bluuebunny/crossref_metadata_2025_split huggingface dataset:
C. elegans toxicant responses vary among genetically diverse individuals
Authors: Widmayer Samuel J. , Crombie Timothy A. , Nyaanga Joy N. , Evans Kathryn S. , Andersen Erik C. 
Published: July 2022

ABSTRACTComprehensive chemical hazard risk evaluations require reproducible, efficient, and informative experimental workflows in tractable model systems that allow for high replication within exposure cohorts. Additionally, the genetic variability of toxicant responses among individuals in humans and mammalian models requires practically untenable sample sizes. Caenorhabditis elegans is a premier toxicology model that has revolutionized our understanding of cellular responses to environmental pollutants and boasts robust genomic resources and high levels of genetic variation across the species. In this study, we performed dose-response analysis across 23 environmental toxicants using eight C. elegans strains representative of species-wide genetic diversity. We observed substantial variation in EC10 estimates and slope parameter estimates of dose-response curves of different strains, demonstrating that genetic background is a significant driver of differential toxicant susceptibility. We also showed that, across all toxicants, at least one C. elegans strain exhibited a significantly different EC10 or slope estimate compared to the reference strain, N2 (PD1074), indicating that population-wide differences among strains are necessary to understand responses to toxicants. Moreover, we quantified the heritability of responses to each toxicant dose and observed a correlation between the dose closest to the species-agnostic EC10 estimate and the dose that exhibited the most heritable response. Taken together, these results provide robust evidence that heritable genetic variation explains differential susceptibility across an array of environmental pollutants and that genetically diverse C. elegans strains should be deployed to aid high-throughput toxicological screening efforts.
Free-Standing Multilayer Films as Growth Factor Reservoirs for Future Wound Dressing Applications
Authors: Hautmann Adrian , Kedilaya Devaki , Stojanović Sanja , Radenković Milena , Marx Christian K. , Najman Stevo , Pietzsch Markus , Mano João F. , Groth Thomas 
Published: July 2022

AbstractChronic skin wounds place a high burden on patients and health care systems. The use of angiogenic and mitogenic growth factors (GF) can facilitate the healing but GF are quickly inactivated by the wound environment if added exogenously. Here, free-standing multilayer films (FSF) are fabricated from chitosan (CHI) and alginate (ALG) as opposing polyelectrolytes in an alternating manner using layer-by-layer technique (LbL). One hundred bilayers form an about 450 µm thick, detachable free-standing film (N-FSF) that is subsequently crosslinked by either ethyl (dimethylaminopropyl) carbodiimide (EDC) combined with N-hydroxysuccinimide (NHS) (E-FSF) or genipin (G-FSF). The characterization of swelling, oxygen permeability and crosslinking density shows reduced swelling and oxygen permeability for both crosslinked films compared to N-FSF. Loading of fibroblast growth factor 2 (FGF2) into the films results in a sustained release of GF from crosslinked in comparison to N-FSF. Biocompatibility studies in vitro with human dermal fibroblasts (HDF) cultured underneath the films demonstrate increased cell growth and cell migration for all films with and without FGF2. Especially G-FSF loaded with FGF2 greatly increases cell proliferation and migration. In vivo biocompatibility studies by subcutaneous implantation in mice show that E-FSF causes a strong inflammatory response while G-FSF is of high biocompatibility. N-FSF also represents a biocompatible film but shows early degradation. All FSF possess antibacterial properties against gram+ and gram-bacteria demonstrated by an agar diffusion disc assay. In summary, FSF made of ALG and CHI crosslinked with genipin can act as a reservoir for the sustained release of FGF2, possessing high biocompatibility in vitro and in vivo. Moreover, G-FSF promotes growth and migration of HDF and has antibacterial properties which makes it an interesting candidate for bioactive wound dressings.
Exportin 1-mediated nuclear/cytoplasmic trafficking controls drug sensitivity of classical Hodgkin lymphoma
Authors: Caillot Mélody , Miloudi Hadjer , Taly Antoine , Maitre Elsa , Saule Simon , Jardin Fabrice , Sola Brigitte 
Published: July 2022

