bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empathic contagious pain and consolation in laboratory rodents: species and sex comparisons
Authors: Du Rui , Luo Wen-Jun , Geng Kai-Wen , Li Chun-Li , Yu Yang , He Ting , Wei Na , Chen Jun 
Published: August 2019

AbstractLaboratory rodents are gregarious in nature and have a feeling of empathy when witnessing a familiar conspecific in pain. The rodent observers express two levels of empathic responses: observational contagious pain (OCP) and consolation. Here we examined the sex and species difference of OCP and consolation in male and female mice and rats. We observed no species difference in both OCP and consolation, but significant species difference in general social (allo-mouth and/or allo-tail sniffing) and non-social (self-grooming) behaviors. For sex difference, male mouse observers showed more allolicking and allogrooming behaviors toward a familiar conspecific in pain during and longer time increase in pain sensitivity after the PDSI than female mouse observers. However, no sex difference was observed in rats. Our results highlighted an evolutionary view of empathy that social animals including rodents also have the ability to feel, recognize, understand and share the other’s distressing states.
Traction forces control cell-edge dynamics and mediate distance-sensitivity during cell polarization
Authors: Messi Zeno , Bornert Alicia , Raynaud Franck , Verkhovsky Alexander 
Published: August 2019

SUMMARYTraction forces are generated by cellular actin-myosin system and transmitted to the environment through adhesions. They are believed to drive cell motion, shape changes, and extracellular matrix remodeling [1–3]. However, most of the traction force analysis has been performed on stationary cells, investigating forces at the level of individual focal adhesions or linking them to static cell parameters such as area and edge curvature [4–10]. It is not well understood how traction forces are related to shape changes and motion, e.g. forces were reported to either increase or drop prior to cell retraction [11–15]. Here, we analyze the dynamics of traction forces during the protrusion-retraction cycle of polarizing fish epidermal keratocytes and find that forces fluctuate in concert with the cycle, increasing during the protrusion phase and reaching maximum at the beginning of retraction. We relate force dynamics to the recently discovered phenomenological rule [16] that governs cell edge behavior during keratocyte polarization: both traction forces and the probability of switch from protrusion to retraction increase with the distance from the cell center. Diminishing traction forces with cell contractility inhibitor leads to decreased edge fluctuations and abnormal polarization, while externally applied force can induce protrusion-retraction switch. These results suggest that forces mediate distance-sensitivity of the edge dynamics and ultimately organize cell-edge behavior leading to spontaneous polarization. Actin flow rate did not exhibit the same distance-dependence as traction stress, arguing against its role in organizing edge dynamics. Finally, using a simple model of actin-myosin network, we show that force-distance relationship may be an emergent feature of such networks.
Spatial variation in introgression along a toad hybrid zone in France
Authors: van Riemsdijk I. , Arntzen J.W. , Bucciarelli G. , McCartney-Melstad E. , Rafajlović M. , Scott P.A. , Toffelmier E. , Shaffer H. B. , Wielstra B. 
Published: August 2019

AbstractThe barrier effect is a restriction of gene flow between diverged populations by barrier genes. Restriction of gene flow and asymmetric introgression over multiple transects indicates species wide (genetic) adaptations, whereas transect-specific barrier loci may indicate local adaptation to gene flow. Asymmetric introgression can be caused by selection, hybrid zone movement, asymmetric reproductive isolation, or a combination of these. We study two widely separated transects (northwest and southeast France) for the 900 km long hybrid zone betweenBufo bufoandB. spinosustoads, using ~1200 markers from restriction-site associated DNA (RAD) sequencing data. Genomic and geographic clines were used to identify outlier markers which show restricted or elevated introgression. Twenty-six barrier markers are shared between transects (the union of 56 and 123 barrier markers identified in each transect), which is more than would be expected by chance. However, the number of barrier markers is twice as high in the southeast transect. In the northwest transect a high amount of (asymmetric) introgression fromB. spinosusintoB. bufois consistent with hybrid zone movement or asymmetric reproductive isolation. In the southeast transect, introgression is symmetric and consistent with a stable hybrid zone. Differences between transects may be related to genetic sub-structure withinB. bufo. A longer period of secondary contact in southeast France appears to result in a relatively stronger barrier effect than in the northwest. TheBufohybrid zone provides an excellent opportunity to separate a general barrier to gene flow from local reductions in gene flow.
β11-12 linker isomerization governs Acid-sensing ion channel desensitization and recovery
Authors: Rook Matthew , Williamson Abby , Lueck John D. , Musgaard Maria , MacLean David M. 
Published: August 2019

