bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted delivery of anti-inflammatory therapy to rheumatoid tissue by fusion proteins containing an IL-4-linked synovial targeting peptide
Authors: Bombardieri Michele , Nissim Ahuva , Mather Stephen , Chernajovsky Yuti , Wythe Sarah , DiCara Danielle , Taher Taher , Finucane Ciara , Jones Rita , Pitzalis Costantino , Man Y. K. Stella 
Published: July 2019

AbstractWe provide first-time evidence that the synovial endothelium-targeting peptide (SyETP) CKSTHDRLC successfully delivers conjugated IL-4 to human rheumatoid synovium transplanted into SCID mice. SyETP, previously isolated by in vivo phage display and shown to preferentially localize to synovial xenografts, was linked by recombinant technology to hIL-4 via an MMP-cleavable sequence. Both IL-4 and the MMP-cleavable sequence were shown to be functional. IL-4-SyETP augmented production of IL-1ra by synoviocytes stimulated with IL-1[beta] in a dose-dependent manner. In vivo imaging confirmed increased retention of SyETP-linked-IL-4 in synovial grafts which was enhanced by increasing number of copies (one to three) in the constructs. Strikingly, SyETP delivered bioactive IL-4 in vivo as demonstrated by increased pSTAT6 in synovial grafts. Thus, this study provides proof of concept for peptide-tissue-specific targeted immunotherapy in rheumatoid arthritis. This technology is potentially applicable to other biological therapies providing enhanced potency to inflammatory sites and reducing systemic toxicity.
Predicting Prostate Cancer Aggressiveness through a Nanoparticle Test
Authors: Huo Qun , Sullivan Shannon , Hallquist Hillari , Litherland Sally , Decker David , Rivera-Ramirez Inoel 
Published: July 2019

AbstractProstate cancer (PCa) is the most common malignancy and the second leading cause of cancer death in American men. Due to the lack of accurate tests to distinguish aggressive cancer from indolent tumor, prostate cancer is often over-treated. Post-surgery pathology analysis revealed that 30% of tumors removed by radical prostatectomy are deemed clinically insignificant and would not have required such invasive treatment.^1^ Over-diagnosis and treatment of low-risk prostate cancer has serious and long-lasting side effect: as high as 70% of the patients who receive radical prostatectomy treatment will suffer a loss of sexual potency that cannot be remedied by drugs such as sildenafil citrate.^2^ We herein report a simple nanoparticle-serum protein adsorption test that not only can distinguish prostate cancer from normal and benign conditions, but also is capable of predicting the aggressiveness of prostate cancer quantitatively. This new test could potentially deliver the long-expected and very much needed solution for better individualization of prostate cancer treatment.
Multifunction moonlighting and intrinsically disordered proteins: Information catalysis, nonrigid molecule symmetries, and the 'logic gate' spectrum
Authors: Wallace Rodrick 
Published: July 2019

AbstractIntrinsically disordered proteins (IDP) appear far more likely to engage in functional moonlighting than well-structured proteins. The recent use of nonrigid molecule theory to address IDP structure and dynamics produces this result directly: Mirror image subgroup or subgroupoid tiling matching of the molecular fuzzy lock-and-key can be much richer for IDPs since the number of possible group or groupoid symmetries can grow exponentially with molecule length, while tiling matching for 3D structured proteins is relatively limited. A simple information catalysis model suggests how this mechanism can produce a vast spectrum of biological 'logic gates' having subtle properties far beyond familiar AND, OR, XOR, etc. behaviors. Inferring the general from the particular, the analysis adds weight to arguments that a fundamental defining characteristic of the living state is the operation of chemical or other cognitive processes at virtually every scale and level of organization.
Dynamical patterns of human postural responses to emotional stimuli
Authors: Perakakis Pandelis , Vila Jaime , Idrissi Sofia , Ivanov Plamen 
Published: July 2019

