bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid phase separation in vesicles enhances TRAIL-mediated cytotoxicity
Authors: Vu Timothy , Peruzzi Justin A. , Sant’Anna Lucas E. , Kamat Neha P. 
Published: October 2021

AbstractLigand spatial presentation and density play important roles in many signaling pathways mediated by cell receptors and are critical parameters when designing protein-conjugated therapeutic nanoparticles. Currently, Janus particles are most often used to spatially control ligand conjugation, but the technological challenge of manufacturing Janus particles limits adoption for translational applications. Here, we demonstrate that lipid phase separation can be used to spatially control protein presentation onto lipid vesicles. We used this system to study the density dependence of TNF-related apoptosis inducing ligand (TRAIL), a model therapeutic protein that exhibits greater cytotoxicity to cancer cells when conjugated onto a vesicle surface than when administered as a soluble protein. Using assays for apoptosis and caspase activity, we show that phase separated TRAIL vesicles induced higher cytotoxicity to Jurkat cancer cells than uniformly-conjugated TRAIL vesicles, and enhanced cytotoxicity was dependent on the TRAIL domain density. We then assessed this relationship in other cancer cell lines and demonstrated that phase separated TRAIL vesicles only enhanced cytotoxicity through one TRAIL receptor, DR5, while another TRAIL receptor, DR4, was unaffected by the TRAIL density. These results indicate unique signaling requirements for each TRAIL receptor and how TRAIL therapy could be tailored depending on the relative levels of expression for cancer receptors of interest. Overall, this work demonstrates a readily adoptable method to control protein conjugation and density on bilayer vesicles that can be easily adopted to other therapeutic nanoparticle systems to improve receptor signaling of nanoparticles targeted to cancer and diseased cells.
CTCF blocks anti-sense transcription initiation at divergent gene promoters
Authors: Luan Jing , Syrett Camille M. , Vermunt Marit W. , Coté Allison , Tome Jacob M. , Zhang Haoyue , Huang Anran , Luppino Jennifer M. , Keller Cheryl A. , Giardine Belinda M. , Zhang Shiping , Dunagin Margaret C. , Zhang Zhe , Joyce Eric F. , Lis John T. , Raj Arjun , Hardison Ross C. , Blobel Gerd A. 
Published: October 2021

AbstractTranscription at most promoters is divergent, initiating at closely spaced oppositely oriented core promoters to produce sense transcripts along with often unstable upstream antisense (uasTrx). How antisense transcription is regulated and to what extent it is coordinated with sense transcription is largely unknown. Here by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters, the great majority of which bear proximal CTCF binding sites. Genome editing, chromatin conformation studies, and high-resolution transcript mapping revealed that precisely positioned CTCF directly suppresses the initiation of uasTrx, in a manner independent of its chromatin architectural function. Primary transcript RNA FISH revealed co-bursting of sense and anti-sense transcripts is disfavored, suggesting CTCF-regulated competition for transcription initiation. In sum, CTCF shapes the transcriptional landscape in part by suppressing upstream antisense transcription.
Identification, Characterization and Synthesis of Natural Parasitic Cysteine Protease Inhibitors – More Potent Falcitidin Analogs
Authors: Brinkmann Stephan , Semmler Sandra , Kersten Christian , Patras Maria A. , Kurz Michael , Fuchs Natalie , Hammerschmidt Stefan J. , Legac Jennifer , Hammann Peter E. , Vilcinskas Andreas , Rosenthal Philip. J. , Schirmeister Tanja , Bauer Armin , Schäberle Till F. 
Published: October 2021

ABSTRACTProtease inhibitors represent a promising therapeutic option for the treatment of parasitic diseases such as malaria and human African trypanosomiasis. Falcitidin was the first member of a new class of inhibitors of falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum. Using a metabolomics dataset of 25 Chitinophaga strains for molecular networking enabled identification of over 30 natural analogs of falcitidin. Based on MS/MS spectra, they vary in their amino acid chain length, sequence, acyl residue, and C-terminal functionalization; therefore, they were grouped into the four falcitidin peptide families A-D. The isolation, characterization and absolute structure elucidation of two falcitidin-related pentapeptide aldehyde analogs by extensive MS/MS spectrometry and NMR spectroscopy in combination with advanced Marfey’s analysis was in agreement with the in silico analysis of the corresponding biosynthetic gene cluster. Total synthesis of chosen pentapeptide analogs followed by in vitro testing against a panel of proteases revealed selective parasitic cysteine protease inhibition and additionally low-micromolar inhibition of α-chymotrypsin. The pentapeptides investigated here showed superior inhibitory activity compared to falcitidin.
Evaluation of small non-coding RNAs as a possible epigenetic mechanism mediating the transition from biotrophy to necrotrophy in the life cycle of Phytophthora infestans
Authors: González-Tobón Juliana , Rodríguez-Jaramillo Alejandra , Forero Laura Milena , González Laura Natalia , Danies Giovanna , Restrepo Silvia 
Published: October 2021

