bluuebunny/crossref_metadata_2025 huggingface dataset:
IFNβ enhances mesenchymal stromal (Stem) cells immunomodulatory function through STAT1-3 activation and mTOR-associated promotion of glucose metabolism
Authors: Vigo Tiziana , La Rocca Claudia , Faicchia Deriggio , Procaccini Claudio , Ruggieri Maddalena , Salvetti Marco , Centonze Diego , Matarese Giuseppe , Uccelli Antonio ,   on behalf of the MSRUN Network
Published: January 2019

Administration of mesenchymal stem cells (MSC) ameliorate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), at both clinical and neuropathological levels. The therapeutic properties of MSC in EAE are mainly mediated by the modulation of pathogenic immune response, but other neurotropic effects, including decreased demyelination and axonal loss as well as promotion of tissue repair, play also a role. Properly controlled phase II clinical trials to explore the potential of MSC transplantation as a treatment for MS are underway. Interferon beta (IFNβ) is an approved treatment for relapsing-remitting and secondary progressive MS. Here, we explored the possibility that IFNβ might influence the therapeutic potential of MSC, in view of possible synergistic effects as add-on therapy. IFNβ enhanced the immunomodulatory functions of MSC and induced the expression of secretory leukocyte protease inhibitor (Slpi) and hepatocyte growth factor (Hgf), two soluble mediators involved in immune and regenerative functions of MSC. At molecular level, IFNβ induced a rapid and transient phosphorylation of STAT1 and STAT3, the transcription factors responsible for Slpi and Hgf induction. Concomitantly, IFNβ dynamically affected the activity of mTOR, a key checkpoint in the control of metabolic pathways. Indeed, the impairment of mTOR activity observed early upon exposure to IFNβ, was followed by a long-lasting induction of mTOR signaling, that was associated with an increased glycolytic capacity in MSC. When induced to switch their energetic metabolism towards glycolysis, MSC showed an improved ability to control T-cell proliferation. These results suggest that modifications of MSC energetic metabolism induced by IFNβ may contribute to promote MSC immunomodulatory function and support a role for metabolic pathways in the therapeutic function of MSC. Altogether, these findings support the idea of a combined treatment for MS, in which the immunomodulatory and possibly regenerative activity of MSC could be enhanced by the administration of IFNβ.
TRAIL inhibits RANK signaling and suppresses osteoclast activation via inhibiting lipid raft assembly and TRAF6 recruitment
Authors: Liao Hsiu-Jung , Tsai Hwei-Fang , Wu Chien-Sheng , Chyuan I.-Tsu , Hsu Ping-Ning
Published: January 2019

Human osteoclast formation from mononuclear phagocyte precursors involves interactions between members of the tumor necrosis factor (TNF) ligand superfamily and their receptors. Recent evidence indicated that TNF-α-related apoptosis-inducing ligand (TRAIL) induces osteoclast differentiation via a TRAF6-dependent signaling pathway; but paradoxically, it inhibits RANK ligand (RANKL)-induced osteoclast differentiation. Although a number of signaling pathways were linked to the RANK and osteoclastogenesis, it is not known how TRAIL regulates RANK signaling. In this study, we demonstrate that TRAIL regulates RANK-induced osteoclastogenesis in terms of the assembly of lipid raft-associated signaling complexes. RANKL stimulation induced recruitment of TRAF6, c-Src, and DAP-12 into lipid rafts. However, the RANKL-induced assembly of lipid raft-associated signaling complexes and TRAF6 recruitment was abolished in the presence of TRAIL. TRAIL-induced dissociation of RANKL-induced lipid raft signaling complexes was reversed by treatment with TRAIL receptor (TRAIL-R) siRNA or an anti-TRAIL-R blocking antibody, indicating that TRAIL mediates suppression of RANKL-induced lipid raft signaling via interactions with TRAIL-R. Finally, we demonstrated that TRAIL suppressed inflammation-induced bone resorption and osteoclastogenesis in a collagen-induced arthritis (CIA) rat animal model. Our results provide a novel apoptosis-independent role of TRAIL in regulating RANK signaling and suppresses osteoclast activation via inhibiting lipid raft assembly and TRAF6 recruitment.
Human proximal tubular cells can form calcium phosphate deposits in osteogenic culture: role of cell death and osteoblast-like transdifferentiation
Authors: Priante Giovanna , Ceol Monica , Gianesello Lisa , Furlan Claudio , Del Prete Dorella , Anglani Franca
Published: January 2019

Nephrocalcinosis is a clinicopathological entity characterized by microscopic calcium crystals in the renal parenchyma, within the tubular lumen or in the interstitium. Crystal binding to tubular cells may be the cause underlying nephrocalcinosis and nephrolithiasis. Pathological circumstances, such as acute cortical necrosis, may induce healthy cells to acquire a crystal-binding phenotype. The present study aimed to investigate whether human renal proximal tubular cells (HK-2 cells) can form calcium phosphate deposits under osteogenic conditions, and whether apoptosis and/or osteogenic-like processes are involved in cell calcification. HK-2 cells were cultured in standard or osteogenic medium for 1, 5, and 15 days. Von Kossa staining and ESEM were used to analyze crystal deposition. Apoptosis was investigated, analyzing caspase activation by in-cell Western assay, membrane translocation of phosphotidylserine by annexin V-FITC/propidium iodide staining, and DNA fragmentation by TUNEL assay. qRT/PCR, immunolabeling and cytochemistry were performed to assess osteogenic activation (Runx2, Osteonectin, Osteopontin and ALP), and early genes of apoptosis (BAX, Bcl-2). HK-2 cell mineralization was successfully induced on adding osteogenic medium. Calcium phosphate deposition increased in a time-dependent manner, and calcified cell aggregates exhibited characteristic signs of apoptosis. At 15 days, calcifying HK-2 cells revealed osteogenic markers, such as Runx2, ALP, osteonectin and osteopontin. Monitoring the processes at 1, 5, and 15 days showed apoptosis starting already after 5 days of osteogenic induction, when the first small calcium phosphate crystals began to appear on areas where cell aggregates were in apoptotic conditions. The cell death process proved caspase-dependent. The importance of apoptosis was reinforced by the time-dependent increase in BAX expression, starting from day 1. These findings strongly support the hypothesis that apoptosis triggered HK-2 calcification even before any calcium phosphate crystal deposition or acquisition of an osteogenic phenotype.
The palladacycle complex AJ-5 induces apoptotic cell death while reducing autophagic flux in rhabdomyosarcoma cells
Authors: Bleloch Jenna Susan , du Toit André , Gibhard Liezl , Kimani Serah , Ballim Reyna Deeya , Lee Minkyu , Blanckenberg Angelique , Mapolie Selwyn , Wiesner Lubbe , Loos Ben , Prince Sharon
Published: January 2019

