bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative splicing preferentially increases transcript diversity associated with stress responses in the extremophyteSchrenkiella parvula
Authors: Wijesinghege Chathura , Tran Kieu-Nga , Dassanayake Maheshi 
Published: October 2022

AbstractAlternative splicing extends the coding potential of genomes by creating multiple isoforms from one gene. Isoforms can render transcript specificity and diversity to initiate multiple responses required during transcriptome adjustments in stressed environments. Although the prevalence of alternative splicing is widely recognized, how diverse isoforms facilitate stress adaptation in plants that thrive in extreme environments are unexplored. Here we examine how an extremophyte model,Schrenkiella parvula, coordinates alternative splicing in response to high salinity compared to a salt-stress sensitive model,Arabidopsis thaliana. We use Iso-Seq to generate full length reference transcripts and RNA-seq to quantify differential isoform usage in response to salinity changes. We find that single-copy orthologs whereS. parvulahas a higher number of isoforms than A. thaliana as well as S. parvula genes observed and predicted using machine learning to have multiple isoforms are enriched in stress associated functions. Genes that showed differential isoform usage were largely mutually exclusive from genes that were differentially expressed in response to salt.S. parvulatranscriptomes maintained specificity in isoform usage assessed via a measure of expression disorderdness during transcriptome reprogramming under salt. Our study adds a novel resource and insight to study plant stress tolerance evolved in extreme environments.
A taxonomic revision of the genusHydnora(Hydnoraceae)
Authors: Hatt Sebastian A. , Thorogood Chris J. , Bolin Jay F. , Musselman Lytton J. , Cameron Duncan D. , Grace Olwen M. 
Published: October 2022

SummaryA systematic monograph is presented for Hydnora (Hydnoraceae), a poorly known genus of holoparasitic plants distributed across Africa, Madagascar and southern Arabia. Species ofHydnoraare characterised by their underground habit, unusual fleshy flowers and complete absence of leaves or photosynthetic tissue. This is the first detailed monograph of the genus Hydnora since 1935 and is informed by a comprehensive survey of herbarium specimens and literature. Detailed descriptions, full synonymy, distribution maps and discussion concerning confusable taxa are provided for each species, along notes on ethnobotany, ecology and conservation. We place particular emphasis on the taxonomic value of osmophore geometry and positioning in living and dried material, which are highly consistent within species. We also provide the first detailed assessment of host range across the genus.Hydnora hanningtoniiRendle andH. solmsianaDinter are reinstated from synonymy, andH. boliniiHatt is newly described here. The infrageneric classification is reviewed and a key is provided for both living and dried material. Species are accompanied by both illustrations and photographs of living and dried material where possible.
Experienced social partners hinder learning performance in naive clonal fish
Authors: Francisco Fritz A. , Lukas Juliane , Stöcker Almond , Romanczuk Pawel , Bierbach David 
Published: October 2022

AbstractSocial learning can facilitate information spread within groups and is generally assumed to increase learning efficiency in animals. Here, we asked how individual learning is affected by skill level of a demonstrator present during learning. We predicted that both task-naive and task-experienced individuals benefit from a task-experienced, conspecific demonstrator. We used the all-female clonal Amazon molly (Poecilia formosa) for our experiments. We further propose a model framework which lets us directly relate each research question to a single model parameter. First, following a classical conditioning paradigm over five days, half the fish were trained to find food inside a cylinder, while the others were provided with food randomly dispersed in their tank. As a result trained individuals visited the cylinder with a higher likelihood than randomly fed individuals and showed consistent individual differences in their learning performance. In a second step, we allowed these fish to observe a conspecific while we continued (for those trained) or started (for naives) individual training. We found that trained individuals did not benefit from a partner, regardless of the partners’ proficiency, but showed higher average performances compared to naives. Naive individuals showed a decrease in learning performance when paired with experienced partners but not when paired with other naive ones. Our results suggest that Amazon mollies learn a foraging task individually and differ consistently in their individual learning ability. Further, social learning depends on own, as well as the demonstrator’s skill level in a way that observing informed conspecifics may hamper own learning.HighlightsNaturally clonal fish learn operant conditioning tasksIndividuals show consistent differences in learning abilitiesExperienced social partners are not helpful during learning
Explainable Machine Learning to Identify Patient-specific Biomarkers for Lung Cancer
Authors: Sobhan Masrur , Mondal Ananda Mohan 
Published: October 2022

