bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormalities of signal transduction networks in chronic schizophrenia
Authors: McGuire Jennifer L. , Depasquale Erica A. , Funk Adam J. , O’Donnovan Sinead M. , Hasselfeld Kathryn , Marwaha Shruti , Hammond John H. , Hartounian Vahram , Meador-Woodruff James H. , Meller Jarek , McCullumsmith Robert E.
Published: August 2017

Schizophrenia is a serious neuropsychiatric disorder characterized by disruptions of brain cell metabolism, microstructure, and neurotransmission. All of these processes require coordination of multiple kinase-mediated signaling events. We hypothesize that imbalances in kinase activity propagate through an interconnected network of intracellular signaling with potential to simultaneously contribute to many or all of the observed deficits in schizophrenia. We established a workflow distinguishing schizophrenia-altered kinases in anterior cingulate cortex using a previously published kinome array data set. We compared schizophrenia-altered kinases to haloperidol-altered kinases, and identified systems, functions, and regulators predicted using pathway analyses. We used kinase inhibitors with the kinome array to test hypotheses about imbalance in signaling and conducted preliminary studies of kinase proteins, phosphoproteins, and activity for kinases of interest. We investigated schizophrenia-associated single nucleotide polymorphisms in one of these kinases, AKT, for genotype-dependent changes in AKT protein or activity. Kinome analyses identified new kinases as well as some previously implicated in schizophrenia. These results were not explained by chronic antipsychotic treatment. Kinases identified in our analyses aligned with cytoskeletal arrangement and molecular trafficking. Of the kinases we investigated further, AKT and (unexpectedly) JNK, showed the most dysregulation in the anterior cingulate cortex of schizophrenia subjects. Changes in kinase activity did not correspond to protein or phosphoprotein levels. We also show that AKT single nucleotide polymorphism rs1130214, previously associated with schizophrenia, influenced enzyme activity but not protein or phosphoprotein levels. Our data indicate subtle changes in kinase activity and regulation across an interlinked kinase network, suggesting signaling imbalances underlie the core symptoms of schizophrenia.
CRISPR-Cas9 mediated one-step disabling of pancreatogenesis in pigs
Authors: Wu Jun , Vilarino Marcela , Suzuki Keiichiro , Okamura Daiji , Bogliotti Yanina Soledad , Park Insung , Rowe Joan , McNabb Bret , Ross Pablo Juan , Belmonte Juan Carlos Izpisua
Published: August 2017

Genome editing using programmable nucleases has revolutionized biomedical research. CRISPR-Cas9 mediated zygote genome editing enables high efficient production of knockout animals suitable for studying development and relevant human diseases. Here we report efficient disabling pancreatogenesis in pig embryos via zygotic co-delivery of Cas9 mRNA and dual sgRNAs targeting the PDX1 gene, which when combined with chimeric-competent human pluriopotent stem cells may serve as a suitable platform for the xeno-generation of human tissues and organs in pigs.
Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies
Authors: Kullberg Joel , Hedström Anders , Brandberg John , Strand Robin , Johansson Lars , Bergström Göran , Ahlström Håkan
Published: August 2017

Computed Tomography (CT) allows detailed studies of body composition and its association with metabolic and cardiovascular disease. The purpose of this work was to develop and validate automated and manual image processing techniques for detailed and efficient analysis of body composition from CT data. The study comprised 107 subjects examined in the Swedish CArdioPulmonary BioImage Study (SCAPIS) using a 3-slice CT protocol covering liver, abdomen, and thighs. Algorithms were developed for automated assessment of liver attenuation, visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, thigh muscles, subcutaneous, subfascial (SFAT) and intermuscular adipose tissue. These were validated using manual reference measurements. SFAT was studied in selected subjects were the fascia lata could be visually identified (approx. 5%). In addition, precision of manual measurements of intra- (IPAT) and retroperitoneal adipose tissue (RPAT) and deep- and superficial SAT was evaluated using repeated measurements. Automated measurements correlated strongly to manual reference measurements. The SFAT depot showed the weakest correlation (r = 0.744). Automated VAT and SAT measurements were slightly, but significantly overestimated (≤4.6%, p ≤ 0.001). Manual segmentation of abdominal sub-depots showed high repeatability (CV ≤ 8.1%, r ≥ 0.930). We conclude that the low dose CT-scanning and automated analysis makes the setup suitable for large-scale studies.
Controlled self-organization of polymer nanopatterns over large areas
Authors: Eryilmaz Ilknur Hatice , Mohanraj John , Dal Zilio Simone , Fraleoni-Morgera Alessandro
Published: August 2017

Self-assembly methods allow to obtain ordered patterns on surfaces with exquisite precision, but often lack in effectiveness over large areas. Here we report on the realization of hierarchically ordered polymethylmethacrylate (PMMA) nanofibres and nanodots over large areas from solution via a fast, easy and low-cost method named ASB-SANS, based on a ternary solution that is cast on the substrate. Simple changes to the ternary solution composition allow to control the transition from nanofibres to nanodots, via a wide range of intermediate topologies. The ternary solution includes the material to be patterned, a liquid solvent and a solid substance able to sublimate. The analysis of the fibres/dots width and inter-pattern distance variations with respect to the ratio between the solution components suggests that the macromolecular chains mobility in the solidified sublimating substance follows Zimm-like models (mobility of macromolecules in diluted liquid solutions). A qualitative explanation of the self-assembly phenomena originating the observed nanopatterns is given. Finally, ASB-SANS-generated PMMA nanodots arrays have been used as lithographic masks for a silicon substrate and submitted to Inductively Coupled Plasma-Reactive Ion Etching (ICP-RIE). As a result, nanopillars with remarkably high aspect ratios have been achieved over areas as large as several millimeters square, highlighting an interesting potential of ASB-SANS in practical applications like photon trapping in photovoltaic cells, surface-enhanced sensors, plasmonics.
ROS-induced Oxidative Injury involved in Pathogenesis of Fungal Keratitis via p38 MAPK Activation
Authors: Hua Xia , Chi Wei , Su Long , Li Jin , Zhang Zongduan , Yuan Xiaoyong
Published: August 2017

