bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel meiotic protein required for homolog pairing and regulation of synapsis in C. elegans
Authors: Kim Hyung Jun , Dernburg Abby F.
Published: June 2022

Interactions between chromosomes and LINC (Linker of Nucleoskeleton and Cytoskeleton) complexes in the nuclear envelope (NE) promote homolog pairing and synapsis during meiosis. By tethering chromosomes to cytoskeletal motors, these connections lead to rapid, processive chromosome movements along the NE. This activity is usually mediated by telomeres, but in the nematode Caenorhabditis elegans special chromosome regions called “Pairing Centers” (PCs) have acquired this meiotic function. Through a genetic screen for mutations that cause meiotic nondisjunction, we discovered an uncharacterized meiosis-specific NE protein, MJL-1 (MAJIN-Like-1) that is essential for interactions between PCs and LINC complexes. MJL-1 colocalizes with PCs and LINC complexes during pairing and synapsis. Mutations in MJL-1 disrupt these interactions and eliminate active chromosome movements. mjl-1 mutants display promiscuous nonhomologous synapsis, reduced clustering of PCs, and severely impaired homolog pairing. MJL-1 likely interacts directly with SUN-1 and DNA-binding proteins to connect PCs to the LINC complex. Similarities in the molecular architecture of chromosome-LINC complex attachments between C. elegans and other organisms suggest that these connections may play previously unrecognized roles during meiosis across eukaryotes.
Enhanced mitochondrial biogenesis promotes neuroprotection in human stem cell derived retinal ganglion cells of the central nervous system
Authors: Surma Michelle , Anbarasu Kavitha , Dutta Sayanta , Olivera Perez Leonardo J. , Huang Kang-Chieh , Meyer Jason S. , Das Arupratan
Published: June 2022

Mitochondrial dysfunctions are widely afflicted in central nervous system (CNS) disorders with minimal understanding on how to improve mitochondrial homeostasis to promote neuroprotection. Here we used human stem cell differentiated retinal ganglion cells (hRGCs) of the CNS, which are highly sensitive towards mitochondrial dysfunctions due to their unique structure and function, to identify mechanisms for improving mitochondrial quality control (MQC). We found that hRGCs are efficient in maintaining mitochondrial homeostasis through rapid degradation and biogenesis of mitochondria under acute damage. Using a glaucomatous Optineurin mutant (E50K) stem cell lines, we saw that at basal level mutant hRGCs possess less mitochondrial mass and suffer mitochondrial swelling due to excess ATP production load. Activation of mitochondrial biogenesis through pharmacological inhibition of the Tank binding kinase 1 (TBK1) restored energy homeostasis, mitigated mitochondrial swelling with neuroprotection against acute mitochondrial damage for glaucomatousE50KhRGCs, revealing a novel neuroprotection mechanism.
The effect of transverse wavefront width on specular neutron reflection
Authors: Majkrzak C. F. , Berk N. F. , Maranville B. B. , Dura J. A. , Jach T.
Published: June 2022

In the analysis of neutron scattering measurements of condensed matter structure, it normally suffices to treat the incident and scattered neutron beams as if composed of incoherent distributions of plane waves with wavevectors of different magnitudes and directions that are taken to define an instrumental resolution. However, despite the wide-ranging applicability of this conventional treatment, there are cases, such as specular neutron reflectometry, in which the structural length scales of the scattering object require that the wavefunction of an individual neutron in the beam be described by a spatially localized packet – in particular with respect to the transverse extent of its wavefronts (i.e. normal to the packet's mean direction of propagation). It is shown in the present work that neutron diffraction patterns observed for periodic transmission phase gratings, as well as specular reflection measurements from patterned thin films with repeat units of the order of micrometres, can be accurately described by associating an individual neutron with a wave packet and treating a beam as a collection of independent packets. In these cases, accurate analysis requires that the transverse spatial extent of a neutron packet wavefront be accounted for in addition to the angular divergence of the beam that is characterized by a distribution of packet mean wavevector directions. It is shown how a measure of the effective transverse spatial extent of the neutron packet – over which its wavefronts are of sufficient uniformity to produce coherent scattering – can be determined by employing reference diffraction gratings and patterned thin films of known structure and composition.
Symmetry of antiferroelectric crystals crystallized in polar point groups
Authors: Shan Pai , Long Xifa
Published: June 2022

