bluuebunny/crossref_metadata_2025_split huggingface dataset:
B vitamin quantification in lentil seed tissues using ultra-performance liquid chromatography-selected reaction monitoring mass spectrometry
Authors: Marshall Jeremy , Vargas Ana , Bett Kirstin 
Published: December 2022

AbstractLentils are an important source of macronutrients, including protein and fiber, as well as micronutrients such as vitamins and minerals, especially in a plant-based diet. Quantifying variation among genotypes, including wild germplasm, is desirable to better understand the genetics of differential B vitamins content for breeding of this trait and to understand their potential contributions to the lentil crop. We analyzed thirty-four cultivated and three wild genotypes for vitamins B1, B2, B3, B5, B6, B7, and B9. Seeds were assayed whole, and separated into cotyledons only, or seed coats only. Variation for all B vitamins was observed across the cultivars. Overall, cotyledons had higher concentrations of B1 and B3, while seed coats had higher concentrations of B2, B5, B6, and B9. Wild accessions had the highest concentrations of vitamin B9 and were also among the highest for vitamin B2. These results demonstrate the differential distribution of B vitamins across seed tissues and lentil genotypes, and that dehulling prior to consumption results in the loss of B vitamins otherwise available in whole seeds. They also indicate there is genetic variability which could be used to increase B-vitamin levels in lentil via breeding.
Savory Signaling: T1R umami receptor modulates endoplasmic reticulum calcium store content and release dynamics in airway epithelial cells
Authors: McMahon Derek B , Jolivert Jennifer F. , Kuek Li Eon , Adappa Nithin D. , Palmer James N. , Lee Robert J 
Published: December 2022

AbstractT1Rs are expressed in solitary chemosensory cells of the upper airway where they detect apical glucose levels and repress bitter taste receptor Ca2+ signaling pathways. Microbial growth leads to a decrease in apical glucose levels. T1Rs detect this change and liberate bitter taste receptor signaling, initiating an innate immune response to both kill and expel pathogens through releasing antimicrobial peptides and increasing nitric oxide production and ciliary beat frequency. However, chronic inflammation due to disease, smoking, or viral infections causes a remodeling of the airway epithelial. The resulting squamous metaplasia causes a loss of multi-ciliated cells and solitary chemosensory cells, replaced by basal epithelial cells. To understand how T1R function is altered during disease, we used basal epithelial cells as a model to study the function of T1R3 on Ca2+signaling dynamics. We found that both T1R1 and T1R3 detect amino acids and signal via cAMP, increasing the responsiveness of the cells to Ca2+signaling stimuli. Either knocking down T1R1/3 or treating wild-type cells with MEM amino acids caused a reduction in ER Ca2+content through a non-cAMP signaled pathway. Treatment with amino acids led to a reduction in downstream denatonium-induced Ca2+-signaled caspase activity. Thus, amino acids may be used to reduce unwanted apoptosis signaling in treatments containing bitter compounds.
Homeostasis in Networks with Multiple Inputs
Authors: de Oliveira Madeira João Luiz , Antoneli Fernando 
Published: December 2022

AbstractHomeostasis, also known as adaptation, refers to the ability of a system to counteract persistent external disturbances and tightly control the output of a key observable. Existing studies on homeostasis in network dynamics have mainly focused on ‘perfect adaptation’ in deterministic single-input single-output networks where the disturbances are scalar and affect the network dynamics via a pre-specified input node. In this paper we provide a full classification of all possible network topologies capable of generating infinitesimal homeostasis in arbitrarily large and complex multiple-input parameter networks. Working in the framework of ‘infinitesimal homeostasis’ allows us to make no assumption about how the components are interconnected and the functional form of the associated differential equations, apart from being compatible with the network architecture. Remarkably, we show that there are just three distinct ‘mechanisms’ that generate infinitesimal homeostasis. Each of these three mechanisms generates a rich class of well-defined network topologies – calledhomeostasis subnetworks. Most importantly, we show that these classes of homeostasis subnetworks provides a topological basis for the classification of ‘homeostasis types’: the full set of all possible multiple-input parameter networks can be uniquely decomposed into these special homeostasis subnetworks. We build on previous work that treated the cases of single-input node and multiple-input node, both with a single scalar input parameter. Furthermore, we identify a new phenomenon that occurs in the multiparameter setting, that we callhomeostasis mode interaction, in analogy with the well-known characteristic of multiparameter bifurcation theory.
Target Recycling Amplification Process for Digital Detection of Exosomal MicroRNAs Through Photonic Resonator Absorption Microscopy
Authors: Wang Xiaojing , Shepherd Skye , Li Nantao , Che Congnyu , Song Tingjie , Xiong Yanyu , Palm Isabella Rose , Zhao Bin , Kohli Manish , Demirci Utkan , Lu Yi , Cunningham Brian T. 
Published: December 2022

