bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG Changes during Odor Perception and Discrimination
Authors: Morozova Marina , Bikbavova Alsu , Bulanov Vladimir , Lebedev Mikhail A. 
Published: December 2022

AbstractBrain-Computer Interfaces (BCIs) are devices designed for communication between the central nervous system and a computer. The communication can occur through different sensory modalities, and most commonly visual and auditory systems are used. We suggest that BCIs can be expanded by the incorporation of olfactory modality. To probe the modulation of EEG activity by odorants, we implemented two olfactory tasks: one that required attention to perception of odors, and the second one where participants discriminated consecutively presented odors. EEG recordings were conducted in 13 healthy participants while they performed the tasks following computer-generated verbal instructions. Respiratory activity was recorded to relate EEG modulations to the breath cycle. Theta activity responses were observed over the frontal EEG leads approximately 2 s after the inhalation. This theta activity was different depending on whether or not the inhaled air contained an odorant, and cognitive load also had an effect. We conclude that the frontal theta rhythm is reflective of the neural processing of odors. As such, it could be incorporated in the olfactory-based BCIs which take odors either as inputs or outputs. These BCIs could improve olfactory training needed for conditions like anosmia and hyposmia, and mild cognitive impairment.
Genome-wide analysis of dry (Tamar) Date palm fruit color
Authors: Younuskunju Shameem , Mohamoud Yasmin A. , Mathew Lisa Sara , Mayer Klaus F. X. , Suhre Karsten , Malek Joel A. 
Published: December 2022

AbstractDate palm (Phoenix dactylifera) fruit are an economically and culturally significant crop in the Middle East and North Africa. There are hundreds of different commercial cultivars producing dates with distinctive shapes, colors, and sizes. Genetic studies of some Date palm traits have been performed, including for date palm sex-determination, sugar content and fresh fruit colour. In this study, we used genome sequences and image data of 199 dry date fruit (Tamar) samples collected from 14 countries to identify genetic loci associated with the color of this fruit stage. Here, we find loci across multiple linkage groups (LG) associated with dry fruit color phenotype. We recover the previously identified VIR genotype associated with fresh fruit yellow or red color and new associations with the lightness and darkness of dry fruit. This study will add resolution to our understanding of the date palm fruit color phenotype especially at the most commercially important tamar stage.
Detection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in ovarian cancer
Authors: Dondi Arthur , Lischetti Ulrike , Jacob Francis , Singer Franziska , Borgsmüller Nico , Coelho Ricardo ,   Tumor Profiler Consortium, Heinzelmann-Schwarz Viola , Beisel Christian , Beerenwinkel Niko 
Published: December 2022

AbstractUnderstanding the complex background of cancer requires genotype-phenotype information in single-cell resolution. Here, we perform long-read single-cell RNA sequencing (scRNA-seq) on clinical samples from three ovarian cancer patients presenting with omental metastasis and increase the PacBio sequencing depth to 12,000 reads per cell. Our approach captures 152,000 isoforms, of which over 52,000 are novel. Isoform-level analysis accounting for non-coding isoforms reveals 20% overestimation of protein-coding gene expression on average. We also detect cell type-specific isoform and poly-adenylation site usage in tumor and mesothelial cells, and find that mesothelial cells transition into cancer-associated fibroblasts in the metastasis, partly through the TGF-β/miR-29/Collagen axis. Furthermore, we identify gene fusions, including an experimentally validatedIGF2BP2::TESPA1fusion, which is misclassified as highTESPA1expression in matched short-read data, and call mutations confirmed by targeted NGS cancer gene panel results. With these findings, we envision long-read scRNA-seq to become increasingly relevant in oncology and personalized medicine.
MicroRNA397 regulates tolerance to drought and fungal infection by regulating lignin deposition in chickpea root
Authors: Sharma Nilesh Kumar , Gupta Santosh Kumar , Irulappan Vadivelmurugan , Yadav Shalini , Francis Aleena , Senthil-Kumar Muthappa , Chattopadhyay Debasis 
Published: December 2022