SummaryPhytophthora infestans, causal agent of late blight disease of potatoes, causes billion-dollar losses worldwide each year. This plant pathogen is a hemibiotroph, first feeding on the host and later killing it. Even though the transcription dynamics of this transition are characterized, the role that small non-coding RNAs (sRNAs) might have is still unknown. Furthermore, a bioinformatic pipeline to search and analyze sRNAs in P. infestans, is needed. Using our proposed pipeline, 146 sRNAs were found to be significantly differentially expressed between the evaluated stages of the pathogen’s life cycle. One hundred of these sRNAs were successfully annotated and classified into nine functional categories. The expression of the genes associated to ten of these sRNAs was validated via qRT-PCR. Among these, the expression levels of genes encoding for effectors were inversely correlated to that of the sRNAs aligning to them, which is expected if sRNAs are indeed regulating their expression. This correlation was not clear for sRNAs in other functional categories and should not be confused with strict causality. This study works as a starting point for considering sRNAs as role players in the transition from biotrophy to necrotrophy in P. infestans when infecting Solanum tuberosum.
Biological Flora of the British Isles: Salvia pratensis
Authors: Moughan Joseph , McGinn Kevin J. , Jones Laura , Rich Tim C. G. , Waters Elliot , de Vere Natasha 
Published: October 2021

Abstract

This account presents information on all aspects of the biology of Salvia pratensis L. (Meadow Clary) that are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the standard framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, history and conservation.

Salvia pratensis is an erect, rosette‐forming, perennial herb with a broad native distribution covering much of Europe—from the British Isles, Spain and Morocco in the west, across Europe into Asia, as far east as the Urals. In the British Isles, the species is nationally scarce, confined to a few south‐ to west‐facing sites with calcareous soils in Southern England and one site in Wales. It is predominately found in unimproved pasture, hay meadows and grassy verges, but can occur on the fringes of scrub or woodland. Although the species is abundant in central Europe, changes to land management since the mid‐20th century have resulted in fragmented and threatened populations in several European countries. It is cultivated as an ornamental, as is S. × sylvestris, the hybrid with S. nemorosa.

Populations are typically gynodioecious, having both female (male‐sterile) and hermaphrodite individuals at variable proportions. The species has a mixed mating system and is self‐compatible via insect pollination, but predominantly outcrosses. Honeybees and bumblebees are abundant pollinators, but a diverse range of bee species and other insect species visit S. pratensis flowers. Inbreeding depression has been documented, presenting a conservation concern for small, fragmented populations.

The species is the focus of conservation efforts and has been reintroduced to sites where it had become locally extinct in Britain. To sustain favourable habitat, site management should maintain low soil nutrient levels, and prevent scrub encroachment and the dominance of coarse grasses. The removal of sward by hay cutting or grazing after plants have flowered and set seed is advised, in addition to maintaining a degree of disturbance to provide bare patches of soil for seedling recruitment.
Virtual Water Flows in Internal and External Agricultural Product Trade in Central Asia
Authors: Zhou Xinyao , Han Shumin , Li Huilong , Ren Dandan , Sheng Zhuping , Yang Yonghui 
Published: October 2021

AbstractCentral Asia exports large amounts of virtual water through agricultural trade, a key factor for overexploitation of water resources in the region. Most studies analyze Central Asia’s virtual water outflows to the outside world, while ignore the agricultural trade within the region and the varying impacts of virtual water flows on the individual countries. In this study, the changes in virtual water flows embedded in trade with outside regions (external) and Central Asia countries (internal) were analyzed for the period 2000–2018 for wheat, cotton, and livestock. The results show that while Central Asia exported, respectively, 194.3 and 101.8 km3 of virtual water to the outside world through cotton and wheat trade, it imported 53.7 km3 of virtual water via livestock trade. Also, while cotton‐based virtual water outflows decreased, wheat‐based virtual water outflows increased. Total virtual water flows in internal trade reached 71.2 km3, with flow originating mainly from Kazakhstan and heading to other four countries through wheat trade.Kazakhstan was the largest net exporter of virtual water through wheat trade, Uzbekistan was the second‐largest net exporter through cotton trade. Green water (precipitation water used by crops) was dominant in virtual water flow related to wheat and blue water (surface water or groundwater used by crops) was dominant in virtual water flow related to cotton. Uzbekistan and Turkmenistan were most directly influenced by the virtual water trade.
Effects of Reservoir Levels on Arizona National Recreation Area Visitation, Visitor Spending, and Local Economies
Authors: Duval Dari , Bickel Ashley K. , Frisvold George B. 
Published: October 2021