AbstractBackgroundLung cancer is the leading cause of death compared to other cancers in the USA. The overall survival rate of lung cancer is not satisfactory even though there are cutting-edge treatment methods for cancers. Genomic profiling and biomarker gene identification of lung cancer patients may play a role in the therapeutics of lung cancer patients. The biomarker genes identified by most of the existing methods (statistical and machine learning based) belong to the whole cohort or population. That is why different people with the same disease get the same kind of treatment, but results in different outcomes in terms of success and side effects. So, the identification of biomarker genes for individual patients is very crucial for finding efficacious therapeutics leading to precision medicine.MethodsIn this study, we propose a pipeline to identify lung cancer class-specific and patient-specific key genes which may help formulate effective therapies for lung cancer patients. We have used expression profiles of two types of lung cancers, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and Healthy lung tissues to identify LUAD- and LUSC-specific (class-specific) and individual patient-specific key genes using an explainable machine learning approach, SHaphley Additive ExPlanations (SHAP). This approach provides scores for each of the genes for individual patients which tells us the attribution of each feature (gene) for each sample (patient).ResultIn this study, we applied two variations of SHAP - tree explainer and gradient explainer for which tree-based classifier, XGBoost, and deep learning-based classifier, convolutional neural network (CNN) were used as classification algorithms, respectively. Our results showed that the proposed approach successfully identified class-specific (LUAD, LUSC, and Healthy) and patient-specific key genes based on the SHAP scores.ConclusionThis study demonstrated a pipeline to identify cohort-based and patient-specific biomarker genes by incorporating an explainable machine learning technique, SHAP. The patient-specific genes identified using SHAP scores may provide biological and clinical insights into the patient’s diagnosis.
Social rank influences relationships between hormones and oxidative stress in a cichlid fish
Authors: Culbert Brett M. , Border Shana E. , Fialkowski Robert J. , Bolitho Isobel , Dijkstra Peter D. 
Published: October 2022

AbstractAn individual’s social environment can have widespread effects on their physiology, including effects on oxidative stress and hormone levels. Many studies have posited that variation in oxidative stress experienced by individuals of different social ranks might be due to endocrine differences, however, few studies have evaluated this hypothesis. Here, we assessed whether a suite of markers associated with oxidative stress in different tissues (blood, plasma, liver, or gonads) had social rank-specific relationships with circulating testosterone or cortisol levels in males of a cichlid fish,Astatotilapia burtoni. Across all fish, blood DNA damage (a global marker of oxidative stress) and gonadal synthesis of reactive oxygen species (as indicated by NADPH-oxidase (NOX) activity) were lower when testosterone was high. High DNA damage in both the blood and gonads was associated with high cortisol in subordinates, but low cortisol in dominants. Additionally, high cortisol was associated with greater production of reactive oxygen species (greater NOX activity) in both the gonads (dominants only) and liver (dominants and subordinates). In general, high testosterone was associated with lower oxidative stress across both social ranks, whereas high cortisol was associated with lower oxidative stress in dominants and higher oxidative stress in subordinates. Taken together, our results show that differences in the social environment can lead to contrasting relationships between hormones and oxidative stress.
Type 2 Inflammation Drives an Airway Basal Stem Cell Program Through Insulin Receptor Substrate Signaling
Authors: Wang Xin , Hallen Nils R. , Lee Minkyu , Samuchiwal Sachin , Ye Qihua , Buchheit Kathleen M. , Maxfield Alice Z. , Roditi Rachel E. , Bergmark Regan W. , Bhattacharyya Neil , Ryan Tessa , Gakpo Deb , Raychaudhuri Soumya , Dwyer Dan , Laidlaw Tanya M. , Boyce Joshua A. , Gutierrez-Arcelus Maria , Barrett Nora A. 
Published: October 2022

ABSTRACTBackgroundChronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2 (T2) inflammatory disease associated with an increased number of airway basal epithelial cells (BCs). Recent studies have identified transcriptionally distinct BCs, but functional data are lacking and the molecular pathways that support or inhibit human BC proliferation and differentiation are largely unknown.ObjectiveTo determine the role of T2 cytokines in regulating airway BCsMethodsSingle cell and bulk RNA-sequencing of sinus and lung airway epithelial cells was analyzed. Human sinus BCs were stimulated with IL-4 and IL-13 in the presence and absence of IL4R inhibitors. Confocal analysis of human sinus tissue and murine airway was performed. Murine BC subsets were sorted for RNA sequencing and functional assays. Fate labeling was performed in a murine model of tracheal injury and repair.ResultsHere we find two subsets of BCs in human and murine respiratory mucosa distinguished by the expression of BC adhesion molecule (BCAM). BCAM expression identifies airway stem cells among P63+KRT5+NGFR+ BCs. In the sinonasal mucosa, BCAMhiBCs expressingTSLP,IL33,CCL26,and the canonical BC transcription factorTP63are increased in patients with CRSwNP. In cultured BCs, IL-4/13 increases expression ofBCAMandTP63through an Insulin Receptor Substrate (IRS)-dependent signaling pathway that is increased in CRSwNP.ConclusionsThese findings establish BCAM as a marker of airway stem cells among the BC pool and demonstrate that airway epithelial remodeling in T2 inflammation extends beyond goblet cell metaplasia to the support of a BC stem state poised to perpetuate inflammation.CAPSULE SUMMARYType 2 cytokines drive an airway stem cell program through IRS signalingKEY MESSAGESTwo subsets of airway BCs have distinct transcriptional signatures and functionHigh levels of BCAM expression mark the earliest BC progenitorIL-4 and IL-13 upregulate BCAM and P63 in an IRS-dependent fashion which prevents BC differentiation to secretory epithelial cellsBCAMhiBCs are increased in CRSwNP
Intermittent hypoxia therapy engages multiple longevity pathways to double lifespan inC.elegans
Authors: Pitt Jason N. , Chavez Eduardo , Provencher Kathryn M. , Chen Michelle , Tran Christina , Tran Jennifer , Huang Karen , Vaid Anuj , Abadir Marian L , Arang Naheed , Leiser Scott F. , Roth Mark B. , Kaeberlein Matt 
Published: October 2022

AbstractGenetic activation of the hypoxia response robustly extends lifespan inC. elegans, while environmental hypoxia shows more limited benefit. Here we describe an intermittent hypoxia therapy (IHT) able to double the lifespan of wildtype worms. The lifespan extension observed in IHT does not require HIF-1 but is partially blocked by loss of DAF-16/FOXO. RNAseq analysis shows that IHT triggers a transcriptional state distinct from continuous hypoxia and affects down-stream genes of multiple longevity pathways. We performed a temperature sensitive forward genetic screen to isolate mutants with delayed nuclear localization of DAF-16 in response to IHT and suppression of IHT longevity. One of these mutations mapped to the enzyme Inositol Polyphosphate MultiKinase (IPMK-1).ipmk-1mutants, likedaf-16mutants, partially suppress the benefits of IHT, while other effectors of phosphatidyl inositol signaling pathways (PLCβ4, IPPK, Go/iα) more robustly suppress IHT longevity.One-Sentence SummaryIntermittent hypoxia therapy is frequency dependent, HIF independent, and requires FOXO, PLCβ, Go/iα, IPMK, and IPPK.
Neurofeedback training can modulate task-relevant memory replay rate in rats
Authors: Gillespie Anna K. , Astudillo Maya Daniela A. , Denovellis Eric L. , Desse Sachi , Frank Loren M. 
Published: October 2022

SUMMARYHippocampal replay – the time-compressed, sequential reactivation of ensembles of neurons related to past experience – is a key neural mechanism of memory consolidation. Replay typically coincides with a characteristic pattern of local field potential activity, the sharp-wave ripple (SWR). Reduced SWR rates are associated with cognitive impairment in multiple models of neurodegenerative disease, suggesting that a clinically viable intervention to promote SWRs and replay would prove beneficial. We therefore developed a neurofeedback paradigm for rat subjects in which SWR detection triggered rapid positive feedback in the context of a memory-dependent task. This training protocol increased the prevalence of task-relevant replay during the targeted neurofeedback period by changing the temporal dynamics of SWR occurrence. This increase was also associated with neural and behavioral forms of compensation after the targeted period. These findings reveal short-timescale regulation of SWR generation and demonstrate that neurofeedback is an effective strategy for modulating hippocampal replay.
DNA-encoded library (DEL)-enabled discovery of proximity-inducing small molecules
Authors: Mason Jeremy W. , Hudson Liam , Westphal Matthias V. , Tutter Antonin , Michaud Gregory , Shu Wei , Ma Xiaolei , Coley Connor W. , Clemons Paul A. , Bonazzi Simone , Berst Frédéric , Zécri Frédéric J. , Briner Karin , Schreiber Stuart L. 
Published: October 2022

