bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentially inappropriate medication in long-term care wards of a veteran hospital in Taiwan: Investigation using a spreadsheet-based rapid assessment tool
Authors: Wang Ying-Mei , Shen Hung-Wei , Chen Tzeng-Ji
Published: January 2023

Background:

Multimorbidity and polypharmacy increase in the aging population and are accompanied by the use of potentially inappropriate medications (PIMs) and adverse drug events (ADEs). This study developed a rapid assessment tool to investigate PIM use among patients in long-term care wards.

Methods:

We retrospectively collected the data of patients in long-term care wards of a veteran hospital in Taiwan between July 2019 and June 2020. The patients with chronic diseases and medications were selected. The data, including gender, age, diagnosis, and medications, were deidentified. Nonchronic disease diagnosis and short-term and topical use medications were excluded. We used Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA) and the 2019 version of the Beers Criteria to establish a rapid assessment tool. The correlations between the prevalence of PIM use and age, the number of diagnoses, and the number of medications were analyzed using SPSS version 23.

Results:

A total of 176 patients were included in this study, of which 76.7% (n = 135) were male and 23.3% (n = 41) were female. The average age of men was 82.1 years and that of women was 83.4 years. The average number of diagnoses for men was 5.5, and that for women was 7.3. The average number of medications for men was 5.8, and that for women was 6.5. The prevalence of PIM use was 59.1% (n = 104). Logistic regression revealed that the prevalence of PIM use may be associated with the number of medications (p < 0.001; odds ratio = 1.378). Decision tree analysis revealed that patients who simultaneously used more than four medications exhibited a higher risk of PIM.

Conclusion:

PIM use is a key factor causing ADEs among older adults. Therefore, comprehensive assessment of PIM use is necessary. This study designed a rapid assessment tool to simultaneously integrate and evaluate medications. Future studies may investigate the effectiveness of the proposed assessment tool.
Examination of 2D frontal and sagittal markerless motion capture: Implications for 2D and 3D markerless applications
Authors: Wade Logan , Needham Laurie , Evans Murray , McGuigan Polly , Colyer Steffi , Cosker Darren , Bilzon James
Published: January 2023

This study examined if occluded joint locations from markerless motion capture produced 2D joint angles with reduced accuracy compared to visible joints, and if 2D frontal plane joint angles were usable for practical applications. Fifteen healthy participants performed over-ground walking whilst recorded by fifteen marker-based cameras and two machine vision cameras (frontal and sagittal plane). Repeated measures Bland-Altman analysis illustrated that markerless standard deviation of bias (random differences) for the occluded-side hip and knee joint angles in the sagittal plane were double that of the camera-side (visible) hip and knee. Camera-side sagittal plane knee and hip angles were near or within marker-based error values previously observed. While frontal plane random differences accounted for 35-46% of total range of motion at the hip and knee, systematic and random differences (−4.6-1.6 ± 3.7-4.2°) were actually similar to previously reported marker-based error values. This was not true for the ankle, where random difference (±12°) was still too high for practical applications. Our results add to previous literature, highlighting shortcomings of current pose estimation algorithms and labelled datasets. As such, this paper finishes by reviewing marker-based methods for creating anatomically accurate markerless training data.
Accounting for unobserved spatial variation in step selection analyses of animal movement via spatial random effects
Authors: Guillen Rafael Arce , Lindgren Finn , Muff Stefanie , Glass Thomas W. , Breed Greg A. , Schlägel Ulrike E.
Published: January 2023

Step selection analysis (SSA) is a common framework for understanding animal movement and resource selection using telemetry data. Such data are, however, inherently autocorrelated in space, a complication that could impact SSA-based inference if left unaddressed. Accounting for spatial correlation is standard statistical practice when analyzing spatial data, and its importance is increasingly recognized in ecological models (e.g., species distribution models). Nonetheless, no framework yet exists to account for such correlation when analyzing animal movement using SSA.

Here, we extend the popular methodIntegrated Step Selection Analysis(iSSA) by including aGaussian Field(GF) in the linear predictor to account for spatial correlation. For this, we use the Bayesian frameworkR-INLAand theStochastic Partial Differential Equations(SPDE) technique.

