bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Pancreatic Cancer Microbiome Using Endoscopic Ultrasound–Guided Fine-Needle Aspiration–Derived Samples
Authors: Nakano Shintaro , Kawamoto Yasuyuki , Komatsu Yoshito , Saito Rika , Ito Ken , Yamamura Takahiro , Harada Kazuaki , Yuki Satoshi , Kawakubo Kazumichi , Sugiura Ryo , Kato Shin , Hirata Koji , Hirata Hajime , Nakajima Masahito , Furukawa Ryutaro , Takishin Yunosuke , Nagai Kousuke , Yokota Isao , Ota Keisuke H. , Nakaoka Shinji , Kuwatani Masaki , Sakamoto Naoya
Published: June 2022

Objectives

Most previous studies have analyzed bacteria in tumors using resected pancreatic cancer (PC) tissues, because it is difficult to obtain tissue samples from unresectable advanced PC. We aimed to determine whether minimal tissue obtained by endoscopic ultrasound–guided fine-needle aspiration is useful for microbiome analysis.

Methods

Thirty PC and matched duodenal and stomach tissues (N = 90) were prospectively collected from 30 patients who underwent endoscopic ultrasound–guided fine-needle aspiration. Bacterial DNA was extracted, and 16S rRNA sequencing was performed. The primary outcome was the success rate of bacterial detection in tumors. Bacterial diversity and structure were investigated.

Results

The bacterial detection rates were 80%, 100%, and 97% in PC, gastric, and duodenal samples, respectively. Pancreatic cancer tissues showed a lower α-diversity and a significantly different microbial structure than stomach and duodenal tissues. Proteobacteria were more abundant, whereas Firmicutes, Bacteroidetes, and Fusobacteria were less abundant in PC tissues than in stomach and duodenal tissues. Acinetobacter was more abundant in PC tissues than in stomach and duodenal tissues, and Delftia was more frequently detected in resectable PC.

Conclusions

Endoscopic ultrasound–guided fine-needle aspiration samples were valuable for PC microbiome analysis, revealing that the bacterial composition of PC is different from that of the stomach and duodenum.
A Study of the Association Between Carotid Artery Curvature and Intracranial Aneurysms
Authors: Zhao Jun , Xiang Xiang , Zhang Hongxia , Ye Ying , He Zhaohui
Published: June 2022

Background:

Carotid artery curvature is considered a sign of a weak vessel wall, and we hypothesize that a weak vascular wall under the effect of hemodynamics may cause intracranial aneurysms.

Materials and Methods:

The general data of 534 patients with aneurysms and 473 control patients were retrospectively analyzed in a case-control study. Carotid artery curvature was characterized as none, tortuosity, kinking, and coiling by computed tomography angiography images. Univariate analysis was performed to determine the degree of carotid artery tortuosity and to analyze the general data between the aneurysm group and the control group, and then, multivariate statistical logistic regression analysis was used to analyze the statistical significance of the univariate analysis. Finally, the correlation between aneurysm-related features and carotid artery curvature was analyzed.

Results:

Univariate analysis showed that kinking was significantly related to the occurrence of intracranial aneurysms (P=0.009). The results of multivariate regression analysis showed that kinking was an independent risk factor for the occurrence of aneurysms (odds ratio: 1.942; 95% confidence interval: 1.387-2.720 for model 1; odds ratio: 1.995; 95% confidence interval: 1.419-2.805 for model 2). In the analysis of the correlation between the characteristics of intracranial aneurysms and the curvature of the internal carotid artery, there was no correlation between the curvature of the internal carotid artery and the size, location or number of aneurysms, or whether the intracranial aneurysm was ruptured.

Conclusion:

Intracranial aneurysms are associated with carotid artery curvature. Kinking of the internal carotid artery may indicate a higher risk for aneurysm formation.
Utilization of Family as Faculty: A Patient Directed Simulation Education to Improve Patient and Family Communication during Patient-Family Centered Rounds (PFCR)
Authors: Asuncion Arsenia M. , Quintos-Alagheband Maria Lyn , Leavens-Maurer Jill , Akerman Meredith , Janicke Patricia , Cavanaugh Sean
Published: June 2022

Introduction:

Patient-family-centered care (PFCC) is based on the understanding that the family is the child’s source of strength and support. Effective communication between families and providers is an essential component of PFCC. Our interprofessional team designed an initiative to improve medical providers’ communication in partnership with the Patient and Family Advisory Council (PFAC). Strategies included the creation of a competency rubric and simulation curriculum using the family as faculty. The SMART aim was to improve the percentage of respondents who answered “Always” to doctor communication domains from 72% to 75.6% in Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) by December 2020.

