bluuebunny/crossref_metadata_2025 huggingface dataset:
Curbing zoonotic disease spread in multi-host-species systems will require integrating novel data streams and analytical approaches: evidence from a scoping review of bovine tuberculosis
Authors: Conteddu Kimberly , English Holly M. , Byrne Andrew W. , Amin Bawan , Griffin Laura L. , Kaur Prabhleen , Morera-Pujol Virginia , Murphy Kilian J. , Salter-Townshend Michael , Smith Adam F. , Ciuti Simone
Published: May 2023

Background

Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving human, domestic animal, wildlife and environmental factors, which require sophisticated collaborative approaches.

Objective

We undertook a scoping review of multi-host bTB epidemiology to identify recent trends in species publication focus, methodologies, scales and One Health approaches. We aimed to identify research gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses.

Results

The review included 167 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to the multi-host episystems of southern Africa. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Surprisingly, only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios.

Conclusions

Significant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a “virtuous cycle” of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.
Invariant relationship unites REM and NonREM sleep
Authors: Zhdanova Irina V. , Kharchenko Vasili
Published: May 2023

Establishing structural and functional links between two distinct types of sleep, rapid-eye-movement (REM) and non-REM (NREM), that alternate and form several sleep cycles per night, has posed a significant challenge. Here we demonstrate a simple invariant relationship where the product of the duration of NREM sleep episode and intensity of subsequent REM sleep episode remains constant over successive sleep cycles of normal human sleep. This Sleep Cycle Invariant (SCI), previously predicted by a quantitative model of sleep dynamics, supports the structural and functional unity of NREM and REM sleep. The significance of SCI for understanding normal sleep and sleep disorders is highlighted by alterations in REM sleep intensity and NREM sleep episode duration being a hallmark of major depression.

One-Sentence Summary

The duration of NREM sleep and intensity of REM sleep have an invariant relationship across normal sleep cycles of one night.
Elucidation of multiple high-resolution states of human MutSβ by cryo-EM reveals interplay between ATP/ADP binding and heteroduplex DNA recognition
Authors: Lee Jung-Hoon , Thomsen Maren , Daub Herwin , Thieulin-Pardo Gabriel , Steinbacher Stefan C. , Sztyler Agnieszka , Dahiya Vinay , Neudegger Tobias , Dominguez Celia , Iyer Ravi R. , Wilkinson Hilary A. , Monteagudo Edith , Plotnikov Nikolay V. , Felsenfeld Dan P. , Haque Tasir S. , Finley Michael , Boudet Julien , Vogt Thomas F. , Prasad Brinda C.
Published: May 2023

Human and mouse genetic studies have demonstrated a role for DNA mismatch repair (MMR) molecular machines in modulating the rate of somatic expansion of the huntingtin (HTT)CAG repeats, and onset and progression of Huntington’s Disease (HD). MutSβ, a key component of the MMR pathway, is a heterodimeric protein of MSH2 and MSH3 that recognizes and initiates the repair of extrahelical DNA extrusions. Loss-of-function of mouseMsh3and reduced-expression alleles of humanMSH3lead to slower rates of somatic expansion and delayed disease onset in humans, signifying MSH3 as a promising therapeutic target for HD. Here we report biochemical and cryo-electron microscopy analyses of human MutSβ, demonstrating MutSβ undergoes conformational changes induced by nucleotide and DNA binding. We present multiple conformations of MutSβ including the DNA-free MutSβ compatible with homoduplex DNA binding, two distinct structures of MutSβ bound to (CAG)2DNA, a sliding clamp form and a DNA-unbound, ATP-bound conformation. Along with evidence for novel conformational states adopted by MutSβ to initiate the MMR cascade, these structures provide a foundation for structure-guided drug discovery.
Investigating the causal effects of childhood and adulthood adiposity on later life mental health outcome: a Mendelian randomisation study
Authors: Pathak Sweta , Richardson Tom G , Sanderson Eleanor , Åsvold Bjørn Olav , Bhatta Laxmi , Brumpton Ben
Published: May 2023

Background

Obesity particularly during childhood is considered a global public health crisis and has been linked with later life health consequences including mental health.However, there is lack of causal understanding if childhood adiposity has a direct effect on mental health or has an indirect effect after accounting for adulthood body size.

Objective

To investigate the total and direct effect of childhood adiposity on later life anxiety and depression.

Method

Two-sample Mendelian randomization (MR) was performed to estimate the total effect and direct effect (accounting for adulthood body size) of childhood body size on anxiety and depression. We used summary statistics from a genome-wide association study (GWAS) of UK Biobank (n=453,169) and large-scale consortia of anxiety (Million Veteran Program) and depression (Psychiatric Genomics Consortium) (n=175,163 and n=173,005, respectively).

