bluuebunny/crossref_metadata_2025 huggingface dataset:
Strain estimation in aortic roots from 4D echocardiographic images using medial modeling and deformable registration
Authors: Aggarwal Ankush , Mortensen Peter , Hao Jilei , Kaczmarczyk Łukasz , Cheung Albert T. , Al Ghofaily Lourdes , Gorman Robert C. , Desai Nimesh D. , Bavaria Joseph E. , Pouch Alison M.
Published: November 2022

Even though the central role of mechanics in cardiovascular system is widely recognized, estimating mechanical deformation and strains in-vivo remains an ongoing practical challenge. Herein, we present a semi-automated framework to estimate strains from four-dimensional (4D) echocardiography images and apply it to the aortic roots of patients with normal trileaflet aortic valves (TAV) and congenital bicuspid aortic valves (BAV). The method is based on fully nonlinear shell-based kinematics, which divides the strains into in-plane (shear and dilatational) and out-of-plane components. The results indicate that, even for size-matched non-aneurysmal aortic roots, BAV patients experience larger regional shear strains in their aortic roots. This elevated strains might be a contributing factor to the higher risk of aneurysm development in BAV patients. The proposed framework is openly available and applicable to any tubular structures.
Peroxisome Biogenesis Disorders in the Zellweger Spectrum: Ophthalmic Findings from a New Natural History Study Cohort and Scoping Literature Review
Authors: Yergeau Christine , Coussa Razek Georges , Antaki Fares , Argyriou Catherine , Koenekoop Robert K. , Braverman Nancy E.
Published: November 2022

Background

Zellweger Spectrum Disorder (ZSD) is caused by bi-allelic defects in any of 13PEXgenes, resulting in failure to form functional peroxisomes. Individuals manifest a wide spectrum of clinical phenotypes and severity, but almost all have retinal degeneration leading to blindness. The onset, extent and progression of retinal findings has not been well-described and there are no therapies for treating vision loss. With expanding research and trials on retinal gene therapy for genetic disorders, it is now crucial to understand the natural history of vision loss in ZSD for defining reliable endpoints for upcoming interventional trials.

Here we describe ophthalmic findings in the largest number of ZSD patients to date.

Methods

We reviewed ophthalmology records from our retrospective longitudinal cohort of 66 patients, and cross-sectional ophthalmic findings from 79 patients reported in the literature. We divided patients by severe, intermediate or mild disease based on genotypes or their reported disease severity.

Results

We found that visual acuity (VA) declines slowly (+0.01 Logmar/year) with a mean of 0.93 Logmar (0 = normal vision, 1 = legal blindness) in all 53 intermediate-mild patients with available data. Longitudinal VA data revealed slow loss over time and legal blindness onset at average age 7.8 years. Fundoscopy showed retinal pigmentation, macular abnormalities, small or pale optic discs and attenuated vessels with higher prevalence in milder severity groups and did not change with age. Electroretinogram (ERG) tracings were diminished in 93% of patients, 40% of which were extinguished. ERG responses did not change over time in patients with multiple ERGs. Optical coherence tomography (OCT), reported only in milder patients, revealed cystoid macular edema or macular schisis in 16/21 (age 1.8-30 years). Serial OCTs showed evolution or stable macular edema.

Conclusions

Although limited by retrospective data, we highlight several useful conclusions (1) VA slowly deteriorates and is without clear association with disease severity, (2) serial ERGs are not useful for documenting vision loss progression and (3) intraretinal cysts may be common in ZSD. This study indicates that systematically reporting multiple measures will be required for accurately assessing visual function in the ZSD population, including measures of functional vision.
Early-life language deprivation affects specific neural mechanisms of semantic representations
Authors: Wang Xiaosha , Wang Bijun , Bi Yanchao
Published: November 2022

One signature of the human brain is its ability to derive knowledge from language inputs, in addition to nonlinguistic sensory channels such as vision and touch. How does human language experience specifically modulate the way in which semantic knowledge is stored in the human brain? We investigated this question using a unique early-life language-deprivation human model: early deaf adults who are born to hearing parents and thus had delayed acquisition of any natural human language (speech or sign), with early deaf adults who acquired sign language from birth as nonlinguistic sensory experience controls. Neural responses in a meaning judgment task with 90 written words that were familiar to both groups were measured using fMRI. The early language-deprived group, compared with the deaf control group, showed reduced semantic sensitivity, in both multivariate pattern (semantic structure encoding) and univariate (abstractness effect) analyses, in the left dorsal anterior temporal lobe (dATL). These results provide positive, causal evidence that the neural semantic representation in dATL is specifically supported by language, as a unique mechanism of representing (abstract) semantic space, beyond the sensory-derived semantic representations distributed in the other cortical regions.
Self-Harm by nurses and midwives: a study of hospital presentations
Authors: Groves Samantha , Lascelles Karen , Bale Liz , Brand Fiona , Casey Deborah , Hawton Keith
Published: November 2022

Background

Nursing professionals are an occupational group at increased risk of suicide, but little is known about self-harm in this population.

