bluuebunny/crossref_metadata_2025 huggingface dataset:
A combined experimental-computational approach uncovers a role for the Golgi matrix protein Giantin in breast cancer progression
Authors: Ghannoum Salim , Fantini Damiano , Zahoor Muhammad , Reiterer Veronika , Phuyal Santosh , Netto Waldir Leoncio , Sørensen Øystein , Iyer Arvind , Sengupta Debarka , Prasmickaite Lina , Mælandsmo Gunhild Mari , Köhn-Luque Alvaro , Farhan Hesso
Published: May 2022

Few studies so far have investigated the impact of different cell migration traits on tumor progression. To address this, we developed a mathematical model wherein cells migrate in two-dimensional space, divide, die or intravasate into the vasculature. Exploring a wide range of speed and persistence combinations, we find that tumor growth positively correlates with increasing speed and higher persistence. As a biologically relevant example, we focused on Golgi fragmentation induced by depletion of Giantin, a Golgi matrix protein, the downregulation of which correlates with poor patient survival. Applying the migration and invasion traits of Giantin depleted cells to our mathematical model, we predict that loss of Giantin increases the number of intravasating cells. This prediction was validated, by showing that circulating tumor cells express significantly less Giantin than primary tumor cells. Altogether, our computational model identifies cell migration traits that regulate tumor progression and uncovers a role of Giantin in breast cancer progression.
Using genomes and evolutionary analyses to screen for host-specificity and positive selection in the plant pathogen Xylella fastidiosa
Authors: Batarseh Tiffany N. , Morales-Cruz Abraham , Ingel Brian , Roper M. Caroline , Gaut Brandon S.
Published: May 2022

Xylella fastidiosa infects several economically important crops in the Americas, and it also recently emerged in Europe. Here, using a set of Xylella genomes reflective of the genus-wide diversity, we performed a pan-genome analysis based on both core and accessory genes, for two purposes: i) to test associations between genetic divergence and plant host species and ii) to identify positively selected genes that are potentially involved in arms-race dynamics. For the former, tests yielded significant evidence for specialization of X. fastidiosa to plant host species. This observation contributes to a growing literature suggesting that the phylogenetic history of X. fastidiosa lineages affects host range. For the latter, our analyses uncovered evidence of positive selection across codons for 5.3% (67 of 1,257) of core genes and 5.4% (201 of 3,691) of accessory genes; these genes are candidates to encode interacting factors with plant and insect hosts. Most of these genes had unknown functions, but we identified some tractable candidates including nagZ_2, which encodes a beta-glucosidase that is important for Neisseria gonorrhoeae biofilm formation; cya, which modulates gene expression in pathogenic bacteria; and barA, a membrane associated histidine kinase that has roles in cell division, metabolism, and pili formation.

ABSTRACT IMPORTANCE

Xylella fastidiosa causes devasting diseases to several critical crops. Because X. fastidiosa colonizes and infects many plant species, it is important to understand whether the genome of X. fastidiosa has genetic determinants that underlie specialization to specific host plants. We analyzed genome sequences of X. fastidiosa to investigate evolutionary relationships and to test for evidence of positive selection on specific genes. We found a significant signal between genome diversity and host plants, consistent with bacterial specialization to specific plant hosts. By screening for positive selection, we identified both core and accessory genes that may affect pathogenicity, including genes involved in biofilm formation.
Genomic And Molecular Characterization Of The Wheat Streak Mosaic Virus Resistance Locus 2 (Wsm2) In Common Wheat (Triticum Aestivum. L)
Authors: Xie Yucong , Nachappa Punya , Nalam Vamsi , Pearce Stephen
Published: May 2022

Wheat streak mosaic virus is an economically important viral pathogen that threatens global wheat production, particularly in the Great Plains region of the United States. The Wsm2 locus confers resistance to WSMV and has been widely deployed in common wheat varieties adapted to this region. Characterizing the underlying causative genetic variant would contribute to our understanding of viral resistance mechanisms in crops and aid the development of perfect markers for breeding.

In this study, Wsm2 flanking markers were mapped to a 4.0 Mbp region of the wheat reference genome containing 142 candidate genes. Haplotype analysis in seventeen wheat genotypes collected from different agroecological zones indicated that Wsm2 lies in a dynamic region of the genome with extensive structural variation, and that it is likely absent from available genome assemblies of common wheat varieties.

Exome sequencing of the variety ‘Snowmass,’ which carries Wsm2, revealed several loss-of-function mutations and copy number variants in the 142 candidate genes within the Wsm2 interval. Six of these genes are differentially expressed in ‘Snowmass’ compared to ‘Antero,’ a variety lacking Wsm2, including a gene that encodes a nucleotide-binding site leucine-rich repeat (NBS-LRR) type protein with homology to RPM1. A de novo assembly of unmapped RNA-seq reads identified nine transcripts expressed only in ‘Snowmass,’ three of which are also induced in response to WSMV inoculation. This study sheds light on the variation underlying Wsm2 and provides a list of candidate genes for subsequent validation.
Microglial P2X4 receptors promote ApoE degradation and cognitive deficits in Alzheimer disease
Authors: Hua Jennifer , Garcia de Paco Elvira , Linck Nathalie , Maurice Tangui , Desrumaux Catherine , Manoury Bénédicte , Rassendren François , Ulmann Lauriane
Published: May 2022

