bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphocyte activation gene 3 (Lag3) expression is increased in prion infections but does not modify disease progression
Authors: Liu Yingjun , Sorce Silvia , Nuvolone Mario , Domange Julie , Aguzzi Adriano 
Published: September 2018

AbstractPrion diseases, Alzheimer’s disease and Parkinson’s disease (PD) are fatal degenerative disorders that share common neuropathological and biochemical features, including the aggregation of pathological protein conformers. Lymphocyte activation gene 3 (Lag3, also known as CD223) is a member of the immunoglobulin superfamily of receptors expressed on peripheral immune cells, microglia and neurons, which serves as a receptor for α-synuclein aggregates in PD. Here we examined the possible role of Lag3 in the pathogenesis of prion diseases. Through quantitative real-time PCR and RNA-sequencing, we found that the expression levels of Lag3 were relatively low in the adult mouse brains, yet its expression was increased after prion infection. However, we failed finding significant differences regarding the incubation time, PrPSc load, neurodegeneration, astrocyte and microglia reactions and inflammatory gene expression between the Lag3 knockout mice and wild-type littermate controls after prion infection. We conclude that loss of Lag3 has no significant influence on prion disease pathogenesis. Considering that Lag3 is an immune checkpoint receptor, our results suggest that immune checkpoint inhibition (an increasingly prevalent therapeutic modality against many types of cancer) might not exert positive or negative effects on the progression of prion diseases.
Developmental transitions in amygdala PKC isoforms and AMPA receptor expression associated with threat memory in infant rats
Authors: Opendak Maya , Zanca Roseanna M. , Anane Eben , Serrano Peter A. , Sullivan Regina M. 
Published: September 2018

AbstractAlthough infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our results show that memory-related molecules did not change in pups too young to learn threat (PN8) but were activated in pups old enough to learn (PN12), with increased PKMζ-PKCι/λ and GluA2 similar to that observed in adult memory, but with an uncharacteristic decrease in GluA1. This molecular signature and behavioral avoidance of the conditioned odor was recapitulated in PN8 pups injected with CORT before conditioning to precociously induce learning. Blocking learning via CORT inhibition in older pups (PN12) blocked the expression of these molecules. PN16 pups showed a more adult-like molecular cascade of increased PKMζ-PKCι/λ and GluA1–2. Finally, at all ages, zeta inhibitory peptide (ZIP) infusions into the amygdala 24 hr after conditioning blocked memory. Together, these results identify unique features of memory processes across early development: AMPAR subunits GluA1/2 and PKC isoform expression are differentially used, which may contribute to mechanisms of early life forgetting.
Design of polarization-insensitive high-visibility silicon-on-insulator quantum interferometer
Authors: Zhang Jingjing , Guo Kai , Gao Minghong , Gao Yang , Yang Junbo 
Published: September 2018

AbstractWe based on integrated silicon-on-insulator platforms design the key components of an on-chip interferometer, beam splitter and directional coupler included, valid in high-visibility interference at telecommunication wavelengths. Special attention is given to the equal-proportion beam splitting and directional coupling, which is achieved by carefully designing the geometric dimension of multi-mode interferometer structure. The proposed interferometer facilitates low loss, broad operating bandwidth, anticipated large tolerance on size variation induced in fabrication procedures, based on a particular wafer with silicon layer thickness of 320 nm. The most highlight property of polarization-insensitive, enables the path-selective qubits generation for bi-polarization that further makes possible quantum key distribution using high dimensional protocols. We numerically demonstrate interference at 1550 nm with visibilities of 99.50% and 93.99% for transverse-electric and transverse-magnetic polarization, respectively, revealing that the proposed interferometer structure is well capable of on-chip optical control especially in quantum optics regime.
Arc/Arg3.1 has an activity-regulated interaction with PICK1 that results in altered spatial dynamics
Authors: Goo Brandee M. S. S. , Sanstrum Bethany J. , Holden Diana Z. Y. , Yu Yi , James Nicholas G. 
Published: September 2018