Symmetry is an essential concept in physics, chemistry and materials science. Comprehensive, authoritative and accessible symmetry theory can provide a strong impetus for the development of related materials science. Through the sustained efforts of physicists and crystallographers, researchers have mastered the relationship between structural symmetry and ferroelectricity, which demands crystallization in the 10 polar point groups. However, the symmetry requirement for antiferroelectricity is still ambiguous, and polar crystals possessing antiferroelectricity seem contradictory. This work systematically and comprehensively studies the transformation of dipole moments under symmetry operations, using accessible geometric methods and group theory. The results indicate crystals that crystallize in polar point groups 2 (C
2), m (C
1h), mm2 (C
2v), 4 (C
4), 4mm (C
4v), 3m (C
3v), 6 (C
6) and 6mm (C
6v) also possess anti-polar structure and are capable of Kittel-type antiferroelectricity. The anti-polar direction of each point group is also highlighted, which could provide a straightforward guide for antiferroelectric property measurement. Like ferroelectric crystals, antiferroelectric crystals belonging to polar point groups have great potential to become a family of important multifunctional electroactive and optical materials. This contribution refines antiferroelectric theory, will help facilitate and stimulate the discovery and rational design of novel antiferroelectric crystals, and enrich the potential functional applications of antiferroelectric materials.
Development of CryoVR, a virtual reality training system for hands-on cryoEM operations
Authors: Dong Jiahui , Li Daoyi , Ozcan Kadir , Wan Dayu , Jiang Wen , Chen Yingjie
Published: June 2022

Cryogenic electron microscopy (cryoEM) has emerged as a revolutionary method for solving high-resolution structures and studying the dynamics of macromolecular complexes and viruses in near-native states. However, the availability of the equipment, and the time and cost needed for training, severely limit the opportunities for training. To solve these problems, a virtual reality-based training system, CryoVR, has been developed to prepare trainees before operating real-world cryoEM equipment. This paper describes the design and assessment of CryoVR (available at https://www.purdue.edu/cryoVR), which helps users learn cryoEM experimental procedures in a virtual environment, allowing immersive training with step-by-step tutorials with vivid visual, audio and text guidance. Implemented as a training step before a novice user interacts with the expensive real-world cryoEM equipment, CryoVR can help users to become familiar with hands-on operational procedures through multiple training modules and earning certificates after passing the built-in Exam mode. Qualitative evaluation and feedback of CryoVR from users with various levels of cryoEM experience indicate the substantial value of CryoVR as a tool for a comprehensive cryoEM procedural training.
Evaluation and analysis of digital language archives development platforms: a parametric approach
Authors: Bharti Sneha , Singh Ranjeet Kumar
Published: June 2022

Purpose

While the obstacles of archiving endangered languages are significant, the question of which platform is best for building a digital language archive is constantly present. The purpose of this study is to evaluate and analyse digital language archives development platforms, such as content management systems (CMSs), digital repositories and archival collections management systems (ACMSs) using parameters that have been specified. The authors selected Mukurtu CMS, which is based on Drupal CMS; DSpace as the digital repository software; and ArchivesSpace as an ACMS in this study.

Design/methodology/approach

The current research is supported by a study of the literature and a detailed exploration of different systems used to develop digital language archives. The whole research is carried out in three steps: literature searching; identification of relevant literature; and parameter identification, exploration of tools and data reporting and analysis.

Findings

Following the technical and feature analysis of these tools, it can be concluded that they are more or less comparable, as well as constantly evolving, updating and having a bigger community base. It may be determined that DSpace is the most popular platform, but the other two, particularly ArchivesSpaces, are fierce competitors.

Research limitations/implications

This study outlines the technical prerequisites for creating a digital language archive, which will be useful to IT personnel working on these projects. The research is also useful for tool developers as it allows them to incorporate missing functionality and technical standards by comparing them to alternatives. The parameters established in this study can be used for similar studies in other domains, as well as for evaluating existing digital language archives.

Practical implications

The findings of this study have broad practical implications, and they can assist archivists, linguists, language communities and library and information science professionals in choosing an appropriate platform for building a digital language archive.

Originality/value

This study finds that there is relatively little effort made towards reviewing digital language archiving and the systems that are used to do it; thus, this study is carried out to assess and analyse digital language archive creation systems based on defined parameters. The parameters were discovered through a combination of the available literature and tool discovery. Using a parametric approach to evaluate tools yields unique insights and quickly reveals system flaws.
Configurations of financing instruments for supply chain cost reduction: evidence from Chinese manufacturing companies
Authors: Li Lixu , Wang Zhiqiang , Zhao Xiande
Published: June 2022

Purpose

Although supply chain finance (SCF) aims to optimize capital flows in the supply chain process, its effectiveness in improving cost performance remains controversial. From the perspective of efficiency motives, this study aims to explore how the combinations of SCF solutions and traditional financing instruments lead to supply chain cost reduction.

Design/methodology/approach

A mixed-method approach is used in this study. First, using the fuzzy-set qualitative comparative analysis (fsQCA), the authors analyze 405 survey data across four industries in China and identify the configurations of financing instruments for supply chain cost reduction. Second, to better understand the reasons behind each configuration, the authors conduct the content analysis on the interview data composed of 24 Chinese companies.

Findings

The authors find that the effectiveness of SCF solutions for supply chain cost reduction is related to the focal company's use of traditional financing instruments. Moreover, compared with guaranteed financing, companies that use credit financing are more likely to adopt SCF solutions to achieve supply chain cost reduction. Finally, the effectiveness of SCF solutions in reducing supply chain costs varies greatly across industries.

Practical implications

The study’s findings provide insights for policymakers and SCF practitioners in the aspects of simplifying the SCF application.