Numerous evidence support that microglia contributes to the progression of Alzheimer’s disease. P2X4 receptors are ATP-gated channels, which are de novo expressed in a subset of reactive microglia associated to various pathological contexts, contributing to microglial functions. Here, we investigated the role of P2X4 in the context of Alzheimer disease (AD). In both human AD brain and APPswe/PSEN1dE9 mice, P2X4 is almost exclusively expressed in plaque associated microglia. Genetic deletion of P2rx4 results in the reversal of cognitive declines and in a lower amount of soluble Aß1 −42 in 12 months old APP/PS1 mice, while no obvious alteration of plaque associated microglia characteristics is observed. Using proteomic, we identified ApoE as a specific P2X4 interacting protein. We found that P2X4 regulates lysosomal cathepsin B activity promoting ApoE degradation; P2rx4 deletion results in higher amount of intracellular and secreted ApoE in both BMDM and microglia from APP/PS1 brain. Our results support that microglial P2X4 promotes lysosomal ApoE degradation, indirectly altering Aß peptide clearance, which in turn might promote synaptic dysfunctions and cognitive deficits. Our findings also uncover a specific interplay between purinergic signaling, microglial ApoE, sAß species and cognitive deficits associated with AD.
Polo-like kinase-1 Inhibitors and the Antiandrogen Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling
Authors: Patterson Jesse C. , Varkaris Andreas , Croucher Peter J. P. , Ridinger Maya , Dalrymple Susan , Nouri Mannan , Xie Fang , Varmeh Shohreh , Jonas Oliver , Whitman Matthew A. , Chen Sen , Rashed Saleh , Makusha Lovemore , Luo Jun , Isaacs John T. , Erlander Mark G. , Einstein David J. , Balk Steven P. , Yaffe Michael B.
Published: May 2022

Abiraterone, a standard treatment for metastatic castrate-resistant prostate cancer (mCRPC), slows disease progression by abrogating androgen synthesis and antagonizing the androgen receptor (AR). We report that inhibitors of the mitotic kinase Plk1, including the clinically active third-generation Plk1 inhibitor onvansertib, when co-administered with abiraterone, synergistically kill cancer cells from a wide variety of tumor types in an androgen-independent manner, both in vitro and in vivo. Abiraterone treatment alone results in defects in mitotic spindle orientation, failure of complete chromosome condensation, and upregulation of mitosis and mitotic-spindle related gene sets independently of its effects on AR signaling. These effects, while mild following abiraterone monotherapy, result in profound sensitization to the anti-mitotic effects of Plk1 inhibition, leading to spindle assembly checkpoint-dependent mitotic cell death and entosis. In a murine PDX model of mCRPC, combined onvansertib and abiraterone resulted in enhanced mitotic arrest and dramatic inhibition of tumor cell growth compared to either agent alone.

STATEMENT OF SIGNIFICANCE

A phase 2 clinical trial is underway (NCT03414034) testing combined Plk1 inhibitor onvansertib and abiraterone in mCRPC patients with nascent abiraterone resistance. Our work establishes a mechanistic basis for that trial and indicates that combined abiraterone and onvansertib co-treatment may have broad utility for cancer treatment beyond mCRPC.
Tracking single cell evolution via clock-like chromatin accessibility
Authors: Xiao Yu , Jin Wan , Ju Lingao , Fu Jie , Wang Gang , Yu Mengxue , Chen Fangjin , Qian Kaiyu , Wang Xinghuan , Zhang Yi
Published: May 2022

Single cell chromatin accessibility sequencing (scATAC) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Here, we show a simple, accurate and phenotypic-neutral measure of cell developmental hierarchy -- the fraction of accessible clock-like loci. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. We developed a method, EpiTrace, that counts the fraction of opened clock-like loci from scATAC data to determine cell age and perform lineage tracing. EpiTrace works in various cell lineages and animal species, shows concordance with known developmental hierarchies, correlates well with DNA methylation-based clocks, and is complementary with mutation-based lineage tracing, RNA velocity, and stemness predictions. Applying EpiTrace to scATAC data revealed a multitude of novel biological insights with clinically relevant implications, ranging from hematopoiesis, organ development, tumor biology and immunity to cortical gyrification. Our work discovered a universal epigenomic hallmark during cellular development, which facilitates the study of cellular hierarchies and organismal aging.
The limits to ecological limits to diversification
Authors: Etienne Rampal S. , Haegeman Bart , Dugo-Cota Álvaro , Vilà Carles , Gonzalez-Voyer Alejandro , Valente Luis
Published: May 2022

