bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing Primary transcriptional responses to short term heat shock in paired fraternal lymphoblastoid lines with and without Down syndrome
Authors: Cardiello Joseph F. , Westfall Jessica , Dowell Robin , Allen Mary Ann 
Published: January 2023

AbstractHeat shock stress induces genome wide changes in transcription regulation, activating a coordinated cellular response to enable survival. Using publicly available transcriptomic and proteomic data sets comparing individuals with and without trisomy 21, we noticed many heat shock genes are up-regulated in blood samples from individuals with trisomy 21. Yet no major heat shock response regulating transcription factor is encoded on chromosome 21, leaving it unclear why trisomy 21 itself would cause a heat shock response, or how it would impact the ability of blood cells to subsequently respond when faced with heat shock stress. To explore these issues in a context independent of any trisomy 21 associated co-morbidities or developmental differences, we characterized the response to heat shock of two lymphoblastoid cell lines derived from brothers with and without trisomy 21. To carefully compare the chromatin state and the transcription status of these cell lines, we measured nascent transcription, chromatin accessibility, and single cell transcript levels in the lymphoblastoid cell lines before and after acute heat shock treatment. The trisomy 21 cells displayed a more robust heat shock response after just one hour at 42°C than the matched disomic cells. We suggest multiple potential mechanisms for this increased heat shock response in lymphoblastoid cells with trisomy 21 including the possibility that cells with trisomy 21 may exist in a hyper-reactive state due to chronic stresses. Whatever the mechanism, abnormal heat shock response in individuals with Down syndrome may hobble immune responses during fever and contribute to health problems in these individuals.
Lhcb9-dependent photosystem I structure in moss reveals evolutionary adaptation to changing light conditions during aquatic-terrestrial transition
Authors: Sun Haiyu , Shang Hui , Pan Xiaowei , Li Mei 
Published: January 2023

AbstractIn plants and green algae, light-harvesting complexes I and II (LHCI and LHCII) constitute the antennae of photosystem I (PSI), thus effectively increasing the cross-section of the PSI core. The mossPhyscomitrium patens(P. patens) represents a well-studied evolutionary intermediate between green algae and flowering plants.P. patenspossesses at least three types of PSI with different antenna sizes. The largest PSI form (PpPSI-L) exhibits a unique organization found neither in flowering plants nor in algae. Its formation is mediated by theP. patens-specific LHC protein, Lhcb9. While previous studies revealed the overall architecture of thePpPSI-L, its assembly details and the relationship between differentPpPSI types remain unclear. Here, we report a high-resolution structure of thePpPSI-L. We identified 14 PSI core subunits, one Lhcb9, one phosphorylated LHCII trimer, and eight LHCI monomers arranged as two belts. Our structural analysis established the essential role of Lhcb9 and the phosphorylated LHCII in stabilizing the complex. In addition, our results suggest thatPpPSI switches between three different types, which share identical modules. This feature may contribute to the quick and dynamic adjustment of the light-harvesting capability of PSI under different light conditions.
Yeast eukaryotic initiation factor 4B remodels the mRNA entry site on the small ribosomal subunit
Authors: Datey Ayushi , Khaja Faisal Tarique , Rahil Huma , Hussain Tanweer 
Published: January 2023

AbstractEukaryotic initiation factor 4B (eIF4B) belongs to the eIF4 group of factors that help in mRNA recruitment to the ribosomal preinitiation complex (PIC) in all eukaryotic organisms. eIF4B stimulates the helicase activity of eIF4A and helps in the formation of the 48S PIC by facilitating mRNA recruitment. However, there is no clear understanding of the location of eIF4B on the 40S and how eIF4B helps in the recruitment of mRNAs. In this work using cryo-electron microscopy, we show that yeast eIF4B binds to the 40S ribosomal subunit at the mRNA entry channel making contacts with ribosomal proteins uS10, uS3, and eS10 and ribosomal rRNA helix h16. The yeast eIF4B position on the 40S overlaps with the RRM domain of eIF3g indicating that the binding of eIF4B may trigger the relocation of the eIF3 b-g-i module to the subunit interface. The 40S head is in partially open conformation that may facilitate the release of eIF3j and hence aid mRNA recruitment and scanning. The structural analysis of yeast eIF4B-bound ribosomal complex provides insight into possible events during mRNA recruitment.
Towards development of serum substitute medium to induce osteoclast differentiation of human peripheral blood derived monocytes
Authors: Ansari Sana , Ito Keita , Hofmann Sandra 
Published: January 2023

