bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake dynamics in the Lactose permease (LacY) membrane protein transporter
Authors: Kimanius D. , Lindahl E. , Andersson M. 
Published: September 2018

AbstractThe sugar transporter Lactose permease (LacY) of Escherichia coli has become a prototype to understand the underlying molecular details of membrane transport. Crystal structures have trapped the protein in sugar-bound states facing the periplasm, but with narrow openings unable to accommodate sugar. Therefore, the molecular details of sugar uptake remain elusive. In this work, we have used extended simulations and metadynamics sampling to explore a putative sugar-uptake pathway and associated free energy landscape. We found an entrance at helix-pair 2 and 11, which involved lipid head groups and residues Gln 241 and Gln 359. Furthermore, the protein displayed high flexibility on the periplasmic side of Phe 27, which is located at the narrowest section of the pathway. Interactions to Phe 27 enabled passage into the binding site, which was associated with a 24 ± 4 kJ/mol binding free energy in excellent agreement with an independent binding free energy calculation and experimental data. Two free energy minima corresponding to the two possible binding poses of the lactose analog β-D-galactopyranosyl-1-thio-β-D-galactopyranoside (TDG) were aligned with the crystal structure-binding pocket. This work outlines the chemical environment of a putative periplasmic sugar pathway and paves way for understanding substrate affinity and specificity in LacY.
Diversity and Functional Evolution of Terpene Synthases in Dictyostelid Social Amoebae
Authors: Chen Xinlu , Köllner Tobias G. , Shaulsky Gad , Jia Qidong , Dickschat Jeroen S. , Gershenzon Jonathan , Chen Feng 
Published: September 2018

AbstractDictyostelids, or social amoebae, have a unique life style in forming multicellular fruiting bodies from unicellular amoeboids upon starvation. Recently, dictyostelids were found to contain terpene synthase (TPS) genes, a gene type of secondary metabolism previously known to occur only in plants, fungi and bacteria. Here we report an evolutionary functional study of dictyostelid TPS genes. The number of TPS genes in six species of dictyostelids examined ranges from 1 to 19; and the model species Dictyostelium purpureum contains 12 genes. Using in vitro enzyme assays, the 12 TPS genes from D. purpureum were shown to encode functional enzymes with distinct product profiles. The expression of the 12 TPS genes in D. purpureum is developmentally regulated. During multicellular development, D. purpureum releases a mixture of volatile terpenes dominated by sesquiterpenes that are the in vitro products of a subset of the 12 TPS genes. The quality and quantity of the terpenes released from D. purpureum, however, bear little resemblance to those of D. discoideum, a closely related dictyostelid. Despite these variations, the conserved clade of dictyostelid TPSs, which have an evolutionary distance of more than 600 million years, has the same biochemical function, catalyzing the formation of a sesquiterpene protoillud-7-ene. Taken together, our results indicate that the dynamic evolution of dictyostelid TPS genes includes both purifying selection of an orthologous group and species-specific expansion with functional divergence. Consequently, the terpenes produced by these TPSs most likely have conserved as well as species-adaptive biological functions as chemical languages in dictyostelids.
Effect of Vitis vinifera hydroalcoholic extract against oxaliplatin neurotoxicity: in vitro and in vivo evidence
Authors: Micheli Laura , Mattoli Luisa , Maidecchi Anna , Pacini Alessandra , Ghelardini Carla , Di Cesare Mannelli Lorenzo 
Published: September 2018

AbstractOxaliplatin treatment is associated with the development of a dose-limiting painful neuropathy impairing patient’s quality of life. Since oxidative unbalance is a relevant mechanism of oxaliplatin neurotoxicity, we assessed the potential antioxidant properties of Vitis vinifera extract in reducing oxaliplatin-induced neuropathy as a valuable therapeutic opportunity. A hydroalcoholic extract of Vitis vinifera red leaf was characterized and tested in primary rat astrocyte cells treated with oxaliplatin (100 μM). Oxaliplatin lethality in the human adenocarcinoma cell line HT-29 was evaluated in the absence and presence of the extract. In vivo, pain hypersensitivity was measured in a rat model of neuropathy induced by oxaliplatin and ex vivo molecular targets of redox balance were studied. Vitis vinifera extract (50 μg mL−1, 4 h incubation) significantly reduced the oxaliplatin-dependent superoxide anion increase and lipid peroxidation in rat astrocytes but did not interfere with the mortality elicited by oxaliplatin in HT-29 cancer cells. In oxaliplatin-treated rats, a repeated daily administration of the Vitis vinifera extract (300 mg kg−1, p.o.) significantly prevented mechanical and thermal hypersensitivity to noxious and non noxious stimuli. mRNA and protein levels of Nrf2 were normalized in spinal cord and DRGs. Moreover, in the spinal cord, the extract significantly decreased the activation of astrocytes. Vitis vinifera reduced oxidative damages and relieved pain without influencing oxaliplatin anti-cancer activity.
A polymorphism in the fatty acid desaturase-2 gene is associated with the arachidonic acid metabolism in pigs
Authors: Gol Sofia , Pena Ramona N. , Rothschild Max F. , Tor Marc , Estany Joan 
Published: September 2018

