bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadband Tuning the Voltage Dependence of a Sodium Channel
Authors: McCord Eedann , Wisedchaisri Goragot , Catterall William A.
Published: November 2020

Voltage-gated sodium channels initiate action potentials in prokaryotes and in many eukaryotic cells, including vertebrate nerve and muscle. Their activation is steeply voltage-dependent, but it is unclear how the voltage sensitivity is set or whether it can be broadly shifted to positive voltages. Here we show that the voltage dependence of activation (VA) of the ancestral bacterial sodium channel NaVAb can be progressively shifted from −118 mV to +35 mV in chimeras with increasing numbers of amino acid residues from the extracellular half of the voltage sensor of human NaV1.7 channels. In a minimal chimera in which only 32 residues were transferred, we analyzed the effects of six additional mutations of conserved amino acid residues singly, in pairs, and as triple mutations. The resulting chimeric mutants exhibited a broad range of voltage sensitivity from VA=−118 mV to VA=+120 mV. Three mutations (N48K, L112A, and M119V) shifted VAto +61 mV when substituted in NaVAb itself, and substitution of two additional Cys residues in the Cys-free background of NaVAb further shifted VAto +105 mV. In these mutants, measurement of gating currents revealed that the voltage dependence of gating charge movement (VQ) shifted to positive membrane potentials as much or more than VA, confirming that the gating charges are trapped in their resting positions by these VA-shifting mutations. Our results demonstrate broadband shifting of VAand VQof a sodium channel across a range of 240 mV and provide a toolbox of methods and constructs to analyze sodium channel structure and function in the resting state at 0 mV and in activated states at positive membrane potentials.

GRAPHICAL ABSTRACT

The complete range of broadband tuning of voltage-dependent activation of a sodium channel.
Anti-COVID-19 efficacy of ivermectin in the golden hamster
Authors: de Melo Guilherme Dias , Lazarini Françoise , Larrous Florence , Feige Lena , Kergoat Lauriane , Marchio Agnès , Pineau Pascal , Lecuit Marc , Lledo Pierre-Marie , Changeux Jean-Pierre , Bourhy Hervé
Published: November 2020

The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and more than 1.2 million human deaths around the globe1, and most of the severe cases of COVID-19 in humans are associated with neurological symptoms such as anosmia and ageusia, and uncontrolled inflammatory immune response2–5. Among therapeutic options6–8, the use of the anti-parasitic drug ivermectin (IVM), has been proposed, given its possible anti-SARS-CoV-2 activity9. Ivermectin is a positive allosteric modulator of the α-7 nicotinic acetylcholine receptor10, which has been suggested to represent a target for the control of Covid-19 infection11, with a potential immunomodulatory activity12. We assessed the effects of IVM in SARS-CoV-2-intranasally-inoculated golden Syrian hamsters. Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced theIl-6/Il-10ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.
Three-dimensional ATUM-SEM reconstruction and analysis of hepatic endoplasmic reticulum-organelle interactions
Authors: Jiang Yi , Li Linlin , Chen Xi , Liu Jiazheng , Yuan Jingbin , Xie Qiwei , Han Hua
Published: November 2020

The endoplasmic reticulum (ER) is a contiguous and complicated membrane network in eukaryotic cells, and membrane contact sites (MCSs) between the ER and other organelles perform vital cellular functions, including lipid homeostasis, metabolite exchange, calcium level regulation, and organelle division. Here, we establish a whole pipeline to reconstruct all ER, mitochondria, lipid droplets, lysosomes, peroxisomes, and nuclei by automated tape-collecting ultramicrotome scanning electron microscopy (ATUM-SEM) and deep-learning techniques, which generates an unprecedented 3D model for mapping liver samples. Furthermore, the morphology of various organelles is systematically analyzed. We found that the ER presents with predominantly flat cisternae and is knitted tightly all throughout the intracellular space and around other organelles. In addition, the ER has a smaller volume-to-membrane surface area ratio than other organelles, which suggests that the ER could be more suited for functions that require a large membrane surface area. Moreover, the MCSs between the ER and other organelles are explored. Our data indicate that ER-mitochondrial contacts are particularly abundant, especially for branched mitochondria. In addition, ER contacts with lipid droplets, lysosomes, and peroxisomes are also plentiful. In summary, we design an efficient method for obtaining a 3D reconstruction of biological structures at a nanometer resolution. Our study also provides the first 3D reconstruction of various organelles in liver samples together with important information fundamental for biochemical and functional studies in the liver.
In vivostabilization of endogenous chloroplast RNAs by customized artificial pentatricopeptide repeat proteins
Authors: Manavski Nikolay , Meteignier Louis-Valentin , Rojas Margarita , Brachmann Andreas , Barkan Alice , Hammani Kamel
Published: November 2020