AbstractExportin 1 (XPO1) is the main nuclear export receptor that controls the subcellular trafficking and the functions of major regulatory proteins. XPO1 is overexpressed in various cancers and small inhibitors of nuclear export (SINEs) have been developed to inhibit XPO1. In primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL), the XPO1 gene may be mutated on one nucleotide and encodes the mutant XPO1E571K. To understand the impact of mutation on protein function, we studied the response of PMBL and cHL cells to selinexor, a SINE, and ibrutinib, an inhibitor of Bruton tyrosine kinase. XPO1 mutation renders lymphoma cells more sensitive to selinexor due to a faster degradation of mutant XPO1 compared to the wild-type. We further showed that a mistrafficking of p65 (RELA) and p52 (NFκB2) transcription factors between the nuclear and cytoplasmic compartments accounts for the response towards ibrutinib. XPO1 mutation may be envisaged as a biomarker of the response of PMBL and cHL cells and other B-cell hemopathies, to SINEs and drugs that target even indirectly the NFκB signaling pathway.
PhenoTrack3D: an automatic high-throughput phenotyping pipeline to track maize organs over time
Authors: Daviet Benoit , Fernandez Romain , Cabrera-Bosquet Llorenç , Pradal Christophe , Fournier Christian 
Published: July 2022

AbstractBackgroundHigh-throughput phenotyping platforms allow the study of the form and function of a large number of genotypes subjected to different growing conditions (GxE). A number of image acquisition and processing pipelines have been developed to automate this process, for micro-plots in the field and for individual plants in controlled conditions. Capturing shoot development requires extracting from images both the evolution of the 3D plant architecture as a whole, and a temporal tracking of the growth of its organs.ResultsWe propose PhenoTrack3D, a new pipeline to extract a 3D+t reconstruction of maize at organ level from plant images. It allows the study of plant architecture and individual organ development over time during the entire growth cycle. PhenoTrack3D improves a former method limited to 3D reconstruction at a single time point [Artzetet al., 2019] by (i) a novel stem detection method based on deep-learning and (ii) a new and original multiple sequence alignment method to perform the temporal tracking of ligulated leaves. Our method exploits both the consistent geometry of ligulated leaves over time and the unambiguous topology of the stem axis. Growing leaves are tracked afterwards with a distance-based approach. This pipeline is validated on a challenging dataset of 60 maize hybrids imaged daily from emergence to maturity in the PhenoArch platform (ca. 250,000 images). Stem tip was precisely detected over time (RMSE < 2.1cm). 97.7% and 85.3% of ligulated and growing leaves respectively were assigned to the correct rank after tracking, on 30 plants x 43 dates. The pipeline allowed to extract various development and architecture traits at organ level, with good correlation to manual observations overall, on random subsets of 10 to 355 plants.ConclusionsWe developed a novel phenotyping method based on sequence alignment and deep-learning. It allows to characterise automatically and at a high-throughput the development of maize architecture at organ level. It has been validated for hundreds of plants during the entire development cycle, showing its applicability to the GxE analyses of large maize datasets.
Orally administered niclosamide-based organic/inorganic hybrid suppresses SARS-CoV-2 infection
Authors: Jin Geun-woo , Choi Goeun , Rejinold N. Sanoj , Piao Huiyan , Ryu Young Bae , Kwon Hyung-Jun , Lee In Chul , Choy Jin-Ho 
Published: July 2022

AbstractThe COVID-19 pandemic is a serious global health threat mainly due to the surging cases along with new variants of COVID-19. Though global vaccinations have indeed some effects on the virus spread, its longevity is still unknown. Therefore an orally administrable anti-viral agent against SARS-CoV-2 would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we repurposed niclosamide (NIC), an FDA approved anthelmintic drug in to MgO, which was further coated with hydroxyl propyl methyl cellulose (HPMC) to get the de-sired product called NIC-MgO-HPMC, which has improved anti-SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of NIC-MgO-HPMC on SARS-CoV-2 replication leads to the prevention of inflammation as well as lung injury. These data strongly support that repurposed NIC-MgO-HPMC could be highly beneficial for controlling the ongoing pandemic thereby achieving an endemic phase.
Dietary change without caloric restriction maintains a youthful profile in ageing yeast
Authors: Horkai Dorottya , Houseley Jonathan 
Published: July 2022