Methods:

Pediatric residents, medical students, faculty, nurses, and PFAC members formed a Quality Improvement (QI) team to address PFCR competency. The team created a PFCC checklist to address competency. PFAC volunteers served as standardized parents in an in situ simulation of PFCR scenarios involving interprofessional in-patient teams. Evaluators observed rounds for the pre and postintervention assessment using the checklist. The outcome measure was the percentage of respondents who answered “Always” in the HCAPHS domain for physician communication. The process measure was the PFCR pre and postintervention, using Fisher’s exact test for analysis.

Results:

Using a statistical process chart (SPC), HCAHPS data from 2018 to 2020 showed that we exceeded our aim of >5% increase in the physician communication performance. Pre-post intervention data showed improvement in PFCR competency.

Conclusion:

Family as faculty simulation led to improved physician communication, translating to improved performance in the HCAHPS score and PFCR competency communication domains.
Reducing the Time to Blood Administration after Pediatric Injury: A Quality Improvement Initiative
Authors: Sullivan Travis M. , Milestone Zachary P. , Alberto Emily C. , Waibel Elizabeth M. , Gestrich-Thompson Waverly V. , Tempel Peyton E. , Fritzeen Jennifer L. , O’Connell Karen J. , Cheng Jacob , Burd Randall S.
Published: June 2022

Introduction:

Hemorrhage is the leading cause of preventable death in pediatric trauma patients. Timely blood administration is associated with improved outcomes in children and adults. This study aimed to identify delays to transfusion and improve the time to blood administration among injured children.

Methods:

A multidisciplinary team identified three activities associated with blood transfusion delays during the acute resuscitation of injured children. To address delays related to these activities, we relocated the storage of un-crossmatched blood to the emergency department (ED), created and disseminated an intravenous access algorithm, and established a nursing educator role for resuscitations. We performed comparative and regression analyses to identify the impact of these factors on the timeliness and likelihood of blood administration.

Results:

From January 2017 to June 2021, we treated 2159 injured children and adolescents in the resuscitation area, 54 (2.5%) of whom received blood products in the ED. After placing a blood storage refrigerator in the ED, we observed a centerline change that lowered the adjusted time-to-blood administration to 17 minutes (SD 11), reducing the time-to-blood administration by 11 minutes (β = −11.0, 95% CI = −22.0 to −0.9). The likelihood of blood administration was not changed after placement of the blood refrigerator. We observed no reduction in time following the implementation of the intravenous access algorithm or a nursing educator.

Conclusions:

Relocation of un-crossmatched blood storage to the ED decreased the time to blood transfusion. This system-based intervention should be considered a strategy for reducing delays in transfusion in time-critical settings.
Rheumatology Clinic Staff Needs
Authors: Tong Michelle , Gilmore-Bykovskyi Andrea , Block Laura , Ramly Edmond , White Douglas W. , Messina Monica L. , Bartels Christie M.
Published: June 2022

Objective

Patients with rheumatologic conditions are at elevated risk of cardiovascular disease (CVD) due to inflammatory and traditional risk factors, such as high blood pressure (BP) and smoking. However, rheumatology clinics rarely address traditional risk factors, although they are routinely assessed and modifiable in primary care. The present study sought to (1) characterize rheumatology clinic staff's work process for addressing high BP and smoking and (2) identify barriers and strategies for effective management of these risk factors.

Methods

We conducted 7 focus groups with medical assistants, nurses, and scheduling staff from 4 adult rheumatology clinics across 2 health systems (BP focus groups, n = 23; smoking, n = 20). Transcripts were analyzed using thematic analysis to elucidate barriers and strategies.

Results

We found 3 clinic work processes for the management of high BP and smoking risk: (1) risk identification, (2) follow-up within the clinic, and (3) follow-up with primary care and community resources. Within these processes, we identified barriers and strategies grouped into themes: (1) time, (2) clinic workflows, (3) technology and resources, (4) staff's attitudes and knowledge, and (5) staff's perceptions of patients. The most pervasive barriers were (1) no structured system for follow-up and (2) staff confidence and skill in initiating conversations about health-related behavior change.

Conclusions

Our study identified generalizable gaps in rheumatology staff's work processes and competencies for addressing high BP and smoking in patients. Future efforts to support staff needs should target (1) systems for follow-up within and outside the clinic and (2) conversation support tools.
The emergence of supergenes from inversions in Atlantic salmon
Authors: Stenløkk Kristina , Saitou Marie , Rud-Johansen Live , Nome Torfinn , Moser Michel , Árnyasi Mariann , Kent Matthew , Barson Nicola Jane , Lien Sigbjørn
Published: June 2022