AbstractExosomal microRNAs (miRNAs) have considerable potential as pivotal biomarkers to monitor cancer development, dis-ease progression, treatment effects and prognosis. Here, we report an efficient target recycling amplification process (TRAP) for the digital detection of exosomal miRNAs using photonic resonator absorption microscopy (PRAM). Through toehold-mediated DNA strand displacement reactions, we achieve multiplex digital detection with sub-attomolar sensitivity in 20 minutes, robust selectivity for single nucleotide variants, and a broad dynamic range from 1 aM to 1 pM. We then applied our TRAP system to quantify miRNA in exosomal total RNAs isolated from human cancer cell lines. Compared with traditional qRT-PCR methods, TRAP showed similar accuracy in profiling exosomal miRNAs derived from cancer cells, but also exhibited at least 31-fold and 61-fold enhancement in the limits of miRNA-375 and miRNA-21 detection, respectively. The TRAP approach is ideal for exosomal or circulating miRNA biomarker quantification, where the miRNAs are present in low concentrations or sample volume, with potentials for frequent, low-cost, and minimally invasive point-of-care testing.
A CXCR3-activating peptide increases Tear Break Up Time and corrects corneal haze in a rabbit model of environmental dry eye
Authors: Wells Alan , Wang Yadong , Shao Hanshuang , Sohnen Peri , Swamynathan Shivalingappa K. 
Published: December 2022

AbstractPurposeEnvironmentally-triggered dry eye disease (DED) or keratoconjunctivitis sicca (KCS), which constitutes the majority of DED cases, currently is palliatively treated with aqueous replacement solutions that do not target the dysfunction of the mucin and lipid components of tears. Herein, we tested whether a peptide that increased goblet cell numbers in a model of scleral chemical injury would also improve tear quality in environmental DED.MethodsEnvironmental DED was established by exposing New Zealand white rabbits (8 per group, female) to 20% humidity with rapid air replacement and b.i.d. atropine sulfate eyedrops for 3 weeks prior to test article administration; this continued for the subsequent 3 weeks of testing. Animals were dosed by (A) saline, (B) b.i.d. eyedrop of peptide in saline, (C) b.i.d. eyedrop of peptide in coacervate, or (D) weekly subconjunctival injection of peptide.ResultsThe environmental DED was established with both Schirmer and TBUT being reduced by from baseline at the start of test article; these levels were maintained as low through the testing period. All three treatment regimens increased TBUT approximately 3x to levels greater than prior to desiccation, with little effect on Schirmer. Corneal haze was present in all eyes after induction, and largely cleared up by all three treatments. End of study enucleation of the eye did not show any changes in goblet cells numbers, which remained high throughout the induction and treatment.ConclusionsThe treatment of environmental DED/KCS with a peptide that activates CXCR3 improved tear quality and reversed corneal pathology by promoting tear stability, while not affecting aqueous volume of the tears.
Zinc and laboratory emerge date impact honey bee gut microbiota and survival
Authors: Soares Kilmer Oliveira , Ricke Dylan , de Oliveira Celso José Bruno , Lima Marcos Venâncio , Mrofchak Ryan , Rodrigues Adriana Evangelista , Madden Christopher , Johnson Reed , Hale Vanessa L. 
Published: December 2022