SummaryPlants deposit lignin in the secondary cell wall as a common response to drought and pathogen attacks. Cell wall localized multicopper oxidase family enzymes LACCASES (LACs) catalyze the formation of monolignol radicals and facilitate lignin formation. We show an upregulation of the expression of severalLACgenes and a downregulation of microRNA397 (CamiR397) in response to natural drought in chickpea roots. CamiR397 was found to targetLAC4andLAC17Lout of twenty annotatedLACs in chickpea. CamiR397 and its target genes are expressed in root. Overexpression of CamiR397 reduced expression ofLAC4andLAC17Land lignin deposition in chickpea root xylem causing reduction in xylem diameter. Downregulation of CamiR397 activity by expressing a short tandem target mimic (STTM397) construct increased root lignin deposition in chickpea. CamiR397-overexpressing (miR397OX) and STTM397 chickpea lines showed sensitivity and tolerance, respectively, to drought. Infection with a fungal pathogenMacrophomina phaseolina, responsible for dry root rot disease in chickpea, induced local lignin deposition andLACgene expression. CamiR397-overexpressing and STTM397 chickpea lines showed more sensitivity and tolerance, respectively, to dry root rot. Our results demonstrated the regulatory role of CamiR397 in root lignification during drought and dry root rot in an agriculturally important crop chickpea.
Phylogenomic analyses shed light on the relationships of chiton superfamilies and shell-eye evolution
Authors: Liu Xu , Sigwart Julia D. , Sun Jin 
Published: December 2022

AbstractMollusca is the second-largest animal phylum with over 100,000 species among eight distinct taxonomic classes. Across 1000 living species in the class Polyplacophora, chitons have a relatively constrained morphology but with some notable deviations. Several genera possess “shell eyes”, true eyes with a lens and retina that are embedded within the dorsal shells, which represent the most recent evolution of animal eyes. The phylogeny of major chiton clades is mostly well established, in a set of superfamily and higher-level taxa supported by various approaches including multiple gene markers, mitogenome-phylogeny and phylotranscritomic approaches as well as morphological studies. However, one critical lineage has remained unclear:Schizochitonwas controversially suggested as a potential independent origin of chiton shell eyes. Here, with the draft genome sequencing ofSchizochiton incisus(superfamily Schizochitonoidea) plus assembly of transcriptome data from other polyplacophorans, we present phylogenetic reconstructions using both mitochondrial genomes and phylogenomic approaches with multiple methods. Phylogenetic trees from mitogenomic data are inconsistent, reflecting larger scale confounding factors in molluscan mitogenomes. A consistent robust topology was generated with protein coding genes using different models and methods. Our results support Schizochitonoidea is a sister group to other Chitonoidea in Chitonina, in agreement with established classification. This suggests that the earliest origin of shell eyes is in Schizochitonoidea, which were also gained secondarily in other genera in Chitonoidea. Our results have generated a holistic review of the internal relationship within Polyplacophora, and a better understanding on the evolution of Polyplacophora.
Deuterated buprenorphine retains pharmacodynamic properties of buprenorphine and resists metabolism to the active metabolite norbuprenorphine in rats
Authors: Janganati Venumadhav , Salazar Paloma , Parks Brian J. , Gorman Gregory S. , Prather Paul L. , Peterson Eric C. , Alund Alexander W. , Moran Jeffery H. , Crooks Peter A. , Brents Lisa K. 
Published: December 2022

ABSTRACTAn active metabolite of buprenorphine (BUP), called norbuprenorphine (NorBUP), is implicated in neonatal opioid withdrawal syndrome when BUP is taken during pregnancy. Therefore, reducing or eliminating metabolism of BUP to NorBUP is a novel strategy that will likely lower total fetal exposure to opioids and thus improve offspring outcomes. Precision deuteration alters pharmacokinetics of drugs without altering pharmacodynamics. Here, we report the synthesis and testing of deuterated buprenorphine (BUP-D2). We determined opioid receptor affinities of BUP-D2 relative to BUP with radioligand competition receptor binding assays, and the potency and efficacy of BUP-D2 relative to BUP to activate G-proteins via opioid receptors with [35S]GTPγS binding assays in homogenates containing the human mu, delta, or kappa opioid receptors. The antinociceptive effects of BUP-D2 and BUP were compared using the warm-water tail withdrawal assay in rats. Blood concentration versus time profiles of BUP, BUP-D2, and NorBUP were measured in rats following intravenous BUP-D2 or BUP injection. The synthesis provided a 48% yield and the product was ≥99% deuterated. Like BUP, BUP-D2 had sub-nanomolar affinity for opioid receptors. BUP-D2 also activated opioid receptors and induced antinociception with equal potency and efficacy as BUP. The maximum concentration and the area under the curve of NorBUP in the blood of rats that received BUP-D2 were over 19- and 10-fold lower, respectively, than in rats that received BUP. These results indicate that BUP-D2 retains key pharmacodynamic properties of BUP and resists metabolism to NorBUP and therefore holds promise as an alternative to BUP.GRAPHICAL ABSTRACT
Structure of VanS from Vancomycin-Resistant Enterococci: A Sensor Kinase with Weak ATP Binding
Authors: Grasty Kimberly C. , Guzik Claudia , D’Lauro Elizabeth J. , Padrick Shae B. , Beld Joris , Loll Patrick J. 
Published: December 2022

