bluuebunny/crossref_metadata_2025_split huggingface dataset:
General route to design polymer molecular weight distributions through flow chemistry
Authors: Walsh Dylan J. , Schinski Devin A. , Schneider Robert A. , Guironnet Damien 
Published: June 2020

AbstractThe properties of a polymer are known to be intrinsically related to its molecular weight distribution (MWD); however, previous methodologies of MWD control do not use a design and result in arbitrary shaped MWDs. Here we report a precise design to synthesis protocol for producing a targeted MWD design with a simple to use, and chemistry agnostic computer-controlled tubular flow reactor. To support the development of this protocol, we constructed general reactor design rules by combining fluid mechanical principles, polymerization kinetics, and experiments. The ring opening polymerization of lactide, the anionic polymerization of styrene, and the ring opening metathesis polymerization are used as model polymerizations to develop the reactor design rules and synthesize MWD profiles. The derivation of a mathematical model enables the quantitative prediction of the experimental results, and this model provides a tool to explore the limits of any MWD design protocol.
Evolution of generalist resistance to herbicide mixtures reveals a trade-off in resistance management
Authors: Comont David , Lowe Claudia , Hull Richard , Crook Laura , Hicks Helen L. , Onkokesung Nawaporn , Beffa Roland , Childs Dylan Z. , Edwards Robert , Freckleton Robert P. , Neve Paul 
Published: June 2020

AbstractIntense selection by pesticides and antibiotics has resulted in a global epidemic of evolved resistance. In agriculture and medicine, using mixtures of compounds from different classes is widely accepted as optimal resistance management. However, this strategy may promote the evolution of more generalist resistance mechanisms. Here we test this hypothesis at a national scale in an economically important agricultural weed: blackgrass (Alopecurus myosuroides), for which herbicide resistance is a major economic issue. Our results reveal that greater use of herbicide mixtures is associated with lower levels of specialist resistance mechanisms, but higher levels of a generalist mechanism implicated in enhanced metabolism of herbicides with diverse modes of action. Our results indicate a potential evolutionary trade-off in resistance management, whereby attempts to reduce selection for specialist resistance traits may promote the evolution of generalist resistance. We contend that where specialist and generalist resistance mechanisms co-occur, similar trade-offs will be evident, calling into question the ubiquity of resistance management based on mixtures and combination therapies.
The phytopathogenic fungus Sclerotinia sclerotiorum detoxifies plant glucosinolate hydrolysis products via an isothiocyanate hydrolase
Authors: Chen Jingyuan , Ullah Chhana , Reichelt Michael , Beran Franziska , Yang Zhi-Ling , Gershenzon Jonathan , Hammerbacher Almuth , Vassão Daniel G. 
Published: June 2020

AbstractBrassicales plants produce glucosinolates and myrosinases that generate toxic isothiocyanates conferring broad resistance against pathogens and herbivorous insects. Nevertheless, some cosmopolitan fungal pathogens, such as the necrotrophic white mold Sclerotinia sclerotiorum, are able to infect many plant hosts including glucosinolate producers. Here, we show that S. sclerotiorum infection activates the glucosinolate-myrosinase system, and isothiocyanates contribute to resistance against this fungus. S. sclerotiorum metabolizes isothiocyanates via two independent pathways: conjugation to glutathione and, more effectively, hydrolysis to amines. The latter pathway features an isothiocyanate hydrolase that is homologous to a previously characterized bacterial enzyme, and converts isothiocyanate into products that are not toxic to the fungus. The isothiocyanate hydrolase promotes fungal growth in the presence of the toxins, and contributes to the virulence of S. sclerotiorum on glucosinolate-producing plants.
Organic NIR-II molecule with long blood half-life for in vivo dynamic vascular imaging
Authors: Li Benhao , Zhao Mengyao , Feng Lishuai , Dou Chaoran , Ding Suwan , Zhou Gang , Lu Lingfei , Zhang Hongxin , Chen Feiya , Li Xiaomin , Li Guangfeng , Zhao Shichang , Jiang Chunyu , Wang Yan , Zhao Dongyuan , Cheng Yingsheng , Zhang Fan 
Published: June 2020