Aims

To investigate the characteristics of nurses and midwives who present to hospital following self-harm.

Method

We used data from the Oxford Monitoring System for Self-Harm to identify nurses and midwives who presented to the general hospital in Oxford during 2010-2020 following an episode of self-harm and received a psychosocial assessment.

Results

During the eleven-year study period, 107 presentations of self-harm involving 81 nurses and midwives were identified. Self-poisoning was the most common self-harm method, with antidepressants and paracetamol most frequently involved. A large proportion had consumed alcohol prior to or during the self-harm act. Some individuals had high suicide intent. Common issues preceding self-harm included problems with a partner, psychiatric disorder, problems with employment, and alcohol misuse. A range of aftercare options were offered following hospital presentation.

Limitations

This study was limited to data from a single hospital.

Conclusion

Prevention and management of self-harm within this occupational group requires preventative strategies and availability of interventions addressing the range of factors that may contribute to self-harm, especially relationship problems, psychiatric disorders, employment problems, and alcohol misuse.
Diversity and level of evidence evaluation of commercial pharmacogenomic testing for mental health
Authors: Morosoli José J. , Lind Penelope A. , Spears Kristina , Pratt Gregory , Medland Sarah E.
Published: November 2022

This study examined arrays offered by commercial pharmacogenomic (PGx) testing services for mental health care in Australia and the United States, with a focus on utility for non-European populations. Seven of the 14 testing services we identified provided the manifests of their arrays. We examined allele frequencies for each variant using data from the Allele Frequency Aggregator1(ALFA), genome Aggregation Database2(gnomAD), Exome Aggregation Consortium2(ExAC), and Japanese Multi Omics Reference Panel3, and examined genetic heterogeneity. We also analyzed meta-data from the Pharmacogenomic Knowledge Base4(PharmGKB) and explored the biogeographical origin of supporting evidence for clinical annotations. Most arrays included the minimum allele set recommended by Bousman et al5. However, few arrays includedHLA-AorHLA-B. The most diverse allele frequencies were seen for variants inCYP3A5, ADRA2AandGNB3, with European and African populations showing the largest differences. Most evidence listed in PharmGKB originated from European or unknown ancestry samples.
Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine
Authors: Yamamoto Shohei , Oshiro Yusuke , Inamura Natsumi , Nemoto Takashi , Horii Kumi , Okudera Kaori , Konishi Maki , Ozeki Mitsuru , Mizoue Tetsuya , Sugiyama Haruhito , Aoyanagi Nobuyoshi , Sugiura Wataru , Ohmagari Norio
Published: November 2022

Background

Epidemiological data regarding differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination are scarce.

Methods

We repeatedly assessed the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants.

Results

A total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (per 30 days [95% CI]) was slower after 3-dose (25% [23–26]) than 2-dose (36% [35–37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9–22]); 3-dose plus infection (21% [17–25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3-dose, except for sex (lower in female participants) and immunosuppressant use. Antibody waning was faster in older participants, females, and alcohol drinkers after 2-dose, whereas it did not differ after 3-dose across except sex.

Conclusions

The 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection further enhanced its durability. The antibody levels at a given time point and waning speed after 2-dose differed across background factors; however, these differences mostly diminished after 3-dose.
PIQUE: An ImageJ plugin for the quantification of toroidal nuclei in biological images
Authors: Pons Carles , Mauvezin Caroline
Published: November 2022

The toroidal nucleus is a novel chromosomal instability (CIN) biomarker which complements the micronucleus. Understanding the specific biological stresses leading to the formation of each CIN-associated phenotype requires the evaluation of large panels of biological images collected from different genetic backgrounds and environmental conditions. However, the quantification of toroidal nuclei is currently a manual process which is unviable on a large scale. Here, we present PIQUE (Processing of Images for the QUantification of toroidal nuclEi), a tool that automates the identification of toroidal nuclei, minimizing false positives while highly agreeing with the manual quantifications. Additionally, PIQUE identifies micronuclei for a convenient comparison of both CIN biomarkers. PIQUE is an open-source ImageJ plugin with a user-friendly interface that enables a wide scientific community to easily study the novel toroidal nucleus for the analysis of CIN levels in cellular models.

Availability

The plugin, the user manual, and the images used for the evaluation of PIQUE are available upon request from the authors.

