bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global patterns in the evolutionary relations between seed mass and germination traits
Authors: Maleki Keyvan , Vandelook Filip , Saatkamp Arne , Maleki Kourosh , Heshmati Siavash , Soltani Elias 
Published: April 2024

AbstractDuring stressful climatic periods, plant populations face significant challenges, especially during germination and seedling establishment. Theoretical studies present conflicting findings regarding the relationship between seed size and germination rate. Some analyses suggest that species with larger seeds should exhibit rapid germination, while others point to faster germination in smaller seeds. This discrepancy can, for example, be attributed to the higher vulnerability of larger seeds to post-dispersal seed predation. To assess the correlation between seed mass and seed germination characteristics at a global scale, we performed a rigorous meta-analysis of published data sources, covering a wide range of germination traits across 1877 species with diverse dormancy types and global distribution. Additionally, we investigated the potential relationship between seed mass and dormancy level. Our findings revealed contrasting responses of germination traits to seed mass, suggesting complex eco-evolutionary correlations among these traits. Trade-offs and corelated evolution likely played an important role in the evolutionary history of seed mass, with seed mass displaying notable trait conservation across the phylogeny. Interestingly, our study demonstrated that seed dormancy exhibited trade-offs with post-germination traits and seed mass. The meta-analysis demonstrated that any changes in the relationship between seed mass and dormancy is dependent on dormancy types with physiological dormancy showing lower seed mass while other dormancy types were has a higher seed mass. These results underscore the critical role of seed mass in shaping plant performance and provide valuable insights into plant trait evolution. Our findings clearly indicate that the hypothesis of larger seeds conferring advantages in both pre- and post-germination traits might not be empirically true in all cases as theoretical studies suggest and that this relationship is complex and varies among species and growth forms. We interpret these results within the context of germination strategies and correlated evolution between seed dormancy and seed mass. Considering these traits in future analyses of plant germination strategies and species distributions is crucial. Factors such as lifespan, seed mass, and germination-related traits should be carefully considered to gain a comprehensive understanding of plant adaptation to challenging environmental conditions.
Colonization ofAnopheles coustani, a neglected malaria vector in Madagascar
Authors: Andrianinarivomanana Tsarasoa M. , Randrianaivo Fenomiaranjara T. , Andriamiarimanana Mandaniaina R. , Razafimamonjy Mihary R. , Velonirina Haja J.S , Puchot Nicolas , Girod Romain , Bourgouin Catherine 
Published: April 2024

AbstractAnopheles coustanihas long be recognized as a secondary malaria vector in Africa. It has recently been involved in the transmission of bothPlasmodium falciparumandPlasmodium vivaxin Madagascar. As most secondary malaria vector,An. coustaniis mainly biting outdoor, which renders the control of this mosquito species difficult by the classical malaria control measures as the use of bed nets or indoor residual spraying of insecticides. The absence of a colony hinders a better understanding of its biology and vector competence towards the development of adapted mosquito control strategies. Here, we report the first successful establishment of anAn. coustanicolony from mosquito collected in Madagascar. We used a forced copulation procedure as this mosquito species will not mate in cages. We describe our mosquito colonization procedure with detailed biological features as larval to adult development and survival, recorded over the first six critical generations. The procedure should be easily applicable toAn. coustanifrom different African countries, facilitating local investigation onAn. coustanivector competence and insecticide resistance using the colony as a reference.
Classifying cell cycle states and a quiescent-like G0 state using single-cell transcriptomics
Authors: O‘Connor Samantha A. , Garcia Leonor , Hoover Rori , Patel Anoop P. , Bartelle Benjamin B. , Hugnot Jean-Philippe , Paddison Patrick J. , Plaisier Christopher L. 
Published: April 2024

