bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Ranking Of Enhancer Networks Facilitates The Discovery Of Epigenetic Markers In Cancer
Authors: Wang Qi , Wu Yonghe , Vorberg Tim , Eils Roland , Herrmann Carl
Published: November 2020

Regulation of gene expression through multiple epigenetic components is a highly combinatorial process. Alterations in any of these layers, as is commonly found in cancer diseases, can lead to a cascade of downstream effects on tumor suppressor or oncogenes. Hence, deciphering the effects of epigenetic alterations on regulatory elements requires innovative computational approaches that can benefit from the huge amounts of epigenomic datasets that are available from multiple consortia, such as Roadmap or BluePrint. We developed a software tool named Irene (Integrative Ranking of Epigenetic Network of Enhancers), which performs quantitative analyses on differential epigenetic modifications through an integrated, network-based approach. The method takes into account the additive effect of alterations on multiple regulatory elements of a gene. Applying this tool to well-characterized test cases, it successfully found many known cancer genes from publicly available cancer epigenome datasets.
Cutting through the noise: reducing bias in motor adaptation analysis
Authors: Blustein Daniel H. , Shehata Ahmed W. , Kuylenstierna Erin S. , Englehart Kevin B. , Sensinger Jonathon W.
Published: November 2020

During goal-directed movements, the magnitude of error correction by a person on a subsequent movement provides important insight into a person’s motor learning dynamics. Observed differences in trial-by-trial adaptation rates might indicate different relative weighting placed on the various sources of information that inform a movement, e.g. sensory feedback, control predictions, or internal model expectations. Measuring this trial-by-trial adaptation rate is not straightforward, however, since externally observed data are masked by noise from several sources and influenced by inaccessible internal processes. Adaptation to perturbation has been used to measure error adaptation as the introduced external disturbance is sufficiently large to overshadow other noise sources. However, perturbation analysis is difficult to implement in real-world scenarios, requires a large number of movement trials to accommodate infrequent perturbations, and the paradigm itself might affect the movement dynamics being observed. Here we focus on error adaptation during unperturbed and naturalistic movements. With increasing motor noise, the conventional estimation of trial-by-trial adaptation increases, a counterintuitive finding that is the consequence of systematic bias in the estimate due to noise masking the learner’s intention. We present an analytic solution relying on stochastic signal processing to reduce this effect of noise, producing an estimate of motor adaptation with reduced bias. The result is an improved estimate of trial-by-trial adaptation in a human learner compared to conventional methods. We demonstrate the effectiveness of the new method in analyzing simulated and empirical movement data under different noise conditions. The analytic approach is applicable across different types of movements in varied contexts and should replace the regression analysis method in future motor analysis studies.

Author Summary

When a person makes a movement, a motor error is typically observed that then drives motor planning corrections on subsequent movements. This error correction provides insight into how the nervous system is operating, particularly in regard to how much confidence a person places in different sources of information such as sensory feedback or motor command reproducibility. Traditional analysis of movement has required carefully controlled laboratory conditions, limiting the usefulness of motor analysis in clinical and everyday environments. Here we present a new computational method that can be accurately applied to typical movements. Counterintuitive findings of the established approach are corrected by the proposed method. This method will provide a common framework for researchers to analyze movements while extending dynamic motor adaptation analysis capabilities to clinical and non-laboratory settings.
mTORC1 and JUN are activated after deletion of Prohibitin 1 in Schwann cells and may link mitochondrial dysfunction to demyelination
Authors: Della-Flora Nunes Gustavo , Wilson Emma R. , Hurley Edward , He Bin , O’Malley Bert W. , Poitelon Yannick , Wrabetz Lawrence , Feltri M. Laura
Published: November 2020

Schwann cell (SC) mitochondria are quickly emerging as an important regulator of myelin maintenance in the peripheral nervous system (PNS). However, the mechanisms underlying demyelination in the context of mitochondrial dysfunction in the PNS are incompletely understood. We recently showed that conditional ablation of the mitochondrial protein Prohibitin 1 (Phb1) in SCs causes a severe and fast progressing demyelinating peripheral neuropathy, but the mechanism that causes failure of myelin maintenance remained unknown. Here, we report that mTORC1 and JUN are continuously activated in the absence ofPhb1, likely due to mitochondrial damage. Moreover, we demonstrate that these pathways are involved in the demyelination process, and that inhibition of mTORC1 using rapamycin partially rescues the demyelinating pathology. Therefore, we propose that mTORC1 and JUN may play a critical role as executioners of demyelination in the context of perturbations to SC mitochondria.
Silencing SmD1 in Solanaceae alters susceptibility to root-knot nematodes
Authors: Mejias Joffrey , Chen Yongpan , Truong Nhat-My , Mulet Karine , Jaubert-Possamai Stéphanie , Abad Pierre , Favery Bruno , Quentin Michaël
Published: November 2020