AbstractArachidonic acid (C20:4) is related to a wide range of biological effects including lipid homeostasis. The fatty acid desaturase-2 (FADS2) gene encodes for the delta-6-desaturase, which is involved in the biosynthesis of C20:4 from linoleic acid (C18:2). The purpose of this study was to characterise mutations in the promoter of the porcine FADS2, evaluating in particular the effect of one haplotype tagging polymorphism (rs321384923A > G) on the biosynthesis pathway of C20:4. A total of 1,192 Duroc barrows with records on fatty acid composition in muscle and subcutaneous fat were genotyped. Pigs carrying the A allele showed, irrespective of fat content, both enhanced FADS2 expression and higher C20:4 in muscle and exhibited increased ratios of C20:4 to C18:2 and of C20:4 to eicosadienoic acid (C20:2) in both muscle and adipose tissue. Despite the inverse relationship observed between C20:4 and fat content, the rs321384923 polymorphism had no impact on lean weight. It is concluded that the haplotype encompassing the rs321384923 polymorphism at the porcine FADS2 affects the n-6 fatty acid profile by specifically modifying the desaturation efficiency of C18:2 to C20:4 rather than by concomitant variations in C18:2 following changes in fat content.
Polycomb Repressive Complex 2 is essential for development and maintenance of a functional TEC compartment
Authors: Singarapu Nandini , Ma Keyue , Reeh Kaitlin A. G. , Shen Jianjun , Lancaster Jessica N. , Yi Song , Xie Huafeng , Orkin Stuart H. , Manley Nancy R. , Ehrlich Lauren I. R. , Jiang Ning , Richie Ellen R. 
Published: September 2018

AbstractThymic epithelial cells (TEC) are essential for thymocyte differentiation and repertoire selection. Despite their indispensable role in generating functional T cells, the molecular mechanisms that orchestrate TEC development from endodermal progenitors in the third pharyngeal pouch (3rd PP) are not fully understood. We recently reported that the T-box transcription factor TBX1 negatively regulates TEC development. Although initially expressed throughout the 3rd PP, Tbx1 becomes downregulated in thymus-fated progenitors and when ectopically expressed impairs TEC progenitor proliferation and differentiation. Here we show that ectopic Tbx1 expression in thymus fated endoderm increases expression of Polycomb repressive complex 2 (PRC2) target genes in TEC. PRC2 is an epigenetic modifier that represses gene expression by catalyzing trimethylation of lysine 27 on histone H3. The increased expression of PRC2 target genes suggests that ectopic Tbx1 interferes with PRC2 activity and implicates PRC2 as an important regulator of TEC development. To test this hypothesis, we used Foxn1Cre to delete Eed, a PRC2 component required for complex stability and function in thymus fated 3rd PP endoderm. Proliferation and differentiation of fetal and newborn TEC were disrupted in the conditional knockout (EedCKO) mutants leading to severely dysplastic adult thymi. Consistent with PRC2-mediated transcriptional silencing, the majority of differentially expressed genes (DEG) were upregulated in EedCKO TEC. Moreover, a high frequency of EedCKO DEG overlapped with DEG in TEC that ectopically expressed Tbx1. These findings demonstrate that PRC2 plays a critical role in TEC development and suggest that Tbx1 expression must be downregulated in thymus fated 3rd PP endoderm to ensure optimal PRC2 function.
Modeling of mesenchymal hybrid epithelial state and phenotypic transitions in EMT and MET processes of cancer cells
Authors: He Peng , Qiu Kang , Jia Ya 
Published: September 2018