Supergenes link allelic combinations into non-recombining units known to play an essential role in maintaining adaptive genetic variation. However, because supergenes can be maintained over millions of years by balancing selection and typically exhibit strong recombination suppression, both the underlying functional variants and how the supergenes are formed are largely unknown. Particularly, questions remain over the importance of inversion breakpoint sequences and whether supergenes capture pre-existing adaptive variation or accumulate this following recombination suppression. To investigate the process of supergene formation, we identified inversion polymorphisms in Atlantic salmon by assembling eleven genomes with nanopore long-read sequencing technology. A genome assembly from the sister species, brown trout, was used to determine the standard state of the inversions. We found evidence for adaptive variation through genotype–environment associations, but not for the accumulation of deleterious mutations. One young 3 Mb inversion segregating in North American populations has captured adaptive variation that is still segregating within the standard arrangement of the inversion, while some adaptive variation has accumulated after the inversion. This inversion and two others had breakpoints disrupting genes. Three multigene inversions with matched repeat structures at the breakpoints did not show any supergene signatures, suggesting that shared breakpoint repeats may obstruct supergene formation.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
Unbalanced selection: the challenge of maintaining a social polymorphism when a supergene is selfish
Authors: Tafreshi Alireza G. , Otto Sarah P. , Chapuisat Michel
Published: June 2022

Supergenes often have multiple phenotypic effects, including unexpected detrimental ones, because recombination suppression maintains associations among co-adapted alleles but also allows the accumulation of recessive deleterious mutations and selfish genetic elements. Yet, supergenes often persist over long evolutionary periods. How are such polymorphisms maintained in the face of selection, drive and drift? We present a population genetic model that investigates the conditions necessary for a stable polymorphic equilibrium when one of the supergene haplotypes is a selfish genetic element. The model fits the characteristics of the Alpine silver ant,Formica selysi, in which a large supergene underlies colony social organization, and one haplotype distorts Mendelian transmission by killing progeny that did not inherit it. The model shows that such maternal-effect killing strongly limits the maintenance of social polymorphism. Under random mating, transmission ratio distortion prevents rare single-queen colonies from invading populations of multiple-queen colonies, regardless of the fitness of each genotype. A stable polymorphic equilibrium can, however, be reached when high rates of assortative mating are combined with large fitness differences among supergene genotypes. The model reveals that the persistence of the social polymorphism is non-trivial and expected to occur only under restrictive conditions that deserve further empirical investigation.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
Sex chromosomes as supergenes of speciation: why amphibians defy the rules?
Authors: Dufresnes Christophe , Crochet Pierre-André
Published: June 2022

As reflected by the two rules of speciation (Haldane's rule and the large X-/Z-effect), sex chromosomes are expected to behave like supergenes of speciation: they recombine only in one sex (XX females or ZZ males), supposedly recruit sexually antagonistic genes and evolve faster than autosomes, which can all contribute to pre-zygotic and post-zygotic isolation. While this has been mainly studied in organisms with conserved sex-determining systems and highly differentiated (heteromorphic) sex chromosomes like mammals, birds and some insects, these expectations are less clear in organismal groups where sex chromosomes repeatedly change and remain mostly homomorphic, like amphibians. In this article, we review the proposed roles of sex-linked genes in isolating nascent lineages throughout the speciation continuum and discuss their support in amphibians given current knowledge of sex chromosome evolution and speciation modes. Given their frequent recombination and lack of differentiation, we argue that amphibian sex chromosomes are not expected to become supergenes of speciation, which is reflected by the rarity of empirical studies consistent with a ‘large sex chromosome effect’ in frogs and toads. The diversity of sex chromosome systems in amphibians has a high potential to disentangle the evolutionary mechanisms responsible for the emergence of sex-linked speciation genes in other organisms.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
Searching for signatures of sexually antagonistic selection on stickleback sex chromosomes
Authors: Dagilis Andrius J. , Sardell Jason M. , Josephson Matthew P. , Su Yiheng , Kirkpatrick Mark , Peichel Catherine L.
Published: June 2022

Intralocus sexually antagonistic selection occurs when an allele is beneficial to one sex but detrimental to the other. This form of selection is thought to be key to the evolution of sex chromosomes but is hard to detect. Here we perform an analysis of phased young sex chromosomes to look for signals of sexually antagonistic selection in the Japan Sea stickleback (Gasterosteus nipponicus). Phasing allows us to date the suppression of recombination on the sex chromosome and provides unprecedented resolution to identify sexually antagonistic selection in the recombining region of the chromosome. We identify four windows with elevated divergence between the X and Y in the recombining region, all in or very near genes associated with phenotypes potentially under sexually antagonistic selection in humans. We are unable, however, to rule out the alternative hypothesis that the peaks of divergence result from demographic effects. Thus, although sexually antagonistic selection is a key hypothesis for the formation of supergenes on sex chromosomes, it remains challenging to detect.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
Genomic architecture and functional effects of potential human inversion supergenes
Authors: Campoy Elena , Puig Marta , Yakymenko Illya , Lerga-Jaso Jon , Cáceres Mario
Published: June 2022