Rhabdomyosarcoma (RMS) forms in skeletal muscle and is the most common soft tissue sarcoma in children and adolescents. Current treatment is associated with debilitating side effects and treatment outcomes for patients with metastatic disease are dismal. Recently, a novel binuclear palladacycle, AJ-5, was shown to exert potent cytotoxicity in melanoma and breast cancer and to present with negligible adverse effects in mice. This study investigates the anti-cancer activity of AJ-5 in alveolar and embryonal RMS. IC50 values of ≤ 0.2 µM were determined for AJ-5 and it displayed a favourable selectivity index of >2. Clonogenic and migration assays showed that AJ-5 inhibited the ability of RMS cells to survive and migrate, respectively. Western blotting revealed that AJ-5 induced levels of key DNA damage response proteins (γH2AX, p-ATM and p-Chk2) and the p38/MAPK stress pathway. This correlated with an upregulation of p21 and a G1 cell cycle arrest. Annexin V-FITC/propidium iodide staining revealed that AJ-5 induced apoptosis and necrosis. Apoptosis was confirmed by the detection of cleaved PARP and increased levels and activity of cleaved caspases-3, -7, -8 and -9. Furthermore, AJ-5 reduced autophagic flux as shown by reduced LC3II accumulation in the presence of bafilomycin A1 and a significant reduction in autophagosome flux J. Finally, pharmacokinetic studies in mice show that AJ-5 has a promising half-life and that its volume of distribution is high, its clearance low and its intraperitoneal absorption is good. Together these findings suggest that AJ-5 may be an effective chemotherapeutic with a desirable mechanism of action for treating drug-resistant and advanced sarcomas.
Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture
Authors: Stewart Emma R. , Turner Robert M. L. , Newling Katherine , Ridings-Figueroa Rebeca , Scott Victoria , Ashton Peter D. , Ainscough Justin F. X. , Coverley Dawn
Published: January 2019

The inactive X chromosome (Xi) serves as a model for establishment and maintenance of repressed chromatin and the function of polycomb repressive complexes (PRC1/2). Here we show that Xi transiently relocates from the nuclear periphery towards the interior during its replication, in a process dependent on CIZ1. Compromised relocation of Xi in CIZ1-null primary mouse embryonic fibroblasts is accompanied by loss of PRC-mediated H2AK119Ub1 and H3K27me3, increased solubility of PRC2 catalytic subunit EZH2, and genome-wide deregulation of polycomb-regulated genes. Xi position in S phase is also corrupted in cells adapted to long-term culture (WT or CIZ1-null), and also accompanied by specific changes in EZH2 and its targets. The data are consistent with the idea that chromatin relocation during S phase contributes to maintenance of epigenetic landscape in primary cells, and that elevated soluble EZH2 is part of an error-prone mechanism by which modifying enzyme meets template when chromatin relocation is compromised.
Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity
Authors: Liu Longqi , Liu Chuanyu , Quintero Andrés , Wu Liang , Yuan Yue , Wang Mingyue , Cheng Mengnan , Leng Lizhi , Xu Liqin , Dong Guoyi , Li Rui , Liu Yang , Wei Xiaoyu , Xu Jiangshan , Chen Xiaowei , Lu Haorong , Chen Dongsheng , Wang Quanlei , Zhou Qing , Lin Xinxin , Li Guibo , Liu Shiping , Wang Qi , Wang Hongru , Fink J. Lynn , Gao Zhengliang , Liu Xin , Hou Yong , Zhu Shida , Yang Huanming , Ye Yunming , Lin Ge , Chen Fang , Herrmann Carl , Eils Roland , Shang Zhouchun , Xu Xun
Published: January 2019

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generate the first single cell integrated map of chromatin accessibility and transcriptome in early embryos and demonstrate the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states. The ability to obtain these two layers of omics data will help provide more accurate definitions of “single cell state” and enable the deconvolution of regulatory heterogeneity from complex cell populations.
Learning to optimize perceptual decisions through suppressive interactions in the human brain
Authors: Frangou Polytimi , Emir Uzay E. , Karlaftis Vasilis M. , Nettekoven Caroline , Hinson Emily L. , Larcombe Stephanie , Bridge Holly , Stagg Charlotte J. , Kourtzi Zoe
Published: January 2019