AbstractActivity-regulated cytoskeleton-associated protein (Arc; also known as Arg3.1) is an immediate early gene product that is transcribed in dendritic spines and, to date, has been best characterized as a positive regulator of AMPAR endocytosis during long-term depression (LTD) through interaction with endocytic proteins. Here, we show that protein interacting with C terminal kinase 1 (PICK1), a protein known to bind to the GluA2 subunit of AMPARs and associated with AMPAR trafficking, was pulled-down from brain homogenates and synaptosomes when using Arc as immobilized bait. Fluctuation and FLIM-FRET-Phasor analysis revealed direct interaction between these proteins when co-expressed that was increased under depolarizing conditions in live cells. At the plasma membrane, Arc-mCherry oligomerization was found to be concentration dependent. Additionally, co-expression of Arc-mCherry and EGFP-PICK1 followed by depolarizing conditions resulted in significant increases in the number and size of puncta containing both proteins. Furthermore, we identified the Arc binding region to be the first 126 amino acids of the PICK1 BAR domain. Overall, our data support a novel interaction and model where PICK1 mediates Arc regulation of AMPARs particularly under depolarizing conditions.
Development of multi-layered and multi-sensitive polymeric nanocontainers for cancer therapy: in vitro evaluation
Authors: Toniolo Gianluca , Efthimiadou Eleni K. , Kordas George , Chatgilialoglu Chryssostomos 
Published: September 2018

AbstractNanoscale drug delivery systems represent a promising strategy to treat cancer and to overcome the side effects of chemotherapy. In particular, hollow polymeric nanocontainers have attracted great interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of stimuli-responsive materials capable of responding to the biochemical alterations of the tumour microenvironment. Here are reported the synthesis, characterization and in vitro evaluation of a three-stimuli-sensitive hollow nanocontainer consisting of three different shells, each one sensitive to a specific tumoral stimulus: in order pH, temperature and reducing environment. To test its properties, daunorubicin was used as a model drug, for which the nanocontainers exhibited excellent encapsulation ability. The in vitro drug release behaviour was studied under different conditions, where the system proved capable of responding to the selected tumoral stimuli by releasing a larger amount of drug than in physiological environment. The hollow system itself showed negligible cytotoxicity but the loaded nanocontainers and free drug showed identical cytotoxicity and intracellular localization. Therefore, this formulation can be considered as a promising platform to develop an injectable delivery system capable of improving systematic toxicity without affecting or reducing the activity of the encapsulated drug.
Pyrophosphate inhibits gluconeogenesis by restricting UDP-glucose formation in vivo
Authors: Ferjani Ali , Kawade Kensuke , Asaoka Mariko , Oikawa Akira , Okada Takashi , Mochizuki Atsushi , Maeshima Masayoshi , Hirai Masami Yokota , Saito Kazuki , Tsukaya Hirokazu 
Published: September 2018