Supergenes are involved in adaptation in multiple organisms, but they are little known in humans. Genomic inversions are the most common mechanism of supergene generation and maintenance. Here, we review the information about two large inversions that are the best examples of potential human supergenes. In addition, we do an integrative analysis of the newest data to understand better their functional effects and underlying genetic changes. We have found that the highly divergent haplotypes of the 17q21.31 inversion of approximately 1.5 Mb have multiple phenotypic associations, with consistent effects in brain-related traits, red and white blood cells, lung function, male and female characteristics and disease risk. By combining gene expression and nucleotide variation data, we also analysed the molecular differences between haplotypes, including gene duplications, amino acid substitutions and regulatory changes, and identifyCRHR1, KANLS1andMAPTas good candidates to be responsible for these phenotypes. The situation is more complex for the 8p23.1 inversion, where there is no clear genetic differentiation. However, the inversion is associated with several related phenotypes and gene expression differences that could be linked to haplotypes specific of one orientation. Our work, therefore, contributes to the characterization of both exceptional variants and illustrates the important role of inversions.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
Microglia shape the embryonic development of mammalian respiratory networks
Authors: Cabirol Marie-Jeanne , Cardoit Laura , Courtand Gilles , Mayeur Marie-Eve , Simmers John , Pascual Olivier , Thoby-Brisson Muriel
Published: June 2022

Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT, Pu.1+/+) mouse brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preBötzinger complex (preBötC)). In transgenic mice depleted of microglia (Pu.1-/- mutant), we performed anatomical staining, calcium imaging and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preBötC at E16.5 and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preBötC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5 Pu.1-/- embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development.
Conjugative IncC plasmid entry triggers the SOS response and promotes effective transfer of the integrative antibiotic resistance element SGI1
Authors: Pons Marine C. , Praud Karine , Re Sandra Da , Cloeckaert Axel , Doublet Benoît
Published: June 2022

The broad host range IncC plasmid family and the integrative mobilizable Salmonella Genomic Island 1 (SGI1) and its derivatives enable the spread of medically-important antibiotic resistance genes among Gram-negative pathogens. Although several aspects of the complex functional interactions between IncC plasmids and SGI1 have been recently deciphered regarding their conjugative transfer and incompatibility, the biological signal resulting in the hijacking of the conjugative plasmid by the integrative mobilizable element remains unknown. Here, we demonstrate that the conjugative entry of IncC/IncA plasmids is detected at an early stage by SGI1 through the transient activation of the SOS response, which induces the expression of the SGI1 master activators SgaDC, shown to play a crucial role in the complex biology between SGI1 and IncC plasmids. Besides, we developed an original tripartite conjugation approach to directly monitor SGI1 mobilization in a time-dependent manner following conjugative entry of IncC plasmids. Finally, we propose an updated biological model of the conjugative mobilization of the chromosomal resistance element SGI1 by IncC plasmids.

IMPORTANCE

Antimicrobial resistance has become a major public health issue, particularly with the increase in multidrug resistance (MDR) in both animal and human pathogenic bacteria, and with the emergence of resistance to medically important antibiotics. The spread between bacteria of successful mobile genetic elements such as conjugative plasmids and integrative elements conferring multidrug resistance is the main driving force in the dissemination of acquired antibiotic resistances among Gram-negative bacteria. Broad-host range IncC plasmids and their integrative mobilizable SGI1 counterparts contribute to the spread of critically-important resistance genes (e.g., ESBLs, and carbapenemases). A better knowledge of the complex biology of these broad-host range mobile elements will help to understand the dissemination of antimicrobial resistance genes that occurred across γ-proteobacteria borders.
AAV-mediated neuronal expression of a scFv antibody selective for Aβ oligomers protects synapses and rescues memory in Alzheimer models
Authors: Selles Maria Clara , Fortuna Juliana T.S. , Cercato Magali C. , Santos Luis Eduardo , Domett Luciana , Bitencourt Andre L.B. , Carraro Mariane Favero , Souza Amanda S. , Janickova Helena , de Souza Jorge M. , Alves-Leon Soniza , Prado Vania F. , Prado Marco A. M. , Epstein Alberto L. , Salvetti Anna , Arancio Ottavio , Klein William L. , Sebollela Adriano , De Felice Fernanda G. , Jerusalinsky Diana A. , Ferreira Sergio T.
Published: June 2022

Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) has been implicated in synapse failure and memory impairment in Alzheimer’s disease. Here, we show that treatment with NUsc1, a single-chain variable fragment antibody (scFv) that selectively targets AβOs, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AβOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices, and inhibited AβO binding to neurons and AβO-induced loss of dendritic spine loss in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AβOs and, importantly, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer’s disease model mice. These results support the feasibility of gene-mediated immunotherapy using single-chain antibodies as a potential therapeutic approach in Alzheimer’s disease.
Exogenous NaV1.1 activity in excitatory and inhibitory neurons reverts Dravet syndrome comorbidities when delivered post-symptom onset in mice with Dravet
Authors: Fadila Saja , Beucher Bertrand , Reyes Iria González-Dopeso , Mavashov Anat , Brusel Marina , Anderson Karen , Goldberg Ethan M , Ricobaraza Ana , Hernandez-Alcoceba Ruben , Kremer Eric J , Rubinstein Moran
Published: June 2022