Translating noisy sensory signals to perceptual decisions is critical for successful interactions in complex environments. Learning is known to improve perceptual judgments by filtering external noise and task-irrelevant information. Yet, little is known about the brain mechanisms that mediate learning-dependent suppression. Here, we employ ultra-high field magnetic resonance spectroscopy of GABA to test whether suppressive processing in decision-related and visual areas facilitates perceptual judgments during training. We demonstrate that parietal GABA relates to suppression of task-irrelevant information, while learning-dependent changes in visual GABA relate to enhanced performance in target detection and feature discrimination tasks. Combining GABA measurements with functional brain connectivity demonstrates that training on a target detection task involves local connectivity and disinhibition of visual cortex, while training on a feature discrimination task involves inter-cortical interactions that relate to suppressive visual processing. Our findings provide evidence that learning optimizes perceptual decisions through suppressive interactions in decision-related networks.
Author Correction: Intestinal microbiome adjusts the innate immune setpoint during colonization through negative regulation of MyD88
Authors: Koch Bjørn E. V. , Yang Shuxin , Lamers Gerda , Stougaard Jens , Spaink Herman P.
Published: January 2019

The original version of this Article contained an error in the spelling of the author Shuxin Yang, which was incorrectly given as Shuxing Yang. This has now been corrected in both the PDF and HTML versions of the Article.
Proline 411 biases the conformation of the intrinsically disordered plant UVR8 photoreceptor C27 domain altering the functional properties of the peptide
Authors: Wu Min , Farkas Daniel , Eriksson Leif A. , Strid Åke
Published: January 2019

UVR8 (UV RESISTANCE LOCUS 8) is a UV-B photoreceptor responsible for initiating UV-B signalling in plants. UVR8 is a homodimer in its signalling inactive form. Upon absorption of UV radiation, the protein monomerizes into its photoactivated state. In the monomeric form, UVR8 binds the E3 ubiquitin ligase COP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1), triggering subsequent UV-B-dependent photomorphogenic development in plants. Recent in vivo experiments have shown that the UVR8 C-terminal region (aa 397–423; UVR8C27) alone is sufficient to regulate the activity of COP1. In this work, CD spectroscopy and NMR experiments showed that the UVR8C27 domain was non-structured but gained secondary structure at higher temperatures leading to increased order. Bias-exchange metadynamics simulations were also performed to evaluate the free energy landscape of UVR8C27. An inverted free energy landscape was revealed, with a disordered structure in the global energy minimum. Flanking the global energy minimum, more structured states were found at higher energies. Furthermore, stabilization of the low energy disordered state was attributed to a proline residue, P411, as evident from P411A mutant data. P411 is also a key residue in UVR8 binding to COP1. UVR8C27 is therefore structurally competent to function as a molecular switch for interaction of UVR8 with different binding partners since at higher free energies different structural conformations are being induced in this peptide. P411 has a key role for this function.
Retrieval of retrained and reconsolidated memories are associated with a distinct neural network
Authors: Bavassi Luz , Forcato Cecilia , Fernández Rodrigo S. , De Pino Gabriela , Pedreira María E. , Villarreal Mirta F.
Published: January 2019

Consolidated memories can persist from a single day to years, and persistence is improved by retraining or retrieval-mediated plasticity. One retrieval-based way to strengthen memory is the reconsolidation process. Strengthening occurs simply by the presentation of specific cues associated with the original learning. This enhancement function has a fundamental role in the maintenance of memory relevance in animals everyday life. In the present study, we made a step forward in the identification of brain correlates imprinted by the reconsolidation process studying the long-term neural consequences when the strengthened memory is stable again. To reach such a goal, we compared the retention of paired-associate memories that went through retraining process or were labilizated-reconsolidated. Using functional magnetic resonance imaging (fMRI), we studied the specific areas activated during retrieval and analyzed the functional connectivity of the whole brain associated with the event-related design. We used Graph Theory tools to analyze the global features of the network. We show that reconsolidated memories imprint a more locally efficient network that is better at exchanging information, compared with memories that were retrained or untreated. For the first time, we report a method to elucidate the neural footprints associated with a relevant function of memory reconsolidation.
Differences in the influenza-specific CD4 T cell immunodominance hierarchy and functional potential between children and young adults
Authors: Shannon Ian , White Chantelle L. , Murphy Amy , Qiu Xing , Treanor John J. , Nayak Jennifer L.
Published: January 2019

Studies of the B cell repertoire suggest that early childhood influenza infections profoundly shape later reactivity by creating an “imprint” that impacts subsequent vaccine responses and may provide lasting protection against influenza strains within the same viral group. However, there is little known about how these early childhood influenza exposures shape CD4 T cell reactivity later in life. To investigate the effect of age on influenza-specific CD4 T cell specificity and functionality, reactivity in cohorts of 2 year old children and young adult subjects was compared. Intracellular cytokine staining was used to determine the viral antigen specificity and expression levels of various cytokines following stimulation of peripheral blood mononuclear cells with complete peptide pools representing the entire translated sequences of the pH1, H3, HA-B, NP, and M1 proteins. We found that the influenza protein-specific immunodominance pattern in children differs from that in young adults, with much lower reactivity to the NP internal virion protein in young children. Alterations in CD4 T cell functionality were also noted, as responding CD4 T cells from children produced less IFNγ and were less likely to express multiple cytokines. These differences in the repertoire of influenza-specific CD4 T cells available for recall on influenza challenge in early childhood could possibly contribute to early imprinting of influenza-specific immunity as well as the increased susceptibility of children to this viral infection.
Discrete Structure of the Brain Rhythms
Authors: Perotti L. , DeVito J. , Bessis D. , Dabaghian Y.
Published: January 2019

