bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Three-way fusion image segmentation for early esophageal cancer detection
Authors: Ren Xintong , Zhang Zhen , Jiang Junchao , Li Guodong , Jiang Jiahua , Ren Wuwei , Jia Xinyong
Published: August 2022

Objective

Esophageal cancer (EC) is a prevalent malignancy worldwide. Early-stage esophageal cancer (EEC) diagnostics is crucial for improving patient survival. However, EC is highly aggressive with a poor prognosis, even for experienced endoscopists. To address these problems, this study aims to develop a novel computer-aided diagnosis (CAD) method to improve the accuracy and efficiency of EEC diagnostics.

Methods

Three-way fusion CAD method that employs multiple frameworks, including the hybrid task cascade ResNeXt101 with deformable convolutional networks, to accurately detect EC. Our method incorporates dual annotation categories on ME-NBI imaging from a local perspective and one category on LCE imaging from an broader perspective. This integration provides a substantial improvement of accuracy over traditional CAD technologies.

Results

Our three-way fusion CAD method achieved top performances of 0.923 mAP on ME-NBI and 0.862 mAP on LCE, demonstrating superior diagnostic performance compared to traditional CAD methods. Furthermore, the treatment boundary mAP is expected to be even higher by definition in clinical settings. Our method also achieved promising precision and recall rates of 93.98% and 93.05% for ME-NBI, and 82.89% and 88.32% for LCE, respectively.

Conclusions

Our novel three-way fusion CAD method accurately detects EC in both ME-NBI and LCE imaging, providing accurate treatment boundaries on both image and patient levels. Our approach shows potential for clinical application, with promising mAP, precision, and recall rates. Further work will focus on collecting and analyzing patient data to improve the method’s real-time performance in clinical settings.
A sagittal gradient of pathological and compensatory effects of neurophysiological slowing in Parkinson’s disease
Authors: Wiesman Alex I. , da Silva Castanheira Jason , Degroot Clotilde , Fon Edward A. , Baillet Sylvain ,   PREVENT-AD Research Group,   Quebec Parkinson Network
Published: August 2022

Using magnetoencephalographic imaging and extensive clinical and neuropsychological assessments, we show that patients with Parkinson’s disease (PD; N = 79) exhibit a slowing of neurophysiological activity relative to healthy adults (N = 65), which relates to motor and cognitive abilities. Importantly, the association between neurophysiological slowing and PD clinical features varies systematically across the cortex along a sagittal gradient: cortical slowing is associated with worse impairment in dorsal-posterior cortices, and this association is reversed in ventral-anterior cortical regions. This pathological-to- compensatory anatomical gradient is sensitive to differences in patients’ individual clinical profiles, and co- localizes with normative atlases of neurotransmitter receptor/transporter density. Long-range functional connectivity between posterior regions and parietal and frontal cortices is also significantly shifted towards lower frequencies in PD, demonstrating a novel network-level slowing effect. Taken together, these findings demonstrate the multifaceted nature of neurophysiological slowing in patients with PD, with anatomically-dependent clinical relevance to motor and cognitive symptoms.
Plasmodesmata-located proteins regulate plasmodesmal function at specific cell interfaces in Arabidopsis
Authors: Li Zhongpeng , Liu Su-Ling , Montes-Serey Christian , Walley Justin W. , Aung Kyaw
Published: August 2022

Plasmodesmata (PD) are membrane-lined channels connecting adjoining plant cells. PD control symplasmic intercellular communication by allowing molecules to move between cells. Plant polysaccharide callose (ß-1,3-glucan) is deposited at PD, affecting plasmodesmal function; however, the regulation of PD at different cell interfaces is largely unknown. This study discovered that two PD-located proteins, PDLP5 and PDLP6, are expressed in non-overlapping cell types. The constitutive expression of PDLP5 and PDLP6 results in the overaccumulation of PD callose at different cell interfaces and starch hyperaccumulation in different cell types within mature leaves. Using a proximity labeling approach, we identified sucrose synthase 6 (SUS6) as a functional partner of PDLP6. We further demonstrated that PDLP6 physically and genetically interacts with SUS6. In addition, callose synthase 7 (CalS7) interacts with both SUS6 and PDLP6 and is required for PDLP6’s function. We propose that PDLP6-SUS6-CalS7 forms a callose synthase complex in the vasculature to regulate the plasmodesmal function.
The evolution of two transmissible leukaemias colonizing the coasts of Europe
Authors: Bruzos Alicia L. , Santamarina Martín , García-Souto Daniel , Díaz Seila , Rocha Sara , Zamora Jorge , Lee Yunah , Viña-Feás Alejandro , Quail Michael A. , Otero Iago , Pequeño-Valtierra Ana , Temes Javier , Rodriguez-Castro Jorge , Villanueva Antonio , Costas Damián , Rodríguez Rosana , Prieto Tamara , Tomás Laura , Alvariño Pilar , Alonso Juana , Cao Asunción , Iglesias David , Carballal María J. , Amaral Ana M. , Balseiro Pablo , Calado Ricardo , El Khalfi Bouchra , Izagirre Urtzi , de Montaudouin Xavier , Pade Nicolas G. , Probert Ian , Ricardo Fernando , Ruiz Pamela , Skazina Maria , Smolarz Katarzyna , Pasantes Juan J. , Villalba Antonio , Ning Zemin , Ju Young Seok , Posada David , Demeulemeester Jonas , Baez-Ortega Adrian , Tubio Jose M. C.
Published: August 2022