AbstractThe VanRS two-component system regulates the resistance phenotype of vancomycin-resistant enterococci (VRE). VanS is a sensor histidine kinase that responds to the presence of vancomycin by autophosphorylating and subsequently transferring the phosphoryl group to the response regulator, VanR. The phosphotransfer activates VanR as a transcription factor, which initiates the expression of resistance genes. Structural information about VanS proteins has remained elusive, hindering the molecular-level understanding of their function. Here, we present X-ray crystal structures for the catalytic and ATP-binding (CA) domains of two VanS proteins, derived from VRE types A and C. Both proteins adopt the canonical Bergerat fold that has been observed for CA domains of other prokaryotic histidine kinases. We attempted to determine structures for the nucleotide-bound forms of both proteins; however, despite repeated efforts, these forms could not be crystallized, prompting us to measure the proteins’ binding affinities for ATP. Unexpectedly, both CA domains displayed low affinities for the nucleotide, withKDvalues in the low millimolar range. Since theseKDvalues are comparable to intracellular ATP concentrations, this weak substrate binding could reflect a way of regulating expression of the resistance phenotype.
Cell polarity opposes Jak-STAT mediated Escargot activation that drives intratumor heterogeneity in aDrosophilatumor model
Authors: Chatterjee Deeptiman , Cong Fei , Wang Xian-Feng , Costa Caique Almeida Machado , Huang Yi-Chun , Deng Wu-Min 
Published: December 2022

SUMMARYIn proliferating neoplasms, microenvironment-derived selective pressures promote tumor heterogeneity by imparting diverse capacities for growth, differentiation and invasion. However, what makes a tumor cell respond to signaling cues differently from a normal cell is not well understood. In theDrosophilaovarian follicle cells, apicobasal-polarity loss induces heterogenous epithelial multilayering. When exacerbated by oncogenic-Notch expression, this multilayer displays an increased consistency in the occurrence of morphologically distinguishable cells adjacent to the polar follicle cells. Polar cells release the Jak-STAT ligand Unpaired (Upd), in response to which, neighboring polarity-deficient cells exhibit a precursor-like transcriptomic state. Using single-cell transcriptomics, we discovered the ectopic activation of the Snail-family transcription factor Escargot (Esg) in these cells. We also characterized similar relationship between Upd and Esg during early follicular development, where the establishment of polarity determines follicle-cell differentiation. Overall, our results indicate that epithelial-cell polarity acts as a gatekeeper against microenvironmental selective pressures that drive heterogeneity.
Ultrafast molecular dynamics observed within a dense protein condensate
Authors: Galvanetto Nicola , Ivanović Miloš T. , Chowdhury Aritra , Sottini Andrea , Nüesch Mark F. , Nettels Daniel , Best Robert B. , Schuler Benjamin 
Published: December 2022

AbstractMany biological macromolecules can phase-separate in the cell and form highly concentrated condensates. The mesoscopic dynamics of these assemblies have been widely characterized, but their behavior at the molecular scale has remained more elusive. Here we investigate condensates of two highly charged disordered human proteins as a characteristic example of liquid-liquid phase separation. The dense phase is 1000 times more concentrated and has 300 times higher bulk viscosity than the dilute phase. However, single-molecule spectroscopy in individual droplets reveals that the polypeptide chains are remarkably dynamic, with sub-microsecond reconfiguration times. We rationalize this behavior with large-scale all-atom molecular-dynamics simulations, which reveal an unexpectedly similar short-range molecular environment in the dense and dilute phases, suggesting that local biochemical processes and interactions can remain exceedingly rapid in phase-separated systems.
Improved Yield for the Enzymatic Synthesis of Radiolabeled Nicotinamide Adenine Dinucleotide
Authors: Eller Jared , Goyal Shivansh , Cambronne Xiaolu A. 
Published: December 2022

