bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic polarization vision in mantis shrimps
Authors: Daly Ilse M. , How Martin J. , Partridge Julian C. , Temple Shelby E. , Marshall N. Justin , Cronin Thomas W. , Roberts Nicholas W. 
Published: July 2016

AbstractGaze stabilization is an almost ubiquitous animal behaviour, one that is required to see the world clearly and without blur. Stomatopods, however, only fix their eyes on scenes or objects of interest occasionally. Almost uniquely among animals they explore their visual environment with a series pitch, yaw and torsional (roll) rotations of their eyes, where each eye may also move largely independently of the other. In this work, we demonstrate that the torsional rotations are used to actively enhance their ability to see the polarization of light. Both Gonodactylus smithii and Odontodactylus scyllarus rotate their eyes to align particular photoreceptors relative to the angle of polarization of a linearly polarized visual stimulus, thereby maximizing the polarization contrast between an object of interest and its background. This is the first documented example of any animal displaying dynamic polarization vision, in which the polarization information is actively maximized through rotational eye movements.
Golgi membrane fission requires the CtBP1-S/BARS-induced activation of lysophosphatidic acid acyltransferase δ
Authors: Pagliuso Alessandro , Valente Carmen , Giordano Lucia Laura , Filograna Angela , Li Guiling , Circolo Diego , Turacchio Gabriele , Marzullo Vincenzo Manuel , Mandrich Luigi , Zhukovsky Mikhail A. , Formiggini Fabio , Polishchuk Roman S. , Corda Daniela , Luini Alberto 
Published: July 2016

AbstractMembrane fission is an essential cellular process by which continuous membranes split into separate parts. We have previously identified CtBP1-S/BARS (BARS) as a key component of a protein complex that is required for fission of several endomembranes, including basolateral post-Golgi transport carriers. Assembly of this complex occurs at the Golgi apparatus, where BARS binds to the phosphoinositide kinase PI4KIIIβ through a 14-3-3γ dimer, as well as to ARF and the PKD and PAK kinases. We now report that, when incorporated into this complex, BARS binds to and activates a trans-Golgi lysophosphatidic acid (LPA) acyltransferase type δ (LPAATδ) that converts LPA into phosphatidic acid (PA); and that this reaction is essential for fission of the carriers. LPA and PA have unique biophysical properties, and their interconversion might facilitate the fission process either directly or indirectly (via recruitment of proteins that bind to PA, including BARS itself).
Host genotype and age shape the leaf and root microbiomes of a wild perennial plant
Authors: Wagner Maggie R. , Lundberg Derek S , del Rio Tijana G. , Tringe Susannah G. , Dangl Jeffery L. , Mitchell-Olds Thomas 
Published: July 2016

AbstractBacteria living on and in leaves and roots influence many aspects of plant health, so the extent of a plant’s genetic control over its microbiota is of great interest to crop breeders and evolutionary biologists. Laboratory-based studies, because they poorly simulate true environmental heterogeneity, may misestimate or totally miss the influence of certain host genes on the microbiome. Here we report a large-scale field experiment to disentangle the effects of genotype, environment, age and year of harvest on bacterial communities associated with leaves and roots ofBoechera stricta(Brassicaceae), a perennial wild mustard. Host genetic control of the microbiome is evident in leaves but not roots, and varies substantially among sites. Microbiome composition also shifts as plants age. Furthermore, a large proportion of leaf bacterial groups are shared with roots, suggesting inoculation from soil. Our results demonstrate how genotype-by-environment interactions contribute to the complexity of microbiome assembly in natural environments.
Homologous recombination-dependent repair of telomeric DSBs in proliferating human cells
Authors: Mao Pingsu , Liu Jingfan , Zhang Zepeng , Zhang Hong , Liu Haiying , Gao Song , Rong Yikang S. , Zhao Yong 
Published: July 2016