Root-knot nematodes (RKNs) are among the most damaging pests of agricultural crops. Indeed, Meloidogyne is an extremely polyphagous genus of nematodes that can infect thousands of plant species. A few genes for resistance (R-genes) to RKNs suitable for use in crop breeding have been identified, and new virulent strains and species of nematode emerge rendering these R-genes ineffective. Effective parasitism is dependent on the secretion, by the RKN, of effectors targeting plant functions, which mediate the reprogramming of root cells into specialised feeding cells. These cells, the giant cells, are essential for RKN development and reproduction. The EFFECTOR 18 protein (EFF18) from M. incognita interacts with the spliceosomal protein SmD1 in Arabidopsis, disrupting its function in alternative splicing regulation and modulating the giant cell transcriptome. We show here that EFF18 is a conserved RKN-specific effector. We also show here that EFF18 effectors also target SmD1 in Nicotiana benthamiana and Solanum lycopersicum. The alteration of SmD1 expression by virus-induced gene silencing (VIGS) in Solanaceae affects giant cell formation and nematode development. Thus, SmD1 is a susceptibility gene and a promising target for the development of broad resistance, especially in Solanaceae, for the control of Meloidogyne spp.
Heightened β-adrenergic receptor function in the TgF344-AD rat model drives synaptic potentiation and supports learning and memory
Authors: Goodman Anthoni M. , Langner Bethany M. , Jackson Nateka , Alex Capri , McMahon Lori L.
Published: November 2020

The central noradrenergic (NA) system is critical for maintenance of attention, behavioral flexibility, spatial navigation, and learning and memory, those cognitive functions lost first in early Alzheimer’s disease (AD). In fact, the locus coeruleus (LC), the sole source of norepinephrine (NE) for >90% of the brain, is the first site of pathological tau accumulation in human AD with axon loss throughout forebrain, including hippocampus. The dentate gyrus (DG) is heavily innervated by LC-NA axons, where released norepinephrine (NE) acts on β-adrenergic receptors (ARs) at excitatory synapses from entorhinal cortex (EC) to facilitate long-term synaptic plasticity and memory formation. These synapses dysfunction in early AD prior to cognitive impairment. In the TgF344-AD rat model, degeneration of LC-NA axons in hippocampus recapitulates human AD, providing a preclinical model to investigate synaptic and behavioral consequences. Using immunohistochemistry, Western blot analysis, and brain slice electrophysiology in 6-9 month old wild type and TgF344-AD rats, we discovered that loss of LC-NA axons co-insides with heightened β-AR function at medial perforant path-dentate granule cell synapses (MPP-DCG) that is responsible for the increase in LTP magnitude at these synapses. Furthermore, novel object recognition is facilitated in TgF344-AD rats that requires β-ARs, and pharmacological blockade of β-ARs unmasks a deficit in extinction learning only in TgF344-AD rats, indicating a greater reliance on β-ARs in both behaviors. Thus, a compensatory increase in β-AR function during prodromal AD in TgF344-AD rats heightens synaptic plasticity and preserves some forms of learning and memory.

Significance Statement

The locus coeruleus (LC), a brain region located in the brainstem which is responsible for attention and arousal, is damaged first by Alzheimer’s disease pathology. The LC sends axons to hippocampus where released norepinephrine (NE) modulates synaptic function required for learning and memory. How degeneration of LC axons and loss of NE in hippocampus in early AD impacts synaptic function and learning and memory is not well understood despite the importance of LC in cognitive function. We used a transgenic AD rat model with LC axon degeneration mimicking human AD and found that heightened function of β adrenergic receptors in the dentate gyrus increased synaptic plasticity and preserved learning and memory in early stages of the disease.
Automated and customizable quantitative image analysis of wholeC. elegansgermlines
Authors: Toraason Erik , Adler Victoria L. , Kurhanewicz Nicole A. , DiNardo Acadia , Saunders Adam M. , Cahoon Cori K. , Libuda Diana E.
Published: November 2020

Arranged in a spatial-temporal gradient for germ cell development, the adult germline ofCaenorhabditis elegansis an excellent system for understanding the generation, differentiation, function, and maintenance of germ cells. Imaging wholeC. elegansgermlines along the distal-proximal axis enables powerful cytological analyses of germ cell nuclei as they progress from the pre-meiotic tip through all the stages of meiotic prophase I. To enable high-throughput image analysis of wholeC. elegansgonads, we developed a custom algorithm and pipelines to function with image processing software that enables: 1) quantification of cytological features at single nucleus resolution from immunofluorescence images; and, 2) assessment of these individual nuclei based on their position within the germline. We demonstrate the capability of our quantitative image analysis approach by analyzing multiple cytological features of meiotic nuclei in wholeC. elegansgermlines. First, we quantify double strand DNA breaks (DSBs) per nucleus by analyzing DNA-associated foci of the recombinase RAD-51 at the single-nucleus resolution in the context of whole germline progression. Second, we quantify the DSBs that are licensed for crossover repair by analyzing foci of MSH-5 and COSA-1 when they associate with the synaptonemal complex during meiotic prophase progression. Finally, we quantify P-granule composition across the whole germline by analyzing the colocalization of PGL-1 and ZNFX-1 foci. Our image analysis pipeline is an adaptable and useful method for researchers spanning multiple fields utilizing theC. elegansgermline as a model system.
Accessing NCBI data using the NCBI Sequence Viewer and Genome Data Viewer (GDV)
Authors: Rangwala Sanjida H. , Kuznetsov Anatoliy , Ananiev Victor , Asztalos Andrea , Borodin Evgeny , Evgeniev Vladislav , Joukov Victor , Lotov Vadim , Pannu Ravinder , Rudnev Dmitry , Shkeda Andrew , Weitz Eric M. , Schneider Valerie A.
Published: November 2020

