bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incomplete Reprogramming of DNA Replication Timing in Induced Pluripotent Stem Cells
Authors: Edwards Matthew M. , Wang Ning , Massey Dashiell J. , Egli Dieter , Koren Amnon 
Published: June 2023

AbstractInduced pluripotent stem cells (iPSC) are a widely used cell system and a foundation for cell therapy. Differences in gene expression, DNA methylation, and chromatin conformation, which have the potential to affect differentiation capacity, have been identified between iPSCs and embryonic stem cells (ESCs). Less is known about whether DNA replication timing – a process linked to both genome regulation and genome stability – is efficiently reprogrammed to the embryonic state. To answer this, we profiled and compared genome-wide replication timing between ESCs, iPSCs, and cells reprogrammed by somatic cell nuclear transfer (NT-ESCs). While NT-ESCs replicated their DNA in a manner indistinguishable from ESCs, a subset of iPSCs exhibit delayed replication at heterochromatic regions containing genes downregulated in iPSC with incompletely reprogrammed DNA methylation. DNA replication delays were not the result of gene expression and DNA methylation aberrations and persisted after differentiating cells to neuronal precursors. Thus, DNA replication timing can be resistant to reprogramming and lead to undesirable phenotypes in iPSCs, establishing it as an important genomic feature to consider when evaluating iPSC lines.
CREATION AND CHARACTERIZATION OF A RECOMBINANT MAMMALIAN ORTHOREOVIRUS EXPRESSING HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 PEPTIDES
Authors: Jandick Nicole A. , Miller Cathy L. 
Published: June 2023

AbstractMammalian orthoreovirus (MRV) is an oncolytic virus that has been tested in over 30 clinical trials. Increased clinical success has been achieved when MRV is used in combination with other onco-immunotherapies. This has led the field to explore the creation of recombinant MRVs which incorporate immunotherapeutic sequences into the virus genome. This work focuses on creation and characterization of a recombinant MRV, S1/HER2nhd, which expresses three human epidermal growth factor receptor 2 (HER2) peptides (E75, AE36, and GP2) known to induce HER2 specific CD8+ and CD4+ T cells. We show S1/HER2nhd expresses HER2 peptides in infected cells and on the virion, and infects, replicates, and reduces HER2+ breast cancer cell survival. The oncolytic properties of MRV combined with HER2 peptide expression holds potential as a vaccine to prevent recurrences of HER2 expressing cancers.
Exploring the Interactive Effects of Seed and Site Limitation on Recruitment Dynamics inPanicum hallii
Authors: Razzaque Samsad , Juenger Thomas E 
Published: June 2023

AbstractSeedling recruitment is a critical life history stage that is likely driven by the interplay of seed and microsite limitation and their interaction with seed traits. Here, we performed a factorial experiment involving seed addition and surface soil disturbance to explore the combined effects of seed and site availability using genotypes characterized by varying seed mass and dormancy traits. Additionally, we included hybrids that exhibited recombined seed trait relationships compared to natural genotypes, allowing us to assess the impact of specific seed traits on establishment across different sites. We detected a significant three-way interaction between seed addition, site conditions, and soil surface disturbance, influencing both seedling and adult recruitment inPanicum hallii, a perennial grass found in coastal mesic (lowland) and inland xeric (upland) habitats. This recruitment pattern suggests that lowland and upland establishment at foreign site is constrained by the interplay of seed and site limitations. Notably, soil surface disturbance facilitated recruitment of the upland genotype while constraining recruitment of the lowland genotype across all sites. Our results highlight the importance of seed size and dormancy as key factors impacting recruitment, suggesting a potential interactive relationship between these traits.
On the origin of F-wave: involvement of central synaptic mechanisms
Authors: Özyurt M. Görkem , Nascimento Filipe , Brownstone Robert M. , Beato Marco 
Published: June 2023

AbstractNeurophysiological methods are used widely to gain information about motoneuron excitability and axon conduction in neurodegenerative diseases. The F-wave is a common biomarker used to test motoneuron properties in the diagnosis of neurological diseases. Although the origin of the F-wave is a subject of debate, the most widely accepted mechanism posits that the F-wave is generated by the backfiring of motoneurons stimulated antidromically from the periphery. In this study, we developed anex vivomouse sciatic nerve-attached spinal cord preparation with sensory axons severed in which stimulation of the whole sciatic nerve or its tibial branch evoked responses with the electrophysiological signatures of F-waves. Manipulations of synaptic transmission by either removal of extracellular calcium or block of post-synaptic glutamate receptors abolished these responses. These results suggest that F-waves are mediated by spinal microcircuits activated by recurrent motor axon collaterals via glutamatergic synapses.
In situ spatial reconstruction of distinct normal and pathological cell populations within the human adrenal gland
Authors: Fu Rui , Walters Kathryn , Koc Katrina , Baldwin Amber , Clay Michael , Kiseljak-Vassiliades Katja , Fishbein Lauren , Mukherjee Neelanjan 
Published: June 2023