AbstractAcid-sensing ion channels (ASICs) are neuronal sodium-selective channels activated by reductions in extracellular pH. Structures of the three presumptive functional states, high-pH resting, low-pH desensitized, and toxin-stabilized open, have all been solved for chicken ASIC1. These structures, along with prior functional data, suggest that the isomerization or flipping of the β11-12 linker in the extracellular, ligand-binding domain is an integral component of the desensitization process. To test this, we combined fast perfusion electrophysiology, molecular dynamics simulations and state-dependent non-canonical amino acid cross-linking. We find that both desensitization and recovery can be accelerated by orders of magnitude by mutating resides in this linker or the surrounding region. Furthermore, desensitization can be suppressed by trapping the linker in the resting state, indicating that isomerization of the β11-12 linker is not merely a consequence of, but a necessity for the desensitization process in ASICs.
Comparison of Leptospira species isolated from environmental water and soil in Japan
Authors: Masuzawa Toshiyuki , Uno Rurika , Matsuhashi Nana , Yamaguchi Masaya , Xu Jun , Nakamura Shuichi 
Published: August 2019

AbstractLeptospira was isolated from environmental water in central Japan using selective medium comprising five antibiotics, namely sulfamethoxazole, trimethoprim, amphotericin B, fosfomycin, and 5‐fluorouracil. Of 100 water samples 57 (57%) were culture‐positive and 50 pure cultures were isolated. Of the 50 cultures isolated from water 48 were classified into a saprophytic clade on the basis of 16S ribosomal RNA gene sequences. However, it was previously reported that isolates from soil in Japan belonged to pathogenic, intermediate, and saprophytic clades, the current findings suggest less diversity of Leptospira species in environmental water than that in soil in Japan.
Impact value of laparoscopic ultrasound over triphasic computed tomography in the management of hepatic focal lesions
Authors: Seleem Mohammed I. , Salaam Mohammed A. 
Published: August 2019

AimIntraoperative ultrasound has an established role in hepatic resections for patients who undergo surgery for potential liver resection. The aim of the present study was to evaluate the impact of laparoscopic intraoperative ultrasonography (LUS) findings compared to pre‐operative triphasic computed tomography (TCT) findings in the management of hepatic focal lesions.Patient and methodsEighty‐seven patients with 192 hepatic focal lesions underwent preoperative TCT and intraoperative LUS evaluation. Data in each case were collected, including number, site and size of hepatic focal lesions.ResultsThere were 112 lesions detected on preoperative TCT, and 80 additional new lesions (42 per cent) were detected in 50 patients, as confirmed by LUS. Twenty‐three lesions (12 per cent) in 20 patients were treated by resection or ablation, and correct staging of the tumours was possible in 61 patients (70 per cent).ConclusionThe use of LUS can be considered a cornerstone for any contemplated hepatic surgery, as it corrects the staging of these lesions. In addition, the present study proved that LUS is more sensitive than TCT in detecting liver tumours, especially smaller lesions and those on the inferior and diaphragmatic surfaces of the liver.
A pace and shape perspective on fertility
Authors: Baudisch Annette , Stott Iain 
Published: August 2019

Abstract

Ageing is ubiquitous to all organisms, but ageing does not always mean senescence. Counter to most evolutionary theories of ageing, the patterns of mortality and reproduction may remain unchanged or improve with age, as well as deteriorate. Describing this diversity presents a challenge to eco‐evolutionary demography. The pace–shape framework of mortality tackled this challenge to qualify and quantify orthogonal components of ageing patterns in mortality. Here, we extend this framework to fertility.