Result

Univariable MR did not indicate genetically predicted effects of childhood body size with later life anxiety (beta=-0.05, 95% CI=-0.13, 0.02), and depression (OR=1.06, 95% CI=0.94, 1.20). However, using multivariable MR, we observed that the higher body size in childhood reduced the risk of later life anxiety (beta=-0.19, 95% CI=-0.29, -0.08) and depression (OR=0.83, 95% CI=0.71, 0.97). Both univariable and multivariable MR indicated that higher body size in adulthood increased the risk of later life anxiety and depression.

Conclusion

Our findings suggest that the higher body size in childhood has a protective effect on later life anxiety and depression, if obesity is not present into adulthood. Higher body size in adulthood was a risk factor for later life anxiety and depression.
Wildfire exposure and academic performance in Brazil: a causal inference approach for spatiotemporal data
Authors: McGrath Sean , Mukherjee Rajarshi , Réquia Weeberb J. , Lee Wan-Chen
Published: May 2023

As the frequency and intensity of wildfires are projected to globally amplify due to climate change, there is a growing need to quantify the impact of exposure to wildfires in vulnerable populations such as adolescents. In our study, we applied rigorous causal inference methods to estimate the effect of wildfire exposure on academic performance of high school students in Brazil between 2009 and 2015. Using longitudinal data from 8,183 high schools across 1,571 municipalities in Brazil, we estimated that the average performance in most academic subjects decreases under interventions that increase wildfire exposure, e.g., a decrease of 1.8% (p= 0.01) in the natural sciences when increasing the wildfire density from 0.0035 wildfires/km2(first quantile in the sample) to 0.0222 wildfires/km2(third quartile). Furthermore, these effects considerably worsened over time and were worse in regions with lower income. Our findings highlight the adverse impact of wildfires on educational outcomes.
Effects of Equine-Assisted Therapy on Recovery after Stroke – A Systematic Review
Authors: Trunk Bettina Hanna , Gharabaghi Alireza
Published: May 2023

Background

Equine-Assisted Therapy (EAT) can boost well-being and recovery of patients with neurological or psychiatric disorders.

Objective

The goal of this systematic review is to gain a better understanding of the effects of EAT on recovery after stroke.

Methods

A systematic literature search was performed in the following databases: PubMed, Web of Science and Scopus. Furthermore, reference lists from the articles included were screened. English-written articles published between 2000-2023 that reported on health-related effects of EAT (applied with both horses and riding simulators) on stroke recovery in patients aged between 18 and 85 were included. Methodological quality was assessed by the Mixed Methods Appraisal Tool.

Results

Following the screening of 2030 and retrieval of 33 articles respectively, 14 studies were included in this systematic review (437 patients, mean age range: 40 – 70 years). Since several of these studies lacked important methodological information, the overall methodological quality varied. Thirteen studies reported physical findings (balance, gait, postural coordination, activities of daily living, lower extremity motor impairment, motor function and hand strength), and seven studies reported further health-related outcomes (cognition, quality of life, depression and perception of the intervention, muscle thickness and trunk muscle activity). The findings suggest positive effects of EAT on stroke recovery in different health-related outcomes, whereas the most consistent beneficial effects were reported for balance and gait.

Conclusion

EAT appears to be a promising multimodal intervention for the recovery of different functions after stroke. However, evidence is sparse and methodological quality limited. Future research should investigate the effects of EAT on stroke recovery more systematically.
Surveillance strategies for the detection of new SARS-CoV-2 variants across epidemiological contexts
Authors: Oliveira Roster Kirstin I. , Kissler Stephen M. , Omoregie Enoma , Wang Jade C. , Amin Helly , Di Lonardo Steve , Hughes Scott , Grad Yonatan H.
Published: May 2023

Rapid identification of new SARS-CoV-2 variants is a critical component of the public health response to the COVID-19 pandemic. However, we lack a quantitative framework to assess the expected performance of sampling strategies in varying epidemic contexts. To address this gap, we used a multi-patch stochastic model of SARS-CoV-2 spread in New York City to evaluate the impact of the volume of testing and sequencing, geographic representativeness of sampling, location and timing of variant emergence, and relative variant transmissibility on the time to first detection of a new variant. The strategy of targeted sampling of likely emergence locations offered the most improvement in detection speed. Increasing sequencing capacity reduced detection time more than increasing testing volumes. The relative transmissibility of the new variant and the epidemic context of variant emergence also influenced detection times, showing that individual surveillance strategies can result in a wide range of detection outcomes, depending on the underlying dynamics of the circulating variants. These findings help contextualize the design, interpretation, and trade-offs of genomic surveillance strategies.
Trends in the 30-year span of Noninfectious Cardiovascular Implantable Electronic Device Complications in Olmsted County
Authors: Kowlgi Gurukripa N. , Vaidya Vaibhav , Dai Ming-Yan , Mishra Rahul , Hodge David O. , Deshmukh Abhishek J. , Mulpuru Siva K. , Friedman Paul A. , Cha Yong- Mei
Published: May 2023

Background

Cardiovascular implantable electronic devices (CIEDs) such as permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices alleviate morbidity and mortality in various diseases. There is a paucity of real-world data on CIED complications and trends.

