bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thuricin Z: A Narrow‐Spectrum Sactibiotic that Targets the Cell Membrane
Authors: Mo Tianlu , Ji Xinjian , Yuan Wei , Mandalapu Dhanaraju , Wang Fangting , Zhong Yuting , Li Fuyou , Chen Qin , Ding Wei , Deng Zixin , Yu Shaoning , Zhang Qi 
Published: September 2019

AbstractSactionine‐containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post‐translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S‐adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow‐spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin‐sectioning transmission electron microscopy, scanning electron microscopy, and large‐unilamellar‐vesicle‐based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.
An analytical perturbative solution to the Merton–Garman model using symmetries
Authors: Calmet Xavier , Wiesendanger Shaw Nathaniel 
Published: September 2019

AbstractIn this paper, we introduce an analytical perturbative solution to the Merton–Garman model. It is obtained by doing perturbation theory around the exact analytical solution of a model which possesses a two‐dimensional Galilean symmetry. We compare our perturbative solution of the Merton–Garman model to Monte Carlo simulations and find that our solutions perform surprisingly well for a wide range of parameters. We also show how to use symmetries to build option pricing models. Our results demonstrate that the concept of symmetry is important in mathematical finance.
microRNA‐599 promotes apoptosis and represses proliferation and epithelial‐mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2‐depentent Notch signaling pathway
Authors: Wang Duo‐Ping , Tang Xiao‐Zhun , Liang Quan‐Kun , Zeng Xian‐Jie , Yang Jian‐Bo , Xu Jian 
Published: September 2019

AbstractAlthough papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA‐599 (miR‐599) on proliferation, apoptosis, and epithelial‐mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual‐luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR‐599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR‐559. In addition, the expression of Bax and E‐cadherin was elevated while that of Hey2, Notch1, Delta‐like1, Hes1, N1ICD, Jagged1, Snail, Slug, N‐cadherin and Vimentin, and Bcl‐2 was reduced in cells treated with upregulated miR‐599 or downregulated Hey2. Moreover, miR‐599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR‐599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.
Klinische Charakteristika, Ressourcenverbrauch, Lebensqualität und Versorgungssituation beim Dravet-Syndrom in Deutschland
Authors: Kalski Malin , Schubert-Bast Susanne , Kieslich Matthias , Leyer Anne‑Christine , Polster Tilman , Herting Arne , Mayer Thomas , Trollmann Regina , Neubauer Bernd A. , Bettendorf Ulrich , Bast Thomas , Wiemer-Kruel Adelheid , von Spiczak Sarah , Kurlemann Gerhard , Wolff Markus , Kluger Gerhard , Carroll Joe , Macdonald Daniel , Pritchard Clive , Irwin John , Klein Karl Martin , Rosenow Felix , Strzelczyk Adam , Kay Lara 
Published: September 2019

Zusammenfassung
Fragestellung
Ziel der prospektiven, multizentrischen Studie ist die Erfassung klinischer Charakteristika, des Ressourcenverbrauches sowie der Lebensqualität bei Patienten mit der Diagnose eines Dravet-Syndroms (DS) und deren Eltern in Deutschland.

Methoden
Die Datenerhebung erfolgte mit einem validierten retrospektiven Fragebogen über 3 bzw. 12 Monate sowie mit einem prospektiven Tagebuch über 3 Monate. Es wurden Daten zur Anfallssituation, Medikamenteneinnahme, Therapieinanspruchnahme sowie zu direkten und indirekten Kosten und zur Lebensqualität erhoben. Die Fragebögen und das Tagebuch wurden den Eltern über den Dravet-Syndrom e. V. sowie beteiligte Zentren ausgehändigt.

Ergebnisse
Der Fragebogen wurde von 93 Eltern der DS-Patienten und das Tagebuch von 77 ausgefüllt. Das mittlere Alter der Patienten betrug 10 Jahre (Spannweite 15 Monate bis 33,7 Jahre). Die Zeit bis zur Syndromdiagnose eines DS war in den letzten beiden Jahrzehnten deutlich kürzer. In den letzten 12 Monaten ereignete sich bei 95 % der Patienten mindestens ein epileptischer Anfall. Als anfallsauslösende Faktoren wurden Fieber (93,4 %), Aufregung (56 %), Schlafmangel (51,6 %) und starke körperliche Anstrengung (50,5 %) berichtet. Die Lebenszeitprävalenz des Status epilepticus lag bei 77 %, und bei 28 % war mindestens 1 Episode eines Status epilepticus innerhalb des letzten Jahres aufgetreten. Die Lebensqualität (QoL) der Patienten war niedriger als die der Allgemeinbevölkerung, und von 46 % der Eltern wurden Depressionssymptome berichtet. Die direkten Kosten in 3 Monaten betrugen 6043 € pro Patient. Den größten Kostenfaktor stellten die stationären Kosten dar (1702 €), gefolgt von den Leistungen für Pflege (1130 €), den Kosten für die antikonvulsiven Medikamente (892 €) und für Therapien (559 €). Bei den Müttern betrugen die gesamten indirekten Kosten 4399 € und bei den Vätern 391 € bezogen auf 3 Monate.