This study was to explore the mechanism by which reactive oxygen species (ROS)-induced oxidative stress involved in the pathogenesis of fungal keratitis using an in vivo experimental keratitis mouse model and an in vitro culture model of human corneal epithelial cells (HCECs). Compared to normal control mice and HCECs, ROS production was markedly increased in fungal corneas and HCECs exposed to Candida albicans, accompanied by p38 mitogen-activated protein kinases (MAPK) activation. Increased products of oxidative markers, malondialdehyde (MDA), 4–hydroxynonenal (HNE), mitochondria DNA 8-OHdG and aconitase-2 were observed in fungal infected corneas and HCECs. Fungal infection also increased the mRNA expression and protein production of heme oxygenase-1 (HMOX1) and cyclooxygenase-2 (COX2), with suppressed levels of antioxidant enzymes, superoxide dismutase-1 (SOD1), glutathione peroxidase-1 (GPx1) and peroxiredoxin-4 (PRDX4). Interestingly, the levels of ROS, oxidative markers and oxygenases were significantly reduced by co-cultured p38 inhibitor SB203580. Furthermore, SB203580 restored the levels of antioxidant enzymes suppressed by fungus. Our findings demonstrated for the first time that ROS-induced oxidative injury is involved in pathogenesis of fungal keratitis via p38 MAPK pathway, suggesting the novel therapeutic targets for the potential treatment of fungal keratitis.
Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology
Authors: Bertoni Martino , Kiefer Florian , Biasini Marco , Bordoli Lorenza , Schwede Torsten
Published: August 2017

Cellular processes often depend on interactions between proteins and the formation of macromolecular complexes. The impairment of such interactions can lead to deregulation of pathways resulting in disease states, and it is hence crucial to gain insights into the nature of macromolecular assemblies. Detailed structural knowledge about complexes and protein-protein interactions is growing, but experimentally determined three-dimensional multimeric assemblies are outnumbered by complexes supported by non-structural experimental evidence. Here, we aim to fill this gap by modeling multimeric structures by homology, only using amino acid sequences to infer the stoichiometry and the overall structure of the assembly. We ask which properties of proteins within a family can assist in the prediction of correct quaternary structure. Specifically, we introduce a description of protein-protein interface conservation as a function of evolutionary distance to reduce the noise in deep multiple sequence alignments. We also define a distance measure to structurally compare homologous multimeric protein complexes. This allows us to hierarchically cluster protein structures and quantify the diversity of alternative biological assemblies known today. We find that a combination of conservation scores, structural clustering, and classical interface descriptors, can improve the selection of homologous protein templates leading to reliable models of protein complexes.
Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani
Authors: Saini Shalini , Bharati Kavita , Shaha Chandrima , Mukhopadhyay Chinmay K.
Published: August 2017

Micronutrients are essential for survival and growth for all the organisms including pathogens. In this manuscript, we report that zinc (Zn) chelator N,N,N’,N’-tetrakis(2-pyridinylmethyl)-1,2-ethylenediamine (TPEN) affects growth and viability of intracellular pathogen Leishmania donovani (LD) by a concentration and time dependent manner. Simultaneous addition of zinc salt reverses the effect of TPEN. Further experiments provide evidence of apoptosis-like death of the parasite due to Zn-depletion. TPEN treatment enhances caspase-like activity suggesting increase in apoptosis-like events in LD. Specific inhibitors of cathepsin B and Endoclease G block TPEN-induced leishmanial death. Evidences show involvement of reactive oxygen species (ROS) potentially of extra-mitochondrial origin in TPEN-induced LD death. Pentavalent antimonials remained the prime source of treatment against leishmaniasis for several decades; however, antimony-resistant Leishmania is now common source of the disease. We also reveal that Zn-depletion can promote apoptosis-like death in antimony-resistant parasites. In summary, we present a new finding about the role of zinc in the survival of drug sensitive and antimony-resistant LD.
Differences between the most used equations in BAT-human studies to estimate parameters of skin temperature in young lean men
Authors: Martinez-Tellez Borja , Sanchez-Delgado Guillermo , Acosta Francisco M. , Alcantara Juan M. A. , Boon Mariëtte R. , Rensen Patrick C. N. , Ruiz Jonatan R.
Published: August 2017