AbstractTelomeres prevent chromosome ends from being recognized as double-stranded breaks (DSBs). Meanwhile, G/C-rich repetitive telomeric DNA is susceptible to attack by DNA-damaging agents. How cells balance the need to protect DNA ends and the need to repair DNA lesions in telomeres is unknown. Here we show that telomeric DSBs are efficiently repaired in proliferating cells, but are irreparable in stress-induced and replicatively senescent cells. Using the CRISPR-Cas9 technique, we specifically induce DSBs at telomeric or subtelomeric regions. We find that DSB repair (DSBR) at subtelomeres occurs in an error-prone manner resulting in small deletions, suggestive of NHEJ. However, DSBR in telomeres involves ‘telomere-clustering’, 3′-protruding C-rich telomeric ssDNA, and HR between sister-chromatid or interchromosomal telomeres. DSBR in telomeres is suppressed by deletion or inhibition of Rad51. These findings reveal proliferation-dependent DSBR in telomeres and suggest that telomeric HR, which is normally constitutively suppressed, is activated in the context of DSBR.
Cavity-enhanced Raman microscopy of individual carbon nanotubes
Authors: Hümmer Thomas , Noe Jonathan , Hofmann Matthias S. , Hänsch Theodor W. , Högele Alexander , Hunger David 
Published: July 2016

AbstractRaman spectroscopy reveals chemically specific information and provides label-free insight into the molecular world. However, the signals are intrinsically weak and call for enhancement techniques. Here, we demonstrate Purcell enhancement of Raman scattering in a tunable high-finesse microcavity, and utilize it for molecular diagnostics by combined Raman and absorption imaging. Studying individual single-wall carbon nanotubes, we identify crucial structural parameters such as nanotube radius, electronic structure and extinction cross-section. We observe a 320-times enhanced Raman scattering spectral density and an effective Purcell factor of 6.2, together with a collection efficiency of 60%. Potential for significantly higher enhancement, quantitative signals, inherent spectral filtering and absence of intrinsic background in cavity-vacuum stimulated Raman scattering render the technique a promising tool for molecular imaging. Furthermore, cavity-enhanced Raman transitions involving localized excitons could potentially be used for gaining quantum control over nanomechanical motion and open a route for molecular cavity optomechanics.
ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer
Authors: Deblois Geneviève , Smith Harvey W. , Tam Ingrid S. , Gravel Simon-Pierre , Caron Maxime , Savage Paul , Labbé David P. , Bégin Louis R. , Tremblay Michel L. , Park Morag , Bourque Guillaume , St-Pierre Julie , Muller William J. , Giguère Vincent 
Published: July 2016

AbstractDespite the initial benefits of treating HER2-amplified breast cancer patients with the tyrosine kinase inhibitor lapatinib, resistance inevitably develops. Here we report that lapatinib induces the degradation of the nuclear receptor ERRα, a master regulator of cellular metabolism, and that the expression of ERRα is restored in lapatinib-resistant breast cancer cells through reactivation of mTOR signalling. Re-expression of ERRα in resistant cells triggers metabolic adaptations favouring mitochondrial energy metabolism through increased glutamine metabolism, as well as ROS detoxification required for cell survival under therapeutic stress conditions. An ERRα inverse agonist counteracts these metabolic adaptations and overcomes lapatinib resistance in a HER2-induced mammary tumour mouse model. This work reveals a molecular mechanism by which ERRα-induced metabolic reprogramming promotes survival of lapatinib-resistant cancer cells and demonstrates the potential of ERRα inhibition as an effective adjuvant therapy in poor outcome HER2-positive breast cancer.
Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution
Authors: Luo Bangwei , Wang Jinsong , Liu Zongwei , Shen Zigang , Shi Rongchen , Liu Yu-Qi , Liu Yu , Jiang Man , Wu Yuzhang , Zhang Zhiren 
Published: July 2016

AbstractInflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental and of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia and macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice and chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, and exogenous erythropoietin enhances this resolution in WT and CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris and enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions.
Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids
Authors: Jin Haibao , Jiao Fang , Daily Michael D. , Chen Yulin , Yan Feng , Ding Yan-Huai , Zhang Xin , Robertson Ellen J. , Baer Marcel D. , Chen Chun-Long 
Published: July 2016

