bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides
Authors: Greco Ines , Molchanova Natalia , Holmedal Elin , Jenssen Håvard , Hummel Bernard D. , Watts Jeffrey L. , Håkansson Joakim , Hansen Paul R. , Svenson Johan 
Published: August 2020

AbstractThe use of non-standard toxicity models is a hurdle in the early development of antimicrobial peptides towards clinical applications. Herein we report an extensive in vitro and in vivo toxicity study of a library of 24 peptide-based antimicrobials with narrow spectrum activity towards veterinary pathogens. The haemolytic activity of the compounds was evaluated against four different species and the relative sensitivity against the compounds was highest for canine erythrocytes, intermediate for rat and human cells and lowest for bovine cells. Selected peptides were additionally evaluated against HeLa, HaCaT and HepG2 cells which showed increased stability towards the peptides. Therapeutic indexes of 50–500 suggest significant cellular selectivity in comparison to bacterial cells. Three peptides were administered to rats in intravenous acute dose toxicity studies up to 2–8 × MIC. None of the injected compounds induced any systemic toxic effects in vivo at the concentrations employed illustrating that the correlation between the different assays is not obvious. This work sheds light on the in vitro and in vivo toxicity of this class of promising compounds and provides insights into the relationship between the different toxicity models often employed in different manners to evaluate the toxicity of novel bioactive compounds in general.
Automated and rapid self-report of nociception in transgenic mice
Authors: Black Christopher J. , Allawala Anusha B. , Bloye Kiernan , Vanent Kevin N. , Edhi Muhammad M. , Saab Carl Y. , Borton David A. 
Published: August 2020

AbstractThere are currently no rapid, operant pain behaviors in rodents that use a self-report to directly engage higher-order brain circuitry. We have developed a pain detection assay consisting of a lick behavior in response to optogenetic activation of predominantly nociceptive peripheral afferent nerve fibers in head-restrained transgenic mice expressing ChR2 in TRPV1 containing neurons. TRPV1-ChR2-EYFP mice (n = 5) were trained to provide lick reports to the detection of light-evoked nociceptive stimulation to the hind paw. Using simultaneous video recording, we demonstrate that the learned lick behavior may prove more pertinent in investigating brain driven pain processes than the reflex behavior. Within sessions, the response bias of transgenic mice changed with respect to lick behavior but not reflex behavior. Furthermore, response similarity between the lick and reflex behaviors diverged near perceptual threshold. Our nociceptive lick-report detection assay will enable a host of investigations into the millisecond, single cell, neural dynamics underlying pain processing in the central nervous system of awake behaving animals.
Asynchrony among insect pollinator groups and flowering plants with elevation
Authors: Adedoja Opeyemi , Kehinde Temitope , Samways Michael J. 
Published: August 2020

AbstractMountains influence species distribution through differing climate variables associated with increasing elevation. These factors determine species niche ranges and phenology. Although the distribution patterns of some specific insect groups relative to elevation have been determined, how differing environmental conditions across elevation zones differentially influence the phenology of various insect groups is largely unknown. This is important in this era of rapid climate change. We assess here how species composition and seasonal peaks in abundance among different insect pollinator groups and flowering plants differ across four floristically distinct elevation zones up a sentinel mountain subject to strong weather events. We sampled insect pollinators in four major groups (bees, wasps, beetles and flies) over two spring seasons. Pollinator species composition across all elevation zones tracks flowering plant species composition. In terms of abundance, beetles were the dominant group across the three lower zones, but declined greatly in the summit zone, where flies and bees were more abundant. Bee abundance peaked earlier than the other groups across all four elevation zones, where there were significant peaks in abundance. Bee abundance peaked earlier than flowering plants at the middle zone and slightly later than flowering plants at the base zone, suggesting a mismatch. We conclude that, while elevation shapes species distribution, it also differentially influences species phenology. This may be of great significance in long-term assessment of species distribution in sensitive mountain ecosystems.
RNA polymerase II subunit D is essential for zebrafish development
Authors: Maeta Masanari , Kataoka Miku , Nishiya Yusuke , Ogino Kazutoyo , Kashima Makoto , Hirata Hiromi 
Published: August 2020