Objectives

Describe trends in noninfectious CIED complications over the past three decades in Olmsted County.

Methods

The Rochester Epidemiology Project is a medical records linkage system comprising records of over 500,000 residents of Olmsted County from 1966-current. CIED implants between 1988-2018 were determined. Trends in noninfectious complications within 30 days of implant were analyzed.

Results

175 out of 2536 (6.9%) patients who received CIED experienced device complications. 3.8% of the implants had major complications requiring intervention. Lead dislodgement was the most common (2.9%), followed by hematoma (2.1%). Complications went up from 1988 to 2005, then showed a downtrend until 2018, driven by a decline in hematomas in the last decade (p<0.01). Those with complications were more likely to have prosthetic valves. Obesity appeared to have a protective effect in a multivariate regression model. The mean Charlson comorbidity score has trended up over the 30 years.

Conclusions

Our study describes a real-world trend of CIED complications over three decades. Lead dislodgements and hematomas were the most common complications. Complications have declined over the last decade due to safer practices and a better understanding of anticoagulant management.
Habituation to visual stimuli is personality-independent in a jumping spider
Authors: Beydizada Narmin Ilgar , Cannone Francesco , Pekár Stano , Baracchi David , De Agrò Massimo
Published: May 2023

1

Jumping spiders display some of the richest visually-mediated behaviors in nature. Vision is indeed the most important sensory modality in these spiders where motion detection and response to visual stimuli allow key behaviors such as hunting, escaping from predators, and mating. These spiders have been used in various experiments demonstrating the existence of good associative learning and memory abilities, whose mechanism parallels that found in vertebrates. Here we focused on the habituation and dis-habituation (H/DH) paradigm, indicating either a gradual decrease in responsiveness to repeated visual stimuli (H), or a recovery of the habituated stimulus (DH). H is an elementary form of non-associative learning and memory, which is expected to vary from individual to individual. The link between personality and H/DH has been shown in many vertebrates, but rarely in invertebrates. To tackle this question we tested whether personality affects H/DH in the jumping spiderMenemerus semilimbatus.In our protocol, habituation was assessed by presenting repeatedly a visual stimulus on a screen to spiders tethered on a locomotor compensator. In the same individuals, personality (namely boldness) was assessed in a walking arena equipped with a shelter. We found thatM. semilimbatushabituated and dishabituated to our visual stimulus and that they differed in personality along a shy-bold axis. However, contrary to our expectations, personality was not related to learning. We discussed the results and speculated that the nature (neutral value) of the stimulus might have played a role in making learning independent from personality.
New parameters for the in vitro development of cell lines from fish species
Authors: de Oliveira Furo Ivanete , Nogueira Lygia S. , de Sousa Rodrigo Petry Corrêa , Silva-Oliveira Glaucia Caroline , Santos da Silva Diovanna Mirella dos , Costa-Malaquias Allan , de Oliveira Edivaldo H.C
Published: May 2023

The establishment of cell lines from fish species is becoming important because of the increase in interest of these cells for viral analysis, environmental monitoring and cytogenetic studies. However, there is some discussion about the best conditions for maintaining these cells. We describe here a protocol for primary cell lines which we have found to be reliable. Fin biopsies from two species,Geophagus proximusandAstyanax bimaculatus, were isolated and cultured. We used three culture media (Leibovitz-L15, Dulbecco s Modified Eagle Medium-DMEM and 199) with or without the addition of AmnioMax and a standard temperature of 29ºC. The results showed that 199 medium was less efficient for both species. However, the cells ofG. proximushad better proliferation in DMEM and L-15 media, whileA. bimaculatuscells fared better in DMEM medium. The high concentration of L-glutamine and branched-chain amino acids (BCAAs) in the DMEM and L15 media was probably important for better adaptation of these cells. Furthermore, the addition of AmnioMax, a supplement rich in L-glutamine, increased cell proliferation in both species. Thus, the protocol initially established was tested in other tissues (fin, gills and kidney) of other fish species from the Amazon region. The cells were maintained in L-15 medium supplemented with 20% FBS (Fetal Bovine Serum) and 5% AmnioMax. It was observed that the cells were successfully subcultured and had a good proliferation, also the morphological characteristics were preserved. Thus, the methodology described in this research represents an innovative tool for the establishing of fish cell.
Cardiomyopathy-Associated Variants Alter the Structure and Function of the α-Actinin-2 Actin-Binding Domain
Authors: Atang Alexandra E , Rebbeck Robyn T. , Thomas David D. , Avery Adam W.
Published: May 2023

Hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM) are characterized by thickening, thinning, or stiffening, respectively, of the ventricular myocardium, resulting in diastolic or systolic dysfunction that can lead to heart failure and sudden cardiac death. Recently, variants in theACTN2gene, encoding the protein α-actinin-2, have been reported in HCM, DCM, and RCM patients. However, functional data supporting the pathogenicity of these variants is limited, and potential mechanisms by which these variants cause disease are largely unexplored. Currently, NIH ClinVar lists 34ACTN2missense variants, identified in cardiomyopathy patients, which we predict are likely to disrupt actin binding, based on their localization to specific substructures in the α-actinin-2 actin binding domain (ABD). We investigated the molecular consequences of three ABD localized, HCM-associated variants: A119T, M228T and T247M. Using circular dichroism, we demonstrate that the mutant ABD proteins can attain a well-folded state. However, thermal denaturation studies show that all three mutations are destabilizing, suggesting a structural disruption. Importantly, A119T decreased actin binding, and M228T and T247M cause increased actin binding. We suggest that altered actin binding underlies pathogenesis for cardiomyopathy mutations localizing to the ABD of α-actinin-2.
Computational framework for statistical epistasis supports XOR penetrance function in a living system
Authors: Batista Sandra , Madar Vered Senderovich , Freda Philip J. , Bhandary Priyanka , Ghosh Attri , Chitre Apurva S. , Palmer Abraham A. , Moore Jason H.
Published: May 2023

Statistical epistasis has been studied extensively because of its potential to provide evidence for genetic interactions for phenotypes, but there have been methodological limitations to its exhaustive, widespread application. We present new algorithms for the interaction coefficients for standard regression models for epistasis that permit many varied encodings for the interaction terms for loci and efficient memory usage. The algorithms are given for two-way and three-way epistasis and may be generalized to higher order epistasis. Statistical tests for the interaction coefficients are also provided. We also present an efficient matrix based algorithm for permutation testing for two-way epistasis. We offer a proof and experimental evidence that methods that look for epistasis only at loci that have main effects may not be justified. Given the computational efficiency of the algorithm, we applied the method to a rat data set and mouse data set, with at least 10000 loci and 1000 samples each, using the standard Cartesian encoding and the XOR penetrance function for the interactions, to test for evidence of statistical epistasis for the phenotype of body mass index. This study revealed that the XOR penetrance function found greater evidence for statistical epistasis in many more pairs of loci in both data sets and in the rat data set, those pairs of loci found using the XOR penetrance function are enriched for biologically relevant pathways.

Author summary

Epistasis, the interaction between two or more genes, is likely integral to the study of genetics and present throughout nature. Yet, it is seldom fully explored as most approaches primarily focus on single-locus effects (such as GWAS), partly because analyzing all pairwise and higher-order interactions requires significant computational resources. Many current methods for epistasis detection only consider a Cartesian encoding for interaction terms. This is likely limiting as epistatic interactions can evolve to produce varied relationships between genes, some non-linear. In this work we describe computationally efficient algorithms for the detection of statistical epistasis that allow for varied interaction encodings for modeling epistasis. Our methodology efficiently detects pairwise and three-way epistatic interactions in two closely related species (rat and mouse) under both Cartesian and XOR interaction encodings. Our results in both species show that many biologically relevant epistatic relationships would have been undetected if only one interaction encoding was applied providing evidence that more varied models for interaction may need to be applied to describe epistasis that occurs in living systems.
Functionally redundant formate dehydrogenases enable formate-dependent growth inMethanococcus maripaludis
Authors: Halim Mohd Farid Abdul , Fonseca Dallas R , Niehaus Thomas D , Costa Kyle C
Published: May 2023

Methanogens are essential for the complete remineralization of organic matter in anoxic environments. Most cultured methanogens are hydrogenotrophic, using H2as an electron donor to reduce CO2to CH4, but in the absence of H2many can also use formate. Formate dehydrogenase (Fdh) is essential for formate oxidation, where it transfers electrons for reduction of coenzyme F420or to a flavin-based electron bifurcating reaction catalyzed by heterodisulfide reductase (Hdr), the terminal reaction of methanogenesis. How these competing reactions are coordinated is unknown. Furthermore, methanogens that use formate encode at least two isoforms of Fdh in their genomes, but how these different isoforms participate in methanogenesis is also unknown. UsingMethanococcus maripaludis, we undertook a biochemical characterization of both Fdh isoforms involved in methanogenesis. Both Fdh1 and Fdh2 interacted with Hdr to catalyze the flavin-based electron bifurcating reaction, and both reduced F420at similar rates. F420reduction preceded flavin-based electron bifurcation activity for both enzymes. In a Δfdh1mutant background, a suppressor mutation was required for Fdh2 activity. Genome sequencing revealed that this mutation resulted in loss of a specific molybdopterin transferase (moeA), allowing for Fdh2-dependent growth. This suggests that both isoforms of Fdh are functionally redundant, but their activitiesin vivomay be limited by gene regulation under different growth conditions. Together these results expand our understanding of formate oxidation and the role of Fdh in methanogenesis.
Comparing FRET pairs that report on intersubunit rotation in bacterial ribosomes
Authors: Das Ananya , Bao Chen , Ermolenko Dmitri N.
Published: May 2023