Transmissible cancers are malignant cell clones that spread among individuals through transfer of living cancer cells. Several such cancers, collectively known as bivalve transmissible neoplasia (BTN), are known to infect and cause leukaemia in marine bivalve molluscs. This is the case of BTN clones affecting the common cockle,Cerastoderma edule, which inhabits the Atlantic coasts of Europe and north-west Africa. To investigate the origin and evolution of contagious cancers in common cockles, we collected 6,854C. edulespecimens and diagnosed 390 cases of BTN. We then generated a reference genome for the species and assessed genomic variation in the genomes of 61 BTN tumours. Analysis of tumour-specific variants confirmed the existence of two cockle BTN lineages with independent clonal origins, and gene expression patterns supported their status as haemocyte-derived marine leukaemias. Examination of mitochondrial DNA sequences revealed several mitochondrial capture events in BTN, as well as co-infection of cockles by different tumour lineages. Mutational analyses identified two lineage-specific mutational signatures, one of which resembles a signature associated with DNA alkylation. Karyotypic and copy number analyses uncovered genomes marked by pervasive instability and polyploidy. Whole-genome duplication, amplification of oncogenesCCND3andMDM2, and deletion of the DNA alkylation repair geneMGMT, are likely drivers of BTN evolution. Characterization of satellite DNA identified elements with vast expansions in the cockle germ line, yet absent from BTN tumours, suggesting ancient clonal origins. Our study illuminates the evolution of contagious cancers under the sea, and reveals long-term tolerance of extreme instability in neoplastic genomes.
A yeast-based system to study SARS-CoV-2 Mpro structure and to identify nirmatrelvir resistant mutations
Authors: Ou Jin , Lewandowski Eric M. , Hu Yanmei , Lipinski Austin A. , Morgan Ryan T. , Jacobs Lian M.C. , Zhang Xiujun , Bikowitz Melissa J. , Langlais Paul , Tan Haozhou , Wang Jun , Chen Yu , Choy John S.
Published: August 2022

The SARS-CoV-2 main protease (Mpro) is a major therapeutic target. The Mpro inhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As Mpro inhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as a proxy for Mpro activity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays showed that an E166R substitution conferred strong nirmatrelvir resistance while an E166N mutation compromised activity. On the other hand, N142A and P132H mutations caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of Mpro E166R, and Mpro E166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of Mpro that may arise as Mpro antivirals become more widely used.
CSL-Tox: An open-source analytical framework for the comparison of short-term and long-term toxicity end points and exploring the opportunities for decreasing in-vivo studies conducted for drug development programs
Authors: Naga Doha , Dimitrakopoulou Smaragda , Roberts Sonia , Husar Elisabeth , Mohr Susanne , Booler Helen , Musvasva Eunice
Published: August 2022

In-vivo toxicity assessment is an important step prior to clinical development and is still the main source of data for overall risk assessment of a new molecular entity (NCE). All in-vivo studies are performed according to regulatory requirements and many efforts have been exerted to minimize these studies in accordance with the (Replacement, Reduction and Refinement) 3Rs principle. Many aspects of in-vivo toxicology packages can be optimized to reduce animal use, including the number of studies performed as well as study durations, which is the main focus of this analysis. We performed a statistical comparison of adverse findings observed in 116 short-term versus 78 long-term studies in order to explore the possibility of using only short-term studies as a prediction tool for the longer-term effects. Annotation of treatment related findings was one of the challenges faced during this work. A specific focus was therefore put on the summary and conclusion sections of the reports since they contain expert assessments on whether the findings were considered adverse or were attributed to other reasons. Our analysis showed a general good concordance between short-term and long-term toxicity findings for large molecules and the majority of small molecules. Less concordance was seen for certain “target organ systems findings’. While this work supports the minimization of in-vivo study durations, a larger-scale effort would be needed to provide more evidence. We therefore present the steps performed in this study as an open-source R workflow (CSL-Tox) and we provide the dataset used in the work to allow researchers to reproduce such analysis and to promote large-scale application of this study.
The Defenders of the Alveolus Succumb in COVID-19 Pneumonia to SARS-CoV-2, Necroptosis, Pyroptosis and Panoptosis
Authors: Schifanella Luca , Anderson Jodi , Wieking Garritt , Southern Peter J. , Antinori Spinello , Galli Massimo , Corbellino Mario , Lai Alessia , Klatt Nichole , Schacker Timothy W. , Haase Ashley T.
Published: August 2022