AbstractFetal bovine serum (FBS) is a widely used supplement in cell culture media despite its known drawbacks, including ethical, safety, and scientific issues. To overcome the drawbacks of using FBS in cell culture, a defined serum substitute medium needs to be developed. The development of such a medium depends on the cell type, which makes it impossible to use one universal serum substitute medium for all cells. Osteoclasts are large, multinucleated cells originated from the hematopoietic stem cell lineage that play an important role in regulating bone mass and quality. To date, no defined serum substitute medium formulations have been reported for osteoclast differentiation of monocytes derived from peripheral blood mononuclear cells (PBMCs). Here, we have attempted to develop such a serum substitute medium for the osteoclastogenesis process in a stepwise approach. Essential components were added to the medium while monocytes were cultured in 96-well plates and in Osteo-Assay well plates to analyze the formation of tartrate resistant acid phosphatase (TRAP) expressing multinucleated osteoclasts with distinct actin ring and to analyze the resorption activity of mature osteoclasts for 21 days, respectively. The serum substitute medium was aimed at supporting monocyte and later osteoclast survival, differentiation of monocytes towards multinucleated osteoclasts, and the resorption of mineralized matrix as a measure of functionality. All points were achieved after 21 days of culture in the developed serum substitute medium. This serum substitute medium could potentially replace FBS in osteoclastogenesis studies eliminating its debated use. Moreover, the well-defined serum substitute environment simplifies the study of factors released by the cells that were so far overwhelmed by the complexity of FBS.
Evolution of two gene networks underlying adaptation to drought stress in the wild tomatoSolanum chilense
Authors: Wei Kai , Sharifova Saida , Zhao Xiaoyun , Sinha Neelima , Nakayama Hokuto , Tellier Aurélien , Silva-Arias Gustavo A 
Published: January 2023

AbstractDrought stress is a key factor limiting plant growth and the colonization of arid habitats by plants. Here, we study the evolution of gene expression response to drought stress in a wild tomato,Solanum chilensenaturally occurring around the Atacama Desert in South America. We conduct a transcriptome analysis of plants under standard and drought experimental conditions to understand the evolution of drought-response gene networks. We identify two main regulatory networks corresponding to two typical drought-responsive strategies: cell cycle and fundamental metabolic processes. We estimate the age of the genes in these networks and the age of the gene expression network, revealing that the metabolic network has a younger origin and more variable transcriptome than the cell-cycle network. Combining with analyses of population genetics, we found that a higher proportion of the metabolic network genes show signatures of recent positive selection underlying recent adaptation withinS. chilense,while the cell-cycle network appears of ancient origin and is more conserved. For both networks, however, we find that genes showing older age of selective sweeps are the more connected in the network. Adaptation to southern arid habitats over the last 50,000 years occurred inS. chilenseby adaptive changes core genes with substantial network rewiring and subsequently by smaller changes at peripheral genes.
Hyperparasitism and the evolution of parasite virulence
Authors: Wood Jason , Ashby Ben 
Published: January 2023

AbstractHyperparasites (species which parasitise other parasites) are common in natural populations, affecting many parasitic taxa, including: eukaryotic parasites; bacterial and fungal pathogens. Hyperparasitism is therefore likely to shape the ecology and evolution of many host-parasite systems, representing a promising method for biocontrol (e.g., treating antimicrobial resistant infections). However, the eco-evolutionary consequences of hyperparasitism have received little attention. We use a host-parasite-hyperparasite model to explore how introducing a hyperparasite drives the evolution of parasite virulence, and what impact this has on the host population. We show when the introduction of a hyperparasite selects for higher or lower parasite virulence, and the changes in virulence experienced by the host population. Crucially, we show that variation in the direct effects of hyperparasites on virulence and transmission, and the probability of co-transmission, can lead to a previously unseen hysteresis effect, whereby small shifts in hyperparasite characteristics can lead to sudden shifts in parasite virulence. We also show that hyperparasites can induce diversification in parasite virulence, leading to the coexistence of high and low virulence strains. Our results show hyperparasites can have dramatic effects on the evolution of parasite virulence, and that the use of hyperparasites in biocontrol should be approached with caution.
Method for assessing coating uniformity of angioplasty balloons coated with poly(lactic-co-glycolic acid) nanoparticles loaded with quercetin
Authors: Zieschang Allison D. , Hoffseth Kevin F. , Dugas Tammy R. , Astete Carlos E. , Boldor Dorin 
Published: January 2023