Cold exposure is necessary to activate human brown adipose tissue (BAT), resulting in heat production. Skin temperature is an indirect measure to monitor the body’s reaction to cold. The aim of this research was to study whether the most used equations to estimate parameters of skin temperature in BAT-human studies measure the same values of temperature in young lean men (n = 11: 23.4 ± 0.5 years, fat mass: 19.9 ± 1.2%). Skin temperature was measured with 26 ibuttons at 1-minute intervals in warm and cold room conditions. We used 12 equations to estimate parameters of mean, proximal, and distal skin temperature as well as skin temperature gradients. Data were analysed with Temperatus software. Significant differences were found across equations to measure the same parameters of skin temperature in warm and cold room conditions, hampering comparison across studies. Based on these findings, we suggest to use a set of 14 ibuttons at anatomical positions reported by ISO STANDARD 9886:2004 plus five ibuttons placed on the right supraclavicular fossa, right middle clavicular bone, right middle upper forearm, right top of forefinger, and right upper chest.
Natural (∆9-THC) and synthetic (JWH-018) cannabinoids induce seizures by acting through the cannabinoid CB1 receptor
Authors: Malyshevskaya Olga , Aritake Kosuke , Kaushik Mahesh K. , Uchiyama Nahoko , Cherasse Yoan , Kikura-Hanajiri Ruri , Urade Yoshihiro
Published: August 2017

Natural cannabinoids and their synthetic substitutes are the most widely used recreational drugs. Numerous clinical cases describe acute toxic symptoms and neurological consequences following inhalation of the mixture of synthetic cannabinoids known as “Spice.” Here we report that an intraperitoneal administration of the natural cannabinoid Δ9-tetrahydrocannabinol (10 mg/kg), one of the main constituent of marijuana, or the synthetic cannabinoid JWH-018 (2.5 mg/kg) triggered electrographic seizures in mice, recorded by electroencephalography and videography. Administration of JWH-018 (1.5, 2.5 and 5 mg/kg) increased seizure spikes dose-dependently. Pretreatment of mice with AM-251 (5 mg/kg), a cannabinoid receptor 1-selective antagonist, completely prevented cannabinoid-induced seizures. These data imply that abuse of cannabinoids can be dangerous and represents an emerging public health threat. Additionally, our data strongly suggest that AM-251 could be used as a crucial prophylactic therapy for cannabinoid-induced seizures or similar life-threatening conditions.
Metamaterial Perfect Absorber Analyzed by a Meta-cavity Model Consisting of Multilayer Metasurfaces
Authors: Bhattarai Khagendra , Silva Sinhara , Song Kun , Urbas Augustine , Lee Sang Jun , Ku Zahyun , Zhou Jiangfeng
Published: August 2017

We demonstrate that the metamaterial perfect absorber behaves as a meta-cavity bounded between a resonant metasurface and a metallic thin-film reflector. The perfect absorption is achieved by the Fabry-Perot cavity resonance via multiple reflections between the “quasi-open” boundary of resonator and the “close” boundary of reflector. The characteristic features including angle independence, ultra-thin thickness and strong field localization can be well explained by this meta-cavity model. With this model, metamaterial perfect absorber can be redefined as a meta-cavity exhibiting high Q-factor, strong field enhancement and extremely high photonic density of states, thereby promising novel applications for high performance sensor, infrared photodetector and cavity quantum electrodynamics devices.
NF-κB inhibitors, unique γ-pyranol-γ-lactams with sulfide and sulfoxide moieties from Hawaiian plant Lycopodiella cernua derived fungus Paraphaeosphaeria neglecta FT462
Authors: Li Chun-Shun , Sarotti Ariel M. , Huang Peng , Dang Uyen T. , Hurdle Julian G. , Kondratyuk Tamara P. , Pezzuto John M. , Turkson James , Cao Shugeng
Published: August 2017

LC-UV/MS-based metabolomic analysis of the Hawaiian endophytic fungus Paraphaeosphaeria neglecta FT462 led to the identification of four unique mercaptolactated γ-pyranol–γ-lactams, paraphaeosphaerides E–H (1–4) together with one γ-lactone (5) and the methyl ester of compound 2 (11). The structures of the new compounds (1–5 and 11) were elucidated through the analysis of HRMS and NMR spectroscopic data. The absolute configuration was determined by chemical reactions with sodium borohydride, hydrogen peroxide, α-methoxy-α-(trifluoromethyl)phenylacetyl chlorides (Mosher reagents), and DP4 + NMR calculations. All the compounds were tested against STAT3, A2780 and A2780cisR cancer cell lines, E. coli JW2496, and NF-κB. Compounds 1 and 3 strongly inhibited NF-κB with IC50 values of 7.1 and 1.5 μM, respectively.
Focusing analytes from 50 μL into 500 pL: On-chip focusing from large sample volumes using isotachophoresis
Authors: van Kooten Xander F. , Truman-Rosentsvit Marianna , Kaigala Govind V. , Bercovici Moran
Published: August 2017

The use of on-chip isotachophoresis assays for diagnostic applications is often limited by the small volumes of standard microfluidic channels. Overcoming this limitation is particularly important for detection of ‘discrete’ biological targets (such as bacteria) at low concentrations, where the volume of processed liquid in a standard microchannel might not contain any targets. We present a novel microfluidic chip that enables ITP focusing of target analytes from initial sample volumes of 50 μL into a concentrated zone with a volume of 500 pL, corresponding to a 100,000-fold increase in mean concentration, and a 300,000-fold increase in peak concentration. We present design considerations for limiting sample dispersion in such large-volume focusing (LVF) chips and discuss the trade-off between assay time and Joule heating, which ultimately governs the scalability of LVF designs. Finally, we demonstrate a 100-fold improvement of ITP focusing performance in the LVF chip as compared to conventional microchannels, and apply this enhancement to achieve highly sensitive detection of both molecular targets (DNA, down to 10 fM) and whole bacteria (down to 100 cfu/mL).
Metal concentrations and distributions in the human olfactory bulb in Parkinson’s disease
Authors: Gardner Bronwen , Dieriks Birger V. , Cameron Steve , Mendis Lakshini H. S. , Turner Clinton , Faull Richard L. M. , Curtis Maurice A.
Published: August 2017