AbstractErotic scenes and images of mutilated bodies are emotional stimuli that have repeatedly shown to evoke specific neurophysiological responses associated with enhanced attention and perceptual processing. Remarkably however, only a handful of studies have investigated human motor reactions to emotional activation as a direct index of physical approximation or withdrawal. Given the inconclusive results of these studies, the approach-avoidance distinction, one of the most salient concepts in human motivational research, remains a broadly exploited hypothesis that has never been empirically demonstrated. Here, we investigate postural responses elicited by discrete emotional stimuli in healthy young adults. We discover that both positive and negative affective pictures induce a significant posterior deviation from postural baseline equilibrium. Further, we find that neutral pictures also evoke posterior deviation, although with a less pronounced amplitude. Exploring the dynamical evolution of postural responses to emotional pictures at high temporal resolution, we uncover a characteristic profile that remains stable for stimuli from all three affective categories. In contrast, the postural response amplitude is modulated by the emotional content of the stimulus. Our observations do not support the interpretation of postural responses to affective picture-viewing as approach-avoidance behavior. Instead, our findings indicate the involvement of a previously unrecognized motor component of the physiological mechanism underlying human orienting responses.
Low dose IR-induced IGF-1-sCLU expression: a p53-repressed expression cascade that interferes with TGF&x00DF;1 signaling to confer survival
Authors: Willson David , Boothman David , Klokov Dmitry , Leskov Konstantin , Araki Shinako , Zou Yonglong , Goetz Eva , Luo Xiuquan 
Published: July 2019

AbstractTo better understand tissue responses after low IR doses, we generated a reporter system using human clusterin promoter fused to firefly luciferase (hCLUp-Luc). Secretory clusterin (sCLU), an extra-cellular molecular chaperone, induced by low doses of cytotoxic agents, clears cell debris promoting survival. Low dose IR (&gt;2 cGy) exposure induced hCLUp-Luc activity with peak levels at 96 h, consistent with endogenous sCLU levels. As doses increased (&gt;1 Gy), sCLU induction amplitudes increased and time to peak response decreased. sCLU expression was stimulated by IGF-1, but suppressed by p53. Responses in transgenic hCLUp-Luc reporter mice after low IR doses showed that specific tissues (i.e., colon, spleen, mammary, thymus, bone marrow) of female mice induced hCLUp-Luc activity more than male mice after whole body &gt;10 cGy. Tissue-specific, non-linear dose- and time-responses of hCLUp-Luc and endogenous sCLU levels were noted. Colon maintained homeostatic balance after 10 cGy. Bone marrow responded with delayed, but prolonged and elevated expression. Intraperitoneal administration of the &x03B1;-TGF&x00DF;1 (1D11) antibody, but not a control antibody (13C4), immediately following IR exposure abrogated CLU induction responses. Induction in vivo also correlated with Smad signaling via activated TGF&x00DF;1 after IR. Mechanistically, media with elevated sCLU levels suppressed signaling, blocked apoptosis and increased survival of TGF&x00DF;1-exposed tumor or normal cells. Thus, sCLU is a TGF-&x00DF;1-induced pro-survival, potential bystander factor expressed in certain exposed tissues that, in turn, abrogates TGF&x00DF;1 signaling and may promote wound healing and likely contributes to a pro-tumor growth microenvironment.
Variety in evolutionary strategies favours biodiversity in habitats of moderate productivity
Authors: Pierce Simon 
Published: July 2019

AbstractThe mechanism whereby biodiversity varies between habitats differing in productivity is a missing link between ecological and evolutionary theory with vital implications for biodiversity conservation, management and the assessment of ecosystem services. A unimodal, humped-back relationship, with biodiversity greatest at intermediate productivities, is evident when plant, animal and microbial communities are compared across productivities in nature. However, the mechanistic, evolutionary basis of this observation remains enigmatic. We show, for natural and semi-natural plant communities across a range of bioclimatic zones, that biodiversity is greatest where communities include species with widely divergent values for phenotypic traits involved in resource economics and reproductive timing, coinciding with intermediate biomass production, whilst each productivity extreme is associated with small numbers of specialised species with similar trait values. Our data demonstrate that evolution can generate a greater range of phenotypes where large, fast-growing species are prevented from attaining dominance and extreme adaptation to a harsh abiotic environment is not a prerequisite for survival.
The use of DCEEG to estimate functional and metabolic state of nervous tissue of the brain at hyper- and hypoventilation
Authors: Murik Sergey 
Published: July 2019