The alveolar type II (ATII) pneumocyte has been called the defender of the alveolus because, amongst the cell’s many important roles, repair of lung injury is particularly critical. We investigated the extent to which SARS-CoV-2 infection incapacitates the ATII reparative response in fatal COVID-19 pneumonia, and describe massive infection and destruction of ATI and ATII cells. We show that both type I interferon-negative infected ATII and type I-interferon-positive uninfected ATII cells succumb to TNF-induced necroptosis, BTK-induced pyroptosis and a new PANoptotic hybrid form of inflammatory cell death that combines apoptosis, necroptosis and pyroptosis in the same cell. We locate pathway components of these cell death pathways in a PANoptosomal latticework that mediates emptying and disruption of ATII cells and destruction of cells in blood vessels associated with microthrombi. Early antiviral treatment combined with inhibitors of TNF and BTK could preserve ATII cell populations to restore lung function and reduce hyperinflammation from necroptosis, pyroptosis and panoptosis.

Graphic

Highlights

In fatal COVID-19 pneumonia, the initial destruction of Type II alveolar cells by SARS-CoV-2 infection is amplified by infection of the large numbers of spatially contiguous Type II cells supplied by the proliferative reparative response.

Interferon-negative infected cells and interferon-positive uninfected cells succumb to inflammatory forms of cell death, TNF-induced necroptosis, BTK-induced pyroptosis, and PANoptosis.

All of the cell death pathway components, including a recently identified NINJ1 component, are localized in a PANoptosome latticework that empties in distinctive patterns to generate morphologically distinguishable cell remnants.

Early combination treatment with inhibitors of SARS-CoV-2 replication, TNF and BTK could reduce the losses of Type II cells and preserve a reparative response to regenerate functional alveoli.
Heart Rate Variability During Mindful Breathing Meditation
Authors: Natarajan Aravind
Published: August 2022

In this article, we discuss Heart Rate Variability (HRV) measured during mindful breathing meditation. We provide a pedagogical computation of 2 commonly used HRV metrics, i.e. the root mean square of successive differences (RMSSD) and the standard deviation of RR intervals (SDRR), in terms of Fourier components. It is shown that the RMSSD preferentially weights higher frequency Fourier modes, making it unsuitable as a biosignal for mindful breathing meditation which encourages slow breathing. We propose a new metric called the autonomic balance index (ABI) which uses Respiratory Sinus Arrhythmia to quantify the fraction of HRV contributed by the parasympathetic nervous system. We apply this metric to HRV data collected during two different meditation techniques, and show that the ABI is significantly elevated during mindful breathing, making it a good signal for biofeedback during meditation sessions.
Fadrozole-mediated sex reversal in the embryonic chicken gonad involves a PAX2 positive undifferentiated supporting cell state
Authors: Estermann Martin A. , Smith Craig A.
Published: August 2022

Gonadal sex differentiation among vertebrates involves divergent fates of a common groups of progenitor cells present in both presumptive ovaries and testes. The first cell type to differentiate gives rise to pre-Sertoli cells in the testis, and pre-follicular cells in the ovary. These cells derive form a common lineage of so-called “supporting cells”. In birds and other egg-laying vertebrates, locally synthesised estrogen has a central role in ovarian development and influence the fate of these supporting cells. Manipulation of estrogen levels during embryonic development induces gonadal sex reversal, providing an experimental setting to evaluate the process of gonadal sex differentiation. Recently, we identified PAX2 as a novel marker of the undifferentiated supporting cell lineage in the chicken embryo, expressed in both sexes prior to overt gonadal sex differentiation. PAX2 expression is downregulated at the onset of gonadal sex differentiation in both males and females. The analysis of this undifferentiated supporting cell marker, together with Sertoli (male) and pre-granulosa (female) will enhance our understanding of supporting cell differentiation. Here we characterized the supporting cells differentiation process and identified undifferentiated supporting cells in estrogen-mediated sex reversal experiments. Female embryos treated with the aromatase inhibitor fadrozole developed ovotestis, containing pre-granulosa cells, Sertoli cells and PAX2 positive undifferentiated supporting cells. In contrast, male embryos treated with 17β-estradiol showed no PAX2+ undifferentiated gonadal supporting cells. Fadrozole time-course as well as multiple dose analysis suggests that supporting cell transdifferentiation involves a dedifferentiation event into a PAX2+ undifferentiated supporting cell state, followed by a redifferentiation towards the opposite sex lineage.
Warm blood meal increases digestion rate and milk protein production to maximize reproductive output for the tsetse fly, Glossina morsitans
Authors: Benoit Joshua B. , Lahondère Chloé , Attardo Geoffrey M. , Michalkova Veronika , Oyen Kennan , Xiao Yanyu , Aksoy Serap
Published: August 2022

