properties. From the analyses of the crystal structure and luminescent spectra, we observed four discernible Bi3+ luminescent centers with peaks at ~363.3, ~403.1, ~437.7, and ~494.5 nm. Moreover, due to the complex energy transfer processes among these Bi3+ centers, their relative emission intensity tightly depended on the incident excitation wavelength. Interestingly, the as-prepared phosphor could generate warm white light/tunable emission by changing the concentration of Eu3+ ions or adjusting the excitation wavelength. The energy transfer mechanism from Bi3+ to Eu3+ was confirmed via an electric dipole-dipole interaction, the energy transfer efficiencies $$({\eta }_{T})$$
(

η

T

)
from Bi3+ to Eu3+ were 50.84% and 40.17% monitoring at 410 and 485 nm, respectively. The internal quantum efficiency of the optimized Ba9Lu2Si6O24:Bi3+, Eu3+ phosphor was calculated to be 42.6%. In addition, the configurational coordinate model was carried out to explain the energy decrease of the phonon-electron coupling effect.