The National Center for Biotechnology Information (NCBI) is an archive providing free access to a wide range and large volume of biological sequence data and literature. Staff scientists at NCBI analyze user-submitted data in the archive, producing gene and SNP annotation and generating sequence alignment tools. NCBI's flagship genome browser, Genome Data Viewer (GDV), displays our in-house RefSeq annotation; is integrated with other NCBI resources such as Gene, dbGaP, and BLAST; and provides a platform for customized analysis and visualization. Here, we describe how members of the biomedical research community can use GDV and the related NCBI Sequence Viewer (SV) to access, analyze, and disseminate NCBI and custom biomedical sequence data. In addition, we report how users can add SV to their own web pages to create a custom graphical sequence display without the need for infrastructure investments or back-end deployments.
Tomographic reconstruction using tilted Laue analyser-based X-ray phase-contrast imaging
Authors: Chalmers M. C. , Kitchen M. J. , Uesugi K. , Falzon G. , Quin P. , Pavlov K. M.
Published: November 2020

Analyser-based phase-contrast imaging (ABPCI) is a highly sensitive phase-contrast imaging method that produces high-contrast images of weakly absorbing materials. However, it is only sensitive to phase gradient components lying in the diffraction plane of the analyser crystal [i.e. in one dimension (1-D)]. In order to accurately account for and measure phase effects produced by the wavefield-sample interaction, ABPCI and other 1-D phase-sensitive methods must achieve 2-D phase gradient sensitivity. An inclined geometry method was applied to a Laue geometry setup for X-ray ABPCI through rotation of the detector and object about the optical axis. This allowed this traditionally 1-D phase-sensitive phase-contrast method to possess 2-D phase gradient sensitivity. Tomographic datasets were acquired over 360° of a multi-material phantom with the detector and sample tilted by 8°. The real and imaginary parts of the refractive index were reconstructed for the phantom.
Design simulations of a horizontally deflecting high-heat-load monochromator
Authors: Brumund Philipp , Reyes-Herrera Juan , Detlefs Carsten , Morawe Christian , Sanchez del Rio Manuel , Chumakov Aleksandr I.
Published: November 2020

The performance of a liquid-nitrogen-cooled high-heat-load monochromator with a horizontal scattering plane has been analysed, aiming to preserve the high quality of the X-ray beam in the vertical plane for downstream optics. Using finite-element analysis, height profiles of the crystal surface for various heat loads and the corresponding slope errors in the meridional and sagittal planes were calculated. Then the angular distortions of the reflected beam in both meridional and sagittal planes were calculated analytically and also modelled by ray tracing, revealing a good agreement of the two approaches. The results show that with increasing heat load in the crystal the slope errors of the crystal surface reach their smallest values first in the sagittal and then in the meridional plane. For the considered case of interest at a photon energy of 14.412 keV and the Si(111) reflection with a Bragg angle of 7.88°, the angular distortions of the reflected beam in the sagittal plane are an order of magnitude smaller than in the meridional one. Furthermore, they are smaller than the typical angular size of the beam source at the monochromator position. For a high-heat-load monochromator operating in the horizontal scattering plane, the sagittal angular distortions of the reflected beam appear in the vertical plane. Thus, such an instrument perfectly preserves the high quality of the X-ray beam in the vertical plane for downstream optics. Compared with vertical scattering, the throughput of the monochromatic beam with the horizontal scattering plane is reduced by only 3.3% for the new EBS source, instead of 34.3% for the old ESRF-1 machine. This identifies the horizontal-scattering high-heat-load monochromator as a device essentially free of the heat-load effects in the vertical plane and without significant loss in terms of throughput.
High-performance macromolecular data delivery and visualization for the web
Authors: Sehnal David , Svobodová Radka , Berka Karel , Rose Alexander S. , Burley Stephen K. , Velankar Sameer , Koča Jaroslav
Published: November 2020

Biomacromolecular structural data make up a vital and crucial scientific resource that has grown not only in terms of its amount but also in its size and complexity. Furthermore, these data are accompanied by large and increasing amounts of experimental data. Additionally, the macromolecular data are enriched with value-added annotations describing their biological, physicochemical and structural properties. Today, the scientific community requires fast and fully interactive web visualization to exploit this complex structural information. This article provides a survey of the available cutting-edge web services that address this challenge. Specifically, it focuses on data-delivery problems, discusses the visualization of a single structure, including experimental data and annotations, and concludes with a focus on the results of molecular-dynamics simulations and the visualization of structural ensembles.
Choosing to be homeless? Persistent rough sleeping and the perverse incentives of social policy in England
Authors: Bowpitt Graham
Published: November 2020

Purpose

With the temporary housing of rough sleepers in response to the Covid-19 emergency, some commentators have been tempted to believe that the rising population of rough sleepers in the UK has finally been reversed. This paper aims to examine the choices made by persistent rough sleepers and how far they are influenced by the perverse incentives of social policies, in order to challenge the view that they sleep rough out of choice.