Analogous to the logic of the mortality framework, we define a perspective, a framework and novel methods for the pace and shape of fertility. These distinguish between orthogonal components of time‐scale (pace) and distribution (shape) of reproduction over adult life span.

Our pace and shape framework mirrors that of mortality, through a shift of perspective from the mother giving birth, to the offspring being born. Our new measures overcome many problems associated with measuring natural fertility trajectories, have both a clear biological and mathematical interpretation, can be intuitively visualized and satisfy and extend important conditions of the pace–shape paradigm.

A comprehensive framework of fertility pace–shape facilitates ecological and evolutionary research addressing interactions and trade‐offs between components of birth and death patterns, across the whole tree of life. The burgeoning emergence of large comparative demographic data sources across wide environmental, geographical, temporal and phylogenetic ranges, combined with pace–shape measures, opens the door to comparative analyses of ageing which were never possible before.
Telomere length and aging‐related outcomes in humans: A Mendelian randomization study in 261,000 older participants
Authors: Kuo Chia‐Ling , Pilling Luke C. , Kuchel George A. , Ferrucci Luigi , Melzer David 
Published: August 2019

AbstractInherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging‐related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40–70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow‐up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate‐adjusted p‐values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92–0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06–1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age‐related health outcomes. Telomere lengthening may offer little gain in later‐life health status and face increasing cancer risks.
Increase in nonnative understorey vegetation cover after nonnative conifer removal and passive restoration
Authors: Sample Martha , Aslan Clare E. , Policelli Nahuel , Sanford Robert L. , Nielsen Erik , Nuñez Martín A. 
Published: August 2019

AbstractNonnative conifers are widespread in the southern hemisphere, where their use as plantation species has led to adverse ecosystem impacts sometimes intensified by invasion. Mechanical removal is a common strategy used to reduce or eliminate the negative impacts of nonnative conifers, and encourage native regeneration. However, a variety of factors may preclude active ecological restoration following removal. As a result, passive restoration – unassisted natural vegetation regeneration – is common following conifer removal. We asked, ‘what is the response of understorey cover to removal of nonnative conifer stands followed by passive restoration?' We sampled understorey cover in three site types: two‐ to ten‐year‐old clearcuts, native forest and current plantations. We then grouped understorey species by origin (native/nonnative) and growth form, and compared proportion and per cent cover of these groups as well as of bare ground and litter between the three site types. For clearcuts, we also analysed the effect of time since clearcut on the studied variables. We found that clearcuts had a significantly higher average proportion of nonnative understorey vegetation cover than native forest sites, where nonnative vegetation was nearly absent. The understorey of clearcut sites also averaged more overall vegetation cover and more nonnative vegetation cover (in particular nonnative shrubs and herbaceous species) than either plantation or native forest sites. Notably, 99% of nonnative shrub cover in clearcuts was the invasive nonnative species Scotch broom (Cytisus scoparius). After ten years of passive recovery since clearcutting, the proportion of understorey vegetation cover that is native has not increased and remains far below the proportion observed in native forest sites. Reduced natural regeneration capacity of the native ecosystem, presence of invasive species in the surrounding landscape and land‐use legacies from plantation forestry may inhibit native vegetation recovery and benefit opportunistic invasives, limiting the effectiveness of passive restoration in this context.Abstract in Spanish is available with online material.
Nitrated food proteins induce a regulatory immune response associated with allergy prevention after oral exposure in a Balb/c mouse food allergy model
Authors: Samadi Nazanin , Klems Martina , Heiden Denise , Bauer Renate , Kitzmüller Claudia , Weidmann Eleonore , Ret Davide , Ondracek Anna S. , Duschl Albert , Horejs‐Hoeck Jutta , Untersmayr Eva 
Published: August 2019