Pentatricopeptide repeat (PPR) proteins are helical repeat-proteins that bind RNA in a modular fashion with a sequence-specificity that can be manipulated by the use of an amino acid code. As such, PPR repeats are promising scaffolds for the design of RNA binding proteins for synthetic biology applications. However, thein vivofunctional capabilities of artificial PPR proteins built from consensus PPR motifs are just starting to be explored. Here, we reportin vivofunctions of an artificial PPR protein, dPPRrbcL, made of consensus PPR motifs that were designed to bind a sequence near the 5’ end ofrbcLtranscripts in Arabidopsis chloroplasts. We used a functional complementation assay to demonstrate that this protein bound its intended RNA target with specificityin vivoand that it substituted for a natural PPR protein by stabilizing processedrbcLmRNA. We targeted a second protein of analogous design to thepetL5’ UTR, where it substituted for the native stabilizing PPR protein PGR3, albeit inefficiently. These results showed that artificial PPRs can be engineered to functionally mimic the class of native PPR proteins that serve as physical barriers against exoribonucleases.
Frameshift and frame-preserving mutations in zebrafishpresenilin 2affect different cellular functions in young adult brains
Authors: Barthelson Karissa , Pederson Stephen Martin , Newman Morgan , Jiang Haowei , Lardelli Michael
Published: November 2020

Background

Mutations inPRESENILIN 2(PSEN2) cause early disease onset familial Alzheimer’s disease (EOfAD) but their mode of action remains elusive. One consistent observation for allPRESENILINgene mutations causing EOfAD is that a transcript is produced with a reading frame terminated by the normal stop codon – the “reading frame preservation rule”. Mutations that do not obey this rule do not cause the disease. The reasons for this are debated.

Methods

A frameshift mutation (psen2N140fs) and a reading frame-preserving mutation (psen2T141_L142delinsMISLISV) were previously isolated during genome editing directed at the N140 codon of zebrafishpsen2(equivalent to N141 of humanPSEN2). We mated a pair of fish heterozygous for each mutation to generate a family of siblings including wild type and heterozygous mutant genotypes. Transcriptomes from young adult (6 months) brains of these genotypes were analysed. Bioinformatics techniques were used to predict cellular functions affected by heterozygosity for each mutation.

Results

The reading frame preserving mutation uniquely caused subtle, but statistically significant, changes to expression of genes involved in oxidative phosphorylation, long term potentiation and the cell cycle. The frameshift mutation uniquely affected genes involved in Notch and MAPK signalling, extracellular matrix receptor interactions and focal adhesion. Both mutations affected ribosomal protein gene expression but in opposite directions.

Conclusion

A frameshift and frame-preserving mutation at the same position in zebrafishpsen2cause discrete effects. Changes in oxidative phosphorylation, long term potentiation and the cell cycle may promote EOfAD pathogenesis in humans.
Salicylate, Bile Acids and Extreme Acid Cause Fitness Tradeoffs for Multidrug Pumps inEscherichia coliK-12
Authors: Schaffner Samantha H. , Lee Abigail V. , Pham Minh T. N. , Kassaye Beimnet B. , Li Haofan , Tallada Sheetal , Lis Cassandra , Lang Mark , Liu Yangyang , Ahmed Nafeez , Galbraith Logan G. , Moore Jeremy P. , Bischof Katarina M. , Slonczewski Joan L.
Published: November 2020

The aspirin derivative salicylate selects against bacterial multidrug efflux pumps ofEscherichia coliK-12 such as MdtEF-TolC and EmrAB-TolC, and acid stress regulators such as GadE. Salicylate uptake is driven by the transmembrane pH gradient (ΔpH) and the proton motive force (PMF) which drives many efflux pumps. We used flow cytometry to measure the fitness tradeoffs of salicylate, bile acids, and extreme low pH forE. colicultured with pump deletants. The AcrAB-TolC efflux pump conferred a fitness advantage in the presence of bile acids, an efflux substrate. Without bile acids, AcrA incurred a small fitness cost. The fitness advantage with bile acids was eliminated by the PMF uncoupler CCCP. The Gad acid fitness island encodes components of MdtEF-TolC (an acid-adapted efflux pump) as well as acid regulator GadE. The fitness advantage ofE. colicocultured with a Gad deletant (Δslp-gadX) was lost in the presence of salicylate. Salicylate caused an even larger fitness cost for GadE. MdtE incurred negative or neutral fitness under all media conditions, as did EmrA. But when the competition cycle included two hours at pH 2, MdtE conferred a fitness advantage. The MdtE advantage required the presence of bile acids. Thus, the MdtEF-TolC pump is useful toE. colifor transient extreme acid exposure comparable to passage through the acidic stomach. Salicylate selects against some multidrug efflux pumps, whereas bile acids selects for them; and these fitness tradeoffs are amplified by extreme acid.

IMPORTANCE

Control of drug resistance in gut microbial communities is a compelling problem for human health. Growth of gut bacteria is limited by host-produced acids such as bile acids, and may be modulated by plant-derived acids such as salicylic acid. Membrane-soluble organic acids can control bacterial growth by disrupting membranes, decreasing cell pH, and depleting PMF. Our flow cytometry assay measures the fitness effects of exposure to membrane-soluble organic acids, with growth cycles that may include a period of extreme acid. We find that extreme-acid exposure leads to a fitness advantage for a multidrug pump, MdtEF-TolC, which otherwise incurs a large fitness cost. Thus, organic acids and stomach acid may play important roles in controlling multidrug resistance in the gut microbiome. Therapeutic acids might be developed to limit the prevalence of multidrug resistance pumps in environmental and host-associated communities.
STAT3 inhibits Myocardin induced cardiac hypertrophy
Authors: Liao Xing-Hua , Xiang Yuan , Li Jia-Peng , Li Hui , Huang You , Shen Chao , Zhang Hui-Min , Zhang Tong-Cun
Published: November 2020

Background

In order to explore the molecular mechanism of cardiomyocyte-dependent myocardial gene expression and cardiomyocyte differentiation in cardiac hypertrophy, and to provide new insights for cardiac hypertrophy.