Design/methodology/approach

Evidence for this paper is derived from two teams of frontline service providers with routine familiarity with the rough sleeping population: a street outreach team and a team of support workers working with adults with multiple and complex needs. Primary data from focus groups were combined with the secondary analysis of both numerical and narrative accounts routinely recorded by both teams.

Findings

The exercise of agency by persistent rough sleepers is constrained by a mixed baggage of complex needs, past negative risk assessments, limited resources and regulatory deterrents to generate choices to reject help that appear irrational. These need to be understood if recent policy initiatives to end rough sleeping are to be effective.

Originality/value

The paper draws on the experience and comprehensive records of practitioners with intimate knowledge of the rough sleeping population. It extends narrative accounts of causes by focusing on key choices to show how the perverse incentives of policy combine with personal factors to incline rough sleeping to persist.
Understanding the customer psychology of impulse buying during COVID-19 pandemic: implications for retailers
Authors: Naeem Muhammad
Published: November 2020

Purpose

During COVID-19 pandemic, the use of social media enhances information exchange at a global level; therefore, customers are more aware and make backup plans to take optimal decisions. This study explores the customer psychology of impulse buying during COVID-19 pandemic.

Design/methodology/approach

The researcher, being a social constructionist, aims at understanding social patterns in impulsive buying strategies during COVID-19 pandemic. Forty UK consumers were participated using the telephonic interview method with the purpose to maintain social distancing practices.

Findings

Results revealed that vulnerable group of people, fear of illness, fear of empty shelves, fear of price increase and social inclination to buy extra for staying at home, increased panic impulsive buying behaviour among customers. Many people socially interpreted the evidence of death rate and empty shelves, which led to more disinformation, rumours and sensationalism, which increased customers' impulsive buying behaviour. Finally, risk of going outside, COVID-19 outbreak among employees of local retail stores, and health professionals' recommendations to stay at home, led to impulsive buying behaviour.

Originality/value

This study has constructed a research framework of customer psychology of impulse buying based on the results of this study and fear and perceived risk theories. The study also explains how the fear of fear, risk perception and conformist tendency enhanced impulsive buying during COVID-19 pandemic. This study has discussed specific implications for retailers.
Collaboration between supply chain partners: when does it matter? Evidence from collaborative profiles
Authors: Kumar Gopal
Published: November 2020

Purpose

Considering the limitations of supply chain collaboration (SCC) literature, the purpose of this paper is to develop SCC framework and analyze the SCC practice based on the framework. The framework incorporating internal and external knowledge sharing under a collaborative culture (CC) and problem-solving environment preceded by preparedness is required.

Design/methodology/approach

To achieve successful collaboration, this paper encompasses problem-solving and performance measurement, preparedness, culture, relationship strength (RS) and gives resource sharing and planning as internal and external focused perspectives. Exploratory methods are used to analyze the data from industries.

Findings

CC, RS and preparedness are crucial that reflect the health of collaboration. Three levels of collaboration practice – good, moderate and weak – are prominent where the extent of SCC practice seems weak. Collaborative activities that matter more are identified. Market-based knowledge sharing is important for good and moderate SCC, while weaker collaboration does not focus on it. Interestingly, this paper finds an increasing level of collaboration may not always result in increased performance. Firms from the pharmaceutical, automobile and electrical/electronic industry tended to practice higher collaboration as compared to other industries.

Originality/value

By integrating market-driven management, resource-based view, and contingency theory, the SCC framework gives a new perspective. Joint planning and resource sharing are categorized as internal and external focused functional areas. The paper identifies three profiles of collaboration and discusses the importance of SCC activities in achieving performance.
Quantification of financial consequences of buildings' ageing: analysis of panel building-level data from the Polish office space market
Authors: Kołodziejczyk Bolesław , Osiichuk Dmytro , Mielcarz Paweł
Published: November 2020

Purpose

Relying on a unique proprietary Polish office market space database, the paper attempts to quantify the impact of buildings' age on the financial performance of real estate assets.

Design/methodology/approach

Panel econometric modeling was utilized to disentangle the impact of buildings' functional obsolescence and technical deterioration on their long-term financial performance.

Findings

In line with casual empiricism, our findings show a negative associative link between properties' age and potential lease revenue. The concomitant stickiness of service charges presages a possible long-term deterioration of financial outcomes of real estate investments. While older buildings generally have higher occupancy rates, the absorption rates are found to be negatively affected by the properties' age. On the bright side, the elasticity of vacancy rate with respect to rental rates is found to decrease as buildings get older. Further, the rent differential is confirmed to be more pronounced in higher age properties hinting at an existing potential for price discrimination, which may at least partially compensate for stagnant rents.