We show through a simulation study that our method provides unbiased fixed effects estimates, quantifies their uncertainty well and improves the predictions. In addition, we demonstrate the practical utility of our method by applying it to three wolverine (Gulo gulo) tracks.

Our method solves the problems of assuming spatially independent locations in the SSA framework. In addition, it offers new possibilities for making long-term predictions of habitat usage.
Effect of oncolytic virotherapy on immune microenvironment in immune subtypes identified in gastric cancer and hepatocellular carcinoma
Authors: Wang Ziyi , Peng Shuguang , Chen Xi , Xie Zhen , Li Shao
Published: January 2023

Tumor occurrence and progression are significantly influenced by immunity, and the immune infiltration and immune-related gene expression in solid tumors are closely correlated to the response of patients to immunotherapy. In this study, the level of tumor infiltrating immune cells in gastric cancer and hepatocellular carcinoma samples from the TCGA database were assessed using ssGSEA, and the tumor samples were divided into two subtypes (Imm_H and Imm_L) with different immune cell infiltration level. The differences in immune cell percentage and immune checkpoint gene expression between the two subtypes indicated that the Imm_H group had higher levels of immune infiltration, but also more infiltrated immunosuppressive cells and higher mRNA levels of immune checkpoint genes. Then the immune subtype-specific gene network was built and the main modules representing the genes and functions that differ between the two immune subtypes were identified. To explore the effect of oncolytic virus on tumor immune microenvironment, we constructed the previously developed synthetic adenovirus containing the synthetic sensory switch gene circuit, assessed the antitumor effect in mouse models, and measured the proportion of different cell types by single-cell RNA sequencing. The results showed that synthetic oncolytic virus inhibited tumor development and altered the proportion of infiltrating immune cells, suggesting that synthetic oncolytic virus may have different mechanism on the two immune subtypes.

Graphical abstract
Metacommunity Structure Preserves Genome Diversity in the Presence of Gene-specific Selective Sweeps
Authors: Pompei Simone , Bella Edoardo , Weitz Joshua S. , Grilli Jacopo , Lagomarsino Marco Cosentino
Published: January 2023

The horizontal transfer of genes is fundamental for the eco-evolutionary dynamics of microbial communities, such as oceanic plankton, soil, and the human microbiome. In the case of an acquired beneficial gene, classic population genetics would predict a genome-wide selective sweep, whereby the genome spreads clonally with the gene, removing genome diversity. Instead, several sources of metagenomic data show the existence of “gene-specific sweeps”, whereby a beneficial gene spreads across a bacterial community, maintaining genome diversity. Several hypotheses have been proposed to explain this process, including the decreasing gene flow between ecologically distant populations, frequency-dependent selection from linked deleterious allelles, and very high rates of horizontal gene transfer. Here, we propose an additional possible scenario grounded in eco-evolutionary principles. Specifically, we show by a mathematical model and simulations that a metacommunity where species can occupy multiple patches helps maintain genome diversity. Assuming a scenario of patches dominated by single species, our model predicts that diversity only decreases moderately upon the arrival of a new beneficial gene, and that losses in diversity can be quickly restored. We explore the generic behavior of diversity as a function of three key parameters, frequency of insertion of new beneficial genes, migration rates and horizontal transfer rates.Our results provides a testable explanation for how diversity can be maintained given gene-specific sweeps even in the absence of high horizontal gene transfer rates.
Inducible TRAP RNA profiling reveals host genes expressed in Arabidopsis cells haustoriated by downy mildew
Authors: Asai Shuta , Cevik Volkan , Jones Jonathan D.G. , Shirasu Ken
Published: January 2023