AbstractDNA-directed RNA polymerase II (pol II) is composed of ten core and two dissociable subunits. The dissociable subcomplex is a heterodimer of Rpb4/Polr2d and Rpb7/Polr2g, which are encoded by RPB4/polr2d and RPB7/polr2g genes, respectively. Functional studies of Rpb4/Polr2d in yeast have revealed that Rpb4 plays a role primarily in pol II-mediated RNA synthesis and partly in various mRNA regulations including pre-mRNA splicing, nuclear export of mRNAs and decay of mRNAs. Although Rpb4 is evolutionally highly conserved from yeast to human, it is dispensable for survival in budding yeast S. cerevisiae, whereas it was indispensable for survival in fission yeast S. pombe, slime molds and fruit fly. To elucidate whether Rpb4/Polr2d is necessary for development and survival of vertebrate animals, we generated polr2d-deficient zebrafish. The polr2d mutant embryos exhibited progressive delay of somitogenesis at the onset of 11 h postfertilization (hpf). Mutant embryos then showed increased cell death at 15 hpf, displayed hypoplasia such as small eye and cardiac edema by 48 hpf and prematurely died by 60 hpf. In accordance with these developmental defects, our RT-qPCR revealed that expression of housekeeping and zygotic genes was diminished in mutants. Collectively, we conclude that Rpb4/Polr2d is indispensable for vertebrate development.
Entry of Panton–Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus into the hospital: prevalence and population structure in Heidelberg, Germany 2015–2018
Authors: Klein Sabrina , Hannesen Julius , Zanger Philipp , Heeg Klaus , Boutin Sébastien , Nurjadi Dennis 
Published: August 2020

AbstractStaphylococcus aureus is one of the major pathogens causing community—and healthcare-acquired infections. The presence of the virulence factor Panton–Valentine leukocidin (PVL) is associated with recurrent infection and clinical severity and generally regarded as a feature of community associated-methicillin-resistant Staphylococcus aureus (MRSA). To date, the focus of PVL-positive MRSA in hospitalized patients has been on outbreaks. We aimed to investigate whether PVL-positive MRSA has penetrated the community-hospital barrier by determining the prevalence of PVL in MRSA of hospitalized patients. MRSA strains isolated from patients hospitalized > 48 h in Heidelberg University Hospital between 2015 and 2018 Isolates were analysed for the presence of PVL and subjected to spa-typing. PVL-positive MRSA were then characterized by whole genome sequencing. We analysed 740 MRSA isolates in the study period and identified 6.2% (n = 46) PVL-positivity. 32.6% of PVL-positive MRSA met the criteria for nosocomial acquisition. The most frequent clones among the PVL-positive strains were ST80-t044 (21.7%, n = 10/46) and ST8-t008 (19.5%, n = 9/46). WGS identified three possible transmission clusters involving seven patients. In conclusion, we found successful epidemic PVL-positive MRSA clones entering the hospital and causing nosocomial infections. Preventive measures and constant surveillance should be maintained to prevent transmissions and clonal outbreaks.
Epidemiology of human papillomavirus-related oropharyngeal cancer in a classically low-burden region of southern Europe
Authors: Mena M. , Frias-Gomez J. , Taberna M. , Quirós B. , Marquez S. , Clavero O. , Baena A. , Lloveras B. , Alejo M. , León X. , García J. , Mesía R. , Bermejo O. , Bonfill T. , Aguila A. , Guix M. , Hijano R. , Pavón M. A. , Torres M. , Tous S. , Clèries R. , Alemany L. 
Published: August 2020