The ingestion of blood represents a significant pressure that immediately increases water, oxidative, and thermal stress, but provides a significant nutrient source to generate resources necessary for the development of progeny. Thermal stress has been assumed to solely be a negative byproduct that has to be alleviated to prevent stress. Here, we examined if the short thermal bouts incurred during a warm blood meal are beneficial to reproduction. To do so, we examined the duration of pregnancy and milk gland protein expression in the tsetse fly, Glossina morsitans, that consumed a warm or cool blood meal. We noted that an optimal temperature for blood ingestion yielded a reduction in the duration of pregnancy. This decline in the duration of pregnancy is due to increased rate of blood digestion when consuming warm blood. This increased digestion likely provided more energy that leads to increased expression of transcript for milk-associated proteins. The shorter duration of pregnancy is predicted to yield an increase in population growth compared to those that consume cool or above host temperatures. These studies provide evidence that consumption of a warm blood meal is likely beneficial for specific aspects of vector biology.
HiCAT: A tool for automatic annotation of centromere structure
Authors: Gao Shenghan , Yang Xiaofei , Zhao Xixi , Wang Bo , Ye Kai
Published: August 2022

Significant improvements in long-read sequencing technologies have unlocked complex genomic areas, such as centromeres, in the genome and introduced the centromere annotation problem. Currently, centromeres are annotated in a semi-manual way. Here, we propose HiCAT, a generalizable automatic centromere annotation tool, based on hierarchical tandem repeat mining and maximization of tandem repeat coverage to facilitate decoding of centromere architecture. We applied HiCAT to human CHM13-T2T and gapless Arabidopsis thaliana genomes. Our results not only were generally consistent with previous inferences but also greatly improved annotation continuity and revealed additional fine structures, demonstrating HiCAT’s performance and general applicability.
The glycolipid GlcCer is recruited into the viral envelope to promote phenuivirus binding to host cells
Authors: Uckeley Zina M. , Mazelier Magalie , Lüchtenborg Christian , Winter Sophie L. , Schad Paulina , Chlanda Petr , Brügger Britta , Lozach Pierre-Yves
Published: August 2022

Virus–receptor interactions largely contribute to the tropism and outcome of an infection. Here, we found that the glycolipid glucosylceramide (GlcCer) is a major component of Uukuniemi phenuivirus and allows viral binding to host cells. A lipidomic analysis with mass spectrometry revealed the lipidome of UUKV particles and indicated that GlcCer was enriched in both infected cells and viral particles. In addition, the infectivity of UUKV depended on the conversion of ceramide (Cer) into GlcCer in the Golgi network of producer cells. In contrast, depletion of GlcCer in virions profoundly impaired the attachment of UUKV and other related viruses to target cells. Furthermore, competing GlcCer ligands prevented virus binding to various cell types. Altogether, our results demonstrate that glycolipids are essential structural determinants of the virions necessary for virus attachment to host cells and have strong implications for future work on the identification of virus receptors.
Chemical compositions of essential oils, antimicrobial effect and antioxidant activity studies of Hyoscyamus niger L. from Turkey
Authors: İnci Şule , Sancar Pelin Yilmaz , Demirpolat Azize , Kirbag Sevda , Civelek Semsettin
Published: August 2022

In this study, essential oil components of the Hyoscyamus niger L. plant and their antimicrobial and antioxidant properties were determined. The essential oils were obtained separately from both the aerial parts and seeds of the plant using the hydrodistillation method. Antimicrobial activity was determined using the disk diffusion method. Total antioxidant level (TAS), total oxidant level (TOS), and 2.2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity were detected for the antioxidant activity of the plant. The main essential oil components of the above-ground parts Hyoscyamus niger were determined as major components the phytol 52.09%, hexahydrofarnesyl acetone 19.66 %. H. niger seeds were hydrodistilled separately, obtaining yields of 0.7% (v w-1) of yellow oils. In the essential oils of H. niger seeds, forty-one components were identified representing 99.0% of the oils. According to the results of the analysis hexahydrofarnesyl acetone 46.36%, hexanal 9.05% as major components. It was determined that the methanol extracts of the above-ground H. niger inhibited the growth of pathogenic microorganisms at different rates (13-32 mm). TAS value of methanol extracts of H. niger was calculated as 3.7705 mmol, while the TOS value was calculated as 6.9403 μmol. It was determined that the scavenging effects of the DPPH radical increase, depend on increasing concentrations.
A resource for the comparison and integration of heterogeneous microbiome networks
Authors: Hu Zhenjun , Kishore Dileep , Wang Yan , Birzu Gabriel , DeLisi Charles , Korolev Kirill , Segrè Daniel
Published: August 2022

