bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a Deep Learning Ultrasonography Model to Classify Thyroid Nodules as Benign
Authors: Peddakama Rishi
Published: January 2023

1.

Thyroid cancer, or the occurrence of rapid cell growth in the thyroid gland located near the neck, is the fastest growing cancer among women. Papillary thyroid cancer leads to hormonal imbalances thus causing periods of fatigue, difficulty breathing, and an overall decrease in one’s quality of life.

Unsurprisingly, the need for a quick diagnosis of thyroid cancer has become ever more important. Deep learning is a subset of machine learning that may improve the diagnostic performance of ultrasound, including in the evaluation of thyroid nodules (irregular growths that develop on the gland) for benign vs. malignant disease. Currently, the standard method to differentiate benign or malignant thyroid nodules is an invasive test known as Fine Needle Aspirations (FNAs) that is uncomfortable and may lead to unwanted outcomes such as bleeding, and infection.

We propose using a convolutional neural network with a foundation rooted in two pre-trained networks, VGG-16 and InceptionV3, to train a model on the publicly available Thyroid Digital Image Database to accurately classify thyroid nodules on ultrasonography into those that are malignant or benign; a non-invasive strategy.

The data was augmented using industry-standard methods and provisioned into train/test/validation sets obtaining 88% accuracy and an area under the receiver operating characteristic (ROC) of 0.929 (signifying a high sensitivity).

Based on the model’s results, it is conceived that a convolutional neural network can serve as an accurate classifier of malignant/benign thyroid nodules from an ultrasound and enhance a diagnostic strategy to reduce unnecessary FNA procedures.
Defining Cardiac Nerve Architecture During Development, Disease, and Regeneration
Authors: Salamon Rebecca J. , Halbe Poorva , Kasberg William , Bae Jiyoung , Audhya Anjon , Mahmoud Ahmed I.
Published: January 2023

Cardiac nerves regulate neonatal mouse heart regeneration and are susceptible to pathological remodeling following adult injury. Understanding cardiac nerve remodeling can lead to new strategies to promote cardiac repair. Our current understanding of cardiac nerve architecture has been limited to two-dimensional analysis. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling tools to define cardiac nerve architecture and neurovascular association during development, disease, and regeneration. Our results demonstrate that cardiac nerves sequentially associate with coronary veins and arteries during development. Remarkably, our results reveal that parasympathetic nerves densely innervate the ventricles. Furthermore, parasympathetic and sympathetic nerves develop synchronously and are intertwined throughout the ventricles. Importantly, the regenerating myocardium reestablishes physiological innervation, in stark contrast to the non-regenerating heart. Mechanistically, reinnervation during regeneration is dependent on collateral artery formation. Our results reveal how defining cardiac nerve remodeling during homeostasis, disease, and regeneration can identify new therapies for cardiac disease.
A stronger association of depression with rheumatoid arthritis in presence of obesity and hypertriglyceridemia
Authors: Shand Grayden , Fuller Daniel T. , Lufkin Leon , Lovelett Carly , Pal Nabendu , Mondal Sumona , Sur Shantanu
Published: January 2023

Background

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic and systemic inflammation. Recent research underscores the role of chronic inflammation in multiple common RA comorbidities such as depression, obesity, and cardiovascular diseases (CVDs), suggesting a potential overlap of the pathogenic mechanisms for RA. However, it is not well understood how the coexistence of these comorbid conditions impacts the risk of RA and whether any such association relates to the inflammatory status of the body.

Methods

We used data from the 2007-2010 United States National Health and Nutrition Examination Survey (NHANES) database and compared RA prevalence between subsamples with the presence of any two conditions among depression, obesity, and hypertriglyceridemia (HTG). Each subsample was further divided into three categories based on the serum level of the inflammatory marker C-reactive protein (CRP) and analyzed for statistically significant differences using three-way χ2tests of independence.

Results

The study was conducted on 4,136 patients who fulfilled the inclusion criteria (representing 163,540,241 individuals after adjustment for sampling weights). Rates of depression, obesity, and HTG were found to be significantly higher (P< 0.001) among the subjects with RA compared with the control population with no arthritis. The presence of depression along with obesity or HTG showed a noticeably higher RA prevalence but such an association was not observed for the combination of obesity and HTG. The synergistic effect of HTG with depression was found to be most prominent at a medium CRP level (1-3 mg/L), while for obesity, the effect was observed across all CRP levels examined. These findings were further confirmed by the three-way χ2test for independence.

Conclusions

The presence of obesity or HTG in subjects suffering from depression might pose an increased risk of RA. Inflammatory mechanisms potentially play an important underlying role as suggested by the strong dependency of the association to CRP level. Identification of synergistic associations between RA risk conditions could provide useful information to predict the development and progress of RA.
CircPLXNA2affects the proliferation and apoptosis of myoblast throughcircPLXNA2/gga-miR-12207-5P/MDM4axis
Authors: Dong Xu , Xing Jia-bao , Liu Qingchun , Ye Mao , Zhou Zhen , Li Yantao , Li Zhenhui , Nie Qinghua
Published: January 2023

Background

circRNAs are new-identified special endogenous RNA molecules that covalently close a loop by backsplicing with pre-mRNA.