Mediated by elongation factor G (EF-G), ribosome translocation along mRNA is accompanied by rotational movement between ribosomal subunits. Here, we reassess whether the intersubunit rotation requires GTP hydrolysis by EF-G or can occur spontaneously. To that end, we employ two independent FRET assays, which are based on labeling either ribosomal proteins (bS6 and bL9) or rRNAs (h44 of 16S and H101 of 23S rRNA). Both FRET pairs reveal three FRET states, corresponding to the non-rotated, rotated and semi-rotated conformations of the ribosome. Both FRET assays show that in the absence of EF-G, pre-translocation ribosomes containing deacylated P-site tRNA undergo spontaneous intersubunit rotations between non-rotated and rotated conformations. While the two FRET pairs exhibit largely similar behavior, they substantially differ in the fraction of ribosomes showing spontaneous fluctuations. Nevertheless, instead of being an invariable intrinsic property of each FRET pair, the fraction of spontaneously fluctuating molecules changes in both FRET assays depending on experimental conditions. Our results underscore importance of using multiple FRET pairs in studies of ribosome dynamics and highlight the role of thermally-driven large-scale ribosome rearrangements in translation.
Parallels and contrasts between the cnidarian and bilaterian maternal-to-zygotic transition are revealed inHydractiniaembryos
Authors: Ayers Taylor N. , Nicotra Matthew L. , Lee Miler T.
Published: May 2023

Embryogenesis requires coordinated gene regulatory activities early on that establish the trajectory of subsequent development, during a period called the maternal-to-zygotic transition (MZT). The MZT comprises transcriptional activation of the embryonic genome and post-transcriptional regulation of egg-inherited maternal mRNA. Investigation into the MZT in animals has focused almost exclusively on bilaterians, which include all classical models such as flies, worms, sea urchin, and vertebrates, thus limiting our capacity to understand the gene regulatory paradigms uniting the MZT across all animals. Here, we elucidate the MZT of a non-bilaterian, the cnidarianHydractinia symbiolongicarpus. Using parallel poly(A)-selected and non poly(A)-dependent RNA-seq approaches, we find that the Hydractinia MZT is composed of regulatory activities analogous to many bilaterians, including cytoplasmic readenylation of maternally contributed mRNA, delayed genome activation, and separate phases of maternal mRNA deadenylation and degradation that likely depend on both maternally and zygotically encoded clearance factors, including microRNAs. But we also observe massive upregulation of histone genes and an expanded repertoire of predicted H4K20 methyltransferases, aspects thus far unique to the Hydractinia MZT and potentially underlying a novel mode of early embryonic chromatin regulation. Thus, similar regulatory strategies with taxon-specific elaboration underlie the MZT in both bilaterian and non-bilaterian embryos, providing insight into how an essential developmental transition may have arisen in ancestral animals.
High-resolution molecular atlas of a lung tumor in 3D
Authors: Pentimalli Tancredi Massimo , Schallenberg Simon , León-Periñán Daniel , Legnini Ivano , Theurillat Ilan , Thomas Gwendolin , Boltengagen Anastasiya , Fritzsche Sonja , Nimo Jose , Ruff Lukas , Dernbach Gabriel , Jurmeister Philipp , Murphy Sarah , Gregory Mark T. , Liang Yan , Cordenonsi Michelangelo , Piccolo Stefano , Coscia Fabian , Woehler Andrew , Karaiskos Nikos , Klauschen Frederick , Rajewsky Nikolaus
Published: May 2023

Cells live and interact in three-dimensional (3D) cellular neighborhoods. However, histology and spatial omics methods mostly focus on 2D tissue sections. Here we present a 3D spatial atlas of a routine clinical sample, an aggressive human lung carcinoma, by combiningin situquantification of 960 cancer-related genes across ∼340,000 cells with measurements of tissue-mechanical components. 3D cellular neighborhoods subdivided the tumor microenvironment into tumor, stromal, and immune multicellular niches. Interestingly, pseudotime analysis suggested that pro-invasive epithelial-to-mesenchymal transition (EMT), detected in stroma-infiltrating tumor cells, already occurred in one region at the tumor surface. There, myofibroblasts and macrophages specifically co-localized with pre-invasive tumor cells and their multicellular molecular signature identified patients with shorter survival. Moreover, cytotoxic T-cells did not infiltrate this niche but colocalized with inhibitory dendritic and regulatory T cells. Importantly, systematic scoring of cell-cell interactions in 3D neighborhoods highlighted niche-specific signaling networks accompanying tumor invasion and immune escape. Compared to 2D, 3D neighborhoods improved the characterization of immune niches by identifying dendritic niches, capturing the 3D extension of T-cell niches and boosting the quantification of niche-specific cell-cell interactions, including druggable immune checkpoints. We believe that 3D communication analyses can improve the design of clinical studies investigating personalized, combination immuno-oncology therapies.
Melanocytes Exhibit Distinct Cell States Governed by A Gene Regulatory Network Under Stochastic Influence
Authors: Aggarwal Ayush , Nasreen Ayesha , Sahoo Sarthak , Faruq Mohammed , Pandey Rajesh , Jolly Mohit K , Singh Abhyudai , Gokhale Rajesh S , Natarajan Vivek T
Published: May 2023