Methods

Cardiac myocytes were isolated from day 1-3 Sprague-Dawley rat pups. Real time quantitative PCR, western blot and immunocytochemistry Assay were used to detect the expression and localization of related genes. CO-IP was used to detect direct protein interactions between Myocardin and STAT3. Luciferase reporter assay and chromatin immunoprecipitation were used to detect the binding of Myocardin to the promoter of a downstream target gene. Microinjection of zebrafish embryos was used to examine the effects of STAT3 and Myocardin interactions on cardiac development in vivo

Results

The N-terminus of STAT3 directly binds to the basic domain of myocardin and inhibits the transcriptional activity of Myocardin-mediated cardiac-specific genes ANF and α-actinin, thereby inhibiting their expression, and further inhibit myocardin-mediated cardiac hypertrophy in vivo.

Conclusions

In summary, our report states that signal transduction and transcriptional activation factor 3 (STAT3) are inhibitors of the major cardiac hypertrophic transcription factor Myocardiin, which is required for cardiomyocyte differentiation. The STAT3-cardiacin interaction identified nuclear hormone receptor-mediated and cardiac-specific gene-regulated convergence sites and suggested a possible mechanism for cardioprotective effects.
Dynamic integration and segregation of amygdala subregional functional circuits linking to physiological arousal
Authors: Zeng Yimeng , Tao Fuxiang , Cui Zaixu , Wu Liyun , Xu Jiahua , Dong Wenshan , Liu Chao , Yang Zhi , Qin Shaozheng
Published: November 2020

The dynamical organization of brain networks is essential to support human cognition and emotion for rapid adaption to ever-changing environment. As the core nodes of emotion-related brain circuitry, the basolateral amygdala (BLA) and centromedial amygdala (CMA) as two major amygdalar nuclei, are recognized to play distinct roles in affective functions and internal states, via their unique connections with cortical and subcortical structures in rodents. However, little is known how the dynamical organization of emotion-related brain circuitry reflects internal autonomic responses in humans. Using resting-state functional magnetic resonance imaging (fMRI) with K-means clustering approach in a total of 79 young healthy individuals (cohort 1: 42; cohort 2: 37), we identified two distinct states of BLA- and CMA-based intrinsic connectivity patterns, with one state (integration) showing generally stronger BLA- and CMA-based intrinsic connectivity with multiple brain networks, while the other (segregation) exhibiting weaker yet dissociable connectivity patterns. In an independent cohort 2 of fMRI data with concurrent recording of skin conductance, we replicated two similar dynamic states and further found higher skin conductance level in the integration than segregation state. Moreover, machine learning-based Elastic-net regression analyses revealed that time-varying BLA and CMA intrinsic connectivity with distinct network configurations yield higher predictive values for spontaneous fluctuations of skin conductance level in the integration than segregation state. Our findings highlight dynamic functional organization of emotion-related amygdala nuclei circuits and networks and its links to spontaneous autonomic arousal in humans.
English rural policing: job stress and psychological distress
Authors: Houdmont Jonathan , Jachens Liza , Randall Raymond , Colwell Jim
Published: November 2020

Purpose

Job stressor exposure is associated with mental health in police officers. Police stress research rarely draws a distinction between urban and rural policing, raising the possibility that stressors specific to the rural context remain unidentified and their implications unknown. This may hinder actions to protect the mental health of those involved in policing rural communities.

Design/methodology/approach

Among rural policing teams in an English county police force this study used an exploratory sequential mixed method design to (1) identify and quantify exposure to rural policing stressors and (2) examine links between job stressor exposure and psychological distress.

Findings

Interviews (N = 34) identified three rural policing job stressor themes: (1) job demands, (2) isolation and (3) critical decisions. Survey data (N = 229) indicated significant differences in exposure by rank to demand and critical decision stressors, with police community support officers (PCSOs) reporting lower exposure than officers of constable and sergeant rank. Overall, 44% of respondents reported symptoms of psychological distress indicative of likely minor psychiatric disorder; higher levels of psychological distress were associated with higher stressor exposure across all three job stressor themes for PCSOs and constables and within the job demand theme for sergeants.

Originality/value

Findings point towards practical actions focussed on resource provision for officers and a research strategy to ameliorate the impact of stressors in English rural policing.
Novel mutations in Chinese hypotrichosis simplex patients associated with LSS gene
Authors: Hua Shengyuan , Ding Yu , Zhang Jia , Qian Qiufang , Li Ming
Published: November 2020

Hypotrichosis simplex (HS) is a rare form of hereditary alopecia caused by a variety of genetic mutations. Currently, only four studies regarding LSS‐related HS have been reported. In this study, we try to make a definite diagnosis in two unrelated Chinese families with three pediatric patients clinically suspected of HS. Whole‐exome sequencing (WES) was performed for these two families to reveal the pathogenic mutation. WES revealed two different compound heterozygous mutations in LSS in two probands that confirmed the diagnosis, including three novel mutations. In this paper, we describe a new accompanying phenotype of teeth dysplasia in a HS patient. Moreover, we provide a review of all reported LSS mutation‐related patients and infer some potential genotype–phenotype correlations for the first time.
Health inequalities, fundamental causes and power: towards the practice of good theory
Authors: McCartney Gerry , Dickie Elinor , Escobar Oliver , Collins Chik
Published: November 2020