AbstractSingle-cell transcriptomics has unveiled a vast landscape of cellular heterogeneity in which the cell cycle is a significant component. We trained a high-resolution cell cycle classifier (ccAFv2) using single cell RNA-seq (scRNA-seq) characterized human neural stem cells. The ccAFv2 classifies six cell cycle states (G1, Late G1, S, S/G2, G2/M, and M/Early G1) and a quiescent-like G0 state (Neural G0), and it incorporates a tunable parameter to filter out less certain classifications. The ccAFv2 classifier performed better than or equivalent to other state-of-the-art methods even while classifying more cell cycle states, including G0. We demonstrate that the ccAFv2 classifier effectively generalizes the S, S/G2, G2/M, and M/Early G1 states across cell types derived from all three germ layers. While the G0, G1, and Late G1 states perform well in neuroepithelial cell types, their accuracy is lower in other cell types. However, misclassifications are confined to the G0, G1, and Late G1 states. We showcased the versatility of ccAFv2 by successfully applying it to classify cells, nuclei, and spatial transcriptomics data in humans and mice, using various normalization methods and gene identifiers. We provide methods to regress the cell cycle expression patterns out of single cell or nuclei data to uncover underlying biological signals. The classifier can be used either as an R package integrated with Seurat or a PyPI package integrated with SCANPY. We proved that ccAFv2 has enhanced accuracy, flexibility, and adaptability across various experimental conditions, establishing ccAFv2 as a powerful tool for dissecting complex biological systems, unraveling cellular heterogeneity, and deciphering the molecular mechanisms by which proliferation and quiescence affect cellular processes.
Integrative machine learning approaches for predicting disease risk using multi-omics data from the UK Biobank
Authors: Aguilar Oscar , Chang Cheng , Bismuth Elsa , Rivas Manuel A. 
Published: April 2024

AbstractWe train prediction and survival models using multi-omics data for disease risk identification and stratification. Existing work on disease prediction focuses on risk analysis using datasets of individual data types (metabolomic, genomics, demographic), while our study creates an integrated model for disease risk assessment. We compare machine learning models such as Lasso Regression, Multi-Layer Perceptron, XG Boost, and ADA Boost to analyze multi-omics data, incorporating ROC-AUC score comparisons for various diseases and feature combinations. Additionally, we train Cox proportional hazard models for each disease to perform survival analysis. Although the integration of multi-omics data significantly improves risk prediction for 8 diseases, we find that the contribution of metabolomic data is marginal when compared to standard demographic, genetic, and biomarker features. Nonetheless, we see that metabolomics is a useful replacement for the standard biomarker panel when it is not readily available.
Functional diversities within neurons and astrocytes in the adult rat auditory cortex revealed by single-nucleus RNA sequencing
Authors: Aydin Aysegul Gungor , Lemenze Alexander , Bieszczad Kasia M 
Published: April 2024

AbstractThe mammalian cerebral cortex is composed of a rich diversity of cell types. Cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions. To investigate the breadth of transcriptional diverse cell types in the sensory cortex, we have used single-nucleus RNA sequencing (snRNA-seq) in the auditory cortex of the adult rat. A variety of unique excitatory and inhibitory neuron types were identified. In addition, we report for the first time a diversity of astrocytes in the auditory cortex that may represent functionally unique subtypes. Together, these results pave the way for building models of how neurons in the sensory cortex work in concert with astrocytes at synapses to fulfill high-cognitive functions like learning and memory.
Sequence, Structural and Functional Diversity of the Ubiquitous DNA/RNA-Binding Alba Domain
Authors: Jaiganesh Jagadeesh , Vembar Shruthi Sridhar 
Published: April 2024