Melanocytes serve as a protector of the skin against external stressors such as ultraviolet radiations. While melanocytes remain functional for nearly the entire lifespan of an individual, how they respond efficiently and survive such insults remain elusive. Here, we show the co-existence of multiple distinct states of normal human epidermal melanocytes (NHEMs). Using a progressive pigmentation model, we show that stochasticity in gene expression can lead to the co-existence of multiple melanocyte states. Using active enhancers and gene expression footprint, we identified state-specific transcription factors and constructed a gene regulatory network (GRN). The GRN couples pigmentation and cell cycle regulators and explains the co-existence and transitions of the melanocyte states. Finally, we show that NHEMs respond to external cues by altering the cell state dynamics. These results demonstrate that stochasticity in gene expression followed by epigenetic modification leads to the co-existence of multiple melanocyte states enabling an efficient response to environmental cues.
Life cycle-coupled evolution of mitosis in close relatives of animals
Authors: Shah Hiral , Olivetta Marine , Bhickta Chandni , Ronchi Paolo , Trupinić Monika , Tromer Eelco C. , Tolić Iva M. , Schwab Yannick , Dudin Omaya , Dey Gautam
Published: May 2023

Eukaryotes have evolved towards one of two extremes along a spectrum of strategies for remodelling the nuclear envelope (NE) during cell division: disassembling the NE in an open mitosis or constructing an intranuclear spindle in a closed mitosis. Both classes of mitotic remodelling involve key differences in the core division machinery, but the evolutionary reasons for adopting a specific mechanism are unclear. Here, we use an integrated comparative genomics and ultrastructural imaging approach to investigate mitotic strategies in Ichthyosporea, close relatives of animals and fungi. We show that species within this clade have diverged towards either a fungal-like closed or an animal-like open mitosis, most likely to support distinct multi- or uninucleated states. Our results suggest that multinucleated life cycles favour the evolution of closed mitosis.

One-Sentence Summary

Mitotic specialization in animal relatives reveal that multinucleated life cycles favor the evolution of closed mitosis
Exploring the influence of lean manufacturing and total quality management practices on environmental sustainability: the moderating role of quality culture
Authors: Jum’a Luay , Alkalha Ziad , Al Mandil Karam , Alaraj Maher
Published: May 2023

Purpose

Organizations have released the importance of lean manufacturing practices (LMPs) and total quality management (TQM) in enhancing competitiveness. However, the implementation of LMPs and TQM becomes more complex when discerning the environmental sustainability position. The complexity stems from the fact that LMPs and TQM are more intricate because of cultural differences. Thus, this study aims to tackle the aforementioned phenomenon by investigating the impact of LMPs and TQM on environmental sustainability moderated by quality culture.

Design/methodology/approach

A survey was distributed among small and medium enterprises (SMEs) in Jordan; thus, 315 valid responses were received. Partial least square structural equation modelling was used to analyze the data and test hypotheses.

Findings

The findings showed that environmental sustainability was significantly impacted by all the LMP practices except Kanban and all the TQM practices except statistical process control. Moreover, quality culture significantly and negatively moderated the relationship between TQM and environmental sustainability. However, the influence of LMPs on environmental sustainability was not significantly moderated by quality culture.

Practical implications

This study has implications for policymakers in SMEs, supply chain managers and academics regarding the importance of LMPs and TQM systems for implementing environmental sustainability and the role of quality culture.

Social implications

This study provides guidelines for decision-makers on the pathways that enable them to sustain the environment to safeguard the natural ecosystem and natural resources for upcoming generations.

Originality/value

The originality of this study stems from the alignment of LMPs and TQM in enhancing environmental sustainability, taking into consideration the role of quality culture in SMEs, where previous studies failed short to investigate this phenomenon.
The isomorphism of educational providers in the New Zealand tertiary market
Authors: Wang Jenny Jing
Published: May 2023

Purpose

The purpose of this paper is to explain how aspects of institutional theory can be used to explain how tertiary educational providers must necessarily adopt the same features while competing in the market for students. Using new institutional sociology (NIS), the authors seek to explain this phenomena and how such diverse private providers have borrowed from the polytechnics and universities to share the same institutional features.

Design/methodology/approach

This paper employs NIS to explain how tertiary educational providers must necessarily adopt the same features while competing in the market for students. In the last few decades, the Auckland tertiary market for overseas students has enjoyed strong growth before Covid-19.

Findings

Decoupling provides a link between NIS and legitimacy theory in that it explains how symbolic strategies are aimed at some kind of legitimization rather than directed at technical efficiencies. It is argued that the public tertiary providers are more prone to decoupling than PTEPs because they are less attentive to costs due to their more monopolistic position in the market.