AbstractCaloric restriction increases lifespan and improves ageing health, but it is unknown whether these outcomes can be separated or achieved through less severe interventions. Here we show that an unrestricted galactose diet in early life minimises change during replicative ageing in budding yeast, irrespective of diet later in life. Lifespan and average mother cell division rate are comparable between glucose and galactose diets, but markers of senescence and the progressive dysregulation of gene expression observed on glucose are minimal on galactose, showing these to be associated rather than intrinsic aspects of the replicative ageing process. Respiration on galactose is critical for minimising hallmarks of ageing, and forced respiration during ageing on glucose by over-expression of the mitochondrial biogenesis factor Hap4 also has the same effect though only in a fraction of cells. This fraction maintains Hap4 activity to advanced age with low senescence and a youthful gene expression profile, whereas other cells in the same population lose Hap4 activity, undergo dramatic dysregulation of gene expression and accumulate fragments of chromosome XII (ChrXIIr), which are tightly associated with senescence. Our findings support the existence of two separable ageing trajectories in yeast. We propose that a complete shift to the healthy ageing mode can be achieved in wild-type cells through dietary change in early life without restriction.
Deep mutational scanning and massively parallel kinetics of plasminogen activator inhibitor-1 functional stability
Authors: Haynes Laura M. , Huttinger Zachary M. , Yee Andrew , Kretz Colin A. , Siemieniak David R. , Lawrence Daniel A. , Ginsburg David 
Published: July 2022

ABSTRACTPlasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (SERPIN) superfamily of proteins, is unique among SERPINs for exhibiting a spontaneous conformational change to a latent or inactive state. The functional half-life for this transition at physiologic temperature and pH is ~1-2 h. To better understand the molecular mechanisms underlying this transition, we now report on the analysis of a comprehensive PAI-1 variant library expressed on filamentous phage and selected for functional stability after 48 h at 37 °C. Of the 7,201 possible single amino acid substitutions in PAI-1, we identify 439 that increase the functional stability of PAI-1 beyond that of the wild-type protein and 1,549 that retain inhibitory activity toward PAI-1’s canonical target protease (urokinase-like plasminogen activator, uPA), while exhibiting functional stability less than or equal to that of wild-type PAI-1. Missense mutations that increase PAI-1 functional stability are concentrated in highly flexible regions within the PAI-1 structure. Finally, we developed a method for simultaneously measuring the functional half-lives of hundreds of PAI-1 variants in a multiplexed, massively parallel manner, quantifying the functional half-lives for 697 single missense variants of PAI-1 by this approach. Overall, these findings provide novel insight into the mechanisms underlying PAI-1’s latency transition and provide a database for interpreting human PAI-1 genetic variants.
A new multidimensional approach to measuring the middle class dynamics: evidence from Morocco
Authors: Daoudim Fouzia , Bakass Fatima 
Published: July 2022

Purpose
This paper aims to propose a dynamic multidimensional approach to identify the middle class and then to reliably study the structural changes that have marked it in terms of demographic and socioeconomic characteristics and aspirations.

Design/methodology/approach
This study uses Moroccan data from the 2007 and 2014 household expenditure surveys. The method consists in applying a factor analysis of mixed data on a set of variables inspired by Bourdieu’s concepts of social space and forms of capital, then performing a hierarchical ascending classification consolidated by the k-means clustering, along with adopting the same indicators and weighting for both years studied to ensure reliable comparison.

Findings
The classification results identified three social classes whose changing size reveals a decline of the lower class and an expansion of the upper and middle classes. Some characteristics of the middle class are becoming close to those of the upper class, like fertility behavior, while a significant gap remains between the two classes in other characteristics, like education. Moreover, middle-class perceptions reflect their downgrading, confirming that the so-called decline of the middle class is more related to feelings than to objective realities.