AbstractThe incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing in some regions. Nevertheless, the epidemiology of this disease has not been extensively investigated in southern Europe. We conducted a retrospective cohort study of patients diagnosed with primary oropharyngeal cancer from 1991 to 2016. Cancer tissues underwent histopathological evaluation, DNA quality control, HPV-DNA detection and p16INK4aimmunohistochemistry. Data were collected from medical records. Factors associated with HPV positivity and time trends were evaluated with multivariable Bayesian models. The adjusted prevalence of HPV-related cases in 864 patients with a valid HPV-DNA result was 9.7%, with HPV-DNA/p16INK4adouble positivity being considered. HPV-related oropharyngeal cancer was likely to occur in non-smokers and non-drinkers, to be located in the tonsil or diagnosed at advanced stages. Time-trend analysis showed an increasing risk of HPV-related oropharyngeal cancer in the most recent periods (5-year period increase of 30%). This increase was highest and with a clear increasing trend only in the most recent years (2012–2016). The prevalence of HPV-related oropharyngeal cancer started to sharply increase in the most recent years in our setting, as occurred two decades ago in areas where most oropharyngeal cancer cases are currently HPV-related. Our results provide a comprehensive assessment of the epidemiological landscape of HPV-related oropharyngeal cancer in a region of southern Europe.
Manuka honey microneedles for enhanced wound healing and the prevention and/or treatment of Methicillin-resistant Staphylococcus aureus (MRSA) surgical site infection
Authors: Frydman Galit H. , Olaleye David , Annamalai Damodaran , Layne Kim , Yang Illina , Kaafarani Haytham M. A. , Fox James G. 
Published: August 2020

AbstractManuka honey (MH) is currently used as a wound treatment and suggested to be effective in Methicillin-resistantStaphylococcus aureus(MRSA) elimination. We sought to optimize the synthesis of MH microneedles (MHMs) while maintaining the MH therapeutic effects. MHMs were synthesized using multiple methods and evaluated with in vitro assays. MHMs demonstrated excellent bactericidal activity against MRSA at concentrations ≥ 10% of honey, with vacuum-prepared honey appearing to be the most bactericidal, killing bacterial concentrations as high as 8 × 107 CFU/mL. The wound-healing assay demonstrated that, at concentrations of 0.1%, while the cooked honey had incomplete wound closure, the vacuum-treated honey trended towards faster wound closure. In this study, we demonstrate that the method of MHM synthesis is crucial to maintaining MH properties. We optimized the synthesis of MHMs and demonstrated their potential utility in the treatment of MRSA infections as well as in wound healing. This is the first report of using MH as a substrate for the formation of dissolvable microneedles. This data supports the need for further exploration of this new approach in a wound-healing model and opens the door for the future use of MH as a component of microneedle scaffolds.
Timing for antioxidant-priming against rice seed ageing: optimal only in non-resistant stage
Authors: Xu Ling-xiang , Xin Xia , Yin Guang-kun , Zhou Ji , Zhou Yuan-chang , Lu Xin-xiong 
Published: August 2020

AbstractSeed deterioration due to ageing strongly affects both germplasm preservation and agricultural production. Decelerating seed deterioration and boosting seed viability become increasingly urgent. The loss of seed viability is inevitable even under cold storage. For species with short-lived seed or for regions with poor preservation infrastructure where cold storage is not readily available, seed enhancement is more reliable to increase seed viability and longevity. Antioxidant priming as a way of seed enhancement usually improves seed germination. As for post-priming survival, however, significant uncertainty exists. The controversy lies particularly on seeds of high germination percentage (GP > 95%) whose viability is hardly improvable and the benefits of priming depend on prolonging seed longevity. Therefore, this study timed antioxidant priming to prolong the longevity of high-viability seeds under artificially accelerated ageing (AAA). Rice (Nipponbare) seeds (GP > 97%) under room-temperature-storage (RTS) for 6 months. were resistant to AAA first with little viability loss for a certain period, the resistant stage. This resistance gradually vanished without GP change, during a prolonged RTS period which was named the vulnerable stage. According to the results, although antioxidant priming severely curtailed the resistant stage for seeds with a long plateau in the survival curve, it decelerated viability loss for seeds in the vulnerable stage. In complement to seed storage, priming potentially retains high seed GP which would decrease without seed enhancement. To maximize the benefits of priming for high-GP seeds, two time points are advised as the start of a time window for priming: (1) just at the end of the resistant stage without notable viability loss, which is hard to grasp by GP monitoring; (2) slight but identifiable GP decline.
A model of the PI cycle reveals the regulating roles of lipid-binding proteins and pitfalls of using mosaic biological data
Authors: Mazet Francoise , Tindall Marcus J. , Gibbins Jonathan M. , Fry Michael J. 
Published: August 2020