Reducing health inequalities remains a challenge for policy makers across the world. Beginning from Lewin’s famous dictum that “there is nothing as practical as a good theory”, this paper begins from an appreciative discussion of ‘fundamental cause theory’, emphasizing the elegance of its theoretical encapsulation of the challenge, the relevance of its critical focus for action, and its potential to support the practical mobilisation of knowledge in generating change. Moreover, it is argued that recent developments in the theory, provide an opportunity for further theoretical development focused more clearly on the concept of power (Dickie et al. 2015). A critical focus on power as the essential element in maintaining, increasing or reducing social and economic inequalities – including health inequalities – can both enhance the coherence of the theory, and also enhance the capacity to challenge the roots of health inequalities at different levels and scales. This paper provides an initial contribution by proposing a framework to help to identify the most important sources, forms and positions of power, as well as the social spaces in which they operate. Subsequent work could usefully test, elaborate and adapt this framework, or indeed ultimately replace it with something better, to help focus actions to reduce inequalities.
Community pharmacy and public health: preserving professionalism by extending the pharmacy gaze?
Authors: Atkin Karl , Madden Mary , Morris Stephanie , Gough Brendan , McCambridge Jim
Published: November 2020

Community pharmacy faces ongoing challenges to its economic and social standing. A concern to legitimate professional status explains the attraction of public health. Interventions currently advocated by UK State‐sponsored health care seek to reconcile the autonomous ‘entrepreneurial’ patient with market‐driven solutions. Engaging critically with recent Foucauldian sociological work on pharmacy as a conduit for disciplinary power, we explore how professional ambiguity is exploited to ‘manage’ the subjectivities of community pharmacists. Locating our discussion in the observed empirical realities of pharmacy practice (the inclusion of alcohol and other ‘healthy living’ advice in the Medicines Use Review), we connect unresolved historical debates in community pharmacy with current ongoing (neoliberal) changes in policy and pharmacy business practices, drawing attention to the poor evidence base underpinning healthy living activities in community pharmacy. Our findings show how community pharmacists struggle to provide meaningful advice, valued by patients. Instead of enhancing professional status, ‘add‐on’ public health roles created the risk of offering little more than an essentialised enactment of consumerist health care. Understanding how patients conceptualise drinking and ‘healthy living’ in relation to their long‐term health, using more open discussions, including the negotiation (rather than provision) of information, could help community pharmacists challenge the current professional vulnerabilities they face.
Enhancement of microbiome management by machine learning for biological wastewater treatment
Authors: Cai Wenfang , Long Fei , Wang Yunhai , Liu Hong , Guo Kun
Published: November 2020

Here we propose to develop microbiome‐based machine learning models to predict the response of biological wastewater treatment systems to environmental or operational disturbances or to design specific microbiomes to achieve a desired system function. These machine learning models can be used to enhance the stability of microbiome‐based biological systems and warn against the failure of these systems.
Global Common Goods for Health: Towards a New Framework for Global Financing
Authors: Soucat Agnès , Kickbusch Ilona
Published: November 2020

The COVID‐19 pandemic, which has brought the world economy to an unprecedented synchronized recession, makes for a profound collective global experience. It should urge us to reshape our collective actions.
Stock Markets and Competition: What Does A Concentrated Stock Market Tell Us About Competition In The Economy?
Authors: Triggs Adam
Published: November 2020

The paper presents analysis of market concentration in Australia’s stock market and explores what this might tell us about the state of competition in the real economy. It finds that, on most measures, Australia’s stock market is highly concentrated but is becoming less concentrated over time. Many studies, including leading books on competition policy, have used stock market concentration as a proxy for market concentration in the economy, usually due to data constraints. The paper warns against this. Using the stock market for competition analysis incorrectly defines markets and competition, excludes most competitors, ignores important market dynamics and leads to erroneous results. Declining stock market concentration should not be taken as a sign that competition in the economy is improving.
Modelling Asymmetry and Leverage in Cryptocurrencies and Emerging Financial Markets
Authors: Omane‐Adjepong Maurice , Alagidede Imhotep Paul
Published: November 2020

This paper investigates asymmetry and local leverage behaviour in individual and aggregate markets of leading cryptocurrencies, and compares such characteristics to diverse traditional emerging asset classes. Generally different from the cryptocurrencies, the results show diffuse evidence of asymmetry and a significant presence of local leverage in the emerging markets. New findings indicate that mega‐size cryptocurrencies like Bitcoin and Ripple exhibit return‐volatility behaviour whereby volatility changes in their markets increase rather by a response to positive shocks than by a response to negative shocks. Akin to safe net assets, particularly gold, the inverse asymmetric reactions of the cryptocurrency markets position them distinctively from the existing emerging markets, suggestive that the digital assets stand to offer potentials beyond being diversifiers.
G6PD overexpression protects from oxidative stress and age‐related hearing loss
Authors: Bermúdez‐Muñoz Jose M. , Celaya Adelaida M. , Hijazo‐Pechero Sara , Wang Jing , Serrano Manuel , Varela‐Nieto Isabel
Published: November 2020

