bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of candidate virulence loci in Striga hermonthica, a devastating parasite of African cereal crops
Authors: Qiu Suo , Bradley James M. , Zhang Peijun , Chaudhuri Roy , Blaxter Mark , Butlin Roger K. , Scholes Julie D.
Published: January 2022

Parasites have evolved proteins, Virulence Factors (VFs), that facilitate plant colonization, yet VFs mediating parasitic plant-host interactions are poorly understood. Striga hermonthica is an obligate, root-parasitic plant of cereal hosts in sub-Saharan Africa, causing devastating yield losses. Understanding the molecular nature and allelic variation of VFs in S. hermonthica is essential for breeding resistance and delaying the evolution of parasite virulence.

We assembled the S. hermonthica genome and identified secreted proteins by in silico prediction. Pooled sequencing of parasites growing on a susceptible and a strongly resistant rice host allowed us to scan for loci where selection imposed by the resistant host had elevated the frequency of alleles contributing to successful colonisation.

Thirty-eight putatively secreted VFs had extremely different allele frequencies with functions including host cell wall modification, protease inhibitors, oxidoreductase and kinase activities. These candidate loci had significantly higher Tajima’s D than the genomic background, consistent with balancing selection.

Our results reveal diverse strategies used by S. hermonthica to overcome different layers of host resistance. Understanding the maintenance of variation at virulence loci by balancing selection will be critical to managing the evolution of virulence as a part of a sustainable control strategy.
Growth orientations, rather than heterogeneous growth rates, dominate jaw joint morphogenesis in the larval zebrafish
Authors: Godivier Josepha , Lawrence Elizabeth A. , Wang Mengdi , Hammond Chrissy L. , Nowlan Niamh C.
Published: January 2022

In early limb embryogenesis, synovial joints acquire specific shapes which determine joint motion and function. The process by which the opposing cartilaginous joint surfaces are moulded into reciprocal and interlocking shapes, called joint morphogenesis, is one of the least understood aspect of joint formation and the cell-level dynamics underlying it are yet to be unravelled. In this research, we quantified key cellular dynamics involved in growth and morphogenesis of the zebrafish jaw joint and synthesised them in a predictive computational simulation of joint development. Cells in larval zebrafish jaw joints labelled with cartilage markers were tracked over a forty-eight hour time window using confocal imaging. Changes in distance and angle between adjacent cell centroids resulting from cell rearrangement, volume expansion and extracellular matrix (ECM) deposition were measured and used to calculate the rate and direction of local tissue deformations. We observed spatially and temporally heterogeneous growth patterns with marked anisotropy over the developmental period assessed. There was notably elevated growth at the level of the retroarticular process of the Meckel’s cartilage, a feature known to undergo pronounced shape changes during zebrafish development. Analysis of cell dynamics indicated a dominant role for cell volume expansion in growth, with minor influences from ECM volume increases and cell intercalation. Cell proliferation in the joint was minimal over the timeframe of interest. Synthesising the dynamic cell data into a finite element model of jaw joint development resulted in accurate shape predictions. Our biofidelic computational simulation demonstrated that zebrafish jaw joint growth can be reasonably approximated based on cell positional information over time, where cell positional information derives mainly from cell orientation and cell volume expansion. By modifying the input parameters of the simulation, we were able to assess the relative contributions of heterogeneous growth rates and of growth orientation. The use of uniform rather than heterogeneous growth rates only minorly impacted the shape predictions whereas isotropic growth fields resulted in altered shape predictions. The simulation results suggest that growth anisotropy is the dominant influence on joint growth and morphogenesis. This study addresses the gap of the cellular processes underlying joint morphogenesis, with implications for understanding the aetiology of developmental joint disorders such as developmental dysplasia of the hip and arthrogryposis.
Common Dynamic Determinants Govern Quorum Quenching Activity in N-terminal Serine Hydrolases
Authors: Surpeta Bartlomiej , Grulich Michal , Palyzová Andrea , Marešová Helena , Brezovsky Jan
Published: January 2022

Growing concerns about microbial antibiotic resistance have motivated extensive research into ways of overcoming antibiotic resistance. Quorum quenching (QQ) processes disrupt bacterial communication via quorum sensing, which enables bacteria to sense the surrounding bacterial cell density and markedly affects their virulence. Due to its indirect mode of action, QQ is believed to exert limited pressure on essential bacterial functions and may thus avoid inducing resistance. Although many enzymes display QQ activity against various bacterial signaling molecules, their mechanisms of action are poorly understood, limiting their potential optimization as QQ agents. Here we evaluate the capacity of three N-terminal serine hydrolases to degrade N-acyl homoserine lactones that serve as signaling compounds for Gram-negative bacteria. Using molecular dynamics simulations of the free enzymes and their complexes with two signaling molecules of different lengths, followed by quantum mechanics/molecular mechanics molecular dynamics simulations of their initial catalytic steps, we clarify the molecular processes underpinning their QQ activity. We conclude that all three enzymes degrade bacterial signaling molecules via similar reaction mechanisms. Moreover, we experimentally confirmed the activity of two penicillin G acylases from Escherichia coli (ecPGA) and Achromobacter spp. (aPGA), adding these biotechnologically well-optimized enzymes to the QQ toolbox. We also observed enzyme- and substrate-dependent differences in the catalytic actions of these enzymes, arising primarily from the distinct structures of their acyl-binding cavities and the dynamics of their molecular gates. As a consequence, the first reaction step catalyzed by ecPGA with a longer substrate had an elevated energy barrier because its shallow acyl binding site could not accommodate a productive substrate-binding configuration. Conversely, aPGA in complex with both substrates exhibited unfavorable energetics in both reaction steps due to the dynamics of the residues gating the acyl binding cavity entrance. Finally, the energy barriers of the second reaction step catalyzed by Pseudomonas aeruginosa acyl-homoserine lactone acylase with both substrates were higher than in the other two enzymes due to the unique positioning of Arg297β in this enzyme. The discovery of these dynamic determinants will guide future efforts to design robust QQ agents capable of selectively controlling virulence in resistant bacterial species.
An atlas of fish genome evolution reveals delayed rediploidization following the teleost whole-genome duplication
Authors: Parey Elise , Louis Alexandra , Montfort Jérôme , Guiguen Yann , Crollius Hugues Roest , Berthelot Camille
Published: January 2022

