bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome size, genetic diversity, and phenotypic variability imply the effect of genetic variation instead of ploidy on trait plasticity in the cross-pollinated tree species of mulberry
Authors: Gnanesh Belaghihalli N , Mondal Raju , Arunakumar GS , Manojkumar HB , Singh Pradeep , Bhavya MR , Sowbhagya P , Burji Shreyas M , Mogili T , Sivaprasad V 
Published: April 2023

AbstractGenome size, genetic diversity, and phenotypic vitiation were estimated to develop a model-based population structure and identify ploidy-associated traits of a wide collection of cross-pollinated, highly heterozygous tree species ofMorus.Elucidation of genome size (GS), genetic and phenotypic variation is the fundamental aspect of crop improvement programs. Mulberry is a cross-pollinated, highly heterozygous tree eudicot, and comprised of huge ploidy variation with great adaptability across the world. However, because of inadequate information on GS, ploidy-associated traits, as well as the correlation between genetic and phenotypic variation hinder the further improvement of mulberry. In this present research, a core set of 157 germplasm accessions belonging to eight accepted species ofMorusincluding promising functional varieties were chosen to represent the genetic spectrum from the whole germplasm collection. To estimate the GS, accessions were subjected to flow cytometry (FCM) analysis and the result suggested that four different ploidies (2n=2x, 3x, 4x, and 6x) with GS ranging from 0.72±0.005 (S-30) to 2.89±0.015 (M. serrata), accounting ∼4.01 fold difference. The predicted polyploidy was further confirmed with metaphase chromosome count. In addition, the genetic variation was estimated by selecting a representative morphologically, diverse population of 82 accessions comprised of all ploidy variations using simple sequence repeats (SSR). The estimated average Polymorphism Information Content (PIC) and expected heterozygosity showed high levels of genetic diversity. Additionally, three populations were identified by the model-based population structure (k=3) with a moderate level of correlation between the populations and different species of mulberry, which imply the effect of genetic variation instead of ploidy on trait plasticity that could be a consequence of the high level of heterozygosity imposed by natural cross-pollination. Further, the correlation between ploidies, especially diploid and triploid with selected phenotypic traits was identified, however, consistency could not be defined with higher ploidy levels (>3x). Moreover, incite gained here can serve as a platform for future omics approaches to the improvement of mulberry traits.
Lectins in pistils play a key role in self-incompatibility in the heterostylousLinum perenne
Authors: Levchuk Hanna , Makhno Yuliia , Costa Maria Manuela Ribeiro , Lenhard Michael 
Published: April 2023

AbstractSelf-incompatibility is one of the mechanisms preventing inbreeding in populations, based on the failure of pollen grains to germinate or of pollen tubes to grow normally in incompatible crosses. A unique model for studying this process are heterostylous species, in which self-incompatibility alleles are closely linked to flower morphological traits. One such species isL. perenne, a classic distylous species with reciprocal herkogamy and complete self-incompatibility strongly linked. The mechanism of self-pollen recognition is poorly understood in most heterostylous species, includingL. perenne. As self-incompatibility in other systems is based on protein-protein interactions and many extracellular proteins are glycosylated, one of the possible participants in this process may be lectins. Therefore, we aimed to investigate the lectin activity in pistils and stamens ofL. perenneL-morph and S-morph plants and to establish whether these lectins take part in self-incompatibility. We show that pistil-derived galactose-specific Ca2+-independent lectins from the respective other morph can overcome self-incompatibility in heterostylousL. perenne. This may be due to the presence of some lectins that are specific for arabinose and xylose. Our results suggest that lectins participate in signaling pathways for recognition at the pollen-stigma interface and are involved in the regulation of the self-incompatibility process inL. perenne.
A hybrid demultiplexing strategy that improves performance and robustness of cell hashing
Authors: Li Lei , Sun Jiayi , Fu Yanbin , Changrob Siriruk , McGrath Joshua J.C. , Wilson Patrick C. 
Published: April 2023