Originality/value

This study contributes to the current literature by addressing the theory–practice gap related to SCF. The study also provides new understandings of factors related to supply chain cost reduction, as well as factors that influence SCF adoption.
Portfolio diversification impact of oil and asymmetric interaction between oil, equity and bonds in the global market: fresh evidence from alternative approaches
Authors: Hatemi-J Abdulnasser , Roca Eduardo , Mustafa Alan
Published: June 2022

Purpose

In addition to the seminal approach of Markowitz (1952) that is based on finding the optimal budget shares for minimizing risk, the authors also make use of the approach developed by Hatemi-J and El-Khatib (2015), which is built on finding the weights as budget shares for maximizing the risk-adjusted return of the underlying portfolio. For testing the stability of the portfolio benefits, the asymmetric interaction between oil, equity and bonds is tested.

Design/methodology/approach

Oil is a major investment commodity. The literature shows mixed results regarding oils' ability to provide diversification benefits. This paper re-examines this issue by applying a new portfolio optimization approach.

Findings

The authors find that oil still yields portfolio diversification benefits; contrary to the traditional Markowitz portfolio approach, the asymmetric causality test results show that oil does not cause bonds for either positive or negative changes; however, oil does cause stocks but only for stocks' negative changes. Hence, oil can still make the returns of a portfolio of stocks and bonds unstable through oil's effect on stocks.

Originality/value

This is the first attempt to investigate the potential portfolio diversification benefits of stocks, bonds and oil by using the combination of risk and return explicitly in the optimization problem. The new insights provided by this article might be valuable to the investors, financial institutions and policy makers.
The primacy of corporate brand trust for new market entrants
Authors: Mal Carmen Iuliana , Davies Gary
Published: June 2022

Purpose

The purpose of this paper is to test if the order in which potential customers receive company related information and product related information about a new brand can influence their trust and purchase intentions towards that brand. The empirical context is when both product and company are new to a market and share a brand name.

Design/methodology/approach

Two experiments, each involving a different product type, are used to test whether higher trust and purchase intentions towards a new brand are likely when company related information is provided first compared to when product related information is provided first.

Findings

Company related information is more diagnostic than product related information and carries more weight in initial consumer trust judgements particularly when it is evaluated first. There is a similar primacy effect on purchase intentions but one mediated by initial trust. The effect is more pronounced for product types that involve a higher perceived risk when buying.

Research limitations/implications

This paper adds to our understanding of the respective roles of corporate and product communication in the process of brand trust formation for newly launched brands by evidencing and explaining primacy effects related to the greater diagnosticity of corporate brand information.

Practical implications

Market entrants should communicate information about their company before promoting their products.

Originality/value

While prior work has shown that both company and product related information can influence customers’ trust towards a new brand, there has been no assessment of the benefits from ordering these communications. The focus here is then on the processes involved in brand trust formation, rather than on identifying specific antecedents of brand trust.
Enrichment Mechanism and Prospects of Deep Oil and Gas
Authors: HAO Fang
Published: June 2022

With the deepening of oil and gas exploration, the importance of depth is increasingly highlighted. The risk of preservation of storage space in deep reservoirs is greater than that in shallow and medium layers. Deep layers mean older strata, more complex structural evolution and more complex hydrocarbon accumulation processes, and even adjustment and transformation of oil and gas reservoirs. This paper systematically investigates the current status and research progress of deep oil and gas exploration around the world and looks forward to the future research focus of deep oil and gas. In the deep, especially the ultra‐deep layers, carbonate reservoirs play a more important role than clastic rocks. Karst, fault‐karst and dolomite reservoirs are the main types of deep and ultra‐deep reservoirs. The common feature of most deep large and medium‐sized oil and gas reservoirs is that they formed in the early with shallow depth. Fault activity and evolution of trap highs are the main ways to cause physical adjustment of oil and gas reservoirs. Crude oil cracking and thermochemical sulfate reduction (TSR) are the main chemical modification effects in the reservoir. Large‐scale high‐quality dolomite reservoirs is the main direction of deep oil and gas exploration. Accurate identification of oil and gas charging, adjustment and reformation processes is the key to understanding deep oil and gas distribution. High‐precision detection technology and high‐precision dating technology are an important guarantee for deep oil and gas research.
The Role of Seal and Source Rocks in Fluid‐rock Interactions and their Reservoir Effects within the Carbonate Deep Burial Realm
Authors: LI Jie , CAI Zhongxian
Published: June 2022