AbstractHoney bees (Apis mellifera) may be exposed to a wide variety of chemicals in the environment, including pesticides, antibiotics, and metals. Zinc, for example, is commonly included in fertilizers, pesticides, and feed additives, and is found in agricultural runoff. Honey bees can be exposed to zinc directly or indirectly by consuming zinc-contaminated nectar and pollen. However, there is a paucity of studies addressing the putative effects of zinc on honey bee’s health. In this study, we tested the effects of zinc on honey bee survivorship and gut microbiota. To evaluate survivorship, we exposed bees to six concentrations of zinc (0, 50, 100, 250, 500, or 1000 mg/L) and assessed survival daily for 10 days. To evaluate effects of zinc on gut microbiota, we exposed bees to 5 or 100 mg/L zinc. Bees were sampled before (day 0) and after zinc exposure (days 3, 6, and 9). Abdominal contents underwent DNA extraction and 16S rRNA sequencing (V3-V4) on an Illumina MiSeq. Sequences were filtered and processed through QIIME2 and DADA2. Zinc treatment had minimal effects on bacterial DNA concentrations and absolute cell counts while emerge date (the date a bee emerged from the brood comb) had a significant effect with decreased bacterial concentrations and cell counts observed at later emerge dates. Survival was only minimally impacted (>89% survival) at zinc concentrations up to 100 mg/L. Zinc had limited effects on overall gut microbial composition, diversity, and taxonomic abundances, with the greatest differences noted in the bee group exposed to the higher concentration of zinc (100 mg/L). In this group, several beneficial taxa (Lactobacillus, Rhizobiaceae,Gilliamella) were found at reduced abundances, whilePaenibacillus, a potentially pathogenic taxa, was found at increased abundances. This suggests that zinc exposure, even at relatively low levels, may negatively impact honey bee health, even if survivorship is not dramatically impacted. Notably, emerge date effects were also observed in microbial composition. These results demonstrate the need to include assessments of honey bee gut microbiota in addition to other metrics of honey bee health and survivorship when evaluating the potential effects of agrochemicals on honey bees
Bridging the gap between formal theory and scientific reform practices
Authors: Buzbas Erkan , Devezer Berna 
Published: December 2022

AbstractA core problem that has been addressed in the scientific reform movement so far is the low rates of reproducibility of research results. Mainstream reform literature aimed at increasing reproducibility rates by implementing changes in research practice and scientific policy. At the sidelines of reform, theoreticians have worked on understanding the underlying causes of irreproducibility from ground up. Each approach faces its own challenges. While mainstream focus on swift practical changes has not been buttressed by sound theoretical arguments, theoretical work is slow and initially is only capable of answering questions in idealized setups, removed from real life constraints. In this article, we continue to develop theoretical foundations in understanding non-exact replications and meta-hypothesis tests in multi-lab replication studies, juxtapose these theoretical intuitions with practical reform examples, and expose challenges we face. In our estimation, a major challenge in the next generation of the reform movement is to bridge the gap between theoretical knowledge and practical advancements.
Understanding pediatric long COVID using a tree-based scan statistic approach: An EHR-based cohort study from the RECOVER Program
Authors: Lorman Vitaly , Rao Suchitra , Jhaveri Ravi , Case Abigail , Mejias Asuncion , Pajor Nathan M. , Patel Payal , Thacker Deepika , Bose-Brill Seuli , Block Jason , Hanley Patrick C. , Prahalad Priya , Chen Yong , Forrest Christopher B. , Bailey L. Charles , Lee Grace M. , Razzaghi Hanieh 
Published: December 2022

STRUCTURED ABSTRACTObjectivesPost-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.Materials and MethodsWe used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N=1309) to children with (N=6545) and without (N=6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls.ResultsWe found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise.DiscussionOur study addresses methodological limitations of prior studies that rely on pre-specified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes.ConclusionWe identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.LAY SUMMARYPediatric long COVID in children does not currently have a precise clinical definition, in part due to its widely varying presentation in kids. By comparing children diagnosed with long COVID to children who had COVID-19 but were not diagnosed with long COVID, this study identified several groups of symptoms and conditions that are associated with pediatric long COVID. These findings can be used towards developing a precise definition of long COVID in children for use in future studies.
Reliable and generalizable brain-based predictions of cognitive functioning across common psychiatric illness
Authors: Chopra Sidhant , Dhamala Elvisha , Lawhead Connor , Ricard Jocelyn A. , Orchard Edwina R. , An Lijun , Chen Pansheng , Wulan Naren , Kumar Poornima , Rubenstein Arielle , Moses Julia , Chen Lia , Levi Priscila , Holmes Alexander , Aquino Kevin , Fornito Alex , Harpaz-Rotem Ilan , Germine Laura T. , Baker Justin T. , Yeo BT Thomas , Holmes Avram J. 
Published: December 2022