AbstractThe DNA/RNA-binding Alba domain is prevalent across all kingdoms of life. Discovered in archaea more than 40 years ago, this protein domain appears to have evolved from RNA- to DNA- binding, with a concomitant expansion in the range of cellular processes that it regulates. Indeed, Alba domain-containing proteins continue to exhibit functional ingenuity, with their most recent association being R-loop regulation in plants: they accomplish this by binding to DNA:RNA hybrid structures as heterodimers. To further explore Alba diversity and evolutionary relatedness, which could in turn lead to new functional revelations, we employed iterative searches in PSI-BLAST to identify 15161 true Alba domain-containing proteins from the NCBI non-redundant protein database. Next, by building sequence similarity networks (SSNs), we identified 13 distinct clusters representing various Alba subgroups. These included the classic eukaryotic Rpp20/Pop7 and Rpp25/Pop6 proteins as well as novel fungal Alba proteins andPlasmodium-specific Albas. Conservation analysis indicated that, despite overall low primary sequence similarity between the SSN clusters, the homo- or hetero-dimer interface is highly conserved. Furthermore, the presence of the classic Alba fold was confirmed in representative sequences from each cluster by comparison of their Hidden Markov Model (HMM) profiles andab initiothree-dimensional structures. Notably, Alba domains from lower, unicellular eukaryotes and fungal Albas exhibit structural deviations towards their C-terminal end. Finally, phylogenetic analysis, while supporting SSN clustering, revealed the evolutionary branchpoint at which the eukaryotic Rpp20- and Rpp25-like clades emerged from archaeal Albas, and the subsequent taxonomic lineage-based divergence within each clade. Taken together, this comprehensive analysis enhances our understanding of the evolutionary history of Alba domain-containing proteins across diverse organisms, their sequence and structural conservation, and functional implications for genome and RNA biology.
Autonomic Modulation with Mindfulness-Based Stress Reduction in Chronic Kidney Disease: A Randomized Controlled Trial
Authors: Jeong Jinhee , Hu Yingtian , Zanuzzi Matias , DaCosta Dana , Li Sabrina , Park Jeanie 
Published: April 2024

AbstractBackgroundChronic kidney disease (CKD) is characterized by overactivation of the sympathetic nervous system (SNS) that leads to increased cardiovascular disease risk. Despite the deleterious consequences of SNS overactivity, there are very few therapeutic options available to combat sympathetic overactivity.AimTo evaluate the effects of Mindfulness-Based Stress Reduction (MBSR) on SNS activity in CKD patients.MethodParticipants with CKD stages III-IV were randomized to an 8-week MBSR program or Health Education Program (HEP; a structurally parallel, active control group). Primary outcomes were direct intraneural measures of SNS activity directed to muscle (MSNA) via microneurography at rest and during stress maneuvers.Results28 participants (63 ±9 years; 86% males) completed the intervention with 16 in MBSR and 12 in HEP. There was a significant Group (MBSR vs. HEP) by Time (baseline vs. post-intervention) interaction in the change in MSNA reactivity to mental stress (p=0.026), with a significant reduction in the mean change in MSNA over 3 minutes of mental arithmetic at post-intervention (10.6 ± 7.1 to 5.0 ± 5.7 bursts/min, p<0.001), while no change was observed within the HEP group (p=0.773).ConclusionsIn this randomized controlled trial, patients with CKD had an amelioration of sympathetic reactivity during mental stress following 8-weeks of MBSR but not after HEP. Our findings demonstrate that mindfulness training is feasible and may have clinically beneficial effects on autonomic function in CKD.
Stochastic modelling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones
Authors: Hirsch M.G. , Pal Soumitra , Mehrabadi Farid Rashidi , Malikic Salem , Gruen Charli , Sassano Antonella , Pérez-Guijarro Eva , Merlino Glenn , Sahinalp Cenk , Molloy Erin K. , Day Chi-Ping , Przytycka Teresa M. 
Published: April 2024

AbstractCancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present the first formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein–Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data. Applying our model to sublines derived from single cells of a mouse melanoma revealed that sublines with distinct phenotypes are underlined by different patterns of gene expression adaptation, indicating non-genetic mechanisms of cancer evolution. Interestingly, sublines previously observed to be resistant to anti-CTLA-4 treatment showed adaptive expression of genes related to invasion and non-canonical Wnt signaling, whereas sublines that responded to treatment showed adaptive expression of genes related to proliferation and canonical Wnt signaling. Our results suggest that clonal phenotypes emerge as the result of specific adaptivity patterns of gene expression.
Single-embryo metabolomics reveals developmental metabolism in the earlyDrosophila embryo
Authors: Pérez-Mojica J. Eduardo , Madaj Zachary B. , Isaguirre Christine N. , Roy Joe , Lau Kin H. , Sheldon Ryan D. , Lempradl Adelheid 
Published: April 2024