AbstractRecent advances in single cell RNA sequencing allow users to pool multiple samples and demultiplex in downstream analysis, which greatly increase experimental efficiency and cost-effectiveness. Among all the demultiplexing methods, nucleotide barcode-based cell hashing has gained widespread popularity due to its compatibility and simplicity. Despite these advantages, certain issues of this technic remain to be solved, such as challenges in distinguishing true positive from background, high reagent cost for samples with large cell numbers, and unpredictable false negative and false doublet rates. Here, we propose a hybrid demultiplexing strategy that increases calling accuracy and cell recovery of cell hashing without adding experimental cost. In this approach, we computationally cluster all single cells based on their natural genetic variations and assign donor identity by finding the dominant hashtag in each genotype cluster. This hybrid strategy assigns donor identity to any cell that is identified as singlet by either genotype clustering or cell hashing, which allows us to demultiplex most majority of cells even if only a small fraction of cells are labeled with hashtags. When comparing its performance with cell hashing on multiple real-world datasets, this hybrid approach consistently generates reliable demultiplexing results with increased cell recovery and accuracy.Key PointsThe improved cut-off calling tool, HTOreader, accurately distinguishes true positive from background signal for each individual hashtag.The hybrid demultiplexing strategy increases cell recovery of cell hashing by increasing cut-off calling accuracy and decreasing false negative and false double rates.The hybrid strategy enhances cost-effectiveness of cell hashing and consistently produces reliable demultiplexing results, regardless of hashtag staining quality.The hybrid strategy can be seamlessly integrated into a variety of single-cell experimental protocols and analytic pipelines.
Guadalupe fur seal alopecia: a metabolic syndrome associated to climatic anomalies?
Authors: Guzmán-Solís Ariadna A. , Elorriaga-Verplancken Fernando R. , Acevedo-Whitehouse Karina A. 
Published: April 2023

AbstractAlopecia is characterized by the thinning and loss of hair or fur, and has been observed in different marine carnivores. Until recently, there were no records of alopecia in marine mammals from the Northeast Pacific Ocean. However, sightings of juvenile male Guadalupe fur seals with patchy alopecia in the ventral body have been reported in the San Benito Archipelago. This is concerning given that the species is considered endangered under Mexican law and has only started to recover from near extinction less than a century ago. We captured 13 fur seals at San Benito Archipelago during the summer of 2017 and 2018 and collected fur samples for common dermatological analysis, as well as scanning electron microscopy and X-ray spectroscopy. We found marked damage to the structure of guard fur, with loss of integrity, medullary damage and perforations. Damage to secondary underfur hair was less common. We found no evidence of dermatophyte microorganisms or ectoparasites commonly associated with alopecia. We suggest that the damage is caused by metabolic alterations secondary to nutritional stress that is consequential to high sea surface temperatures that alter prey availability. This is the first study of alopecia in an otariid pinniped of the Northeast Pacific Ocean.
Beyond gene-disease validity: capturing structured data on inheritance, allelic-requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions
Authors: Josephs Katherine S , Roberts Angharad M , Theotokis Pantazis , Walsh Roddy , Ostrowski Philip J , Edwards Matthew , Fleming Andrew , Thaxton Courtney , Roberts Jason D , Care Melanie , Zareba Wojciech , Adler Arnon , Sturm Amy C , Tadros Rafik , Novelli Valeria , Owens Emma , Bronicki Lucas , Jarinova Olga , Callewaert Bert , Peters Stacey , Lumbers Tom , Jordan Elizabeth , Asatryan Babken , Krishnan Neesha , Hershberger Ray E , Chahal C. Anwar A. , Landstrom Andrew P. , James Cynthia , McNally Elizabeth M , Judge Daniel P , van Tintelen Peter , Wilde Arthur , Gollob Michael , Ingles Jodie , Ware James S 
Published: April 2023

AbstractBackgroundAs availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including as secondary findings.MethodsWe analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering.ResultsFor 36/65 gene-disease pairs, loss-of-function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using CardiacG2P as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches.ConclusionsAccess to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is pre-requisite for scalable genomic testing.
A rapid review of what organisational level factors support or inhibit the scale and spread of innovations in children’s social care
Authors: Mann Mala , Lifford Kate , O’Connell Susan , Weightman Alison , Searchfield Lydia , Lewis Ruth , Cooper Alison , Edwards Adrian 
Published: April 2023