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose‐6‐phosphate dehydrogenase (G6PD), which catalyzes the rate‐limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD‐Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild‐type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3‐month‐old G6PD‐Tg mice than in wild‐type counterparts, whereas the levels of pro‐apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL+ apoptotic cells were all lower in 9‐month‐old G6PD‐Tg than in wild‐type counterparts. Unexpectedly, G6PD overexpression triggered low‐grade inflammation that was effectively resolved in young mice, as shown by the absence of cochlear cellular damage and macrophage infiltration. Our results lead us to propose that NADPH overproduction from an early stage is an efficient mechanism to maintain the balance between the production of ROS and cellular detoxification power along aging and thus prevents hearing loss progression.
Genes Associated with Calcium Signaling are Involved in Alcohol‐Induced Breast Cancer Growth
Authors: Ho Charles , Lin Chin‐Yo
Published: November 2020

Background

Alcohol consumption is a risk factor for breast cancer, contributing to up to nearly 23,000 new cases each year. Mechanistic studies show that alcohol increases tumor aggressiveness and metastatic potential, promotes angiogenesis, induces chronic inflammation, and dysregulates RNA polymerase III–related genes. Alcohol has also been shown to affect estrogen signaling in breast cancer, including in our study of the transcriptomic effects of alcohol in breast cancer cells.

Methods

To elucidate mechanisms of action of alcohol in breast cancer, we carried out secondary analyses of our alcohol‐responsive transcriptome data using gene ontology and pathway databases and analysis tools and cistromic data analysis of candidate transcription factors which may mediate the transcriptomic alterations. Predicted alcohol‐responsive pathways and mechanisms were perturbed and examined experimentally in breast cancer cells. The clinical relevance of identified genes was determined by expression profiles in patient samples and correlation with disease outcomes and alcohol consumption in previously published study cohorts.

Results

Gene ontology analysis showed that alcohol alters the expression of many metabolism‐related genes, and cistromic data of differentially expressed genes revealed the potential involvement of nuclear factor of activated T cells 3 (NFATC3) in mediating the transcriptomic effects of alcohol. Pathway analysis also predicted regulation of calcium signaling by alcohol in breast cancer cells. Chemical perturbation of this pathway reversed the effect of alcohol on breast cancer cell growth and reduced the elevated cytosolic Ca2+ levels induced by alcohol. Expression levels of alcohol‐responsive genes in tumor samples from breast cancer patients are associated with poor disease outcomes. Moreover, expression of some of these genes was altered in breast cancer patients who consumed alcohol previously as compared to those who did not drink.

Conclusion

Alcohol alters expression of genes that regulate intracellular calcium levels and downstream signaling pathways which drive breast cancer cell proliferation and disease progression.
Are emotionally intelligent people happier? A meta‐analysis of the relationship between emotional intelligence and subjective well‐being using Chinese samples
Authors: Xu Xiaobo , Pang Weiguo , Xia Mengya
Published: November 2020

To assess an overall correlation between emotional intelligence (EI) and subjective well‐being (SWB) within Chinese culture, accounting for possible moderating factors, we conducted a meta‐analysis of 119 correlations obtained from 62 studies with a total sample size of 29,922. The results uncovered a moderately positive correlation,r = .32, 95% CI [0.29, 0.36],p < .001, between EI and SWB. The strength of the correlation was moderated by EI stream, SWB component, participant’s age, and participant’s employment status. Specifically, this association was stronger when EI was measured as self‐report mixed EI,r = .49, and self‐report ability EI,r = .32, than when it was measured as performance‐based ability EI,r = .08. In addition, EI was more strongly associated with the cognitive components of SWB,r = .32, than with the affective component of SWB,r = .29, and the EI–SWB association was stronger in adults,r = .33, than in adolescents,r = .25. Furthermore, EI was more closely related to SWB in working adults,r = .43, compared to students,r = .29, and EI was almost equally associated with SWB across males and females, β = −.08,p = .55. The results, as well as their theoretical and practical implications, are discussed in detail with reference to relevant cross‐cultural theories and comparative empirical findings.
The effect of blood‐flow‐restricted interval training on lactate and H+ dynamics during dynamic exercise in man
Authors: Christiansen Danny , Eibye Kasper , Hostrup Morten , Bangsbo Jens
Published: November 2020

Aim

To assess how blood‐flow‐restricted (BFR) interval‐training affects the capacity of the leg muscles for pH regulation during dynamic exercise in physically trained men.

Methods

Ten men (age: 25 ± 4y; : 50 ± 5 mL∙kg−1∙min−1) completed a 6‐wk interval‐cycling intervention (INT) with one leg under BFR (BFR‐leg; ~180 mmHg) and the other without BFR (CON‐leg). Before and after INT, thigh net H+‐release (lactate‐dependent, lactate‐independent and sum) and blood acid/base variables were measured during knee‐extensor exercise at 25% (Ex25) and 90% (Ex90) of incremental peak power output. A muscle biopsy was collected before and after Ex90 to determine pH, lactate and density of H+‐transport/buffering systems.