AbstractPyrophosphate (PPi) is produced by anabolic reactions and serves as an energy donor in the cytosol of plant cells; however, its accumulation to toxic levels disrupts several common biosynthetic pathways and is lethal. Before acquiring photosynthetic capacity, young seedlings must endure a short but critical heterotrophic period, during which they are nourished solely by sugar produced from seed reserves by the anabolic process of gluconeogenesis. Previously, we reported that excess PPi in H+-PPase-knockout fugu5 mutants of Arabidopsis thaliana severely compromised gluconeogenesis. However, the precise metabolic target of PPi inhibition in vivo remained elusive. Here, CE-TOF MS analyses of major metabolites characteristic of gluconeogenesis from seed lipids showed that the Glc6P;Fru6P level significantly increased and that Glc1P level was consistently somewhat higher in fugu5 compared to wild type. In contrast, the UDP-Glc level decreased significantly in the mutants. Importantly, specific removal of PPi in fugu5, and thus in AVP1pro:IPP1 transgenic lines, restored the Glc1P and the Glc6P;Fru6P levels, increased the UDP-Glc level ~2.0-fold, and subsequently increased sucrose synthesis. Given the reversible nature of the Glc1P/UDP-Glc reaction, our results indicate that UGP-Glc pyrophosphorylase is the major target when excess PPi exerts inhibitory effects in vivo. To validate our findings, we analyzed metabolite responses using a mathematical theory called structural sensitivity analysis (SSA), in which the responses of concentrations in reaction systems to perturbations in enzyme activity are determined from the structure of the network alone. A comparison of our experimental data with the results of pure structural theory predicted the existence of unknown reactions as the necessary condition for the above metabolic profiles, and confirmed the above results. Our data support the notion that H+-PPase plays a pivotal role in cytosolic PPi homeostasis in plant cells. We propose that the combination of metabolomics and SSA is powerful when seeking to identify and predict metabolic targets in living cells.
A Frequency Independent Framework for Synthesis of Programmable Non-reciprocal Networks
Authors: Lu Ruochen , Krol Jack , Gao Liuqing , Gong Songbin 
Published: September 2018

AbstractPassive and linear nonreciprocal networks at microwave frequencies hold great promises in enabling new front-end architectures for wireless communication systems. Their non-reciprocity has been achieved by disrupting the time-reversal symmetry using various forms of biasing schemes, but only over a limited frequency range. Here we demonstrate a framework for synthesizing theoretically frequency-independent multi-port nonreciprocal networks. The framework is highly expandable and can have an arbitrary number of ports while simultaneously sustaining balanced performance and providing unprecedented programmability of non-reciprocity. A 4-port circulator based on such a framework is implemented and tested to produce a broadband nonreciprocal performance from 10 MHz to 900 MHz with a temporal switching effort at 23.8 MHz. With the combination of broad bandwidth, low temporal effort, and high programmability, the framework could inspire new ways of implementing multiple input multiple output (MIMO) communication systems for 5G.
Riemerella anatipestifer AS87_RS09170 gene is responsible for biotin synthesis, bacterial morphology and virulence
Authors: Ren Xiaomei , Wang Xiaolan , Shi Huoying , Zhang Xuemei , Chen Zongchao , Malhi Kanwar Kumar , Ding Chan , Yu Shengqing 
Published: September 2018

AbstractRiemerella anatipestifer is a bacterial pathogen responsible for major economic losses within the duck industry. Recent studies have revealed that biotin biosynthesis is critical for the bacterium’s survival and virulence. We previously found that R. anatipestifer AS87_RS09170, a putative bioF gene, is important for bacterial virulence. In the present study, we characterized the AS87_RS09170 gene in R. anatipestifer strain Yb2. Sequence analysis indicated that the AS87_RS09170 gene is highly conserved among R. anatipestifer strains; the deduced protein harbored the conserved pyridoxal 5′-phosphate binding pocket of 8-amino-7-oxononanoate synthase. Western blot analysis demonstrated that the biotin-dependent enzyme was present in smaller quantities in the mutant strain Yb2ΔbioF compared to that of the wide-type strain Yb2, suggesting that the biotin biosynthesis was defective. The mutant strain Yb2ΔbioF displayed a decreased growth rate at the exponential phase in tryptic soy broth culture and in BeaverBeads Streptavidin treated tryptic soy broth culture, but recovered when biotin was supplemented. In addition, the mutant strain Yb2ΔbioF showed an enhanced biofilm formation, as well as increased adhesion and invasion capacities to duck embryo fibroblasts. Moreover, the mutant strain Yb2ΔbioF exhibited irregular shapes with budding vegetations and relatively thickened cell walls under scanning and transmission electron microscope observation, as well as a reduced capacity to establish systemic infection in a duck infection model. These results provide the first evidence that the R. anatipestifer AS87_RS09170 gene is responsible for biotin synthesis, bacterial morphology and virulence.
Cationic domains in particle-forming and assembly-deficient HBV core antigens capture mammalian RNA that stimulates Th1-biased antibody responses by DNA vaccination
Authors: Krieger Jana , Stifter Katja , Riedl Petra , Schirmbeck Reinhold 
Published: September 2018