Originality/value

Our empirical results confirm the properties' age to be a statistically significant factor in shaping the long-term performance of real estate assets, which should be better accounted for in financial projections for real estate developments.
A framework for integrating strategic HR and knowledge management for innovation performance
Authors: Trivedi Karishma , Srivastava Kailash Bihari Lal
Published: November 2020

Purpose

Organizations that resort to knowledge management (KM) for innovation need to align their organizational strategies for KM success. The purpose of this paper is to develop a conceptual framework depicting the alignment of strategic HR practices with organizational culture and strategy. This alignment posits to leverage KM processes for improving innovation performance in organizations.

Design/methodology/approach

Drawing from configurational–contingent HR perspective, this paper reviews the literature critically to identify the role and relationship among strategic HR practices, organizational culture and business strategy in contributing to KM process and innovation.

Findings

Complementarity between strategic HR practices with business strategy and organizational culture can create a synergistic effect on the KM process for improved innovation performance.

Research limitations/implications

This paper is theoretical. To validate the proposed conceptual framework, it needs empirical verification by future studies.

Practical implications

Managements should configure their HR practices with strategy and enable a knowledge-oriented culture to develop employee capabilities, creating intellectual assets for bringing more innovativeness in organizations.

Originality/value

The paper addresses the gap by relating strategic HR practices, strategy and culture in KM context with firm innovation in a comprehensive model. It is among the few studies to critically review strategic human resource practices-KM relationship from contingent–configurational HR perspective, relevant for HR managers in the current knowledge-based organizations.
Video-modelling as an effective solution for coaching carers of autistic adults
Authors: Cohen Gabriel , McGill Peter
Published: November 2020

Purpose

Teaching skills to autistic individuals can increase independence and quality of life. However, staff supporting such individuals often lack the skills needed to teach skills. This study evaluated the use of digital videos (DVDs) to coach three care staff in teaching tooth-brushing skills to three autistic adults with co-occurring intellectual disabilities.

Design/methodology/approach

Personalized DVDs provided guidance on key elements of teaching new skills, including graded assistance, contingent reinforcement and environmental configuration. Participants watched their DVD six times over several days. Its impact on their teaching performances was evaluated using a multiple-baseline design. Social validity was investigated by distributing a questionnaire among the participants and family members of autistic adults.

Findings

Teaching performances improved substantially following training. The coaching method was rated positively by participants and family members.

Originality/value

Video-modelling technology can be used effectively to provide an efficient, individualized and acceptable method of coaching for care staff.
COVID-19 lockdown: the unspoken toll on the 65+ community in Turkey
Authors: Ates Ozgur
Published: November 2020

Purpose

On March 21, 2020, the Turkish Government imposed a curfew for citizens 65 years old and over and ordered them to stay at home as a measure to protect them against the COVID-19 outbreak. The curfew ended on June 10, 2020, having lasted 82 days. The purpose of this paper is to examine the significant emotional burden on the elderly, as they felt excluded and battled with despair during the lockdown.

Design/methodology/approach

This reflective paper shares the COVID-19 lockdown experiences of the author with a group of elderly residents of a small community in Ankara, Turkey. Through semi-structured interviews and analysis, three overarching themes of the residents’ experience were identified: vulnerability, social isolation/loneliness and ageism.

Findings

The elderly in the community are individuals who get their social interaction outside the home. As a result of the nearly three months of social isolation, they have experienced social disconnection and health problems,

Originality/value

To the best of the author’s knowledge, this is the first attempt to give voice to the silenced group of elderly and share their thoughts and feelings during this difficult COVID-19 lockdown in Turkey.
Elevated atmospheric concentrations of CO2 increase endogenous immune function in a specialist herbivore
Authors: Decker Leslie E. , Jeffrey Christopher S. , Ochsenrider Kaitlin M. , Potts Abigail S. , de Roode Jacobus C. , Smilanich Angela M. , Hunter Mark D.
Published: November 2020

Animals rely on a balance of endogenous and exogenous sources of immunity to mitigate parasite attack. Understanding how environmental context affects that balance is increasingly urgent under rapid environmental change. In herbivores, immunity is determined, in part, by phytochemistry which is plastic in response to environmental conditions. Monarch butterflies Danaus plexippus, consistently experience infection by a virulent parasite Ophryocystis elektroscirrha, and some medicinal milkweed (Asclepias) species, with high concentrations of toxic steroids (cardenolides), provide a potent source of exogenous immunity.

We investigated plant‐mediated influences of elevated CO2 (eCO2) on endogenous immune responses of monarch larvae to infection by O. elektroscirrha. Recently, transcriptomics have revealed that infection by O. elektroscirrha does not alter monarch immune gene regulation in larvae, corroborating that monarchs rely more on exogenous than endogenous immunity. However, monarchs feeding on medicinal milkweed grown under eCO2 lose tolerance to the parasite, associated with changes in phytochemistry. Whether changes in milkweed phytochemistry induced by eCO2 alter the balance between exogenous and endogenous sources of immunity remains unknown.