ABSTRACTEarly embryonic development is characterized by the transition from maternal factor reliance to zygotic control. These processes set the stage for the embryo’s basic structure and cellular differentiation. While relatively detailed knowledge exists of the transcriptional events during early development, little is known about the concurrent metabolic processes. Understanding these processes, however, is important since they are linked to cell fate determination and organ and tissue formation. The primary reasons for the limited progress in the field are technical limitations due to the small amount of material available during early embryonic time windows. Here, we introduce a novel single-embryo methodology that places us in an exciting position to analyze the early embryo’s metabolome and transcriptome in an integrated manner and at high temporal resolution. The resulting data allow us to map concomitant metabolic and transcriptional programs in earlyDrosophilaembryonic development. Our results reveal that a substantial number of metabolites exhibit dynamic patterns with some changing even before the onset of zygotic transcription. dNTPs for example show a temporal pattern that correlates with cell division patterns in the early embryo. In summary, here we present an operationally simple single-embryo metabolomics methodology and provide a detailed picture of early developmental metabolic processes at unprecedented temporal resolution.
Cholesterol Dependence of the Conformational Changes in Metabotropic Glutamate Receptor 1
Authors: Isu Ugochi H. , Badiee Shadi A. , Polasa Adithya , Tabari Seyed H. , Derakhshani-Molayousefi Mortaza , Moradi Mahmoud 
Published: April 2024

AbstractMetabotropic glutamate receptors (mGluRs) are class C G protein-coupled receptors that function as obligate dimers in regulating neurotransmission and synaptic plasticity in the central nervous system. The mGluR1 subtype has been shown to be modulated by the membrane lipid environment, particularly cholesterol, though the molecular mechanisms remain elusive. In this study, we employed all-atom molecular dynamics simulations to investigate the effects of cholesterol on the conformational dynamics of the mGluR1 seven-transmembrane (7TM) domain in an inactive state model. Simulations were performed with three different cholesterol concentrations (0%, 10%, and 25%) in a palmitoyl-oleoyl phosphatidylcholine (POPC) lipid bilayer system. Our results demonstrate that cholesterol induces conformational changes in the mGluR1 dimer more significantly than in the individual protomers. Notably, cholesterol modulates the dynamics and conformations of the TM1 and TM2 helices at the dimer interface. Interestingly, an intermediate cholesterol concentration of 10% elicits more pronounced conformational changes compared to both cholesterol-depleted (0%) and cholesterol-enriched (25%) systems. Specific electrostatic interaction unique to the 10% cholesterol system further corroborate these conformational differences. Given the high sequence conservation of the 7TM domains across mGluR subtypes, the cholesterol-dependent effects observed in mGluR1 are likely applicable to other members of this receptor family. Our findings provide atomistic insights into how cholesterol modulates the conformational landscape of mGluRs, which could impact their function and signaling mechanisms.
Zebrafish arterial valve development occurs through direct differentiation of second heart field progenitors
Authors: Derrick Christopher J. , Eley Lorraine , Alqahtani Ahlam , Henderson Deborah J. , Chaudhry Bill 
Published: April 2024