AbstractBased on the transcriptional regulatory mechanisms between microRNA-200 and transcription factor ZEB in an individual cancer cell, a minimal dynamic model is proposed to study the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) processes of cancer cells. It is shown that each cancer cell can exit in any of three phenotypic states: the epithelial (E) state, the mesenchymal (M) state, and the epithelial/mesenchymal (E/M) hybrid state, and the state of cancer cell can interconvert between different states. The phase diagram shows that there are monostable, bistable, and tristable phenotypic states regions in a parameters plane. It is found that different pathway in the phase diagram can correspond to the EMT or the MET process of cancer cells, and there are two possible EMT processes. It is important that the experimental phenomenon of E/M hybrid state appearing in the EMT process but rather in the MET process can be understood through different pathways in the phase diagram. Our numerical simulations show that the effects of noise are opposite to these of time delay on the expression of transcription factor ZEB, and there is competition between noise and time delay in phenotypic transitions process of cancer cells.
Transcriptomic analysis reveal an efficient osmoregulatory system in Siberian sturgeon Acipenser baeri in response to salinity stress
Authors: Guo Baoying , Tang Zurong , Wu Changwen , Xu Kaida , Qi Pengzhi 
Published: September 2018

AbstractSturgeons are euryhaline fish species that have developed specific mechanisms of osmotic and ion regulation to adapt to waters of varying salinity. For the aim to elucidate the osmoregulation strategy behind its high salinity tolerance of sturgeons, the transcriptomes of gills in Siberian sturgeon Acipenser baeri under salinity stress (30 ppt) were sequenced using deep-sequencing platform Illumina/HiSeq-2500 and differential expression genes (DEGs) were identified. A total of 167, 501, 278 clean reads were obtained and 280, 238 unigenes were composed of those clean reads with the mean length of 520nt, and the N50 of 630 bp. Unigenes Sequence alignment was implemented via KEGG, KOG, NT, NR, PFAM, Swiss-Prot, and GO databases. 62, 242 unigenes (22.21%) were annoated in at least one database. 11380 significantly differentially expressed unigenes were found, 6969 of which were up-regulated and 4411 were down-regulated by salinity stress. Amongst the top 20 KEGG pathways with the most amount of annotation sequences, some pathways such as glycerophospholipid metabolism, fatty-acid biosynthesis, glycolysis/gluconeogenesis, oxidative phosphorylation have been comprehensively proved to be relevant to osmoregulation. Despite of these, three possible osmoregulation-related signaling pathways as lipid metabolism related pathways, tight junction pathway and thyroid hormone signaling pathway have been widely analyzed in the current study. In all DEGs, some of the typical genes involved in osmoregulation, including calcium-transporting ATPase 4 (ATP2B4), Na+/K+-ATPase alpha subunit (α-NKA), potassium-transporting ATPase alpha chain 1 (ATP4A) and Ras GTPase-activating protein (RasGAP) etc were also identified. RNA-seq results were validated with quantitative real-time PCR (qPCR), the 12 selected genes showed a consistent direction in both DGE library and qPCR analysis, proving that the RNA-seq results are reliable. The present results would be helpful to elucidate the osmoregulation mechanism of aquatic animals adapting to salinity challenge.
En Face and Cross-sectional Corneal Tomograms Using Sub-micron spatial resolution Optical Coherence Tomography
Authors: Chen Yu-Tung , Tsai Chia-Ying , Chiu Yu-Kuang , Hsu Ting-Wei , Chen Lily Wei , Chen Wei-Li , Huang Sheng-Lung 
Published: September 2018

AbstractAccurate diagnosis of corneal pathology and morphological identification of different corneal layers require clear delineation of corneal three-dimensional structures and en face or cross-sectional imaging of palisade of Vogt (POV), neovascularization (NV) or corneal nerves. Here we report a prototype of full-field optical coherence tomography (FF-OCT) system with isotropic sub-micron spatial resolution in the en face and cross-sectional views. It can also provide three-dimensional reconstructed images and a large field of view (FOV) by stitching tomograms side by side. We validated the imaging power of this prototype in in vivo rat and rabbit eyes, and quantified anatomical characteristics such as corneal layer thickness, endothelial cell density and the intensity profile of different layers. This FF-OCT delineated the ridge-like structure of POV, corneal nerve bundles, and conjunctival vessels in rat eyes. It also clearly identified the vessel walls and red blood cells in rabbit model of corneal NV. The findings provided by this FF-OCT are expected to facilitate corneal disease diagnosis and treatment.
The lantibiotic nukacin ISK-1 exists in an equilibrium between active and inactive lipid-II binding states
Authors: Fujinami Daisuke , -Mahin Abdullah-Al , Elsayed Khaled M. , Islam Mohammad R. , Nagao Jun-ichi , Roy Urmi , Momin Sabrina , Zendo Takeshi , Kohda Daisuke , Sonomoto Kenji 
Published: September 2018