Abstract

While the theory of micro-evolution by natural selection assigns a crucial role to competition, its role in macroevolution is less clear. Phylogenetic evidence for a decelerating accumulation of lineages suggests a feedback of lineage diversity on diversification, i.e., ecological limits to diversification. However, does this feedback only occur between close relatives, or do distant relatives also influence their diversification? In other words: are there phylogenetic limits to these ecological limits? Islands form ideal systems to answer these questions, because their boundedness facilitates an overview of all potential competitors. The DAISIE (Dynamic Assembly of Island biota through Speciation Immigration and Extinction) framework allows for testing the presence of diversity-dependence on islands given phylogenetic data on colonization and branching times. The current inference models in DAISIE assume that this diversity-dependence only applies within a colonizing clade, which we term clade-specific (CS) diversity-dependence. Here we introduce a new DAISIE model that assumes that diversity-dependence applies to all species regardless of their ancestry, i.e. diversity-dependence applies both to species within the same clade and between different clades. We call this island-wide (IW) diversity-dependence. Here we present a method to compute a likelihood for this model and develop a statistical procedure based on likelihood ratio bootstrapping to compare it to the likelihood of the CS model in order to overcome biases known for standard model selection. We apply it to the diversification ofEleutherodactylusfrogs on Hispaniola. Across the Greater Antilles archipelago, this radiation shows repeated patterns of diversification in ecotypes which are similar across clades. This could be suggestive of overlapping niche space and hence between-clade interactions, i.e. IW diversity-dependence. But it could also be suggestive of only within-clade interactions, because between-clade interactions would have blocked the same ecotype re-appearing. We find that the CS model fits the data much better than the IW model, indicating that different colonizations, while resulting in similar ecotypes, are sufficiently distinct to avoid interacting strongly. We argue that non-overlapping distributions between clades (both spatially and in terms of ecotypes) cannot be used as evidence of CS diversity-dependence, because this pattern may be a consequence of IW diversity-dependence. By contrast, by using phylogenetic data rather than distributional data our method does allow for inferring the phylogenetic limits to ecological limits to diversification. We discuss how our new IW model advances our understanding also in other ways, ranging from identifying priority effects to modelling the spread of an epidemic in island-like systems, such as schools or hospitals.
Identification of two pyruvate transporters inSalmonella entericaserovar Typhimurium and their biological relevance
Authors: Paulini Stephanie , Fabiani Florian D. , Weiß Anna S. , Moldoveanu Ana Laura , Helaine Sophie , Stecher Bärbel , Jung Kirsten
Published: May 2022

Pyruvate (CH3COCOOH) is the simplest of the alpha-keto acids and is at the interface of several metabolic pathways both in prokaryotes and eukaryotes. In an amino acid-rich environment, fast-growing bacteria excrete pyruvate instead of completely metabolizing it. The role of pyruvate uptake in pathological conditions is still unclear. In this study, we identified two pyruvate-specific transporters, BtsT and CstA, inSalmonella entericaserovar Typhimurium (S. Typhimurium). Expression ofbtsTis induced by the histidine kinase/response regulator system BtsS/BtsR upon sensing extracellular pyruvate (threshold 200 μM), whereas expression ofcstAis maximal in the stationary phase. Both pyruvate transporters were found to be important for the uptake of this compound, but also for chemotaxis to pyruvate, survival under oxidative and nitrosative stress, and persistence ofS. Typhimurium in response to gentamicin. Compared with the wild-type, the ΔbtsTΔcstAmutant has disadvantages in antibiotic persistence in macrophages, as well as in colonization and systemic infection in gnotobiotic mice. These data demonstrate the surprising complexity of the two pyruvate uptake systems inS. Typhimurium.
Optimising Elastic Network Models for Protein Dynamics and Allostery: Spatial and Modal Cut-offs and Backbone Stiffness
Authors: Dubanevics Igors , McLeish Tom C.B.
Published: May 2022

The family of coarse-grained models for protein dynamics known as Elastic Network Models (ENMs) require a careful choice of parameters to represent well experimental measurements or fully-atomistic simulations. The most basic ENM that represents each protein residue by a node at the position of its C-alpha atom, all connected by springs of equal stiffness, up to a cut-off in distance. Even at this level, a choice is required of the optimum cut-off distance and the upper limit of elastic normal modes taken in any sum for physical properties, such as dynamic correlation or allosteric effects on binding. Additionally, backbone-enhanced ENM (BENM) may improve the model by allocating a higher stiffness to springs that connect along with the protein backbone. This work reports on the effect of varying these three parameters (distance and mode cutoffs, backbone stiffness) on the dynamical structure of three proteins, Catabolite Activator Protein (CAP), Glutathione S-transferase (GST), and the SARS-CoV- 2 Main Protease (Mpro). Our main results are: (1) balancing B-factor and dispersion-relation predictions, a near-universal optimal value of 8.5 angstroms is advisable for ENMs; (2) inhomogeneity in elasticity brings the first mode containing spatial structure not well-resolved by the ENM typically within the first 20; (3) the BENM only affects modes in the upper third of the distribution, and, additionally to the ENM, is only able to model the dispersion curve better in this vicinity; (4) BENM does not typically affect fluctuation-allostery, which also requires careful treatment of the effector binding to the host protein to capture.
Arabidopsis thalianarosette growth habit is a photomorphogenic trait controlled by the TALE homeodomain protein ATH1 and involves TOR kinase
Authors: Hajibehzad Shahram Shokrian , Silva Savani S. , Peeters Niels , Stouten Evelien , Buijs Guido , Smeekens Sjef , Proveniers Marcel
Published: May 2022