Discoveries of deep high‐quality carbonate reservoirs challenged the general understanding on the evolution of porosity decreasing with depth. New mechanisms of pore generation and preservation in the deep realm require to be proposed. Dolostones in the Feixianguan and Dengying Formations experienced maximum depths in excess of 8000 m, but still retained high porosity. Petrographic observation and homogenization temperatures help to identify products of deep fluid‐rock interactions, visual and experimental porosity were used to quantify reservoir effects, the distribution of products finally being plotted to unravel the mechanisms. Th data reveal that thermochemical sulfate reduction (TSR), burial dissolution and quartz cementation are typical deep fluid‐rock interactions. The SO42– of residual porewater sourced from the evaporative dolomitizing fluid was supplied for TSR in the hydrocarbon column, the TSR‐inducing calcite cements were homogeneously dispersed in the hydrocarbon column. Quartz cementation was caused by the increasing acidity and Si‐rich residual porewater in the oil column. Burial dissolution is forced by organic acid and limited in oil–water contact. This study suggests that seal and source rocks not only play important roles in hydrocarbon accumulation, but also have a general control on the deep fluid‐rock interactions and porosity evolution in the deep burial realm.
Meta‐analysis: risk of hepatitis C virus infection associated with hospital‐based invasive procedures
Authors: Henriot Paul , Castry Mathieu , Luong Nguyen Liem Binh , Shimakawa Yusuke , Jean Kévin , Temime Laura
Published: June 2022

Background

Healthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood‐borne pathogens when compliance with infection control precautions is suboptimal.

Aims

To understand and quantify the role of hospital‐based invasive procedures on hepatitis C virus (HCV) transmission.

Methods

We conducted a systematic review and meta‐analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures. Based on expert opinion, invasive procedures were categorised into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country‐level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed by meta‐regression.

Results

We included 71 studies in the analysis. The most frequently evaluated procedures were blood transfusion (66 measures) and surgery (43 measures). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95% confidence interval: 1.14–1.88) for dental procedures to 3.22 (1.7–6.11) for transplantation. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42–5.88) than for those without a specified/recent date (2.20, 1.77–2.75). In procedure‐specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery.

Conclusions

Various invasive procedures were significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritisation of infection control interventions, especially in high HCV prevalence settings.
GATA2 deficiency and MDS/AML: Experimental strategies for disease modelling and future therapeutic prospects
Authors: Kotmayer Lili , Romero‐Moya Damia , Marin‐Bejar Oskar , Kozyra Emilia , Català Albert , Bigas Anna , Wlodarski Marcin W. , Bödör Csaba , Giorgetti Alessandra
Published: June 2022

The importance of predisposition to leukaemia in clinical practice is being increasingly recognized. This is emphasized by the establishment of a novel WHO disease category in 2016 called “myeloid neoplasms with germline predisposition”. A major syndrome within this group is GATA2 deficiency, a heterogeneous immunodeficiency syndrome with a very high lifetime risk to develop myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). GATA2 deficiency has been identified as the most common hereditary cause of MDS in adolescents with monosomy 7. Allogenic haematopoietic stem cell transplantation is the only curative option; however, chances of survival decrease with progression of immunodeficiency and MDS evolution. Penetrance and expressivity within families carrying GATA2 mutations is often variable, suggesting that co‐operating extrinsic events are required to trigger the disease. Predictive tools are lacking, and intrafamilial heterogeneity is poorly understood; hence there is a clear unmet medical need. On behalf of the ERAPerMed GATA2 HuMo consortium, in this review we describe the genetic, clinical, and biological aspects of familial GATA2‐related MDS, highlighting the importance of developing robust disease preclinical models to improve early detection and clinical decision‐making of GATA2 carriers.
A method based on plateletpheresis to obtain functional platelet,CD3+andCD14+matched populations for research immunological studies
Authors: Pablo‐Torres Carmela , Delgado‐Dolset María Isabel , Sanchez‐Solares Javier , Mera‐Berriatua Leticia , Núñez Martín Buitrago Lucía , Reaño Martos Mar , Bueno José Luis , Escribese Maria M. , Barber Domingo , Gomez‐Casado Cristina
Published: June 2022

Background

In previous studies with peripheral blood cells, platelet factors were found to be associated with severe allergic phenotypes. A reliable method yielding highly concentrated and pure platelet samples is usually not available for immunological studies. Plateletpheresis is widely used in the clinics for donation purposes. In this study, we designed a protocol based on plateletpheresis to obtain Platelet‐Rich Plasma (PRP), Platelet‐Poor Plasma (PPP) as well as CD3+and CD14+cells matched samples from a waste plateletpheresis product for immunological studies.

Methods

Twenty‐seven subjects were voluntarily subjected to plateletpheresis. PRP, PPP and blood cell concentrate contained in a leukocyte reduction system chamber (LRSC) were obtained in this process. CD3+and CD14+cells were isolated from the LRSC by density‐gradient centrifugation and positive magnetic bead isolation. RNA was isolated from PRP, CD3+and CD14+cell samples and used for transcriptomic studies by Affymetrix. PRP and PPP samples were used for platelet protein quantification by multiplex assays.

Results

A reliable high yield method to obtain matched samples of PRP, PPP, CD3+and CD14+from a single donor for RNA and protein analyses has been designed. The RNA quality indicators (RQI) routinely used for other cell types were not suitable for platelet RNA characterization. Despite this, the platelet RNA was valid for transcriptomic studies by Affymetrix, as platelet transcripts obtained in our previous studies were confirmed in PRP samples. Platelet samples were enriched in platelet factors as determined in protein multiplex analysis.