AbstractThe phosphatidylinositol (PI) cycle is central to eukaryotic cell signaling. Its complexity, due to the number of reactions and lipid and inositol phosphate intermediates involved makes it difficult to analyze experimentally. Computational modelling approaches are seen as a way forward to elucidate complex biological regulatory mechanisms when this cannot be achieved solely through experimental approaches. Whilst mathematical modelling is well established in informing biological systems, many models are often informed by data sourced from multiple unrelated cell types (mosaic data) or from purified enzyme data. In this work, we develop a model of the PI cycle informed by experimental and omics data taken from a single cell type, namely platelets. We were able to make a number of predictions regarding the regulation of PI cycle enzymes, the importance of the number of receptors required for successful GPCR signaling and the importance of lipid- and protein-binding proteins in regulating second messenger outputs. We then consider how pathway behavior differs, when fully informed by data for HeLa cells and show that model predictions remain consistent. However, when informed by mosaic experimental data model predictions greatly vary illustrating the risks of using mosaic datasets from unrelated cell types.
Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea–hypopnea syndrome rabbits
Authors: Zhu Dechao , Kang Wenjing , Zhang Shilong , Qiao Xing , Liu Jie , Liu Chunyan , Lu Haiyan 
Published: August 2020

AbstractThe aim of this study was to investigate the effects of mandibular advancement device (MAD) therapy for obstructive sleep apnea–hypopnea syndrome (OSAHS) on hypoxia-inducible factor-1α (HIF-1α), erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in myocardial tissue. New Zealand rabbits were used to develop OSAHS and MAD models. Cone beam computed tomography (CBCT) of the upper airway and polysomnography (PSG) recordings were performed with the animals in the supine position. All of the animals were induced to sleep in a supine position for 4–6 h each day and were observed continuously for 8 weeks. The myocardial tissue of the three groups was dissected to measure the expression of HIF-1α, EPO and VEGF. The results showed that there was higher expression of HIF-1α, EPO and VEGF in the OSAHS group than those in the MAD and control groups. MAD treatment significantly downregulated the expression of HIF-1α, EPO and VEGF in the OSAHS animals. We concluded that MAD treatment could significantly downregulate the increased expression of HIF-1α, EPO and VEGF in OSAHS rabbits, improving their myocardial function.
A study on the response of FRET based DNA aptasensors in intracellular environment
Authors: Ghosh Shreya , Chen Yinghua , Sebastian Jesvin , George Anne , Dutta Mitra , Stroscio Michael A. 
Published: August 2020

AbstractThis paper presents a study of the response of FRET based DNA aptasensors in the intracellular environment. Herein, we extend previous studies of aptasensors functioning in the extracellular environment to detection of antigens in the intracellular environment. An essential step in this research is the use of a novel means of achieving the endocytosis of aptasensors. Specifically, it is demonstrated that functioning aptasensors are successfully endocytosed by functionalizing the aptasensors with endocytosis—inducing DSS peptides.
PRMT1-dependent methylation of BRCA1 contributes to the epigenetic defense of breast cancer cells against ionizing radiation
Authors: Montenegro María F. , González-Guerrero Rebeca , Sánchez-del-Campo Luis , Piñero-Madrona Antonio , Cabezas-Herrera Juan , Rodríguez-López José Neptuno 
Published: August 2020

AbstractThe therapeutic effect of irradiation is thought to come from DNA damage that affects rapidly proliferating cancer cells; however, resistant cells rapidly initiate mechanisms to repair such damage. While DNA repair mechanisms responsible for cancer cell survival following DNA damage are understood, less is known about the epigenetic mechanisms resulting in resistance to radiotherapy. Although changes in DNA methylation are related to mechanisms of long-term resistance, it is more likely that the methylation state of a series of proteins could be responsible for the first-line of defense of cancer cells against irradiation. In this study, we observed that irradiation of breast cancer cells was accompanied by an overproduction in S-adenosylmethionine, which increases the activity of cellular methylases. We found that by activating PRMT1, irradiation triggers a BRCA1-dependent program that results in efficient DNA repair and inhibition of apoptosis. Depletion of PRMT1 in irradiated cells resulted in a switch of BRCA1 functions from repair and survival in the nucleus to activation of cell death signals in the cytoplasm. We conclude that by modulating the cellular localization of BRCA1, PRMT1 is an important regulator of the oncogenic functions of BRCA1, contributing to the epigenetic defense of breast cancer cells against ionizing radiation.
A novel formulation technology for baculoviruses protects biopesticide from degradation by ultraviolet radiation
Authors: Wilson Kenneth , Grzywacz David , Curcic Igor , Scoates Freya , Harper Karen , Rice Annabel , Paul Nigel , Dillon Aoife 
Published: August 2020