The downy mildew oomyceteHyaloperonospora arabidopsidis, an obligate filamentous pathogen, infects Arabidopsis by forming feeding structures called haustoria inside host cells. Previous transcriptome analyses revealed host genes are specifically induced during infection; however, RNA profiling from infected tissues may fail to capture key transcriptional events occurring exclusively in haustoriated host cells where the pathogen injects virulence effectors to modulate host immunity. To determine interactions between Arabidopsis andH. arabidopsidisat the cellular level, we devised a new translating ribosome affinity purification system applicable to inducible, including pathogen-responsive, promoters thus enabling haustoriated cell-specific RNA profiling. Among the host genes specifically expressed inH. arabidopsidis-haustoriated cells, we found genes that promote either susceptibility or resistance to the pathogen, providing new insights into the Arabidopsis/downy mildew interaction. We propose that our novel protocol for profiling cell-specific transcripts will be applicable to several stimulus-specific contexts and other plant-pathogen interactions.
Predicting Protein-encoding Gene Content inEscherichia coliGenomes
Authors: Nguyen Marcus , Elmore Zachary , Ihle Clay , Moen Francesco S. , Slater Adam D. , Turner Benjamin N. , Parrello Bruce , Best Aaron A. , Davis James J.
Published: January 2023

In this study, we built machine learning classifiers for predicting the presence or absence of the variable genes occurring in 10-90% of all publicly available high-qualityEscherichia coligenomes. The BV-BRC genus-specific protein families were used to define orthologs across the set of genomes, and a single binary classifier was built for predicting the presence or absence of each family in each genome. Each model was built using the nucleotide k-mers from a set of 100 conserved genes as features. The resulting set of 3,259 XGBoost classifiers had a per-genome average macro F1 score of 0.944 [0.943-0.945, 95% CI]. We show that the F1 scores are stable across MLSTs, and that the trend can be recapitulated through sampling with a smaller number of core genes or diverse input genomes. Surprisingly, the presence or absence of poorly annotated proteins, including “hypothetical proteins”, were easily predicted (F1 = 0.902 [0.898-0.906, 95% CI]). Models for proteins with horizontal gene transfer-related functions, including transposition- (F1 = 0.895 [0.882-0.907, 95% CI]), phage- (F1 = 0.872 [0.868-0.876, 95% CI]), and plasmid-related (F1 = 0.824 [0.814-0.834, 95% CI]) functions had slightly lower F1 scores, but were still accurate. Finally, we applied the models to a holdout set of 419 diverseE. coligenomes that were isolated from freshwater environmental sources and observed an average per-genome F1 score of 0.880 [0.876-0.883, 95% CI], demonstrating the extensibility of the models. Overall, this study provides a framework for predicting variable gene content using a limited amount of input sequence data.

Importance

Having the ability to predict the protein-encoding gene content of a genome is important for a variety of bioinformatic tasks, including assessing genome quality, binning genomes from shotgun metagenomic assemblies, and assessing risk due to the presence of antimicrobial resistance (AMR) and other virulence genes. In this study, we built a series of binary classifiers for predicting the presence or absence of variable genes occurring in 10-90% of all publicly availableE. coligenomes. Overall, the results show that a large portion of theE. colivariable gene content can be predicted with high accuracy, including genes with functions relating to horizontal gene transfer.
Convex representation of metabolic networks with Michaelis-Menten kinetics
Authors: Taylor Josh A. , Rapaport Alain , Dochain Denis
Published: January 2023

Polyhedral models of metabolic networks are computationally tractable and can predict some cellular functions. A longstanding challenge is incorporating metabolites without losing tractability. In this paper, we do so using a new second-order cone representation of the Michaelis-Menten kinetics. The resulting model consists of linear stoichiometric constraints alongside second-order cone constraints that couple the reaction fluxes to metabolite concentrations.

We formulate several new problems around this model: conic flux balance analysis, which augments flux balance analysis with metabolite concentrations; dynamic conic flux balance analysis; and finding minimal cut sets of networks with both reactions and metabolites. Solving these problems yields information about both fluxes and metabolite concentrations. They are second-order cone or mixed-integer second-order cone programs, which, while not as tractable as their linear counterparts, can nonetheless be solved at practical scales using existing software.
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

Heat 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

In 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

Eukaryotic 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

Fetal 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

Drought 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

Abstract

Hyperparasites (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

Significance

Drug-coated angioplasty balloons (DCBs) are used to treat peripheral artery disease, and proper dosage depends on coating characteristics like uniformity and number of layers.

Aim

Quantify 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.

Approach

Images 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).

Results

Higher 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.

Conclusion

There 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

Background

‘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’.

Results

We 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.

Conclusions

We 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

Cerenkov (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.