Contact

carles.pons@irbbarcelona.organdcaroline.mauvezin@ub.edu
Age-related changes in “cortical” 1/f dynamics are linked to cardiac activity
Authors: Schmidt Fabian , Danböck Sarah K. , Trinka Eugen , Klein Dominic P. , Demarchi Gianpaolo , Weisz Nathan
Published: November 2022

The power of electrophysiologically measured cortical activity decays with an approximately1/fXfunction. The slope of this decay (i.e. the spectral exponent,X) is modulated by various factors such as age, cognitive states or psychiatric/neurological disorders. Interestingly, a mostly parallel line of research has also uncovered similar effects for the spectral slope in the electrocardiogram (ECG). This raises the question whether these bodywide changes in spectral slopes are (in-)dependent. Focusing on well-established age-related changes in spectral slopes we analyzed a total of 1282 recordings of magnetoencephalography (MEG) resting state measurements with concurrent ECG in an age-diverse sample (18-88 years). Using a diverse array of analytical approaches, we demonstrate that the aperiodic signal recorded via surface electrodes/sensors originates from multiple physiological sources. Furthermore, our results suggest that common “artifact” rejection approaches (i.e. ICA) may not be sufficient to separate cardiac from neural activity. In particular, significant parts of age-related changes in aperiodic activity normally interpreted to be of neural origin can be explained by cardiac activity. Moreover, our results suggest that changes (flattening/steepening) of the spectral slope with age are dependent on the recording site and investigated frequency range. Our results highlight the complexity of aperiodic activity while raising concerns when interpreting aperiodic activity as “cortical“ without considering physiological influences.
Incoherent merger network for robust ratiometric gene expression response
Authors: Kwon Ukjin , Huang Hsin-Ho , Chávez Jorge L. , Beabout Kathryn , Harbaugh Svetlana , Vecchio Domitilla Del
Published: November 2022

A ratiometric response gives an output that is proportional to the ratio between the magnitudes of two inputs. Ratio computation has been observed in nature and is also needed in the development of smart probiotics and organoids. Here, we achieve ratiometric gene expression response in bacteriaE. coliwith the incoherent merger network. In this network, one input molecule activates expression of the output protein while the other molecule activates an intermediate protein that enhances the output’s degradation. When degradation rate is first order and faster than dilution, the output responds linearly to the ratio between the input molecules’ levels over a wide range withR2close to 1. Response sensitivity can be quantitatively tuned by varying the output’s translation rate. Furthermore, ratiometric responses are robust to global perturbations in cellular components that influence gene expression because such perturbations affect the output through an incoherent feedforward loop. This work demonstrates a new molecular signal processing mechanism for multiplexed sense-and-respond circuits that are robust to intra-cellular context.
Antifungal activity of selected lactic acid bacteria from olive drupes
Authors: Riolo Mario , Luz Carlos , Santilli Elena , Meca Giuseppe , Cacciola Santa Olga
Published: November 2022

In this study, 16 Lactobacilli (LABs) isolated from the drupes of olive (Olea europaea) oil varieties were identified asLactiplantibacillus plantarum(seven isolates),Pediococcus pentosaceus(six isolates),Enterococcus faecium(two isolates) andStreptococcus salivarius(a single isolate) by peptide mass fingerprinting and sequencing of the 16S rRNA. Antifungal activity of LABs and their cell-free fermentates (CFSs) against several plant pathogenic fungi and oomycetes (fungisensu lato), includingAlternaria, Aspergillus Colletotrichum, Penicillium, PlenodomusandPhytophthora, was evaluatedin vitrousing the culture overlaying and the agar diffusion tests. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined. LABs showed antifungal activity against the fungisensu latotested. The most noticeable inhibitory activity was shown by isolates ofL. plantarumandP. pentosaceusagainstFusarium oxysporum, Colletotrichumspecies andPenicillium nordicum. Chemical analysis revealed CFSs contained acid lactic and variable quantities of 14 diverse phenolic acids and 26 volatile organic compounds (VOCs). No obvious correlation was found between the metabolic profile of LABs and their antifungal efficacy. However, it is the first time that the potential of fermentates of LABs, recovered from drupes of olive oil varieties, as natural fungicides, was demonstrated.
DNA-caged Nanoparticles via Electrostatic Self-Assembly
Authors: Jergens Elizabeth , de Araujo Fernandes-Junior Silvio , Cui Yixiao , Robbins Ariel , Castro Carlos E. , Poirier Michael G. , Gurcan Metin N. , Otero Jose J. , Winter Jessica O.
Published: November 2022

DNA-modified nanoparticles enable DNA sensing and therapeutics in nanomedicine and are also crucial for nanoparticle self-assembly with DNA-based materials. However, methods to conjugate DNA to nanoparticle surfaces are limited, inefficient, and lack control. Inspired by DNA tile nanotechnology, we demonstrate a new approach to nanoparticle modification based on electrostatic attraction between negatively charged DNA tiles and positively charged nanoparticles. This approach does not disrupt nanoparticle surfaces and leverages the programmability of DNA nanotechnology to control DNA presentation. We demonstrated this approach using a variety of nanoparticles, including polymeric micelles, polystyrene beads, gold nanoparticles, and superparamagnetic iron oxide nanoparticles with sizes ranging from 5-20 nm in diameter. DNA cage formation was confirmed through transmission electron microscopy (TEM), neutralization of zeta potential, and a series of fluorescence experiments. DNA cages present “handle” sequences that can be used for reversible target attachment or self-assembly. Handle functionality was verified in solution, at the solid-liquid interface, and inside fixed cells, corresponding to applications in biosensing, DNA microarrays, and erasable immunocytochemistry. These experiments demonstrate the versatility of the electrostatic DNA caging approach and provide a new pathway to nanoparticle modification with DNA that will empower further applications of these materials in medicine and materials science.
A Peptide Triple Agonist of GLP-1, Neuropeptide Y1, and Neuropeptide Y2 Receptors Promotes Glycemic Control and Weight Loss
Authors: Chichura Kylie S. , Elfers Clinton T. , Salameh Therese , Kamat Varun , Chepurny Oleg G. , McGivney Aelish , Milliken Brandon T. , Holz George G. , Applebey Sarah V. , Hayes Matthew R. , Sweet Ian R. , Roth Christian L. , Doyle Robert P.
Published: November 2022

Mechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery include changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism. These agonists also promote insulin-independent Y1-R-mediated glucose uptake in muscle tissueex vivoand more profound reductions in food intake and body weight than liraglutide when administered to diet-induced obese rats. Our findings support a role for Y1-R signaling in glucoregulation and highlight the therapeutic potential of simultaneous receptor targeting to achieve long-term benefits for millions of patients.
Linking Gene Expression to Clinical Outcomes in Pediatric Crohn’s Disease Using Machine Learning
Authors: Chen Kevin A , Nishiyama Nina , Kennedy Ng Meaghan M , Shumway Alexandra , Joisa Chinmaya U , Schaner Matthew R , Lian Grace , Beasley Caroline , Zhu Lee-Ching , Bantumilli Surekha , Kapadia Muneera R , Gomez Shawn M , Furey Terrence S , Sheikh Shehzad Z
Published: November 2022

Introduction

Pediatric Crohn’s disease (CD) is the fastest growing age group and is characterized by frequent disease complications. We sought to analyze both ileal and colonic gene expression in a cohort of pediatric CD patients and apply machine learning-based models to predict risk of developing future complications.

Methods

RNA-seq was generated from matched ileal and colonic biopsies from formalin-fixed, paraffin-embedded (FFPE) tissue obtained from patients with non-stricturing/non-penetrating, treatment-naïve CD and from controls. Clinical outcomes including development of strictures or fistulas, progression to surgery, and remission were analyzed first using differential expression. Machine learning models were then developed for each outcome, combining gene expression and clinical factors. Models were assessed using area under the receiver operating characteristic curve (AUROC).

Results

56 patients with CD and 46 controls were included. Differential expression analysis revealed a distinct colonic transcriptome for patients who developed strictures, with downregulation of pathways related to inflammation and extra-cellular matrix production. In contrast, there were few differentially expressed genes for other outcomes and for ileal tissue. Despite this, machine learning-based models were able to incorporate colonic gene expression and clinical characteristics to predict outcomes with high accuracy. Models showed an AUROC of 0.84 for strictures, 0.83 for remission, and 0.75 for surgery. Certain genes with potential prognostic importance for strictures (REG1A, MMP3, and DUOX2) were not identified in single gene differential analysis but were found to have strong contributions to predictive models.

Conclusions

Our findings in FFPE tissue support the importance of colonic gene expression and the potential for machine learning-based models in predicting outcomes for pediatric CD.
Adenovirus type 34 and HVR1-deleted Adenovirus type 5 do not bind to PF4: clearing the path towards vectors without thrombosis risk
Authors: Sallard Erwan , Pembaur Daniel , Schröer Katrin , Schellhorn Sebastian , Koukou Georgia , Schmidt Natascha , Zhang Wenli , Kreppel Florian , Ehrhardt Anja
Published: November 2022

The adenoviral vector based AstraZeneca and Janssen COVID vaccines have been associated with rare cases of thrombosis, a condition which depends on adenovirus binding to the blood protein Platelet Factor 4 (PF4).

In order to identify adenoviruses with low or absent affinity for PF4, we screened dozens of types from various adenovirus species, and Adenovirus type 5 (Ad5) derived vectors carrying genetic or chemical modifications of different hexon hyper-variable regions (HVR). For this purpose, we established an armamentarium of techniques including ELISA-qPCR and Aggregate Pull-Down (APD), which enabled fast and sensitive assessments of virus-protein interactions.

Unlike most tested serotypes, Ad34 did not bind to PF4. Likewise, the deletion or shielding of the HVR1 loop of Ad5 seemingly ablated its PF4 binding. Therefore, we showed that PF4 binds to adenovirus hexon through interactions dependent on HVR1, and identified vectors that may avoid or decrease the risk of thrombosis and represent safer candidates for vaccine or gene therapy vector development.
NOX2 Inhibition Enables Retention of the Circadian Clock in BV2 Microglia and Primary Macrophages
Authors: Muthukumarasamy Iswarya , Buel Sharleen M. , Hurley Jennifer M. , Dordick Jonathan S.
Published: November 2022