Results

After INT, net H+ release (BFR‐leg: 15 ± 2; CON‐leg: 13 ± 3; mmol·min−1; Mean ± 95% CI), net lactate‐independent H+ release (BFR‐leg: 8 ± 1; CON‐leg: 4 ± 1; mmol·min−1) and net lactate‐dependent H+ release (BFR‐leg: 9 ± 3; CON‐leg: 10 ± 3; mmol·min−1) were similar between legs during Ex90 (P > .05), despite a ~142% lower muscle intracellular‐to‐interstitial lactate gradient in BFR‐leg (−3 ± 4 vs 6 ± 6 mmol·L−1; P < .05). In recovery from Ex90, net lactate‐dependent H+ efflux decreased in BFR‐leg with INT (P < .05 vs CON‐leg) owing to lowered muscle lactate production (~58% vs CON‐leg, P < .05). Net H+ gradient was not different between legs (~19%, P > .05; BFR‐leg: 48 ± 30; CON‐leg: 44 ± 23; mmol·L−1). In BFR‐leg, NHE1 density was higher than in CON‐leg (~45%; P < .05) and correlated with total‐net H+‐release (r = 0.71; P = .031) and lactate‐independent H+ release (r = 0.74; P = .023) after INT, where arterial [] and standard base excess in Ex25 were higher in BFR‐leg than CON‐leg.

Conclusion

Compared to a training control, BFR‐interval training increases the capacity for pH regulation during dynamic exercise mainly via enhancement of muscle lactate‐dependent H+‐transport function and blood H+‐buffering capacity.
Influence of blood haemoglobin concentration on renal haemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep
Authors: Lankadeva Yugeesh R. , May Clive N. , Cochrane Andrew D. , Marino Bruno , Hood Sally G. , McCall Peter R. , Okazaki Nobuki , Bellomo Rinaldo , Evans Roger G.
Published: November 2020

Aim

Blood transfusion may improve renal oxygenation during cardiopulmonary bypass (CPB). In an ovine model of experimental CPB, we tested whether increasing blood haemoglobin concentration [Hb] from ~7 g dL−1 to ~9 g dL−1 improves renal tissue oxygenation.

Methods

Ten sheep were studied while conscious, under stable isoflurane anaesthesia, and during 3 hours of CPB. In a randomized cross‐over design, 5 sheep commenced bypass at a high target [Hb], achieved by adding 600 mL donor blood to the priming solution. After 90 minutes of CPB, PlasmaLyte® was added to the blood reservoir to achieve low target [Hb]. For the other 5 sheep, no blood was added to the prime, but after 90 minutes of CPB, 800‐900 mL of donor blood was given to achieve a high target [Hb].

Results

Overall, CPB was associated with marked reductions in renal oxygen delivery (−50 ± 12%, mean ± 95% confidence interval) and medullary tissue oxygen tension (PO2, −54 ± 29%). Renal fractional oxygen extraction was 17 ± 10% less during CPB at high [Hb] than low [Hb] (P = .04). Nevertheless, no increase in tissue PO2 in either the renal medulla (0 ± 6 mmHg change, P > .99) or cortex (−19 ± 13 mmHg change, P = .08) was detected with high [Hb].

Conclusions

In experimental CPB blood transfusion to increase Hb concentration from ~7 g dL−1 to ~9 g dL−1 did not improve renal cortical or medullary tissue PO2 even though it decreased whole kidney oxygen extraction.
The absence of functional bassoon at cone photoreceptor ribbon synapses affects signal transmission at Off cone bipolar cell contacts in mouse retina
Authors: Babai Norbert , von Wittgenstein Julia , Gierke Kaspar , Brandstätter Johann Helmut , Feigenspan Andreas
Published: November 2020

Aim

Off cone bipolar cells of the mammalian retina connect to cone photoreceptor synaptic terminals via non‐invaginating flat contacts at a considerable distance from the only established neurotransmitter release site so far, the synaptic ribbon. Diffusion from the ribbon synaptic active zone is considered the most likely mechanism for the neurotransmitter glutamate to reach postsynaptic receptors on the dendritic tips of Off cone bipolar cells. We used a mutant mouse with functionally impaired photoreceptor ribbon synapses to investigate the importance of intact ribbon synaptic active zones for signal transmission at Off cone bipolar cell contacts.

Methods

Whole‐cell patch‐clamp recordings from Off cone bipolar cells in a horizontal slice preparation of wildtype (Bsnwt) and mutant (BsnΔEx4/5) mouse retina were applied to investigate signal transmission between cone photoreceptors and Off cone bipolar cells. The distribution of postsynaptic glutamate receptors in Off cone bipolar cell dendrites was studied using multiplex immunocytochemistry.

Results

Tonic synaptic activity and evoked release were significantly reduced in mutant animals. Vesicle replenishment rates and the size of the readily releasable pool were likewise decreased. The precisely timed transient current response to light offset changed to a sustained response in the mutant, exemplified by random release events only loosely time‐locked to the stimulus. The kainate receptor distribution in postsynaptic Off cone bipolar cell dendritic contacts in BsnΔEx4/5 mice was largely disturbed.