Originality/value
Middle class studies are generally based on a single criterion (income or consumption) with somewhat arbitrary boundaries that are often ill-suited to developing countries. This paper proposes a new dynamic multidimensional approach to overcome these problems while adopting a new technique for reliable intertemporal comparisons.
Heterogeneous deformation of friction stir welded aluminum alloy 6061 in tension and high cycle fatigue
Authors: Dai Yajun , Liu Chang , Zhan Min , Wang Xiangyu , He Chao , Wang Qingyuan 
Published: July 2022

PurposeThe investigations provide a basis for the optimization of the alloy 6061-T6 friction stir welding (FSW) process to improve the mechanical properties of welded joints.Design/methodology/approachThe local deformation of the FSW joint in tension and fatigue test were experimentally investigated by digital image correlation (DIC) technique.FindingsThe local stress-strain behaviors of the sub-regions show that the plastic strain always concentrated at the heat affected zone (HAZ) on the advancing side both in tension and high cycle fatigue and eventually leads to the final fracture. The evolution of the plastic strain at very low stress is extremely slow and accounts for most of the total fatigue life. However, the local deformation exhibits a sudden increase just before the fatigue failure.Originality/valueBased on the experimental data, the result indicates that the HAZ is the weakest zone across the weld and the strain localization in high cycle fatigue is very harmful and unpredictable for the FSW joints.
The contagious servant leadership: exploring the role of servant leadership in leading employees to servant colleagueship
Authors: Khan Muhammad Mumtaz , Mubarik Muhammad Shujaat , Ahmed Syed Saad , Islam Tahir , Khan Essa 
Published: July 2022

PurposeThis paper intends to ascertain whether servant leadership can trigger servant colleagueship among subordinates. Additionally, the study is set out to divulge the mediating role of self-transcendence relating servant leadership to servant colleagueship.Design/methodology/approachData were collected from the respondents in three waves that were two months apart. In the first wave, employees rated their managers' servant leadership behavior. In the second wave, employees rated their self-transcendence, and finally, they rated their colleague-directed servant behavior. The final sample size for the study was 209 employees employed in the service sector. Structural equational modeling through Smart-PLS and hierarchical regression through SPSS were used for data analysis.FindingsThe study found servant leadership to be related to self-transcendence and employees' enacted servant colleagueship. Additionally, the study found self-transcendence to mediate the relationship between servant leadership and servant colleagueship.Originality/valueThe study has established the previously unexplored mediating role of self-transcendence linking servant leadership to servant colleagueship. The study is also the first to empirically test the relationship between self-transcendence and servant colleagueship.
Management and landscape of shelterbelts contribute to butterfly and flowering plant diversity in northern Japan
Authors: Nakahama Naoyuki , Hayamizu Masato , Iwasaki Kenta , Nitta Noritoshi 
Published: July 2022

AbstractA considerably large number of shelterbelts were established in Japan to increase crop yields in agricultural landscapes. Shelterbelt landscapes have multiple functions; they not only help to control wind damage but also to conserve biodiversity, including forest and grassland species. However, previous studies on biodiversity conservation in shelterbelts, and the target taxa were limited since this aspect of shelterbelts has not received much attention in Japan. This study examines the effects of shelterbelts and their regeneration on the diversity of butterflies and flowering plants in the Tokachi region of Hokkaido, Japan. Using a transect method, we compared environmental factors, butterfly, and flowering plant diversity in four habitats: inside forest, forest edge, regeneration sites, and semi‐natural grasslands which include shelterbelts and surrounding landscapes. There were significant differences in photosynthetically active radiation (PAR) among habitats, with higher PAR corresponding to higher numbers of butterfly species and individuals, and flowering plant species and flowers. Nonmetric multidimensional scaling results also showed that the species composition of flowering plants and butterflies differed among habitats. In addition, indicator value analysis showed that semi‐natural grasslands and regeneration sites were characterized by endangered butterflies and their host plants. Our results indicated that shelterbelt regeneration and the surrounding environment (e.g., semi‐natural grasslands) contributed to the diversity of butterflies and flowering plants, including endangered species. Future studies evaluating the diversity of various taxa would provide a more comprehensive understanding of the effects of shelterbelts on biodiversity conservation.
Seed germinability in the endangered Pulsatilla cernua (Ranunculaceae) following cold storage for up to 31 years
Authors: Harimoto Shota , Kataoka Hiroyuki , Kubo Masako 
Published: July 2022