Sustained neuroinflammation is a major contributor to the progression of neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD) diseases. Neuroinflammation, like other cellular processes, is affected by the circadian clock. Microglia, the resident immune cells in the brain, act as major contributors to neuroinflammation and are under the influence of the circadian clock. Microglial responses such as activation, recruitment, and cytokine expression are rhythmic in their response to various stimuli. While the link between circadian rhythms and neuroinflammation is clear, significant gaps remain in our understanding of this complex relationship. To further our understanding of this relationship, we studied the interaction between the microglial circadian clock and the enzyme NADPH Oxidase Isoform 2 (NOX2), an enzyme essential for the production of reactive oxygen species (ROS) in oxidative stress, an integral characteristic of neuroinflammation. We examined BV2 microglia over circadian time, demonstrating oscillations of the clock genesPer2andBmal1and the NOX2 subunitsgp91phoxandp47phox. We discovered the BV2 microglial clock exerted significant control over NOX2 expression and that the inhibition of NOX2 enabled the microglia to retain a functional circadian clock while reducing levels of ROS and inflammatory cytokines. These trends were mirrored in mouse bone marrow-derived primary macrophages. Our findings indicate NOX2 plays a crucial role in the interaction between the circadian clock and the activation of microglia/macrophages into their pro-inflammatory state.
Genetic association models are robust to common population kinship estimation biases
Authors: Hou Zhuoran , Ochoa Alejandro
Published: November 2022

Common genetic association models for structured populations, including Principal Component Analysis (PCA) and Linear Mixed-effects Models (LMM), model the correlation structure between individuals using population kinship matrices, also known as Genetic Relatedness Matrices or “GRMs”. However, the most common kinship estimators can have severe biases that were only recently determined. Here we characterize the effect of these kinship biases on genetic association. We employ a large simulated admixed family and genotypes from the 1000 Genomes Project, both with simulated traits, to evaluate key kinship estimators. Remarkably, we find practically invariant association statistics for kinship matrices of different bias types (matching all other features). We then prove using statistical theory and linear algebra that LMM association tests are invariant to these kinship biases, and PCA approximately so. Our proof shows that the intercept and relatedness effect coefficients compensate for the kinship bias, an argument that extends to generalized linear models. As a corollary, association testing is also invariant to changing the reference ancestral population of the kinship matrix. Lastly, we observed that all kinship estimators, except for popkin ROM, can give improper non-positive semidefinite matrices, which can be problematic although some LMMs handle them surprisingly well, and condition numbers can be used to choose kinship estimators. Overall, we find that existing association studies are robust to kinship estimation bias, and our calculations may help improve association methods by taking advantage of this unexpected robustness, as well as help determine the effects of kinship bias in related problems.
The grape powdery mildew resistance lociRen2, Ren3, Ren4D, Ren4U, Run1, Run1.2b, Run2.1, andRun2.2activate different transcriptional responses toErysiphe necator
Authors: Massonnet Mélanie , Riaz Summaira , Pap Dániel , Figueroa-Balderas Rosa , Walker M. Andrew , Cantu Dario
Published: November 2022

Multiple grape powdery mildew (PM) genetic resistance (R) loci have been found in wild grape species. Little is known about the defense responses associated with eachRlocus. In this study, we compare the defense mechanisms associated with PM resistance in interspecific crosses segregating for a singleRlocus fromMuscadinia rotundifolia(Run1, Run1.2b, Run2.1, Run2.2),Vitis cinerea(Ren2),V. romanetii(Ren4DandRen4U), and the interspecific hybrid Villard blanc (Ren3). By combining optical microscopy, visual scoring, and biomass estimation, we show that the eightRloci confer resistance by limiting infection at different stages. We assessed the defense mechanisms triggered in response to PM at 1 and 5 days post inoculation (dpi) via RNA sequencing. To account for the genetic differences between species, we developed for each accession a diploid synthetic reference transcriptome by incorporating into thePN40024reference homozygous and heterozygous sequence variants andde novoassembled transcripts. Most of theRloci exhibited a higher number of differentially expressed genes (DEGs) associated with PM resistance at 1 dpi compared to 5 dpi, suggesting that PM resistance is mostly associated with an early transcriptional reprogramming. Comparison of the PM resistance-associated DEGs showed a limited overlap between pairs ofRloci, and nearly half of the DEGs were specific to a singleRlocus. The largest overlap of PM resistance-associated DEGs was found betweenRen3+,Ren4D+, andRen4U+genotypes at 1 dpi, and betweenRen4U+andRun1+accessions at 5 dpi. TheRen3+,Ren4D+, andRen4U+were also found to have the highest number ofRlocus-specific DEGs in response to PM. Both shared andRlocus-specific DEGs included genes from different defense-related categories, indicating that the presence ofE. necatortriggered distinct transcriptional responses in the eightRloci.
Optimizing the Martini 3 force field reveals the effects of the intricate balance between protein-water interaction strength and salt concentration on biomolecular condensate formation
Authors: Zerze Gül H.
Published: November 2022