AbstractA primary aim of precision psychiatry is the establishment of predictive models linking individual differences in brain functioning with clinical symptoms. In particular, cognitive impairments are transdiagnostic, treatment resistant, and contribute to poor clinical outcomes. Recent work suggests thousands of participants may be necessary for the accurate and reliable prediction of cognition, calling into question the utility of most patient collection efforts. Here, using a transfer-learning framework, we train a model on functional imaging data from the UK Biobank (n=36,848) to predict cognitive functioning in three transdiagnostic patient samples (n=101-224). The model generalizes across datasets, and brain features driving predictions are consistent between populations, with decreased functional connectivity within transmodal cortex and increased connectivity between unimodal and transmodal regions reflecting a transdiagnostic predictor of cognition. This work establishes that predictive models derived in large population-level datasets can be exploited to boost the prediction of cognitive function across clinical collection efforts.
Genomic, Functional and Structural Analyses Reveal Mechanisms of Evolutionary Innovation within the Sea Anemone 8 Toxin Family
Authors: Ashwood Lauren M. , Elnahriry Khaled A. , Stewart Zachary K. , Shafee Thomas , Naseem Muhammad Umair , Szanto Tibor G. , van der Burg Chloé A. , Smith Hayden L. , Surm Joachim M. , Undheim Eivind A.B. , Madio Bruno , Hamilton Brett R. , Guo Shaodong , Wai Dorothy C.C. , Coyne Victoria L. , Phillips Matthew J. , Dudley Kevin J. , Hurwood David A. , Panyi Gyorgy , King Glenn F. , Pavasovic Ana , Norton Raymond S. , Prentis Peter J. 
Published: December 2022

AbstractShK fromStichodactyla helianthushas established the therapeutic potential of sea anemone venom peptides, but many lineage-specific toxin families in actinarians remain uncharacterised. One such peptide family, sea anemone 8 (SA8), is present in all five sea anemone superfamilies. We explored the genomic arrangement and evolution of the SA8 gene family inActinia tenebrosaandTelmatactis stephensoni, characterised the expression patterns of SA8 sequences, and examined the structure and function of SA8 from the venom ofT.stephensoni. We identified ten SA8 genes in two clusters and six SA8 genes in five clusters forT. stephensoniandA. tenebrosa, respectively. Nine SA8T. stephensonigenes were found in a single cluster and an SA8 peptide encoded by an inverted SA8 gene from this cluster was recruited to venom. We show that SA8 genes in both species are expressed in a tissue-specific manner and the inverted SA8 gene has a unique tissue distribution. While functional activity of the SA8 putative toxin encoded by the inverted gene was inconclusive, its tissue localisation is similar to toxins used for predator deterrence. We demonstrate that, although mature SA8 putative toxins have similar cysteine spacing to ShK, SA8 peptides are distinct from ShK peptides based on structure and disulfide connectivity. Our results provide the first demonstration that SA8 is a unique gene family in actiniarians, evolving through a variety of structural changes including tandem and proximal gene duplication and an inversion event that together allowed SA8 to be recruited into the venom ofT.stephensoni.
SMRT-AgRenSeq-d in potato (Solanum tuberosum) identifies candidates for the nematode resistance Gpa5
Authors: Wang Yuhan , Brown Lynn H , Adams Thomas M , Cheung Yuk Woon , Li Jie , Young Vanessa , Todd Drummond T , Armstrong Miles R , Neugebauer Konrad , Kaur Amanpreet , Harrower Brian , Oome Stan , Wang Xiaodan , Bayer Micha , Hein Ingo 
Published: December 2022