ABSTRACTLabeled β-nicotinamide adenine dinucleotide (NAD) analogs have been critical for uncovering new biochemical connections and quantitating enzymatic activity. They function as tracers for enzymology, flux analyses, and in situ measurements. Nevertheless, there is limited availability of specific types of analogs, especially radiolabeled NAD analogs. Here, we describe an improved enzymatic synthesis reaction for32P-NAD+with a yield of 98% ± 1%, using lowered concentrations of reactants and standard equipment. This represents the highest reported yield for the enzymatic synthesis of NAD+to date. With the high yield we were able to directly use the reaction product to generate derivatives, such as32P-NADP. The high-yield enzymatic synthesis is versatile for a broad variety of labels and NAD derivatives. Its advantages include lowered concentrations of reactants, providing sufficient amounts of product for downstream applications, and minimizing intermediate purification steps.
Impact of growth-promoting alternatives on weight gain and gut microbial diversity and activity in piglets
Authors: Palanee Jason , Gagnon Nathalie , Lauzon Karoline , Méthot Steve , Blais Mylène , Talbot Guylaine , Guay Frédéric , Lessard Martin , Yergeau Étienne , Poulin-Laprade Dominic 
Published: December 2022

AbstractIn swine husbandry, weaning is a critical event for piglets which causes environmental, nutritional, and psychological stresses, with consequences such as intestinal dysbiosis. To counteract this issue, producers resorted to the use of in-feed antimicrobials to prevent post-weaning diarrhea and to promote growth for increased animal performance. However, the use of antibiotic for growth promotion was banned in many countries. In-feed supplements have great potential as alternative strategies. This study evaluated the effect on gut microbial activity, microbiome, and animal performance of combinations of peri-weaning feeding strategies such as bovine colostrum, medium-chain fatty acids and yeast extract. We quantified weight gain, intestinal pH, volatile fatty acids, and characterized the gut microbiota on ileum, cecum, and colon digestates. Overall, the feed supplements had limited impact on weight gain and volatile fatty acids production. However, the combined treatments have demonstrated a modulatory effect on gut microbiota which supports a potential role as an alternative to growth-promoting antibiotic in the swine industry.
Robust SARS-CoV-2 antibody and T cell immunity following three COVID-19 vaccine doses in inflammatory bowel disease patients receiving anti-TNF or alternative treatments
Authors: Zhang Eva , Nguyen Thi H O , Allen Lilith F , Kedzierski Lukasz , Rowntree Louise C , Chang So Young , Zhang Wuji , Habel Jennifer R , Foo Isabelle J , Menon Tejas , Mitchell Jeni , Leong Rupert W , Bond Katherine A , Williamson Deborah A , Kedzierska Katherine , Christensen Britt 
Published: December 2022

ABSTRACTBACKGROUND AND AIMSVaccine-mediated immune responses in patients with inflammatory bowel disease (IBD) may be influenced by IBD therapies. We investigated in-depth humoral and T-cell responses to SARS-CoV-2 vaccination in IBD patients following three COVID-19 vaccine doses.METHODSImmune responses of 100 SARS-CoV-2-uninfected IBD patients on varying treatments were compared to healthy controls (n=35). Anti-S1/2 and anti-RBD SARS-CoV-2-specific antibodies, CD4+and CD8+T-cell responses were measured at baseline and at five time-points after COVID-19 vaccination.RESULTSAnti-S1/2 and anti-RBD antibody concentrations at ∼1 month after second dose vaccination were significantly lower in anti-TNF-treated patients compared to non-TNF IBD patients and healthy controls (126.4 vs 262.1 and 295.5, p<0.0001). Anti-S1/2 antibodies remained reduced in anti-TNF treated patients before and after the third dose (285.7 vs 365.3,p=0.03), although anti-RBD antibodies reached comparable titres to non-TNF patients. Anti-RBD antibodies were higher in the vedolizumab group than controls after second dose (4.2 vs 3.6, p=0.003). Anti-TNF monotherapy was associated with increased CD4+and CD8+T-cell activation compared to combination anti-TNF patients after second dose, but comparable after third dose. Overall, IBD patients demonstrated similar CD4+/CD8+T-cell responses compared to healthy controls regardless of treatment regimen.CONCLUSIONSAnti-TNFs impaired antibody concentrations when compared to non-TNF patients and controls after two vaccine doses. These differences were not observed after the third vaccine dose. However, vaccine induced SARS-CoV-2-specific T cell responses are robust in anti-TNF-treated patients. Our study supports the need for timely booster vaccination particularly in anti-TNF treated patients to minimise the risk of severe SARS-CoV-2 infection.
Avoidance learning reduces intricate covariation between boldness and foraging behavior in a generalist predator
Authors: Kuo Chi-Yun , Chin Hao-En , Wu Yu-Che 
Published: December 2022