In Parkinson’s disease (PD), the olfactory bulb is typically the first region in the body to accumulate alpha-synuclein aggregates. This pathology is linked to decreased olfactory ability, which becomes apparent before any motor symptoms occur, and may be due to a local metal imbalance. Metal concentrations were investigated in post-mortem olfactory bulbs and tracts from 17 human subjects. Iron (p < 0.05) and sodium (p < 0.01) concentrations were elevated in the PD olfactory bulb. Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation. Zinc was high in these regions, and free zinc was detected in Lewy bodies, mitochondria, and lipofuscin of cells in the anterior olfactory nucleus. Increased iron and sodium in the human PD olfactory bulb may relate to the loss of olfactory function. In contrast, colocalization of free zinc and alpha-synuclein in the anterior olfactory nucleus implicate zinc in PD pathogenesis.
Origins of Dirac cone formation in AB3 and A3B (A, B = C, Si, and Ge) binary monolayers
Authors: Qin Xuming , Wu Yuqin , Liu Yi , Chi Baoqian , Li Xiaowu , Wang Yin , Zhao Xinluo
Published: August 2017

Compared to the pure two-dimensional (2D) graphene and silicene, the binary 2D system silagraphenes, consisting of both C and Si atoms, possess more diverse electronic structures depending on their various chemical stoichiometry and arrangement pattern of binary components. By performing calculations with both density functional theory and a Tight-binding model, we elucidated the formation of Dirac cone (DC) band structures in SiC3 and Si3C as well as their analogous binary monolayers including SiGe3, Si3Ge, GeC3, and Ge3C. A “ring coupling” mechanism, referring to the couplings among the six ring atoms, was proposed to explain the origin of DCs in AB3 and A3B binary systems, based on which we discussed the methods tuning the SiC3 systems into self-doped systems. The first-principles quantum transport calculations by non-equilibrium Green’s function method combined with density functional theory showed that the electron conductance of SiC3 and Si3C lie between those of graphene and silicene, proportional to the carbon concentrations. Understanding the DC formation mechanism and electronic properties sheds light onto the design principles for novel Fermi Dirac systems used in nanoelectronic devices.
Infrared probe of pseudogap in electron-doped Sr2IrO4
Authors: Seo J. H. , Ahn G. H. , Song S. J. , Chen X. , Wilson S. D. , Moon S. J.
Published: August 2017

We report on infrared spectroscopy experiments on the electronic response in (Sr1−x
La
x
)2IrO4 (x = 0, 0.021, and 0.067). Our data show that electron doping induced by La substitution leads to an insulator-to-metal transition. The evolution of the electronic structure across the transition reveals the robustness of the strong electronic correlations against the electron doping. The conductivity data of the metallic compound show the signature of the pseudogap that bears close similarity to the analogous studies of the pseudogap in the underdoped cuprates. While the low energy conductivity of the metallic compound is barely frequency dependent, the formation of the pseudogap is revealed by the gradual suppression of the featureless conductivity below a threshold frequency of about 17 meV. The threshold structure develops below about 100 K which is in the vicinity of the onset of the short-range antiferromagnetic order. Our results demonstrate that the electronic correlations play a crucial role in the anomalous charge dynamics in the (Sr1−x
La
x
)2IrO4 system.
A mutation in the melon Vacuolar Protein Sorting 41prevents systemic infection of Cucumber mosaic virus
Authors: Giner Ana , Pascual Laura , Bourgeois Michael , Gyetvai Gabor , Rios Pablo , Picó Belén , Troadec Christelle , Bendahmane Abdel , Garcia-Mas Jordi , Martín-Hernández Ana Montserrat
Published: August 2017

In the melon exotic accession PI 161375, the gene cmv1, confers recessive resistance to Cucumber mosaic virus (CMV) strains of subgroup II. cmv1 prevents the systemic infection by restricting the virus to the bundle sheath cells and impeding viral loading to the phloem. Here we report the fine mapping and cloning of cmv1. Screening of an F2 population reduced the cmv1 region to a 132 Kb interval that includes a Vacuolar Protein Sorting 41 gene. CmVPS41 is conserved among plants, animals and yeast and is required for post-Golgi vesicle trafficking towards the vacuole. We have validated CmVPS41 as the gene responsible for the resistance, both by generating CMV susceptible transgenic melon plants, expressing the susceptible allele in the resistant cultivar and by characterizing CmVPS41 TILLING mutants with reduced susceptibility to CMV. Finally, a core collection of 52 melon accessions allowed us to identify a single amino acid substitution (L348R) as the only polymorphism associated with the resistant phenotype. CmVPS41 is the first natural recessive resistance gene found to be involved in viral transport and its cellular function suggests that CMV might use CmVPS41 for its own transport towards the phloem.
Prevalence, Awareness and Associated Risk Factors of Diabetes among Adults in Xi’an, China
Authors: Hu Meiqin , Wan Yi , Yu Lifen , Yuan Jing , Ma Yonghong , Hou Bin , Jiang Xun , Shang Lei
Published: August 2017