Teleost fishes are ancient tetraploids stemming from an ancestral whole-genome duplication that may have contributed to the impressive diversification of this clade. Whole-genome duplications can occur via self-doubling (autopolyploidy) or via hybridization between different species (allopolyploidy). The mode of tetraploidization conditions evolutionary processes by which duplicated genomes return to a diploid state through meiosis resolution and subsequent genetic divergence (cytological and genetic rediploidization). How teleosts became tetraploid remains unresolved, leaving a fundamental gap to interpret their functional evolution. As legacy of the whole genome duplication, identifying orthologous and paralogous genomic regions across teleosts is challenging, hindering genome-wide investigations into their polyploid history. Here, we combine tailored gene phylogeny methodology together with a state-of-the-art ancestral karyotype reconstruction to establish the first high-resolution comparative atlas of paleopolyploid regions across 74 teleost genomes. We then leverage this atlas to investigate how rediploidization occurred in teleosts at the genome-wide level. We uncover that some duplicated regions maintained tetraploidy for over 60 million years, with three chromosome pairs diverging genetically only after the separation of major teleost families. This evidence suggests that the teleost ancestor was an autopolyploid. Further, we find evidence for biased gene retention along several duplicated chromosomes, contradicting current paradigms that asymmetrical evolution is specific to allopolyploids. Altogether, our results offer novel insights into genome evolutionary dynamics following ancient polyploidizations in vertebrates.
Dissecting the interactions of PINK1 with the TOM complex in depolarized mitochondria
Authors: Maruszczak Klaudia K. , Jung Martin , Rasool Shafqat , Trempe Jean-François , Rapaport Doron
Published: January 2022

Mitochondria dysfunction is involved in the pathomechanism of many illnesses including Parkinson’s disease. PINK1, which is mutated in some cases of familiar Parkinsonism, is a key component in the degradation of damaged mitochondria by mitophagy. The accumulation of PINK1 on the mitochondrial outer membrane (MOM) of compromised organelles is crucial for the induction of mitophagy, but the molecular mechanism of this process is still unresolved. Here, we investigate the association of PINK1 with the TOM complex. We demonstrate that PINK1 heavily relies on the import receptor TOM70 for its association with mitochondria and directly interacts with this receptor. The structural protein TOM7 appears to play only a moderate role in PINK1 association with the TOM complex, probably due to its role in stabilizing this complex. PINK1 requires the TOM40 pore lumen for its stable interaction with the TOM complex and apparently remains there during its further association with the MOM. Overall, this study provides new insights on the role of the individual TOM subunits in the association of PINK1 with the MOM of depolarized mitochondria.
Histopathological analysis of selected organs of Oreochromis niloticus due to sub-lethal industrial effluents exposure
Authors: Jabeen Ghazala , Ishaq Sarwat , Manzoor Farkhanda
Published: January 2022

On a daily basis, our environment is exposed to tons of a composite of industrial effluents, which has a negative impact on commercial fish production and, as a result, on humans. Present study was designed to evaluate the acute, sub-chronic, and chronic toxicity of a composite of raw industrial effluent from Sunder Industrial Estate in the freshwater fish Oreochromis niloticus biosystem by investigating at the histopathological changes in different organs such as heart, kidney, and muscle after exposure. Fish was exposed to 1/3rd, 1/5th and 1/10th of predetermined LC50. Significant histopathological alterations in heart (myocarditis, pericardium bending and lifting) kidney (renal tube degeneration, glomerulus structural alteration and necrotic proximal tubule) and muscle (inflammation, atrophy and tumor) were observed in treated groups. After the sub-lethal exposure histological alteration index (HAI) was highest in chronic group as compared to the acute and sub-chronic group as HAI group D> HAI group C> HAI group B. Moreover physicchemical parameters of water were found to be out of the range of the APHA standard approach.
Whole Exome Sequencing detects PYGM variants in two adults with McArdle disease
Authors: Thomas-Wilson Amanda , Dharmadhikari Avinash V , Heymann Jonas J , Jobanputra Vaidehi , DiMauro Salvatore , Hirano Michio , Naini Ali B , Ganapathi Mythily
Published: January 2022