Here, we demonstrate that Arabidopsis rosette habit is abona fidephotomorphogenic trait controlled by the homeodomain protein ATH1. In light,ATH1expression at the SAM is induced by broad wavelengths, mediated through multiple photoreceptors, and requires inactivation of COP1 and PIF photomorphogenesis inhibitors. Such inducedATH1prevents elongation of rosette internodes by maintaining the rib zone area of the SAM in an inactive state. In the absence of light, Arabidopsis plants cannot complete seedling establishment after germination due to inactivity of the shoot apical meristem (SAM). Light requirement for SAM activation can be overcome by availability to the meristem of metabolizable sugars, such as sucrose. However, under these conditions plants fail to establish a typical compact rosette and display a caulescent growth habit. We show that this is due to insufficient expression ofATH1at the SAM. ATH1 induction restores rosette habit in dark-grown plants through inhibition ofPIFgene expression. Together, this suggests that a SAM-specific, double-negative ATH1-PIF feedback loop is at the basis of Arabidopsis rosette habit. Induction ofATH1expression and restoration of rosette habit in darkness also occurs at increased levels of sucrose. Both sugar and light signals that induceATH1are mediated by TOR kinase. Overall, these results support a fundamental role for ATH1 in Arabidopsis rosette habit and further strengthen a role for TOR kinase as a central hub for integration of energy and light signals controlling organogenesis at the SAM.
Wild-type IDH1 inhibition enhances chemotherapy response in melanoma
Authors: Zarei Mehrdad , Hajihassani Omid , Hue Jonathan J. , Graor Hallie J. , Rathore Moeez , Vaziri-Gohar Ali , Asara John M. , Winter Jordan M. , Rothermel Luke D.
Published: May 2022

Malignant melanoma is one of the most common types of cancer in the United States. Despite recent and well-described progress in melanoma treatment, advanced disease still carries a poor prognosis for many patients and chemotherapy has been appropriately abandoned as a front-line option. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme is protective to cancer cells under metabolic stress, including oxidative damage by conventional chemotherapy and nutrient limitation characteristic of the tumor microenvironment. Specifically, the cytosolic enzyme generates NADPH to maintain redox homeostasis. IDH1 also supports mitochondrial function through anaplerosis of its reaction product, α-ketoglutarate. We show that melanoma patients express higher levels of the wtIDH1 enzyme compared to normal skin tissue, and elevated wtIDH1 expression portends poor patient survival. Knockdown of IDH1 by RNA interference inhibited cell proliferation and migration under low nutrient levels. Suppression of IDH1 expression in melanoma also decreased NADPH and glutathione levels, resulting in increased reactive oxygen species. An FDA-approved inhibitor of mutant IDH1, ivosidenib (AG-120), exhibited potent anti-wtIDH1 properties under low magnesium and nutrient levels, reflective of the tumor microenvironmentin natura. Similarly, findings were replicated in murine models of melanoma. Further, wtIDH1 inhibition was synergistic to conventional anti-melanoma chemotherapy in pre-clinical models. This work points to a novel and readily available combination treatment strategy for patients with advanced and refractory melanoma.
Isolation of bat sarbecoviruses of SARS-CoV-2 clade, Japan
Authors: Murakami Shin , Kitamura Tomoya , Matsugo Hiromichi , Kamiki Haruhiko , Oyabu Ken , Sekine Wataru , Takenaka-Uema Akiko , Sakai-Tagawa Yuko , Kawaoka Yoshihiro , Horimoto Taisuke
Published: May 2022

Betacoronaviruses have caused 3 outbreaks in the past 2 decades. SARS-CoV-2, in particular, has caused a serious pandemic. As the betacoronaviruses are considered to originate from bats, surveillance of bat betacoronaviruses is crucial for understanding the mechanism of cross-species transition and potential for future outbreaks. We previously detected and characterized a SARS-CoV-2-related sarbecovirus, Rc-o319, fromRhinolophus cornutusin Japan. Here, we detected several bat sarbecoviruses of the SARS-CoV-2 clade fromR. cornutusin multiple locations in Japan, and successfully isolated them using Vero/TMPRSS2 cells stably expressingR. cornutusACE2 (Vero-RcACE2). The coding sequences of S1 region varied among isolates, whereas other genetic regions were highly conserved. Isolates were efficiently grown in Vero-RcACE2 cells, but did not replicate in Vero/TMPRSS2 cells stably expressing human ACE2, suggesting a narrow host range. Further long-term epidemiological studies of sarbecoviruses in wildlife are expected to facilitate the assessment of the risk of their spillover potential.
Predicting 3D RNA structure from solely the nucleotide sequence using Euclidean distance neural networks
Authors: Sha Congzhou M. , Wang Jian , Dokholyan Nikolay V.
Published: May 2022

Fast and accurate 3D RNA structure prediction remains a major challenge in structural biology, mostly due to the size and flexibility of RNA molecules, as well as lack of diverse experimentally determined structures of RNA molecules. Unlike DNA structure, RNA structure is far less constrained by base pair hydrogen bonding, resulting in an explosion of potential stable states. Here, we propose a convolutional neural network which predicts all pairwise distances between residues in an RNA, using a recently described smooth parametrization of Euclidean distance matrices. We achieve high accuracy predictions on RNAs up to 100 nucleotides in length in fractions of a second, a factor of 107 faster than existing molecular dynamics-based methods. We also convert our coarse-grained machine learning output into an all-atom model using discrete molecular dynamics with constraints. Our proposed computational pipeline accurately predicts all-atom RNA models solely from the nucleotide sequence.
Spontaneous genomic variation as a survival strategy of nosocomial S. haemolyticus
Authors: Bouchami Ons , Machado Miguel , Carriço João André , Melo-Cristino José , de Lencastre Herminia , Miragaia Maria
Published: May 2022