AbstractThe lantibiotic nukacin ISK-1 exerts antimicrobial activity through binding to lipid II. Here, we perform NMR analyses of the structure of nukacin ISK-1 and the interaction with lipid II. Unexpectedly, nukacin ISK-1 exists in two structural states in aqueous solution, with an interconversion rate on a time scale of seconds. The two structures differ in the relative orientations of the two lanthionine rings, ring A and ring C. Chemical shift perturbation induced by the titration of lipid II reveals that only one state was capable of binding to lipid II. On the molecular surface of the active state, a multiple hydrogen-bonding site formed by amino acid residues in the ring A region is adjacent to a hydrophobic surface formed by residues in the ring C region, and we propose that these sites interact with the pyrophosphate moiety and the isoprene chain of the lipid II molecule, respectively.
Environnement social, incorporation biologique et inégalités sociales de santé
Authors: Delpierre Cyrille , Castagné Raphaële , Lang Thierry , Kelly-Irving Michelle 
Published: September 2018

Le gradient social de santé renvoie au fait que plus on s’élève dans la hiérarchie sociale meilleur est l’état de santé. La compréhension de la construction du gradient constitue un enjeu majeur en épidémiologie sociale. Une approche originale consiste à s’intéresser à la façon dont les différentes expositions associées à l’environnement social (chimiques, physiques, comportementales, psychosociales, etc.) s’expriment in fine biologiquement pour influencer positivement ou négativement la santé, renvoyant au concept d’incorporation biologique. Des données issues des modèles animaux et de l’épidémiologie dite « life course » permettent d’éclairer sous un jour nouveau les mécanismes biologiques potentiellement en jeu. Les découvertes récentes issues du champ de l’épigénétique permettent de mieux comprendre comment l’environnement social, notamment précoce, peut influencer le fonctionnement biologique sur le long terme, voire sur plusieurs générations. Les travaux sur l’incorporation biologique du social en lien avec l’épigénétique sont encore très largement à consolider, mais ils pourraient constituer un changement de perspective en biologie humaine notamment en reconsidérant l’influence de l’environnement sur le fonctionnement biologique, ce qui n’est pas sans conséquence en termes d’interventions en santé publique.
Visual Distraction During Sleep Induction with Propofol in Pediatric Patients – Can Cartoon Watching Influence the Sedative Dose?
Authors: Tschiedel Eva , Beckers Kristina , Große-Lordemann Anja , Basu Oliver , Felderhoff-Müser Ursula , Dohna-Schwake Christian 
Published: September 2018

Abstract
Background In general anesthesia, cartoon watching and playing video games reduce anxiety in children. It is unknown whether watching a video in the intervention room has a similar effect, and therefore is able to reduce sedative doses in children undergoing small medical procedures. Aim of this prospective study was to determine the effect of watching a standardized cartoon immediately before and during sleep induction for deep sedation on consumption of propofol in children.
Patients and Methods 50 children aged 2–14 years undergoing deep sedation were randomly assigned to 2 groups: (A) watching or (B) not watching a standardized videoclip during sleep induction with propofol. The achievement of predefined sedation depth was objectified by measuring Comfort Score (aim 10–14) and Bispectral Index (aim 50–60).
Results The median sleep induction dose of propofol did not differ in both groups (A: 1.76 (0.62–4.37) mg/kg; B: 1.37 (0.66–5.26) mg/kgKG; p=0.65). Cartoon watching was associated with shorter sleep onset latency (A: 120 (60–480)s; B: 240 (40–600)s; p=0.043). Subgroup analysis reveals this especially for school children and girls. In both groups no complications occurred.
Conclusion Children watching a standard cartoon during sleep induction for deep sedation have a shorter sleep onset time but sedative dose is not reduced.
Hausärztliche Demenzdiagnostik – Einstellungen, Vorgehensweisen und Herausforderungen von Hausärzten in Rheinland-Pfalz
Authors: Wangler Julian , Fellgiebel Andreas , Jansky Michael 
Published: September 2018