The study aimed to investigate the prevalence, awareness, treatment and glycaemic control of diabetes and its associated risk factors among adults in Xi’an, China. We collected data among participants aged 18 years or older through a self-developed questionnaire and an additional health examination. A total of 8150 participants were included, with an overall prevalence of diabetes of 8.0%. Among 655 participants with diabetes, 52.5% were aware they had diabetes, 48.1% took antidiabetic treatment, and 19.1% had their fasting blood glucose level at less than 7.0 mmol/l. Older age, lower educational level, higher body mass index, larger waist circumference, having an unhealthy diet and having more comorbidities were positively associated with the risk of diabetes. Participants who were older, who had higher education and who had more comorbidities were more aware that they had diabetes. Being older age, having higher education and having more comorbidities were also factors for better treatment. Participants who were older were more likely to have their glucose level controlled. The prevalence of diabetes among adults in Xi’an is high, with suboptimal awareness, treatment, and glycaemic control rates. Comprehensive integrated strategies based on risk factors should be implemented to improve the prevention and glycaemic control of diabetes.
A Metabolomics Signature Linked To Liver Fibrosis In The Serum Of Transplanted Hepatitis C Patients
Authors: Cano Ainara , Mariño Zoe , Millet Oscar , Martínez-Arranz Ibon , Navasa Miquel , Falcón-Pérez Juan Manuel , Pérez-Cormenzana Miriam , Caballería Joan , Embade Nieves , Forns Xavier , Bosch Jaume , Castro Azucena , Mato José María
Published: August 2017

Liver fibrosis must be evaluated in patients with hepatitis C virus (HCV) after liver transplantation because its severity affects their prognosis and the recurrence of HCV. Since invasive biopsy is still the gold standard to identify patients at risk of graft loss from rapid fibrosis progression, it becomes crucial the development of new accurate, non-invasive methods that allow repetitive examination of the patients. Therefore, we have developed a non-invasive, accurate model to distinguish those patients with different liver fibrosis stages. Two hundred and three patients with HCV were histologically classified (METAVIR) into five categories of fibrosis one year after liver transplantation. In this cross-sectional study, patients at fibrosis stages F0-F1 (n = 134) were categorised as “slow fibrosers” and F2-F4 (n = 69) as “rapid fibrosers”. Chloroform/methanol serum extracts were analysed by reverse ultra-high performance liquid chromatography coupled to mass spectrometry. A diagnostic model was built through linear discriminant analyses. An algorithm consisting of two sphingomyelins and two phosphatidylcholines accurately classifies rapid and slow fibrosers after transplantation. The proposed model yielded an AUROC of 0.92, 71% sensitivity, 85% specificity, and 84% accuracy. Moreover, specific bile acids and sphingomyelins increased notably along with liver fibrosis severity, differentiating between rapid and slow fibrosers.
Structures of Medicago truncatula L-Histidinol Dehydrogenase Show Rearrangements Required for NAD+ Binding and the Cofactor Positioned to Accept a Hydride
Authors: Ruszkowski Milosz , Dauter Zbigniew
Published: August 2017

Plants, lower eukaryotes, bacteria, and archaebacteria synthesise L-histidine (His) in a similar, multistep pathway that is absent in mammals. This makes the His biosynthetic route a promising target for herbicides, antifungal agents, and antibiotics. The last enzyme of the pathway, bifunctional L-histidinol dehydrogenase (HDH, EC 1.1.1.23), catalyses two oxidation reactions: from L-histidinol (HOL) to L-histidinaldehyde and from L-histidinaldehyde to His. Over the course of the reaction, HDH utilises two molecules of NAD+ as the hydride acceptor. The object of this study was the HDH enzyme from the model legume plant, Medicago truncatula (MtHDH). Three crystal structures complexed with imidazole, HOL, and His with NAD+ provided in-depth insights into the enzyme architecture, its active site, and the cofactor binding mode. The overall structure of MtHDH is similar to the two bacterial orthologues whose three-dimensional structures have been determined. The three snapshots, with the MtHDH enzyme captured in different states, visualise structural rearrangements that allow for NAD+ binding for the first time. Furthermore, the MtHDH complex with His and NAD+ displays the cofactor molecule situated in a way that would allow for a hydride transfer.
Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment
Authors: Yeku Oladapo O. , Purdon Terence J. , Koneru Mythili , Spriggs David , Brentjens Renier J.
Published: August 2017

Chimeric antigen receptor (CAR) T cell therapy has shown limited efficacy for the management of solid tumor malignancies. In ovarian cancer, this is in part due to an immunosuppressive cytokine and cellular tumor microenvironment which suppresses adoptively transferred T cells. We engineered an armored CAR T cell capable of constitutive secretion of IL-12, and delineate the mechanisms via which these CAR T cells overcome a hostile tumor microenvironment. In this report, we demonstrate enhanced proliferation, decreased apoptosis and increased cytotoxicity in the presence of immunosuppressive ascites. In vivo, we show enhanced expansion and CAR T cell antitumor efficacy, culminating in improvement in survival in a syngeneic model of ovarian peritoneal carcinomatosis. Armored CAR T cells mediated depletion of tumor associated macrophages and resisted endogenous PD-L1-induced inhibition. These findings highlight the role of the inhibitory microenvironment and how CAR T cells can be further engineered to maintain efficacy.
Erosion potential of the Yangtze Delta under sediment starvation and climate change
Authors: Yang H. F. , Yang S. L. , Xu K. H. , Wu H. , Shi B. W. , Zhu Q. , Zhang W. X. , Yang Z.
Published: August 2017