Schlussfolgerung
Das Dravet-Syndrom ist mit häufigen, oft therapierefraktären epileptischen Anfällen und Status epilepticus vergesellschaftet. Diese Studie zeigt die erhebliche Krankheitslast und die damit verbundenen Einschränkungen in der Lebensqualität sowie die hohen direkten und indirekten Kosten auf. Um eine Verbesserung der Lebensqualität bei Patienten mit DS und deren Eltern zu erreichen, bedarf es neuer Therapie- und Versorgungskonzepte.
Mathematical modeling of the glucagon challenge test
Authors: Masroor Saeed , van Dongen Marloes G. J. , Alvarez-Jimenez Ricardo , Burggraaf Koos , Peletier Lambertus A. , Peletier Mark A. 
Published: September 2019

AbstractA model for the homeostasis of glucose through the regulating hormones glucagon and insulin is described. It contains a subsystem that models the internalization of the glucagon receptor. Internalization is a mechanism in cell signaling, through which G-protein coupled receptors are taken from the surface of the cell to the endosome. The model is used to interpret data from a glucagon challenge test in which subjects have been under treatment with a novel glucagon receptor anti-sense drug which is aimed at reducing the number of receptors in the liver. It is shown how the receptor internalization results in tolerance of the blood glucose concentration to glucagon-induced hyperglycemia. We quantify the reduction of the number of receptors using the model and the data before and after treatment.
The role of business in sustainable development and peacebuilding: Observing interaction effects
Authors: Miklian Jason 
Published: September 2019

AbstractHow can we better understand the complex interaction effects that are triggered when businesses and international government agencies become partners in social development? To answer, this article presents field experiences of Heineken in the Democratic Republic of Congo, ethnic cleansing in Myanmar, and the United Nations Global Compact in Dubai, to show the impact of key multi-stakeholder business-development policies as experienced by millions of people. These cases help us understand business and sustainable development interactions by exploring existing research gaps regarding issues of discourse, guidance, and legitimacy. This article has four aims: (1) to show that business-development interactions are much more complex than most case studies are able to encapsulate; (2) to explore how unintended ripple effects of even the most promising “win-win” business-development policies can carry catastrophic consequences; (3) to illustrate the potential benefits of a novel methodology for future research on business, global governance, and sustainable development; and (4) to show how business and development concerns interconnect across and through the macro- and meso-levels of analysis down to local livelihood interactions and impacts. I contextualize these experiences to emerging scholarship, opening avenues for building theory and improving policy on business, development, and peace.
International Order in Historical East Asia: Tribute and Hierarchy Beyond Sinocentrism and Eurocentrism
Authors: Kang David C. 
Published: September 2019

AbstractIR theorizing about international order has been profoundly, perhaps exclusively, shaped by the Western experiences of the Westphalian order and often assumes that the Western experience can be generalized to all orders. Recent scholarship on historical East Asian orders challenges these notions. The fundamental organizing principle in historical East Asia was hierarchy, not sovereign equality. The region was characterized by hegemony, not balance of power. This emerging research program has direct implications for enduring questions about the relative importance of cultural and material factors in both international orders and their influence on behavior—for describing and explaining patterns of war and peace across time and space, for understanding East Asia as a region made up of more than just China, and for more usefully comparing East Asia, Europe, and other regions of the world.
Comparison of nasal and olfactory functions between two surgical approaches for the treatment of concha bullosa: a randomised clinical trial
Authors: Andaloro C , La Mantia I , Castro V , Grillo C 
Published: September 2019