AbstractMany predators avoid unprofitable prey by learning to use visual features of the prey as reliable indicators of quality. Despite a rich literature on avoidance learning, we are still in the process of understanding how individuals might change their behavior towards unprofitable prey as information accumulates, the individual-level variation in avoidance foraging behavior, and whether learning would preserve or reduce this variation. In this study, we investigated how avoidance foraging behavior varied in a generalist lizard predator in relation to sex, population of origin, and boldness and tested the effects of learning on the variation in avoidance foraging behavior. We collected data on boldness and avoidance foraging behavior in individuals from two allopatric populations and compared variation in behavior at the beginning and end of learning experiments, in which individuals were presented with normal- and bitter-tasting prey that also differed consistently in color. We found that even though bitter prey elicited strong negative responses, lizards overall did not avoid consuming fewer such prey with learning. Instead, lizards learned to prioritize on palatable prey as they acquired more information. Our data revealed intricate covariation between boldness and avoidance foraging behavior, and the form of this covariation varied between populations, sex, and prey color. Learning overall reduced individual variation in foraging behavior, as well as the degree of covariation with boldness. Our findings highlighted the nuanced manners in which avoidance foraging behavior might manifest and suggested that learning could quickly mitigate fitness difference due to variation in behavior.Lay SummaryPredators can learn to avoid unprofitable prey using certain visual cues or signals, but avoidance foraging behavior can manifest in more subtle ways than simply “to eat or not to eat”. We reported changes in foraging sequence and priority in a generalist lizard predator after learning and found that the nature of these changes depended on sex, population of origin, boldness, and prey color. We also found that learning made individuals more similar in behavior.
Two extreme Loss-of-FunctionGRIN2B-mutations are detrimental to tri-heteromeric NMDAR-function, but rescued by pregnanolone-sulfate
Authors: Kellner Shai , Berlin Shai 
Published: December 2022

AbstractMutations within various N‐methyl-D-aspartate receptor (NMDAR) subunits are tightly associated with severe pediatric neurodevelopmental disorders and encephalopathies (here denotedGRINopathies), for which there are no treatments. NMDARs are tetrameric receptors and can be found at the membrane of neurons in various compositions, namely in di- or tri-heteromeric forms. The GluN2B subunit appears very early in development and, therefore, prenatally this subunit is predominantly found within di-heteromeric receptors, exclusively composed of the GluN1 and GluN2B subunits. Postnatally, however, the GluN2A subunit undergoes rapid increase in expression, giving rise to the appearance of tri-heteromers containing the GluN1, GluN2A and GluN2B-subunits. The latter are emerging as the principal receptor-type postnatally. Despite more than a decade of research of numerousGRINopathies, not much is known regarding the effect ofGRINvariants when these are assembled within tri-heteromers. Here, we have systematically examined how twode novo GRIN2Bvariants (G689C and G689S) affect the function of di- and tri-heteromers. We show that whereas a single mutated subunit readily instigates a dominant negative effect over glutamate affinity of tri-heteromers, it does not dominate other features of the receptor, notably potentiation by pregnanolone-sulfate (PS). This led us to explore PS as a potential treatment for these two severe loss-of-function (LoF) mutations in cultured neurons, in which case we indeed find that the neurosteroid rescues current amplitudes. Together, we present the first report to examine LoFGRIN2Bmutations in the context of di- and tri-heteromeric receptors. We also provide the first demonstration of the positive outcome of the use of aGRIN2B-relevant potentiator in the context of tri-heteromers. Our results highlight the importance of examining how different mutations affect features in various receptor subtypes, as these could not have been deduced from observations performed on purely di-heteromers. Together, our study contributes to the ongoing efforts invested towards understanding the pathophysiology ofGRINopathiesas well as provides insights towards a potential treatment.