AbstractReal-time monitoring of vessel dysfunction is of great significance in preclinical research. Optical bioimaging in the second near-infrared (NIR-II) window provides advantages including high resolution and fast feedback. However, the reported molecular dyes are hampered by limited blood circulation time (~ 5–60 min) and short absorption and emission wavelength, which impede the accurate long-term monitoring. Here, we report a NIR-II molecule (LZ-1105) with absorption and emission beyond 1000 nm. Thanks to the long blood circulation time (half-life of 3.2 h), the fluorophore is used for continuous real-time monitoring of dynamic vascular processes, including ischemic reperfusion in hindlimbs, thrombolysis in carotid artery and opening and recovery of the blood brain barrier (BBB). LZ-1105 provides an approach for researchers to assess vessel dysfunction due to the long excitation and emission wavelength and long-term blood circulation properties.
Asymmetric one-pot transformation of isoflavones to pterocarpans and its application in phytoalexin synthesis
Authors: Ciesielski Philipp , Metz Peter 
Published: June 2020

AbstractPhytoalexins have attracted much attention due to their health-promoting effects and their vital role in plant health during the last years. Especially the 6a-hydroxypterocarpans glyceollin I and glyceollin II, which may be isolated from stressed soy plants, possess a broad spectrum of bioactivities such as anticancer activity and beneficial contributions against western diseases by anti-oxidative and anti-cholesterolemic effects. Aiming for a catalytic asymmetric access to these natural products, we establish the asymmetric syntheses of the natural isoflavonoids (−)-variabilin, (−)-homopterocarpin, (−)-medicarpin, (−)-3,9-dihydroxypterocarpan, and (−)-vestitol by means of an asymmetric transfer hydrogenation (ATH) reaction. We successfully adapt this pathway to the first catalytic asymmetric total synthesis of (−)-glyceollin I and (−)-glyceollin II. This eight-step synthesis features an efficient one-pot transformation of a 2′-hydroxyl-substituted isoflavone to a virtually enantiopure pterocarpan by means of an ATH and a regioselective benzylic oxidation under aerobic conditions to afford the susceptible 6a-hydroxypterocarpan skeleton.
Harmonization of quality metrics and power calculation in multi-omic studies
Authors: Tarazona Sonia , Balzano-Nogueira Leandro , Gómez-Cabrero David , Schmidt Andreas , Imhof Axel , Hankemeier Thomas , Tegnér Jesper , Westerhuis Johan A. , Conesa Ana 
Published: June 2020

AbstractMulti-omic studies combine measurements at different molecular levels to build comprehensive models of cellular systems. The success of a multi-omic data analysis strategy depends largely on the adoption of adequate experimental designs, and on the quality of the measurements provided by the different omic platforms. However, the field lacks a comparative description of performance parameters across omic technologies and a formulation for experimental design in multi-omic data scenarios. Here, we propose a set of harmonized Figures of Merit (FoM) as quality descriptors applicable to different omic data types. Employing this information, we formulate the MultiPower method to estimate and assess the optimal sample size in a multi-omics experiment. MultiPower supports different experimental settings, data types and sample sizes, and includes graphical for experimental design decision-making. MultiPower is complemented with MultiML, an algorithm to estimate sample size for machine learning classification problems based on multi-omic data.
Incidence and risk factors for heat-related illness (heatstroke) in UK dogs under primary veterinary care in 2016
Authors: Hall Emily J. , Carter Anne J. , O’Neill Dan G. 
Published: June 2020

AbstractAs climate change causes global temperatures to rise, heat-related illness, a potentially fatal condition in dogs, will become an ever-greater threat. This study aimed to report the incidence, fatality and canine risk factors of heat-related illness in UK dogs under primary veterinary care in 2016. The VetCompassTMprogramme collects de-identified electronic patient records from UK veterinary practices for research. From the clinical records of 905,543 dogs under veterinary care in 2016, 395 confirmed heat-related illness events were identified. The estimated 2016 incidence of heat-related illness was 0.04% (95% CI 0.04-0.05%), with an event fatality rate of 14.18% (95% CI 11.08 – 17.96%). Multivariable analysis identified significant risk factors including breed (e.g. Chow Chow, Bulldog and French Bulldog), higher bodyweight relative to the breed/sex mean and being over two years of age. Dogs with a brachycephalic skull shape and dogs weighing over 50 kg were also at greater risk. As we move into an ever-warmer world, veterinary professionals may need to include resistance to heat-related illness amongst their rationales when advising owners on breed selection. Breeding for good respiratory function and maintaining a healthy bodyweight should be considered key welfare priorities for all dogs to limit the risk of heat-related illness.
Constructing arrays of nucleosome positioning sequences using Gibson Assembly for single-molecule studies
Authors: Spakman Dian , King Graeme A. , Peterman Erwin J. G. , Wuite Gijs J. L. 
Published: June 2020