AbstractPulsatilla cernua is an endangered species in Japan and its seeds are often stored for long periods. However, the shelf life of these seeds is unclear. We conducted germination tests using P. cernua seeds that had been stored in a refrigerator at approximately 6°C for up to 31 years. Germination tests were conducted at 25°C under dark conditions. We assessed seed weight, number of germinated seeds, seedling development, and time to germination over a 30‐day period for each collection year. The highest germination rate was from seeds collected in the current year (2019; 82.7%). Germination rates remained high in seeds that had been stored for up to 7 years (>46%). However, there was a marked decline in germinability after the eighth year of storage and germination was not observed in seeds that had been stored for longer than 15 years. Approximately 20% of current‐year seeds and seeds that had been stored for up to 6 years developed into seedlings, but no seedlings developed from seeds that had been stored for 7 years or longer. The germination rate and the time to germination decreased and increased, respectively, with storage time. These results show that the shelf life of P. cernua seeds in cold storage at 6°C is approximately 6 years. To facilitate the ex situ conservation of this species, the germinability of stored seeds at lower temperatures and under other germination test conditions should be explored in future studies.
Not a Priority: Infertile Women and the Symbolic Politics of IVF in 1980s Britain
Authors: Beers Laura 
Published: July 2022

AbstractThis article considers the early debates over state funding for in vitro fertilisation (IVF) treatment following the birth of Louise Brown in 1978 as a lens through which to re‐evaluate attitudes towards womanhood, maternity and sexuality in 1980s Britain. The state's reluctance to devote resources to IVF reflected, in no small part, the financial imperatives on an overstretched National Health Service. Beyond financial considerations, the question of IVF funding sparked deeply gendered debates over the politics and social significance of motherhood and mothering, and the state's role in family planning and maternal and child welfare. In short, debates over IVF operated as a form of symbolic politics. Stakeholders – including patients’ advocates, women's associations, feminist activists and religious leaders – drew a clear link between the female body and the body politic and sought to articulate a policy towards both IVF treatment and infertile women more broadly that reflected their understanding of women's place within modern British society. Despite holding widely divergent views about gender, sexuality and motherhood, women's and religious groups found common ground in opposing state funding of IVF. This coalition facilitated the state's decision not to prioritise funding for IVF even as neighbouring countries, including Germany and France, embraced the procedure to help combat demographic decline.
THE INFORMAL CONSTITUTION OF STATE CENTRALITY: Governing Street Businesses in (Post‐)Pandemic Chengdu, China
Authors: Jin Yi , Zhao Yimin 
Published: July 2022

AbstractAs part of China's endeavour to modernize and internationalize its cities, it has repeatedly eliminated street markets and street vendors. But in the (post‐)pandemic context, regulating street businesses inclusively turned out to be an efficient way to generate jobs that has been widely promoted. This turn reveals a new pattern in China's urban governance that might contribute to rethinking the state–informality nexus. In this article we draw on observations and interviews in Chengdu and on critical discourse analyses of related government documents and news reports to suggest that there is an underlying logic of control that governs the state's new tactics for regulating street businesses. We examine three tactics—performative tactics of regulation, spatial tactics of control and temporal tactics of contingency—to uncover the state's centrality and the tactics it uses to consolidate such centrality in the name of informality. Regarding informality and state centrality as conditions for each other allows us to interrogate both the internal logic of control and its manifestations in everyday statehood. Within the informal constitution of state centrality, everyday negotiations and contestations of spatial claims eventually render the ‘ordinary state’ a hegemonic locus that shapes urban experiences and politics.