Naturally occurring microbial communities often comprise thousands of taxa involved in complex networks of interactions. These interactions can be mediated by several mechanisms, including the competition for resources, the exchange of signals and nutrients, cell-cell contact and antibiotic warfare. In addition to direct measurements and computational predictions of interactions, abundant data on microbial co-occurrence associations can be inferred from correlations of taxa across samples, which can be estimated from metagenomic, and amplicon datasets. The analysis and interpretation of interaction and correlation networks are limited by the challenge of comparing across different datasets, due to heterogeneity of the data itself and to the lack of a platform to facilitate such comparisons. Here, we introduce the Microbial Interaction Network Database (MIND) - a web-based platform for the integrative analysis of different types of microbial networks, freely available athttp://microbialnet.org/. In addition to containing a growing body of curated data, including amplicon-based co-occurrence networks, genome-scale model-derived networks, metabolic influence networks and horizontal gene transfer networks, MIND allows users to upload and analyze newly generated networks using a JSON format and standard NCBI taxonomy. The platform provides convenient functions to compare and query multiple networks simultaneously, and to visualize and export networks and datasets. Through some illustrative examples, we demonstrate how the platform might facilitate discoveries and help generate new hypotheses on host-associated and environmentally important microbial ecosystems through the power of knowledge integration.
circAβ RNA drives the formation and deposition of β-amyloid plaques in the sporadic Alzheimer’s disease
Authors: Mo Dingding
Published: August 2022

β-amyloid peptides (Aβ) play key causal role in Alzheimer’s disease (AD). However, the mechanisms of Aβ biogenesis in sporadic AD are still largely unknown. Moreover, current AD mouse models which overexpress mutated human APP and presenilin proteins can only mimic limited characteristics of familial AD. We recently discovered an alternative Aβ production pathway from Aβ175, an Aβ peptide containing polypeptide translated from circular circAβ-a RNA generated via backsplicing of the APP gene transcript. Here, wildtype human circAβ-a RNA was overexpressed in wildtype mouse frontal cortex. Results showed that circAβ-a overexpression drove intracellular Aβ accumulation and extensive depositions of neuronal Aβ plaques in mouse brain in vivo. This recapitulates the critical Aβ hallmarks of sporadic AD and represents a sporadic AD mouse model. In summary, the causal relationship between circAβ RNA overexpression and AD pathology was demonstrated. This novel AD mouse model will accelerate disease-modifying drug development of this detrimental neurodegenerative disease.
An Effective mRNA-LNP Vaccine Against the Lethal Plague Bacterium
Authors: Kon Edo , Levy Yinon , Elia Uri , Cohen Hila , Hazan-Halevy Inbal , Aftalion Moshe , Ezra Assaf , Bar-Haim Erez , Naidu Gonna Somu , Diesendruck Yael , Rotem Shahar , Ad-El Nitay , Goldsmith Meir , Mamroud Emanuelle , Peer Dan , Cohen Ofer
Published: August 2022

Plague is a rapidly deteriorating contagious disease that has killed millions of people during the history of mankind and is caused by the gram-negative bacterium Yersinia pestis. Currently, the disease is treated effectively with antibiotics. However, in the case of an outbreak caused by a multiple-antibiotic-resistant strain, alternative countermeasures are required. Despite the many efforts to develop a safe vaccine against the disease, there is still no vaccine approved for use in western countries. mRNA Lipid Nanoparticle (mRNA-LNP) vaccines have been demonstrated during the Covid-19 pandemic to be a versatile, clinically relevant, and rapidly manufactured vaccine platform. However, harnessing this platform for bacterial pathogens remains a formidable challenge. Here, we describe the design of several mRNA-LNP vaccine versions against Y. pestis, based on the F1 capsular antigen. We demonstrate that mRNA-LNP vaccines encoding the F1 antigen with either no signal sequences or conjugated to human Fc, provide substantial cellular and humoral responses. Most importantly, these vaccine candidates fully protect animals against Y. pestis infection. The results of this study suggest that mRNA-LNPs can be effective as anti-bacterial vaccines, and further developed to combat other bacterial pathogens, which are urgently needed, given the looming threat of antibiotic resistance.

One-Sentence Summary

A novel mRNA-LNP vaccine against Y. pestis, the etiological agent of plague and the first documented mRNA-LNP vaccine to protect against a lethal bacterial pathogen infection.
Genomic characterization of Francisella tularensis and other diverse Francisella species from complex samples
Authors: Wagner David M. , Birdsell Dawn N. , McDonough Ryelan F. , Nottingham Roxanne , Kocos Karisma , Celona Kimberly , Özsürekci Yasemin , Öhrman Caroline , Karlsson Linda , Myrtennäs Kerstin , Sjödin Andreas , Johansson Anders , Keim Paul S. , Forsman Mats , Sahl Jason W.
Published: August 2022