Conclusion

Our results suggest a major role of functional ribbon synaptic active zones for signal transmission and postsynaptic glutamate receptor organization at flat Off cone bipolar cell contacts.
Chemical composition, characteristics concerned with fermentative quality and microbial population of ensiled pearl millet and sorghum stover in semi‐arid West Africa
Authors: Cai Yimin , Du Zhumei , Yamasaki Seishi , Jethro Delma B. , Man Nignan
Published: November 2020

To effectively utilize crop by‐product resources for ruminant feed in semi‐arid West Africa, we studied the chemical composition, characteristics concerned with fermentative quality, and microbial population of ensiled pearl millet stover (PMS) and sorghum stover (SS) in Mozambique. After panicle harvest, the PMS and SS were exposed in the field for 7, 21, 35, 49, 63, 77, 91, and 120 days under natural weather conditions. The fresh stover silages were prepared and stored for 120 days. With increased exposure time, the dry matter, neutral detergent fiber, acid detergent lignin, and neutral detergent insoluble nitrogen contents increased, whereas the crude protein, ether extract, gross energy, digestible energy, metabolizable energy, and true protein contents decreased. After 120 days of field exposure, aerobic bacteria dominated both stovers, and lactic acid bacteria (LAB) decreased to below detectable levels. After 120 days of ensiling, LAB dominated the silage of both crops, while the harmful microorganisms as aerobic bacteria, coliform bacteria, yeast, and mold were reduced or below detectable levels. Both silages did not produce more lactic acid to reduce the pH value, but they preserved nutrients well during ensiling. Therefore, PMS and SS can be prepared as silage for ruminant feed in semi‐arid West Africa.
Effect of ovarian storage time at 4 degrees C on cumulus cell apoptosis in porcine antral follicles
Authors: Chi Yafei , Peng Boya , Lu Jing
Published: November 2020

The present study was conducted to investigate the effect of cold storage time on apoptosis of cumulus cells (CCs) from porcine ovaries, and to compare the sensitivity of four apoptosis‐detection methods. Porcine ovaries were stored in physiological saline solution at 4°C for 0, 7, 24 and 48 hr, and then cumulus cells or granulosa cells (GCs) in antral follicles were retrieved to detect cell apoptosis. Cumulus cells isolated from stored ovaries for 24 hr presented obvious apoptosis using terminal deoxynucleotidyl transferase (TdT)‐mediated d‐UTP nick end‐labeling (TUNEL) assay. A typical DNA ladder pattern of apoptosis was observed in GCs 24 hr post storage treatment. The mean Olive Tail Moment of CCs was significantly increased after 24 hr using comet assay; however, the mean tail migration and mean tail DNA increased gradually after 7 hr of storage. In addition, annexin V/PI staining assay showed an obvious increase in apoptotic CCs (Annexin V positive, PI negative) 7 hr after treatment, and the apoptotic rate reached to a peak at 24 hr followed by a decline after 48 hr of storage to the level at 7 hr. In conclusion, cold storage of porcine ovary in physiological saline solution induced a time‐dependent increase in apoptosis of cumulus cells, and annexin V/PI staining combined with comet assay provided a sensitive and reliable method to detect early damages in cumulus cells induced by cold storage of ovary.
Relationship between litter size at birth and within‐litter birth weight characteristics in laboratory mice as pilot animal for pig
Authors: Ogawa Shinichiro , Satoh Masahiro
Published: November 2020

We investigated the relationship between litter size at birth and within‐litter birth weight (BW) characteristics of laboratory mice as a pilot mammal for pig. We obtained records of number born alive (NBA) and total and mean litter BW (LWB, MWB), and maximum and minimum values of within‐litter BW (MaxIWB, MinIWB), range and standard deviation (Range, SDIWB), skewness (Skew), and kurtosis (Kurt) of within‐litter BW for 656 litters at first parity. Pearson's correlations of NBA were highly positive with LWB (0.92), weakly negative with MWB (–0.31), MaxIWB (–0.19), and MinIBW (–0.33), and those of MWB were negligible with Range, SDIWB, Skew, and Kurt (–0.10 to 0.06). Estimated heritabilities, treated as dam traits, were 0.32 for NBA, 0.39 for LWB, 0.24 for MWB, 0.28 for MaxIWB, 0.05 for MinIWB, 0.16 for Range, 0.17 for SDIWB, and 0.00 for Skew and Kurt. Estimated genetic correlation between NBA and LWB was high (0.95). Therefore, LWB could be promising for efficiently improving NBA. The estimated genetic correlation of NBA was negligible with MWB (0.00), positive with MaxIWB (0.10), Range (0.48), and SDIWB (0.36), and negative with MinIWB (–0.36), suggesting that selection for increased NBA brings larger SDIWB and lighter MinIWB.
Anxiety and verbal learning in typically developing primary school children: Less efficient but equally effective
Authors: Butcher Phillipa R. , Heubeck Bernd G. , Welvaert Marijke
Published: November 2020

Background

Despite evidence that high levels of anxiety can impair Working Memory (WM) functioning, little is known about how anxiety is associated with classroom learning activities, which make high demands on verbal WM.

Aims

To investigate the association between anxiety and learning on a task which makes high demands on verbal WM.

Sample

Participants were 119 typically developing, Australian elementary school children (M age = 9.25 years; SD = 7.6 months).

Method

In individual testing sessions, measures of trait anxiety (Spence Childhood Anxiety Scales) and state anxiety (Visual Analogue scale) were made. The Rey Auditory Verbal Learning Test, which makes similar demands on WM to many classroom activities, was administered.