Zusammenfassung
Hintergrund Regelmäßig wird moniert, dass die Erkennung von Demenzerkrankungen in der hausärztlichen Versorgung nicht effektiv genug sei, besonders mit Blick auf frühe Demenzstadien. Studien lassen vermuten, dass unter Allgemeinmedizinern diverse Vorbehalte hinsichtlich der Demenzdiagnostik bestehen. Welche Ursachen diese haben und welche konkreten Positionen sowie Strategien Hausärzte bei der Versorgung von Demenzpatienten vertreten, wurde bislang kaum untersucht. Ziel der Studie war es, Einstellungen von Hausärzten in Bezug auf die Demenzdiagnostik genauer zu beleuchten, verbreitete Herausforderungen im Praxisalltag herauszuarbeiten sowie Ansatzpunkte für eine Optimierung abzuleiten.
Methoden Mittels schriftlicher Befragung, die auf Basis einer separaten Interview-Vorstudie fundiert, wurden zwischen November 2017 und Januar 2018 insgesamt 425 Hausärzte in Rheinland-Pfalz befragt.
Ergebnisse Ein beträchtlicher Teil der befragten Hausärzte hat sich aus der Demenzdiagnostik zurückgezogen und delegiert die Betreuung von Demenzpatienten ausschließlich an die Facharztebene. Aus den Ergebnissen lassen sich verschiedene Vorbehalte und Herausforderungen verdichten, die der Effektivität der hausärztlichen Demenzversorgung entgegenwirken: 1) geringe subjektive Wirksamkeitswahrnehmung beim Krankheitsbild Demenz, 2) differenzialdiagnostische Abklärung als Hürde, 3) Schwierigkeiten bei der Arzt-Patient-Kommunikation, 4) mangelnde Honorierung, 5) geringe Einbeziehung des Praxispersonals, 6) negativere Einstellungen zur Demenzdiagnostik durch Fehlen geriatrischer Weiterbildung, 7) begrenzte Zusammenarbeit mit und Kenntnis von regionalen Beratungs- und Versorgungsangeboten.
Schlussfolgerung Aus der Analyse gehen mehrere Ansatzpunkte hervor, auf deren Basis sich die hausarztbasierte Demenzversorgung weiter verbessern ließe. Hierbei handelt es sich um 1) verstärktes Bewusstsein für Handlungsoptionen jenseits therapeutischer Interventionen, 2) Differenzialdiagnostik und Behandlungspfade, 3) Arzt-Patient-Kommunikation sowie 4) Honorierung und Anreize, 5) Involvierung des Praxispersonals, 6) höhere Sensitivität durch geriatrische Weiterbildung, 7) Kooperation mit Beratungs- und Versorgungsnetzwerken.
Chronische Lymphatische Leukämie
Authors: Schneider Christof , Steinbrecher Daniela , Stilgenbauer Stephan 
Published: September 2018

ZusammenfassungDie chronische lymphatische Leukämie ist eine Erkrankung mit sehr heterogenem Verlauf. Mithilfe verschiedener Faktoren können Abschätzungen bezüglich des
Krankheitsverlaufs erfolgen und individualisierte Therapien angewandt werden. Zielgerichtete Therapien, die sich gegen das B-Zell-Rezeptor-Signalling oder das
anti-apoptotische Protein BCL-2 richten, bieten die Möglichkeit einer chemotherapie-freien Behandlung. Diese Therapien zeigen bei quasi allen Patienten,
insbesondere auch nach intensiver Vortherapie und bei Hochrisikogenetik, ein gutes Ansprechen und lange Überlebenszeiten.
Formation and Properties of Fibrin Clots Resulting from Staphylocoagulase (SC) Action
Authors: Kopeć M , Węgrzynowicz Z , Budzyński A. Z , Jeljaszewicz J , Latallo Z. S , Lipiński B , Kowalski E 
Published: September 2018

SummarySome properties of the fibrin clots formed under the influence of staphylocoagulase (SC) and thrombin were compared.1. Mechanical properties of SC-induced clots were found to be different from thrombin-induced clots. Maximal amplitude in TEG was significantly smaller in the case of SC.2. In the system containing all other necessary components for fibrin stabilization, SC in contrasts to thrombin did not produce stabilized clots. It was shown that this was due to the lack of FSF activation by SC. SC induced fibrin was easily stabilized by the addition of FSF activated by thrombin. No difference in sialic acid content has been found when SC and thrombin induced fibrins were compared.3. Neither clotting nor esterase activity of SC were inhibited by heparin and hirudin.4. Fibrinogen degradation products (FDP) inhibit clotting activity of SC. Both early and late FDP seem to affect this activity in a similar degree, whereas early FDP show much more pronounced effect in the case of thrombin induced clotting.5. The SC-clots are much more resistant to plasmin action, although SC itself does not inhibit plasmin caseinolytic activity.6. The significance of these findings is discussed.