In the cytoplasm, circRNAs would act as molecular sponges to bind with specific miRNA to promote the expression of target genes. However, there is still in its fancy of knowing circRNA functional alternation in skeletal myogenesis. In this study, we favor a model to identify the circRNA-miRNA-mRNA interaction network in which the axis may be implicated in the progression of chicken primary myoblasts (CPMs) myogenesis by a combination of multi-omics (i.e., circRNA-seq and ribo-seq).

Results

In total, 314 circRNA-miRNA-mRNA regulatory axis containing 66 circRNAs, 70 miRNAs, and 24 mRNAs that may be relevant to myogenesis were collected. With these, thecircPLXNA2-gga-miR-12207-5P-MDM4axis aroused our research interest. ThecircPLXNA2is highly differentially expressed during differentiation versus proliferation. It was demonstrated thatcircPLXNA2inhibited the process of apoptosis while at the same time stimulating cell proliferation.

Furthermore, we demonstrated thatcircPLXNA2could inhibit the repression ofgga-miR-12207-5ptoMDM4by directing binding togga-miR-12207-5p, thereby restoringMDM4expression.

Conclusions

CircPLXNA2could function as a competing endogenous RNA (ceRNA) to inhibit the repression ofgga-miR-12207-5ptoMDM4by directing binding togga-miR-12207-5p, thereby recovering the expression ofMDM4.
Neural Synchronization as a Function of Engagement with the Narrative
Authors: Ohad Tal , Yeshurun Yaara
Published: January 2023

We can all agree that a good story engages us, however, agreeing which story is good is far more debatable. In this study, we explored whether engagement with a narrative synchronizes listeners’ brain responses, by examining individual differences in engagement to the same story. To do so, we pre-registered and re-analyzed a previously collected dataset by Chang et al. (2021) of functional Magnetic Resonance Imaging (fMRI) scans of 25 participants who listened to a one-hour story and answered questionnaires. We assessed the degree of their overall engagement with the story and their engagement with the main characters. The questionnaires revealed individual differences in engagement with the story, as well as different valence towards specific characters. Neuroimaging data showed that the auditory cortex, the default mode network (DMN) and language regions were involved in processing the story. Increased engagement with the story was correlated with increased neural synchronization within regions in the DMN (especially the medial prefrontal cortex), as well as regions outside the DMN such as the dorso-lateral prefrontal cortex and the reward system. Interestingly, positively and negatively engaging characters elicited different patterns of neural synchronization. Finally, engagement increased functional connectivity within and between the DMN, the dorsal attention network and the control network. Taken together, these findings suggest that engagement with a narrative synchronizes listeners’ responses in regions involved in mentalizing, reward, working memory and attention. By examining individual differences in engagement, we revealed that these synchronization patterns are due to engagement, and not due to differences in the narrative’s content.
Functional Organization of Auditory and Reward Systems in Aging
Authors: Belden Alexander , Quinci Milena Aiello , Geddes Maiya , Donovan Nancy J. , Hanser Suzanne B. , Loui Psyche
Published: January 2023

The intrinsic organization of functional brain networks is known to change with age, and is affected by perceptual input and task conditions. Here, we compare functional activity and connectivity during music listening and rest between younger (N=24) and older (N=24) adults, using whole brain regression, seed-based connectivity, and ROI-ROI connectivity analyses. As expected, activity and connectivity of auditory and reward networks scaled with liking during music listening in both groups. Younger adults show higher within-network connectivity of auditory and reward regions as compared to older adults, both at rest and during music listening, but this age-related difference at rest was reduced during music listening, especially in individuals who self-report high musical reward. Furthermore, younger adults showed higher functional connectivity between auditory network and medial prefrontal cortex (mPFC) that was specific to music listening, whereas older adults showed a more globally diffuse pattern of connectivity, including higher connectivity between auditory regions and bilateral lingual and inferior frontal gyri. Finally, connectivity between auditory and reward regions was higher when listening to music selected by the participant. These results highlight the roles of aging and reward sensitivity on auditory and reward networks. Results may inform the design of music- based interventions for older adults, and improve our understanding of functional network dynamics of the brain at rest and during a cognitively engaging task.
Scribe: next-generation library searching for DDA experiments
Authors: Searle Brian C. , Shannon Ariana E. , Wilburn Damien Beau
Published: January 2023

Spectrum library searching is a powerful alternative to database searching for data dependent acquisition experiments, but has been historically limited to identifying previously observed peptides in libraries. Here we present Scribe, a new library search engine designed to leverage deep learning fragmentation prediction software such as Prosit. Rather than relying on highly curated DDA libraries, this approach predicts fragmentation and retention times for every peptide in a FASTA database. Scribe embeds Percolator for FDR correction and an interference tolerant label-free quantification integrator to enable an end-to-end proteomics workflow. By leveraging expected relative fragmentation and retention time values, we find that library searching with Scribe can outperform traditional database searching tools, both in terms of sensitivity and quantitative precision. Scribe and its graphical interface are easy to use, freely accessible, and fully open source.
Assessment of structural behaviour of new L-asparaginase and SAXS data-based evidence for catalytic activity in its monomeric form
Authors: Mihooliya Kanti N. , Nandal Jitender , Kalidas Nidhi , Ashish  , Chand Subhash , Verma Dipesh K. , Bhattacharyya Mani S. , Sahoo Debendra K.
Published: January 2023