Neuronal activity in the brain generates synchronous oscillations of the Local Field Potential (LFP). The traditional analyses of the LFPs are based on decomposing the signal into simpler components, such as sinusoidal harmonics. However, a common drawback of such methods is that the decomposition primitives are usually presumed from the onset, which may bias our understanding of the signal’s structure. Here, we introduce an alternative approach that allows an impartial, high resolution, hands-off decomposition of the brain waves into a small number of discrete, frequency-modulated oscillatory processes, which we call oscillons. In particular, we demonstrate that mouse hippocampal LFP contain a single oscillon that occupies the θ-frequency band and a couple of γ-oscillons that correspond, respectively, to slow and fast γ-waves. Since the oscillons were identified empirically, they may represent the actual, physical structure of synchronous oscillations in neuronal ensembles, whereas Fourier-defined “brain waves” are nothing but poorly resolved oscillons.
A cryogenic spin-torque memory element with precessional magnetization dynamics
Authors: Rowlands G. E. , Ryan C. A. , Ye L. , Rehm L. , Pinna D. , Kent A. D. , Ohki T. A.
Published: January 2019

We present a study of precessional magnetization switching in orthogonal spin-torque spin-valve devices at low temperatures. The samples consist of a spin-polarizing layer that is magnetized out-of-the film plane and an in-plane magnetized free and reference magnetic layer separated by non-magnetic metallic layers. We find coherent oscillations in the switching probability, characterized by high speed switching (~200 ps), error rates as low as 10−5 and decoherence effects at longer timescales (~1 ns). Our study, which is conducted over a wide range of parameter space (pulse amplitude and duration) with deep statistics, demonstrates that the switching dynamics are likely dominated by the action of the out-of-plane spin polarization, in contrast to in-plane spin-torque from the reference layer, as has been the case in most previous studies. Our results demonstrate that precessional spin-torque devices are well suited to a cryogenic environment, while at room temperature they have so far not exhibited coherent or reliable switching.
Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males
Authors: Cleophas Maartje C. P. , Ratter Jacqueline M. , Bekkering Siroon , Quintin Jessica , Schraa Kiki , Stroes Erik S. , Netea Mihai G. , Joosten Leo A. B.
Published: January 2019

Sodium butyrate is well-known for its immune-modulatory properties. Studies until now only focused on the in vitro effects of butyrate or assessed local effects in the gut upon butyrate administration. In this trial, we studied the systemic anti-inflammatory effects induced by sodium butyrate supplementation in humans. Nine healthy (Lean) and ten obese (metabolic syndrome group, MetSyn) males were given 4 grams sodium butyrate daily for 4 weeks. PBMCs were isolated before and after supplementation for direct stimulation experiments and induction of trained immunity by oxidized low-density lipoprotein (oxLDL), β-glucan, or Bacillus Calmette-Guérin vaccine (BCG). Butyrate supplementation moderately affected some of the cytokine responses in the MetSyn group. In the direct stimulation setup, effects of butyrate supplementation were limited. Interestingly, butyrate supplementation decreased oxLDL-induced trained immunity in the MetSyn group for LPS-induced IL-6 responses and Pam3CSK4-induced TNF-α responses. Induction of trained immunity by β-glucan was decreased by butyrate in the MetSyn group for Pam3CSK4-induced IL-10 production. In this study, while having only limited effects on the direct stimulation of cytokine production, butyrate supplementation significantly affected trained immunity in monocytes of obese individuals with metabolic complications. Therefore, oral butyrate supplementation may be beneficial in reducing the overall inflammatory status of circulating monocytes in patients with metabolic syndrome.
GLUT1 and GLUT3 involvement in anthocyanin gastric transport- Nanobased targeted approach
Authors: Oliveira Hélder , Roma-Rodrigues Catarina , Santos Ana , Veigas Bruno , Brás Natércia , Faria Ana , Calhau Conceição , de Freitas Victor , Baptista Pedro V. , Mateus Nuno , Fernandes Alexandra R. , Fernandes Iva
Published: January 2019

Anthocyanins may protect against a myriad of human diseases. However few studies have been conducted to evaluate their bioavailability so their absorption mechanism remains unclear. This study aimed to evaluate the role of two glucose transporters (GLUT1 and GLUT3) in anthocyanins absorption in the human gastric epithelial cells (MKN-28) by using gold nanoparticles to silence these transporters. Anthocyanins were purified from purple fleshed sweet potatoes and grape skin. Silencing of GLUT1 and/or GLUT3 mRNA was performed by adding AuNP@GLUT1 and/or AuNP@GLUT3 to MKN-28 cells. Downregulation of mRNA expression occurred concomitantly with the reduction in protein expression. Malvidin-3-O-glucoside (Mv3glc) transport was reduced in the presence of either AuNP@GLUT1 and AuNP@GLUT3, and when both transporters were blocked simultaneously. Peonidin-3-(6′-hydroxybenzoyl)-sophoroside-5-glucoside (Pn3HBsoph5glc) and Peonidin-3-(6′-hydroxybenzoyl-6″-caffeoyl)-sophoroside-5-glucoside (Pn3HBCsoph5glc) were assayed to verify the effect of the sugar moiety esterification at glucose B in transporter binding. Both pigments were transported with a lower transport efficiency compared to Mv3glc, probably due to steric hindrance of the more complex structures. Interestingly, for Pn3HBCsoph5glc although the only free glucose is at C5 and the inhibitory effect of the nanoparticles was also observed, reinforcing the importance of glucose on the transport regardless of its position or substitution pattern. The results support the involvement of GLUT1 and GLUT3 in the gastric absorption of anthocyanins.
TRPC5 ion channel permeation promotes weight gain in hypercholesterolaemic mice
Authors: Rode Baptiste , Yuldasheva Nadira Y. , Baxter Paul D. , Sedo Alicia , Ainscough Justin F. , Shires Michael , Kearney Mark T. , Bailey Marc A. , Wheatcroft Stephen B. , Beech David J.
Published: January 2019