Dravet syndrome (DS), an intractable childhood epileptic encephalopathy with a high fatality rate, is caused by loss-of-function mutations in one allele of SCN1A, which encodes NaV1.1. In contrast to other epilepsies, pharmaceutical treatment for DS is limited. Here, we demonstrate that viral vector-mediated delivery of a codon-modified SCN1A cDNA improves DS comorbidities in juvenile and adolescent DS mice (Scn1aA1783V/WT). Notably, bilateral vector injections into the hippocampus or thalamus of DS mice improved the survival of the mice, reduced the occurrence of epileptic spikes, provided protection from thermally-induced seizures, and corrected background electrocorticography activity. Together, our results provide a proof-of-concept for the potential of SCN1A delivery as a therapeutic approach for infants and adolescents with DS-associated comorbidities.
Seeing the forest and the tree: Building representations of both individual and collective dynamics with transformers
Authors: Liu Ran , Azabou Mehdi , Dabagia Max , Xiao Jingyun , Dyer Eva L.
Published: June 2022

Complex time-varying systems are often studied by abstracting away from the dynamics of individual components to build a model of the population-level dynamics from the start. However, when building a population-level description, it can be easy to lose sight of each individual and how they contribute to the larger picture. In this paper, we present a novel transformer architecture for learning from time-varying data that builds descriptions of both the individual as well as the collective population dynamics. Rather than combining all of our data into our model at the onset, we develop a separable architecture that operates on individual time-series first before passing them forward; this induces a permutation-invariance property and can be used to transfer across systems of different size and order. After demonstrating that our model can be applied to successfully recover complex interactions and dynamics in many-body systems, we apply our approach to populations of neurons in the nervous system. On neural activity datasets, we show that our model not only yields robust decoding performance, but also provides impressive performance in transfer across recordings of different animals without any neuron-level correspondence. By enabling flexible pre-training that can be transferred to neural recordings of different size and order, our work provides a first step towards creating a foundation model for neural decoding.
How long can tardigrades survive in anhydrobiotic state? Searching on tardigrade anhydrobiosis patterns
Authors: Kaczmarek Łukasz , Roszkowska Milena , Gołdyn Bartłomiej , Wojciechowska Daria , Księżkiewicz Zofia , Fiałkowska Edyta , Pluskota Mateusz , Kmita Hanna
Published: June 2022

Anhydrobiosis is a desiccation tolerance that denotes the ability to survive almost complete dehydration without sustaining damage. However, knowledge on the survival capacity of anhydrobiosis in various species of tardigrades is still very limited. Our research has compared anhydrobiotic capacities of four tardigrade species: Echiniscus testudo, Paramacrobiotus experimentalis, Pseudohexapodibius degenerans and Macrobiotus pseudohufelandi, which differ in feeding behaviour, habitats occupied, and which belong to different genera. Moreover, in the case of Ech. testudo two populations-from urban and natural habitats-were analysed. Clear differences in the anhydrobiotic capacity were observed among different tardigrade species. These differences appear to be determined by the habitat, but not by the nutritional behaviour of the species sharing the habitat type. Moreover, the results indicated that the longer tun state duration, the more time was necessary for the animals to return to activity.
A Machine Learning Approach Towards the Differentiation Between Interoceptive and Exteroceptive Attention
Authors: Zuo Zoey X. , Price Cynthia J. , Farb Norman A. S.
Published: June 2022

Interoception, the representation of the body’s internal state, plays a central role in emotion, motivation, and wellbeing. Interoceptive attention is qualitatively different from attention to the external senses and may recruit a distinct neural system, but the neural separability of interoceptive and exteroceptive attention is unclear. We used a machine learning approach to classify neural correlates of interoceptive and exteroceptive attention in a randomized control trial of interoceptive training (MABT). Participants in the training and control groups attended fMRI assessment before and after an 8-week intervention period (N = 44 scans). The imaging paradigm manipulated attention targets (breath vs. visual stimulus) and reporting demands (active reporting vs. passive monitoring). Machine learning models achieved high accuracy in distinguishing between interoceptive and exteroceptive attention using both in-sample and more stringent out-of-sample tests. We then explored the potential of these classifiers in “reading out” mental states in a sustained interoceptive attention task. Participants were classified as maintaining an active reporting state for only ∼90s of each 3-minute sustained attention period. Within this active period, interoceptive training enhanced participants’ ability to sustain interoceptive attention. These findings demonstrate that interoceptive and exteroceptive attention engage reliable and distinct neural networks; machine learning classifiers trained on this distinction show promise for assessing the stability of interoceptive attention, with implications for the future assessment of mental health and treatment response.
Thinking like a structural biologist: A pocket-based 3D molecule generative model fueled by electron density
Authors: Wang Lvwei , Bai Rong , Shi Xiaoxuan , Zhang Wei , Cui Yinuo , Wang Xiaoman , Wang Cheng , Chang Haoyu , Zhang Yingsheng , Zhou Jielong , Peng Wei , Zhou Wenbiao , Huang Bo
Published: June 2022