AbstractAn ability to develop sequence-defined synthetic polymers that both mimic lipid amphiphilicity for self-assembly of highly stable membrane-mimetic 2D nanomaterials and exhibit protein-like functionality would revolutionize the development of biomimetic membranes. Here we report the assembly of lipid-like peptoids into highly stable, crystalline, free-standing and self-repairing membrane-mimetic 2D nanomaterials through a facile crystallization process. Both experimental and molecular dynamics simulation results show that peptoids assemble into membranes through an anisotropic formation process. We further demonstrated the use of peptoid membranes as a robust platform to incorporate and pattern functional objects through large side-chain diversity and/or co-crystallization approaches. Similar to lipid membranes, peptoid membranes exhibit changes in thickness upon exposure to external stimuli; they can coat surfaces in single layers and self-repair. We anticipate that this new class of membrane-mimetic 2D nanomaterials will provide a robust matrix for development of biomimetic membranes tailored to specific applications.
The molecular landscape of high-risk early breast cancer: comprehensive biomarker analysis of a phase III adjuvant population
Authors: Wilson Timothy R , Yu Jianjun , Lu Xuyang , Spoerke Jill M , Xiao Yuanyuan , O’Brien Carol , Savage Heidi M , Huw Ling-Yuh , Zou Wei , Koeppen Hartmut , Forrest William F , Fridlyand Jane , Fu Ling , Tam Rachel , Schleifman Erica B , Sumiyoshi Teiko , Molinero Luciana , Hampton Garret M , O’Shaughnessy Joyce A , Lackner Mark R 
Published: July 2016

AbstractBreast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. We sought to characterize the molecular landscape of high-risk breast cancer patients enrolled onto an adjuvant chemotherapy study to understand how disease subsets and tumor immune status impact survival. DNA and RNA were extracted from 861 breast cancer samples from patients enrolled onto the United States Oncology trial 01062. Samples were characterized using multiplex gene expression, copy number, and qPCR mutation assays. HR+patients with aPIK3CAmutant tumor had a favorable disease-free survival (DFS; HR 0.66,P=0.05), however, the prognostic effect was specific to luminal A patients (Luminal A: HR 0.67,P=0.1; Luminal B: HR 1.01,P=0.98). Molecular subtyping of triple-negative breast cancers (TNBCs) suggested that the mesenchymal subtype had the worst DFS, whereas the immunomodulatory subtype had the best DFS. Profiling of immunologic genes revealed that TNBC tumors (n=280) displaying an activated T-cell signature had a longer DFS following adjuvant chemotherapy (HR 0.59,P=0.04), while a distinct set of immune genes was associated with DFS in HR+cancers. Utilizing a discovery approach, we identified genes associated with a high risk of recurrence in HR+patients, which were validated in an independent data set. Molecular classification based on PAM50 and TNBC subtyping stratified clinical high-risk patients into distinct prognostic subsets. Patients with high expression of immune-related genes showed superior DFS in both HR+and TNBC. These results may inform patient management and drug development in early breast cancer.
Footprints reveal direct evidence of group behavior and locomotion in Homo erectus
Authors: Hatala Kevin G. , Roach Neil T. , Ostrofsky Kelly R. , Wunderlich Roshna E. , Dingwall Heather L. , Villmoare Brian A. , Green David J. , Harris John W. K. , Braun David R. , Richmond Brian G. 
Published: July 2016

AbstractBipedalism is a defining feature of the human lineage. Despite evidence that walking on two feet dates back 6–7 Ma, reconstructing hominin gait evolution is complicated by a sparse fossil record and challenges in inferring biomechanical patterns from isolated and fragmentary bones. Similarly, patterns of social behavior that distinguish modern humans from other living primates likely played significant roles in our evolution, but it is exceedingly difficult to understand the social behaviors of fossil hominins directly from fossil data. Footprints preserve direct records of gait biomechanics and behavior but they have been rare in the early human fossil record. Here we present analyses of an unprecedented discovery of 1.5-million-year-old footprint assemblages, produced by 20+ Homo erectus individuals. These footprints provide the oldest direct evidence for modern human-like weight transfer and confirm the presence of an energy-saving longitudinally arched foot in H. erectus. Further, print size analyses suggest that these H. erectus individuals lived and moved in cooperative multi-male groups, offering direct evidence consistent with human-like social behaviors in H. erectus.
A Rational Approach for the Identification of Non-Hydroxamate HDAC6-Selective Inhibitors
Authors: Goracci Laura , Deschamps Nathalie , Randazzo Giuseppe Marco , Petit Charlotte , Dos Santos Passos Carolina , Carrupt Pierre-Alain , Simões-Pires Claudia , Nurisso Alessandra 
Published: July 2016