AbstractBackgroundFood allergy is associated with a high personal health and economic burden. For immunomodulation toward tolerance, food compounds could be chemically modified, for example, by posttranslational protein nitration, which also occurs via diet‐derived nitrating agents in the gastrointestinal tract.ObjectiveWe sought to analyze the effect of pretreatment with nitrated food proteins on the immune response in a mouse food allergy model and on human monocyte‐derived dendritic cells (moDCs) and PBMCs.MethodsThe model allergen ovalbumin (OVA) was nitrated in different nitration degrees, and the secondary structures of proteins were determined by circular dichroism (CD). Allergy‐preventive treatment with OVA, nitrated OVA (nOVA), and maximally nitrated OVA (nOVAmax) were performed before mice were immunized with or without gastric acid‐suppression medication. Antibody levels, regulatory T‐cell (Treg) numbers, and cytokine levels were evaluated. Human moDCs or PBMCs were incubated with proteins and evaluated for expression of surface markers, cytokine production, and proliferation of Th2 as well as Tregs.ResultsIn contrast to OVA and nOVA, the conformation of nOVAmax was substantially changed. nOVAmax pretreated mice had decreased IgE as well as IgG1 and IgG2a levels and Treg numbers were significantly elevated, while cytokine levels remained at baseline level. nOVAmax induced a regulatory DC phenotype evidenced by a decrease of the activation marker CD86 and an increase in IL‐10 production and was associated with a higher proliferation of memory Tregs.ConclusionOral pretreatment with highly nitrated proteins induces a tolerogenic immune response in the food allergy model and in human immune cells.
Effects of poloxamer‐based thermo‐sensitive sol–gel agent on urethral stricture after transurethral resection of the prostate for benign prostatic hyperplasia: a multicentre, single‐blinded, randomised controlled trial
Authors: Chung Jae Hoon , Kim Kyu Shik , Choi Jae Duck , Kim Tae Hyo , Lee Ki Soo , Oh Cheol Young , Noh Joon Hwa , Kim Jun Seok , Kim Won Tae , Lee Seung Hwan , Kim Jae Heon , Kim Tae Nam , Huh Wan , Lee Seung Wook 
Published: August 2019

ObjectiveTo evaluate the effectiveness of poloxamer‐based thermo‐sensitive sol–gel instillation, after transurethral resection of the prostate (TURP), for preventing urethral stricture.Patients and MethodsIn all, 198 patients underwent TURP for benign prostatic hyperplasia. Recruited patients were randomly divided into two groups: groups A and B. Patients in Group A (100 patients, experimental group) received poloxamer‐based thermo‐sensitive sol–gel instillation and patients in the Group B (98 patients, control group) received lubricant instillation after TURP. Each patient was evaluated at 4 (V1), 12 (V2), and 24 weeks (V3) after TURP. The effectiveness of poloxamer‐based thermo‐sensitive sol–gel instillation was evaluated based on the International Prostate Symptom Score (IPSS), IPSS‐Quality of Life (QoL), Overactive bladder questionnaire (OAB‐q), maximum urinary flow rate (Qmax), post‐void residual urine volume (PVR), and cystoscopy.ResultsAmongst the initial 198 participants, 80 patients in Group A and 83 in Group B completed the study. There were no significant differences in IPSS‐QoL and OAB‐q between the groups. However, Qmax was significantly different between groups A and B, at a mean (SD) of 18.92 (9.98) vs 15.58 (9.24) mL/s (P = 0.028) at 24 weeks after TURP. On cystoscopic examination, urethral stricture after TURP was found in two of the 80 patients in Group A and 10 of 83 in Group B (P = 0.023).ConclusionsPoloxamer‐based thermo‐sensitive sol–gel instillation after TURP lowered the incidence of urethral stricture.
Considerations for improved performance of competition association assays analysed with the Motulsky–Mahan's “kinetics of competitive binding” model
Authors: Georgi Victoria , Dubrovskiy Alexey , Steigele Stephan , Fernández‐Montalván Amaury E. 
Published: August 2019