We fed monarchs two species of milkweed; A. curassavica (medicinal) and A. incarnata (non‐medicinal) grown under ambient CO2 (aCO2) or eCO2. We then measured endogenous immune responses (phenoloxidase activity, haemocyte concentration and melanization strength), along with foliar chemistry, to assess mechanisms of monarch immunity under future atmospheric conditions.

The melanization response of late‐instar larvae was reduced on medicinal milkweed in comparison to non‐medicinal milkweed. Moreover, the endogenous immune responses of early‐instar larvae to infection by O. elektroscirrha were generally lower in larvae reared on foliage from aCO2 plants and higher in larvae reared on foliage from eCO2 plants. When grown under eCO2, milkweed plants exhibited lower cardenolide concentrations, lower phytochemical diversity and lower nutritional quality (higher C:N ratios). Together, these results suggest that the loss of exogenous immunity from foliage under eCO2 results in increased endogenous immune function.

Animal populations face multiple threats induced by anthropogenic environmental change. Our results suggest that shifts in the balance between exogenous and endogenous sources of immunity to parasite attack may represent an underappreciated consequence of environmental change.
Salmon on the lam: Drivers of escaped farmed fish abundance in rivers
Authors: Mahlum Shad , Vollset Knut Wiik , Barlaup Bjørn T. , Skoglund Helge , Velle Gaute
Published: November 2020

The production of Atlantic salmon in aquaculture has grown substantially over the last 40 years. The unintentional release of domesticated salmon poses a significant risk to the long‐term persistence of wild Atlantic salmon populations through ecological interactions and genetic introgression. Our ability to link aquaculture production to farmed escaped salmon in rivers is still limited and hinders identifying the appropriate production capacity of salmon aquaculture to reduce unwanted interactions between wild and escaped Atlantic salmon.

Here we use a 14‐year dataset of farmed escapee abundance in rivers to model how the a priori selected covariables of wild salmon abundance, aquaculture intensity, river discharge, hydropower and fjord placement of the river affects escapee abundance across 54 rivers in western Norway. Then, we evaluate the predictive strength of the model to provide context for its use to minimize escapees.

We found that the abundance of escaped farmed Atlantic salmon in rivers is correlated to aquaculture intensity. Furthermore, the abundance of wild Atlantic salmon, mean yearly discharge, and the interaction between fjord placement and wild salmon abundance were important predictors of escapee abundance in rivers.

The model was 40% accurate when predicting the abundance of farmed escaped salmon in rivers. However, the accuracy improved to 75% when using risk categories derived from modelled intrusion rates that induced long‐term genetic changes to the wild population (low < 4%, medium 4%–10%, and high > 10% escaped farmed salmon).

Synthesis and applications. This study links aquaculture production, at relevant spatiotemporal scales (75 km from rivers), to the abundance of escaped farmed Atlantic salmon in rivers, and provides governmental agencies with a tool to help regulate domesticated salmon production based on the carrying capacity of the system to buffer against introgression between conspecifics. Furthermore, understanding this relationship will be beneficial when establishing new aquaculture sites in pristine ecosystems where they would overlap with wild Atlantic salmon. Finally, future mitigation efforts should continue to focus on new technologies (e.g. triploid females) that can eliminate the risk of introgression without limiting aquaculture production.
Hometown identity of financial officials, financial development and promotion of officials in China
Authors: Yin Haiyuan , Chen Baifan
Published: November 2020

By collecting the hometown information of financial officials, and the data of provincial governors and secretaries of the provincial Communist Party of China (CPC) in China from 2001 to 2017, we have proved the causality relationship among financial officials' hometown identity, financial development and the promotion of local officials. Empirical results show that financial officials' hometown identity significantly increases the promotion probability of provincial governors and secretaries of the provincial CPC committee. We also confirmed the positive relationship between financial officials' hometown identity and financial development. This may be because financial officials prefer their hometown when allocating financial resources. It is further found that financial development plays an intermediary role between the financial officials' hometown identity and local officials' promotion.
Investigating the validity of the Wong and Law Emotional Intelligence Scale in a Nepali student sample
Authors: Sochos Antigonos , Prasad Regmi Murari , Basnet Dess Mardan
Published: November 2020

This paper investigates the cross‐cultural validity of the Wong and Law Emotional Intelligence Scale. Two samples of university students were recruited: 504 from a Nepali university and 260 from a UK university. In relation to culture, structural equation modelling analyses provided support for the scale's configural invariance and the configural, metric, and scalar invariance of two if its subscales. Evidence for measurement invariance was also found in relation to gender in both samples. Tentative analyses suggested that the correlation between self and other emotion appraisal was stronger among UK participants and that UK participants scored higher on the Other Emotion Appraisal subscale. No gender differences on emotional intelligence were found in the Nepali sample, while among UK students, males scored higher on Regulation of Emotion and lower on Other Emotion Appraisal than females. In the Nepali sample, science students scored lower on various aspects of emotional intelligence than humanities students.
USP7, negatively regulated by miR‐409‐5p, aggravates hypoxia‐induced cardiomyocyte injury
Authors: Xue Qiang , Yang Dong , Zhang Jilei , Gan Pin , Lin Chunrong , Lu Yibing , Zhang Weihua , Zhang Li , Guang Xuefeng
Published: November 2020