McArdle disease is a progressive and debilitating glycogen storage disease with typical onset in late childhood. Here we describe a former competitive athlete with early adult onset McArdle disease and a septuagenarian with a history of exercise-intolerance since adolescence who was evaluated for proximal muscle weakness. Exome sequencing identified bi-allelic variants in PYGM gene for both cases. The former athlete has the common, well-known pathogenic variant p.(Arg50Ter) in trans with a novel missense variant, p.(Asp694Glu). The second individual has a previously described homozygous missense variant, p.(Arg771Gln). Here, we describe the clinical course, enzyme-testing results using muscle tissue and molecular findings for the individuals, and add to the knowledge of the genotypic spectrum of this disorder.
Crystal structure, DFT and Hirshfeld surface analysis of N-acetyl-t-3-methyl-r-2,c-6-diphenylpiperidine
Authors: Periyannan P. , Beemarao M. , Karthik K . , Ponnuswamy S. , Ravichandran K.
Published: January 2022

In the title compound [systematic name: 1-(3-methyl-2,6-diphenylpiperidin-1-yl)ethanone], C20H23NO, the piperidine ring adopts a distorted boat conformation, while the phenyl rings subtend a dihedral angle 65.1 (2)°. In the crystal, molecules are linked by C—H...O hydrogen bonds into chains extending along the b-axis direction. The DFT/B3LYP/6–311 G(d,p) method was used to determine the HOMO–LUMO energy levels. A Hirshfeld surface analysis was conducted to verify the contributions of the different intermolecular interactions, indicating that the important contributions to the crystal packing are from H...H (73.2%), C...H (18.4%) and O...H (8.4%) interactions.
The impact of national culture on COVID-19 pandemic outcomes
Authors: He Zhaochen , Jiang Yixiao , Chakraborti Rik , Berry Thomas D.
Published: January 2022

Purpose

This study aims to uncover the extent to which cultural traits may explain the puzzling international divergence in COVID-19 outcomes, and how those traits interact with state action to produce compliance with pandemic health policy.

Design/methodology/approach

A theoretical framework illustrates the surprising possibility that culture and state action may not reinforce each other but rather act as substitutes in eliciting anti-pandemic behavior. This possibility is tested empirically in two specifications: a cross-sectional regression that includes several novel COVID-related measures, and a panel model that controls for contemporaneous disease burden. Across these models, we use the measures of national culture developed by Hofstede (1984) and a newer metric developed by Schwartz (1990).

Findings

Individualism and egalitarianism have a positive effect on disease prevalence, while cultural heterogeneity was associated with a more robust public health response. Consistent with our model, we find that culture and state action served as substitutes in motivating compliance with COVID-19 policy.

Practical implications

The results of this study imply that culture and state interact in determining the effectiveness of public health measures aimed at combating COVID-19; these results recommend culturally aware state intervention when combating pandemics.

Originality/value

This study offers several new contributions. First, it proposes a model to help contextualize the empirical analysis. Second, it examines a wider range of traits than previous studies, including cultural homogeneity and the Schwartz variables. Third, it employs a richer econometric specification that explores the interaction between state and culture in a panel context.
Research on the reliable test range of four-point supported piezoelectric dynamometer
Authors: Zhang Jun , Ma Yixuan , Ren Zongjin , Bai Tao , Hu Peikai , Wang Zunhao
Published: January 2022

Purpose

The purpose of this paper is to improve the reliability of the force measurement system by determining the reliable test range of dynamometer.

Design/methodology/approach

Based on the principle of leverage and moment balance, a general force distribution model is applicable in where the test point is located either inside or outside the support region of four three-component force links of dynamometer is established. After corroborating the correctness of the model through verification experiments, the boundary conditions that each three-component force link should satisfy are analyzed by considering the characteristic of the dynamometer components comprehensively. Furthermore, the reliable test range of dynamometer is determined, followed by a calibration experiment to verify its rationality.

Findings

The relationships between the reliable test range and the tested force, the bolt pre-tightening force and the bearing capacity of quartz wafers are clarified. Further, the experimental calibration results show that when the test point is within the reliable test range, the three-directional output voltage of dynamometer has excellent linearity and repeatability. The nonlinearity and repeatability in X-, Y- and Z-directions are all less than 1.1%.

Originality/value

A general mathematical model of force distribution of four three-component force links is constructed, which provides a theoretical basic for the mechanical analysis of multi-sensors’ dynamometer. Comprehensively considering the performance of dynamometer components, the value of measured force and the pre-tightening force, the simultaneous equations of reliable test range are deduced, which limits the boundary of allowable test position of piezoelectric dynamometer.
Functional Traits 2.0: The power of the metabolome for ecology
Authors: Walker Tom W. N. , Alexander Jake M. , Allard Pierre‐Marie , Baines Oliver , Baldy Virginie , Bardgett Richard D. , Capdevila Pol , Coley Phyllis D. , David Bruno , Defossez Emmanuel , Endara María‐José , Ernst Madeleine , Fernandez Catherine , Forrister Dale , Gargallo‐Garriga Albert , Jassey Vincent E. J. , Marr Sue , Neumann Steffen , Pellissier Loïc , Peñuelas Josep , Peters Kristian , Rasmann Sergio , Roessner Ute , Sardans Jordi , Schrodt Franziska , Schuman Meredith C. , Soule Abrianna , Uthe Henriette , Weckwerth Wolfram , Wolfender Jean‐Luc , van Dam Nicole M. , Salguero‐Gómez Roberto
Published: January 2022