Francisella tularensis, the bacterium that causes the zoonosis tularemia, and its genetic near neighbor species, can be difficult or impossible to cultivate from complex samples. Thus, there is a lack of genomic information for these species that has, among other things, limited the development of robust detection assays for F. tularensis that are both specific and sensitive. The objective of this study was to develop and validate approaches to capture, enrich, sequence, and analyze Francisella DNA present in DNA extracts generated from complex samples. RNA capture probes were designed based upon the known pan genome of F. tularensis and other diverse species in the family Francisellaceae. Probes that targeted genomic regions also present in non-Francisellaceae species were excluded, and probes specific to particular Francisella species or phylogenetic clades were identified. The capture-enrichment system was then applied to diverse, complex DNA extracts containing low-level Francisella DNA, including human clinical tularemia samples, environmental samples (i.e., animal tissue and air filters), and whole ticks/tick cell lines, which was followed by sequencing of the enriched samples. Analysis of the resulting data facilitated rigorous and unambiguous confirmation of the detection of F. tularensis or other Francisella species in complex samples, identification of mixtures of different Francisella species in the same sample, analysis of gene content (e.g., known virulence and antimicrobial resistance loci), and high-resolution whole genome-based genotyping. The benefits of this capture-enrichment system include: even very low target DNA can be amplified; it is culture-independent, reducing exposure for research and/or clinical personnel and allowing genomic information to be obtained from samples that do not yield isolates; and the resulting comprehensive data not only provide robust means to confirm the presence of a target species in a sample, but also can provide data useful for source attribution, which is important from a genomic epidemiology perspective.
Analysis of Inbred Mouse strains’ High-Impact Genotype-phenotype Hypotheses (AIMHIGH) reveals novel disease-causing candidate genes
Authors: Yoo Boyoung , Nair Surag , Fang Zhuoqing , Arora Rushil , Wang Meiyue , Peltz Gary , Bejerano Gill
Published: August 2022

Inbred mouse strains reveal the molecular basis of mammalian traits and diseases, particularly recessive ones. We utilized mouse community curated resources to set up an automated screen to discover novel testable gene function hypotheses. Using 11,832 community contributed strain-differentiating experiments and trait presence/absence scoring, we searched for all experiments where strains can be split by their phenotypic values (e.g., high vs. low responders). Then, using 48 sequenced strains, we found one or more candidate gene for each experiment where homozygous high-impact variants (such as stopgain, frameshifts) segregate strains into these same binary grouping. Our approach rediscovered 212 known gene-phenotype relationships, almost always highlighting potentially novel causal variants, as well as thousands of gene function hypotheses. To help find the most exciting hypotheses, we improved the state of the art in machine learning driven literature-based discovery (LBD). Reading on our top 3 ranked candidate genes per experiment reveals 80% of rediscovered relationships, compared to 5% reading at random. We proposed 1,842 novel gene-phenotype testable hypotheses using our approach. We built a web portal at aimhigh.stanford.edu to allow researchers to view all our testable hypotheses in detail. Our open-source code can be rerun as more sequenced strains and phenotyping experiments become available.
Global patterns of diversity and metabolism of microbial communities in deep-sea hydrothermal vent deposits
Authors: Zhou Zhichao , St. John Emily , Anantharaman Karthik , Reysenbach Anna-Louise
Published: August 2022

Background

When deep-sea hydrothermal fluids mix with cold oxygenated fluids, minerals precipitate out of solution and form hydrothermal deposits. These actively venting deep-sea hydrothermal vent deposits support a rich diversity of thermophilic microorganisms which are involved in a range of carbon, sulfur, nitrogen, and hydrogen metabolisms. Global patterns of thermophilic microbial diversity in deep-sea hydrothermal ecosystems have illustrated the strong connectivity between geological processes and microbial colonization, but little is known about the genomic diversity and physiological potential of these novel taxa. Here we explore this genomic diversity in 42 metagenomes from four deep-sea hydrothermal vent fields and a deep-sea volcano collected from 2004 to 2018, and document their potential implications in biogeochemical cycles.

Results

Our dataset represents 3,635 metagenome-assembled genomes encompassing 511 novel genera, with 395 Bacteria and 116 Archaea, providing many targets for cultivation of novel archaeal and bacterial families. Notably, 52% (206) of the novel bacterial genera and 72% (84) of the novel archaeal genera were found at the deep-sea Brothers volcano, many of which were endemic to the volcano. We report some of the first examples of medium to high-quality MAGs from phyla and families never previously identified, or poorly sampled, from deep-sea hydrothermal environments. We greatly expand the novel diversity of Thermoproteia, Patescibacteria (Candidate Phyla Radiation, CPR), and Chloroflexota found at deep-sea hydrothermal vents and identify a small sampling of two potentially novel phyla, designated JALSQH01 and JALWCF01. Metabolic pathway analysis of metagenomes provides insights into the prevalent carbon, nitrogen, sulfur and hydrogen metabolic processes across all sites, and illustrates sulfur and nitrogen metabolic ‘handoffs’ in community interactions. We confirm that Campylobacteria and Gammaproteobacteria occupy similar ecological guilds but their prevalence in a particular site is driven by shifts in the geochemical environment.