Condensation/dissolution has become a widely acknowledged biological macromolecular assembly phenomenon in subcellular compartmentalization. MARTINI force field offers a coarse-grained protein model with a resolution that preserves molecular details with an explicit (CG) solvent. Despite its relatively higher resolution, it can still achieve condensate formation in reasonable computing time with explicit solvent and ionic species. Therefore, it is highly desirable to tune this force field to be able to reproduce the experimentally observed properties of the condensate formation. In this work, we studied the condensate formation of the low-sequence complexity (LC) domain of FUsed in Sarcoma (FUS) protein using a MARTINI 3 force field by systematically modifying (increasing) the protein-water interaction strength and varying salt concentration. We found that the condensate formation is sensitive both to the protein-water interaction strength and the presence of salt. While the unmodified MARTINI force field yields a complete collapse of proteins into one dense phase (i.e., no dilute phase), we reported a range of modified protein-water interaction strength that is capable of capturing the experimentally found transfer free energy between dense and dilute phases. We also found that the condensates lose their spherical shape upon the addition of salt, especially when the protein-water interactions are weak. Inter-chain amino acid contact map analysis showed one explanation for this observation: the protein-protein contact fraction reduces as salt is added to systems (when the protein-water interactions are weak), consistent with electrostatic screening effects. This reduction might be responsible for the condensates becoming nonspherical upon the addition of salt by reducing the need for minimizing interfacial area. However, as the protein-water interactions become stronger to the extent that makes the transfer free energy agree well with experimentally observed transfer free energy, we found an increase in protein-protein contact fraction upon the addition of salt, consistent with the salting-out effects. Therefore, we concluded that there is an intricate balance between screening effects and salting-out effects upon the addition of salt and this balance is highly sensitive to the strength of protein-water interactions.
Configurational entropy-based screening and selection of hydrophilic polymers using the tripartite split green fluorescent protein
Authors: Banerjee Shounak , Minko Yury , Anaya Elizabeth S , Sasiene Zachary J , Schmidt Jurgen G , Strauss Charlie E M , Waldo Geoffrey S
Published: November 2022

Measuring the entropic properties of polymers such as proteins is critical to accurate prediction of their functional properties. However, the measurement of configurational entropy is possible only by low throughput techniques such as calorimetry, NMR and CD spectroscopy. Moreover, to our knowledge no system exists that allows molecular selection/enrichment based on the molecules configurational entropy. We tested the ability of the scalable tripartite GFP system to offer fine resolution of differences in configurational entropy in molecules and to isolate molecules based on their configurational entropy. The system was able to both finely resolve molecules with different configurational entropies, as well as capture them for isolation. We were able to tune the sensitivity of the system by using different mutations of the protein components. Lastly, we were able to apply the system to polypeptoid molecules and posit that the system may be applied to any other hydrophilic polymer of up to 10^3 repeating units.
Bursting Translation on Single mRNAs in Live Cells
Authors: Livingston Nathan M. , Kwon Jiwoong , Valera Oliver , Saba James A. , Sinha Niladri K. , Reddy Pranav , Nelson Blake , Wolfe Clara , Ha Taekjip , Green Rachel , Liu Jian , Wu Bin
Published: November 2022

Stochasticity has emerged as a mechanism to control gene expression. Much of this so-called “noise” has been attributed to bursting transcription. However, the stochasticity of translation has not similarly been investigated due to a lack of enabling imaging technologies. We developed techniques to track single mRNAs and their translation in live cells for hours, allowing measurement of previously uncharacterized translation dynamics. We applied genetic and pharmacological perturbations to control translation kinetics. Like transcription, translation is not a constitutive process but instead cycles between inactive and active states or “bursts”. But unlike transcription, which is largely frequency modulated, complex structure in the 5’-untranslated region alters burst amplitude. Bursting frequency can be controlled through cap-proximal sequences andtrans-acting factors such as eIF4F. We coupled single molecule imaging with stochastic modeling to deduce the fundamental kinetic parameters of translational bursting, a new dimension of translational control.

Highlights

Long-term tracking of single mRNAs reveals multi-state, bursting translation

Structure in the 5’-untranslated region modulates translational burst amplitude

5’-cap proximal sequences modulate translational burst frequency

mTOR signaling adjusts translation bursting to respond to environmental cues
Localization ofKif1cmRNA to cell protrusions dictates binding partner specificity of the encoded protein
Authors: Norris Megan L. , Mendell Joshua T.
Published: November 2022

Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In non-neuronal cells, a subset of mRNAs localize to cell protrusions and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show thatKif1cmRNA localization does not regulate KIF1C protein abundance, distribution, or ability to traffic other mRNAs. Conversely, robustKif1cmRNA localization is required for directed cell migration. We used mass spectrometry to identify binding partners of endogenous KIF1C, which revealed dramatic dysregulation of the number and identity of KIF1C interactors in response toKif1cmRNA mis-localization. These results therefore uncovered a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein-protein interactions. We anticipate that this mechanism is not limited toKif1cand is likely to be a general principle used by protrusion-enriched mRNAs in non-neuronal cells.
STAMarker: Determining spatial domain-specific variable genes with saliency maps in deep learning
Authors: Zhang Chihao , Dong Kangning , Aihara Kazuyuki , Chen Luonan , Zhang Shihua
Published: November 2022

