bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse species-specific phenotypic consequences of loss of function sorting nexin 14 mutations
Authors: Bryant Dale , Seda Marian , Peskett Emma , Maurer Constance , Pomeranz Gideon , Ghosh Marcus , Hawkins Thomas A. , Cleak James , Datta Sanchari , Hariri Hanaa , Eckert Kaitlyn M. , Jafree Daniyal J. , Walsh Claire , Demetriou Charalambos , Ishida Miho , Alemán-Charlet Cristina , Vestito Letizia , Seselgyte Rimante , McDonald Jeffrey G. , Bitner-Glindzicz Maria , Hemberger Myriam , Rihel Jason , Teboul Lydia , Henne W. Mike , Jenkins Dagan , Moore Gudrun E. , Stanier Philip 
Published: August 2020

AbstractMutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) in both humans and dogs. Studies implicating the phenotypic consequences of SNX14 mutations to be consequences of subcellular disruption to autophagy and lipid metabolism have been limited to in vitro investigation of patient-derived dermal fibroblasts, laboratory engineered cell lines and developmental analysis of zebrafish morphants. SNX14 homologues Snz (Drosophila) and Mdm1 (yeast) have also been conducted, demonstrated an important biochemical role during lipid biogenesis. In this study we report the effect of loss of SNX14 in mice, which resulted in embryonic lethality around mid-gestation due to placental pathology that involves severe disruption to syncytiotrophoblast cell differentiation. In contrast to other vertebrates, zebrafish carrying a homozygous, maternal zygotic snx14 genetic loss-of-function mutation were both viable and anatomically normal. Whilst no obvious behavioural effects were observed, elevated levels of neutral lipids and phospholipids resemble previously reported effects on lipid homeostasis in other species. The biochemical role of SNX14 therefore appears largely conserved through evolution while the consequences of loss of function varies between species. Mouse and zebrafish models therefore provide valuable insights into the functional importance of SNX14 with distinct opportunities for investigating its cellular and metabolic function in vivo.
Molecular fluorescence spectroscopy with multi-way analysis techniques detects spectral variations distinguishing uninfected serum versus dengue or chikungunya viral infected samples
Authors: Santos Marfran C. D. , Monteiro Joelma D. , Araújo Josélio M. G. , Lima Kássio M. G. 
Published: August 2020

AbstractSignificant attempts are being made worldwide in an attempt to develop a tool that, with a simple analysis, is capable of distinguishing between different arboviruses. Herein, we employ molecular fluorescence spectroscopy as a sensitive and specific rapid tool, with simple methodology response, capable of identifying spectral variations between serum samples with or without the dengue or chikungunya viruses. Towards this, excitation emission matrices (EEM) of clinical samples from patients with dengue or chikungunya, in addition to uninfected controls, were separated into a training or test set and analysed using multi-way classification models such as n-PLSDA, PARAFAC-LDA and PARAFAC-QDA. Results were evaluated based on calculations of accuracy, sensitivity, specificity and F score; the most efficient model was identified to be PARAFAC-QDA, whereby 100% was obtained for all figures of merit. QDA was able to predict all samples in the test set based on the scores present in the factors selected by PARAFAC. The loadings obtained by PARAFAC can be used in future studies to prove the direct or indirect relationship of spectral changes caused by the presence of these viruses. This study demonstrates that molecular fluorescence spectroscopy has a greater capacity to detect spectral variations related to the presence of such viruses when compared to more conventional techniques.
Non-invasive in-vivo 3-D imaging of small animals using spatially filtered enhanced truncated-correlation photothermal coherence tomography
Authors: Tavakolian Pantea , Roointan Sohrab , Mandelis Andreas 
Published: August 2020

AbstractWe present enhanced truncated-correlation phototothermal coherence tomography (eTC-PCT) for non-invasive three-dimensional imaging of small animals. Tumor detection is reported in a mouse thigh by injecting cancerous cells in the thigh followed by eTC-PCT imaging. Detection of the tumor 3 days after injection may lead to potential for using the eTC-PCT method for cancer treatment studies. eTC-PCT was also applied successfully to non-invasive in-vivo mouse brain structural imaging. A unique spatial-gradient-gate adaptive filter was introduced in a scanned mode along the (x,y) coordinates of camera images from different sub-cranial depths, revealing absorber true spatial extent from diffusive photothermal images and restoring pre-diffusion lateral image resolution beyond the Rayleigh criterion limit in diffusion-wave imaging science. The spatial resolution and contrast enhancement demonstrated in photothermal in-vivo and ex-vivo images of the mouse brain revealed not only vascular structures but also other brain structures, such as the brain hemispheres, cerebellum, and olfactory lobes.
Flavagline synthetic derivative induces senescence in glioblastoma cancer cells without being toxic to healthy astrocytes
Authors: Harmouch Ezeddine , Seitlinger Joseph , Chaddad Hassan , Ubeaud-Sequier Geneviève , Barths Jochen , Saidu Sani , Désaubry Laurent , Grandemange Stéphanie , Massfelder Thierry , Fuhrmann Guy , Fioretti Florence , Dontenwill Monique , Benkirane-Jessel Nadia , Idoux-Gillet Ysia 
Published: August 2020

AbstractGlioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. It is the most invasive type of glioma developed from astrocytes. Until today, Temozolomide (TMZ) is the only standard chemotherapy for patients with GBM. Even though chemotherapy extends the survival of patients, there are many undesirable side effects, and most cases show resistance to TMZ. FL3 is a synthetic flavagline which displays potent anticancer activities, and is known to inhibit cell proliferation, by provoking cell cycle arrest, and leads to apoptosis in a lot of cancer cell lines. However, the effect of FL3 in glioblastoma cancer cells has not yet been examined. Hypoxia is a major problem for patients with GBM, resulting in tumor resistance and aggressiveness. In this study, we explore the effect of FL3 in glioblastoma cells under normoxia and hypoxia conditions. Our results clearly indicate that this synthetic flavagline inhibits cell proliferation and induced senescence in glioblastoma cells cultured under both conditions. In addition, FL3 treatment had no effect on human brain astrocytes. These findings support the notion that the FL3 molecule could be used in combination with other chemotherapeutic agents or other therapies in glioblastoma treatments.
Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism
Authors: Limbocker Ryan , Mannini Benedetta , Ruggeri Francesco S. , Cascella Roberta , Xu Catherine K. , Perni Michele , Chia Sean , Chen Serene W. , Habchi Johnny , Bigi Alessandra , Kreiser Ryan P. , Wright Aidan K. , Albright J. Alex , Kartanas Tadas , Kumita Janet R. , Cremades Nunilo , Zasloff Michael , Cecchi Cristina , Knowles Tuomas P. J. , Chiti Fabrizio , Vendruscolo Michele , Dobson Christopher M. 
Published: August 2020

AbstractThe onset and progression of numerous protein misfolding diseases are associated with the presence of oligomers formed during the aberrant aggregation of several different proteins, including amyloid-β (Aβ) in Alzheimer’s disease and α-synuclein (αS) in Parkinson’s disease. These small, soluble aggregates are currently major targets for drug discovery. In this study, we show that trodusquemine, a naturally-occurring aminosterol, markedly reduces the cytotoxicity of αS, Aβ and HypF-N oligomers to human neuroblastoma cells by displacing the oligomers from cell membranes in the absence of any substantial morphological and structural changes to the oligomers. These results indicate that the reduced toxicity results from a mechanism that is common to oligomers from different proteins, shed light on the origin of the toxicity of the most deleterious species associated with protein aggregation and suggest that aminosterols have the therapeutically-relevant potential to protect cells from the oligomer-induced cytotoxicity associated with numerous protein misfolding diseases.
Lionheart LincRNA alleviates cardiac systolic dysfunction under pressure overload
Authors: Kuwabara Yasuhide , Tsuji Shuhei , Nishiga Masataka , Izuhara Masayasu , Ito Shinji , Nagao Kazuya , Horie Takahiro , Watanabe Shin , Koyama Satoshi , Kiryu Hisanori , Nakashima Yasuhiro , Baba Osamu , Nakao Tetsushi , Nishino Tomohiro , Sowa Naoya , Miyasaka Yui , Hatani Takeshi , Ide Yuya , Nakazeki Fumiko , Kimura Masahiro , Yoshida Yoshinori , Inada Tsukasa , Kimura Takeshi , Ono Koh 
Published: August 2020

AbstractRecent high-throughput approaches have revealed a vast number of transcripts with unknown functions. Many of these transcripts are long noncoding RNAs (lncRNAs), and intergenic region-derived lncRNAs are classified as long intergenic noncoding RNAs (lincRNAs). Although Myosin heavy chain 6 (Myh6) encoding primary contractile protein is down-regulated in stressed hearts, the underlying mechanisms are not fully clarified especially in terms of lincRNAs. Here, we screen upregulated lincRNAs in pressure overloaded hearts and identify a muscle-abundant lincRNA termed Lionheart. Compared with controls, deletion of the Lionheart in mice leads to decreased systolic function and a reduction in MYH6 protein levels following pressure overload. We reveal decreased MYH6 results from an interaction between Lionheart and Purine-rich element-binding protein A after pressure overload. Furthermore, human LIONHEART levels in left ventricular biopsy specimens positively correlate with cardiac systolic function. Our results demonstrate Lionheart plays a pivotal role in cardiac remodeling via regulation of MYH6.
Oxytocin facilitates valence-dependent valuation of social evaluation of the self
Authors: Wang Danyang , Ma Yina 
Published: August 2020