Hypoxia‐induced apoptosis is linked to the pathogenesis of myocardial infarction (MI) and heart failure. Ubiquitin‐specific peptidase 7 (USP7) is related to catabolic/pro‐apoptotic signaling. However, its role in cardiomyocyte injury is unclear. In this study, we aimed to investigate the role and the underlying regulatory mechanism of USP7 in MI. H9c2 cardiomyocytes were cultured in hypoxia to establish an in vitro model of myocardial hypoxic/ischemic injury. Sprague‐Dawley (SD) rats were used to establish animal models with MI. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot assays were performed to evaluate the expression levels of miR‐409‐5p, USP7, and p53, respectively. After USP7 and miR‐409‐5p were selectively regulated in H9c2 cells, the inflammatory response, apoptosis, and cell viability were detected by ELISA, flow cytometry, and MTT assay, respectively. The interaction between USP7 and miR‐409‐5p was determined by bioinformatics analysis, qRT‐PCR, Western blot, and dual‐luciferase reporter assay. LVEF, LVIDd, and LVIDs of rats after MI were also measured. USP7 expression was markedly elevated while miR‐409‐5p expression was significantly down‐regulated in H9c2 cells under hypoxic culture. Augmentation of USP7 expression led to a dramatic promotion of hypoxia‐induced apoptosis of cardiomyocytes, accompanied by an increase in the secretion of the cytokines IL‐1β, TNF‐α, and IL‐6. Myocardial injury markers LDH, cTnI, and CK‐MB expressions were also increased. Besides, overexpression of USP7 aggravated left ventricular remodeling and decreased left ventricular function of the rats. Conversely, the up‐regulation of miR‐409‐5p expression protected H9c2 cells from apoptosis and inhibited the release of cytokines and myocardial injury. Left ventricular remodeling and left ventricular function were also improved by miR‐409‐5p overexpression. Furthermore, USP7 was identified as a target of miR‐409‐5p and the overexpression of miR‐409‐5p reversed the effects of USP7 on H9c2 cells. USP7 exacerbates myocardial ischemic injury by promoting inflammation and apoptosis of cardiomyocytes, and the up‐regulation of its expression is partly caused by the down‐regulation of miR‐409‐5p expression.
Riociguat: Clinical research and evolving role in therapy
Authors: Klinger James R. , Chakinala Murali M. , Langleben David , Rosenkranz Stephan , Sitbon Olivier
Published: November 2020

Riociguat is a first‐in‐class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT‐1 (PAH) and CHEST‐1 (CTEPH) studies, with significant improvements in the primary endpoint of 6‐minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as an inhibitor of cGMP metabolism. As with other approved therapies for PAH, riociguat has antifibrotic, antiproliferative and anti‐inflammatory effects, in addition to vasodilatory properties. This has led to further clinical studies in patients who do not achieve a satisfactory clinical response with phosphodiesterase type‐5 inhibitors. Riociguat has also been evaluated in patients with World Health Organization group 2 and 3 pulmonary hypertension, and other conditions including diffuse cutaneous systemic sclerosis, Raynaud's phenomenon and cystic fibrosis. This review evaluates the results of the original clinical trials of riociguat for the treatment of PAH and CTEPH, and summarises the body of work that has examined the safety and efficacy of riociguat for the treatment of other types of pulmonary hypertension.
Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype
Authors: Marjanovic Irena , Karan‐Djurasevic Teodora , Kostic Tatjana , Virijevic Marijana , Vukovic Nada Suvajdzic , Pavlovic Sonja , Tosic Natasa
Published: November 2020

Introduction

Acute myeloid leukemia with normal karyotype (AML‐NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes.

Methods

In this study, we investigated expression level of both genes in 111 adult AML‐NK at diagnosis and examined their prognostic potential.

Results

BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC+/or MN1+ status was not associated with the presence of FLT3‐ITD mutations, but exhibited strong correlation with NPM1wt status (P < .001). Therefore, among BAALC+/or MN1+ patients the most frequent ones were FLT3‐ITD‐/NPM1‐ double negative patients with intermediate prognosis. When BAALC+/or MN1+ patients were divided into BAALChigh/BAALClow (21/21) and MN1high/MN1low (21/22) groups, we detected that BAALChigh/or MN1high patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALChigh/or MN1high patients had shorter disease‐free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3‐ITD‐/NPM1‐ group of patients that are lacking reliable prognostic markers, where OS in BAALChigh/or MN1high was only 5 months vs 25 months in BAALClow/or MN1low.