AbstractPotato is the third most important food crop in the world. Diverse pathogens threaten sustainable crop production but can be controlled, in many cases, through the deployment of disease resistance genes belonging to the family of nucleotide-binding, leucine-rich-repeat (NLR) genes.To identify functional NLRs in established varieties, we have successfully established SMRT-AgRenSeq in tetraploid potatoes and have further enhanced the methodology by including dRenSeq in an approach that we term SMRT-AgRenSeq-d. The inclusion of dRenSeq enables the filtering of candidates after the association analysis by establishing a presence/absence matrix across resistant and susceptible potatoes that is translated into an F1 score. Using a SMRT-RenSeq based sequence representation of the NLRome from the cultivar Innovator, SMRT-AgRenSeq-d analyses reliably identified the late blight resistance benchmark genesR1, R2-like, R3aandR3bin a panel of 117 varieties with variable phenotype penetrations. All benchmark genes were identified with an F1 score of 1 which indicates absolute linkage in the panel.When applied to the elusive nematode disease resistance geneGpa5that controls the Potato Cyst Nematode (PCN) speciesGlobodera pallida(pathotypes Pa2/3), SMRT-AgRenSeq-d identified nine strong candidates. These map to the previously established position on potato chromosome 5 and are potential homologs of the late blight resistance geneR1.Assuming that NLRs are involved in controlling many types of resistances, SMRT-AgRenSeq-d can readily be applied to diverse crops and pathogen systems. In potato, SMRT-AgRenSeq-d lends itself, for example, to further study the elusive PCN resistancesH1orH3for which phenotypic data exist.
Template-Directed RIG-I Agonist Assembly for Targeted Cancer Immunotherapy
Authors: Ghosh Subrata K. , Robertson Neil , Crosier Edward , Dudley Michael , Liu Qiyong P. , Medarova Zdravka 
Published: December 2022

AbstractRecent developments in the use of pattern recognition receptors (PRRs) aim to harness the innate power of the immune system for cancer therapy. Understanding how to recruit PRRs, such as RIG-I, in a tumor-selective manner is critical for its adoption in the clinic. We describe the use of a tumor-selective template-based agonist of RIG-I to induce type-I IFN signaling and tumor cell apoptosis. The agonist, termed ss-ppp-miRNA-21, comprises a single stranded RNA oligonucleotide modified with a 5’-triphosphate and complementary to an endogenous miRNA enriched in tumor cells. We demonstrate the efficacy of the template-directed approach and detail mechanistic studies validating the hypothesis of a template-directed RIG-I agonist assembly using miRNA-21 as a target. The template-directed strategy described here moves us closer to making RIG-I a clinically relevant target in oncology because it achieves targeted activation of innate immunity in the tumor microenvironment in the context of systemic agonist injection.
Proximity labelling allows to study novel factors in chloroplast developmenta
Authors: Wurzinger Bernhard , Stael Simon , Leonardelli Manuela , Perolo Carlo , Melzer Michael , Chaturvedi Palak , Afjehi-Sadat Leila , Weckwerth Wolfram , Teige Markus 
Published: December 2022

AbstractChloroplast development is initiated by light-signals triggering the expression of nuclear encoded chloroplast genes in a first phase, followed by massive structural changes in the transition from proplastids to mature chloroplasts in the second phase. While the molecular players involved in the first phase are currently emerging, regulatory components of the second phase, demanding high plastid translational capacity and RNA processing, are still enigmatic. This is mostly due to the very limited amount of plant material at the early phases of development that makes biochemical studies such as identifying protein interaction networks very difficult. To overcome this problem, we developed a TurboID-based proximity labelling workflow that requires only very limited sample amounts to obtain mechanistic insights into protein interaction networks present in the early stages of plastid development. We used the CGL20a protein, a novel factor involved in chloroplast development, as bait forin vivoproximity labelling in developing seedlings 7 days after germination. We found that CGL20a resides in a nexus of RNA binding proteins mainly associated to ribosomal RNA (rRNA) including different ribosome-associated proteins.One-sentence summaryThe use of plastid-specific in vivo proximity labelling in Arabidopsis seedlings allows to identify novel components in chloroplast development in higher plants.