The present study reports the structural and functional characterization of a new glutaminase-free recombinant L-asparaginase (PrASNase) from Pseudomonas resinovorans IGS-131. PrASNase showed substrate specificity to L-asparagine, and its kinetic parameters, Km, Vmax, and kcatwere 9.49×10-3M, 25.13 IUmL-1min-1, and 3.01×103s-1, respectively. The CD spectra showed that PrASNase consists of 30.9% α-helix and 69.1% other structures in its native form. FTIR was used for the functional characterization, and molecular docking predicted that the substrate interacts with serine, alanine, and glutamine in the binding pocket of PrASNase. Different from known asparaginases, structural characterization by small-angle X-ray scattering (SAXS) and analytical ultracentrifugation (AUC) unambiguously revealed PrASNase to exist as a monomer in solution at low temperatures and oligomerized to a higher state with temperature rise. Through SAXS studies and enzyme assay, PrASNase was found to be mostly monomer and catalytically active at 37°C. Furthermore, this glutaminase-free PrASNase showed killing effects against WIL2-S and TF-1.28 cells with IC50of 7.4 µg.mL-1and 5.6 µg.mL-1, respectively. This is probably the first report with significant findings of fully active L-asparaginase in monomeric form using SAXS and AUC and demonstrates the potential of PrASNase in inhibiting cancerous cells, making it a potential therapeutic candidate.

HIGHLIGHTS

A new L-asparaginase (PrASNase) was structurally and functionally characterized.

SAXS revealed PrASNase is functionally active in monomeric form and oligomerizes with temperature rise.

Monomeric PrASNase showed an IC50value of 7.4 and 5.6 µg mL-1against WIL2-S and TF-1.28 cells.

Cytotoxicity of PrASNase against leukemic cell lines showed its potential as a biotherapeutic.

GRAPHICAL ABSTRACT
Multi-Criteria Ambulance Location Problem: better to treat some fast, or more in time?
Authors: Münch Johanna , Leithäuser Neele , Moos Michael , Werner Jennifer , Scherer Guido
Published: January 2023

For the location optimization of several ambulance stations, we outline a multi-criteria integer program to maximize the reached population within different time bounds. This technique is based on a realistic driving time estimation for ambulances on a detailed road network. The results show that, depending on which time bound is more valued, ambulance stations are more likely to be located in urban areas or evenly distributed across the study region. We used this model for real-world studies in Southwest Germany, where several ambulance station locations were optimized simultaneously.
Molecular characterization of nervous system organization in the hemichordateSaccoglossus kowalevskii
Authors: Andrade Lopéz José M. , Pani Ariel M. , Wu Mike , Gerhart John , Lowe Christopher J.
Published: January 2023

Hemichordates are an important group for investigating the evolution of bilaterian nervous systems. As the closest chordate outgroup with a bilaterally symmetric adult body plan, hemichordates are particularly informative for exploring the origins of chordates. Despite the importance of hemichordate neuroanatomy for testing hypotheses on deuterostome and chordate evolution, adult hemichordate nervous systems have not been comprehensively described using molecular techniques, and classic histological descriptions disagree on basic aspects of nervous system organization. A molecular description of hemichordate nervous system organization is important for both anatomical comparisons across phyla and for attempts to understand how conserved gene regulatory programs for ectodermal patterning relate to morphological evolution in deep time. Here, we describe the basic organization of the adult hemichordateSaccoglossus kowalevskiinervous system using immunofluorescence,in situhybridization, and transgenic reporters to visualize neurons, neuropil, and key neuronal cell types. Consistent with previous descriptions, we found theS. kowalevskiinervous system consists of a pervasive nerve plexus that is concentrated in the anterior, along with nerve cords on both the dorsal and ventral sides. Neuronal cell types exhibited clear anteroposterior and dorsoventral regionalization in multiple areas of the body. We observed spatially demarcated expression patterns for many genes involved in synthesis or transport of neurotransmitters and neuropeptides but did not observe clear distinctions between putatively centralized and decentralized portions of the nervous system. In the trunk, there is a clear division of cell types between the dorsal and ventral cords suggesting differences in function. The plexus shows regionalized structure and is consistent with the proboscis base as a major site for information processing rather than the dorsal nerve cord. The absence of neural processes crossing the basement membrane into muscle and extensive axonal varicosities suggest that volumetric transmission may play an important role in neural function. These data now facilitate more informed neural comparisons between hemichordates and other groups and contribute to broader debates on the origins and evolution of bilaterian nervous systems.
Composition of nasopharyngeal microbiota in individuals with SARS-CoV-2 infection across three COVID-19 waves in India
Authors: Bose Tungadri , Wasimuddin  , Acharya Varnali , Pinna Nishal Kumar , Kaur Harrisham , Ranjan Manish , Jandhyala SaiKrishna , Nagabandi Tulasi , Varma Binuja , Tallapaka Karthik Bharadwaj , Sowpati Divya Tej , Haque Mohammed Monzoorul , Dutta Anirban , Siva Archana Bharadwaj , Mande Sharmila S.
Published: January 2023