Staphylococcus haemolyticus is one of the most important nosocomial human pathogens frequently isolated in bloodstream and medical devices related infections. This species is notorious for its multidrug resistance and genome plasticity. However, its mechanisms of evolution and adaptation are still poorly explored. In this study we aimed to characterize the strategies of genetic and phenotypic diversity in S. haemolyticus. Here, we analyzed an invasive S. haemolyticus strain, recovered from a bloodstream infection, for genetic and phenotypic stability after serial passage in vitro (>400 generations) in the absence and presence of sub-inhibitory concentrations of a beta-lactam antibiotic. We performed PFGE of the culture and five colonies at seven time points during stability assays were analyzed for beta-lactams susceptibility, hemolysis, mannitol fermentation and biofilm production. We compared their whole genome regarding chromosomal structure, gene content and mutations and preformed phylogenetic analysis based on core SNPs. We observed a high instability in the PFGE profiles at the different time points during serial passage in vitro in the absence of antibiotic. However, no variation was observed in PFGE patterns in the presence of beta-lactams. Analysis of WGS data for individual colonies collected at different time points showed the occurrence of six large-scale genomic deletions within the oriC environ (36 kbp-348 kbp) in the cell populations analyzed, smaller deletions in non-OriC environ region as well as non-synonymous mutations in clinically relevant genes. The regions of deletion and point mutations included genes encoding amino acid and metal transporters, resistance to environmental stress and beta-lactams, virulence, mannitol fermentation, metabolic processes and IS elements. A parallel variation was additionally detected in clinically significant phenotypic traits such as mannitol fermentation, beta-lactams resistance, hemolysis and biofilm formation. All the genetic variants analyzed were closely related in their core genome (13-292 SNPs). Our results suggest that S. haemolyticus populations are composed of subpopulations of genetic and phenotypic variants that might be affected in antibiotic and stress resistance, specific metabolic processes and virulence. The maintenance of subpopulations in different physiological states might be a strategy to adapt rapidly to a stress situation imposed by the host particularly in the hospital environment.
The time-resolved atomic, molecular and optical science instrument at the Linac Coherent Light Source
Authors: Walter Peter , Osipov Timur , Lin Ming-Fu , Cryan James , Driver Taran , Kamalov Andrei , Marinelli Agostino , Robinson Joe , Seaberg Matthew H. , Wolf Thomas J. A. , Aldrich Jeff , Brown Nolan , Champenois Elio G. , Cheng Xinxin , Cocco Daniele , Conder Alan , Curiel Ivan , Egger Adam , Glownia James M. , Heimann Philip , Holmes Michael , Johnson Tyler , Lee Lance , Li Xiang , Moeller Stefan , Morton Daniel S. , Ng May Ling , Ninh Kayla , O'Neal Jordan T. , Obaid Razib , Pai Allen , Schlotter William , Shepard Jackson , Shivaram Niranjan , Stefan Peter , Van Xiong , Wang Anna Li , Wang Hengzi , Yin Jing , Yunus Sameen , Fritz David , James Justin , Castagna Jean-Charles
Published: May 2022

The newly constructed time-resolved atomic, molecular and optical science instrument (TMO) is configured to take full advantage of both linear accelerators at SLAC National Accelerator Laboratory, the copper accelerator operating at a repetition rate of 120 Hz providing high per-pulse energy as well as the superconducting accelerator operating at a repetition rate of about 1 MHz providing high average intensity. Both accelerators power a soft X-ray free-electron laser with the new variable-gap undulator section. With this flexible light source, TMO supports many experimental techniques not previously available at LCLS and will have two X-ray beam focus spots in line. Thereby, TMO supports atomic, molecular and optical, strong-field and nonlinear science and will also host a designated new dynamic reaction microscope with a sub-micrometer X-ray focus spot. The flexible instrument design is optimized for studying ultrafast electronic and molecular phenomena and can take full advantage of the sub-femtosecond soft X-ray pulse generation program.
A novel method of identifying sewing damage in single jersey fabrics
Authors: Yıldız Esra Zeynep , Pamuk Oktay
Published: May 2022

Purpose

This paper suggests a new method for determining the sewing damage that occurs in single jersey fabrics based on the calculation of the needle hole area. This paper also aims to investigate the effects of material type, sewing parameters, and repeated washing cycles on sewing damage by using this method.

Design/methodology/approach

Six knitted fabrics, differing in structure and raw material, were produced. Samples were sewn using different sewing parameters, and they were subjected to ten washing cycles. Values of average needle hole area, an objective indicator of sewing damage, were calculated before and after repeated washing cycles using image analysis software and were evaluated statistically.

Findings

The results showed that the average needle hole area calculated via the image analysis software effectively estimates sewing damage as the results obtained were compatible with those stated in the literature. Furthermore, fabric type, sewing direction, sewing thread type, and needle size significantly affected the sewing damage. However, stitch density did not affect the sewing damage. When the effect of washing cycles was compared, it was seen that washing leads to an increase in sewing damage.