AbstractObjectiveConcha bullosa may be associated with paranasal sinus infections and nasal obstruction. Middle concha mucosa membranes have olfactory neurofibrils. This study investigated the impact of routinely used concha bullosa surgery techniques – crushing and lateral laminectomy – on nasal and olfactory functions.MethodsForty-three adult patients who had undergone surgery for a symptomatic concha bullosa completed the odour test, nasal obstruction visual analogue scale, 22-item Sino-Nasal Outcome Test, and peak nasal inspiratory flow test, pre-operatively and three months post-operatively. The pre- and post-operative results within and between the two treatment groups were compared.ResultsIntragroup comparison of mean pre- versus post-treatment changes revealed statistically significant findings for the nasal obstruction visual analogue scale, Sino-Nasal Outcome Test, peak nasal inspiratory flow and olfaction tests (allp< 0.05). However, there were no statistically significant changes when comparing the scores between the groups (intergroup comparison).ConclusionLateral laminectomy and crushing in concha bullosa surgery have no negative effects on olfactory function. Concha bullosa surgery provides positive outcomes regarding nasal complaints in symptomatic patients.
The association between intimate partner violence against women and newborn telomere length
Authors: Chan Ko Ling , Lo Camilla K. M. , Ho Frederick K. , Leung Wing Cheong , Yee Benjamin K. , Ip Patrick 
Published: September 2019

AbstractIntimate partner violence (IPV) against women negatively impacts infant health. However, its impact on infant’s biology, in particular on telomere length (TL) is unknown. The aim of this study was to examine the association between IPV against women before childbirth and cord blood TL in their newborn. A total of 774 pregnant women in the 20th–24th week of gestation were recruited at a public hospital in Hong Kong. The mothers’ exposure to IPV before childbirth, demographic characteristics, obstetric outcomes, health and mental health were measured at the time of recruitment and 4 weeks after childbirth. Umbilical cord blood was collected by midwives at the time of delivery. The newborn TL was quantified using quantitative PCR method and expressed in T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). After adjusting for a number of confounding variables, the mothers’ exposure to any IPV before childbirth (β = −0.08, 95% CI = −0.14, −0.01) was associated with shorter TL. Specifically, psychological abuse against women before childbirth (β = −0.08, 95% CI = −0.15, −0.02) and sexual abuse against women before childbirth (β = −0.22, 95% CI = −0.43 to −0.01) were significantly associated with reduced newborn TL. This study is the first to provide evidence of an association between IPV against women before childbirth and TL shortening in their newborns. Through TL- dependent transcription and epigenetic mechanisms, our finding suggests maternal exposure to IPV may exert a life-long impact on the offspring’s health.
Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia
Authors: Kumar Vivek , Ailawadhi Sikander , Bojanini Leyla , Mehta Aditya , Biswas Suman , Sher Taimur , Roy Vivek , Vishnu Prakash , Marin-Acevedo Julian , Alegria Victoria R. , Paulus Aneel , Aulakh Sonikpreet , Iqbal Madiha , Manochakian Rami , Tan Winston , Chanan-Khan Asher , Ailawadhi Meghna 
Published: September 2019

AbstractWith improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17–1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12–1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5–1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41–1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003–2015 (SIR 1.36; 95% CI:1.3–1.42) as compared to 1973–1982 (SIR 1.19; 95% CI:1.12–1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31–1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13–1.19, p < 0.001). In a multivariate analysis, the hazard of developing SPMs was higher among men, post-chemotherapy, recent years of diagnosis, advanced age, and non-Whites. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL.
Stromal cells downregulate miR-23a-5p to activate protective autophagy in acute myeloid leukemia
Authors: Ganesan Saravanan , Palani Hamenth Kumar , Lakshmanan Vairavan , Balasundaram Nithya , Alex Ansu Abu , David Sachin , Venkatraman Arvind , Korula Anu , George Biju , Balasubramanian Poonkuzhali , Palakodeti Dasaradhi , Vyas Neha , Mathews Vikram 
Published: September 2019

AbstractComplex molecular cross talk between stromal cells and the leukemic cells in bone marrow is known to contribute significantly towards drug-resistance. Here, we have identified the molecular events that lead to stromal cells mediated therapy-resistance in acute myeloid leukemia (AML). Our work demonstrates that stromal cells downregulate miR-23a-5p levels in leukemic cells to protect them from the chemotherapy induced apoptosis. Downregulation of miR-23a-5p in leukemic cells leads to upregulation of protective autophagy by targeting TLR2 expression. Further, autophagy inhibitors when used as adjuvants along with conventional drugs can improve drug sensitivity in vitro as well in vivo in a mouse model of leukemia. Our work also demonstrates that this mechanism of bone marrow stromal cell mediated regulation of miR-23a-5p levels and subsequent molecular events are relevant predominantly in myeloid leukemia. Our results illustrate the critical and dynamic role of the bone marrow microenvironment in modulating miRNA expression in leukemic cells which could contribute significantly to drug resistance and subsequent relapse, possibly through persistence of minimal residual disease in this environment.
The structural basis for RNA selectivity by the IMP family of RNA-binding proteins
Authors: Biswas Jeetayu , Patel Vivek L. , Bhaskar Varun , Chao Jeffrey A. , Singer Robert H. , Eliscovich Carolina 
Published: September 2019