Spatial transcriptomics characterizes gene expression profiles while retaining the information of the spatial context, providing an unprecedented opportunity to understand cellular systems. One of the essential tasks in such data analysis is to determine spatially variable genes (SVGs), which demonstrate spatial expression patterns. Existing methods only consider genes individually and fail to model the inter-dependence of genes. To this end, we present an analytic tool STAMarker for robustly determining spatial domain-specific SVGs with saliency maps in deep learning. STAMarker is a three-stage ensemble framework consisting of graphattention autoencoders, multilayer perceptron (MLP) classifiers, and saliency map computation by the backpropagated gradient. We illustrate the effectiveness of STAMarker and compare it with three competing methods on four spatial transcriptomic data generated by various platforms. STAMarker considers all genes at once and is more robust when the dataset is very sparse. STAMarker could identify spatial domain-specific SVGs for characterizing spatial domains and enable in-depth analysis of the region of interest in the tissue section.
5-(4-Methoxyphenyl)-1-[4-(4-methoxyphenyl)thiazol-2-yl]-3-[4-(prop-2-ynyloxy)phenyl]-4,5-dihydro-1H-pyrazole
Authors: Archana Sreeramapura D. , Nagma Banu Holalagudu A. , Kalluraya Balakrishna , Yathirajan Hemmige S. , Balerao Rishik , Butcher Ray J.
Published: November 2022

The title compound, C29H25N3O3S, crystallizes in the monoclinic space group P21/n. The molecule contains a central four-ring system in which all of the rings are almost coplanar. Both the 4-methoxyphenyl ring and the prop-2-ynyloxy substituent are disordered over two equivalent conformations with occupancy ratios of 0.903 (2):0.097 (2) and 0.776 (5):0.224 (5), respectively. In the crystal, π–π interactions [centroid–centroid distance = 3.7327 (11) Å] between the dihydropyrazole ring and the 4-methoxyphenyl ring link the molecules into centrosymmetric dimers. In addition, there are weak C—H...S, C—H...N and C—H...O interactions, which link the molecules into a complex three-dimensional array.
Five-dimensional memristive Hopfield neural network dynamics analysis and its application in secure communication
Authors: Yin Xinxing , Chen Juan , Yu Wenxin , Huang Yuan , Wei Wenxiang , Xiang Xinjie , Yan Hao
Published: November 2022

Purpose

This study aims to improve the complexity of chaotic systems and the security accuracy of information encrypted transmission. Applying five-dimensional memristive Hopfield neural network (5D-HNN) to secure communication will greatly improve the confidentiality of signal transmission and greatly enhance the anticracking ability of the system.

Design/methodology/approach

Chaos masking: Chaos masking is the process of superimposing a message signal directly into a chaotic signal and masking the signal using the randomness of the chaotic output. Synchronous coupling: The coupled synchronization method first replicates the drive system to get the response system, and then adds the appropriate coupling term between the drive The synchronization error and the coupling term of the system will eventually converge to zero with time. The synchronization error and coupling term of the system will eventually converge to zero over time.

Findings

A 5D memristive neural network is obtained based on the original four-dimensional memristive neural network through the feedback control method. The system has five equations and contains infinite balance points. Compared with other systems, the 5D-HNN has rich dynamic behaviors, and the most unique feature is that it has multistable characteristics. First, its dissipation property, equilibrium point stability, bifurcation graph and Lyapunov exponent spectrum are analyzed to verify its chaotic state, and the system characteristics are more complex. Different dynamic characteristics can be obtained by adjusting the parameter k.

Originality/value

A new 5D memristive HNN is proposed and used in the secure communication
CEO demographics and gender diversity in senior management in large Scandinavian firms
Authors: Garcia-Blandon Josep , Argilés-Bosch Josep , Ravenda Diego
Published: November 2022

Purpose

This study aims to investigate whether chief executive officer (CEO) demographics are associated with gender diversity in senior management in the Scandinavia region.

Design/methodology/approach

The research design draws on multivariate cross-sectional analysis. The demographic characteristics examined are gender, age and education. A total of six hypotheses are developed and tested. The sample includes the largest 106 public firms from Denmark, Finland, Norway and Sweden.

Findings

Results show that firms with female CEOs have more women in senior management than other firms. However, neither age nor level of formal education of CEOs shows significant results, with the exception of CEOs holding MBA degrees, who are associated with fewer women in these positions. Interestingly, the association between educational background and gender diversity is principally driven by study-abroad experiences. Finally, results show that gender diversity in senior management has an important country component, whereas the industry component is negligible.