AbstractSignificanceDrug-coated angioplasty balloons (DCBs) are used to treat peripheral artery disease, and proper dosage depends on coating characteristics like uniformity and number of layers.AimQuantify coating uniformity and correlate fluorescence intensity to drug loading for DCBs coated with 5, 10, 15, or 20 layers of poly(lactic-co-glycolic acid) nanoparticles (NPs) entrapped with quercetin.ApproachImages of DCBs were acquired using fluorescence microscopy. Coating uniformity was quantified from histograms and horizontal line profiles, and cracks on the balloons were measured and counted. Fluorescence intensity was correlated with the drug loading of quercetin found from gravimetric analysis coupled with high-performance liquid chromatography (HPLC).ResultsHigher numbers of coating layers on DCBs may be associated with less uniform coatings. Cracks in the coating were present on all balloons, and the length of cracks was not significantly different between balloons coated with different numbers of layers or balloons coated with the same number of layers. A strong positive correlation was identified between fluorescence intensity and drug loading.ConclusionThere may be a relationship between the number of NP layers and the uniformity of the coating, but further investigation is needed to confirm this. Fluorescence intensity appears to be a strong predictor of drug loading on DCBs coated with quercetin-entrapped NPs, demonstrating that fluorescent imaging may be a viable alternative to drug release studies.
Genome assembly of the hybrid grapevineVitis‘Chambourcin’
Authors: Patel Sagar , Harris Zachary N. , Londo Jason P. , Miller Allison , Fennell Anne 
Published: January 2023

AbstractBackground‘Chambourcin’ is a French-American interspecific hybrid grape variety grown in the eastern and midwestern United States and used for making wine. Currently, there are few genomic resources available for hybrid grapevines like ‘Chambourcin’.ResultsWe assembled the genome of ‘Chambourcin’ using PacBio HiFi long-read sequencing, Bionano optical map sequencing and Illumina short read sequencing. We produced an assembly for ‘Chambourcin’ with 26 scaffolds with an N50 length of 23.3 Mb and an estimated BUSCO completeness of 97.9%. 33,791 gene models were predicted, of which 81% (27,075) were functionally annotated using Gene Ontology and KEGG pathway analysis. We identified 16,056 common orthologs between ‘Chambourcin’ gene models,V. vinifera‘PN40024’ 12X.v2, VCOST.v3, Shine Muscat (Vitis labruscana x V. vinifera) andV. ripariaGloire. A total of 1,606 plant transcription factors representing 58 different gene families were identified in ‘Chambourcin’. Finally, we identified 304,571 simple sequence repeats (SSRs), repeating units of 1-6 base pairs in length in the ‘Chambourcin’ genome assembly.ConclusionsWe present the genome assembly, genome annotation, protein sequences and coding sequences reported for ‘Chambourcin’. The ‘Chambourcin’ genome assembly provides a valuable resource for genome comparisons, functional genomic analysis and genome-assisted breeding research.
Radiances of Cerenkov-Emitting Isotopes on the IVIS
Authors: Pratt Edwin C. , Shaffer Travis M. , Bauer David , Lewis Jason S. , Grimm Jan 
Published: January 2023