Multiple variants of the SARS-CoV-2 virus have been plaguing the world through successive waves of infection over the past three years. Studies by independent research groups across geographies have shown that the microbiome composition in COVID-19 patients (CP) differ from that of healthy individuals (CN). However, such observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern. We also present the variations in microbiota of symptomatic vs asymptomatic COVID-19 patients. The nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The generaStaphylococcus,Anhydrobacter,Thermus, andAerococcuswere observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection. To our knowledge, this is the first longitudinal study which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Such studies not only pave way for better understanding of the disease pathophysiology but also help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.
Rice potassium transporter OsHAK18 mediates phloem K+loading and redistribution
Authors: Shen Like , Wu Qi , Fan Wenxia , Luan Junxia , Li Na , Chen Di , Tian Quanxiang , Jing Wen , Zhang Wenhua
Published: January 2023

High-Affinity K+transporters/K+Uptake Permeases/K+Transporters (HAK/KUP/KT) are important pathways mediating K+transport across cell membrane, which function in maintaining K+homeostasis during plant growth and stress response. An increasing number of studies have shown that HAK/KUP/KT transporters play important roles in potassium uptake and root-to-shoot translocation. However, whether some HAK/KUP/KT transporters mediate K+redistribution in phloem remains unknown. In this study, we revealed that a phloem-localized HAK/KUP/KT transporter, OsHAK18 operated as a typical KUP/HAK/KT transporter mediating cell K+uptake when expressed in yeast,E. coliandArabidopsis. It was localized at plasma membrane. Disruption ofOsHAK18rendered rice seedlings insensitive to low-K+stress. Compared with WT, theoshak18mutants accumulated more K+in shoots but less K+in roots, leading to a higher shoot/root ratio of K+per plant. Although disruption ofOsHAK18doesn’t affect root K+uptake and K+level in xylem sap, it significantly decreases phloem K+concentration and inhibits root-to-shoot-to-root K+translocation in split-root assay. These results reveal that OsHAK18 mediates phloem K+loading and redistribution, whose disruption is favor of shoot K+retention under low-K+stress. Our findings not only reveal a unique function of rice HAK/KUP/KT family member, but also provide a promising strategy to improve rice tolerance under K+deficiency.
EZH2mutations in follicular lymphoma distort H3K27me3 profiles and alter transcriptional responses to PRC2 inhibition
Authors: Romero Pierre , Richart Laia , Aflaki Setareh , Burton Megan , Michaud Audrey , Masliah-Planchon Julien , Kuhnowski Frédérique , Méaudre Céline , Luscan Armelle , Hamza Abderaouf , Legoix Patricia , Vincent-Salomon Anne , Wassef Michel , Holoch Daniel , Margueron Raphaël
Published: January 2023

Mutations in chromatin regulators or their histone substrates are widespread in cancer and often play decisive roles in tumorigenesis. These include Polycomb Repressive Complex 2 (PRC2), a histone H3 lysine 27 methyltransferase that shows distinct alterations in each of a range of tumor types. Mechanistically, this tumor-type specificity is poorly understood. Here, we model several of these alterations in a single isogenic system in order to reveal their comparative impacts on chromatin and transcription. Focusing then on gain-of-function substitutions in catalytic subunit EZH2, which occur in ∼25% of follicular lymphomas, we show thatEzh2Y641Finduces aberrant H3K27 methylation patterns even without wild-typeEzh2, and that these are alleviated by partial PRC2 inhibition.Ezh2Y641Falso causes gains in existing H3K27 acetylation peaks and extensive gene expression changes. Remarkably,Ezh2Y641Ftransforms the transcriptomic response to PRC2 inhibition, leading notably to the induction of antigen presentation genes in mutant cells. Using a unique longitudinal cohort of FL patient samples we further strengthen the link betweenEZH2mutation status and abnormal H3K27 methylation. This analysis also uncovered unexpected variability in the mutational landscape of successive biopsies from the same patient that points to the frequent co-existence of different clones. On a clinical level, this urges caution when stratifying patients based on single tumor sampling. Altogether, our results provide a mechanistic foundation for understanding how oncogenic PRC2 mutations disrupt chromatin and transcription, and the therapeutic vulnerabilities this creates.
MitoMouse is a model reconstruction of murine mitochondrial metabolism
Authors: Chapman Stephen P. , Molinié Thibaut , Mourier Arnaud , Habermann Bianca H.
Published: January 2023