AbstractThe human histone deacetylase isoform 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, being interesting for the treatment of multiple tumour types and neurodegenerative conditions. Currently, most HDAC inhibitors in preclinical or clinical evaluations are non-selective inhibitors, characterised by a hydroxamate zinc-binding group (ZBG) showing off-target effects and mutagenicity. The identification of selective HDAC6 inhibitors with novel chemical properties has not been successful yet, also because of the absence of crystallographic information that makes the rational design of HDAC6 selective inhibitors difficult. Using HDAC inhibitory data retrieved from the ChEMBL database and ligand-based computational strategies, we identified 8 original new non-hydroxamate HDAC6 inhibitors from the SPECS database, with activity in the low μM range. The most potent and selective compound, bearing a hydrazide ZBG, was shown to increase tubulin acetylation in human cells. No effects on histone H4 acetylation were observed. To the best of our knowledge, this is the first report of an HDAC6 selective inhibitor bearing a hydrazide ZBG. Its capability to passively cross the blood-brain barrier (BBB), as observed through PAMPA assays and its low cytotoxicity in vitro, suggested its potential for drug development.
Sox transcription in sarcosine utilization is controlled by Sigma54 and SoxR in Bacillus thuringiensis HD73
Authors: Peng Qi , Liu Chunxia , Wang Bo , Yang Min , Wu Jianbo , Zhang Jie , Song Fuping 
Published: July 2016

AbstractSarcosine oxidase catalyzes the oxidative demethylation of sarcosine to yield glycine, formaldehyde and hydrogen peroxide. In this study, we analyzed the transcription and regulation of the sox locus, including the sarcosine oxidase-encoding genes in Bacillus thuringiensis (Bt). RT-PCR analysis revealed that the sox locus forms two opposing transcriptional units: soxB (soxB/E/F/G/H/I) and soxR (soxR/C/D/A). The typical −12/−24 consensus sequence was located 15 bp and 12 bp from the transcriptional start site (TSS) of soxB and soxC, respectively. Promoter-lacZ fusion assays showed that the soxB promoter is controlled by the Sigma54 factor and is activated by the Sigma54-dependent transcriptional regulator SoxR. SoxR also inhibits its own expression. Expression from the PsoxCR promoter, which is responsible for the transcription of soxC, soxD, and soxA, is Sigma54-dependent and requires SoxR. An 11-bp inverted repeat sequence was identified as SoxR binding site upstream of the soxB TSS. Purified SoxR specifically bound a DNA fragment containing this region. Mutation or deletion of this sequence abolished the transcriptional activities of soxB and soxC. Thus, SoxR binds to the same sequence to activate the transcription of soxB and soxC. Sarcosine utilization was abolished in soxB and soxR mutants, suggesting that the sox locus is essential for sarcosine utilization.
A novel quantitation approach for maximizing detectable targets for offensive/volatile odorants with diverse functional groups by thermal desorption-gas chromatography-mass spectrometry
Authors: Kim Yong-Hyun , Kim Ki-Hyun 
Published: July 2016

AbstractA multitude of analytical systems are needed to analyze diverse odorants with various functionalities. In this study, an experimental method was developed to assess the maximum covering range of odorants using a single experimental setup consisting of a thermal desorber-gas chromatography-mass spectrometry system. To this end, a total of 20 offensive odorants (aldehyde, ketone, ester, alcohol, aromatic, sulfide, amine, and carboxyl) were selected and tested by a single system. The analytical results of standards and environmental samples were evaluated in a number of respects. In the analysis of the standards, all targets were quantified via Carbopack (C + B + X) tube sampling while operating the thermal desorber at −25 °C. The method detection limits of 18 targets (exception of 2 out of the 20 targets: acetaldehyde and methanethiol) were excellent (mean 0.04 ± 0.03 ppb) in terms of their odor threshold values (74.7 ± 140 ~ 624 ± 1,729 ppb). The analysis of organic fertilizer plant samples at a pig farm (slurry treatment facility, compost facility, and ambient air) confirmed the presence of 18 odorants from 0.03 ppb (dimethyldisulfide, ambient sample) to 522 ppb (methyl ethyl ketone, slurry treatment facility). As such, our method allowed simultaneous quantitation of most key odorants with sufficient reliability and sensitivity.
The In-Plane Anisotropy of WTe2 Investigated by Angle-Dependent and Polarized Raman Spectroscopy
Authors: Song Qingjun , Pan Xingchen , Wang Haifeng , Zhang Kun , Tan Qinghai , Li Pan , Wan Yi , Wang Yilun , Xu Xiaolong , Lin Miaoling , Wan Xiangang , Song Fengqi , Dai Lun 
Published: July 2016