Conclusions

We have developed a method that yields not only high content and pure platelet samples from a single donor but also CD3+and CD14+matched samples that can be used for RNA and protein analyses in immunological studies.
Learning how to learn from social feedback: The origins of early vocal development
Authors: Elmlinger Steven L. , Schwade Jennifer A. , Vollmer Laura , Goldstein Michael H.
Published: June 2022

Infants’ prelinguistic vocalizations reliably organize vocal turn‐taking with social partners, creating opportunities for learning to produce the sound patterns of the ambient language. This social feedback loop supporting early vocal learning is well‐documented, but its developmental origins have yet to be addressed. When do infants learn that their non‐cry vocalizations influence others? To test developmental changes in infant vocal learning, we assessed the vocalizations of 2‐ and 5‐month‐old infants in a still‐face interaction with an unfamiliar adult. During the still‐face, infants who have learned the social efficacy of vocalizing increase their babbling rate. In addition, to assess the expectations for social responsiveness that infants build from their everyday experience, we recorded caregiver responsiveness to their infants’ vocalizations during unstructured play. During the still‐face, only 5‐month‐old infants showed an increase in vocalizing (a vocal extinction burst) indicating that they had learned to expect adult responses to their vocalizations. Caregiver responsiveness predicted the magnitude of the vocal extinction burst for 5‐month‐olds. Because 5‐month‐olds show a vocal extinction burst with unfamiliar adults, they must have generalized the social efficacy of their vocalizations beyond their familiar caregiver. Caregiver responsiveness to infant vocalizations during unstructured play was similar for 2‐ and 5‐month‐olds. Infants thus learn the social efficacy of their vocalizations between 2 and 5 months of age. During this time, infants build associations between their own non‐cry sounds and the reactions of adults, which allows learning of the instrumental value of vocalizing.
Participation of children and young people with cerebral palsy in activities of daily living in rural Uganda
Authors: Andrews Carin , Namaganda Lukia Hamid , Imms Christine , Eliasson Ann‐Christin , Asige Elizabeth , Wanjala Godfrey , Kakooza‐Mwesige Angelina , Forssberg Hans
Published: June 2022

Aim

To compare the participation attendance and involvement of children and young people with and without cerebral palsy (CP) in a low‐resource area of Uganda.

Method

Eighty‐two children and young people with CP aged 6 to 22 years (49 males, 33 females) and 81 age‐ and sex‐matched peers without CP (6 to 22 years; 48 males, 33 females) participated in this population‐based, cross‐sectional study. Data on attendance and involvement in 20 home and community activities were obtained using Picture My Participation, an instrument intended to measure participation in children with disabilities, particularly in low‐ and middle‐income countries. Non‐parametric statistical methods were used to assess between‐group differences. Effect size estimates were calculated.

Results

Pooled attendance across all activities was lower in children and young people with CP than in children and young people without CP (p < 0.001) and for each activity item (p = 0.004 to p < 0.001). The effect sizes for each activity were 0.2 to 0.7. Between‐group differences were larger for community activities than for home activities. Pooled involvement across all activities was less in the group with CP (p < 0.001) and for each activity (p = 0.014 to p < 0.001). The effect sizes for each activity were 0.2 to 0.5. Children and young people in Gross Motor Function Classification System (GMFCS) levels I and II had higher attendance (p < 0.001) and involvement (p = 0.023) than those in GMFCS levels III to V.

Interpretation

Participation of young people living with CP in Uganda was restricted, especially for community activities. There is a need to identify context‐specific participation barriers and develop strategies to overcome them.

What this paper adds

Children and young people with cerebral palsy (CP) attended all activities less than their peers without CP.

Differences in attendance were larger for community‐based activities than home activities.

When attending activities, children and young people with CP were less involved than their peers.

Children and young people with milder impairments attended less frequently than their peers without CP.

Children and young people with milder impairments attended more frequently than their peers with severe impairments.
Co‐evolutionary adaptations of Acinetobacter baumannii and a clinical carbapenemase‐encoding plasmid during carbapenem exposure
Authors: Zhang Linyue , Fu Ying , Zhang Linghong , Xu Qingye , Yang Yunxing , He Jintao , Leptihn Sebastian , Loh Belinda , Moran Robert A. , van Schaik Willem , Toleman Mark Alexander , Chen Qiong , Liu Lilin , Yu Yunsong , Hua Xiaoting
Published: June 2022