Originality/value

Originally, the market was dominated by the local universities and polytechnics with few private providers. Currently, private providers cater for a large share of the certificate and diploma market and have a growing stake in the degree market. As these changes came about so, more diverse private providers entered the market. This paper explains how these diverse entrants came to share the same organizational features.
Mediating role of emotional intelligence between organizational climate, and transfer of learning among civil service employees
Authors: Oluwafemi Olaolu Joseph , Ametepe Paul Kojo
Published: May 2023

Purpose

Despite the enormous investment in employee training, training effectiveness is often hampered by insufficient transfer of learning (TOL) among trainees, making the return on training investment suboptimal. The challenge of effective TOL among employees is enormous, including personal and organizational factors, and research exploring this is inconclusive. This study aims to investigate organizational climate and TOL and the mediating role of emotional intelligence.

Design/methodology/approach

Applying identical elements and social cognitive theories, the study used multistage sampling techniques through purposive, convenience and simple random sampling collected using validated measures of the study constructs formed into a survey questionnaire. Multiple Regression and Process Macro were used to analyze the data.

Findings

Results revealed significant relationships between formalization, performance feedback, employee participation, innovation and flexibility with TOL. Organizational climate dimensions jointly and independently predicted TOL. However, only formalization was inversely related to TOL. Emotional intelligence partially mediates the relationship between organizational climate dimensions and TOL. The study recommends the need for managers to encourage autonomy, creativity and flexibility and provide honest and valid feedback to foster the TOL.

Originality/value

By addressing the limitations of other studies, this study advances knowledge by underlining the significance of including and further exploring the mediating role of trainees’ emotional intelligence on the relationship between organizational climate (formalization, performance feedback, employee participation, innovation and flexibility) and TOL.
Spray‐drying microencapsulation of blackcurrant and cocoa polyphenols using underexplored plant‐based protein sources
Authors: Hoskin Roberta Targino , Grace Mary H. , Xiong Jia , Lila Mary Ann
Published: May 2023

The performance of buckwheat protein (BK) and chia seed protein (CP) as drying carriers for the microencapsulation of polyphenols extracted from blackcurrant pomace and cocoa powder was investigated. Four experimental groups were evaluated (BK–BC: blackcurrant pomace extract with buckwheat protein; CP–BC: blackcurrant pomace extract with chia:pea protein blend; BK–CC: cocoa extract with buckwheat protein; and CP–CC: cocoa extract with chia:pea protein blend) to determine physicochemical attributes, phytochemical content, antioxidant activity, and polyphenol in vitro bioaccessibility. Nonconventional, underexploited protein sources such as chia/pea protein blend and buckwheat protein efficiently produced functional microparticles with attractive color and texture, low hygroscopicity (<20% increase in moisture content when exposed to 86% relative humidity for 1 week), solubility above 50% at pH 7 and 10, and uniform particle size (29 < D4,3 < 56 µm). Besides this, the protein–polyphenol microparticles concentrated and protected health‐relevant polyphenol content. Anthocyanins were detected in blackcurrant treatments (around 20 mg cyanidin‐3‐O‐glucoside equivalents/g), while proanthocyanidins (PAC) were the most prevalent polyphenols in cocoa treatments (>100 mg PAC B2/g). Monomers were the main class of PAC in both BK–CC and CP–CC treatments. All protein–polyphenol treatments reduced both reactive oxygen species and nitric oxide production in lipopolysaccharide‐activated cells (p < 0.05). The polyphenol recovery index was high (>70%) for both oral and gastric phases, and BK‐derived groups had better bioaccessibility index compared to BC or CC alone (noncomplexed). This research provided a framework for delivery of high‐value ingredients to attend to an emerging market centered on protein‐rich, clean label plant‐based food products.

Practical Application

Practical Application: The protein–polyphenol complexation is a robust method to produce phytochemical‐rich food ingredients for the food industry with enhanced physicochemical, sensory, and bioaccessibility performance. In this study, we investigated practical aspects regarding the production and quality of protein–polyphenol particles, such as the spray‐drying efficiency, phytochemical content, physicochemical attributes, antioxidant activity, and polyphenol bioaccessibility. This study unveils the potential of underexplored buckwheat and chia seeds (alone or combined with pea protein) as encapsulation carriers for fruit polyphenols to diversify the protein options available for products directed to the wellness market.
Who fares better in teamwork?
Authors: Yildirim Huseyin
Published: May 2023

This article establishes a tenuous link between ability and relative well‐being in teamwork. It shows that higher‐ability or lower‐cost members can easily fare worse than their lower‐ability counterparts due to free‐riding. The extent of free‐riding hinges crucially on log‐concavity of effort cost, which its convexity restricts little. The article further shows how to compose teams that allocate effort efficiently and equalize payoffs in equilibrium. Efficient teams must have sufficiently diverse abilities and sizes at most the number of cost log‐inflections plus one. These findings can explain the evidence of a significant dislike for teamwork in the workplace and classroom.
Managerial performance evaluation and organizational form
Authors: Krapp Michael , Schultze Wolfgang , Weiler Andreas
Published: May 2023