AbstractMolecular glues and bifunctional compounds that induce protein–protein associations provide a powerful and general mechanism to modulate cell circuitry. We sought to develop a platform for the direct discovery of compounds able to induce association of any two pre-selected proteins, using the first bromodomain of BRD4 and the VHL–elongin C–elongin B (VCB) complex as a test system. Leveraging the screening power of DNA-encoded libraries (DELs), we synthesized ∼one million DNA-encoded compounds that possess a VHL-targeting fragment, a variety of connectors, and a diversity element generated by split- and-pool combinatorial chemistry. By screening our DEL against BRD4BD1in the presence and absence of VCB, we could identify VHL-bound molecules that simultaneously bind BRD4. For highly barcode-enriched library members, ternary complex formation leading to BRD4 degradation was confirmed in cells. Furthermore, a ternary complex crystal structure was obtained for the most enriched library member. Our work provides a foundation for adapting DEL screening to the discovery of proximity-inducing small molecules.Abstract Figure
Local gradient analysis of human brain function using the Vogt-Bailey Index
Authors: Farrugia Christine , Galdi Paola , Irazu Irati Arenzana , Scerri Kenneth , Bajada Claude J. 
Published: October 2022

AbstractIn this work, we take a closer look at the Vogt-Bailey (VB) index, proposed in Ref. [1] as a tool for studying local functional homogeneity in the human cortex. We interpret the VB index in terms of the minimum ratio cut, a parameter that indicates whether a network can easily be disconnected into two parts having a comparable number of nodes. In our case, the nodes of the network consist of a brain vertex/voxel and its nearest neighbours, and a given edge is weighted according to the affinity of the nodes it connects (as reflected by the modified Pearson correlation between their fMRI time series). Consequently, the minimum ratio cut quantifies the degree of small-scale similarity in brain activity: the greater the similarity, the ‘heavier’ the edges and the more difficult it is to disconnect the network, hence the higher the value of the minimum ratio cut. We compare the performance of the VB index with that of the Regional Homogeneity (ReHo) algorithm, commonly used to assess whether voxels in close proximity have synchronised fMRI signals, and find that the VB index is uniquely placed to detect sharp changes in the (local) functional organization of the human cortex.
Effects of Neurofeedback training on performance in laboratory tasks: A systematic review
Authors: Chiasson Payton , Boylan Maeve R. , Elhamiasl Mina , Pruitt Joseph M. , Ranjan Saurabh , Riels Kierstin , Sahoo Ashish K. , Mirifar Arash , Keil Andreas 
Published: October 2022

AbstractNeurofeedback procedures are attracting increasing attention in the neuroscience community. Based on the principle that participants, through suitable feedback, may learn to affect specific aspects of their brain activity, neurofeedback has been applied to basic research, translational, and clinical science alike. A large segment of the extant empirical research as well as review articles have focused on the extent to which neurofeedback interventions affect mental health outcomes, cognitive capacity, aging, and other complex behaviors. Another segment has aimed to characterize the extent to which neurofeedback affects the targeted neural processes. At this time, there is no current systematic review of the effects of neurofeedback on healthy participants’ performance in experimental tasks. Such a review is relevant in this rapidly evolving field because changes in experimental task performance are traditionally considered a hallmark of changing neurocognitive processes, often established in neurotypical individuals. This systematic review addresses this gap in the literature using the PRISMA method, building on earlier reviews on the same topic. Empirical studies using EEG or fMRI to alter brain processes linked to established, well-defined cognitive and affective laboratory tasks were reviewed. Substantial variability was found regarding the nature of the control for placebo effects, the implementation of the feedback, and the neural targets of feedback. Importantly, only a minority of the studies reported statistically meaningful effects of neurofeedback on performance in cognitive and affective tasks. Examining effect sizes and p-values in a subset of studies found no evidence for reporting bias, while also not finding systematic relations between study characteristics such as sample size or experimental control on the one hand and efficacy on the other. Implications for future work are discussed.
Transposable elements orchestrate subgenome-convergent and -divergent transcription in common wheat
Authors: Zhang Yuyun , Li Zijuan , Liu Jinyi , Zhang Yu’e , Ye Luhuan , Peng Yuan , Wang Haoyu , Diao Huishan , Ma Yu , Wang Meiyue , Xie Yilin , Tang Tengfei , Zhuang Yili , Teng Wan , Tong Yiping , Zhang Wenli , Lang Zhaobo , Xue Yongbiao , Zhang Yijing 
Published: October 2022