AbstractTungsten ditelluride (WTe2) is a semi-metallic layered transition metal dichalcogenide with a stable distorted 1T phase. The reduced symmetry of this system leads to in-plane anisotropy in various materials properties. We have systemically studied the in-plane anisotropy of Raman modes in few-layer and bulk WTe2 by angle-dependent and polarized Raman spectroscopy (ADPRS). Ten Raman modes are clearly resolved. Their intensities show periodic variation with sample rotating. We identify the symmetries of the detected modes by quantitatively analyzing the ADPRS results based on the symmetry selection rules. Material absorption effect on the phonon modes with high vibration frequencies is investigated by considering complex Raman tensor elements. We also provide a rapid and nondestructive method to identify the crystallographic orientation of WTe2. The crystallographic orientation is further confirmed by the quantitative atomic-resolution force image. Finally, we find that the atomic vibrational tendency and complexity of detected modes are also reflected in the shrinkage degree defined based on ADPRS, which is confirmed by corresponding density functional calculation. Our work provides a deep understanding of the interaction between WTe2 and light, which will benefit in future studies about the anisotropic physical properties of WTe2 and other in-plane anisotropic materials.
Oxidative Stress Induced by Pt(IV) Pro-drugs Based on the Cisplatin Scaffold and Indole Carboxylic Acids in Axial Position
Authors: Tolan Dina , Gandin Valentina , Morrison Liam , El-Nahas Ahmed , Marzano Cristina , Montagner Diego , Erxleben Andrea 
Published: July 2016

AbstractThe use of Pt(IV) complexes as pro-drugs that are activated by intracellular reduction is a widely investigated approach to overcome the limitations of Pt(II) anticancer agents. A series of ten mono- and bis-carboxylated Pt(IV) complexes with axial indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) ligands were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, 1H and 195Pt NMR spectroscopy. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. All the complexes are able to overcome cisplatin-resistance and the most potent complex, cis,cis,trans-[Pt(NH3)2Cl2(IPA)(OH)] was on average three times more active than cisplatin. Mechanistic studies revealed that the trend in cytotoxicity of the Pt(IV) complexes is primarily consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which in turn results in the loss of mitochondrial membrane potential and apoptosis induction. The role of the indole acid ligand as a redox modulator is discussed.
Potent response of QS-21 as a vaccine adjuvant in the skin when delivered with the Nanopatch, resulted in adjuvant dose sparing
Authors: Ng Hwee-Ing , Fernando Germain J. P. , Depelsenaire Alexandra C. I. , Kendall Mark A. F. 
Published: July 2016

AbstractAdjuvants play a key role in boosting immunogenicity of vaccines, particularly for subunit protein vaccines. In this study we investigated the induction of antibody response against trivalent influenza subunit protein antigen and a saponin adjuvant, QS-21. Clinical trials of QS-21 have demonstrated the safety but, also a need of high dose for optimal immunity, which could possibly reduce patient acceptability. Here, we proposed the use of a skin delivery technology – the Nanopatch – to reduce both adjuvant and antigen dose but also retain its immune stimulating effects when compared to the conventional needle and syringe intramuscular (IM) delivery. We have demonstrated that Nanopatch delivery to skin requires only 1/100th of the IM antigen dose to induce equivalent humoral response. QS-21 enhanced humoral response in both skin and muscle route. Additionally, Nanopatch has demonstrated 30-fold adjuvant QS-21 dose sparing while retaining immune stimulating effects compared to IM. QS-21 induced localised, controlled cell death in the skin, suggesting that the danger signals released from dead cells contributed to the enhanced immunogenicity. Taken together, these findings demonstrated the suitability of reduced dose of QS-21 and the antigen using the Nanopatch to enhance humoral responses, and the potential to increase patient acceptability of QS-21 adjuvant.