A major aim of ecology is to upscale attributes of individuals to understand processes at population, community and ecosystem scales. Such attributes are typically described using functional traits, that is, standardised characteristics that impact fitness via effects on survival, growth and/or reproduction. However, commonly used functional traits (e.g. wood density, SLA) are becoming increasingly criticised for not being truly mechanistic and for being questionable predictors of ecological processes.

This Special Feature reviews and studies how the metabolome (i.e. the thousands of unique metabolites that underpin physiology) can enhance trait‐based ecology and our understanding of plant and ecosystem functioning.

In this Editorial, we explore how the metabolome relates to plant functional traits, with reference to life‐history trade‐offs governing fitness between generations and plasticity shaping fitness within generations. We also identify solutions to challenges of acquiring, interpreting and contextualising metabolome data, and propose a roadmap for integrating the metabolome into ecology.

We next summarise the seven studies composing the Special Feature, which use the metabolome to examine mechanisms behind plant community assembly, plant‐organismal interactions and effects of plants and soil micro‐organisms on ecosystem processes.

Synthesis. We demonstrate the potential of the metabolome to improve mechanistic and predictive power in ecology by providing a high‐resolution coupling between physiology and fitness. However, applying metabolomics to ecological questions is currently limited by a lack of conceptual, technical and data frameworks, which needs to be overcome to realise the full potential of the metabolome for ecology.
Atmospheric resonance: sonic motion and the question of religious mediation
Authors: Eisenlohr Patrick
Published: January 2022

Because of its material characteristics, the sonic poses a challenge to the influential paradigm of religion as mediation. This article makes a case for a neo‐phenomenological analytic of atmospheres in order to do justice to the sonic in anthropological approaches to religion. Approaching the sonic as atmospheric half‐things, I propose a different understanding of religious mediation from the one developed in contexts where images, objects, and technical media dominate. Based on research on the recitation of Urdu devotional poetry among Mauritian Muslims, it is suggested that sonic religion does not function as a stable in‐between connecting humans and the divine. Instead, it operates through processes of resonant bundling, intertwining different strands of lived experience, including religious traditions.
Institutional trust and emergency preparedness: Perceptions of Covid 19 crisis management in Sweden
Authors: Bengtsson Rikard , Brommesson Douglas
Published: January 2022

The Covid 19 pandemic has put the issue of public trust at the centre of political analysis. This article inquires into the level of public trust in Sweden concerning current crisis management as well as preparedness for future crises. The empirical basis for this study consists of unique data generated through two surveys on the Covid 19 virus conducted during 2020 in Sweden. Respondents were asked to assess their trust in different actors' crisis management. In addition, the first survey asked about how the actions of different actors impact on the forward‐oriented trust held in Swedish emergency preparedness for a future severe crisis. Four key findings stand out. First, the results display rather weak levels of interpersonal trust. Second, a surprisingly high level of institutional trust can be found during the initial phase of the pandemic. Simultaneously we see somewhat decreasing levels of trust later during the pandemic. The results include interesting variations across age, gender and education. Third, relating the results to earlier research on trust in Sweden, the results contain indications of stable trust levels despite the all but stable contextual conditions. Fourth, the analysis shows important variations in trust levels among different institutions and layers of government.
Changes in the free amino acid profile of pickling cucumber during lactic acid fermentation
Authors: Moore Jennifer Fideler , DuVivier Rachel , Johanningsmeier Suzanne D.
Published: January 2022

Free amino acid (FAA) profiles of fresh, acidified, naturally fermented, and starter culture fermented cucumbers were analyzed by liquid chromatography triple quadrupole mass spectrometry. Fermented cucumbers contained more total FAA than acidified cucumbers (1,302 ± 102 mg/kg and 635 ± 35 mg/kg, respectively). Total FAA content of fermented cucumber was similar regardless of brine salt levels (2–6% NaCl) and starter culture addition. Glutamine (1491.4 ± 69.3 mg/kg), γ‐aminobutyric acid (GABA, 269.6 ± 21.4 mg/kg), asparagine (113.0 ± 6.4 mg/kg), and citrulline (110.3 ± 8.5 mg/kg) were the most abundant FAA in fresh pickling cucumber, whereas GABA (181.3 ± 21.5 mg/kg), isoleucine (165.2 ± 11.2 mg/kg), leucine (129.8 ± 10.9 mg/kg), and lysine (110.9 ± 5.0 mg/kg) were the most abundant in fermented cucumber. GABA and ornithine were produced during fermentation, indicating glutamate decarboxylase and arginine deiminase activities. Notably, ornithine was significantly higher in natural (63.3 ± 31.5 mg/kg) versus starter culture fermented cucumbers (3.0 ± 0.7 mg/kg). This new information on FAA composition of fresh and fermented pickling cucumbers shows the impact of fermentation conditions on cucumber amino acid profiles while providing insight for manipulating fermentations for health promotion and consumer acceptance.