Originality/value

A review of the existing literature shows that no previous study has evaluated sewing damage using image analysis software. This study proposes a novel objective method to determine the sewing damage that occurs in knitted fabrics.
The effect of production system characteristics on resilience capabilities: a multiple case study
Authors: Dittfeld Hendryk , van Donk Dirk Pieter , van Huet Sam
Published: May 2022

Purpose

To date, the literature has usually assumed that a universal approach to resilience is appropriate in which different resilience capabilities are equally important for all organizations independent of contextual characteristics. In contrast this study investigates if production process characteristics affect resilience capabilities in terms of redundancy, flexibility, agility and collaboration.

Design/methodology/approach

An in-depth exploratory multiple case study was carried out in eight companies across different industries. Data were gathered through multiple interviews with key informants in each company.

Findings

The authors find differences in, and trade-offs between, resilience capabilities and practices related to redundancy, agility and collaboration induced by the different configurations of production system characteristics: especially between discrete and process industries. Further, a major influential characteristic is the production strategy employed (make-to-stock or make-to-order) which stresses or limits collaboration and redundancy.

Originality/value

This is one of the first studies to explore the effects of production system characteristics as a major contingency factor on the resilience capabilities of an organization. As such it provides valuable insights into the development of a more nuanced contingency approach to how organizations can build resilience and employ specific practices that fit their situation.
Interaction training – an enabler for improvement measures within the psychosocial risk assessment process
Authors: Backström Tomas , Berglund Rachael Tripney
Published: May 2022

Purpose

The study objectives were to (1) identify if providing solution-focused interaction training enables managers and employees to develop and implement actions to improve their psychosocial work environment and (2) test a recontextualization of the psychosocial work environment as social structures affecting members of the workplace and verify if social interactions effectively change the local psychosocial work environment.

Design/methodology/approach

The intervention involved training managers, supervisors and employees in solution-focused interaction. This study used a controlled interrupted time-series design, with an intervention and control group (CG) and pre- and post-measurements.

Findings

The psychosocial work environment improved, indicating that the training led to better social interactions, contributing to changes in the social structures within the intervention group (IG). Collective reflection between participants in the take action phase was the key to success. The recontextualization uncovered these mechanisms.

Research limitations/implications

The present study supports a recontextualization of the psychosocial work environment as primarily decided by social structures that emerge in recurrent interactions within work teams. The same social structures also seem to be important for other features of the production system, like job performance.

Practical implications

Training designed to enable high-quality social interactions, like dialogue and collective reflection, has proven to be effective in changing social structures. Moreover, managers may need training in facilitating the collective reflection between participants. Increased focus on social interactions within work teams is suggested for future study of organizational change processes, psychosocial work environment and practical psychosocial work environment management.

Originality/value

The intervention was delivered in the preparation phase to enable an effective take action phase. Both phases are less studied in psychosocial risk assessments research. The recontextualization has never been fully used in psychosocial research.
Past, present and future of research in relationship marketing - a machine learning perspective
Authors: Das Kallol , Mungra Yogesh , Sharma Anuj , Kumar Satish
Published: May 2022

Purpose

This paper aims to take stock of research done in the domain of relationship marketing (RM). Additionally, this article aims to identify the potential areas of future research.

Design/methodology/approach

The authors have used machine learning-based structural topic modelling using R-software to analyse the dataset of 1,905 RM articles published between 1978 and 2020.

Findings

Structural topic modeling (STM) analysis led to identifying 14 topics, out of which 7 (viz. customer loyalty, customer relationship management systems, interfirm and network relationships, relationship selling, services and relationship management, consumer brand relationships and relationship marketing research) have shown a rising trend. The study also proposes a taxonomical framework to summarize RM research.

Originality/value

This is the first comprehensive review of RM research spanning over more than four decades. The study’s insights would benefit future scholars of this field to plan/execute their research for greater publication success. Additionally, managers could use the practical implications for achieving better RM outcomes.
Food delivery before and during the COVID-19 pandemic in Brazil
Authors: Liboredo Juliana Costa , Amaral Cláudia Antônia Alcântara , Carvalho Natália Caldeira
Published: May 2022

Purpose

This study aims to understand consumer behavior related to the purchase of meals by delivery services before and during the coronavirus disease 2019 (COVID-19) pandemic in Brazil.

Design/methodology/approach

An online survey was conducted between September and October 2020. The total number of valid responses was 971.

Findings

About 55% of the participants reported a decrease in consumption or not having consumed food delivery during the pandemic. Of the total, 48.3% feared contracting COVID-19 from food delivery. A significant association was observed between fear of contracting COVID-19 from food delivery and variables such as education level (p = 0.001), observance of social distancing (p = 0.03) and food delivery consumption frequency (p < 0.001). More people were careful about cleaning food packaging (from 12.4% before to 66.1% during the pandemic, p < 0.001) and disposal (from 47.6% before to 66.4% during the pandemic, p < 0.001) and heating the food before consumption (from 7.6% before to 13.7% during the pandemic, p < 0.001) and used payment methods without approximation (from 29.8% before to 43.2% during the pandemic, p < 0.001) compared with the pre-pandemic period. More people also reported that application of security protocols during delivery (from 29.8% before to 43.2% during the pandemic, p < 0.001) and in restaurants (from 7.2% before to 25% during the pandemic, p < 0.001) and possessing knowledge about the financial difficulty of the establishment (from 4.6% before to 17% during the pandemic, p < 0.001) were the most important factors for choosing a food service.