We report for the first time the use of experimental electron density (ED) as training data for the generation of drug-like three-dimensional molecules based on the structure of a target protein pocket. Similar to a structural biologist building molecules based on their ED, our model functions with two main components: a generative adversarial network (GAN) to generate the ligand ED in the input pocket and an ED interpretation module for molecule generation. The model was tested on three targets including kinase (HPK1), protease (Covid19-3CL), and nuclear receptor (VDR), and evaluated with a reference dataset composed of over 8,000 compounds that have their activities reported in the literature. The evaluation examined the chemical validity, chemical space distribution-based diversity, and similarity with reference active compounds concerning the molecular structure and pocket-binding mode. Our model can reproduce classical active compounds and can also generate novel molecules with similar binding modes as active compounds, making it a promising tool for library generation supporting high-throughput virtual screening. Our model is available as an online service to academic users via https://edmg.stonewise.cn/#/create.
Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
Authors: Princová Jarmila , Salat-Canela Clàudia , Daněk Petr , Marešová Anna , de Cubas Laura , Bähler Jürg , Ayté José , Hidalgo Elena , Převorovský Martin
Published: June 2022

Oxidative stress is associated with cardiovascular and neurodegenerative diseases, diabetes, cancer, psychiatric disorders and aging. In order to counteract, eliminate and/or adapt to the sources of stress, cells possess elaborate stress-response mechanisms, which also operate at the level of regulating transcription. Interestingly, it is becoming apparent that the metabolic state of the cell and certain metabolites can directly control the epigenetic information and gene expression. In the fission yeastSchizosaccharomyces pombe, the conserved Sty1 stress-activated protein kinase cascade is the main pathway responding to most types of stresses, and regulates the transcription of hundreds of genes via the Atf1 transcription factor. Here we report that fission yeast cells defective in fatty acid synthesis (cbf11, mga2and ACC/cut6mutants) show increased expression of a subset of stress-response genes. This altered gene expression depends on Sty1, and the Gcn5 and Mst1 histone acetyltransferases, is associated with increased acetylation of histone H3 at lysine 9 in the corresponding gene promoters, and results in increased cellular resistance to oxidative stress. Since both fatty-acid synthesis and histone acetylation compete for the same substrate, acetyl-CoA, we propose that changes in lipid metabolism can regulate the chromatin and transcription of specific stress-response genes, which in turn might help cells to maintain redox homeostasis.
The Role of UBE2-Conjugating Enzymes in the Mechanism of MuRF1 Ubiquitylation
Authors: Dawson Peter W.J. , Baehr Leslie M. , Hughes David C. , Knowles Timothy J. , Sridhar Pooja , Bodine Sue C. , Lai Yu-Chiang
Published: June 2022

MuRF1 (Muscle-specific RING finger protein 1; gene name TRIM63) is a ubiquitin E3 ligase, associated with the progression of muscle atrophy. As a RING (Really Interesting New Gene)-type E3 ligase, its unique activity of ubiquitylation is driven by a specific interaction with UBE2 (ubiquitin conjugating enzyme) to ubiquitylate its substrate protein. The understanding of MuRF1 function remains unclear as candidate UBE2 has not been elucidated and thus the mechanism of ubiquitylation is inconclusive. In the present study, we screened human ubiquitin dependent E2s using in-vitro ubiquitylation assays. We found that MuRF1 engages in ubiquitylation/auto-ubiquitylation with UBE2D, UBE2E, UBE2N/V families and UBE2W. Our result indicated that MuRF1 can cause mono-ubiquitylation, K48, and K63 specific poly-ubiquitin chains in a UBE2-dependent manner. Interestingly, we identified a two-step UBE2-dependent mechanism by which UBE2W allows MuRF1 to mono-ubiquitylate which then acts as an anchor for UBE2N/V and UBE2D generated poly-ubiquitin chain formation. Furthermore, MuRF1 was shown to cooperate with the identified interacting UBE2s to directly ubiquitylate substrates Titin (A168-A170), Desmin, and MYLPF (Myosin Light Chain, Phosphorylatable, Fast Skeletal Muscle; also called Myosin Light Regulatory Chain 2). Our work presents a novel insight into the mechanisms that underpin MuRF1 activity by highlighting the diversity of MuRF1 ubiquitylation enabled by different UBE2s.
Nanog organizes transcription bodies
Authors: Kuznetsova Ksenia , Ugolini Martino , Wu Edlyn , Lalit Manan , Oda Haruka , Sato Yuko , Kimura Hiroshi , Jug Florian , Vastenhouw Nadine
Published: June 2022