Originality/value

The relationship between managers’ demographics and gender diversity among subordinates is a relatively unexplored research issue, as previous works have focused on general comparisons between male and female managers. Furthermore, the Scandinavian context is particularly interesting as this region leads gender equality rankings.
The spatial-temporal evolution analysis of carbon emission of China's thermal power industry based on the three-stage SBM—DEA model
Authors: Xu Guoquan , Feng Shiwei , Guo Shucen , Ye Xiaolan
Published: November 2022

Purpose

China has proposed two-stage goals of carbon peaking by 2030 and carbon neutralization by 2060. The carbon emission reduction effect of the power industry, especially the thermal power industry, will directly affect the progress of the goal. This paper aims to reveal the spatial-temporal characteristics and influencing factors of carbon emission efficiency of the thermal power industry and proposes policy suggestions for realizing China’s carbon peak and carbon neutralization goals.

Design/methodology/approach

This paper evaluates and compares the carbon emission efficiency of the thermal power industry in 29 provinces and regions in China from 2014 to 2019 based on the three-stage slacks-based measure (SBM) of efficiency in data envelopment analysis (DEA) model of undesired output, excluding the influence of environmental factors and random errors.

Findings

Empirical results show that during the sample period, the carbon emission efficiency of China’s thermal power industry shows a fluctuating upward trend, and the carbon emission efficiency varies greatly among the provincial regions. The carbon emission efficiency of the interregional thermal power industry presents a pattern of “eastern > central > western,” which is consistent with the level of regional economic development. Environmental factors such as economic level and environmental regulation level are conducive to the improvement of carbon emission efficiency of the thermal power industry, but the proportion of thermal power generation and industrial structure is the opposite.

Originality/value

This paper adopts the three-stage SBM–DEA model of undesired output and takes CO2 as the undesired output to reveal the spatial-temporal characteristics and influencing factors of carbon emission efficiency in China’s thermal power industry. The results provide a more comprehensive perspective for regional comparative evaluation and influencing factors of carbon emission efficiency in China’s thermal power industry.
Predictive Six Sigma for Turkish manufacturers: utilization of machine learning tools in DMAIC
Authors: Uluskan Meryem , Karşı Merve Gizem
Published: November 2022

Purpose

This study aims to emphasize utilization of Predictive Six Sigma to achieve process improvements based on machine learning (ML) techniques embedded in define, measure, analyze, improve, control (DMAIC). With this aim, this study presents selection and utilization of ML techniques, including multiple linear regression (MLR), artificial neural network (ANN), random forests (RF), gradient boosting machines (GBM) and k-nearest neighbors (k-NN) in the analyze and improve phases of Six Sigma DMAIC.

Design/methodology/approach

A data set containing 320 observations with nine input and one output variables is used. To achieve the objective which was to decrease the number of fabric defects, five ML techniques were compared in terms of prediction performance and best tools were selected. Next, most important causes of defects were determined via these tools. Finally, parameter optimization was conducted for minimum number of defects.

Findings

Among five ML tools, ANN, GBM and RF are found to be the best predictors. Out of nine potential causes, “machine speed” and “fabric width” are determined as the most important variables by using these tools. Then, optimum values for “machine speed” and “fabric width” for fabric defect minimization are determined both via regression response optimizer and ANN surface optimization. Ultimately, average defect number was decreased from 13/roll to 3/roll, which is a considerable decrease attained through utilization of ML techniques in Six Sigma.

Originality/value

Addressing an important gap in Six Sigma literature, in this study, certain ML techniques (i.e. MLR, ANN, RF, GBM and k-NN) are compared and the ones possessing best performances are used in the analyze and improve phases of Six Sigma DMAIC.
Prioritizing the mitigation strategies to lean and green barriers using fuzzy BWM-FTOPSIS method in the food supply chain: an empirical case study
Authors: Srinivasan Kumar , Yadav Vineet Kumar , Kumar Anish , Margabandu Balaganesh , Selvaraj Janish , Kumar Anshu
Published: November 2022

Purpose

This paper aims to assist managers and food supply chain practitioners in efficiently implementing lean and green (LG) practices for sustainability. Examining barriers to LG practices, as well as prioritizing mitigation strategies in the food supply chain, are all part of this work.

Design/methodology/approach

Using a combination of literature review and expert team inputs, this paper investigated the LG barriers and their solutions under PESTEL (Political, Economic, Social, Technological, Environmental and Legal) framework. To prioritize them, this work used the fuzzy best worst method (fuzzy BWM) with the fuzzy technique for order preference by similarity to ideal solution (FTOPSIS).

Findings

From the fuzzy BWM, the economic barriers were identified as the most significant. From the FTOPSIS approach, top management expertise and commitment to adopting LG practices were identified as the best solution for overcoming the barriers.

Practical implications

This paper discusses the barriers and solutions for successfully implementing LG techniques from the real-time food supply chain. The practitioners and food chain managers welcomed the methodology for its use in prioritizing the barriers to LG practices. Conclusions drawn from this work were found to be realistic.

Originality/value

The original contribution of this study is to present the model framework for barriers and solutions of LG practices in the dairy supply chain using the hybrid MCDM technique.