AbstractThe HBV core protein self-assembles into particles and encapsidates immune-stimulatory bacterial RNA through a cationic COOH-terminal (C150–183) domain. To investigate if different cationic domains have an impact on the endogenous RNA-binding of HBV-C antigens in mammalian cells, we developed a strep-tag (st) based expression/purification system for HBV-C/RNA antigens in vector-transfected HEK-293 cells. We showed that HBV-stC but not HBV-stC149 particles (lacking the cationic domain) capture low amounts of mammalian RNA. Prevention of specific phosphorylation in cationic domains, either by exchanging the serine residues S155, S162 and S170 with alanines (HBV-stCAAA) or by exchanging the entire cationic domain with a HIV-tat48–57-like sequence (HBV-stC149tat) enhanced the encapsidation of RNA into mutant core particles. Particle-bound mammalian RNA functioned as TLR-7 ligand and induced a Th1-biased humoral immunity in B6 but not in TLR-7−/− mice by exogenous (protein) and endogenous (DNA) vaccines. Compared to core particles, binding of mammalian RNA to freely exposed cationic domains in assembly-deficient antigens was enhanced. However, RNA bound to non-particulate antigens unleash its Th1-stimulating adjuvant activity by DNA- but not protein-based vaccination. Mammalian RNAs targeted by an endogenously expressed antigen thus function as a natural adjuvant in the host that facilitates priming of Th1-biased immune responses by DNA-based immunization.
Risk factors of chronic kidney diseases in Chinese adults with type 2 diabetes
Authors: Yang Lin , Chu Tsun Kit , Lian Jinxiao , Lo Cheuk Wai , Lau Pak Ki , Nan Hairong , Liang Jun 
Published: September 2018

AbstractIn this study we conducted a cross sectional study to comprehensively evaluated the risk factors of chronic kidney disease (CKD) in a large sample of Chinese adults under primary care for type 2 diabetes mellitus (T2DM). We investigated the risk factors associated with the prevalence of CKD in adults with T2DM, who were enrolled in the Risk Factor Assessment and Management Programme for Patients with Diabetes Mellitus (RAMP-DM) of Hong Kong from July 2014 to June 2017. We collected the individual data of 31,574 subjects, with mean age of 63.0 (±10.8) years and mean DM duration of 7.4 (±6.4) years. Of them 9,386 (29.7%) had CKD and 7,452 (23.6%) had micro- or macro-albuminuria. After adjustment for multiple demographic and lifestyle confounders, we identified several modifiable risk factors associated with higher rate of CKD: obesity (OR = 1.54), current smoking (OR = 1.33), higher systolic blood pressure (OR = 1.01), dyslipidemia (OR = 1.32 and 0.61 for triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)), hyperglycemia (OR = 1.11 for HbA1c), diabetic retinopathy (OR = 1.36 and 2.60 for non-sight and sight threatening retinopathy), and stroke (OR = 1.43). The risk factors of lower dialytic blood pressure and coronary heart disease were identified only in men, whereas peripheral arterial disease only in women. In conclusion, several modifiable and gender specific risk factors were significantly associated with higher prevalence of CKD in Chinese adults with T2DM. The high-risk populations identified in this study shall receive regular screening for renal functions to achieve better patient management in primary care settings.
Computational analysis of the amino acid interactions that promote or decrease protein solubility
Authors: Hou Qingzhen , Bourgeas Raphaël , Pucci Fabrizio , Rooman Marianne 
Published: September 2018