AbstractPeople are eager to know the self in other’s eyes even with personal costs. However, what drives people costly to know evaluations remains unknown. Here we tested the hypothesis of placing subjective value on knowing social evaluations. To quantify the subjective value, we developed apay-to-knowchoice task where individuals trade off profits against knowing social evaluations. Individuals computed independent unknown aversion towards positive and negative social evaluations and placed higher values on knowing social evaluation on positive than negative aspects. Such a valence-dependent valuation of social evaluation was facilitated by oxytocin, a neuropeptide linked to feedback learning and valuation processes, by decreasing values of negative social evaluation. Moreover, individuals scoring high in depression undervalued positive social evaluation, which was normalized by oxytocin. We reveal the psychological and computational processes underlying self-image formation/update and suggest a role of oxytocin in normalizing hypo-valuation of positive social evaluation in depression.
Engineering combinatorial and dynamic decoders using synthetic immediate-early genes
Authors: Ravindran Pavithran T. , Wilson Maxwell Z. , Jena Siddhartha G. , Toettcher Jared E. 
Published: August 2020

AbstractMany cell- and tissue-level functions are coordinated by intracellular signaling pathways that trigger the expression of context-specific target genes. Yet the input–output relationships that link pathways to the genes they activate are incompletely understood. Mapping the pathway-decoding logic of natural target genes could also provide a basis for engineering novel signal-decoding circuits. Here we report the construction of synthetic immediate-early genes (SynIEGs), target genes of Erk signaling that implement complex, user-defined regulation and can be monitored by using live-cell biosensors to track their transcription and translation. We demonstrate the power of this approach by confirming Erk duration-sensing by FOS, elucidating how the BTG2 gene is differentially regulated by external stimuli, and designing a synthetic immediate-early gene that selectively responds to the combination of growth factor and DNA damage stimuli. SynIEGs pave the way toward engineering molecular circuits that decode signaling dynamics and combinations across a broad range of cellular contexts.
Comparative genomics of muskmelon reveals a potential role for retrotransposons in the modification of gene expression
Authors: Yano Ryoichi , Ariizumi Tohru , Nonaka Satoko , Kawazu Yoichi , Zhong Silin , Mueller Lukas , Giovannoni James J. , Rose Jocelyn K. C. , Ezura Hiroshi 
Published: August 2020

AbstractMelon exhibits substantial natural variation especially in fruit ripening physiology, including both climacteric (ethylene-producing) and non-climacteric types. However, genomic mechanisms underlying such variation are not yet fully understood. Here, we report an Oxford Nanopore-based high-grade genome reference in the semi-climacteric cultivar Harukei-3 (378 Mb + 33,829 protein-coding genes), with an update of tissue-wide RNA-seq atlas in the Melonet-DB database. Comparison between Harukei-3 and DHL92, the first published melon genome, enabled identification of 24,758 one-to-one orthologue gene pairs, whereas others were candidates of copy number variation or presence/absence polymorphisms (PAPs). Further comparison based on 10 melon genome assemblies identified genome-wide PAPs of 415 retrotransposon Gag-like sequences. Of these, 160 showed fruit ripening-inducible expression, with 59.4% of the neighboring genes showing similar expression patterns (r > 0.8). Our results suggest that retrotransposons contributed to the modification of gene expression during diversification of melon genomes, and may affect fruit ripening-inducible gene expression.
Single-sulfur atom discrimination of polysulfides with a protein nanopore for improved batteries
Authors: Bétermier Fanny , Cressiot Benjamin , Di Muccio Giovanni , Jarroux Nathalie , Bacri Laurent , Morozzo della Rocca Blasco , Chinappi Mauro , Pelta Juan , Tarascon Jean-Marie 
Published: August 2020