Mitochondria, apart from being the powerhouses of our cells, are key players in cellular metabolism and homeostasis. As a consequence, the core bioenergetics and metabolism of mitochondria are well studied considering the role that dysregulated mitochondrial metabolism plays in disease. Flux Balance Analysis, used in conjunction with metabolic model reconstructions is a powerful computational tool that predicts metabolism. The resulting quantitative descriptions of metabolic dysregulation not only allows current hypotheses to be testedin silico, but can also lead to novel model driven hypotheses that can be experimentally verified. Several metabolic reconstructions for human and mouse metabolism exist, but no model specific to mouse mitochondrial metabolism exists. Here, we have created a mouse-specific mitochondrial metabolic model, mitoMouse, which is based on the high-quality human MitoCore mode. MitoMouse contains 390 genes and 445 metabolites involved in 560 unique reactions, is able to model central carbon metabolism and has been extended to contain reduction of the CoQ complex of Oxidative Phosphorylation by the enzyme DHODH. MitoMOuse was validated to accurately model the important metabolic switch involving CoQ reduction resulting from increased malate import, as recently shown in mouse cardiac tissue. We expect this model to be of immense interest and relevance to researchers working on murine mitochondrial metabolism.
Cognition’s dependence on functional network integrity with age is conditional on structural network integrity
Authors: Liu Xulin , Tyler Lorraine K ,   Cam-CAN, Davis Simon W , Rowe James B , Tsvetanov Kamen A
Published: January 2023

Maintaining good cognitive function is crucial for well-being across the lifespan. We proposed that the degree of cognitive maintenance is determined by the functional interactions within and between large-scale brain networks. Such connectivity can be represented by the white matter architecture of structural brain networks that shape intrinsic neuronal activity into integrated and distributed functional networks. We explored how the function-structure connectivity convergence, and the divergence of functional connectivity from structural connectivity, contribute to the maintenance of cognitive function across the adult lifespan. Multivariate analyses were used to investigate the relationship between function-structure connectivity convergence and divergence with multivariate cognitive profiles, respectively. Cognitive function was increasingly dependent on function-structure connectivity convergence as age increased. The dependency of cognitive function on connectivity was particularly strong for high-order cortical networks and subcortical networks. The results suggest that brain functional network integrity sustains cognitive functions in old age, as a function of the integrity of the brain’s structural connectivity.
The Embryonic Origin of Primordial Germ Cells in the TardigradeHypsibius exemplaris
Authors: Heikes Kira L. , Game Mandy , Smith Frank W. , Goldstein Bob
Published: January 2023

Primordial germ cells (PGCs) give rise to gametes – cells necessary for the propagation and fertility of diverse organisms. Current understanding of PGC development is limited to the small number of organisms whose PGCs have been identified and studied. Expanding the field to include little-studied taxa and emerging model organisms is important to understand the full breadth of the evolution of PGC development. In the phylum Tardigrada, no early cell lineages have been identified to date using molecular markers. This includes the PGC lineage. Here, we describe PGC development in the model tardigradeHypsibius exemplaris. The four earliest-internalizing cells (EICs) exhibit PGC-like behavior and nuclear morphology. The location of the EICs is enriched for mRNAs of conserved PGC markerswiwi1(water bearpiwi1) andvasa. At early stages, bothwiwi1andvasamRNAs are detectable uniformly in embryos, which suggests that these mRNAs do not serve as localized determinants for PGC specification. Only later arewiwi1andvasaenriched in the EICs. Finally, we traced the cells that give rise to the four PGCs. Our results reveal the embryonic origin of the PGCs ofH. exemplarisand provide the first molecular characterization of an early cell lineage in the tardigrade phylum. We anticipate that these observations will serve as a basis for characterizing the mechanisms of PGC development in this animal.
Gre factors protect against phenotypic diversification and cheating inEscherichia colipopulations under toxic metabolite stress
Authors: Sivaloganathan Darshan M. , Wan Xuanqing , Brynildsen Mark P.
Published: January 2023

Nitric oxide (·NO) is one of the toxic metabolites that bacteria can be exposed to within phagosomes. Gre factors, which are also known as transcript cleavage factors or transcription elongation factors, relieve back-tracked transcription elongation complexes by cleaving nascent RNAs, which allows transcription to resume after stalling. Here we discovered that loss of both Gre factors inE. coli, GreA and GreB, significantly compromised ·NO detoxification through a phenotypic diversification of the population. Under normal culturing conditions, both wild-type and ΔgreAΔgreBsynthesized protein uniformly. However, treatment with ·NO led to bimodal protein expression in ΔgreAΔgreB, whereas wild-type remained unimodal. Interestingly, exposure to another toxic metabolite of phagosomes, hydrogen peroxide (H2O2), produced similar results. We found that the diversification in ΔgreAΔgreBcultures requiredE. coliRNAP, occurred at the level of transcription, and could produce cheating where transcriptionally-deficient cells benefit from the detoxification activities of the transcriptionally-proficient subpopulation. Collectively, these results indicate that Gre factors bolster bacterial defenses by preventing phenotypic diversification and cheating in environments with fast-diffusing toxic metabolites.