AbstractBiopesticides are biological pest control agents that are viewed as safer alternatives to the synthetic chemicals that dominate the global insecticide market. A major constraint on the wider adoption of biopesticides is their susceptibility to the ultraviolet (UV: 290–400 nm) radiation in sunlight, which limits their persistence and efficacy. Here, we describe a novel formulation technology for biopesticides in which the active ingredient (baculovirus) is micro-encapsulated in an ENTOSTAT wax combined with a UV absorbant (titanium dioxide, TiO2). Importantly, this capsule protects the sensitive viral DNA from degrading in sunlight, but dissolves in the alkaline insect gut to release the virus, which then infects and kills the pest. We show, using simulated sunlight, in both laboratory bioassays and trials on cabbage and tomato plants, that this can extend the efficacy of the biopesticide well beyond the few hours of existing virus formulations, potentially increasing the spray interval and/or reducing the need for high application rates. The new formulation has a shelf-life at 30 °C of at least 6 months, which is comparable to standard commercial biopesticides and has no phytotoxic effect on the host plants. Taken together, these findings suggest that the new formulation technology could reduce the costs and increase the efficacy of baculovirus biopesticides, with the potential to make them commercially competitive alternatives to synthetic chemicals.
Comparative evaluation of six wireless sensor devices in a high ionizing radiation environment
Authors: Huang Qiang , Jiang Jin , Deng Yongqiang 
Published: August 2020

This paper reports the results of experimental studies of six different wireless sensor nodes and networks under a radiation environment with a dose rate of 20 K Rad (Si)/h. The wireless nodes evaluated are ZigBee, WirelessHART, ISA 100.11a, LoRa, and 433/915 MHz point‐to‐point devices made from commercial off‐the‐shelf (COTS) components. The experiments were carried out using a 60Co gamma source, while the devices are at on‐power operating states, and their operating statuses have been continuously monitored to determine the first instance of failure and the rate of gradual degradation in terms of communication channel performance and quality of the wireless signals. Observations indicate that the different devices and networks exhibit varying levels of radiation tolerance. For example, some can only survive for less than one hour, but others are operating satisfactorily for several hours. Furthermore, before a device suffers a fatal hardware failure, the performance degradation progresses slowly. It is believed that this is the first time that such results are reported in the open literature. Their significance is that the results can provide some practical guidance to select the most suitable wireless devices for the design and construction of remote monitoring systems for high‐level radiation environments.
El Coco Does Not Frighten Anymore: ICC Scrutiny and State Cooperation in Colombia
Authors: Bocchese Marco 
Published: August 2020

Abstract
The preliminary examination of Colombia is widely regarded as a successful instance of positive complementarity. Under the watchful eye of the Office of the Prosecutor (OTP), Colombian authorities have implemented comprehensive reforms and negotiated peace with the country’s main rebellion. That said, how much credit can the International Criminal Court (ICC) claim for these outcomes? And how did ICC–state relations develop over time? Drawing on in-person interviews carried out during a research trip to Bogotá, this article conducts a within-case analysis of the situation of Colombia over fourteen years (2004–18), seeking to explore the motives underlying state compliance with ICC treaty obligations and trace the evolution of ICC–state relations throughout two consecutive administrations of opposite political color. Unsurprisingly, state elites and transitional justice experts push back against the idea that the OTP has held state authorities accountable to domestic and international legal obligations through its lasting monitoring and involvement in internal affairs. Besides, while participants in this study agree on the timeliness of ICC intervention, they are split on their assessments of the Court’s performance. Finally, interviewees tend to agree that, upon giving ‘green light’ to the finalized peace accords in early September 2016, the ICC has at best a marginal role in Colombia’s politics..