AbstractAs the basic building blocks of chromatin, nucleosomes play a key role in dictating the accessibility of the eukaryotic genome. Consequently, nucleosomes are involved in essential genomic transactions such as DNA transcription, replication and repair. In order to unravel the mechanisms by which nucleosomes can influence, or be altered by, DNA-binding proteins, single-molecule techniques are increasingly employed. To this end, DNA molecules containing a defined series of nucleosome positioning sequences are often used to reconstitute arrays of nucleosomes in vitro. Here, we describe a novel method to prepare DNA molecules containing defined arrays of the ‘601’ nucleosome positioning sequence by exploiting Gibson Assembly cloning. The approaches presented here provide a more accessible and efficient means to generate arrays of nucleosome positioning motifs, and facilitate a high degree of control over the linker sequences between these motifs. Nucleosomes reconstituted on such arrays are ideal for interrogation with single-molecule techniques. To demonstrate this, we use dual-trap optical tweezers, in combination with fluorescence microscopy, to monitor nucleosome unwrapping and histone localisation as a function of tension. We reveal that, although nucleosomes unwrap at ~20 pN, histones (at least histone H3) remain bound to the DNA, even at tensions beyond 60 pN.
RPamide neuropeptides NLP-22 and NLP-2 act through GnRH-like receptors to promote sleep and wakefulness in C. elegans
Authors: Van der Auwera Petrus , Frooninckx Lotte , Buscemi Kristen , Vance Ryan T. , Watteyne Jan , Mirabeau Olivier , Temmerman Liesbet , De Haes Wouter , Fancsalszky Luca , Gottschalk Alexander , Raizen David M. , Nelson Matthew D. , Schoofs Liliane , Beets Isabel 
Published: June 2020

AbstractSleep and wakefulness are fundamental behavioral states of which the underlying molecular principles are becoming slowly elucidated. Transitions between these states require the coordination of multiple neurochemical and modulatory systems. In Caenorhabditis elegans sleep occurs during a larval transition stage called lethargus and is induced by somnogenic neuropeptides. Here, we identify two opposing neuropeptide/receptor signaling pathways: NLP-22 promotes behavioral quiescence, whereas NLP-2 promotes movement during lethargus, by signaling through gonadotropin-releasing hormone (GnRH) related receptors. Both NLP-2 and NLP-22 belong to the RPamide neuropeptide family and share sequence similarities with neuropeptides of the bilaterian GnRH, adipokinetic hormone (AKH) and corazonin family. RPamide neuropeptides dose-dependently activate the GnRH/AKH-like receptors GNRR-3 and GNRR-6 in a cellular receptor activation assay. In addition, nlp-22-induced locomotion quiescence requires the receptor gnrr-6. By contrast, wakefulness induced by nlp-2 overexpression is diminished by deletion of either gnrr-3 or gnrr-6. nlp-2 is expressed in a pair of olfactory AWA neurons and cycles with larval periodicity, as reported for nlp-22, which is expressed in RIA. Our data suggest that the somnogenic NLP-22 neuropeptide signals through GNRR-6, and that both GNRR-3 and GNRR-6 are required for the wake-promoting action of NLP-2 neuropeptides.
Mutational analysis of TSC1 and TSC2 in Danish patients with tuberous sclerosis complex
Authors: Rosengren Thomas , Nanhoe Santoesha , de Almeida Luis Gustavo Dufner , Schönewolf-Greulich Bitten , Larsen Lasse Jonsgaard , Hey Caroline Amalie Brunbjerg , Dunø Morten , Ek Jakob , Risom Lotte , Nellist Mark , Møller Lisbeth Birk 
Published: June 2020