Importance

Toxic metabolite stress occurs in a broad range of contexts that are important to human health, microbial ecology, and biotechnology; whereas Gre factors are highly conserved throughout the bacterial kingdom. Here we discovered that the Gre factors ofE. coliprevent phenotypic diversification under toxic metabolite stress. Such conformist regulation improves populationwide removal of those stressors and protects against cheating, where one subpopulation commits resources to counter a threat, and the other subpopulation does not, yet both subpopulations benefit.
MASH Native: A Unified Solution for Native Top-Down Proteomics Data Processing
Authors: Larson Eli J. , Pergande Melissa R. , Moss Michelle E. , Rossler Kalina J. , Wenger R. Kent , Krichel Boris , Josyer Harini , Melby Jake A. , Roberts David S. , Pike Kyndalanne , Shi Zhuoxin , Chan Hsin-Ju , Knight Bridget , Rogers Holden T. , Brown Kyle A. , Ong Irene M. , Jeong Kyowon , Marty Michael , McIlwain Sean J. , Ge Ying
Published: January 2023

Native top-down proteomics (nTDP) integrates native mass spectrometry (nMS) with top-down proteomics (TDP) to provide comprehensive analysis of protein complexes together with proteoform identification and characterization. Despite significant advances in nMS and TDP software developments, a unified and user-friendly software package for analysis of nTDP data remains lacking. Herein, we have developed MASH Native to provide a unified solution for nTDP to process complex datasets with database searching capabilities in a user-friendly interface. MASH Native supports various data formats and incorporates multiple options for deconvolution, database searching, and spectral summing to provide a one-stop shop for characterizing both native protein complexes and proteoforms. The MASH Native app, video tutorials, written tutorials and additional documentation are freely available for download athttps://labs.wisc.edu/gelab/MASH_Explorer/MASHNativeSoftware.php. All data files shown in user tutorials are included with the MASH Native software in the download .zip file.
A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals non-hierarchical model of development
Authors: Lee Julie , Møller Andreas Fønss , Chae Shinhyeok , Bussek Alexandra , Park Tae Joo , Kim Youni , Lee Hyun-Shik , Pers Tune H. , Kwon Taejoon , Sedzinski Jakub , Natarajan Kedar Nath
Published: January 2023

The specialized cell-types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell-fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developingXenopusMCE from pluripotent to mature stages by single-cell transcriptomics, identifying novel, multipotentearly epithelial progenitorsthat execute multi-lineage cues before specialising into late-stage ionocytes, goblet and basal cells. Combiningin silicolineage inference,in situhybridization and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors, chart cell- type emergence and fate progression into specialized cell-types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programmes across vertebrates. We uncover a continuous non-hierarchical model of MCE development alongside a significant data resource for understanding respiratory biology.
Host lifestyle and parasite interspecific facilitation mediate co-infection in a species-poor host-parasite system
Authors: Kmentová Nikol , Cruz-Laufer Armando J. , Milec Leona J. M. , Moons Tanisha , Heeren Senne , van den Hoorn Elze , Thys Kelly J. M. , Makasa Lawrence , Manda Auguste Chocha , Mulungula Pascal Masilya , Van Steenberge Maarten , Jorissen Michiel W. P. , Vanhove Maarten P. M.
Published: January 2023

Despite their important ecological role, questions remain on mechanisms structuring parasite assemblages. We present a simple and endemic host-parasite system of clupeid fishes and monogenean parasites (Kapentagyrus, Dactylogyridae) with contrasting levels of host-specificity from Lake Tanganyika as a model to study parasite distribution patterns and co-infection dynamics in nature. With two parasites, two host species, and three host-parasite combinations between them, this unique system represents the simplest natural host-parasite model that is not trivial. We modelled spatiotemporal dynamics of host-parasite interaction using infection data along the North-South axis of Lake Tanganyika (660 km) over the course of two seasons and four years (1730 fish, 3710 parasites). We found temporal stability of infection, which contrasts with previously reported seasonally driven fluctuations of fish host abundances. We found a difference in spatial structure between the parasite species, confirming that their distributions are only restricted by their most mobile host species. On the host species that is infected by two parasite species, we discovered a positive correlation with host body size for one parasite species, and a negative correlation for the other species. As we also discovered facilitation of infection, this cannot be due to competition. The differences reported between parasite species infecting the same host species further extrapolate the dependence on changes in lifestyle of the host during its ontogenetic development. In conclusion, we show that in a simple, closed system parasite infection dynamics are dependent on a combination of host mobility, host lifestyle changes over ontogenetic development and interspecific interactions between parasites.
EVALUATION AND COMPARISON OF THE ANTIOXIDANT AND FREE RADICAL SCAVENGING PROPERTIES OF MEDICINAL PLANTS BY USING THE DPPH ASSAY IN-VITRO
Authors: Yousaf Hassan
Published: January 2023

Disclaimer

The author(s) have withdrawn their manuscript because it was posted without acknowledging all contributing authors. Therefore, the author(s) do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author:hassanysf98@gmail.com
Transcriptomics of mussel transmissible cancer MtrBTN2 suggests accumulation of multiple cancerous traits and oncogenic pathways shared among bilaterians
Authors: Burioli E.A.V. , Hammel M. , Vignal E. , Vidal-Dupiol J. , Mitta G. , Thomas F. , Bierne N. , Destoumieux-Garzón D. , Charrière G.M.
Published: January 2023