Practical Application

This study reports changes in the free amino acid profiles of raw, fermented and acidified cucumbers, which may be valuable for understanding the impact of these foods on human health and nutrition. This information is useful for food microbiologists studying the metabolism of lactic acid bacteria during fermentation and/or designing starter cultures and could contribute to the development of novel fermented cucumber pickle products with enhanced nutritional value.
Remotely sensed vegetation productivity predicts breeding activity and drought refuges for a threatened bird in semi‐arid Australia
Authors: Young A. R. , Selwood K. E. , Benshemesh J. , Wright J. , Southwell D.
Published: January 2022

Refuges play a critical role protecting species against the effects of climate change. Managing high priority refuges could improve species resilience and facilitate dispersal during periods of environmental change. In this study, we identified drought refuges in semi‐arid Australia for a threatened bird, the malleefowl Leipoa ocellata. Using a Poisson regression model, we quantified the effect of remotely sensed vegetation indices, rainfall, soil moisture and site characteristics on malleefowl breeding activity at 144 sites surveyed from 2000 to 2017 during and after drought. We tested the effect of two vegetation productivity indices on malleefowl breeding activity – the Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) – averaged across three temporal and three spatial scales during the mound building and incubation stage of the breeding cycle. We found that NDVI and EVI were better predictors of malleefowl breeding activity than soil moisture and winter rainfall. The model with the lowest Akaike information criterion value contained NDVI averaged over 3 months (June–August) and a 1‐km radius. Malleefowl breeding activity had a strong positive association with NDVI (0.42 ± se 0.03) and a negative association with slope (−0.34 ± se 0.03) and vegetation patch size (−0.23 ± se 0.02). We found the proportion of refugia (top 20% of predicted breeding activity) in protected areas was highly variable, decreasing from 42% in an extreme wet year (2011) to 14% in an extreme drought year (2007). Expanding the reserve network to include refugia predicted to occur in the south of semi‐arid Victoria could improve resilience of malleefowl to climate change. We demonstrate how remotely sensed vegetation indices combined with citizen science data can identify where to protect native vegetation with high, stable productivity. Our approach could be applied to a broad range of species in semi‐arid regions vulnerable to climate change.
Effects of information on smallholder irrigation farmers’ willingness to pay for groundwater protection
Authors: Alhassan Mustapha , Gustafson Christopher R. , Schoengold Karina
Published: January 2022

In Ghana, groundwater, accessed through wells and boreholes, is generally unregulated and may be contaminated with pollutants including excess nitrates from agricultural chemical fertilizers. Yet, studies estimating how clean groundwater is valued are not available in Ghana. In addition, some research suggests that the pre‐experiment information provided to survey respondents affects their valuation of an identical outcome. This paper estimates smallholder farmers’ preferences for groundwater protection using pre‐experiment information focused on one of two outcomes: environment or health. The double‐bounded contingent valuation (DBCV) approach is used to estimate willingness to pay (WTP) to protect groundwater quality. The estimation accounts for shift and anchoring effects, which are common issues with the DBCV method. The mean WTP from the health (environmental) information subsample is about US$19 (US$17) per acre, and the values are significantly different between the information conditions. The findings shed light on the importance of using precise information in eliciting WTP in a developing country setting.
Party Nomination Strategies in List Proportional Representation Systems
Authors: Buisseret Peter , Folke Olle , Prato Carlo , Rickne Johanna
Published: January 2022

In list proportional representation (PR) systems, parties shape political selection. We propose a theory of party list choice and elections in list PR systems. Our results describe how a party allocates candidates of heterogeneous quality across list ranks depending on (1) its policy goals and (2) its competitive environment. We test our predictions on the universe of Swedish local politicians from 1991 to 2014. Although parties assign better candidates to higher ranks at all ballot levels, the pattern is most pronounced among electorally advantaged parties that have the strongest prospect of controlling the executive. Our findings challenge conventional accounts of candidate selection in which parties prioritize candidate quality in their nomination strategies only when constrained by electoral incentives.
Comparative efficacy between hemodialysis using super high‐flux dialyzer with hemoperfusion and high‐volume postdilution online hemodiafiltration in removing protein bound and middle molecule uremic toxins: A cross‐over randomized controlled trial
Authors: Tiranathanagul Khajohn , Khemnark Nutchaya , Takkavatakarn Kullaya , Limjariyakul Maneerut , Mahatanan Nunta , Chariyavilaskul Pajaree , Wittayalertpanya Supreecha , Susantitaphong Paweena , Eiam‐Ong Somchai
Published: January 2022

Background

Hemodialysis (HD) using super high‐flux dialyzer (HD + SHF) comparably removed uremic toxins to high‐volume postdilution online hemodiafiltration (olHDF). Integration of hemoperfusion (HP) to HD + SHF (HD + SHF + HP) might provide superior uremic toxin removing capability to high‐volume postdilution olHDF.