AbstractThe success of common wheat as the global staple crop is derived from genome diversity and redundancy as a result of allopolyploidization [1-3], giving rise to the major question how the divergent and convergent transcription among different subgenomes are achieved and harmonized in a single cell. The regulatory information is largely encoded in DNA regulatory elements (REs) interpreted by sequence specific transcription factors (TFs). Here, we created a catalog of genome-wide TF-binding sites (TFBS) to assemble an extensive wheat regulatory network comprising connections among 189 TFs and 3,714,431 REs, which enhances the understanding of wheat regulatory mechanisms on an unprecedented scale. A significant fraction of subgenome-divergent TFBS are derived from recent subgenome-asymmetric expansion of particular transposable element (TE) families. In contrary, TFBS derived from ancient TE expansion largely underwent parallel purifying selection during independent evolution of each subgenome, despite extensive unbalanced turnover of flanking TEs. Altogether, the subgenome-convergent and -divergent regulation in common wheat is orchestrated via differential evolutionary selection on paleo- and neo-TEs.
Adaptive Sampling as tool for Nanopore direct RNA-sequencing
Authors: Vries Isabel S. Naarman-de , Gjerga Enio , Gandor Catharina L.A. , Dieterich Christoph 
Published: October 2022

AbstractONT long-read sequencing provides real-time monitoring and controlling of individual nanopores. Adaptive sampling enriches or depletes specific sequences in Nanopore DNA sequencing, but was not applicable to direct sequencing of RNA so far.Here, we identify essential parameter settings for direct RNA sequencing (DRS). We demonstrate the superior performance of depletion over enrichment and show that adaptive sampling efficiently depletes specific transcripts in transcriptome-wide sequencing applications. Specifically, we applied our adaptive sampling approach to polyA+ RNA samples from human cardiomyocytes and mouse whole heart tissue. Herein, we show more than 2.5-fold depletion of highly abundant mitochondrial-encoded transcripts that in normal sequencing account for up to 40% of sequenced bases in heart tissue samples.
High-frequency synthetic apomixis in hybrid rice
Authors: Vernet Aurore , Meynard Donaldo , Lian Qichao , Mieulet Delphine , Gibert Olivier , Bissah Matilda , Rivallan Ronan , Meunier Anne Cécile , Frouin Julien , Taillebois James , Shankle Kyle , Khanday Imtiyaz , Mercier Raphael , Sundaresan Venkatesan , Guiderdoni Emmanuel 
Published: October 2022

AbstractIntroducing asexual reproduction through seeds – apomixis – into crop species could revolutionize agriculture by allowing F1 hybrids with enhanced yield and stability to be clonally propagated. Engineering synthetic apomixis has proven feasible in inbred rice through the inactivation of three genes (MiMe), which results in the conversion of meiosis into mitosis in a line ectopically expressing the BABYBOOM1 (BBM1) parthenogenetic trigger in egg cells. However, only 10–30% of the seeds were clonal. We show here that synthetic apomixis can be induced in a F1 hybrid of rice by inducingMiMemutations and egg cell expression of BBM1 in a single step. We generated hybrid plants that produced more than 95% of clonal seeds across multiple generations. Clonal apomictic plants maintained the phenotype of the F1 hybrid along successive generations. Our results demonstrate that there is no barrier to almost fully penetrant synthetic apomixis in an important crop species, rendering it compatible with use in agriculture.