AbstractAimsBicuspid Aortic Valve (BAV) is the most common congenital heart defect, affecting at least 2% of the population. The embryonic origins of BAV remain poorly understood, limiting the identification of assays for validating patient variants and ultimately causative genes for BAV. In both human and mouse, the left and right leaflets of the arterial valves arise from the outflow tract cushions, with interstitial cells originating from neural crest cells and endocardial-to-mesenchymal transition (EndoMT). In contrast, an EndoMT-independent mechanism of direct differentiation by cardiac progenitors from the second heart field (SHF) is responsible for the formation of the anterior and posterior leaflets. Defects in either of these developmental mechanisms can result in BAV. Although zebrafish have been suggested as a model for human variant testing, their naturally bicuspid arterial valve has not been considered suitable for understanding human arterial valve development. Here, we have set out to investigate to what extent the processes involved in arterial valve development are conserved in zebrafish and ultimately, whether functional testing of BAV variants could be carried out in zebrafish.Methods and ResultsUsing a combination of live imaging, immunohistochemistry and Cre-mediated lineage tracing, we show that the zebrafish arterial valve primordia develop directly from undifferentiated SHF progenitors with no contribution from EndoMT or neural crest, in keeping with the human and mouse anterior and posterior leaflets. Moreover, once formed, these primordia share common subsequent developmental events with all three mammalian arterial valve leaflets.ConclusionsOur work highlights a conserved ancestral mechanism of arterial leaflet formation from the SHF and identifies that development of the zebrafish arterial valve is distinct from that of the atrioventricular valve. Crucially, this confirms the utility of zebrafish for understanding the development of specific BAV subtypes and arterial valve dysplasia, offering potential for high-throughput variant testing.Translational PerspectiveLarge genomic studies of patients with Bicuspid Aortic Valve (BAV) have identified numerous variants predicted to be causative, yet due to a lack of suitable,in vivofunctional assays, advancement of genetic testing, discussion of risk to family members and accurate prognosis is not yet widely possible. Here, we show that zebrafish demonstrate a high level of conservation in arterial valve development with the intercalated leaflets in human, establishing zebrafish as a suitablein vivomodel that can begin to overcome the disconnect between clinical genetics and developmental biology.
Treatment options for Chagas Disease: a systematic review and meta-analysis applied to the preclinical studies using animal models
Authors: Machaca-Luque Laura Yesenia , Candia-Puma Mayron Antonio , Roque-Pumahuanca Brychs Milagros , Barazorda-Ccahuana Haruna Luz , Goyzueta-Mamani Luis Daniel , Galdino Alexsandro Sobreira , Machado-de-Ávila Ricardo Andrez , Giunchetti Rodolfo Cordeiro , Ferraz Coelho Eduardo Antonio , Chávez-Fumagalli Miguel Angel 
Published: April 2024

AbstractChagas disease (CD) is a neglected tropical disease endemic to Latin America and has emerged as a global health concern due to the migration of infected individuals. With its epidemiological complexity, difficulty in obtaining appropriate diagnoses, and poor treatment, the search for novel therapeutic options remains. In this context, we conducted a systematic review and meta-analysis of preclinical studies employing animal models to verify the progress in CD treatment. We searched the PubMed database for CD treatment studies published between 1990 and 2023, adhering to the PRISMA guidelines. Twelve papers met the inclusion criteria. The findings indicate that the fifteen treatment alternatives examined, mainly between 2010 and 2014, demonstrated efficacy in experimental CD models, evidenced by significant parasitemia reduction. Bis-triazole DO870 and VNI were effective in the acute and chronic phases, respectively. However, of these emerging therapies, only posaconazole and fexinidazole have progressed to clinical trials, yielding unsatisfactory outcomes as CD monotherapies. This meta-analysis highlights the existence of promising new drug candidates for CD treatment, but most remain in the preclinical stages. Those that reached clinical trials did not demonstrate optimal results, underscoring the ongoing challenges in CD therapy. Collaborative efforts among the academic community, pharmaceutical industries, funding agencies, and government agencies are urgently needed to accelerate the development of more effective medications against CD.
Green Synthesis of Silver and Gold Nanoparticles by Aqueous Artemisia Pallens Extract
Authors: Verma Ashutosh Kumar 
Published: April 2024

AbstractWe successfully harnessed the potential of Artemisia pallens extracts for the eco-friendly biosynthesis of silver, gold, and silver-gold bimetallic nanoparticles, employing aqueous silver nitrate and chloroauric acid solutions. This innovative approach departs from traditional methods, often involving toxic chemical agents like hydrazine hydrate and sodium borohydride. In the quest for greener protocols, the biological route emerges as a non-toxic, straight-forward, and environmentally sound alternative, opening new avenues for translational research. This article discusses the production of silver, gold, and silver-gold nanoparticles using different species of Artemisia plants. Nanoparticle characterization was carried out using UV-visible spectrophotometry, TEM, XRD, and FTIR techniques. Microwave-assisted synthesis resulted in well-dispersed nanoparticles. In the case of silver nanoparticles, a spherical shape with a size of 6 nm was achieved using the microwave radiation-assisted method, while a size of 20 nm was obtained with UV-assisted synthesis. Gold nanoparticles exhibited diverse shapes, including spherical, triangular, prisms, trapezoids, and hexagonal, with a predominant size of 10 nm. The size range for gold nanoparticles varied from 10 nm to 400 nm.