AbstractThis study estimates the effects of reservoir levels on demand for recreation visits to Lake Powell (Glen Canyon National Recreation Area [NRA]) and Lake Mead NRA, correlating reservoir levels with overnight and total recreation visits. We also consider the effects of closures of recreation access points (such as launch ramps or marinas) when lake levels fall below critical thresholds. Our overall results are similar to past studies, but find that the access point closures are a more robust predictor of visits than simple elevation measures. Policies that manage the Colorado River, including those that seek to maintain reservoir levels above critical levels with the primary goal of preventing water delivery cutbacks, also affect recreation demand and the economies of nearby communities. Our analysis maps changes in visits (from changing elevations) to changes in visitor spending, recreationist user benefits, and regional economic indicators such as value added and employment. Such indicators could be used in future benefit‐cost or economic impact analyses of Colorado River water management policies.
Sample size considerations for stepped wedge designs with subclusters
Authors: Davis‐Plourde Kendra , Taljaard Monica , Li Fan 
Published: October 2021

AbstractThe stepped wedge cluster randomized trial (SW‐CRT) is an increasingly popular design for evaluating health service delivery or policy interventions. An essential consideration of this design is the need to account for both within‐period and between‐period correlations in sample size calculations. Especially when embedded in health care delivery systems, many SW‐CRTs may have subclusters nested in clusters, within which outcomes are collected longitudinally. However, existing sample size methods that account for between‐period correlations have not allowed for multiple levels of clustering. We present computationally efficient sample size procedures that properly differentiate within‐period and between‐period intracluster correlation coefficients in SW‐CRTs in the presence of subclusters. We introduce an extended block exchangeable correlation matrix to characterize the complex dependencies of outcomes within clusters. For Gaussian outcomes, we derive a closed‐form sample size expression that depends on the correlation structure only through two eigenvalues of the extended block exchangeable correlation structure. For non‐Gaussian outcomes, we present a generic sample size algorithm based on linearization and elucidate simplifications under canonical link functions. For example, we show that the approximate sample size formula under a logistic linear mixed model depends on three eigenvalues of the extended block exchangeable correlation matrix. We provide an extension to accommodate unequal cluster sizes and validate the proposed methods via simulations. Finally, we illustrate our methods in two real SW‐CRTs with subclusters.
Prevalence, behavioural, and management outcomes of infants with auditory neuropathy spectrum disorder
Authors: Smalley Jason , Hole Kevin 
Published: October 2021

AimTo provide an overview of electrophysiological and behavioural outcomes from a large UK centres data set on children diagnosed with auditory neuropathy (ANSD) between 2002 and March 2018.MethodA systematic audit was undertaken, collating the electrophysiological data from auditory brainstem response (ABR) follow‐up, risk factors, and later behavioural results/management. These were then compared to look for trends between groups. The study sample consisted of 118 925 infants born, with 46 (0.039%, 0.39 per 1000 births) being diagnosed with congenital ANSD (39 bilateral, seven unilateral).ResultsTwenty‐nine per cent of ears with ANSD had short latency components on ABR testing. Forty‐four per cent of ears with present cochlear microphonics but absent transient‐evoked otoacoustic emissions (TE‐OAE) and no ABR went on to have profound behavioural hearing threshold levels. All but one child went on to show a hearing loss on behavioural testing. ANSD was not confined to the population from neonatal intensive care units: there were three bilateral and five unilateral cases in the typically developing infant population.InterpretationThe incidence of ANSD is higher in this sample than that reported previously in the literature. Children who had cochlear microphonics with absent ABR and absent TE‐OAE had significantly worse later behavioural outcomes than other patterns of electrophysiological results.
Three‐dimensional modeling of the mitral valve for surgical planning in a pediatric patient: A case‐based discussion of the technical challenges of segmentation and printing from 3D transthoracic echocardiographic datasets
Authors: Sturgeon Gregory M. , Andersen Nicholas D. , Campbell Michael J. , Barker Piers C. A. 
Published: October 2021

AbstractAbnormal atrioventricular valve present great challenges to the surgeon in achieving a successful repair, and thus present a great opportunity for enhanced 3D imaging to guide pre‐ and intra‐operative management. Spatial and temporal resolution of 3D echocardiography enables 3D printing of valve morphology. However, non‐linearity, angle dependence, speckle, blur, and resampling complicate segmentation compared to computed tomography (CT) and magnetic resonance imaging (MRI). A case of complex mitral valve disease in a pediatric patient is therefore presented to illustrate the technical challenges of segmentation and 3D printing from echocardiographic data.
Smartphone‐derived keystroke dynamics are sensitive to relevant changes in multiple sclerosis
Authors: Lam Ka‐Hoo , Twose James , McConchie Hannah , Licitra Giovanni , Meijer Kim , de Ruiter Lodewijk , van Lierop Zoë , Moraal Bastiaan , Barkhof Frederik , Uitdehaag Bernard , de Groot Vincent , Killestein Joep 
Published: October 2021