Originality/value

To the best of the authors’ knowledge, this is the first study to explore consumers’ fear of contracting COVID-19 from food delivery and consumer behavior related to food delivery services during the pandemic in Brazil – that is, way to order and payment methods, as well as concern and care related to the purchase of these foods.
The effect of heat treatment on physicochemical properties of skim milk concentrate and spray‐dried skim milk powder
Authors: Bista Archana , Murphy Eoin G , O'Donnell Colm P , O'Shea Norah
Published: May 2022

The aim of this study was to investigate the effect of heat treatment on the physicochemical properties of skim milk concentrate (SMC) and spray‐dried skim milk powder (SMP). The apparent viscosity of high‐heat‐treated SMC was higher than medium‐heat‐treated, low‐heat‐treated and control SMC. The results obtained in this study provide novel insights into the effect of heat treatment on the subsequent powder properties and demonstrated that high‐heat‐treated SMP had significantly higher moisture content, aw, particle size, b* value and the absence of crystallisation than the medium‐heat‐treated, low‐heat‐treated and control SMP samples. Increasing the intensity of heat treatment resulted in different reconstitution behaviours at the same %TS content and wettability.
Angiotensin II receptor blockers (ARBs) and manufacturing contamination: A retrospective National Register Study into suspected associated adverse drug reactions
Authors: Salim Hamisha , Jones Alan M.
Published: May 2022

Aims

The aim of this study was to determine if any suspected adverse drug reactions (ADRs) observed with the use of angiotensin II receptor blockers (ARBs) could be linked to either (a) their unique respective physicochemical and pharmacological profiles and (b) the recently disclosed suspected carcinogenic manufacturing contaminants found in certain sartan drug class batches.

Methods

The pharmacology profiles of ARBs were data‐mined from the Chemical Database of bioactive molecules with drug‐like properties, European Molecular Biology Laboratory (ChEMBL). Suspected ADR data (from 01/2016–10/2022, inclusive) and prescribing rates of ARBs over a 5‐year prescribing window (from 09/2016 to 08/2021, inclusive) were obtained via analysis of the United Kingdom Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card drug analysis profile and Open prescribing databases, respectively.

Results

The overall suspected ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied were found to be different between the sartan drug class members (chi‐squared test, P < .05). There is a greater relative rate of reports for valsartan across all investigated organ classes of ADRs, than other ARBs, despite valsartan's more limited pharmacological profile and similar physicochemical properties to other sartans. The disparity in ADR reporting rates with valsartan vs other ARBs could be due to the dissimilarity in formulation excipients, patient factors and publicity surrounding batch contaminations, amongst others. Cancer‐related ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied are not statistically significant (chi‐squared test, P > .05) based on the datasets used over the 5‐year period.

Conclusion

No connection between ARB pharmacology and their suspected ADRs could be found. No conclusion between sartan batch contaminations and increased suspected cancer‐related ADRs was found.
The role of placebo response in the efficacy outcome assessment in viloxazine extended‐release pivotal trials in paediatric subjects with attention‐deficit/hyperactivity disorder
Authors: Nasser Azmi , Gomeni Roberto , Wang Zhao , Hull Joseph T. , Busse Gregory D. , Melyan Zare , Fava Maurizio , O'Neal Welton , Rubin Jonathan
Published: May 2022

Aims: Four Phase 3 studies evaluated efficacy and safety of viloxazine extended‐release in the treatment of attention‐deficit/hyperactivity disorder (ADHD). The primary efficacy objective—change from baseline in ADHD Rating Scale‐5 (ADHD‐RS‐5) Total score at end of study (EOS)—was not met in one of the studies (812P304). A band‐pass analysis was performed to evaluate the impact of placebo response on the results.

Methods: The distribution of placebo response at EOS of each trial was evaluated. The 2.5th and 97.5th percentiles of the distribution of ADHD‐RS‐5 Total score were used as boundaries for the band‐pass analysis. An independent mixed model for repeated measures analysis was conducted for each trial using all eligible data (active and placebo) from the total and band‐pass filtered populations.

Results: The 2.5th and 97.5th percentiles at EOS were 3.5 and 53.5, respectively. Application of the band‐pass filter (filtering out all subjects [active, n = 305 (32.1%) and placebo, n = 134 (33.5%)] of clinical sites with placebo scores <3.5 or >53.5) revealed statistically significant improvement at the primary endpoint (600‐mg/d viloxazine ER vs. placebo) in Study 812P304 (mean [confidence interval] = 4.9537 [0.5405–9.3669]), previously masked by a high placebo response (mean [confidence interval] = 3.5756 [−0.3332–7.4844]). The outcome of the analysis indicated that the impact of the band‐pass adjustment is greater when placebo response is higher.

Conclusion: This analysis indicated that a higher placebo response in Study 812P304 confounded the assessment of treatment effect. Application of the band‐pass methodology confirmed the positive results of the 3 prior studies and the signal detection confounder in the fourth study.
Living with type 1 diabetes mellitus in emerging adulthood: A qualitative study
Authors: Fioretti Chiara , Mugnaini Chiara
Published: May 2022

Objective

Few studies have investigated the impact of diabetes considering its effects on developmental tasks that are typical of emerging adulthood. The present study aimed to investigate how emerging adults with a chronic condition such as type 1 diabetes mellitus manage with this developmental phase.