AbstractThe IGF2 mRNA-binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine systematic evolution of ligands by exponential enrichment (SELEX) and NMR spectroscopy to demonstrate that the major RNA-binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.
Stable memory with unstable synapses
Authors: Susman Lee , Brenner Naama , Barak Omri 
Published: September 2019

AbstractWhat is the physiological basis of long-term memory? The prevailing view in Neuroscience attributes changes in synaptic efficacy to memory acquisition, implying that stable memories correspond to stable connectivity patterns. However, an increasing body of experimental evidence points to significant, activity-independent fluctuations in synaptic strengths. How memories can survive these fluctuations and the accompanying stabilizing homeostatic mechanisms is a fundamental open question. Here we explore the possibility of memory storage within a global component of network connectivity, while individual connections fluctuate. We find that homeostatic stabilization of fluctuations differentially affects different aspects of network connectivity. Specifically, memories stored as time-varying attractors of neural dynamics are more resilient to erosion than fixed-points. Such dynamic attractors can be learned by biologically plausible learning-rules and support associative retrieval. Our results suggest a link between the properties of learning-rules and those of network-level memory representations, and point at experimentally measurable signatures.
CENP-A nucleosome clusters form rosette-like structures around HJURP during G1
Authors: Andronov Leonid , Ouararhni Khalid , Stoll Isabelle , Klaholz Bruno P. , Hamiche Ali 
Published: September 2019

AbstractCENP-A is an essential histone H3 variant that epigenetically marks the centromeric region of chromosomes. Here we show that CENP-A nucleosomes form characteristic clusters during the G1 phase of the cell cycle. 2D and 3D super-resolution microscopy and segmentation analysis reveal that these clusters encompass a globular rosette-like structure, which evolves into a more compact structure in late G1. The rosette-like clusters contain numerous CENP-A molecules and form a large cellular structure of ∼250–300 nm diameter with remarkably similar shapes for each centromere. Co-localization analysis shows that HJURP, the CENP-A chaperone, is located in the center of the rosette and serves as a nucleation point. The discovery of an HJURP-mediated CENP-A nucleation in human cells and its structural description provide important insights into the mechanism of CENP-A deposition and the organization of CENP-A chromatin in the centromeric region.
Integration of single photon emitters in 2D layered materials with a silicon nitride photonic chip
Authors: Peyskens Frédéric , Chakraborty Chitraleema , Muneeb Muhammad , Van Thourhout Dries , Englund Dirk 
Published: September 2019

AbstractPhotonic integrated circuits (PICs) enable the miniaturization of optical quantum circuits because several optic and electronic functionalities can be added on the same chip. Integrated single photon emitters (SPEs) are central building blocks for such quantum photonic circuits. SPEs embedded in 2D transition metal dichalcogenides have some unique properties that make them particularly appealing for large-scale integration. Here we report on the integration of a WSe2 monolayer onto a Silicon Nitride (SiN) chip. We demonstrate the coupling of SPEs with the guided mode of a SiN waveguide and study how the on-chip single photon extraction can be maximized by interfacing the 2D-SPE with an integrated dielectric cavity. Our approach allows the use of optimized PIC platforms without the need for additional processing in the SPE host material. In combination with improved wafer-scale CVD growth of 2D materials, this approach provides a promising route towards scalable quantum photonic chips.
High levels of AAV vector integration into CRISPR-induced DNA breaks
Authors: Hanlon Killian S. , Kleinstiver Benjamin P. , Garcia Sara P. , Zaborowski Mikołaj P. , Volak Adrienn , Spirig Stefan E. , Muller Alissa , Sousa Alexander A. , Tsai Shengdar Q. , Bengtsson Niclas E. , Lööv Camilla , Ingelsson Martin , Chamberlain Jeffrey S. , Corey David P. , Aryee Martin J. , Joung J. Keith , Breakefield Xandra O. , Maguire Casey A. , György Bence 
Published: September 2019

AbstractAdeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In this study, we observe high levels of AAV integration (up to 47%) into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in cultured murine neurons, mouse brain, muscle and cochlea. Genome-wide AAV mapping in mouse brain shows no overall increase of AAV integration except at the CRISPR/Cas9 target site. To allow detailed characterization of integration events we engineer a miniature AAV encoding a 465 bp lambda bacteriophage DNA (AAV-λ465), enabling sequencing of the entire integrated vector genome. The integration profile of AAV-465λ in cultured cells display both full-length and fragmented AAV genomes at Cas9 on-target sites. Our data indicate that AAV integration should be recognized as a common outcome for applications that utilize AAV for genome editing.