AbstractResearch on batteries mostly focuses on electrodes and electrolytes while few activities regard separator membranes. However, they could be used as a toolbox for injecting chemical functionalities to capture unwanted species and enhance battery lifetime. Here, we report the use of biological membranes hosting a nanopore sensor for electrical single molecule detection and use aqueous sodium polysulfides encountered in sulfur-based batteries for proof of concept. By investigating the host-guest interaction between polysulfides of different chain-lengths and cyclodextrins, via combined chemical approaches and molecular docking simulations, and using a selective nanopore sensor inserted into a lipid membrane, we demonstrate that supramolecular polysulfide/cyclodextrin complexes only differing by one sulfur can be discriminated at the single molecule level. Our findings offer innovative perspectives to use nanopores as electrolyte sensors and chemically design membranes capable of selective speciation of parasitic molecules for battery applications and therefore pave the way towards smarter electrochemical storage systems.
Generation of sintered fault rock and its implications for earthquake energetics and fault healing
Authors: Hirono Tetsuro , Kaneki Shunya , Ishikawa Tsuyoshi , Kameda Jun , Tonoike Naoya , Ito Akihiro , Miyazaki Yuji 
Published: August 2020

AbstractAfter an earthquake, faults can recover strength through fault healing, but the mechanisms responsible are not well understood. Seismic slip may induce sintering, a bonding process between solid particles in contact under high temperatures without melting, which could produce a fault rock with elevated strength and chemical stability. Here we present results from electron microscope analyses that show a typical sintered structure in a black disk-shaped rock from the Chelungpu fault, Taiwan. This structure is experimentally reproducible in simulated fault material, prepared from the local host-rock, by heating at 800–900 °C. Through thermal and kinetic analyses of experimental materials, we show that sintering is an exothermic process which can generate energy to enhance post-slip thermochemical reactions in the fault. We propose that sintering substantially contributes to earthquake energetics and fault healing and that its occurrence can be a useful indicator of past seismic slip.
Fast and slow components of interstadial warming in the North Atlantic during the last glacial
Authors: Margari Vasiliki , Skinner Luke C. , Menviel Laurie , Capron Emilie , Rhodes Rachael H. , Mleneck-Vautravers Maryline J. , Ezat Mohamed M. , Martrat Belen , Grimalt Joan O. , Hodell David A. , Tzedakis Polychronis C. 
Published: August 2020

AbstractThe abrupt nature of warming events recorded in Greenland ice-cores during the last glacial has generated much debate over their underlying mechanisms. Here, we present joint marine and terrestrial analyses from the Portuguese Margin, showing a succession of cold stadials and warm interstadials over the interval 35–57 ka. Heinrich stadials 4 and 5 contain considerable structure, with a short transitional phase leading to an interval of maximum cooling and aridity, followed by slowly increasing sea-surface temperatures and moisture availability. A climate model experiment reproduces the changes in western Iberia during the final part of Heinrich stadial 4 as a result of the gradual recovery of the Atlantic meridional overturning circulation. What emerges is that Greenland ice-core records do not provide a unique template for warming events, which involved the operation of both fast and slow components of the coupled atmosphere–ocean–sea-ice system, producing adjustments over a range of timescales.
Surprising chiral composition changes over the Amazon rainforest with height, time and season
Authors: Zannoni Nora , Leppla Denis , Lembo Silveira de Assis Pedro Ivo , Hoffmann Thorsten , Sá Marta , Araújo Alessandro , Williams Jonathan 
Published: August 2020

AbstractMany biogenic volatile organic compounds (BVOC) are chiral, existing in two mirror image forms called enantiomers. The most abundant atmospheric chiral BVOC is α-pinene (C10H16), whose enantiomeric ratio has been reported to be regiospecific. Here we show with measurements made on a 325 m tower in the Amazon rainforest that the enantiomeric ratio varies unexpectedly (by a factor of ten) with (+)-α-pinene dominating at canopy level and (−)-α-pinene at tower top. The ratio is independent of wind direction, speed and sunlight but shows diurnal temperature dependent enrichment in the (−)-α-pinene enantiomer at the lowest 80 m height. These effects cannot be caused by atmospheric reaction with oxidants,or aerosol uptake. The reversal of chiral ratio at 80 m reveals the presence of a potent uncharacterized local (+)-α-pinene rich source, possibly linked to herbivory and termites. These results suggest the presence of a strong uncharacterized BVOC source that is overlooked in current emission models.
Charge-transfer engineering strategies for tailored ionic conductivity at oxide interfaces
Authors: Gunkel F. , Christensen D. V. , Pryds N. 
Published: August 2020

Based on the example of the p-type LaAlO3/SrTiO3 interface, we discuss charge-transfer phenomena that tailor the ionic conductivity along oxide heterointerfaces, by providing a confined space-charge layer as channel for oxygen ion conduction.
Aktuelle ethische Herausforderungen in der Intensivmedizin angesichts der Corona-Pandemie
Authors: Janssens Uwe 
Published: August 2020