The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells. How proteins of the transcriptional machinery come together to form such bodies, however, is unclear. Here, we take advantage of two large, isolated, and long-lived transcription bodies that reproducibly form during early zebrafish embryogenesis, to characterize the dynamics of transcription body formation. Once formed, these transcription bodies are enriched for initiating and elongating RNA polymerase II, as well as the transcription factors Nanog and Sox19b. Analyzing the events leading up to transcription, we find that Nanog and Sox19b cluster prior to transcription, and independently of RNA accumulation. The clustering of transcription factors is sequential; Nanog clusters first, and this is required for the clustering of Sox19b and the initiation of transcription. Mutant analysis revealed that both the DNA-binding domain, as well as one of the two intrinsically disordered regions of Nanog are required to organize the two bodies of transcriptional activity. Taken together, our data suggests that the clustering of transcription factors dictates the formation of transcription bodies.

HIGHLIGHTS

Transcription factors cluster prior to, and independently of transcription

Nanog organizes transcription bodies: it is required for the clustering of Sox19b as well as RNA polymerase II

This organizing activity requires its DNA binding domain as well as one of its intrinsically disordered regions

Transcription elongation results in the disassembly of transcription factor clusters
Extinction cascades, community collapse, and recovery across a Mesozoic hyperthermal event
Authors: Dunhill Alexander M. , Zarzyczny Karolina , Shaw Jack O. , Atkinson Jed W. , Little Crispin T.S. , Beckerman Andrew P.
Published: June 2022

Biotic interactions and community structure are seldom examined in mass extinction studies but must be considered if we are to truly understand extinction and recovery dynamics at the ecosystem scale. Here, we model shallow marine food web structure across the Toarcian extinction event in the Cleveland Basin, UK using a trait-based inferential modelling framework. First, we subjected our pre-extinction community to extinction cascade simulations in order to identify the nature of extinction selectivity and dynamics. Second, we tracked the pattern and duration of the recovery of ecosystem structure and function following the extinction event. In agreement with postulated scenarios, we found that primary extinctions targeted towards infaunal and epifaunal benthic guilds reproduced the empirical post-extinction community. These results are consistent with geochemical and lithological evidence of an anoxia/dysoxia kill mechanism for this extinction event. Structural and functional metrics show that the extinction event caused a switch from a diverse, stable community with high levels of functional redundancy to a less diverse, more densely connected, and less stable community of generalists. Ecological recovery appears to have lagged behind the recovery of biodiversity, with most metrics only beginning to return to pre-extinction levels ∼7 million years after the extinction event. This protracted pattern supports the theory of delayed benthic ecosystem recovery following mass extinctions even in the face of seemingly recovering taxonomic diversity.
The impact of customer and supplier collaboration on green supply chain performance
Authors: Andalib Ardakani Davood , Soltanmohammadi Asieh , Seuring Stefan
Published: June 2022

Purpose

The purpose of this study is to determine the extent to which institutional pressures affect supplier and customer collaboration and how collaboration explains green supply chain performance using institutional and stakeholder theories.

Design/methodology/approach

The paper builds on empirical evidence gathered from responses of Iranian industrial managers based on a self-administered survey. The hypotheses in the conceptual model are tested using Smart-PLS (partial least square).

Findings

The results provide evidence that regulatory requirements and internal motivators, as institutional pressure, enable customer and supplier collaboration. Furthermore, customer collaboration has a positive effect on supplier collaboration and, consequently, positively affects environmental and economic performance. But supplier collaboration is just positively affecting environmental performances and is not effective on economic performance.

Research limitations/implications

The subject is that the study is a questionnaire-based survey, and the validity and reliability of the results are influenced by the respondents' idiosyncrasies. This study provides a comprehensive model of drivers, supply chain collaboration and performance in the context of the industry sector. The study contributes by providing empirical data with a focus on customer and supplier collaboration and their interrelationship in GSCM modelling.

Originality/value

The current paper is one of the new field of research which demonstrate the significance of customer and supplier collaboration with each other to attain green performance. It also contributes to show the effect of institutional pressure on the customer-supplier collaboration that fosters green performance in the supply chain.
Radar echo simulation of wind turbines array based on scattering center
Authors: Tang Bo , Yang Xiaofeng , Zhang Jiangong , Zhao Zhibin , Chen Hao , Liu Gang
Published: June 2022

Purpose

This paper aims to propose a method for accurate radar echo simulation of wind turbines (WTs) array. It can solve the problem of passive interference from wind farms to neighboring radar stations.

Design/methodology/approach

First of all, the equivalent model of scattering centers of a single WT is obtained by using the spatial spectrum estimation method, and the accuracy of this model is verified by the scaled model experiment; then scattering centers model of WTs array was established by using the spatial coordinate transformation method. According to the position relationship between the model and the radar, and combined with the multipath scattering theory, the radar echo equation of WTs array was deduced. Finally, the simulation analysis is carried out with the four GoldWind 77/1500 WTs as an example and compared with the traditional methods.