AbstractInnovation may provide a means for tackling challenges facing childrens social care, some of them deep-rooted and many exacerbated by COVID-19. Welsh Government has recently committed to a significant 3-year investment to support innovation in adults and childrens social care. The delivery of social care in Wales has a complex and multi-faceted approach, involving collaborative working between a range of organisations, which will likely affect decisions around implementation and scale-up of new and/or existing interventions. The aim of the review was to identify any factors (barriers and enablers) that affect the implementation and scale up of an innovation in childrens social care organisations.Ten studies were identified, comprising three secondary studies (reviews) and seven primary studies. Factors potentially influencing scale and spread of innovation were extracted and categorised. The domains (and sub-domains) covered by included studies were; adopters (staff role/identity; carer input), organisation (capacity to innovate; readiness for change; nature of adoption/funding; extent of change needed; work needed to implement), and wider system (political/policy; regulatory/legal; professional; socio-cultural).Enablers for which a clear consensus seems to be emerging across the literature included: specific training and support for professional staff, support and mutual respect within inter-professional and professional-carer relationships, senior management/leadership buy-in and support, multi-disciplinary communication and joint working, and developing compatible data systems to support joint working/collaboration. Barriers for which a clear consensus seems to be emerging across the literature were: short term or lack of funding (the need for funding was presented as an enabler in some studies), and implementation difficulties (e.g. multiple priorities and changing structures).Policy Implications: This review highlights the complexity of the social care models but provides some clear pointers for policy and practice. The findings indicate the need for: senior management buy-in and support, short and longer term funding, multi-disciplinary communication and joint working, good professional (and professional-carer) relationships with support and mutual respect, and specific training and support for professional staff.The confidence in the evidence is uncertain as the study designs included non-systematic reviews and service evaluations; most studies did not use a formal methodology and all had some quality limitations.
SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration
Authors: Hartmann Jakob , Bajaj Thomas , Otten Joy , Klengel Claudia , Gellner Anne-Kathrin , Junglas Ellen , Hafner Kathrin , Anderzhanova Elmira A , Tang Fiona , Missig Galen , Rexrode Lindsay , Li Katelyn , Pöhlmann Max L , Heinz Daniel E , Lardenoije Roy , Dedic Nina , McCullough Kenneth M , Próchnicki Tomasz , Rhomberg Thomas , Martinelli Silvia , Payton Antony , Robinson Andrew C. , Stein Valentin , Latz Eicke , Carlezon William A , Schmidt Mathias V , Murgatroyd Chris , Berretta Sabina , Klengel Torsten , Pantazopoulos Harry , Ressler Kerry J , Gassen Nils C 
Published: April 2023

SummaryHigh levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. We demonstrate that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. HippocampalSka2knockdown in mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, initiating an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D (GSDMD)-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of postmortem brains demonstrate that SA is hyperactivated in Alzheimer’s disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer’s disease, providing new mechanistic insight into the biology of neuroinflammation.
Let’s make it clear: Systematic exploration of mitochondrial DNA- and RNA-protein complexes by complexome profiling
Authors: Potter Alisa , Cabrera-Orefice Alfredo , Spelbrink Johannes N. 
Published: April 2023

AbstractComplexome profiling (CP) is a powerful tool for systematic investigation of protein interactors that has been primarily applied to study the composition and dynamics of mitochondrial protein complexes. Here, we further optimised this method to extend its application to survey mitochondrial DNA- and RNA-interacting protein complexes. We established that high-resolution clear native gel electrophoresis (hrCNE) is a better alternative to preserve DNA- and RNA-protein interactions that are otherwise disrupted when samples are separated by the widely used blue native gel electrophoresis (BNE). In combination with enzymatic digestion of DNA, our CP approach improved the identification of a wide range of protein interactors of the mitochondrial gene expression system without compromising the detection of other multi-protein complexes. The utility of this approach was particularly demonstrated by analysing the complexome changes in human mitochondria with impaired gene expression after transient, chemically-induced mtDNA depletion. Effects of RNase on mitochondrial protein complexes were also evaluated and discussed. Overall, our adaptations significantly improved the identification of mitochondrial DNA- and RNA-protein interactions by CP, thereby unlocking the comprehensive analysis of a near-complete mitochondrial complexome in a single experiment.
Efflux pumps mediate changes to fundamental bacterial physiology via membrane potential
Authors: Whittle Emily E , Orababa Oluwatosin , Osgerby Alexander , Element Sarah J , Blair Jessica MA , Overton Tim W 
Published: April 2023

AbstractEfflux pumps are well known to be an important mechanism for removing noxious substances such as antibiotics from bacteria. Given that many antibiotics function by accumulating inside bacteria, efflux pumps contribute to resistance. Efflux pump inactivation is a potential strategy to combat antimicrobial resistance, as bacteria would not be able to pump out antibiotics. We recently discovered that the impact of loss of efflux function is only apparent in actively growing cells. We demonstrated that the global transcriptome ofSalmonellaTyphimurium is drastically altered during slower growth leading to stationary phase cells having a re-modelled, less permeable, envelope that prevents antibiotics entering the cell. Here, we investigated the effects of deleting the major efflux pump ofSalmonellaTyphimurium, AcrB, on global gene transcription across growth. We revealed that anacrBknockout entered stationary phase later than the wild type strain SL1344, and displayed increased and prolonged expression of genes responsible for anaerobic energy metabolism. We devised a model linking efflux and membrane potential, whereby deactivation of AcrB prevents influx of protons across the inner membrane and thereby hyperpolarisation. Knockout or deactivation of AcrB was demonstrated to increase membrane potential. We propose that the global transcription regulator ArcBA senses changes to the redox state of the quinol pool (linked to the membrane potential of the bacterium) and coordinates the shift from exponential to stationary phase via the key master regulators RpoS, Rsd, and Rmf. Inactivation of efflux pumps therefore influences the fundamental physiology ofSalmonella, with likely impacts on multiple phenotypes.ImportanceWe demonstrate for the first time that deactivation of efflux pumps brings about changes to gross bacterial physiology and metabolism. Rather than simply being a response to noxious substances, efflux pumps appear to play a key role in maintenance of membrane potential and thereby energy metabolism. This discovery suggests that efflux pump inhibition or inactivation might have unforeseen positive consequences on antibiotic activity. Given that stationary phase bacteria are more resistant to antibiotic uptake, late entry into stationary phase would prolong antibiotic accumulation by bacteria. Furthermore, membrane hyperpolarisation could result in increased generation of reactive species proposed to be important for the activity of some antibiotics. Finally, changes in gross physiology could also explain the decreased virulence of efflux mutants.
APPLICATION OF PLANTS BASED MATERIAL FOR THE MANUFACTURING OF MOSQUITO REPELLENT SURFACE COATING
Authors: Iftikhar Tehreema , Majeed Hammad , Abid Rida , Khan Faheem. A. 
Published: April 2023