Was ist neu?
Empfehlung der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin Angesichts weltweit explodierender Patientenzahlen im Verlauf der Corona-Pandemie und knapper intensivmedizinscher Ressourcen in vielen Ländern mit teilweiser dramatischer Unterversorgung machten sich in Deutschland Sorgen und Ängste in der Bevölkerung breit. Auch die Beschäftigten im Gesundheitswesen stellten sich die Frage, wie mit einer Überlastung des Gesundheitswesens hier umgegangen werden sollte. Zahlreiche Anfragen von besorgten Ärzten aber auch Ethikkomitees bei verschiedenen Fachgesellschaften veranlasste die Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI) gemeinsam mit 7 weiteren Fachgesellschaften eine klinisch-ethische Empfehlung zu „Entscheidungen über die Zuteilung intensivmedizinischer Ressourcen im Kontext der COVID-19-Pandemie“ auszuarbeiten. Die Priorisierung von Patienten soll sich am Kriterium der klinischen Erfolgsaussicht orientieren. Dabei werden – wenn nicht anders vermeidbar – diejenigen Patienten nicht intensivmedizinisch behandelt, bei denen nur eine sehr geringe Aussicht besteht zu überleben. Vorrangig werden demgegenüber diejenigen Patienten intensivmedizinisch behandelt, die durch diese Maßnahmen eine höhere Überlebenswahrscheinlichkeit haben.
Rechtliche Aspekte Solange es vom Gesetzgeber keine Vorgaben hinsichtlich einer Priorisierung bei unzureichenden Ressourcen gibt, müssen Politik und Rechtsprechung den Ärztinnen und Ärzten, die diesem Dilemma ausgesetzt sind, Rückendeckung geben.
Die interdisziplinäre, multimodale Schmerztherapie in der konservativen Wirbelsäulentherapie
Authors: Marnitz Ulf 
Published: August 2020

ZusammenfassungDie interdisziplinäre multimodale Schmerztherapie (IMST) ist als wirksamste Behandlungsform chronischer Rückenschmerzen wiederholt belegt. Dazu wird ein qualifiziertes Behandlerteam aus Ärzten, Psychotherapeuten und Physiotherapeuten benötigt. Deren Handeln orientiert sich an Versorgungsleitlinien, an inzwischen bestehenden, umfangreichen Nachschlagewerken und Handlungsanweisungen. Grundsätzlich zeichnet sich die IMST durch eine bio-psycho-soziale Sichtweise mit einer gemeinsamen Haltung im Heilungsprozess für die Patienten aus.
Fallbericht: Best Supportive Care (BSC) in der Palliativmedizin – was bedeutet BSC eigentlich?
Authors: Kretschmer Eva-Maria , Krones Tanja , Blum David 
Published: August 2020

ZusammenfassungWir berichten über einen multimorbiden 56-jährigen Patienten, welcher mit unbehandelter Tumorerkrankung nach Multiorganversagen auf die Palliativstation verlegt wurde. Aufgrund einer Eisenmangelanämie wurde eine Magen-Darm-Diagnostik zum Ausschluss einer gastrointestinalen Blutung durchgeführt. Diese Untersuchung zeigte ein Adenokarzinom des proximalen Kolons. Im Rahmen der Narkoseeinleitung zur Resektion des Tumors aspirierte der Patient und entwickelte einen schweren septischen Schock mit Multiorganversagen.Entsprechend der interdisziplinären Tumorboardempfehlung für Best Supportive Care (BSC) sowie dem vom Patienten gewünschten Abbruch der Therapie, erfolgte die Zuweisung auf die Palliativstation. Der voll urteilsfähige Patient hatte im Zuge der aus seiner Sicht dramatischen Ereignisse keine weiteren intensivmedizinischen Maßnahmen gewünscht.Im weiteren Verlauf der insgesamt fünfwöchigen Behandlung auf der Palliativstation stabilisierte sich der Patient. Dank intensiver Gespräche mit unterschiedlichen Professionen der Palliativmedizin über Therapieziele und die eigenen Präferenzen beschäftigte sich der Patient mit dem Lebensende und bereitete sich auf den Tod vor. Es zeigte sich, dass die Ablehnung weiterer intensivmedizinischer Maßnahmen aus Patientensicht keinen generellen Verzicht auf die Behandlung der Tumorerkrankung beinhaltete.Schließlich konnte bei vollständiger Rekonvaleszenz die geplante onkologische Therapie mit neoadjuvanter Chemotherapie und Tumorresektion erfolgreich durchgeführt werden.