Results

Neither trait nor state anxiety alone was associated with mean recall across trials, however their interaction showed a significant effect. In children high on both measures of anxiety, learning followed a different trajectory. They learned more slowly on the first three trials than less anxious peers, then caught up on the remaining trials. While their mean recall scores across trials were significantly lower than those of less anxious peers, they retained as many words on the delayed learning trial.

Conclusion

In a group of typically developing children, learning on the early, more demanding learning trials of a verbal learning task was vulnerable to heightened anxiety. However, the extra opportunities to learn on later trials enabled more anxious children to learn as much as their less anxious peers. While they learnt less efficiently, they learnt equally effectively.
Acceptance of outgroup members in schools: Developmental trends and roles of perceived norm of prejudice and teacher support
Authors: Lam Shui‐fong , Shum Kathy Kar‐man , Chan Winnie Wai Lan , Tsoi Emily Wing See
Published: November 2020

Background

Schools around the world are increasingly diverse in ethnicity. Given the importance of peer acceptance in children’s well‐being and development, it is a pressing concern for educators to promote intergroup acceptance in schools.

Aims

First, to examine the developmental trends of acceptance of outgroup members in both the ethnic minority and majority students. Second, to investigate how outgroup acceptance is subject to the interplay between perceived norm of prejudice, a risk factor in the macrosystem, and teacher support, a protective factor in the microsystem.

Sample

The participants were 3,723 students (ethnic majority: 61%; boys: 51.9%; mean age: 13.7) at Grade 2, 5, 8, and 11 from 24 schools in Hong Kong.

Methods

The students were asked to complete a battery of questionnaires regarding their willingness to accept outgroup members in schools, perceived societal norm of prejudice against ethnic minority group, and teacher support they received in schools.

Results

It was found that ethnic minority students accepted outgroup members more than ethnic majority students accepted them. The difference was primarily driven by the low outgroup acceptance of ethnic majority students in Grades 2 and 5. The results of multi‐level analysis revealed that outgroup acceptance was associated negatively with perceived norm of prejudice but positively with teacher support. The negative association between outgroup acceptance and perceived norm of prejudice was attenuated in schools with supportive culture.

Conclusions

The results point to the need of early intervention and the importance of cultivating school culture with strong social emotional support.
CAR‐T TREK through the lymphoma universe, to boldly go where no other therapy has gone before
Authors: Ghilardi Guido , Braendstrup Peter , Chong Elise A. , Schuster Stephen J. , Svoboda Jakub , Ruella Marco
Published: November 2020

Chimeric antigen receptor (CAR) T cells (CART) therapies have changed and continue to change the treatment paradigms for B‐cell malignancies because they can achieve durable complete remission in patients in whom multiple lines of treatment have failed. These unprecedented results have led to the widespread use of anti‐CD19 CART therapy for patients with relapsed and refractory aggressive large B‐cell lymphomas. While long‐term follow‐up data show that about one‐third of patients achieve prolonged complete remission and are potentially cured, the majority of patients either do not respond to CD19 CART therapy or eventually relapse after CD19 CART therapy. These results are, on the one hand, driving intense research into identifying mechanisms of relapse and, on the other hand, inspiring the development of novel strategies to overcome resistance. This review summarizes current clinical outcomes of CART immunotherapy in B‐cell non‐Hodgkin lymphomas, describes the most up‐to‐date understanding of mechanisms of relapse and discusses novel strategies to address resistance to CART therapy. We are indeed at the beginning of a scientific trek to explore the mechanisms of resistance, seek out new, more effective treatment approaches based on these discoveries and to boldly go where no other therapy has gone before!
Second primary malignancy in myelofibrosis patients treated with ruxolitinib
Authors: Polverelli Nicola , Elli Elena M. , Abruzzese Elisabetta , Palumbo Giuseppe A. , Benevolo Giulia , Tiribelli Mario , Bonifacio Massimiliano , Tieghi Alessia , Caocci Giovanni , D'Adda Mariella , Bergamaschi Micaela , Binotto Gianni , Heidel Florian H. , Cavazzini Francesco , Crugnola Monica , Pugliese Novella , Bosi Costanza , Isidori Alessandro , Bartoletti Daniela , Auteri Giuseppe , Latagliata Roberto , Gandolfi Lisa , Martino Bruno , Scaffidi Luigi , Cattaneo Daniele , D’Amore Fabio , Trawinska Malgorzata M. , Stella Rossella , Markovic Uros , Catani Lucia , Pane Fabrizio , Cuneo Antonio , Krampera Mauro , Semenzato Gianpietro , Lemoli Roberto M. , Vianelli Nicola , Breccia Massimo , Russo Domenico , Cavo Michele , Iurlo Alessandra , Palandri Francesca
Published: November 2020

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non‐melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real‐world context. Median follow‐up from starting RUX was 2·9 years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P = 0·01] and thrombocytosis> 400 × 109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P = 0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P = 0·02) and duration of hydroxycarbamide and RUX therapy > 5 years (HR: 3·20, 95%CI: 1·17–8·75, P = 0·02 and HR: 2·93, 95%CI: 1·39–6·17, P = 0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P = 0·03), platelet > 400 × 109/l (HR: 3·30, 95%CI: 1·67–6·50, P = 0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P = 0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.