AbstractMosquitos have been a malice and source of many diseases in humans. Later on, humans understood they learned that plants also possess mosquito-repellent properties. Different insectrepellent coatings are present in the market which are chemically prepared and can be harmful to humans and the environment. Different plants have insect-repellent properties which have been utilized in this research to make a nature-based insect-repellent surface coating.Moringa oleiferaL. andMentha piperitaL. are naturally insect-repellent plants. Nanoparticles increase the surface area and efficiency of extracts of plants. Thus, ZnONP ofMoringa olieferaL. andMentha piperitaL. plants were made characterization was done through UV-vis spectroscopy, FTIR, and PSA. The UV-visible spectrum showed absorption peaks for ZnO nanoparticles at 350nm forMentha piperitaL. and 356nm forMoringa oleiferaL. The particle size analysis indicated the variable sizes of ZnONPs for both plants. FTIR showed vibration peaks from 3341 to 650cm-1forMoringa oleiferaL. and 3393 to 700 cm-1forMentha piperitaL. ZnONPs were used in paint along with water extracts of plants to make the paint insect-repellent in nature. Mosquito repellent activity of paint formulations was also tested againstAedes aegypti.
MANGEM: a web app for Multimodal Analysis of Neuronal Gene expression, Electrophysiology and Morphology
Authors: Olson Robert Hermod , Kalafut Noah Cohen , Wang Daifeng 
Published: April 2023

AbstractSingle-cell techniques have enabled the acquisition of multi-modal data, particularly for neurons, to characterize cellular functions. Patch-seq, for example, combines patch-clamp recording, cell imaging, and single-cell RNA-seq to obtain electrophysiology, morphology, and gene expression data from a single neuron. While these multi-modal data offer potential insights into neuronal functions, they can be heterogeneous and noisy. To address this, machine-learning methods have been used to align cells from different modalities onto a low-dimensional latent space, revealing multi-modal cell clusters. However, the use of those methods can be challenging for biologists and neuroscientists without computational expertise and also requires suitable computing infrastructure for computationally expensive methods. To address these issues, we developed a cloud-based web application, MANGEM (Multimodal Analysis of Neuronal Gene expression, Electrophysiology, and Morphology) athttps://ctc.waisman.wisc.edu/mangem. MANGEM provides a step-by-step accessible and user-friendly interface to machine-learning alignment methods of neuronal multi-modal data while enabling real-time visualization of characteristics of raw and aligned cells. It can be run asynchronously for large-scale data alignment, provides users with various downstream analyses of aligned cells and visualizes the analytic results such as identifying multi-modal cell clusters of cells and detecting correlated genes with electrophysiological and morphological features. We demonstrated the usage of MANGEM by aligning Patch-seq multimodal data of neuronal cells in the mouse visual cortex.Author SummaryThe human brain is made up of billions of tiny cells called neurons, each with their own important job. Scientists are now able to study individual neurons in more detail than ever before using new advanced techniques. They can look at different data of individual neurons like how genes are being used (gene expression), how the neuron responds to electrical signals (electrophysiology), and what it looks like (morphology). By combining all of this information, they can start to group similar neurons together and figure out what they do. However, due to the data complexity, this process can be very complicated and hard for researchers without sufficient computational skills. To address this, we developed a web app, MANGEM (Multimodal Analysis of Neuronal Gene Expression, Electrophysiology, and Morphology). It lets scientists upload their data and select emerging machine-learning approaches to find groups of similar neurons. It also makes interactive visualizations to help them explore the characteristics of neuron groups and understand what they do.