Methods

All 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

Neuromedin 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

Mammalian 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

Human 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

Representing 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.
Plant selection and ecological microhabitat drive domestications of shrub-associated microbiomes in a revegetated shrub ecosystem
Authors: Lai Zongrui , Sun Yanfei , Yu Yang , Liu Zhen , Bai Yuxuan , Qiao Yangui , Miao Lin , She Weiwei , Qin Shugao , Feng Wei
Published: January 2023

Shrubs are used for revegetation of degraded dryland ecosystem worldwide and could recruit large numbers of microbes from the soil; however, the plant-associated microbiome assembly and the effect of plant introduction on the soil microbiomes are not fully understood. We detected shrub-associated microbes from five ecological microhabitats, including the leaves, litter, roots, rhizosphere, and root zone, across four xeric shrub plantations (Artemisia ordosica, Caragana korshinskii, Hedysarum mongolicum, andSalix psammophila). To detect the patterns of shrub-associated microbiome assembly, 16S and ITS2 rRNA gene sequencing was performed. PERMANOVA and differential abundance analysis demonstrated that changes in the bacterial and fungal communities were more dependent on the microhabitats rather than on the plant species, with distinct niche differentiation. Moreover, source tracking and nestedness analysis showed that shrub-associated bacteria were primarily derived from bulk soils and slightly pruned in different microhabitats; however, a similar pattern was not found for fungi. Furthermore, the surrounding zone of roots was a hotpot for microbial recruitments of revegetated shrubs. Null model analysis indicated that homogeneous selection of determinism dominated the bacterial communities, whereas dispersal limitation and undominated process of stochasticity drove the assembly of fungal communities. Our findings indicate that ecological microhabitat of revegetated shrublands was the main predictor of the bacterial and fungal compositional variances. This study will help advance our understanding of the mechanism underlying the plant-soil microbiome feedbacks during the initial plant-establishment period in a dryland ecosystem. Further, this work provides theoretical reference for establishment and sustainable management of shrublands in drylands.
Sleep strengthens resting-state functional communication between brain areas involved in the consolidation of problem-solving skills
Authors: van den Berg Nicholas H. , Smith Dylan , Fang Zhuo , Pozzobon Alyssa , Toor Balmeet , Al-Kuwatli Julia , Ray Laura , Fogel Stuart M.
Published: January 2023

Sleep consolidates procedural memory for motor skills, and this process is associated with strengthened functional connectivity in hippocampal–striatal–cortical areas. It is unknown whether similar processes occur for procedural memory that requires cognitive strategies needed for problem-solving. It is also unclear whether a full night of sleep is indeed necessary for consolidation to occur, compared with a daytime nap. We examined how resting-state functional connectivity within the hippocampal–striatal–cortical network differs after offline consolidation intervals of sleep, nap, or wake. Resting-state fMRI data were acquired immediately before and after training on a procedural problem-solving task that requires the acquisition of a novel cognitive strategy and immediately prior to the retest period (i.e., following the consolidation interval). ROI to ROI and seed to whole-brain functional connectivity analyses both specifically and consistently demonstrated strengthened hippocampal–prefrontal functional connectivity following a period of sleep versus wake. These results were associated with task-related gains in behavioral performance. Changes in functional communication were also observed between groups using the striatum as a seed. Here, we demonstrate that at the behavioral level, procedural strategies benefit from both a nap and a night of sleep. However, a full night of sleep is associated with enhanced functional communication between regions that support problem-solving skills.
Cryo-EM reveals binding of linoleic acid to SARS-CoV-2 spike glycoprotein, suggesting an antiviral treatment strategy
Authors: Toelzer Christine , Gupta Kapil , Berger Imre , Schaffitzel Christiane
Published: January 2023