AbstractCerenkov (or Cherenkov) luminescence occurs when charged particles exceed the phase velocity of a given medium. Cerenkov has gained interest in preclinical space as well as in clinical trials for optical visualization of numerous radionuclides. However, Cerenkov intensity has to be inferred from alternative databases with energy emission spectra, or theoretical fluence estimates. Here we present the largest experimental dataset of Cerenkov emitting isotopes recorded using the IVIS optical imaging system. We report Cerenkov measurements spanning orders of magnitude normalized to the activity concentration for 21 Cerenkov emitting isotopes, covering electron, alpha, beta minus, and positron emissions. Isotopes measured include Carbon-11, Fluorine-18, Phosphorous-32, Scandium-47, Copper-64, Copper-67, Gallium-68, Arsenic-72, Bromine-76, Yttrium-86, Zirconium-89, Yttrium-90, Iodine-124, Iodine-131, Cerium-134, Lutetium-177, Lead-203, Lead-212, Radium-223, Actinium-225, and Thorium-227. We hope this updating resource will serve as a rank ordering for comparing isotopes for Cerenkov luminescence in the visible window and serve as a rule of thumb for comparing Cerenkov intensities in vitro and in vivo.MethodsAll Cerenkov emitting radionuclides were either produced at Memorial Sloan Kettering Cancer Center (Carbon-11,11C; Fluorine-18,18F; Iodine-124,124I), from commercial sources such as Perkin Elmer (Phosphorous-32,32P; Yttrium-90,90Y), Bayer (Radium-223,223Ra, Xofigo), 3D-Imaging (Zirconium-89,89Zr), Nuclear Diagnostic Products (Iodine-131,131I), or from academic collaborators at Washington University at St. Louis (Copper-64,64Cu), University of Wisconsin (Bromine-76,76Br), MD Anderson Cancer Center (Yttrium-86,86Y), Brookhaven National Laboratory (Arsenic-72,72As; Thorium-227,227Th), or Oak Ridge National Laboratory (Cerium-134,134Ce, Actinium-225,225Ac), and Viewpoint Molecular Targeting (Lead-203,203Pb; Lead 212,212Pb). All isotopes were diluted in triplicate on a black bottomed corning 96 well plate to several activity concentrations ranging from 0.1-250 μCi in 100-200 μL of Phosphate Buffered Saline. Cerenkov imaging was acquired on a single Perkin-Elmer Spectrum In-Vivo Imaging System (IVIS) at field of view c with exposures ranging up to 15 minutes or lower provided no part of the image intensity was saturated, or that the activity significantly changed during the exposure. Experimental radiances on the IVIS were calculated from regions of interest drown over each 96 well, and then normalized for the activity present in the well, and the volume the isotope was diluted into.
Neuroanatomical characterization of the Nmu-Cre knock-in mice reveals an interconnected network of unique neuropeptidergic cells
Authors: Medrano Mireia , Allaoui Wissal , Van Bulck Mathias , Thys Sofie , Makrini-Maleville Leila , Seuntjens Eve , De Vos Winnok H. , Valjent Emmanuel , Gaszner Bálazs , Van Eeckhaut Ann , Smolders Ilse , De Bundel Dimitri 
Published: January 2023

AbstractNeuromedin U (NMU) is an evolutionary conserved neuropeptide that has been implicated in multiple processes, such as circadian regulation, energy homeostasis, reward processing and stress coping. Although central expression of NMU has been addressed previously, the lack of specific and sensitive tools has prevented a comprehensive characterization of NMU-expressing neurons in the brain. We have generated a knock-in mouse model constitutively expressing Cre recombinase under theNmupromoter. We have validated the model using a multi-level approach based on quantitative reverse-transcription polymerase chain reactions,in situhybridization, a reporter mouse line and an adenoviral vector driving Cre-dependent expression of a fluorescent protein. Using the Nmu-Cre mouse, we performed a complete mapping of NMU expression in adult mouse brain, unveiling a potential midline NMU modulatory circuit with the ventromedial hypothalamic nucleus (VMH) as a key node. Moreover, immunohistochemical analysis suggested that NMU neurons in the VMH mainly constitute a unique population of hypothalamic cells. Taken together, our results suggest that Cre expression in the Nmu-Cre mouse model largely reflects NMU expression in the adult mouse brain, without altering endogenous NMU expression. Thus, the Nmu-Cre mouse model is a powerful and sensitive tool to explore the role of NMU neurons in mice.
IFI207, a young and fast-evolving antiviral factor, stabilizes STING
Authors: Moran Eileen A. , Salas-Briceno Karen , Aguilera Alexya N. , Keane Thomas M. , Adams David J. , Lilue Jingtao , Ross Susan R. 
Published: January 2023