Method

The present study was conducted in thrice‐a‐week HD patients to compare the efficacy in removing indoxyl sulfate (IS), beta‐2 microglobulin (β2M), and urea between high‐volume postdilution ol‐HDF and HD + SHF + HP, comprising HD + SHF as the main treatment plus HD + SHF + HP 1/week in the first 4 weeks and 1/2 weeks in the second 4 weeks.

Results

Ten prevalent HD patients with blood flow rate (BFR) above 400 ml/min were randomized into two sequences of 8‐week treatment periods of HD + SHF + HP and later high‐volume postdilution olHDF or vice versa. When compared with high‐volume postdilution olHDF (convective volume of 26.02 ± 1.8 L/session), HD + SHF + HP provided comparable values of percentage reduction ratio of IS (52.0 ± 11.7 vs. 56.3 ± 7.5%, p = 0.14) and β2M (83.7 ± 4.9 vs. 84.0 ± 4.3%, p = 0.37) and slightly lower urea reduction ratio. Despite greater dialysate albumin loss (p = 0.008), there was no significant change in serum albumin level in HD + SHF + HP group.

Conclusions

HD + SHF + HP could not provide superior efficacy in removing uremic toxins to high‐volume postdilution olHDF. The use of low BFR of 200 ml/min during the first 2 h of HD + SHF + HP session, according to the instruction of manufacturer, might impair the efficacy of the HD + SHF part in removing uremic toxins.
Do credit unions have distinct objectives? Evidence from executive compensation structures
Authors: van Rijn Jordan , Zeng Shuwei , Hueth Brent
Published: January 2022

Credit unions compete directly with commercial banks in markets for consumer financial services yet receive an exemption from federal corporate income tax. Commercial banks claim that credit unions are no different than banks and that the credit union tax exemption represents an unfair competitive advantage. Credit unions counter that while they offer similar products and services, they differ from commercial banks in terms of structure and mission, given their not‐for‐profit, cooperative status. In this paper, we test for substantive differences in the objective functions of commercial banks and nonprofit credit unions by comparing CEO compensation structures. Drawing on the relevant principal–agent literature, we provide several arguments to support the hypotheses that credit union boards of directors establish lower‐powered incentive contracts with their CEOs relative to similarly sized commercial banks, and offer lower total compensation. We find that credit union CEOs receive approximately 250% less performance‐based compensation relative to CEOs of similarly sized community banks. Bank CEOs also earn approximately 15% to 20% more total compensation on average. The results are generally robust to controlling for CEO‐ and board‐level characteristics, local economic conditions, and institution‐level indicators of size, growth, complexity, liquidity and risk. The findings suggest important differences in incentive structures and objectives between banks and credit unions.
Meta‐analysis of dietary chitosan effects on performance, nutrient utilization, and product characteristics of ruminants
Authors: Harahap Rakhmad P. , Suharti Sri , Ridla Muhammad , Laconi Erika B. , Nahrowi Nahrowi , Irawan Agung , Kondo Makoto , Obitsu Taketo , Jayanegara Anuraga
Published: January 2022

Chitosan (CHI) has been used as a feed additive in ruminant diets, but the effects obtained to date have been varied. This study aimed to evaluate the dietary addition of CHI on performance, nutrient utilization, and product characteristics of ruminants by using a meta‐analysis approach. A total of 15 articles that composed of 21 studies and 57 data points were included in the database. Number of articles reported the effects of dietary CHI addition were six on beef cattle, seven on dairy cows, and two papers on sheep. Data analysis was based on the mixed model methodology, in which CHI addition levels were considered as fixed effects whereas different studies were treated as random effects. Results revealed that, across various studies, CHI decreased ruminal acetate proportion (p < 0.05) and increased propionate proportion (p < 0.01). Dry matter and crude protein digestibility were elevated due to CHI addition (p < 0.05). CHI decreased blood cholesterol level (p < 0.05) and increased monounsaturated fatty acid proportion in the milk (p < 0.05). However, CHI addition had no effect on dry matter intake, milk production, and milk efficiency of ruminants. In conclusion, CHI is able to modify rumen fermentation towards a favorable direction, but it limitedly affects performance of ruminants.
Oleuropein suppresses mitochondrial reactive oxygen species generation possibly via an activation of transient receptor potential V1 and sirtuin‐1 in cultured chicken muscle cells
Authors: Muroi Hikaru , Hori Kouhei , Tokutake Yukako , Hakamata Yuki , Kawabata Fuminori , Toyomizu Masaaki , Kikusato Motoi
Published: January 2022