AbstractA pilot study has been made of the simultaneous DC potential and total slow electrical activity changes during modeling various metabolic and functional states of the human brain. The multi-electrode DCEEG recordings have been performed during the hyperventilation (frequent deep one-minute long breathing motions) and the hypoventilation (voluntary breath holding). It has been shown that the ischemic state occurring in hyperventilation is accompanied by the negative shift of DC potential and increase in the EEG rhythms amplitude. A distention of brain vessels during hypoventilation (voluntary breath-hold) and an improvement of blood supply and thus improvement of vital and functional state of neurons gave rise to an increase in the EEG rhythm amplitude too, though against a background of a positive DC-potential shift. Obtained results are considered in context of the generation of the qualitatively different functional states of brain cells during hyper- and hypoventilation which is reflected in their resting potential and activity. The conducted study shows the prospects for DCEEG and the method we used for DCEEG data processing to understand the character of functional and metabolic changes in the nervous tissue.
Mining SOM expression portraits: Feature selection and integrating concepts of molecular function
Authors: Wirth Henry , von Bergen Martin , Binder Hans 
Published: July 2019

Abstract

Background:

Self organizing maps (SOM) enable the straightforward portraying of high-dimensional data of large sample collections in terms of sample-specific images. The analysis of their texture provides so-called spot-clusters of co-expressed genes which require subsequent significance filtering and functional interpretation. We address feature selection in terms of the gene ranking problem and the interpretation of the obtained spot-related lists using concepts of molecular function.

Results:

Different expression scores based either on simple fold change-measures or on regularized Students t-statistics are applied to spot-related gene lists and compared with special emphasis on the error characteristics of microarray expression data. The spot-clusters are analyzed using different methods of gene set enrichment analysis with the focus on overexpression and/or overrepresentation of predefined sets of genes. Metagene-related overrepresentation of selected gene sets was mapped into the SOM images to assign gene function to different regions. Alternatively we estimated set-related overexpression profiles over all samples studied using a gene set enrichment score. It was also applied to the spot-clusters to generate lists of enriched gene sets. We used the tissue body index data set, a collection of expression data of human tissues, as an illustrative example. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. In addition, we display special sets of housekeeping and of consistently weak and highly expressed genes using SOM data filtering.

Conclusions:

The presented methods allow the comprehensive downstream analysis of SOM-transformed expression data in terms of cluster-related gene lists and enriched gene sets for functional interpretation. SOM clustering implies the ability to define either new gene sets using selected SOM spots or to verify and/or to amend existing ones.
MAP7D2 is a brain expressing X-linked maternal imprinted gene in humans
Authors: Niida Yo , Yachie Akihiro 
Published: July 2019

AbstractIncreasing evidence suggests imprinted genes influence mouse and human behaviors and cognitive functions. Unlike autosomal imprinted genes, X-linked imprinted genes are expressed in a sex-dependent manner because of male hemizygosity. Therefore, these genes could directly affect sex-specific brain functions and sex-biased vulnerability to psychiatric disorders such as autism1. Comparing lymphoblastoid cell lines (LCL) and peripheral blood mononuclear cells (PBMC) from healthy adult male and females, we identified MAP7 domain containing 2 (MAP7D2) as the first human X-linked imprinted gene. Both in LCL and PBMC, MAP7D2 expression was significantly suppressed in males by maternal imprinting. In each female LCL clone, MAP7D2 was expressed higher in paternally derived allele and was affected by X-chromosome inactivation. In female PBMC, however, reactivation of maternal MAP7D2 alleles was observed. MAP7D2 was expressed specifically in the brain among human tissues with unique isoforms. These results predict a crucial role of MAP7D2 for human sex-dependent neurobiological traits.
Precise Molecular Structures of Cysteine, Cystine, Hydrogen-Bonded Dicysteine, Cysteine Dipeptide, Glutathione and Acetyl Cysteine Based on Additivity of Atomic Radii
Authors: Heyrovska Raji 
Published: July 2019