We study the relative efficiency of centralized versus decentralized organizational forms given optimized managerial performance evaluation within an incomplete contracting framework with risk‐averse agents under moral hazard. Decentralization and performance evaluation are complementary control choices and the efficiency of an organizational form depends on the design of performance evaluation. Divisions can make relationship‐specific investments that not only improve firm performance, but also increase compensation risk. We find that pure divisional performance evaluation is optimal under centralization, whereas under decentralization, optimal compensation contracts include a combination of divisional and firm‐wide performance evaluation. When comparing both organizational forms, we find that the optimal form depends on managers’ degree of risk‐aversion and the uncertainty of the business environment. Contrary to previous literature, we find that centralization dominates in many situations, particularly at high degrees of risk‐aversion and high uncertainty.
Açaí palm management disturbs seed rain and soil seed bank of an Amazonian estuarine forest
Authors: da Silva Gabriele Rosa , Tabarelli Marcelo , Jardim Mário Augusto Gonçalves , Cruz Eniel David , Barros Maria Fabíola
Published: May 2023

The exploitation of non‐timber forest products has been proposed as a sustainable way to exploit tropical forests, but such an opportunity remains to be proved. Here, we examine the impact of intensive açaí palm (Euterpe oleracea) management on the seed rain and soil seed bank in an estuarine forest landscape with a long history of forest management by locals in the Amazon region. Seed rain (100 80 cm2 collectors) and soil seed bank (100 30 cm2 samples) were monitored through a year across 20 forest stands, covering a gradient of açaí stem density (50–3575 açaí stems per ha). Seed rain and bank were dominated by açaí seeds (85.5%–85.8%) and by excluding them, seed rain and bank were low density and species poor, capturing a tiny subset from the local (17.91%–19.40%) and landscape woody flora (11.82%–14.55%). Moreover, autochthonous and vertebrated‐dispersed predominated as well as those from tree species considered useful by locals. Overall, açaí stem density positively affected açaí seed abundance in the seed rain and negatively affected seed pools in the bank in relation to abundance of seeds and vertebrated dispersed, while adult tree species richness and density and accessibility to forest stands were associated with more diversified seed pools. Thereby, forest stands are exposed to different levels of açaí management (high vs. low intensity) supported taxonomically distinct seed pools. Our results suggest that açaí intensification disturbs seed rain and soil seed bank with potential impacts on forest regeneration and the forest integrity standards required to consider açaí fruit production as sustainable according to current legislation.
The importance of binding kinetics and drug–target residence time in pharmacology
Authors: Knockenhauer Kevin E. , Copeland Robert A.
Published: May 2023

A dominant assumption in pharmacology throughout the 20th century has been that in vivo target occupancy—and attendant pharmacodynamics—depends on the systemic concentration of drug relative to the equilibrium dissociation constant for the drug–target complex. In turn, the duration of pharmacodynamics is temporally linked to the systemic pharmacokinetics of the drug. Yet, there are many examples of drugs for which pharmacodynamic effect endures long after the systemic concentration of a drug has waned to (equilibrium) insignificant levels. To reconcile such data, the drug–target residence time model was formulated, positing that it is the lifetime (or residence time) of the binary drug–target complex, and not its equilibrium affinity per se, that determines the extent and duration of drug pharmacodynamics. Here, we review this model, its evolution over time, and its applications to natural ligand‐macromolecule biology and synthetic drug–target pharmacology.
Treatment outcomes of immature permanent necrotic evaginated teeth: A retrospective study comparing regenerative endodontic procedures with apexification
Authors: Li Jiahui , Cheng Jing , Yang Fengjiao , Yu Jingjing , Song Guangtai
Published: May 2023

Background

Few studies have compared the outcomes of regenerative endodontic procedures (REPs) and calcium hydroxide apexification focusing on necrotic teeth with dens evaginatus.

Aim

To qualitatively and quantitatively compare the treatment outcomes of REPs and calcium hydroxide apexification in teeth with dens evaginatus.

Design

Immature permanent necrotic evaginated teeth treated with REPs or calcium hydroxide apexification for a follow‐up period of at least 12 months were included. Tooth success and survival rates were analyzed. Changes in radiographic root length, apical diameter, and radiographic root area (RRA) were quantified. Prognostic factors that might influence RRA were identified via multivariate linear regression analysis.

Results

A total of 112 teeth (50 REP cases and 62 apexification cases) with a median follow‐up period of 26.5 months were included. Regenerative endodontic procedures and calcium hydroxide apexification exhibited similar satisfactory success and survival rates (p > .05). Additionally, 88 teeth were quantitatively analyzed. The REP group presented a significantly greater percentage increase in RRA and less decrease in apical diameter than the calcium hydroxide apexification group (p < .05). Teeth treated with REPs and with Stages 7 and 8 of root development showed a better gain in RRA (p < .05).

Conclusion

While REP and calcium hydroxide apexification had similar success and survival rates, teeth with REPs showed an increase in RRA, indicating that REP is the preferred choice.