This study investigated the intracellular mechanism governing the effects of oleuropein (OLE), a phenolic compound of Olea europaea, on mRNA expression of avian uncoupling protein (avUCP) and mitochondrial biogenesis‐related factors, and reactive oxygen species (mitROS) generation in a primary cultured chicken muscle cells. The OLE‐treated cells exhibited increases in Avucp and ATP5a1z expression and a decrease in mitROS generation (p < 0.05), while the effects was canceled by sirtuin‐1 (SIRT1) or transient receptor potential vanilloid 1 (TRPV1) inhibitors, EX‐527 or BCTC, respectively. Intracellular Ca2+ concentration was significantly increased by OLE, while the induction was canceled by BCTC. The study also found that TRPV1 was expressed in the cell membrane and endoplasmic reticulum (ER), and Ca2+ could be released from ER in the OLE‐treated cells. The OLE‐treated cells exhibited increases in the phosphorylation ratio of AMP‐activated protein kinase (AMPK) and peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) protein content. EX‐527 and BCTC inhibitors canceled the effects of OLE on p‐AMPK ratio and PGC‐1α content, while EX‐527 SIRT did not change PGC‐1α content. The results suggest that the OLE effects may be due to Ca2+ release, possibly from TRPV1 at ER, and increased p‐AMPK ratio, followed by SIRT1 activation and PGC‐1α protein expression.
Genetic variants associated with acamprosate treatment response in alcohol use disorder patients: A multiple omics study
Authors: Ho Ming‐Fen , Zhang Cheng , Wei Lixuan , Zhang Lingxin , Moon Irene , Geske Jennifer R. , Skime Michelle K. , Choi Doo‐Sup , Biernacka Joanna M. , Oesterle Tyler S. , Frye Mark A. , Seppala Marvin D. , Karpyak Victor M. , Li Hu , Weinshilboum Richard M.
Published: January 2022

Background and Purpose

Acamprosate is an anti‐craving drug used for the pharmacotherapy of alcohol use disorder (AUD). However, only some patients achieve optimal therapeutic outcomes. This study was designed to explore differences in metabolomic profiles between patients who maintained sobriety and those who relapsed, to determine whether those differences provide insight into variation in acamprosate treatment response phenotypes.

Experimental Approach

We previously conducted an acamprosate trial involving 442 AUD patients, and 267 of these subjects presented themselves for a 3‐month follow‐up. The primary outcome was abstinence. Clinical information, genomic data and metabolomics data were collected. Baseline plasma samples were assayed using targeted metabolomics.

Key Results

Baseline plasma arginine, threonine, α‐aminoadipic acid and ethanolamine concentrations were associated with acamprosate treatment outcomes and baseline craving intensity, a measure that has been associated with acamprosate treatment response. We next applied a pharmacometabolomics‐informed genome‐wide association study (GWAS) strategy to identify genetic variants that might contribute to variations in plasma metabolomic profiles that were associated with craving and/or acamprosate treatment outcome. Gene expression data for induced pluripotent stem cell‐derived forebrain astrocytes showed that a series of genes identified during the metabolomics‐informed GWAS were ethanol responsive. Furthermore, a large number of those genes could be regulated by acamprosate. Finally, we identified a series of single nucleotide polymorphisms that were associated with acamprosate treatment outcomes.

Conclusion and Implications

These results serve as an important step towards advancing our understanding of disease pathophysiology and drug action responsible for variation in acamprosate response and alcohol craving in AUD patients.
The economic benefits of recreation in Canada
Authors: Lloyd‐Smith Patrick
Published: January 2022

Canadians spend approximately 2.2% of the country's gross domestic product on outdoor recreation, but we do not yet know the economic benefits people receive from participating in these activities. I provide the first ever comprehensive assessment of the economic benefits of outdoor recreation in Canada. I use a nationally representative survey of recreational behaviour on over 24,000 Canadians to estimate a Kuhn–Tucker demand model that accounts for substitution between activities and satiation in demand. The results demonstrate that participation in outdoor recreation provides Canadians with $98 billion in annual economic benefits, which is well over twice as large as reported expenditures. I also reveal substantial heterogeneity in recreation benefits across activities and regions in Canada.
Allergenic characterization of Bomb m 4, a 30‐kDa Bombyx mori lipoprotein 6 from silkworm pupa
Authors: Jeong Kyoung Yong , Lee Jong Sun , Yuk Ji Eun , Song Hangyeol , Lee Hye Jung , Kim Kuan Jung , Kim Bum Joon , Lim Kook‐Jin , Park Kyung Hee , Lee Jae‐Hyun , Park Jung‐Won
Published: January 2022

Background

Silkworm pupa (SWP) food anaphylaxis has been described frequently in Asian countries. However, false‐positive reactions by skin pricks and serum IgE (sIgE) tests to the extract complicate diagnosis, requiring identification of clinically relevant major allergens.

Objectives

In this study, we characterized a novel SWP allergen, Bomb m 4, a 30‐kDa lipoprotein, and evaluated its diagnostic sensitivity.

Methods

Bomb m 4 was identified by a proteomic analysis. This recombinant (r)Bomb m 4 was overexpressed in Escherichia coli, and the IgE reactivity by ELISA was compared with other reported allergenic proteins: Bomb m 1 (arginine kinase), 27‐kDa glycoprotein, Bomb m 3 (tropomyosin) using the serum samples from 17 SWP allergic patients and 11 asymptomatic sensitized subjects.

Results

rBomb m 4‐specific IgE was recognized by all 17 SWP allergic patients. The 27‐kDa glycoprotein and Bomb m 1 sIgE were found in 35.3% and 0%, respectively, in the SWP allergic patients. ELISA sIgE reactivity increased significantly, when 4 M urea was added in serum samples. However, only 16% inhibition of sIgE reactivity to the whole SWP extract was exhibited by rBomb m 4, whereas more than 93% of self‐inhibition of rBomb m 4 sIgE was obtained, possibly due to the low abundance of Bomb m 4 in the extract. Three linear epitopes (81–95, 191–205 and 224–238 residues) of rBomb m 4 were identified. These epitopes are shown to be released by pepsin digestion. Receiver operator characteristic (ROC) analysis showed the highest diagnostic value of Bomb m 4 followed by Bomb m 1, 27‐kDa glycoprotein and Bomb m 3.