AbstractStructures of molecules are usually represented by arbitrary line drawings, ball and stick or space filling models. In recent years, the author found that using the appropriate radii of atoms and ions, bond lengths in inorganic, organic and biomolecules and of hydrogen bonds are exact sums of the radii of the adjacent atoms and or ions. This additivity of atomic radii was shown to hold also for the bond lengths in the twenty essential amino acids. On this basis, the atomic structures of the very important molecules mentioned in the title, have been presented here for the first time. It is hoped that these precise structures and their dimensions will shed new light into their role in biochemistry, pharmaceutical chemistry, environmental chemistry, biomedicine and in the mechanism of protein folding.
Balancing noise and plasticity in gene expression
Authors: Bajic Djordje , Poyatos Juan 
Published: July 2019

AbstractCoupling the control of expression stochasticity (noise) with the capacity to expression change (plasticity) can constrain gene function and limit adaptation. Which factors contribute then to modulate this coupling? Transcription re-initiation is generally associated with coupling and this is commonly related to strong chromatin regulation. We alternatively show how strong regulation can however lead to plasticity uncorrelated to noise. The character of the regulation is also relevant, with plastic but noiseless genes usually subjected to broad expression activation whereas plastic and noisy genes experience targeted repression. This differential action is similarly noticed in how histones influence these genes. In contrast, we find that translational mechanisms are the ones separating noise from plasticity in low-plastic genes, a pattern associated with the simplicity of their expression regulation. Neighboring genome architecture as modifier appears then only effective in highly plastic genes. This poses ultimately an interesting paradox between intergenic distances and modulation, with short intergenic distances both associated and not associated with noise at different plasticity levels. Balancing the coupling among different types of expression variability appears thus as a potential shaping force of genome architecture and regulation.
Post-meiotic apozygotic combinatory process in sugar beet (Beta vulgaris L.)
Authors: Levites Evgenii , Kirikovich Svetlana 
Published: July 2019

AbstractThe effect of colchicine on phenotypic classes ratio of the enzyme locus controlling alcohol dehydrogenase (ADH1) in sugar beet agamospermous progenies was analyzed. The obtained data are indicative of the thing that colchicine causes polytenization of homological chromosome regions carrying marker locus Adh1 alleles. Theoretical calculation of the formation of egg cell frequencies and those of further development of cells entering embryogenesis without fertilization, also the diminution calculation of excessive chromosome regions carrying marker locus alleles have been made. The coincidence of theoretical and experimental ratios of phenotypic classes indicates the existence of a post-meiotic apozygotic combinatory process in plants.
Oncogenic KIT mutations induce STAT3-dependent autophagy to support cell proliferation in acute myeloid leukemia
Authors: Larrue Clément , Heydt Quentin , Saland Estelle , Boutzen Héléna , Kaoma Tony , Sarry Jean-Emmanuel , Joffre Carine , Récher Christian 
Published: July 2019

AbstractAutophagy is associated with both survival and cell death in myeloid malignancies. Therefore, deciphering its role in different genetically defined subtypes of acute myeloid leukemia (AML) is critical. Activating mutations of the KIT receptor tyrosine kinase are frequently detected in core-binding factor AML and are associated with a greater risk of relapse. Herein, we report that basal autophagy was significantly increased by the KITD816V mutation in AML cells and contributed to support their cell proliferation and survival. Invalidation of the key autophagy protein Atg12 strongly reduced tumor burden and improved survival of immunocompromised NSG mice engrafted with KITD816V TF-1 cells. Downstream of KITD816V, STAT3, but not AKT or ERK pathways, was identified as a major regulator of autophagy. Accordingly, STAT3 pharmacological inhibition or downregulation inhibited autophagy and reduced tumor growth both in vitro and in vivo. Taken together, our results support the notion that targeting autophagy or STAT3 opens up an exploratory pathway for finding new therapeutic opportunities for patients with CBF-AML or others malignancies with KITD816V mutations.
Quantum optical neural networks
Authors: Steinbrecher Gregory R. , Olson Jonathan P. , Englund Dirk , Carolan Jacques 
Published: July 2019