Methods

30 emerging adults diagnosed with diabetes (18–34 years, females = 19) took part in an autobiographical interview investigating their experience of dealing with type 1 diabetes. Narratives were analysed by means of a qualitative thematic analysis of an inductive type.

Results

Thematic analysis pointed out five thematic areas strictly related to the tasks of emerging adulthood: the development of intimate relationships, university life, work and plans for the future, the achievement of individual autonomy, the construction of an adult identity and family planning. Every thematic area reported a number of subthemes related to specific difficulties experienced by participants in reaching their developmental tasks due to chronic disease. Emerged themes considered both negative and positive outcomes of living with type 1 diabetes mellitus in emerging adulthood, such as a personal growth related to identity development.

Conclusion

The authors discussed results considering complexities and resources associated with diabetes in the light of developmental tasks of emerging adulthood.
Accumulation of misfolded SOD1 outlines distinct patterns of motor neuron pathology and death during disease progression in a SOD1G93A mouse model of amyotrophic lateral sclerosis
Authors: Salvany Sara , Casanovas Anna , Piedrafita Lídia , Gras Sílvia , Calderó Jordi , Esquerda Josep E.
Published: May 2022

Early misfolded superoxide dismutase 1 (mfSOD1) accumulation, motor neuron (MN) degeneration, and microgliosis are hallmark pathological features in SOD1G93A amyotrophic lateral sclerosis (ALS) mice. Because of the different vulnerabilities of distinct MN subtypes, degenerating and surviving MNs coexist in different proportions during disease progression. By examining the expression of misfolded conformers of SOD1 using specific antibodies, we defined distinct MN phenotypes that were evaluated during disease progression and the local neuroinflammatory reaction. The most severe phenotype corresponded to somata of fast‐twitch subtype MNs, which exhibited highly positive mfSOD1 immunostaining and an extreme degree of vacuolar degeneration. Vacuoles, which are of mitochondrial origin, contain mfSOD1 in conjunction with nonmitochondrial proteins, such as chromogranin, CD81, and flotillin. The fusion of ER‐derived vesicles enriched in mfSOD1 with outer mitochondrial membranes is thought to be the primary mechanism for vacuole formation. In addition, the ulterior coalescence of enlarged mitochondria may lead to the formation of giant vacuoles. Vacuolar degeneration is a transient degenerative process occurring early during the presymptomatic stages of the disease in ALS mice. Some vacuolated MNs are also positive for pMLKL, the effector protein of necroptosis. This indicates a newly described mechanism in which extracellular vesicles derived from damaged MNs, via cellular secretion or necroptotic disruption, may be the triggers for initiating neuroinflammation, glial‐mediated neurotoxicity, and disease spreading. Furthermore, as MN degeneration in mutant SOD1 mice is noncell autonomous, the effects of experimentally increasing or decreasing the microglial response on the expression of MN phenotypes were also evaluated, demonstrating bidirectional cross talk signaling between the degree of expression of mfSOD1 and local neuroinflammation. More detailed knowledge regarding these processes occurring long before the end stages of the disease is necessary to identify novel molecular targets for future preclinical testing.
Seven myths of ESG
Authors: Larcker David F. , Tayan Brian , Watts Edward M.
Published: May 2022

Environmental, social and governance (ESG) considerations have dominated the discussion of corporate purpose in recent years. We examine commonly accepted notions about ESG that are foundational to the discussion but receive little critical analysis. We conclude that decisions about ESG would improve if they were based on empirical evidence and theoretical research in this field.
Genome‐wide association studies in Japanese women identified genetic loci associated with wrinkles and sagging
Authors: Okuno Ryosuke , Inoue Yu , Hasebe Yuichi , Igarashi Toshio , Kawagishi‐Hotta Mika , Yamada Takaaki , Hasegawa Seiji
Published: May 2022

Wrinkles and sagging are caused by various factors, such as ultraviolet rays; however, recent findings demonstrated that some individuals are genetically predisposed to these phenotypes of skin aging. The contribution of single nucleotide polymorphisms (SNPs) to the development of wrinkles and sagging has been demonstrated in genome‐wide association studies (GWAS). However, these findings were mainly obtained from European and Chinese populations. Limited information is currently available on the involvement of SNPs in the development of wrinkles and sagging in a Japanese population. Therefore, we herein performed GWAS on wrinkles at the outer corners of the eyes and nasolabial folds in 1041 Japanese women. The results obtained revealed that 5 SNPs (19p13.2: rs2303098 (p = 3.39 × 10−8), rs56391955 (p = 3.39 × 10−8), rs67560822 (p = 3.50 × 10−8), rs889126 (p = 3.78 × 10−8), rs57490083 (p = 3.99 × 10−8)) located within the COL5A3 gene associated with wrinkles at the outer corners of the eyes. Regarding nasolabial folds, 8q24.11 (rs4876369; p = 1.05 × 10−7, rs6980503; p = 1.25 × 10−7, rs61027543; p = 1.25 × 10−7, rs16889363; p = 1.38 × 10−7) was suggested to be associated with RAD21 gene expression. These SNPs have not been reported in other populations, and were first found in Japanese women population. These SNPs may be used as markers to examine the genetic predisposition of individuals to wrinkles and sagging.