Transient Receptor Potential Canonical 5 (TRPC5) is a subunit of a Ca2+-permeable non-selective cationic channel which negatively regulates adiponectin but not leptin in mice fed chow diet. Adiponectin is a major anti-inflammatory mediator and so we hypothesized an effect of TRPC5 on the inflammatory condition of atherosclerosis. Atherosclerosis was studied in aorta of ApoE−/− mice fed western-style diet. Inhibition of TRPC5 ion permeation was achieved by conditional transgenic expression of a dominant negative ion pore mutant of TRPC5 (DNT5). Gene expression analysis in adipose tissue suggested that DNT5 increases transcript expression for adiponectin while decreasing transcript expression of the inflammatory mediator Tnfα and potentially decreasing Il6, Il1β and Ccl2. Despite these differences there was mild or no reduction in plaque coverage in the aorta. Unexpectedly DNT5 caused highly significant reduction in body weight gain and reduced adipocyte size after 6 and 12 weeks of western-style diet. Steatosis and circulating lipids were unaffected but mild effects on regulators of lipogenesis could not be excluded, as indicated by small reductions in the expression of Srebp1c, Acaca, Scd1. The data suggest that TRPC5 ion channel permeation has little or no effect on atherosclerosis or steatosis but an unexpected major effect on weight gain.
Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures
Authors: van der Waals Lizet M. , Laoukili Jamila , Jongen Jennifer M. J. , Raats Danielle A. , Borel Rinkes Inne H. M. , Kranenburg Onno
Published: January 2019

Reactive oxygen species (ROS) function as second messengers in signal transduction, but high ROS levels can also cause cell death. MTH1 dephosphorylates oxidized nucleotides, thereby preventing their incorporation into DNA and protecting tumour cells from oxidative DNA damage. Inhibitors of MTH1 (TH588 and (S)-crizotinib) were shown to reduce cancer cell viability. However, the MTH1-dependency of the anti-cancer effects of these drugs has recently been questioned. Here, we have assessed anti-tumour effects of TH588 and (S)-crizotinib in patient-derived 3D colorectal cancer cultures. Hypoxia and reoxygenation – conditions that increase intracellular ROS levels – increased sensitivity to (S)-crizotinib, but not to TH588. (S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds. Furthermore, we show that both compounds induced DNA damage that could not be prevented by adding the ROS inhibitor N-acetyl-L-cysteine. Moreover, adding ROS-modulating compounds did not alter the reduction in viability in response to TH588 and (S)-crizotinib. We conclude that TH588 and (S)-crizotinib have very clear and distinct anti-tumour effects in 3D colorectal cancer cultures, but that these effects most likely occur through distinct and ROS-independent mechanisms.
A fast and adaptable method for high accuracy integration of the time-dependent Schrödinger equation
Authors: Wells Daniel , Quiney Harry
Published: January 2019

We present an adaptable, fast, and robust method for integrating the time-dependent Schrödinger equation. We apply the method to calculations of High Harmonic (HHG) and Above Threshold Ionisation (ATI) spectra for a single atomic electron in an intense laser field. Our approach implements the stabilized bi-conjugate gradient method (BiCG-STAB) for solving a sparse linear system to evolve the electronic wavefunction in time. The use of this established method makes the propagation scheme less restrictive compared to other schemes which may have particular requirements for the form of the equation, such as use of a three-point finite-difference approximation for spatial derivatives. Our method produces converged solutions significantly faster than existing methods, particularly if high accuracy is required. We demonstrate that this approach is suitable for a range of different parameters and show that in many circumstances significant gains can be made with the use of a fourth-order time propagator as opposed to the more common second-order Crank-Nicolson (CN) method.
A Disease Resistance Elicitor Laminarin Enhances Tea Defense against a Piercing Herbivore Empoasca (Matsumurasca) onukii Matsuda
Authors: Xin Zhaojun , Cai Xiaoming , Chen Shenglong , Luo Zongxiu , Bian Lei , Li Zhaoqun , Ge Lingang , Chen Zongmao
Published: January 2019

The tea plant (Camellia sinensis) suffers heavily from a harmful piercing pest, the tea green leafhopper (TLH)Empoasca(Matsumurasca)onukiiMatsuda. In the present study, we studied the effect of an efficient elicitor of plant disease resistance, the β-1,3-glucan laminarin, on the induced defense against TLH in tea plants. Defense responses elicited by laminarin in tea include the activation of mitogen-activated protein kinases and WRKY, the burst of H2O2, salicylic acid, and abscisic acid, and the accumulation of direct-defense chemicals (including chitinase, phenylalanine ammonia lyase, callose, polyphenol oxidase, and flavonol synthase), as well as the production of volatile compounds. The laminarin-treated tea plants reduced the performance of TLH and enhanced the attractiveness to the egg parasitoid wasp of TLH,Stethynium empoascaeSubba Rao. In the field experiment, laminarin application effectively reduced the number of TLH by attracting parasitoids. These results suggest that laminarin can induce protection against TLH by regulating signaling pathways in tea plant. Our study also proposes an environment friendly strategy for the integrated management of an economically important piercing pest.
An in situ combinatorial methodology to synthesize and screen chemical probes
Authors: van der Zouwen Antonie J. , Lohse Jonas , Wieske Lianne H. E. , Hohmann Katharina F. , van der Vlag Ramon , Witte Martin D.
Published: January 2019