Conclusion

Bomb m 4 is the major allergen of SWP allergic patients. It has cryptic epitopes which are exposed to IgE antibodies with digestive enzymes. This recombinant Bomb m 4 allergen permits exact diagnosis of SWP allergy.
The impact of birthweight on subsequent phenotype of type 2 diabetes in later life
Authors: Paulina Christian , Donnelly Louise A. , Pearson Ewan R.
Published: January 2022

Aims

It is well established that low birthweight is associated with subsequent risk of type 2 diabetes (T2DM). The aim of our study was to use a large birth cohort linked to a national diabetes registry to investigate how birthweight impacts the phenotype at diagnosis of T2DM and the subsequent rate of glycaemic deterioration.

Methods

We linked the Walker Birth Cohort (48,000 births, 1952–1966, Tayside, Scotland) to the national diabetes registry in Scotland (SCI‐Diabetes). Birthweight was adjusted for gestational age. Simple linear regression was performed to assess the impact of the adjusted birthweight on the diabetes phenotype at diagnosis. This was then built up into a multiple regression model to allow for the adjustment of confounding variables. A cox proportional hazards model was then used to evaluate the impact of birthweight on diabetes progression.

Results

Lower birthweights were associated with a 293 day younger age of diagnosis of T2DM per 1 kg reduction in birthweight, p = 0.005; and a 1.29 kg/m2 lower BMI at diagnosis per 1 kg reduction in birthweight, p < 0.001. There was no significant association of birthweight on diabetes progression.

Conclusion

For the first time, we have shown that a lower birthweight is associated with younger onset of T2DM, with those with lower birthweight also being slimmer at diagnosis. These results suggest that lower birthweight impacts on T2DM phenotype via reduced beta‐cell function rather than insulin resistance.
GDNF neurotrophic factor signalling determines the fate of dermal fibroblasts in wound‐induced hair neogenesis and skin regeneration
Authors: Vishlaghi Neda , Rieger Sandra , McGaughey Vanessa , Lisse Thomas S.
Published: January 2022

We propose that GDNF, a glial cell line‐derived neurotrophic factor, can promote hair follicle neogenesis and skin regeneration after wounding by directing the fate of dermal fibroblasts. Our hypothesis is largely based on detailed GDNF and receptor analysis during skin regenerative stages, as well as the induction of GDNF receptors after wounding between the pro‐regenerative spiny mouse (genus Acomys) and its less‐regenerative descendant, the house mouse (Mus musculus). To characterize the GDNF‐target cells, we will conduct a series of lineage‐tracing experiments in conjunction with single‐cell RNA and assay for transposase‐accessible chromatin sequencing experiments. The heterogenetic dynamics of skin regeneration have yet to be fully defined, and this research will help to advance the fields of regenerative medicine and biology. Finally, we believe that stimulating the GDNF signalling pathway in fibroblasts from less‐regenerative animals, such as humans, will promote skin regeneration, morphogenesis and scarless wound healing.
Transcription factor mesenchyme homeobox protein 2 (MEOX2) modulates nociceptor function
Authors: Kokotović Tomislav , Lenartowicz Ewelina M. , Langeslag Michiel , Ciotu Cosmin I. , Fell Christopher W. , Scaramuzza Angelica , Fischer Michael J. M. , Kress Michaela , Penninger Josef M. , Nagy Vanja
Published: January 2022

Mesenchyme homeobox protein 2 (MEOX2) is a transcription factor involved in mesoderm differentiation, including development of bones, muscles, vasculature and dermatomes. We have previously identified dysregulation of MEOX2 in fibroblasts from Congenital Insensitivity to Pain patients, and confirmed that btn, the Drosophila homologue of MEOX2, plays a role in nocifensive responses to noxious heat stimuli. To determine the importance of MEOX2 in the mammalian peripheral nervous system, we used a Meox2 heterozygous (Meox2+/−) mouse model to characterise its function in the sensory nervous system, and more specifically, in nociception. MEOX2 is expressed in the mouse dorsal root ganglia (DRG) and spinal cord, and localises in the nuclei of a subset of sensory neurons. Functional studies of the mouse model, including behavioural, cellular and electrophysiological analyses, showed altered nociception encompassing impaired action potential initiation upon depolarisation. Mechanistically, we noted decreased expression of Scn9a and Scn11a genes encoding Nav1.7 and Nav1.9 voltage‐gated sodium channels respectively, that are crucial in subthreshold amplification and action potential initiation in nociceptors. Further transcriptomic analyses of Meox2+/− DRG revealed downregulation of a specific subset of genes including those previously associated with pain perception, such as PENK and NPY. Based on these observations, we propose a novel role of MEOX2 in primary afferent nociceptor neurons for the maintenance of a transcriptional programme required for proper perception of acute and inflammatory noxious stimuli.