Deltas are widely threatened by sediment starvation and climate change. Erosion potential is an important indicator of delta vulnerability. Here, we investigate the erosion potential of the Yangtze Delta. We found that over the past half century the Yangtze’s sediment discharge has decreased by 80% due to the construction of >50,000 dams and soil conservation, whereas the wind speed and wave height in the delta region have increased by 5–7%, and the sea level has risen at a rate of 3 mm/yr. According to hydrodynamic measurements and analyses of seabed sediments, the period when bed shear stress due to combined current-wave action under normal weather conditions exceeds the critical bed shear stress for erosion (τcr) accounts for 63% of the total observed period on average and can reach 100% during peak storms. This explains why net erosion has occurred in some areas of the subaqueous delta. We also found that the increase with depth ofτcris very gradual in the uppermost several metres of the depositional sequence. We therefore expect that the Yangtze subaqueous delta will experience continuous erosion under sediment starvation and climate change in the next decades of this century or even a few centuries.
Investigation of possible phase transition of the frustrated spin-1/2 J
1-J
2-J
3 model on the square lattice
Authors: Hu Ai-Yuan , Wang Huai-Yu
Published: August 2017

The frustrated spin-1/2 J1-J2-J3 antiferromagnet with exchange anisotropy on the two-dimensional square lattice is investigated. The exchange anisotropy is presented by η with 0 ≤ η < 1. The effects of the J1, J2, J3 and anisotropy on the possible phase transition of the Néel state and collinear state are studied comprehensively. Our results indicate that for J3 > 0 there are upper limits $${J}_{3}^{c}$$

J

3

c

and η
c
values. When 0 < J3 ≤ $${J}_{3}^{c}$$

J

3

c

and 0 ≤ η ≤ η
c
, the Néel and collinear states have the same order-disorder transition point at J2 = J1/2. Nevertheless, when the J3 and η values beyond the upper limits, it is a paramagnetic phase at J2 = J1/2. For J3 < 0, in the case of 0 ≤ η < 1, the two states always have the same critical temperature as long as J2 = J1/2. Therefore, for J2 = J1/2, under such parameters, a first-order phase transition between the two states for these two cases below the critical temperatures may occur. When J2 ≠ J1/2, the Néel and collinear states may also exist, while they have different critical temperatures. When J2 > J1/2, a first-order phase transition between the two states may also occur. However, for J2 < J1/2, the Néel state is always more stable than the collinear state.
RGMa inhibition with human monoclonal antibodies promotes regeneration, plasticity and repair, and attenuates neuropathic pain after spinal cord injury
Authors: Mothe Andrea J. , Tassew Nardos G. , Shabanzadeh Alirezha P. , Penheiro Romeo , Vigouroux Robin J. , Huang Lili , Grinnell Christine , Cui Yi-Fang , Fung Emma , Monnier Philippe P. , Mueller Bernhard K. , Tator Charles H.
Published: August 2017

Traumatic spinal cord injury (SCI) causes a cascade of degenerative events including cell death, axonal damage, and the upregulation of inhibitory molecules which prevent regeneration and limit recovery. Repulsive guidance molecule A (RGMa) is a potent neurite growth inhibitor in the central nervous system, exerting its repulsive activity by binding the Neogenin receptor. Here, we show for the first time that inhibitory RGMa is markedly upregulated in multiple cell types after clinically relevant impact-compression SCI in rats, and importantly, also in the injured human spinal cord. To neutralize inhibitory RGMa, clinically relevant human monoclonal antibodies were systemically administered after acute SCI, and were detected in serum, cerebrospinal fluid, and in the injured tissue. Rats treated with RGMa blocking antibodies showed significantly improved recovery of motor function and gait. Furthermore, RGMa blocking antibodies promoted neuronal survival, and enhanced the plasticity of descending serotonergic pathways and corticospinal tract axonal regeneration. RGMa antibody also attenuated neuropathic pain responses, which was associated with fewer activated microglia and reduced CGRP expression in the dorsal horn caudal to the lesion. These results show the therapeutic potential of the first human RGMa antibody for SCI and uncovers a new role for the RGMa/Neogenin pathway on neuropathic pain.
Global-local processing relates to spatial and verbal processing: implications for sex differences in cognition
Authors: Pletzer Belinda , Scheuringer Andrea , Scherndl Thomas
Published: August 2017

Sex differences have been reported for a variety of cognitive tasks and related to the use of different cognitive processing styles in men and women. It was recently argued that these processing styles share some characteristics across tasks, i.e. male approaches are oriented towards holistic stimulus aspects and female approaches are oriented towards stimulus details. In that respect, sex-dependent cognitive processing styles share similarities with attentional global-local processing. A direct relationship between cognitive processing and global-local processing has however not been previously established. In the present study, 49 men and 44 women completed a Navon paradigm and a Kimchi Palmer task as well as a navigation task and a verbal fluency task with the goal to relate the global advantage (GA) effect as a measure of global processing to holistic processing styles in both tasks. Indeed participants with larger GA effects displayed more holistic processing during spatial navigation and phonemic fluency. However, the relationship to cognitive processing styles was modulated by the specific condition of the Navon paradigm, as well as the sex of participants. Thus, different types of global-local processing play different roles for cognitive processing in men and women.
Role of Smad3 and p38 Signalling in Cigarette Smoke-induced CFTR and BK dysfunction in Primary Human Bronchial Airway Epithelial Cells
Authors: Sailland Juliette , Grosche Astrid , Baumlin Nathalie , Dennis John S. , Schmid Andreas , Krick Stefanie , Salathe Matthias
Published: August 2017