Transmissible cancer cell lines are rare biological entities giving rise to diseases at the crossroads of cancer and parasitic diseases. These malignant cells have acquired the amazing capacity to spread from host to host. They have been described only in dogs, Tasmanian devils and marine bivalves. TheMytilus trossulusBivalve Transmissible Neoplasia 2 (MtrBTN2) lineage has even acquired the capacity to spread inter-specifically between marine mussels of theMytilus eduliscomplex worldwide. To identify the oncogenic processes underpinning the biology of these atypical cancers we performed transcriptomics of MtrBTN2 cells. Differential expression, enrichment, protein-protein interaction network, and targeted analyses were used. Overall, our results suggest the accumulation of multiple cancerous traits that way be linked to the long-term evolution of MtrBTN2. We also highlight that vertebrate and lophotrochozoan cancers could share a large panel of common drivers, which supports the hypothesis of an ancient origin of oncogenic processes in bilaterians.
Spatio-temporal transcriptomic analysis reveals distinct nephrotoxicity, DNA damage and regeneration response after cisplatin
Authors: Wijaya Lukas S. , Kunnen Steven J. , Trairatphisan Panuwat , Fisher Ciaran , Crosby Meredith E. , Schaefer Kai , Bodie Karen , Vaughan Erin E. , Breidenbach Laura , Reich Thomas , Clausznitzer Diana , Bonnet Sylvestre A. , Zheng Sipeng , Pont Chantal , Stevens James L. , Dévédec Sylvia Le , van de Water Bob
Published: January 2023

Nephrotoxicity caused by drug or chemical exposure involves different mechanisms and nephron segments as well as a complex temporal integration of injury and repair responses. Distinct cellular transcriptional programs regulate the time-dependent tissue injury and regeneration responses. Whole kidney transcriptome analysis cannot dissect the complex the nephron segment spatio- temporal injury and regeneration responses. Here, we used laser capture microdissection of formalin- fixed paraffin embedded sections followed by whole genome targeted RNA-sequencing-TempO-Seq and co-expression gene-network (module) analysis to determine the spatial-temporal responses in rat kidney glomeruli (GM), cortical proximal tubules (CPT) and outer-medulla proximal tubules (OMPT) comparison with whole kidney, after a single dose of the nephrotoxicant cisplatin. We demonstrate that cisplatin induced early onset of DNA damage in both CPT and OMPT, but not GM. Sustained DNA damage response was strongest in OMPT coinciding with OMPT specific inflammatory signaling, actin cytoskeletal remodeling and increased glycolytic metabolism coincident with suppression of mitochondrial activity. Later responses reflected regeneration-related cell cycle pathway activation and ribosomal biogenesis in the injured OMPT regions. Activation of modules containing kidney injury biomarkers was strongest in the OMPT, with OMPTCluexpression best correlating with urinary clusterin biomarker measurements compared the correlation of Kim1. Our findings also showed that whole kidney responses were less sensitive than OMPT. In conclusion, our LCM-TempO-Seq method reveals a detailed spatial mechanistic understanding of renal injury/regeneration after nephrotoxicant exposure and identifies the most representative mechanism-based nephron segment specific renal injury biomarkers.
Impact of rare structural variant events in newly diagnosed multiple myeloma
Authors: Chojnacka Monika , Diamond Benjamin , Ziccheddu Bachisio , Rustad Even , Maclachlan Kylee , Papadimitriou Marios , Boyle Eileen M. , Blaney Patrick , Usmani Saad , Morgan Gareth , Landgren Ola , Maura Francesco
Published: January 2023

Whole genome sequencing (WGS) of newly diagnosed multiple myeloma patients (NDMM) has shown recurrent structural variant (SV) involvement in distinct regions of the genome (i.e. hotspots) and causing recurrent copy number alterations. Together with canonical immunoglobulin translocations, these SVs are recognized as “recurrent SVs”. More than half SVs were not involved in recurrent events. The significance of these “rare SVs” has not been previously examined. In this study, we utilize 752 WGS and 591 RNA-seq data from NDMM patients to determine the role of rare SVs in myeloma pathogenesis. 94% of patients harbored at least one rare SV event. Rare SVs showed an SV-class specific enrichment within genes and superenhancers associated with outlier gene expression. Furthermore, known myeloma driver genes recurrently impacted by point mutations were dysregulated by rare SVs. Overall, we demonstrate the association of rare SVs with aberrant gene expression supporting a driver role in myeloma pathogenesis.