Linking of reactive groups and ligands by imine chemistry provides chemical probes that label proteins of interest.
Atomic layer deposition of a SnO2 electron-transporting layer for planar perovskite solar cells with a power conversion efficiency of 18.3%
Authors: Jeong Seonghwa , Seo Seongrok , Park Hyoungmin , Shin Hyunjung
Published: January 2019

High-efficiency planar type perovskite solar cells were fabricated by atomic layer deposition (ALD) of SnO2 and subsequent annealing at 180 °C.
A perovskite oxide with a tunable pore-size derived from a general salt-template strategy as a highly efficient electrocatalyst for the oxygen evolution reaction
Authors: Yu Haoran , Chu Fuqiang , Zhou Xiao , Ji Junling , Liu Yang , Bu Yunfei , Kong Yong , Tao Yongxin , Li Yongxin , Qin Yong
Published: January 2019

A porous perovskite oxide is fabricated by an inorganic salt-template strategy, which exhibits remarkable performance for the oxygen evolution reaction.
Green synthesis of bismuth sulfide nanostructures with tunable morphologies and robust photoelectrochemical performance
Authors: Sun Bing , Feng Tiantian , Dong Jing , Li Xinle , Liu Xuanhe , Wu Jing , Ai Shiyun
Published: January 2019

Green synthesis of tunable Bi2S3 nanomaterials with tailored photoelectrochemical performance was proposed in aqueous medium without any organic reagents.
Effects of pressure on the structure and lattice dynamics of α-glycine: a combined experimental and theoretical study
Authors: Hinton Jasmine K. , Clarke Samantha M. , Steele Brad A. , Kuo I-Feng W. , Greenberg Eran , Prakapenka Vitali B. , Kunz Martin , Kroonblawd Matthew P. , Stavrou Elissaios
Published: January 2019

This concomitant experimental and theoretical study provides a definitive EOS for α-glycine up to the record pressure of 50 GPa.
Experimental and theoretical investigation of long-wavelength fluorescence emission in push–pull benzazoles: intramolecular proton transfer or charge transfer in the excited state?
Authors: Wiethaus Guilherme , Toldo Josene Maria , da Silveira Santos Fabiano , da Costa Duarte Rodrigo , Gonçalves Paulo Fernando Bruno , Rodembusch Fabiano Severo
Published: January 2019

ESIPT is disfavoured and charge-transfer emission, prior to ESIPT, seems to be responsible for long-emission wavelengths.
Variations of the elastic modulus perpendicular to the surface of rubrene bilayer films
Authors: Jhou Yen-Wei , Yang Chun-Kai , Sie Siang-Yu , Chiu Hsiang-Chih , Tsay Jyh-Shen
Published: January 2019

We propose a structural bilayer model successfully explaining the layered nature or characteristics of rubrene films.
Density-based descriptors and exciton analyses for visualizing and understanding the electronic structure of excited states
Authors: Mewes Stefanie A. , Dreuw Andreas
Published: January 2019

Quantum-chemical exciton analysis allows for quantitative, yet facile characterization of excited-state electronic structure and advanced multi-parameter benchmarking.
Na+-binding modes involved in thrombin's allosteric response as revealed by molecular dynamics simulations, correlation networks and Markov modeling
Authors: Xiao Jiajie , Salsbury Freddie R.
Published: January 2019

The monovalent sodium ion (Na+) is a critical modulator of thrombin.
Stimuli-responsive self-assembly of nanoparticles
Authors: Grzelczak Marek , Liz-Marzán Luis M. , Klajn Rafal
Published: January 2019

Ligand-protected nanoparticles can serve as attractive building blocks for constructing complex chemical systems.
An efficient copper-catalyzed synthesis of symmetrical bis(N-arylbenzamide) selenides and their conversion to hypervalent spirodiazaselenuranes and hydroxy congeners
Authors: Kadu Rahul , Batabyal Monojit , Kadyan Heena , Koner Apurba Lal , Kumar Sangit
Published: January 2019

A copper catalyzed efficient synthetic method has been developed to access bis(N-arylbenzamide) selenides from 2-halo-N-arylbenzamide substrates and disodium selenide in HMPA at 110 °C.
Solar-driven carbon dioxide fixation using photosynthetic semiconductor bio-hybrids
Authors: Cestellos-Blanco Stefano , Zhang Hao , Yang Peidong
Published: January 2019

Photosensitization of non-photosynthetic organisms by highly biocompatible gold nanoclusters achieves solar-driven carbon dioxide-to-chemical conversion. Further work explores cytoprotective materials and the photo-induced mechanism of charge transfer.
Ethanol electrooxidation on high-performance mesoporous ZnFe2O4-supported palladium nanoparticles
Authors: Kaedi Fariba , Yavari Zahra , Asmaei Milad , Abbasian Ahmad Reza , Noroozifar Meissam
Published: January 2019

As a catalyst for the electrooxidation of ethanol, a well-dispersed mesoporous ZnFe2O4 powder (ZnFe2O4MP) as a support for Pd nanoparticles (PdNPs) was fabricated using solution combustion synthesis, which is an easy and environmentally friendly method.
A Zn based metal organic framework as a heterogeneous catalyst for C–C bond formation reactions
Authors: Madasamy Kanagaraj , Kumaraguru Shanmugasundaram , Sankar Velayutham , Mannathan Subramaniyan , Kathiresan Murugavel
Published: January 2019

A Zn-Bp-BTC MOF was synthesized and characterized. The Zn-Bp-BTC MOF was successfully employed as a catalyst for Knoevenagel condensation, a multicomponent reaction and in benzimidazole synthesis.
A new strategy to activate graphite oxide as a high-performance cathode material for lithium-ion batteries
Authors: Xie Yongqiang , Li Wei , Hu Guorong , Peng Zhongdong , Cao Yanbing , Du Ke
Published: January 2019

Partially reduced graphite oxide was re-oxidized at a high potential of 5.2 V.
Fundamental scaling laws for the direct-write chemical vapor deposition of nanoscale features: modeling mass transport around a translating nanonozzle
Authors: Drahushuk Lee W. , Govind Rajan Ananth , Strano Michael S.
Published: January 2019

The nanometer placement of nanomaterials, such as nanoribbons and nanotubes, at a specific pitch and orientation on a surface, remains an unsolved fundamental problem in nanotechnology.
Electrochemically induced oxidative S–O coupling: synthesis of sulfonates from sulfonyl hydrazides and N-hydroxyimides or N-hydroxybenzotriazoles
Authors: Terent'ev Alexander O. , Mulina Olga M. , Parshin Vadim D. , Kokorekin Vladimir A. , Nikishin Gennady I.
Published: January 2019

A variety of sulfonates were synthesized from sulfonyl hydrazides and N-hydroxy compounds via electrochemically induced oxidative S–O bond formation.
All-inorganic lead-free perovskites for optoelectronic applications
Authors: Wang Xingtao , Zhang Taiyang , Lou Yongbing , Zhao Yixin
Published: January 2019

All inorganic lead free halide perovskites have successfully emerged as revolutionary optoelectronic semiconductors for use in various applications.
Cobalt(iii)-catalyzed C–H amidation of weakly coordinating sulfoxonium ylides and α-benzoylketene dithioacetals
Authors: Jia Qingqian , Kong Lingheng , Li Xingwei
Published: January 2019

Cobalt(iii)-catalyzed mild C–H amidation of weakly coordinating sulfoxonium ylides and α-benzoylketene dithioacetals has been realized.
Chiral and random arrangements of flavin chromophores along cyclic peptide nanotubes on gold influencing differently on surface potential and piezoelectricity
Authors: Kamano Yusuke , Tabata Yuki , Uji Hirotaka , Kimura Shunsaku
Published: January 2019

Two kinds of peptide nanotubes are prepared from cyclo(β-Asp(flavin)-β-alanine-β-alanine) (C3FAA) and cyclo(β-Asp(flavin)-ethylenediamine-succinic acid) (C3FES).
Control of phase separation behaviour of ionic liquid catalysts with reactants/products toward synthesis of long-chain wax esters at moderate temperatures
Authors: Kohno Yuki , Makino Takashi , Kanakubo Mitsuhiro
Published: January 2019

Phase separation of products from ionic liquid catalysts promotes the equilibrium reaction to prepare long-chain wax esters at moderate temperatures.
Development and use of a multiple-choice item writing flaws evaluation instrument in the context of general chemistry
Authors: Breakall Jared , Randles Christopher , Tasker Roy
Published: January 2019

Multiple-choice (MC) exams are common in undergraduate general chemistry courses in the United States and are known for being difficult to construct. With their extensive use in the general chemistry classroom, it is important to ensure that these exams are valid measures of what chemistry students know and can do. One threat to MC exam validity is the presence of flaws, known as item writing flaws, that can falsely inflate or deflate a student's performance on an exam, independent of their chemistry knowledge. Such flaws can disadvantage (or falsely advantage) students in their exam performance. Additionally, these flaws can introduce unwanted noise into exam data. With the numerous possible flaws that can be made during MC exam creation, it can be difficult to recognize (and avoid) these flaws when creating MC general chemistry exams. In this study a rubric, known as the Item Writing Flaws Evaluation Instrument (IWFEI), has been created that can be used to identify item writing flaws in MC exams. The instrument was developed based on a review of the item writing literature and was tested for inter-rater reliability using general chemistry exam items. The instrument was found to have a high degree of inter-rater reliability with an overall percent agreement of 91.8% and a Krippendorff Alpha of 0.836. Using the IWFEI in an analysis of 1019 general chemistry MC exam items, it was found that 83% of items contained at least one item writing flaw with the most common flaw being the inclusion of implausible distractors. From the results of this study, an instrument has been developed that can be used in both research and teaching settings. As the IWFEI is used in these settings we envision an improvement in MC exam development practice and quality.
A phosphorus-doped carbon sphere supported CoP nanocatalyst for electrochemical hydrogen evolution
Authors: Gao Sen , Yang Maoxia , Li Shaomin , Xia Ji , Mei Jun , Xie Song , Liu Hao
Published: January 2019

An efficient CoP-based HER electrocatalyst was prepared by simple impregnation and phosphorization.
Conversion of dinitrogen to ammonia on Ru atoms supported on boron sheets: a DFT study
Authors: Liu Chuangwei , Li Qinye , Zhang Jie , Jin Yonggang , MacFarlane Douglas R. , Sun Chenghua
Published: January 2019

By first-principles computations, nitrogen becomes activated via distal pathway on the single Ru-atom-embedded two boron monolayers, exhibiting relatively low reaction energy barriers of 0.42 and 0.44 eV, respectively.
Thermally evaporated two-dimensional SnS as an efficient and stable electron collection interlayer for inverted planar perovskite solar cells
Authors: Coskun Hikmet , Isikgor Furkan H. , Chen Zhihui , Imran Muhammad , Li Bichen , Xu Qinghua , Ouyang Jianyong
Published: January 2019

SnS can replace commonly used BCP as the interlayer in inverted PSCs due to its lower cost and improved stability.
Collagen-based breathable, humidity-ultrastable and degradable on-skin device
Authors: Ke Le , Wang Yaping , Ye Xiaoxia , Luo Wei , Huang Xin , Shi Bi
Published: January 2019