Background and PurposeTarget engagement dynamics can influence drugs' pharmacological effects. Kinetic parameters for drug:target interactions are often quantified by evaluating competition association experiments—measuring simultaneous protein binding of labelled tracers and unlabelled test compounds over time—with Motulsky–Mahan's “kinetics of competitive binding” model. Despite recent technical improvements, the current assay formats impose practical limitations to this approach. This study aims at the characterisation, understanding and prevention of these experimental constraints, and associated analytical challenges.Experimental ApproachMonte Carlo simulations were used to run virtual kinetic and equilibrium tracer binding and competition experiments in both normal and perturbed assay conditions. Data were fitted to standard equations derived from the mass action law (including Motulsky–Mahan's) and to extended versions aiming to cope with frequently observed deviations of the canonical traces. Results were compared to assess the precision and accuracy of these models and identify experimental factors influencing their performance.Key ResultsKey factors influencing the precision and accuracy of the Motulsky–Mahan model are the interplay between compound dissociation rates, measurement time and interval frequency, tracer concentration and binding kinetics and the relative abundance of equilibrium complexes in vehicle controls. Experimental results produced recommendations for better design of tracer characterisation experiments and new strategies to deal with systematic signal decay.Conclusions and ImplicationsOur data advances our comprehension of the Motulsky–Mahan kinetics of competitive binding models and provides experimental design recommendations, data analysis tools, and general guidelines for its practical application to in vitro pharmacology and drug screening.
The multifunctional peptide DN‐9 produced peripherally acting antinociception in inflammatory and neuropathic pain via μ‐ and κ‐opioid receptors
Authors: Xu Biao , Zhang Mengna , Shi Xuerui , Zhang Run , Chen Dan , Chen Yong , Wang Zilong , Qiu Yu , Zhang Ting , Xu Kangtai , Zhang Xiaoyu , Liedtke Wolfgang , Wang Rui , Fang Quan 
Published: August 2019

Background and PurposeConsiderable effort has recently been directed at developing multifunctional opioid drugs to minimize the unwanted side effects of opioid analgesics. We have developed a novel multifunctional opioid agonist, DN‐9. Here, we studied the analgesic profiles and related side effects of peripheral DN‐9 in various pain models.Experimental ApproachAntinociceptive effects of DN‐9 were assessed in nociceptive, inflammatory, and neuropathic pain. Whole‐cell patch‐clamp and calcium imaging assays were used to evaluate the inhibitory effects of DN‐9 to calcium current and high‐K+‐induced intracellular calcium ([Ca2+]i) on dorsal root ganglion (DRG) neurons respectively. Side effects of DN‐9 were evaluated in antinociceptive tolerance, abuse, gastrointestinal transit, and rotarod tests.Key ResultsDN‐9, given subcutaneously, dose‐dependently produced antinociception via peripheral opioid receptors in different pain models without sex difference. In addition, DN‐9 exhibited more potent ability than morphine to inhibit calcium current and high‐K+‐induced [Ca2+]i in DRG neurons. Repeated treatment with DN‐9 produced equivalent antinociception for 8 days in multiple pain models, and DN‐9 also maintained potent analgesia in morphine‐tolerant mice. Furthermore, chronic DN‐9 administration had no apparent effect on the microglial activation of spinal cord. After subcutaneous injection, DN‐9 exhibited less abuse potential than morphine, as was gastroparesis and effects on motor coordination.Conclusions and ImplicationsDN‐9 produces potent analgesia with minimal side effects, which strengthen the candidacy of peripherally acting opioids with multifunctional agonistic properties to enter human studies to alleviate the current highly problematic misuse of classic opioids on a large scale.