Mucociliary clearance (MCC) is a major airway host defence system that is impaired in patients with smoking-associated chronic bronchitis. This dysfunction is partially related to a decrease of airway surface liquid (ASL) volume that is in part regulated by apically expressed cystic fibrosis transmembrane conductance regulator (CFTR) and large-conductance, Ca2+-activated, and voltage dependent K+ (BK) channels. Here, data from human bronchial epithelial cells (HBEC) confirm that cigarette smoke not only downregulates CFTR activity but also inhibits BK channel function, thereby causing ASL depletion. Inhibition of signalling pathways involved in cigarette smoke-induced channel dysfunction reveals that CFTR activity is downregulated via Smad3 signalling whereas BK activity is decreased via the p38 cascade. In addition, pre-treatment with pirfenidone, a drug presently used to inhibit TGF-β signalling in idiopathic pulmonary fibrosis, ameliorated BK dysfunction and ASL volume loss. Taken together, our results highlight the importance of not only CFTR but also BK channel function in maintaining ASL homeostasis and emphasize the possibility that pirfenidone could be employed as a novel therapeutic regimen to help improve MCC in smoking-related chronic bronchitis.
N-P Fertilization Stimulates Anaerobic Selenium Reduction in an End-Pit Lake
Authors: Luek Andreas , Rowan David J. , Rasmussen Joseph B.
Published: August 2017

Selenium (Se), an essential micro nutrient, is toxic to aquatic life at slightly higher water concentrations. Watersheds receiving leachate from selenium rich sources require large-scale, long-term treatment to mitigate Se toxicity. We applied the principles of anaerobic bacterial bioreactors, previously successful in small scale Se mitigation, to a whole end-pit lake ecosystem. Fertilization of the lake with N and P increased primary production, creating a meromictic, anoxic layer, and enhanced the habitat for locally present, anaerobic, Se and sulfur reducing bacteria. Within two years, Se concentrations were reduced ten-fold, reaching water-quality guideline values. The successful experiment demonstrated a novel treatment of large volumes of Se-contaminated water, and introduced an inexpensive method to mitigate a persistent aquatic pollutant of global concern.
Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract
Authors: Guo Song-He , Wang Hai-Fang , Nian Zhi-Gang , Wang Yi-Dan , Zeng Qiu-Yao , Zhang Ge
Published: August 2017

Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.
Effect of Surface Plasmon Coupling to Optical Cavity Modes on the Field Enhancement and Spectral Response of Dimer-Based sensors
Authors: Alrasheed Salma , Di Fabrizio Enzo
Published: August 2017

We present a theoretical approach to narrow the plasmon linewidth and enhance the near-field intensity at a plasmonic dimer gap (hot spot) through coupling the electric localized surface plasmon (LSP) resonance of a silver hemispherical dimer with the resonant modes of a Fabry-Perot (FP) cavity. The strong coupling is demonstrated by the large anticrossing in the reflection spectra and a Rabi splitting of 76 meV. Up to 2-fold enhancement increase can be achieved compared to that without using the cavity. Such high field enhancement has potential applications in optics, including sensors and high resolution imaging devices. In addition, the resonance splitting allows for greater flexibility in using the same array at different wavelengths. We then further propose a practical design to realize such a device and include dimers of different shapes and materials.
First-principles calculations on Fe-Pt nanoclusters of various morphologies
Authors: Platonenko Alexander , Piskunov Sergei , Bocharov Dmitry , Zhukovskii Yuri F. , Evarestov Robert A. , Bellucci Stefano
Published: August 2017

Bimetallic FePt nanoparticles with L10 structure are attracting a lot of attention due to their high magnetocrystalline anisotropy and high coercivity what makes them potential material for storage of ultra-high density magnetic data. FePt nanoclusters are considered also as nanocatalysts for growth of carbon nanotubes of different chiralities. Using the DFT-LCAO CRYSTAL14 code, we have performed large-scale spin-polarized calculations on 19 different polyhedral structures of FePt nanoparticles in order to estimate which icosahedral or hcp-structured morphology is the energetically more preferable. Surface energy calculations of all aforementioned nanoparticles indicate that the global minimum corresponds to the nanocluster possessing the icosahedron “onion-like” structure and Fe43Pt104 morphology where the outer layer consists of Pt atoms. The presence of the Pt-enriched layer around FePt core explains high oxidation resistance and environmental stability, both observed experimentally.
Tailoring the thermal conductivity of the powder bed in Electron Beam Melting (EBM) Additive Manufacturing
Authors: Smith C. J. , Tammas-Williams S. , Hernandez-Nava E. , Todd I.
Published: August 2017