AbstractBackgroundTo investigate smartphone keystroke dynamics (KD), derived from regular typing, on sensitivity to relevant change in disease activity, fatigue, and clinical disability in multiple sclerosis (MS).MethodsPreplanned interim analysis of a cohort study with 102 MS patients assessed at baseline and 3‐month follow‐up for gadolinium‐enhancing lesions on magnetic resonance imaging, relapses, fatigue and clinical disability outcomes. Keyboard interactions were unobtrusively collected during typing using the Neurokeys App. From these interactions 15 keystroke features were derived and aggregated using 16 summary and time series statistics. Responsiveness of KD to clinical anchor‐based change was assessed by calculating the area under the receiver operating characteristic curve (AUC). The optimal cut‐point was used to determine the minimal clinically important difference (MCID) and compared to the smallest real change (SRC). Commonly used clinical measures were analyzed for comparison.ResultsA total of 94 patients completed the follow‐up. The five best performing keystroke features had AUC‐values in the range 0.72–0.78 for change in gadolinium‐enhancing lesions, 0.67–0.70 for the Checklist Individual Strength Fatigue subscale, 0.66–0.79 for the Expanded Disability Status Scale, 0.69–0.73 for the Ambulation Functional System, and 0.72–0.75 for Arm function in MS Questionnaire. The MCID of these features exceeded the SRC on group level. KD had higher AUC‐values than comparative clinical measures for the study outcomes, aside from ambulatory function.ConclusionsKeystroke dynamics demonstrated good responsiveness to changes in disease activity, fatigue, and clinical disability in MS, and detected important change beyond measurement error on group level. Responsiveness of KD was better than commonly used clinical measures.
A multicenter retrospective analysis of the clinical and pathological characteristics of 1188 cases of actinic keratosis in different ultraviolet radiation intensity areas of China
Authors: Xu Dan , Sun Jian‐Fang , Qi Rui‐Qun , Zhang Wei , Dong Ling‐Di , Liu Tong‐Yun , Zheng Song , Niu Rui‐Xian , Zhang Juan , Cui Ting‐Ting , He Li , Chen Hong‐Duo 
Published: October 2021

AbstractBackgroundActinic keratosis (AK) is a precancerous disease, caused by ultraviolet radiation (UV).ObjectiveTo analyze the clinical and pathological characteristics of AK in four areas with different ultraviolet radiation intensities.Methods1188 diagnosed AK patients, from January 2000 to July 2015, in dermatology department of four hospitals were collected. The UV intensity of hospital located cities from high to low is Kunming, Yinchuan, Shenyang and Nanjing. The information comes from medical records, and the pathological types and Keratinocyte Intraepithelial Neoplasia (KIN) grades were checked by two experienced pathologists. All information was conducted a retrospective multicenter research.ResultsThe patients were mainly middle‐aged and elderly female, which was in direct contrast to the majority of men in European. The age of onset in Kunming group was lower than that in Yinchuan Group (p = 0.013) and Nanjing Group (p < 0.01). The course of disease in Kunming group was significantly shorter than that in Nanjing Group (p < 0.001). The lesions were almost located in the exposed area. The proportion of unexposed areas in Shenyang group was significantly higher than that in other groups (p < 0.001). There were statistical differences in pathological morphological classification among the four groups. These differences were not affected by age and gender. The number of KIN III grade patients in Shenyang group was significantly higher than that in other three groups (p < 0.05).ConclusionThe Asian patients were mainly female. The clinical characteristics of AK are closely related to UV intensity, and environmental pollution, lifestyle, religious beliefs and other factors are also related.
Efficacy and safety of Resveratrol combined with Ablative Fractional CO2 laser system in the treatment of skin photoaging
Authors: Du Yi‐Mei , Zeng Jing , Li Meng , Wang Yang‐Bin , Wu Yan , Qi Rui‐Qun , Gao Xing‐Hua , Chen Hong‐Duo 
Published: October 2021

AbstractObjectiveTo evaluate the efficacy and safety of resveratrol combined with ablative fractional CO2 laser system (AFL) treating skin photoaging.MethodsThirty‐two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period.ResultsAll subjects in TG achieved improvements of their photoaging signs compared to pre‐treatment both the laser side and the non‐laser side at 6 months (p < 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p < 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p < 0.05). On the non‐laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p < 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG.ConclusionThe resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL.