bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID-19 Pandemic on Undergraduate Research in the Department of Biology at Western University: Effect on project types, learning outcomes, and student perceptions
Authors: Chaplin Ava , Kohalmi Susanne , Simon Anne 
Published: January 2024

AbstractUndergraduate research is a high impact practice that offers numerous benefits to students, academic institutions, and the wider scientific community. Unfortunately, undergraduate research has faced restrictions due to the COVID-19 pandemic. This study aimed to assess how the COVID-19 pandemic has impacted: (1) the number and types of undergraduate research projects performed in the Department of Biology at the University of Western Ontario, and (2) the satisfaction-levels and perceived learning outcomes of students performing these projects. This study also aimed to incorporate a ‘One Health’ framework through an emphasis on stakeholder involvement and the need for future action.A survey of 33 students who completed an undergraduate research project in the Department of Biology in the 2020/2021 academic year, and 68 students who completed an undergraduate research project in the 5 years prior was conducted. In keeping with the One Health approach, key stakeholders were identified, and a stakeholder map was constructed.The number of projects performed did not change dramatically despite COVID-19 restrictions. However, a shift towards dry research was observed with 87.9% of students in the 2020/2021 academic year conducting dry research, compared to 16.4% of students in the 5 years prior. Students who conducted research in the 2020/2021 academic year indicated lower overall levels of satisfaction and enjoyment, though their perceived learning outcomes were consistent with students who completed their projects in the 5 years prior. 53 key stakeholders from academia, government, industry, media, and the public were identified.Students provided invaluable feedback on their undergraduate research experiences that can be used to improve the quality of undergraduate research courses in the Department of Biology in the future. Findings may be of use to other departments and educational institutions that are seeking to improve their own undergraduate research courses amidst the COVID-19 pandemic or looking to incorporate experiential-based learning techniques into existing online courses.
Studying the cellular basis of small bowel enteropathy using high-parameter flow cytometry in mouse models of primary antibody deficiency
Authors: Mohammed Ahmed D. , Ball Ryan A.W. , Jolly Amy , Nagarkatti Prakash , Nagarkatti Mitzi , Kubinak Jason L. 
Published: January 2024

AbstractBackgroundPrimary immunodeficiencies are heritable defects in immune system function. Antibody deficiency is the most common form of primary immunodeficiency in humans, can be caused by abnormalities in both the development and activation of B cells, and may result from B-cell-intrinsic defects or defective responses by other cells relevant to humoral immunity. Inflammatory gastrointestinal complications are commonly observed in antibody-deficient patients, but the underlying immune mechanisms driving this are largely undefined.MethodsIn this study, several mouse strains reflecting a spectrum of primary antibody deficiency (IgA-/-, Aicda-/-, CD19-/-and JH-/-) were used to generate a functional small-bowel-specific cellular atlas using a novel high-parameter flow cytometry approach that allows for the enumeration of 59 unique cell subsets. Using this cellular atlas, we generated a direct and quantifiable estimate of immune dysregulation. This estimate was then used to identify specific immune factors most predictive of the severity of inflammatory disease of the small bowel (small bowel enteropathy).ResultsResults from our experiments indicate that the severity of primary antibody deficiency positively correlates with the degree of immune dysregulation that can be expected to develop in an individual. In the SI of mice, immune dysregulation is primarily explained by defective homeostatic responses in T cell and invariant natural killer-like T (iNKT) cell subsets. These defects are strongly correlated with abnormalities in the balance between protein (MHCII-mediated) versus lipid (CD1d-mediated) antigen presentation by intestinal epithelial cells (IECs) and intestinal stem cells (ISCs), respectively.ConclusionsMultivariate statistical approaches can be used to obtain quantifiable estimates of immune dysregulation based on high-parameter flow cytometry readouts of immune function. Using one such estimate, we reveal a previously unrecognized tradeoff between iNKT cell activation and type 1 immunity that underlies disease in the small bowel. The balance between protein/lipid antigen presentation by ISCs may play a crucial role in regulating this balance and thereby suppressing inflammatory disease in the small bowel.
Harnessing Stress: balancing the Burden of Slightly-Deleterious Variants by a Handicap
Authors: Shamanskiy Victor , Popadin Konstantin 
Published: January 2024

AbstractNumerous empirical studies have revealed epistatic interactions among deleterious variants. In this paper, we assume such interactions are widespread and analyze the resulting shift in mutational burden and average population fitness following the introduction of a strong and universal stress (hereafter “handicap”). We demonstrate that organisms with a low burden of slightly-deleterious variants (SDVs) are more likely to survive exposure to a handicap, whether genetic or environmental, leading to a purifying effect on the population. We further discuss the potential applications of harnessing such interactions for evolutionary and population studies as well as for population management.
Realistic time-lags and litter dynamics alter predictions of plant–soil feedback across generations
Authors: Ou Suzanne X. , Kandlikar Gaurav S. , Warren Magdalena L. , Ke Po-Ju 
Published: January 2024

SummaryPlant–soil feedback is a critical process in natural plant communities. However, it remains unclear whether greenhouse-measured microbial effects manifest in natural systems with temporally separated growing seasons as classic experiments often overlook seasonal time lags and litter dynamics.We modified the classic two-phase experiment to study plant–soil feedback for three Californian annual plant species. Our response phase used soil inoculum obtained either immediately after plant conditioning, after a six-month dry period with the conditioning plant removed, or after a dry period with the litter of the conditioning plant. We characterized soil bacterial and fungal communities in different treatments and employed recent advancement in plant–soil feedback theory to predict plant coexistence.Temporal delays and the presence of litter caused distinct responses in the fungal and bacterial communities, resulting in divergent microbial compositions at the end of the response phases. The delayed response treatments also affected microbially mediated stabilization, fitness differences, and invasion growth rates differently across species pairs, influencing predictions of plant coexistence.Our study highlights that the interplay between seasonal delays and litter dynamics prevents the direct extrapolation of plant–soil feedback measurements across multiple seasons, emphasizing the necessity of considering natural history when predicting microbially mediated plant coexistence.
High variability in the attractiveness of municipally-planted decorative plants to pollinators
Authors: Czaczkes Tomer J. , Breuss Carsten , Kurze Christoph 
Published: January 2024

AbstractInsect populations are declining globally. A major driver of this decline is land use change, including urbanisation. However, urban environments can also offer a wide range of floral resources to pollinators, through ornamental plantings, but these can vary widely in their attractiveness to insects. Often, the largest single planter of ornamental plants in an urban area is the municipality. Here we evaluated the decorative plantings carried out by the city municipality of Regensburg, Germany, by systematically surveying insect visitations on different plant types in late summer, when forage is often limited for pollinators. We found a 130-fold increase from the least to the most attractive plants, and high variation in which insect groups were attracted to which plants. While honey bees, which are not conservation concern, were the most common insect visitors, some decorative plants attracted a very large proportion of wild bees, flies, and wasps. Our results demonstrate that there is great scope for increasing the supply of urban forage to pollinators in general, and specific groups in particular, without requiring new decorative plant types to be sourced or planted. We argue that providing local evidence-based guidance to municipalities offers a quick and potentially cost-neutral method for supporting urban insect populations.
Skewness enables stabilising effect of hierarchy in complex competition networks
Authors: Koch Franziska , Neutel Anje-Margriet , Barnes David K.A. , Allhoff Korinna T. 
Published: January 2024

1AbstractIn observed ecological networks of interference-competition, hierarchy has been shown to generate asymmetric patterns of interaction strengths which enhance system stability. However, it remains unknown whether this stabilising effect of competitive hierarchies depends on the distribution of link strengths. Here, we analysed the relationship between interaction strength distributions, patterning, and system stability. We found that the interaction strengths within 30 observed encrusting, marine bryozoan networks were characterised by a high level of skewness, with many weak and few strong links. We showed that this distribution of link strengths is necessary for the stabilising effect of hierarchy, as skewness enables a patterning that strongly reduces the weight of short and long feedback loops. The stabilising effect of hierarchy did not appear in systems with uniform or normal distributions of interaction strengths. This has important ecological implications, since theoretical studies using random matrices often assume normal or uniform distributions. Since skewed interaction strengths are a common feature of ecological networks, including trophic and mutualistic systems, such theoretical approaches might overlook stabilising mechanisms present in living systems.
AdhE spirosome length in enterohaemorrhagicEscherichia coliis correlated with enzymatic directionality and is perturbed by salicylidene acylhydrazide binding
Authors: Serrano Ester , Tyler Arwen I. I. , Soroor Mostafa , Floria Iris , Kapur Nikil , Roe Andrew J. , Byron Olwyn 
Published: January 2024

ABSTRACTAntibiotics are contraindicated for the treatment of infection enterohemorrhagicEscherichia coli(EHEC), a human pathogen that causes diarrhea or hemorrhagic colitis in humans which can progress to hemolytic uremic syndrome (HUS). As an alternative to the use of antibiotics, previous studies developed the salicylidene acylhydrazides (SA), a family of anti-virulence compounds capable of blocking expression of the type three secretion system (T3SS), thereby reducing bacterial infections. Here we validate AdhE as the anti-virulence protein target of the SA compound ME0054. AdhE is a bidirectional enzyme able to catalyse the conversion of acetyl-CoA to ethanol andvice versa. AdhE oligomerises forming helicoidal filaments heterogeneous in length called spirosomes. In this work, we show that it is possible to partially fractionate AdhE spirosomes using size exclusion chromatography (SEC) and to characterise the spirosome oligomers present in each fraction with biophysical techniques such as small angle X-ray scattering (SAXS) and sedimentation velocity analytical ultracentrifugation (SV-AUC). Also, we observe that short spirosomes are more efficient in the reverse reaction whereas the spirosome length has no impact on the forward reaction. Therefore, for first time, we reveal that AdhE spirosome formation is necessary to regulate the direction of its enzymatic reactions. In addition, we show that ME0054 disrupts AdhE spirosomes, thereby enhancing the conversion of ethanol to acetyl-CoA. Importantly, SV-AUC data show that ME0054 binds to the AdhE filaments. Finally, time-resolved (TR) SAXS allowed us to follow the kinetics of spirosome disruption produced by ME0054, confirming its effectiveness at biologically relevant temperatures and timescales.SIGNIFICANCE STATEMENTThere is an urgent need to develop alternative strategies to combat bacterial infections. Salicylidene acylhydrazides (SA) are able to reduce expression of the bacterial type three secretion system (T3SS), used by many pathogens to manipulate host eukaryotic cells, including our pathogen of interest: enterohaemorrhagicE. coli(EHEC). The mechanism underpinning these compounds is a mystery. Here we show how the SA compound ME0054, by disrupting AdhE spirosomes, enhances metabolic conversion of ethanol to acetyl-CoA. This finding is consistent with the phenotype observed in an EHEC AdhE mutant: alterations in acetate levels and changes in T3SS expression. Our work establishes a crucial mechanistic link between the binding of the SA compound to a key target protein and changes in bacterial metabolism.
Restoring O-glycosylation and expression of MUC2 limits progression of colorectal cancer
Authors: Yang Yian , Yin Yuesong , Xu Wei , Kang Yan , Chen Jiawei , Zou Yanfeng , Xiao Zhigang , Li Zheng , Cao Peiguo 
Published: January 2024

AbstractThis study investigated the molecular mechanisms underlying the regulation of MUC2 expression and O-glycosylation modification in colorectal cancer. In addition, the potential of rosiglitazone to inhibit colorectal cancer by improving MUC2 glycosylation to protect intestinal barrier function was explored. In vitro, lectin staining combined with Co-IP assay was used to detect glycosyltransferases regulating MUC2 O-glycosylation. ChIP and Luciferase experiments were used to verify the transcription factors regulating MUC2 expression level. Samples from CRC patients were used to detect differences in multimolecular expression. The AOM/DSS mouse model was used to validate the effect of rosiglitazone on inhibiting colorectal cancer progression. Our results showed that B3GNT6 acts as a glycosyltransferase to enhance the O-glycosylation level of MUC2 and maintain protein stability to resist degradation by StcE secreting from pathogenic bacteria. Furthermore, KLF4 directly promotes the transcription of B3GNT6 and MUC2, which are regulated by PPARg. Rosiglitazone activated PPARg-KLF4-B3GNT6 axis which increased the expression level and glycosylation of MUC2 and further improved the intestinal mucosal barrier function to delay the development of colorectal cancer in mice. These data suggest that O-glycosylation and expression of MUC2 is key to the maintenance of functional intestinal mucosa and rosiglitazone is a potential colorectal cancer therapeutic agent.
A transcription network underlies the dual genomic coordination of mitochondrial biogenesis
Authors: Zhang Fan , Lee Annie , Freitas Anna , Herb Jake , Wang Zongheng , Gupta Snigdha , Chen Zhe , Xu Hong 
Published: January 2024

AbstractMitochondrial biogenesis requires the expression of genes encoded by both the nuclear and mitochondrial genomes. However, aside from a handful transcriptional factors regulating specific subsets of mitochondrial genes, the overall architecture of the transcriptional control of mitochondrial biogenesis remains to be elucidated. The mechanisms coordinating these two genomes are largely unknown. We performed a targeted RNAi screen in developing eyes with reduced mitochondrial DNA content, anticipating a synergistic disruption of tissue development due to impaired mitochondrial biogenesis and mtDNA deficiency. Among 638 transcription factors annotated in Drosophila genome, 77 were identified as potential regulators of mitochondrial biogenesis. Utilizing published ChIP-seq data of positive hits, we constructed a regulatory network revealing the logic of the transcription regulation of mitochondrial biogenesis. Multiple transcription factors in core layers had extensive connections, collectively governing the expression of nearly all mitochondrial genes, whereas factors sitting on the top layer may respond to cellular cues to modulate mitochondrial biogenesis through the underlying network. CG1603, a core component of the network, was found to be indispensable for the expression of most nuclear mitochondrial genes, including those required for mtDNA maintenance and gene expression, thus coordinating nuclear genome and mtDNA activities in mitochondrial biogenies. Additional genetics analyses validated YL-1, a transcription factor upstream of CG1603 in the network, as a regulator controlling CG1603 expression and mitochondrial biogenesis.
Synthetic Histology Images for Training AI Models: A Novel Approach to Improve Prostate Cancer Diagnosis
Authors: Van Booven Derek J , Chen Cheng-Bang , Kryvenko Oleksander , Punnen Sanoj , Sandoval Victor , Malpani Sheetal , Noman Ahmed , Ismael Farhan , Briseño Andres , Wang Yujie , Arora Himanshu 
Published: January 2024

ABSTRACTProstate cancer (PCa) poses significant challenges for timely diagnosis and prognosis, leading to high mortality rates and increased disease risk and treatment costs. Recent advancements in machine learning and digital imagery offer promising potential for developing automated and objective assessment pipelines that can reduce human capital and resource costs. However, the reliance of AI models on large amounts of clinical data for training presents a significant challenge, as this data is often biased, lacking diversity, and not readily available. Here we aim to address this limitation by employing customized generative adversarial network (GAN) models to produce high-quality synthetic images of different PCa grades (radical prostatectomy (RP)) and needle biopsies, which were customized to account for the granularity associated with each Gleason grade. The generated images were subjected to multiple rounds of benchmarking, quantifications and quality control assessment before being used to train an AI model (EfficientNet) for grading digital histology images of adenocarcinoma specimens (RP sections) and needle biopsies obtained from the PANDA challenge repository. Validation was performed using the AI model trained with synthetic data to grade digital histology from the cancer genome atlas (TCGA) (RP sections) and needle biopsy data from Radboud University Medical Center and Karolinska Institute. Results demonstrated that the AI model trained with a combination of image patches derived from original and enhanced synthetic images outperformed the model trained with original digital histology images. Together, this study demonstrates the potential of customized GAN models to generate a large cohort of synthetic data that can train AI models to effectively grade PCa specimens. This approach could potentially eliminate the need for extensive clinical data for training any AI model in the domain of digital imagery, leading to cost and time-effective diagnosis and prognosis.
Unlocking genome-based prediction and selection in conifers: the key role of within-family prediction accuracy
Authors: Papin Victor , Gorjanc Gregor , Pocrnic Ivan , Bouffier Laurent , Sanchez Leopoldo 
Published: January 2024

AbstractContextGenomic selection is a promising approach for forest tree breeding. However, its advantage in terms of prediction accuracy over conventional pedigree-based methods is unclear and within-family accuracy is rarely assessed.AimsWe used an pedigree-based model (ABLUP) with corrected pedigree data as a baseline reference for assessing the prediction accuracy of genome-based model (GBLUP) at the global and within-family levels in maritime pine (Pinus pinasterAit).MethodsWe sampled 39 full-sib families, each comprising 10 to 40 individuals, to constitute an experimental population of 833 individuals. A stochastic simulation model was also developed to explore other scenarios of heritability, training set size and tagging density.ResultsPrediction accuracies with GBLUP and ABLUP were similar and accuracy with GBLUP within-family was on average zero with large variation between families. Simulations revealed that the number of individuals in the training set was the principal factor limiting GBLUP accuracy in our study and likely in many forest tree breeding programmes. Accurate within-family prediction is possible if 40-65 individuals per full-sib family are included in the genomic training set, from a total of 1600-2000 individuals in the training set.ConclusionSuch conditions lead to a significant advantage of GBLUP over ABLUP in terms of prediction accuracy and more clearly justify the switch to genome-based prediction and selection in forest trees.
Morphological and genetic analysis of inflorescence and flower development in hemp (Cannabis sativaL.)
Authors: Shi Jiaqi , Schilling Susanne , Melzer Rainer 
Published: January 2024

AbstractHemp (Cannabis sativa) is one of the oldest cultivated crops, and its myriad of uses have fascinated humans for millennia. In contemporary agriculture, the seeds are used for high-quality oil, human food, and nutritional supplements. From female inflorescences, secondary compounds (cannabinoids, terpenes, and flavonoids) are isolated that are implicated to have a wide range of medicinal applications. These elements provide hemp with significant market and research value and emphasise the need to thoroughly understand reproductive development in hemp.Here, we present a detailed morphological and molecular analysis of hemp inflorescence and flower development of the cultivar ‘FINOLA’. Hemp is unusual among flowering plants as it is dioecious, i.e. develops male and female plants. We define eight landmark events in male and female flower development and show that developmental differences between male and female plants extend beyond floral morphology, additionally comprising inflorescence structure as well as flowering time. Further, we demonstrate that the time of activation of key reproductive developmental regulators is significantly different in male and female hemp plants. Our comparison of male and female hemp plants shows that developmental pathways diverge very early, already at the two-leaf stage, laying a basis for further exploration into the genetics of sex determination ofC. sativa.