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in the skin and other organs, including brain, heart, lung, kidney and bones. TSC is caused by mutations in TSC1 and TSC2. Here, we present the TSC1 and TSC2 variants identified in 168 Danish individuals out of a cohort of 327 individuals suspected of TSC. A total of 137 predicted pathogenic or likely pathogenic variants were identified: 33 different TSC1 variants in 42 patients, and 104 different TSC2 variants in 126 patients. In 40 cases (24%), the identified predicted pathogenic variant had not been described previously. In total, 33 novel variants in TSC2 and 7 novel variants in TSC1 were identified. To assist in the classification of 11 TSC2 variants, we investigated the effects of these variants in an in vitro functional assay. Based on the functional results, as well as population and genetic data, we classified 8 variants as likely to be pathogenic and 3 as likely to be benign.
GlioM&M: Web-based tool for studying circulating and infiltrating monocytes and macrophages in glioma
Authors: Abels Erik R. , Maas Sybren L. N. , Tai Eric , Ting David T. , Broekman Marike L. D. , Breakefield Xandra O. , El Khoury Joseph 
Published: June 2020

AbstractMonocytes, macrophages and microglia make up a large part of the glioma environment and have an important role in maintaining and propagating glioma progression. Targeting these cells to inhibit their tumor-promoting effect and reprogramming them into an anti-tumor phenotype is a potential therapeutic approach for glioma. In this study we analyzed the transcriptomes of eight different monocyte subgroups derived from the brain and the blood of glioma-bearing mice. We compared the expression profile of blood-derived monocytes versus tumor-infiltrating monocytes and found increased expression of both pro- and anti-inflammatory pathways in tumor infiltrating monocytes. To help disseminate these datasets, we created a user-friendly web-based tool accessible at www.glioma-monocytes.com. This tool can be used for validation purposes and to elucidate gene expression profiles of tumor-interacting monocytes and macrophages as well as blood-derived circulating monocytes. This tool can also be used to identify new markers and targets for therapy in these different cell populations.
RNA sequencing of corneas from two keratoconus patient groups identifies potential biomarkers and decreased NRF2-antioxidant responses
Authors: Shinde Vishal , Hu Nan , Mahale Alka , Maiti George , Daoud Yassine , Eberhart Charles G. , Maktabi Azza , Jun Albert S. , Al-Swailem Samar A. , Chakravarti Shukti 
Published: June 2020

AbstractKeratoconus is a highly prevalent (1 in 2000), genetically complex and multifactorial, degenerative disease of the cornea whose pathogenesis and underlying transcriptomic changes are poorly understood. To identify disease-specific changes and gene expression networks, we performed next generation RNA sequencing from individual corneas of two distinct patient populations - one from the Middle East, as keratoconus is particularly severe in this group, and the second from an African American population in the United States. We conducted a case: control RNA sequencing study of 7 African American, 12 Middle Eastern subjects, and 7 controls. A Principal Component Analysis of all expressed genes was used to ascertain differences between samples. Differentially expressed genes were identified using Cuffdiff and DESeq2 analyses, and identification of over-represented signaling pathways by Ingenuity Pathway Analysis. Although separated by geography and ancestry, key commonalities in the two patient transcriptomes speak of disease - intrinsic gene expression networks. We identified an overwhelming decrease in the expression of anti-oxidant genes regulated by NRF2 and those of the acute phase and tissue injury response pathways, in both patient groups. Concordantly, NRF2 immunofluorescence staining was decreased in patient corneas, while KEAP1, which helps to degrade NRF2, was increased. Diminished NRF2 signaling raises the possibility of NRF2 activators as future treatment strategies in keratoconus. The African American patient group showed increases in extracellular matrix transcripts that may be due to underlying profibrogenic changes in this group. Transcripts increased across all patient samples include Thrombospondin 2 (THBS2), encoding a matricellular protein, and cellular proteins, GAS1, CASR and OTOP2, and are promising biomarker candidates. Our approach of analyzing transcriptomic data from different populations and patient groups will help to develop signatures and biomarkers for keratoconus subtypes. Further, RNA sequence data on individual patients obtained from multiple studies may lead to a core keratoconus signature of deregulated genes and a better understanding of its pathogenesis.
Cell Fate Potential of NG2 Progenitors
Authors: Sánchez-González Rebeca , Bribián Ana , López-Mascaraque Laura 
Published: June 2020

AbstractDetermining the origin of different glial subtypes is crucial to understand glial heterogeneity, and to enhance our knowledge of glial and progenitor cell behavior in embryos and adults. NG2-glia are homogenously distributed in a grid-like manner in both, gray and white matter of the adult brain. While some NG2-glia in the CNS are responsible for the generation of mature oligodendrocytes (OPCs), most of them do not differentiate and they can proliferate outside of adult neurogenic niches. Thus, NG2-glia constitute a heterogeneous population containing different subpopulations with distinct functions. We hypothesized that their diversity emerges from specific progenitors during development, as occurs with other glial cell subtypes. To specifically target NG2-pallial progenitors and to define the NG2-glia lineage, as well as the NG2-progenitor potential, we designed two new StarTrack strategies using the NG2 promoter. These approaches label NG2 expressing progenitor cells, permitting the cell fates of these NG2 progenitors to be tracked in vivo. StarTrack labelled cells producing different neural phenotypes in different regions depending on the age targeted, and the strategy selected. This specific genetic targeting of neural progenitors in vivo has provided new data on the heterogeneous pool of NG2 progenitors at both embryonic and postnatal ages.
ERP mismatch response to phonological and temporal regularities in speech
Authors: Emmendorfer Alexandra K. , Correia Joao M. , Jansma Bernadette M. , Kotz Sonja A. , Bonte Milene 
Published: June 2020

AbstractPredictions of our sensory environment facilitate perception across domains. During speech perception, formal and temporal predictions may be made for phonotactic probability and syllable stress patterns, respectively, contributing to the efficient processing of speech input. The current experiment employed a passive EEG oddball paradigm to probe the neurophysiological processes underlying temporal and formal predictions simultaneously. The component of interest, the mismatch negativity (MMN), is considered a marker for experience-dependent change detection, where its timing and amplitude are indicative of the perceptual system’s sensitivity to presented stimuli. We hypothesized that more predictable stimuli (i.e. high phonotactic probability and first syllable stress) would facilitate change detection, indexed by shorter peak latencies or greater peak amplitudes of the MMN. This hypothesis was confirmed for phonotactic probability: high phonotactic probability deviants elicited an earlier MMN than low phonotactic probability deviants. We do not observe a significant modulation of the MMN to variations in syllable stress. Our findings confirm that speech perception is shaped by formal and temporal predictability. This paradigm may be useful to investigate the contribution of implicit processing of statistical regularities during (a)typical language development.
Preoperative Vitamin D Levels as a Predictor of Transient Hypocalcemia and Hypoparathyroidism After Parathyroidectomy
Authors: Unsal Ilknur Ozturk , Calapkulu Murat , Sencar Muhammed Erkam , Hepsen Sema , Sakiz Davut , Ozbek Mustafa , Cakal Erman 
Published: June 2020

AbstractHypocalcemia is a common problem after parathyroidectomy and/or thyroidectomy. The complication may be transient or permanent. Most cases occur as a result of removal of the parathyroid glands or damage to the glands during neck surgery. The purpose of this study was to evaluate the effect of preoperative vitamin D deficiency in predicting transient hypocalcemia and hypoparathyroidism after parathyroidectomy.Retrospective evaluation was made of 180 patients with primary hyperparathyroidism in respect of serum 25(OH)D, calcium and parathyroid hormone before and after parathyroidectomy. Transient hypocalcemia was defined as corrected calcium ≤ 8.4 mg/dL, and these cases were then evaluated for preoperative 25(OH)D values. Transient hypoparathyroidism has been described as low PTH level immediately after surgery before beginning any supplementation. Permanent hypoparathyroidism is accepted as the need for medical treatment is necessary over 12 months.Both transient hypocalcemia and hypoparathyroidism developed at statistically significantly higher rates in patients with preoperative vitamin D deficiency and vitamin D insufficiency.Vitamin D deficiency is an independent contributor to transient hypocalcemia and hypoparathyroidism following parathyroidectomy.
Serum hepcidin level, iron metabolism and osteoporosis in patients with rheumatoid arthritis
Authors: Sato Hiroe , Takai Chinatsu , Kazama Junichiro James , Wakamatsu Ayako , Hasegawa Eriko , Kobayashi Daisuke , Kondo Naoki , Nakatsue Takeshi , Abe Asami , Ito Satoshi , Ishikawa Hajime , Kuroda Takeshi , Suzuki Yoshiki , Narita Ichiei 
Published: June 2020

AbstractHepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.