OXA‐23 is the predominant carbapenemase in carbapenem‐resistant Acinetobacter baumannii. The co‐evolutionary dynamics of A. baumannii and OXA‐23‐encoding plasmids are poorly understood. Here, we transformed A. baumannii ATCC 17978 with pAZJ221, a blaOXA−23‐containing plasmid from clinical A. baumannii isolate A221, and subjected the transformant to experimental evolution in the presence of a sub‐inhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of blaOXA−23 in pAZJ221, interfering allele dynamics, and chromosomal locus‐level parallelism were observed. To characterize genotype‐to‐phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3′ → 5′) GMP‐metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the effects of these mutations on fitness costs and plasmid kinetics, and the evolved plasmid containing two copies of blaOXA−23 was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of blaOXA−23 increased host fitness under carbapenem pressure but imposed a burden on the host in antibiotic‐free media relative to the ancestral pAZJ221. Overall, our study provides a framework for the co‐evolution of A. baumannii and a clinical blaOXA−23‐containing plasmid in the presence of imipenem, involving early blaOXA−23 duplication followed by chromosomal adaptations that improved the fitness of plasmid‐carrying cells.
Mean‐stress sensitivity of an ultrahigh‐strength steel under uniaxial and torsional high and very high cycle fatigue loading
Authors: Schönbauer Bernd M. , Ghosh Sumit , Karr Ulrike , Pallaspuro Sakari , Kömi Jukka , Frondelius Tero , Mayer Herwig
Published: June 2022

The influence of load ratio on the high and very high cycle fatigue (VHCF) strength of Ck45M steel processed by thermomechanical rolling integrated direct quenching was investigated. Ultrasonic fatigue tests were performed under uniaxial and torsional loading at load ratios ofR = −1, 0.05, 0.3, and 0.5 with smooth specimens and specimens containing artificially introduced defects. Up to 2 × 105 cycles, failure originated from surface aluminate inclusions and pits under both loading conditions. The prevailing fracture mechanisms in the VHCF regime were interior crack initiation under uniaxial loading and surface shear crack initiation under torsional loading. The mean‐stress sensitivity and the fatigue strength were evaluated using fracture mechanics approaches. Equal fatigue limits for uniaxial and torsional loading were determined considering the size of crack initiating defects and the appropriate threshold condition for Mode‐I crack growth. Furthermore, the mean‐stress sensitivity is independent of loading condition and can be expressed by and .
Agglomeration, resource reallocation and domestic value‐added ratio in exports
Authors: Liu Xinheng , Pan Ziyuan , Fang Dongli
Published: June 2022

Using micro merged data of China's customs transaction and National Bureau of Statistics Annual Surveys of Industrial Firms data, this paper analyzes the effect of industrial agglomeration on domestic value‐added in exports to gross exports (DVAR). It is found that industrial agglomeration significantly improves DVAR. Mechanism tests show that industrial agglomeration promotes DVAR by increasing the relative price of imported intermediate inputs and domestic inputs (relative price effect), as well as restrains DVAR by restraining cost markup of firm (cost markup effect). However, the promotion effect of the “relative price effect” is greater than the restraint effect of the “cost markup effect”. In addition, accession to the World Trade Organization and exchange reform strengthen the promotion effect of industrial agglomeration. The result of dynamic decomposition shows that 74.62% of the industry's DVAR increase is attributed to the resource re‐allocation effect, which is an important channel for industrial agglomeration to promote DVAR.
WHOClassification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer
Authors: Kench James G , Amin Mahul B , Berney Daniel M , Compérat Eva M , Cree Ian A , Gill Anthony J , Hartmann Arndt , Menon Santosh , Moch Holger , Netto George J , Raspollini Maria R , Rubin Mark A , Tan Puay Hoon , Tsuzuki Toyonori , Turjalic Samra , van der Kwast Theo H , Zhou Ming , Srigley John R
Published: June 2022

The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in the assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: (1) recognition that prostatic intraepithelial neoplasia (PIN)‐like carcinoma is not synonymous with a pattern of ductal carcinoma, but better classified as a subtype of acinar adenocarcinoma; (2) a specific section on treatment‐related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; (3) a terminology change of basal cell carcinoma to “adenoid cystic (basal cell) cell carcinoma” given the presence of an underlyingMYB::NFIBgene fusion in many cases; (4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and (5) more detailed coverage of intraductal carcinoma of prostate (IDC‐P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC‐P but containing more atypia than typically seen in high‐grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.
Wheat bread fortified with Dictyophora Indusiata powder: evaluation of quality attributes, antioxidant characteristics and bread staling
Authors: Liu Yudi , Zhang Heng , Yu Hongda , Li Jiang , Brennan Margaret A , Brennan Charles S , Qin Yuyue
Published: June 2022

This study aimed to investigate the physical, nutritional, antioxidant and sensory properties, as well as the starch digestibility of wheat bread containing Dictyophora Indusiata powder (DIP) as a functional addition. Results showed that though the specific volume of wheat breads decreased with the addition of DIP, the chewiness showed an increasing trend. The wheat bread containing DIP showed significantly higher (P < 0.05) content of protein and dietary fibre compared to the control bread. On the other hand, with the addition of DIP, the total phenolic content and antioxidant properties of wheat bread significantly (P < 0.05) increased. The moisture and texture of bread during storage improved significantly (P < 0.05), and the enthalpy of bread decreased significantly (P < 0.05) in staling period. In conclusion, the wheat bread added with DIP could be a feasible baking product with improved nutritional, antioxidant properties and bread staling.
Suppression of airway allergic eosinophilia by Hp‐TGM, a helminth mimic of TGF‐β
Authors: Chauché Caroline , Rasid Orhan , Donachie Anne‐Marie , McManus Caitlin M. , Löser Stephan , Campion Tiffany , Richards Josh , Smyth Danielle J. , McSorley Henry J. , Maizels Rick M.
Published: June 2022