Findings

This paper verifies the accuracy of the equivalent model of scattering centers through the WT scaled model experiment, and through simulation analysis, it is found that the result of this method is more consistent with the multipath scattering of radar echo between WTs array in practical engineering than the traditional method.

Originality/value

Based on the theory of high-frequency scattering, this paper introduces scattering centers into the solution of radar echo and considers the multipath scattering of radar echo, then a method for solving the radar echo of WTs array based on scattering centers is proposed.
Topology optimization in magnetic shield design by using density method in combination with CNN
Authors: Isshiki Rie , Kawamata Ryota , Wakao Shinji , Murata Noboru
Published: June 2022

Purpose

The density method is one of the powerful topology optimization methods of magnetic devices. The density method has the advantage that it has a high degree of freedom of shape expression which results in a high-performance design. On the other hand, it has also the drawback that unsuitable shapes for actually manufacturing are likely to be generated, e.g. checkerboards or grayscale. The purpose of this paper is to develop a method that enables topology optimization suitable for fabrication while taking advantage of the density method.

Design/methodology/approach

This study proposes a novel topology optimization method that combines convolutional neural network (CNN) as an effective smoothing filter with the density method and apply the method to the shield design with magnetic nonlinearity.

Findings

This study demonstrated some numerical examples verifying that the proposed method enables to efficiently obtain a smooth and easy-to-manufacture shield shape with high shielding ability. A network architecture suitable as smoothing filter was also exemplified.

Originality/value

In the field of magnetic field analysis, very few studies have verified the usefulness of smoothing by using CNN in the topology optimization of magnetic devices. This paper develops a novel topology optimization method that skillfully combines CNN with the nonlinear magnetic field analysis and also clarifies a suitable network architecture that makes it possible to obtain a target device shape that is easy to manufacture while minimizing the objective function value.
Finite element modeling and simulating pilling of polyester fabric
Authors: Xiao Qi
Published: June 2022

Purpose

The paper aims to build a finite element simulation model for pilling of polyester hairiness on the fabric to study the effects of hairiness performance on pilling and reveal pilling mechanisms.

Design/methodology/approach

The finite element simulation model of pilling of polyester hairiness was established by ABAQUS. Polyester hairiness was treated as elastic thin rod, which was divided by two-node linear three-dimensional truss element. The effects of hairiness elastic modulus, hairiness friction coefficient and hairiness diameter on frictional dissipation energy, strain energy and kinetic energy produced by pilling have been studied. The analysis solution values were compared with the finite element simulation results, which was used to verify finite element simulation.

Findings

The paper provides new insights about how to reveal pilling mechanisms of polyester hairiness with different performance. Comparing finite element simulation results with analysis solutions shows that the fitness is greater than 0.96, which verifies finite element simulation. Larger hairiness elastic modulus gives rise to higher friction dissipation energy and strain energy of hairiness but lower kinetic energy. Increasing friction coefficient enhances friction dissipation and strain energy of hairiness. However, kinetic energy decreases with the increase of friction coefficient. Hairiness diameter also has an important effect on hairiness entanglement and pilling. Increasing hairiness diameter can decrease friction dissipation energy but enhance strain energy and kinetic energy.

Research limitations/implications

Finite element simulation was verified by analysis solutions. The solutions include friction dissipation energy, strain energy and kinetic energy, which cannot measured b experiment. Therefore, researchers are encouraged to simulate pilling to obtain pilling grades, which be compared with experiment results.

Originality/value

Pilling of polyester hairiness was simulated by ABAQUS. This method makes pilling process visualization, and pilling mechanisms was revealed from non-linear dynamics.
Student e-learning service quality, satisfaction, commitment and behaviour towards finance courses in COVID-19 pandemic
Authors: Ali Muhammad , Puah Chin-Hong , Fatima Shafaque , Hashmi Anum , Ashfaq Muhammad
Published: June 2022

Purpose

This research investigates the relationship between e-learning service quality dimensions, student e-learning satisfaction, commitment and behaviour towards finance courses in higher education institutes of Pakistan.

Design/methodology/approach

Due to specific study objectives, the authors gathered sample data of 359 university students who were enrolled in the traditional learning system and shifted to the e-learning environment. The study employed partial least squares-structural equation modelling (PLS-SEM) based approach using Smart PLS version 3.0.

Findings

The results indicated that out of four e-learning service quality dimensions, three dimensions (system quality, course material and instructor quality, information technology (IT) and support service quality) positively impacted student e-learning satisfaction. The other dimension of e-learning service quality (course website quality) showed a positive but insignificant effect on e-learning satisfaction. Additionally, e-learning satisfaction was positively related to e-learning commitment, which, in turn, has a positive and significant influence on student e-learning behaviour towards finance courses.

Originality/value

Overall, the study’s findings provide useful policy implications for higher education institutes, particularly in the coronavirus disease 2019 (COVID-19) pandemic.