Conclusion

Our study of globally-distributed hydrothermal vent deposits provides a significant expansion of microbial genomic diversity associated with hydrothermal vent deposits and highlights the metabolic adaptation of taxonomic guilds. Collectively, our results illustrate the importance of comparative biodiversity studies in establishing patterns of shared phylogenetic diversity and physiological ecology, while providing many targets for enrichment and cultivation of novel and endemic taxa.
The role and mechanism of NRF2 in endothelial cells and smooth muscle cells of pulmonary artery
Authors: Ning Shasha , Guo Xinyue , Zhu Yanan , Li Chenghui , Li Ruixue , Meng Yinan , Luo Weiwei , Lu Dezhang , Yin Yupeng
Published: August 2022

Pulmonary hypertension (PH) is a kind of fatal disease. There are no existing drugs that could reverse the diseas. NF-E2-related factor 2 (NRF2) is one of the most important moleculars in the range of cell protection. We examined the expression of NRF2 in PH models and explored the role of NRF2 in regulating abnormal phenotypes in pulmonary artery cells. We determined the expression level of NRF2 in lung tissues of PH model decreased significantly. We found that NRF2 was reduced in rat pulmonary artery endothelial cells (rPAEC) under hypoxia, while it was overexpressed in rat pulmonary artery smooth muscle cells (rPASMC) under hypoxia. Next, the results showed that knockdown NRF2 in rPAEC promoted endothelial-mesenchymal transformation and upregulated reactive oxygen species level. After the rPASMC was treated with siRNA or activator, we found that NRF2 could promote cell proliferation by regulating PDGFR/ERK1/2 and mTOR/P70S6K pathways, and accelerate cell migration by affecting MMP2/3/7. Therefore, the study suggests that the combination of NRF2 activators should be considered to eliminate the promoting effect of NRF2 activators on proliferation and migration of rPASMC.

Summary statement

Hypoxia regulates NRF2 in PAECs and PASMCs differently. We found that NRF2 could promote cell proliferation by regulating PDGFR/ERK1/2 and mTOR/P70S6K pathways, and accelerate cell migration by affecting MMP2/3/7.
The role of institutional relationships in shaping the career development of emerging artists
Authors: Fillis Ian , Lee Boram , Fraser Ian
Published: August 2022

Purpose

The authors consider the role of institutional relationships in providing an exhibition as a launching platform for emerging artists to develop their careers, as well as contributing to the broader creative economy. The authors view this as an entrepreneurial intervention in challenging the status quo through its potential to stimulate artist career development.

Design/methodology/approach

Data were collected using a case study approach in order to understand the complex inter-relationships between stakeholders of an emerging artists' exhibition at a well-known art institution. A total of 26 interviews were held with a selection of the exhibiting artists, artists from previous years' exhibitions, institution staff, the exhibition selection panel and major prize givers.

Findings

The main relationship value created by the institution as perceived by the exhibiting artists was high-level publicity and exposure of their work. Related benefits such as the potential to build career-enhancing networks were also emphasised. Some of the artists interviewed were aware of the art market structure and how they could create and sustain value within it. Others expressed a lack of awareness of and interest in its operationalisation where more assistance from the institution could help.

Research limitations/implications

This research focussed on the institutional relationships relating to one organisation, albeit one which leads the way in terms of helping to accelerate emerging artist careers. However, best practice lessons emerge from the research in terms of informing similar institutions elsewhere. The authors move beyond quantitative measurement of cultural value activities in developing in-depth qualitative insight into these relationships so that more nuanced understanding is revealed.

Practical implications

There is a need to develop pathways to assist new graduates and for a more strategic focus by art institutions to help develop their careers by creating and sustaining impact and engagement in the marketplace. This will be of interest to policy makers in helping to shape programmes of assistance in the future beyond the art institution. The authors also uncover broader cultural value impacts beyond the exhibition site where these institutional relationships can contribute positively to health and well-being.

Originality/value

The exhibition is one of only a very limited number of similar events throughout the UK and can be viewed as a successful entrepreneurial intervention.
New passive modified atmosphere packaging to extend peaches shelf life at ambient temperature to reduce economic losses
Authors: Sang Xudong , Yang Lijie , Li Dongli , Xu Wencai , Fu Yabo , Shi Jiazi
Published: August 2022

Purpose

Honey peaches are rich in a variety of vitamins and are well known in China as the queen of fruit. However, as highly climacteric fruit, peach is too easy to affect its economic value. In this paper, a new passive modified atmosphere packaging system was proposed to solve the lack of water vapour removal capacity – which is still the technical bottleneck of passive modified atmosphere packaging. This paper aims to address this issue.

Design/methodology/approach

Under the conditions of relative humidity 85−90% and temperature 28°C−38°C, the influence of new passive modified atmosphere packaging on the shelf life and quality of 70% ripe peaches was studied in the paper. The effect of the new passive modified atmosphere packaging (PMAP) on fruit appearance, colour, taste, flavour, soluble solids, Vitamin C and titratable acid was investigated.

Findings

Regardless of whether 1-Methylcyclopropene is added or not, the research results show that the new PMAP has a significant effect on extending the shelf life and maintaining the quality of peaches. Compared with the control group, the shelf life of peaches treated with modified atmosphere packaging and 1-Methylcyclopropene was prolonged by 7 and 11 days, increasing the retailer's revenue by 44 and 75%.