AbstractPhysically motivated quantum algorithms for specific near-term quantum hardware will likely be the next frontier in quantum information science. Here, we show how many of the features of neural networks for machine learning can naturally be mapped into the quantum optical domain by introducing the quantum optical neural network (QONN). Through numerical simulation and analysis we train the QONN to perform a range of quantum information processing tasks, including newly developed protocols for quantum optical state compression, reinforcement learning, black-box quantum simulation, and one-way quantum repeaters. We consistently demonstrate that our system can generalize from only a small set of training data onto inputs for which it has not been trained. Our results indicate that QONNs are a powerful design tool for quantum optical systems and, leveraging advances in integrated quantum photonics, a promising architecture for next-generation quantum processors.
Global perspectives on food fraud: results from a WHO survey of members of the International Food Safety Authorities Network (INFOSAN)
Authors: Spink John , Embarek Peter Ben , Savelli Carmen Joseph , Bradshaw Adam 
Published: July 2019

AbstractThis survey of International Food Safety Authorities Network (INFOSAN) members regarding food fraud prevention, management, education, and information sharing included 166 WHO member states that resulted in 175 responses. The respondents engage in food fraud prevention (70%) or are responsible for food fraud incident response (74%). Nearly all respondents acknowledged a desire for more guidance and information on best practices in managing the full range of “food safety events involving food fraud” (97%), but also for prevention of such events (97%), indicating a need to provide technical support beyond acute incident response. The scope of food fraud covered in the survey comprised the full range of fraudulent activities, including the addition of adulterant-substances, tampering (including mislabeling), theft, smuggling, gray market/diversion, and counterfeiting (intellectual property rights). Key needs included: capacity-building/education; a platform for information sharing; and utilization of INFOSAN as an interagency/intergovernmental collaboration point.
Extracellular vesicles from T cells overexpress miR-146b-5p in HIV-1 infection and repress endothelial activation
Authors: Balducci Estelle , Leroyer Aurélie S. , Lacroix Romaric , Robert Stéphane , Todorova Dilyana , Simoncini Stéphanie , Lyonnet Luc , Chareyre Corinne , Zaegel-Faucher Olivia , Micallef Joëlle , Poizot-Martin Isabelle , Roll Patrice , Dignat-George Françoise 
Published: July 2019

AbstractHuman immunodeficiency virus type 1 (HIV-1) infection promotes a generalized activation of host responses that involves not only CD4 T cells, but also cells of the microenvironment, which are not directly infected, such as endothelial cells. The mechanisms triggering HIV-1-associated vascular alterations remain poorly understood. Extracellular vesicles (EVs), implicated in cell-to-cell communication, have been recently described as carriers of microRNAs (miRNAs). Here, we show that miR-146b-5p is upregulated in both CD4 T cells, CD4 T cell-derived EVs and circulating EVs obtained from antiretroviral therapy-naive HIV-1-infected patients. We further demonstrate that EVs from T cell line overexpressing miR-146b-5p mimics (miR-146b-EVs): 1) protect their miRNA cargo from RNase degradation, 2) transfer miR-146b-5p mimics into endothelial cells and 3) reduce endothelial inflammatory responses in vitro and in vivo in the lungs of mice through the downregulation of nuclear factor-κB-responsive molecules. These data advance our understanding on chronic inflammatory responses affecting endothelial homeostasis, in infectious and non-infectious diseases and pave the way for potential new anti-inflammatory strategies.
Heroic music stimulates empowering thoughts during mind-wandering
Authors: Koelsch Stefan , Bashevkin Tobias , Kristensen Joakim , Tvedt Jonas , Jentschke Sebastian 
Published: July 2019

AbstractIt is generally well-known, and scientifically well established, that music affects emotions and moods. However, only little is known about the influence of music on thoughts. This scarcity is particularly surprising given the importance of the valence of thoughts for psychological health and well-being. We presented excerpts of heroic- and sad-sounding music to n = 62 individuals, and collected thought probes after each excerpt, assessing the valence and the nature of thoughts stimulated by the music. Our results show that mind-wandering emerged during listening to either type of music (heroic, sad), and that the type of music strongly influenced the thought contents during mind-wandering. Heroic-sounding music evoked more positive, exciting, constructive, and motivating thoughts, while sad-sounding music evoked more calm or demotivating thoughts. The results thus indicate that music has a strong effect on the valence of thought contents during mind-wandering, with heroic music evoking more empowering and motivating thoughts, and sad music more relaxing or depressive thoughts. These findings have important implications for the use of music in everyday life to promote health and well-being in both clinical populations and healthy individuals.