AbstractThe solubility of globular proteins is a basic biophysical property that is usually a prerequisite for their functioning. In this study, we probed the solubility of globular proteins with the help of the statistical potential formalism, in view of objectifying the connection of solubility with structural and energetic properties and of the solubility-dependence of specific amino acid interactions. We started by setting up two independent datasets containing either soluble or aggregation-prone proteins with known structures. From these two datasets, we computed solubility-dependent distance potentials that are by construction biased towards the solubility of the proteins from which they are derived. Their analysis showed the clear preference of amino acid interactions such as Lys-containing salt bridges and aliphatic interactions to promote protein solubility, whereas others such as aromatic, His-π, cation-π, amino-π and anion-π interactions rather tend to reduce it. These results indicate that interactions involving delocalized π-electrons favor aggregation, unlike those involving no (or few) dispersion forces. Furthermore, using our potentials derived from either highly or weakly soluble proteins to compute protein folding free energies, we found that the difference between these two energies correlates better with solubility than other properties analyzed before such as protein length, isoelectric point and aliphatic index. This is, to the best of our knowledge, the first comprehensive in silico study of the impact of residue-residue interactions on protein solubility properties.The results of this analysis provide new insights that will facilitate future rational protein design applications aimed at modulating the solubility of targeted proteins.
The role of scene summary statistics in object recognition
Authors: Lauer Tim , Cornelissen Tim H. W. , Draschkow Dejan , Willenbockel Verena , Võ Melissa L.-H. 
Published: September 2018

AbstractObjects that are semantically related to the visual scene context are typically better recognized than unrelated objects. While context effects on object recognition are well studied, the question which particular visual information of an object’s surroundings modulates its semantic processing is still unresolved. Typically, one would expect contextual influences to arise from high-level, semantic components of a scene but what if even low-level features could modulate object processing? Here, we generated seemingly meaningless textures of real-world scenes, which preserved similar summary statistics but discarded spatial layout information. In Experiment 1, participants categorized such textures better than colour controls that lacked higher-order scene statistics while original scenes resulted in the highest performance. In Experiment 2, participants recognized briefly presented consistent objects on scenes significantly better than inconsistent objects, whereas on textures, consistent objects were recognized only slightly more accurately. In Experiment 3, we recorded event-related potentials and observed a pronounced mid-central negativity in the N300/N400 time windows for inconsistent relative to consistent objects on scenes. Critically, inconsistent objects on textures also triggered N300/N400 effects with a comparable time course, though less pronounced. Our results suggest that a scene’s low-level features contribute to the effective processing of objects in complex real-world environments.
Facial expression and oxytocin as possible markers of positive emotions in horses
Authors: Lansade Léa , Nowak Raymond , Lainé Anne-Lyse , Leterrier Christine , Bonneau Coralie , Parias Céline , Bertin Aline 
Published: September 2018

AbstractBehavioural and physiological markers of discrete positive emotions remain little investigated in animals. To characterise new markers in horses, we used tactile stimulations to induce emotional situation of contrasting valence. In the Gentle grooming group (G, N = 13) horses were gently groomed during 11 sessions on the body areas they appreciated the most. Horses in the Standard grooming group (S, N = 14) were groomed using a fixed procedure, reported to induce avoidance reactions in some horses. At session 11, G horses expressed significantly more contact-seeking behaviours than S horses, which expressed significantly more avoidance behaviours. This result suggests positive emotions in G horses and negative emotions in S horses. Blood cortisol, oxytocin, heart rate and heart rate variability never differed between before and after the grooming session. However, after the 11 sessions, basal oxytocin levels were lower in the G than in the S group. This difference was unexpected, but supports studies showing that a low level of basal oxytocin could be a marker of better well-being. Analyses of facial expressions during grooming revealed significant differences between groups. These expressions appear to be more sensitive than behavioural indicators because they alone enabled differentiating emotions according to the group when horses were re-exposed to neutral grooming one year after the treatment.