The COVID-19 pandemic and concomitant lockdowns presented a global health challenge and triggered unprecedented research efforts to elucidate the molecular mechanisms and pathogenicity of SARS-CoV-2. The spike glycoprotein decorating the surface of SARS-CoV-2 virions is a prime target for vaccine development, antibody therapy and serology as it binds the host cell receptor and is central for viral cell entry. The electron cryo-microscopy structure of the spike protein revealed a hydrophobic pocket in the receptor-binding domain that is occupied by an essential fatty acid, linoleic acid (LA). The LA-bound spike protein adopts a non-infectious locked conformation which is more stable than the infectious form and shields important immunogenic epitopes. Here, the impact of LA binding on viral infectivity and replication, and the evolutionary conservation of the pocket in other highly pathogenic coronaviruses, including SARS-CoV-2 variants of concern (VOCs), are reviewed. The importance of LA metabolic products, the eicosanoids, in regulating the human immune response and inflammation is highlighted. Lipid and fatty-acid binding to a hydrophobic pocket in proteins on the virion surface appears to be a broader strategy employed by viruses, including picornaviruses and Zika virus. Ligand binding stabilizes their protein structure and assembly, and downregulates infectivity. In the case of rhinoviruses, this has been exploited to develop small-molecule antiviral drugs that bind to the hydrophobic pocket. The results suggest a COVID-19 antiviral treatment based on the LA-binding pocket.
Higher-order implicit shock-capturing scheme based on linearization of implicit fluxes for the Euler equations
Authors: Mittakolu Roshith , Rani Sarma L. , Sundaram Dilip Srinivas
Published: January 2023

Purpose

A higher-order implicit shock-capturing scheme is presented for the Euler equations based on time linearization of the implicit flux vector rather than the residual vector.

Design/methodology/approach

The flux vector is linearized through a truncated Taylor-series expansion whose leading-order implicit term is an inner product of the flux Jacobian and the vector of differences between the current and previous time step values of conserved variables. The implicit conserved-variable difference vector is evaluated at cell faces by using the reconstructed states at the left and right sides of a cell face and projecting the difference between the left and right states onto the right eigenvectors. Flux linearization also facilitates the construction of implicit schemes with higher-order spatial accuracy (up to third order in the present study). To enhance the diagonal dominance of the coefficient matrix and thereby increase the implicitness of the scheme, wave strengths at cell faces are expressed as the inner product of the inverse of the right eigenvector matrix and the difference in the right and left reconstructed states at a cell face.

Findings

The accuracy of the implicit algorithm at Courant–Friedrichs–Lewy (CFL) numbers greater than unity is demonstrated for a number of test cases comprising one-dimensional (1-D) Sod’s shock tube, quasi 1-D steady flow through a converging-diverging nozzle, and two-dimensional (2-D) supersonic flow over a compression corner and an expansion corner.

Practical implications

The algorithm has the advantage that it does not entail spatial derivatives of flux Jacobian so that the implicit flux can be readily evaluated using Roe’s approximate Jacobian. As a result, this approach readily facilitates the construction of implicit schemes with high-order spatial accuracy such as Roe-MUSCL.

Originality/value

A novel finite-volume-based higher-order implicit shock-capturing scheme was developed that uses time linearization of fluxes at cell interfaces.
Going solo and feeling smart? An exploratory study on shoppers' time valuation and cultural perception
Authors: Wang Xueqin , Wong Yiik Diew , Yuen Kum Fai
Published: January 2023

Purpose

The advent of digitalization and the trend of social distancing coincide with the individualized lifestyle that is emerging among contemporary shoppers. This study explores the unique market of “smart solo shoppers”. Two empirical studies are conducted, which aim to identify the major dimensions of multi-channel shopping activities that are engaged by the shoppers (Study 1, n = 64) and to differentiate the shoppers' valuation of time invested in the distinct dimensions under different cultural influences (Study 2, n = 519).

Design/methodology/approach

A survey questionnaire is used for data collection, and data are analyzed using structural equation modeling.

Findings

Results reveal that the shopping activities converge into four principal dimensions: offline shopping, online shopping, post-shopping delivery and product return activities. Shoppers who perceive offline shopping activities as a time burden and online shopping and delivery activities as venues of value creation are more strongly self-identified as smart solo shoppers. Furthermore, smart solo shoppers who are under a strong influence of individualistic culture are found to spend time on multi-channel shopping to make the right purchase the first time, whereas shoppers perceiving being in a weak individualistic culture prefer to engage online channels while being prepared to return the unwanted purchases.

Originality/value

This study highlights an emerging research field in the nexus of solo consumption and smart shopping. Emphasizing the utility-driven and ego-expressive nature of smart solo shoppers, the authors provide an initial profile of these shoppers based on their time-valuation patterns and the contextual impacts of individualistic culture.