Type 2‐high asthma is a chronic inflammatory disease of the airways which is increasingly prevalent in countries where helminth parasite infections are rare, and characterized by T helper 2 (Th2)‐dependent accumulation of eosinophils in the lungs. Regulatory cytokines such as TGF‐β can restrain inflammatory reactions, dampen allergic Th2 responses, and control eosinophil activation. The murine helminth parasite Heligmosomoides polygyrus releases a TGF‐β mimic (Hp‐TGM) that replicates the biological and functional properties of TGF‐β despite bearing no structural similarity to the mammalian protein. Here, we investigated if Hp‐TGM could alleviate allergic airway inflammation in mice exposed to Alternaria alternata allergen, house dust mite (HDM) extract or alum‐adjuvanted ovalbumin protein (OVA). Intranasal administration of Hp‐TGM during Alternaria exposure sharply reduced airway and lung tissue eosinophilia along with bronchoalveolar lavage fluid IL‐5 and lung IL‐33 cytokine levels at 24 h. The protective effect of Hp‐TGM on airway eosinophilia was also obtained in the longer T‐cell mediated models of HDM or OVA sensitisation with significant inhibition of eotaxin‐1, IL‐4 and IL‐13 responses depending on the model and time‐point. Hp‐TGM was also protective when administered parenterally either when given at the time of allergic sensitisation or during airway allergen challenge. This project has taken the first steps in identifying the role of Hp‐TGM in allergic asthma and highlighted its ability to control lung inflammation and allergic pathology. Future research will investigate the mode of action of Hp‐TGM against airway allergic eosinophilia, and further explore its potential to be developed as a biotherapeutic in allergic asthma.
Calcium controlled NFATc1 activation enhances suppressive capacity of regulatory T cells isolated from generalized vitiligo patients
Authors: Giri Prashant S. , Bharti Ankit H. , Begum Rasheedunnisa , Dwivedi Mitesh
Published: June 2022

NFATs and FOXP3 are linked with impaired regulatory T‐cells (Tregs) in generalized vitiligo (GV). To elucidate calcium mediated NFATc1 signalling pathway and its effect on Treg suppressive capacity in GV. Calcium levels, calcineurin, NFATc1 and GSK‐3β activity and cell proliferation were assessed in 52 GV patients and 50 controls by calcium assay kit, calcineurin phosphatase assay kit, TransAM NFATc1 kit, GSK‐3β ELISA and BrdU cell proliferation assay. Transcripts (CNB, CAM, GSK3B, DYRK1A and calcium channel genes) and protein (IFN‐γ, IL‐10 and TGF‐β) expressions were assessed by qPCR and ELISA, respectively. Reduced plasma and intracellular Tregs calcium levels and ORAI1 transcripts suggested altered calcium homeostasis in GV Tregs (p = 0.00387, p = 0.0048, p < 0.0001), which led to decreased calcineurin and NFATc1 activity in GV Tregs (p = 0.0299, p < 0.0001). CNB and CAM transcripts were reduced in GV Tregs (p < 0.0001, p = 0.0004). GSK‐3β activity, GSK3B and DYRK1A transcripts significantly increased in GV Tregs (p = 0.0134, p < 0.0001 and p < 0.0001). Plasma (p = 0.0225, p = 0.032) and intracellular Treg (p = 0.0035, p = 0.005) calcium levels, calcineurin (p = 0.001) and NFATc1 (p = 0.001, p < 0.0001) activity and ORAI1 (p = 0.0093, p < 0.0001), CAM and CNB (p = 0.0214) transcripts significantly decreased in active vitiligo (AV) and severe GV (sGV) Tregs. Calcium treatment significantly increased intracellular calcium and ORAI1 transcripts in GV Tregs (p = 0.0042, p = 0.0035). Moreover, calcium treatment enhanced calcineurin and NFATc1 activity in GV Tregs (p = 0.0128, p < 0.0001). Remarkably, calcium treatment increased Treg mediated suppression of CD4+ and CD8+ T‐cells (p = 0.015, p = 0.006) in GV and increased Tregs associated cytokines: IL‐10 (p = 0.0323, p = 0.009), TGF‐β (p = 0.0321, p = 0.01) and decreased IFN‐γ production (p = 0.001, p = 0.016) by CD4+ and CD8+ T‐cells. Intracellular calcium levels positively correlated with calcineurin (r = 0.83; p < 0.0001) and NFATc1 (r = 0.61; p < 0.0001) activity, suggesting the enhanced Treg immunosuppressive capacity after calcium treatment. Our study for the first time suggests that reduced plasma calcium and ORAI1 transcripts are linked to calcium uptake defects in Tregs, which leads to reduced calcineurin and NFATc1 activation, thereby contributing to decreased Tregs immunosuppressive capacity in GV. Elevated GSK‐3β activity and GSKB and DYRK1A transcripts are involved in reduced NFATc1 activity in GV Tregs. Overall, the study suggests that calcium‐NFATc1‐signalling pathway is likely to be involved in defective Tregs function and can be implicated for development of effective Treg mediated therapeutics for GV.
Immunogenicity and safety of SpikoGen®, an adjuvanted recombinant SARS‐CoV‐2 spike protein vaccine as a homologous and heterologous booster vaccination: A randomized placebo‐controlled trial
Authors: Tabarsi Payam , Anjidani Nassim , Shahpari Ramin , Roshanzamir Khashayar , Fallah Newsha , Andre Greiciely , Petrovsky Nikolai , Barati Saghar
Published: June 2022