Originality/value

A new integrated structure, which is composed of two types of films with high oxygen and high water vapour permeability was designed for the retail of peaches at room temperature. The former was mainly responsible for regulating the concentration of O2 and CO2, while the latter was for removing water vapour and regulating the relative humidity in PMAP.
Performance analysis and clustering of Italian SA8000-certified food and beverages companies
Authors: De Cristofaro Tiziana , Liberatore Lolita , Casolani Nicola , Nissi Eugenia
Published: August 2022

Purpose

This work aims at discovering the multifaceted business performance of SA8000-certified companies operating in the Italian food and beverages manufacturing industry.

Design/methodology/approach

A clustering based on a principal component analysis considering 20 profitability, productivity and value-added distribution ratios was carried out on a sample of 105 Italian SA8000-certified food and beverages manufacturing companies.

Findings

Two clusters (CL1 and CL2) emerged from the statistical analysis, where CL1 represents 85.71% of the sample. Despite their general and some labour-related features being similar, they show very different performances. While CL2 performs better both within the food and beverage manufacturing industry than CL1, the latter performs similarly to industry, although even lower. Labour productivity pushes the gap between the clusters mostly through sales (generating revenues) and production (in the aspect of generating personnel costs). These findings suggest that a nonunique performance profile of firms SA8000 certified exists and that low performances do not prevent certification.

Originality/value

By focusing on SA8000 standard in the food and beverage sector, the study contributes to the research field by investigating the relationships between corporate social responsibility and firm performance in an important industrial sector for the Italian economy.
Drivers or passengers? A taxonomy of multinationals’ approaches to corporate social responsibility implementation in developing markets
Authors: Tarnovskaya Veronika , Tolstoy Daniel , Melén Hånell Sara
Published: August 2022

Purpose

The purpose of this study is to conduct a systematic literature review that illuminates the current state of knowledge regarding the specific approaches by which multinational corporations (MNCs) implement corporate social responsibility (CSR) on the subsidiary level in developing countries.

Design/methodology/approach

Even though substantial scholarly work has been made to outline MNCs' activities in developing countries, this literature remains fragmented. To support the field in its theoretical as well as empirical advancements, this study conducts a systematic review of this body of literature and content analysis of relevant articles using insights from strategic marketing literature (market driving/proactive and market-driven/reactive approaches).

Findings

The authors synthesize our findings by presenting a taxonomy of proactive/reactive CSR approaches in developing markets along with propositions that can guide future research in this area.

Originality/value

Among the key contributions of this study's literature review is the development of a taxonomy of proactive/reactive CSR, bringing together different and fragmented streams of research and viewing them from strategic marketing (“proactive/reactive”) perspective. The taxonomy and the two ensuing propositions can advance future CSR-related studies with MNCs in focus by providing both theoretical and empirical guidance.
How can machine tool builders capture value from smart services? Avoiding the service and digitalization paradox
Authors: Kamp Bart , Zabala Kristina , Zubiaurre Arantza
Published: August 2022

Purpose

This paper aims to assess the existence of, or the risk of running into, a smart service paradox for industrial firms and how to overcome it.

Design/methodology/approach

A qualitative multiple case study is conducted involving four machine tool builders. The main source of data is formed by semi-structured interviews with service business managers. NVivo software was used to structure the interview harvest.

Findings

The findings reveal that a smart service paradox is a realistic threat for industrial firms, that smart service business development is a supply push affair rather than a matter of demand pull, that two types of permissions need to be granted by prospective users (license to operate and license to charge) and that three intermediate steps need to be undertaken and validated to overcome a smart service paradox: value testing or proofing; value recognition; and value sharing.

Research limitations/implications

This study was vendor-centric and did not involve the industrial customers to whom the smart services were directed. It was based on a small sample, which limits the generalizability of findings to a broader or different (sectoral) context.

Practical implications

Lessons are identified for service managers on how to circumvent a smart service paradox.

Originality/value

This study departs from a value creation-delivery-capture (“business model”) perspective to assess smart service paradox dynamics. By adopting a relational perspective to it, the present paper succeeds in presenting a more granular version of the base business model.
Civil society diplomacy: characterizing collective and connective actions for a shared cause
Authors: Asdourian Bruno
Published: August 2022

Purpose

This study proposes a description of the civil society diplomacy that emerged in the early solutions found to fight the COVID-19 crisis. The author analyses this concept as the intersection of the social movements of individuals and civil society organisations' and international health care. Its purpose is to determine the international structure of the connective actors aimed to find concrete solutions against COVID-19 and to characterize the communication visible on Twitter towards this civil society engagement.

Design/methodology/approach

Based on a data-driven approach, the author collected a large dataset of tweets from Switzerland between March and June 2020 and conducted a computational text analysis methodology.

Findings

The results showed who the participants were, provided a visualisation of the digital networking process between engaged and mentioned participants at national and international levels, and determined the emotions that emerged during three event phases.

Originality/value

The study reveals that features of connective social care actions and strategic collective communication can illustrate civil society diplomacy for a shared cause in times of health crisis.