Conclusion

These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML‐NK patients and especially FLT3‐ITD‐/NPM1‐ patients, transforming this intermediate‐risk group, into a group with an adverse prognosis.
Ambulatory blood pressure and risk of new‐onset atrial fibrillation in treated hypertensive patients
Authors: Coccina Francesca , Pierdomenico Anna M. , Ianni Umberto , De Rosa Matteo , De Luca Andrea , Pirro Davide , Pizzicannella Jacopo , Trubiani Oriana , Cipollone Francesco , Renda Giulia , Pierdomenico Sante D.
Published: November 2020

The aim of this study was to evaluate the influence of clinic and ambulatory blood pressure (BP) on the occurrence of new‐onset atrial fibrillation (AF) in treated hypertensive patients. We studied 2135 sequential treated hypertensive patients aged >40 years. During the follow‐up (mean 9.7 years, range 0.4–20 years), 116 events (new‐onset AF) occurred. In univariate analysis, clinic, daytime, nighttime, and 24‐h systolic BP were all significantly associated with increased risk of new‐onset AF, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.22 (1.11–1.35), 1.36 (1.21–1.53), 1.42 (1.29–1.57), and 1.42 (1.26–1.60), respectively. After adjustment for various covariates in multivariate analysis, clinic systolic BP was no longer associated with increased risk of new‐onset AF, whereas daytime, nighttime, and 24‐h systolic BP remained significantly associated with outcome, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.09 (0.97–1.23), 1.23 (1.10–1.39), 1.16 (1.03–1.31), and 1.22 (1.06–1.40), respectively. Daytime, nighttime, and 24‐h systolic BP are superior to clinic systolic BP in predicting new‐onset AF in treated hypertensive patients. Future studies are needed to evaluate whether a better control of ambulatory BP might be helpful in reducing the occurrence of new‐onset AF.
Genome‐wide association study identifies 7q11.22 and 7q36.3 associated with noise‐induced hearing loss among Chinese population
Authors: Niu Yuguang , Xie Chengyong , Du Zhenhua , Zeng Jifeng , Chen Hongxia , Jin Liang , Zhang Qing , Yu Huiying , Wang Yahui , Ping Jie , Yang Chenning , Liu Xinyi , Li Yuanfeng , Zhou Gangqiao
Published: November 2020

Noise‐induced hearing loss (NIHL) seriously affects the life quality of humans and causes huge economic losses to society. To identify novel genetic loci involved in NIHL, we conducted a genome‐wide association study (GWAS) for this symptom in Chinese populations. GWAS scan was performed in 89 NIHL subjects (cases) and 209 subjects with normal hearing who have been exposed to a similar noise environment (controls), followed by a replication study consisting of 53 cases and 360 controls. We identified that four candidate pathways were nominally significantly associated with NIHL, including the Erbb, Wnt, hedgehog and intraflagellar transport pathways. In addition, two novel index single‐nucleotide polymorphisms, rs35075890 in the intron of AUTS2 gene at 7q11.22 (combined P = 1.3 × 10−6) and rs10081191 in the intron of PTPRN2 gene at 7q36.3 (combined P = 2.1 × 10−6), were significantly associated with NIHL. Furthermore, the expression quantitative trait loci analyses revealed that in brain tissues, the genotypes of rs35075890 are significantly associated with the expression levels of AUTS2, and the genotypes of rs10081191 are significantly associated with the expressions of PTPRN2 and WDR60. In conclusion, our findings highlight two novel loci at 7q11.22 and 7q36.3 conferring susceptibility to NIHL.
Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE−/− Mice
Authors: Wu Yao , Song Fei , Li Yunda , Li Jingzhou , Cui Yukai , Hong Yixiang , Han Weimin , Wu Weiyin , Lakhani Ishan , Li Gang , Wang Yan
Published: November 2020

Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti‐inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulatory effects of acacetin in maintaining endothelial cell function and further investigated whether the flavonoid could attenuate atherosclerosis in apolipoprotein E deficiency (apoE−/−) mice. Different concentrations of acacetin were tested on EA.hy926 cells, either induced or non‐induced by human oxidized low‐density lipoprotein (oxLDL), to clarify its influence on cell viability, cellular reactive oxidative stress (ROS) level, apoptotic ratios and other regulatory effects. In vivo, apoE−/− mice were fed either a Western diet or a chow diet. Acacetin pro‐drug (15 mg/kg) was injected subcutaneously two times a day for 12 weeks. The effects of acacetin on the atherosclerotic process, plasma inflammatory factors and lipid metabolism were also investigated. Acacetin significantly increased EA.hy926 cell viability by reducing the ratios of apoptotic and necrotic cells at 3 μmol/L. Moreover, 3 μmol/L acacetin clearly decreased ROS levels and enhanced reductase protein expression through MsrA and Nrf2 pathway through phosphorylation of Nrf2 and degradation of Keap1. In vivo, acacetin treatment remarkably attenuated atherosclerosis by increasing reductase levels in circulation and aortic roots, decreasing plasma inflammatory factor levels as well as accelerating lipid metabolism in Western diet‐fed apoE−/− mice. Our findings demonstrate the anti‐oxidative and anti‐atherosclerotic effects of acacetin, in turn suggesting its potential therapeutic value in atherosclerotic‐related cardiovascular diseases (CVD).