SpikoGen® is a subunit recombinant spike protein vaccine combined with Advax‐CpG55.2™ adjuvant. This COVID‐19 vaccine was shown to be safe, immunogenic and efficacious in previous clinical trials. This study aimed to assess the safety and immunogenicity of SpikoGen® vaccine as a homologous and heterologous booster vaccination. This double‐blind and randomized placebo‐controlled (5:1) trial was performed on 300 already vaccinated participants. SpikoGen® or saline placebo was administered as a booster dose to participants who had received a full two‐dose COVID‐19 vaccination course. Immunogenicity assessments were done 14 days after the booster dose with the primary immunogenicity outcome seroconversion rate of neutralizing antibodies. Safety outcomes included the incidence of solicited adverse events up to 7 days after the booster dose. SpikoGen® vaccine induced a robust humoral response both as a homologous and heterologous booster, when compared to the placebo. At Day 14, seroconversion of neutralizing antibodies was 76% (95% confidence interval [CI]: 69%–82%) in the SpikoGen® group versus 3% (95% CI: 0%–13%) in the placebo group. The most common local and systemic reported adverse events were injection site pain and fatigue. No serious adverse events were reported. The SpikoGen®‐booster induced cross‐neutralization of other SARS‐CoV‐2 variants. Irrespective of the primary vaccine course received, SpikoGen® vaccine showed promising effects as both a homologous and heterologous booster dose. This vaccine also had a good safety profile with no vaccine‐associated serious adverse events. On the basis of these results, SpikoGen® vaccine has been approved as a booster dose.
Molecular characterization and antimicrobial susceptibility of Corynebacterium pseudotuberculosis isolated from skin abscesses of native Korean goats (Capra hircus coreanae)
Authors: Pathirana Hansani Nilupama Kumari Senarath , Cho Ho-Seong , Cho Yong-Il , Kim Chan-Lan , Wimalasena Sudu Hakuruge Madusha Pramud , Rajapaksha Lansakara Gedara Thilini Ganga , Gunasekara Chathura Wikumpriya Rusiri , Kim Chong-Han , Seo Byoung-Joo , Moon Sung-Hyun , Park Jin-Ho , Shin Gee-Wook
Published: June 2022

Aims

This study aimed to investigate the molecular characterization and antimicrobial susceptibility of Corynebacterium pseudotuberculosis from skin abscesses of Korean native black goats (KNBG, Capra hircus coreanae) in South Korea.

Methods and results

A total of 83 isolates were recovered from skin abscesses of KNBG. Of these isolates, 74 isolates were identified as C. pseudotuberculosis by phospholipase D (PLD) gene-based PCR assay. Each of the isolates possessed all 18 virulence genes (FagA, FagB, FagC, FagD, SigE, SpaC, SodC, PknG, NanH, OppA, OppB, OppC, OppD, OppF, CopC, NrdH and CpaE). The genetic diversity of C. pseudotuberculosis isolates was assessed by the phylogenetic analysis using the concatenated sequences (3073 bp) of five housekeeping genes (fusA, dnaK, infB, groeL1 and leuA) for investigating their genetic diversity. In the results, the isolates belonged to three groups: group 1 (67 isolates), group 2 (one isolate) and group 3 (six isolates) within biovar ovis. However, the groups exhibited low genetic diversity (0.20%–0.41%). In the antimicrobial susceptibility test, most isolates were susceptible to tetracycline, vancomycin, chloramphenicol, ciprofloxacin, erythromycin, enrofloxacin, cefoxitin, ampicillin, gentamycin, cephalothin and doxycycline, whereas they were not susceptible to cefotaxime, trimethoprim and streptomycin.

Conclusion

This results suggest the involvement of relatively few clones of C. pseudotuberculosis in Korea. Further, present isolates can threaten public health due to potentially virulent strains with all 18 virulence genes and non-susceptible strains to clinically important antibiotics (CIA) and highly important antibiotics.

Significance and Impact of the Study

This study is the first to investigate the genetic diversity and potential pathogenicity of C. pseudotuberculosis biovar ovis isolates from skin abscesses of KBNG in South Korea, and could provide useful information in controlling its infections.