Realizing simultaneous high breathability and humidity stability is a critical challenge for on-skin devices. We here developed a breathable, humidity-ultrastable and degradable on-skin device by using cowskin as the substrate, which exhibited ultrahigh water-vapor permeability, good humidity stability, degradability and detection capability.
Enhanced photoluminescence and thermal properties due to size mismatch in Mg2TixGe1−xO4:Mn4+ deep-red phosphors
Authors: Peng Lingling , Chen Wenbo , Cao Shixiu , Liu Bitao , Han Tao , Zhao Lei , Zhao Cong , Li Feng , Li Xiaomin
Published: January 2019

In this study, a warm red phosphor based on the substitution of Ge4+ for Ti4+ in the lattice of Mg2TixGe1−xO4:Mn4+ was prepared by a solid-state reaction route.
PtAu3 cluster complexes with narrow-band emissions for solution-processed organic light emitting diodes
Authors: Natarajan Nagarajan , Shi Lin-Xi , Xiao Hui , Wang Jin-Yun , Zhang Li-Yi , Zhang Xu , Chen Zhong-Ning
Published: January 2019

Solution-processed OLEDs based on PtAu3 cluster complexes show high-efficiency electroluminescence with narrow emission bands through enhancing the co-planarity between their aromatic acetylides and platinum(ii) coordination square planes.
A nanostructured NiO/cubic SiC p–n heterojunction photoanode for enhanced solar water splitting
Authors: Jian Jingxin , Shi Yuchen , Ekeroth Sebastian , Keraudy Julien , Syväjärvi Mikael , Yakimova Rositsa , Helmersson Ulf , Sun Jianwu
Published: January 2019

A 3C-SiC/NiO p–n heterojunction photoanode exhibits a substantially improved photoelectrochemical water-splitting performance in terms of photocurrent, onset potential and fill-factor.
Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome
Authors: Thompson Rachel , Bonne Gisèle , Missier Paolo , Lochmüller Hanns
Published: January 2019

Despite recent scientific advances, most rare genetic diseases — including most neuromuscular diseases — do not currently have curative gene-based therapies available. However, in some cases, such as vitamin, cofactor or enzyme deficiencies, channelopathies and disorders of the neuromuscular junction, a confirmed genetic diagnosis provides guidance on treatment, with drugs available that may significantly alter the disease course, improve functional ability and extend life expectancy. Nevertheless, many treatable patients remain undiagnosed or do not receive treatment even after genetic diagnosis. The growth of computer-aided genetic analysis systems that enable clinicians to diagnose their undiagnosed patients has not yet been matched by genetics-based decision-support systems for treatment guidance. Generating a ‘treatabolome’ of treatable variants and the evidence for the treatment has the potential to increase treatment rates for treatable conditions. Here, we use the congenital myasthenic syndromes (CMS), a group of clinically and genetically heterogeneous but frequently treatable neuromuscular conditions, to illustrate the steps in the creation of a treatabolome for rare inherited diseases. We perform a systematic review of the evidence for pharmacological treatment of each CMS type, gathering evidence from 207 studies of over 1000 patients and stratifying by genetic defect, as treatment varies depending on the underlying cause. We assess the strength and quality of the evidence and create a dataset that provides the foundation for a computer-aided system to enable clinicians to gain easier access to information about treatable variants and the evidence they need to consider.
Hidden or missing outflows in highly obscured galaxy nuclei?
Authors: Falstad N. , Hallqvist F. , Aalto S. , König S. , Muller S. , Aladro R. , Combes F. , Evans A. S. , Fuller G. A. , Gallagher J. S. , García-Burillo S. , González-Alfonso E. , Greve T. R. , Henkel C. , Imanishi M. , Izumi T. , Mangum J. G. , Martín S. , Privon G. C. , Sakamoto K. , Veilleux S. , van der Werf P. P.
Published: January 2019

Context. Understanding the nuclear growth and feedback processes in galaxies requires investigating their often obscured central regions. One way to do this is to use (sub)millimeter line emission from vibrationally excited HCN (HCN-vib), which is thought to trace warm and highly enshrouded galaxy nuclei. It has been suggested that the most intense HCN-vib emission from a galaxy is connected to a phase of nuclear growth that occurs before the nuclear feedback processes have been fully developed.

Aims. We aim to investigate if there is a connection between the presence of strong HCN-vib emission and the development of feedback in (ultra)luminous infrared galaxies ((U)LIRGs).

Methods. We collected literature and archival data to compare the luminosities of rotational lines of HCN-vib, normalized to the total infrared luminosity, to the median velocities of 119 μm OH absorption lines, potentially indicating outflows, in a total of 17 (U)LIRGs.

Results. The most HCN-vib luminous systems all lack signatures of significant molecular outflows in the far-infrared OH absorption lines. However, at least some of the systems with bright HCN-vib emission have fast and collimated outflows that can be seen in spectral lines at longer wavelengths, including in millimeter emission lines of CO and HCN (in its vibrational ground state) and in radio absorption lines of OH.

Conclusions. We conclude that the galaxy nuclei with the highest LHCN − vib/LIR do not drive wide-angle outflows that are detectable using the median velocities of far-infrared OH absorption lines. This is possibly because of an orientation effect in which sources oriented in such a way that their outflows are not along our line of sight also radiate a smaller proportion of their infrared luminosity in our direction. It could also be that massive wide-angle outflows destroy the deeply embedded regions responsible for bright HCN-vib emission, so that the two phenomena cannot coexist. This would strengthen the idea that vibrationally excited HCN traces a heavily obscured stage of evolution before nuclear feedback mechanisms are fully developed.