ABSTRACTMammalian ALR proteins bind nucleic acids and initiate production of type I interferons or inflammasome assembly, thereby contributing to host innate immunity.ALRs are encoded at a single genetic locus. In mice, theAlrlocus is highly polymorphic at the sequence and copy number level. We suggest that one rapidly evolving member of theAlrfamily,Ifi207, was introduced to theMusgenome by a recent recombination event.Ifi207has a large, distinctive repeat region that differs in sequence and length in differentMusstrains. We show that IFI207 plays a key role in the STING-mediated response to cGAMP, DNA, and MLV, and that IFI207 controls MLV infection in vivo. Uniquely, IFI207 acts by stabilizing STING protein via its repeat region. Our studies suggest that under the pressure of host-pathogen coevolution, in a dynamic locus such as theAlr, recombination between gene family members creates new genes with novel and essential functions that play diverse roles in biological processes.
Molecular and functional properties of humanPlasmodium falciparumCSP C-terminus antibodies
Authors: Oludada Opeyemi Ernest , Costa Giulia , Aschner Clare Burn , Obraztsova Anna S. , Prieto Katherine , Canetta Caterina , Hoffman Stephen L. , Kremsner Peter G. , Mordmüller Benjamin , Murugan Rajagopal , Julien Jean-Philippe , Levashina Elena A. , Wardemann Hedda 
Published: January 2023

ABSTRACTHuman monoclonal antibodies (mAbs) against the central repeat and junction domain ofPlasmodium falciparumcircumsporozoite protein (PfCSP) have been studied extensively to guide malaria vaccine design compared to antibodies against the PfCSP C terminus. Here, we describe the molecular characteristics and protective potential of a panel of 73 germline and mutated human mAbs against the highly immunogenic PfCSP C-terminal domain. Two mAbs recognized linear epitopes in the C-terminal linker with sequence similarity to repeat and junction motifs, whereas all others targeted conformational epitopes in the α-thrombospondin repeat (α-TSR) domain. Specificity for the polymorphic Th2R/Th3R but not the conserved RII+ region in the α-TSR was associated withIGHV3-21/IGVL3-21orIGLV3-1gene usage. Although the C terminus specific mAbs showed signs of more efficient affinity maturation and class-switching compared to anti-repeat mAbs, parasite inhibitory activity was limited to a single C-linker reactive mAb with cross-reactivity to the central repeat and junction. The data provide novel insights in the human anti-C-linker and anti-α-TSR antibody response that support exclusion of the PfCSP C terminus from malaria vaccine designs.
Learning to predict future locations with internally generated theta sequences
Authors: Parra-Barrero Eloy , Cheng Sen 
Published: January 2023

AbstractRepresenting past, present and future locations is key for spatial navigation. Indeed, within each cycle of the theta oscillation, the population of hippocampal place cells appears to represent trajectories starting behind the current position of the animal and sweeping ahead of it. In particular, we reported recently that the position represented by CA1 place cells at a given theta phase corresponds to the location where animals were or will be located at a fixed time interval into the past or future assuming the animal ran at its typical, not the current, speed through that part of the environment. This coding scheme leads to longer theta trajectories, larger place fields and shallower phase precession in areas where animals typically run faster. Here we present a mechanistic computational model that accounts for these experimental observations. The model consists of a continuous attractor network with short-term synaptic facilitation and depression that internally generates theta sequences that advance at a fixed pace. Spatial locations are then mapped onto the active units via modified Hebbian plasticity. As a result, neighboring units become associated with spatial locations further apart where animals run faster, reproducing our earlier experimental results. The model also accounts for the higher density of place fields generally observed where animals slow down, such as around rewards. Furthermore, our modeling results reveal that an artifact of the decoding analysis might be partly responsible for the observation that theta trajectories start behind the animal’s current position. Overall, our results shed light on how the hippocampal code might arise from the interplay between behavior, sensory input and predefined network dynamics.