SIGNIFICANCE

Characterization of multiple myeloma genome revealed that more than half structural variants are not involved in recurrent events. Here, we demonstrate that these rare SVs hold potential for myeloma pathogenesis through their gene expression impact. Rare SVs contribute to MM heterogeneity and have implications for development of individualized treatment.
Establishment of primary renal lymphoma model and the clinical relevance
Authors: Li Xiaoxi , Deng Minyao , Zhang Chenxiao , Luo Lingli , Qian Hui
Published: January 2023

Extranodal dissemination was an important feature of aggressive B-cell lymphoma. Due to the lack of available animal model, the causes of extranodal dissemination of lymphoma were largely unknown. Here, we identified a novel cell line, named MA-K, which originated from the Eμ-Myc;Cdkn2a-/-cell line, named MA-LN in this study. Compared to MA-LN, MA-K tended to disseminate in the kidney rather than lymph nodes in lymphoma transplantation model, resembling human primary renal lymphoma. The transcriptome analysis revealed that MA-K had undergone the transcriptional evolution during the culture. Specialized transcriptional pattern analysis, we proposed in this study, identified that FOXO1-BTG1-MYD88 pattern was formed in MA-K. Further analysis found that translation pathway was the most enriched pathway in specially expressed genes (SEGs) in MA-K. Among the SEGs, 3 up-regulated genes, RPLP2, RPS16 and MRPS16, and 5 down-regulated genes, SSPN, CD52, ANKRD37, CCDC82 and VPREB3, in MA-K were identified as promising biomarkers to predict the clinical outcomes of human DLBCL. Moreover, the joint expression of the 5-gene signature could effectively predict clinical outcomes of human DLBCL in triple groups. These findings suggested that the MA-K cell line had strong clinical relevance with human aggressive B-cell lymphoma. Moreover, the MA-K primary renal lymphoma model, as a novel syngenetic mouse model, would be greatly useful for both the basic research on lymphoma dissemination and preclinical efficacy evaluation of chemotherapy and immunotherapy.
EFNB1 level affects drug response in DLBCL cell lines
Authors: Li Xiaoxi , Zhang Chenxiao , Deng Minyao , He Zhengjin , Qian Hui
Published: January 2023

Targeted therapy was a promising therapy for aggressive B-cell lymphoma. However, drug resistance was still an unavoidable problem. Here, we explored the effect of EFNB1 on drug response. Analysis of IC50 data showed that high level of EFNB1 was associated with resistance to most targeted drugs targeting BCR in human DLBCL cell lines. Drug response assay showed that Efnb1 could enhance SRC phosphorylation and increased the sensitivity of cells to SRC inhibitors. Meanwhile, Efnb1 could sensitize cells to most cytotoxic drugs, especially DOX and VCR. Efnb1 could confer cells sensitivity to VCR by enhancing the phosphorylation of Stmn1 at serine 28. Survival analysis revealed that the expression level of genes phosphorylated in Efnb1 cells were associated with poor prognosis of human DLBC. Together, this study revealed that EFNB1 level, as a non-genetic mechanism, greatly affected drug response of targeted drugs and cytotoxic drugs through the phosphorylation network. Our findings would provide important insights into EFNB1-SRC activated B-cell lymphoma and efficacy evaluation.
Mindfulness and anti-consumption behavior: the role of authentic living
Authors: Lin Li Min , Park Hyun Jung
Published: January 2023

Purpose

This study analyzed the relationships among sub-factors of mindfulness and two anti-consumption lifestyles caused by personal and social/environmental concerns. This study also investigated the pursuit of authenticity mediating this relationship.

Design/methodology/approach

A survey based on self-administered questionnaires and structural equation modeling was used to analyze the collected data via Statistical Product Service Solutions (SPSS) 23 and Analysis of MOment Structure (AMOS) 23. Multiple mediation analysis was adopted to investigate the mediating role of authenticity dimensions via SPSS PROCESS macro.

Findings

The relationship between mindfulness and anti-consumption behavior was generally positive. Except for describing and non-judgment, most facets of mindfulness were positively related to anti-consumption patterns. Only the indirect effect of authentic living (AL) was significant in the impact of mindfulness on anti-consumption behavior.

Originality/value

To the authors' knowledge, this study is the first to examine the link between mindfulness and anti-consumption and potential mechanism of anti-consumption – authenticity seeking, extending knowledge about mindfulness and providing insights for environmentalists, public decision-makers, marketers and consumers.
Configuring optimal contextual performance and task performance in offshore business processing organizations
Authors: Hameed Athar , Khwaja Muddasar Ghani , Zaman Umer
Published: January 2023

Purpose

Occupational stress is damaging to employee well-being, causes serious illnesses and costs organizations billions of dollars every year. Mutual gains model of human resource management (HRM) recommends that HRM practices should improve both employee well-being and performance. Offshore business processing organizations (BPO) are renowned to have intense wok environment. The study aimed to deploy mutual gains models in BPO to determine if positive perceptions of HRM practices (or benevolent HRM attributions) can help employees manage their stress better and improve their task performance (TP) and contextual performance (CP). Furthermore, work gratitude (WG) was examined to see if it acted as an intermediary in the relationship between benevolent HRM attributions, employee stress management (SM), TP and CP.

Design/methodology/approach

Primary data of 368 respondents were collected from the employees working in BPO. Structural equation modeling technique was deployed for the testing of causal relationships among constructs. AMOS 24.0 was used for the estimation of theoretical model.

Findings

Empirical outcomes affirmed strongly knitted theoretical associations among the constructs.

Originality/value

This study contributes to literature by proposing a framework which shows how HRM attributions can enhance employee's TP, CP and improve employee SM through the mediating influence of WG.