Metallic powder bed additive manufacturing is capable of producing complex, functional parts by repeatedly depositing thin layers of powder particles atop of each other whilst selectively melting the corresponding part cross-section into each layer. A weakness with this approach arises when melting overhanging features, which have no prior melted material directly beneath them. This is due to the lower thermal conductivity of the powder relative to solid material, which as a result leads to an accumulation of heat and thus distortion. The Electron Beam Melting (EBM) process alleviates this to some extent as the powder must first be sintered (by the beam itself) before it is melted, which results in the added benefit of increasing the thermal conductivity. This study thus sought to investigate to what extent the thermal conductivity of local regions in a titanium Ti-6Al-4V powder bed could be varied by imparting more energy from the beam. Thermal diffusivity and density measurements were taken of the resulting sintered samples, which ranged from being loosely to very well consolidated. It was found that the calculated thermal conductivity at two temperatures, 40 and 730 °C, was more than doubled over the range of input energies explored.
M2-like macrophages in the fibrotic liver protect mice against lethal insults through conferring apoptosis resistance to hepatocytes
Authors: Bai Li , Liu Xin , Zheng Qingfen , Kong Ming , Zhang Xiaohui , Hu Richard , Lou Jinli , Ren Feng , Chen Yu , Zheng Sujun , Liu Shuang , Han Yuan-Ping , Duan Zhongping , Pandol Stephen J.
Published: August 2017

Acute injury in the setting of liver fibrosis is an interesting and still unsettled issue. Most recently, several prominent studies have indicated the favourable effects of liver fibrosis against acute insults. Nevertheless, the underlying mechanisms governing this hepatoprotection remain obscure. In the present study, we hypothesized that macrophages and their M1/M2 activation critically involve in the hepatoprotection conferred by liver fibrosis. Our findings demonstrated that liver fibrosis manifested a beneficial role for host survival and apoptosis resistance. Hepatoprotection in the fibrotic liver was tightly related to innate immune tolerance. Macrophages undertook crucial but divergent roles in homeostasis and fibrosis: depleting macrophages in control mice protected from acute insult; conversely, depleting macrophages in fibrotic liver weakened the hepatoprotection and gave rise to exacerbated liver injury upon insult. The contradictory effects of macrophages can be ascribed, to a great extent, to the heterogeneity in macrophage activation. Macrophages in fibrotic mice exhibited M2-preponderant activation, which was not the case in acutely injured liver. Adoptive transfer of M2-like macrophages conferred control mice conspicuous protection against insult. In vitro, M2-polarized macrophages protected hepatocytes against apoptosis. Together, M2-like macrophages in fibrotic liver exert the protective effects against lethal insults through conferring apoptosis resistance to hepatocytes.
An ultra-compact rejection filter based on spoof surface plasmon polaritons
Authors: Zhao Shumin , Zhang Hao Chi , Zhao Jiahao , Tang Wen Xuan
Published: August 2017

In this paper, we propose a scheme to construct a new type of ultra-compact rejection filter by loading split-ring resonators (SRRs) on the transmission line of spoof surface plasmon polaritons (SPPs). From the dispersion analysis of the spoof SPP transmission line with and without the SRR loading, we clearly reveal the mechanism of the rejection characteristic for this compact filter. Meanwhile, we fabricate two spoof SPPs waveguides loaded with different amounts of metamaterials particles, and experimentally test them using an Agilent Vector Network Analyzer (VNA) and a homemade near-field scanning system. Both the simulated and measured results agree well with our theoretical analysis and demonstrate the excellent filtering characteristics of our design. The isolation of both filters can be less than −20 dB, and even reach −40 dB at rejection frequencies. The proposed rejection and stop-band filters show important potentials to develop integrated plasmonic functional devices and circuits at microwave and terahertz frequencies.
Determination of malachite green, crystal violet, brilliant green and methylene blue by micro-cloud-point extraction and nonlinear laser wave-mixing detection interfaced to micellar capillary electrophoresis
Authors: Pradel Jean Sebastien , Tong William G.
Published: August 2017

A laser wave-mixing CE detection method is reported for separation and detection of malachite green (MG), crystal violet (CV), brilliant green (BG), methylene blue (MB), and the leuco-metabolites of MG and CV residues in aquacultures.
An in-tether chiral center modulates the proapoptotic activity of the KLA peptide
Authors: Li Jingxu , Hu Kuan , Chen Hailing , Wu YuJie , Chen Longjian , Yin Feng , Tian Yuan , Li Zigang
Published: August 2017

We have utilized a novel in-tether chiral center induced helicity strategy (CIH) to develop a potent apoptosis inducer based on apoptotic KLA peptide. For our constructed peptides, the CIH-KLA-(R) epimer exhibited superior cellular uptakes and special mitochondrial targeting when compared with its S counterpart.
Rational design of NIR-emitting iridium(iii) complexes for multimodal phosphorescence imaging of mitochondria under two-photon excitation
Authors: Jin Chengzhi , Guan Ruilin , Wu Jingheng , Yuan Bo , Wang Lili , Huang Juanjuan , Wang Hui , Ji Liangnian , Chao Hui
Published: August 2017

A series of NIR-emitting Ir(iii) complexes were developed for multimodal imaging of mitochondria under two-photon excitation.
Retraction: Facile synthesis of hierarchical Mn3O4 superstructures and efficient catalytic performance
Authors: Simpson Anna
Published: August 2017

Retraction of ‘Facile synthesis of hierarchical Mn3O4 superstructures and efficient catalytic performance’ by Zhixiang Hu et al., Phys. Chem. Chem. Phys., 2016, 18, 26602–26608.
Cyclometalated Pt(ii) complexes with a bidentate Schiff-base ligand displaying unexpected cis/trans isomerism: synthesis, structures and electronic properties
Authors: Poma A. , Forni A. , Baldoli C. , Mussini P. R. , Bossi A.
Published: August 2017

Unexpectedcis/transisomerism in a bis-cyclometalated Pt(ii) complex is investigated by NMR, X-ray diffraction, optical, electrochemical and computational methods and rationalized.