ABSTRACTThe human adrenal gland consists of concentrically organized functionally distinct regions responsible for hormone production. Dysregulation of adrenocortical cell differentiation alters the proportion and organization of the functional zones of the adrenal cortex leading to disease. Current models of adrenocortical cell differentiation are based on mouse studies, but there are known organizational and functional differences between human and mouse adrenal glands. This study aimed to investigate the centripetal differentiation model in the human adrenal cortex and characterize aldosterone-producing micronodules (APMs) to better understand adrenal diseases such as primary aldosteronism. We applied spatially resolvedin situtranscriptomics to human adrenal tissue sections from two individuals and identified distinct cell populations and their positional relationships. The results supported the centripetal differentiation model in humans, with cells progressing from the outer capsule to the zona glomerulosa, zona fasciculata, and zona reticularis. Additionally, we characterized two APMs in a 72-year-old female. Comparison with earlier APM transcriptomes indicated a subset of core genes, but also heterogeneity between APMs. The findings contribute to our understanding of normal and pathological cellular differentiation in the human adrenal cortex.
TRAIL agonists rescue mice from radiation-induced lung injury
Authors: Strandberg Jillian , Louie Anna , Lee Seulki , Hahn Marina , Srinivasan Praveen , George Andrew , De La Cruz Arielle , Zhang Leiqing , Borrero Liz Hernandez , Huntington Kelsey E. , De La Cruz Payton , Seyhan Attila A. , Koffer Paul P. , Wazer David E. , DiPetrillo Thomas A. , Azzoli Christopher G. , Rounds Sharon I. , Graff Stephanie L. , Abbas Abbas E. , Zhou Lanlan , El-Deiry Wafik S. 
Published: June 2023

AbstractCancer therapy is often limited by toxicity from pneumonitis. This often-lethal side effect is known to be impacted by innate immunity, and in particular the pathways regulated by the TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from the lethal effects of radiation. We found that two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound #10 (TIC10/ONC201), could achieve this goal. Both compounds could completely protect mice from lethality by reducing pneumonitis, alveolar-wall thickness, and oxygen desaturation. At the molecular level, this protection appeared to be due to the inhibition of CCl22, a macrophage-derived chemokine previously associated with radiation pneumonitis and pulmonary fibrosis. The discovery that short-term treatment with TRAIL pathway agonists effectively rescues animals from high doses of radiation exposure has important translational implications.One Sentence SummaryPrevention of lethality, pneumonitis, lung fibrosis and skin dermatitis post-ψ-irradiation by short- term treatment with innate immune TRAIL pathway agonists
Enterovirus D68 capsid formation and stability requires acidic compartments
Authors: Galitska Ganna , Jassey Alagie , Wagner Michael A. , Pollack Noah , Jackson William T. 
Published: June 2023

AbstractEnterovirus D68 (EV-D68), a picornavirus traditionally associated with respiratory infections, has recently been linked to a polio-like paralytic condition known as acute flaccid myelitis (AFM). EV-D68 is understudied, and much of the field’s understanding of this virus is based on studies of poliovirus. For poliovirus, we previously showed that low pH promotes virus capsid maturation, but here we show that, for EV-D68, inhibition of compartment acidification during a specific window of infection causes a defect in capsid formation and maintenance. These phenotypes are accompanied by radical changes in the infected cell, with viral replication organelles clustering in a tight juxtanuclear grouping. Organelle acidification is critical during a narrow window from 3-4hpi, which we have termed the “transition point,” separating translation and peak RNA replication from capsid formation, maturation and egress. Our findings highlight that acidification is crucial only when vesicles convert from RNA factories to virion crucibles.ImportanceThe respiratory picornavirus enterovirus D68 is a causative agent of Acute Flaccid Myelitis, a childhood paralysis disease identified in the last decade. Poliovirus, another picornavirus associated with paralytic disease, is a fecal-oral virus which survives acidic environments when passing from host-to-host. Here we follow up on our previous work showing a requirement for acidic intracellular compartments for maturation cleavage of poliovirus particles. Enterovirus D68 requires acidic vesicles for an earlier step, assembly and maintenance of viral particles themselves. These data have strong implications for the use of acidification blocking treatments to combat enterovirus diseases.
Prevalence and distribution of non-typhoidalSalmonella entericaserogroups and serovars isolated from normally sterile sites: a global systematic review
Authors: Hagedoorn Nienke N. , Murthy Shruti , Birkhold Megan , Marchello Christian S. , Crump John A. 
Published: June 2023

SummaryTo inform vaccine development strategies, we aimed to systematically review evidence on the prevalence and distribution of non-typhoidalSalmonella entericaserogroups and serovars. We searched four databases from inception through 4 June 2021. We included articles that reported at least one non-typhoidalSalmonella entericastrain by serogroup or serovar isolated from a normally sterile site. Of serogrouped isolates, we pooled the prevalence of serogroup O:4, serogroup O:9, and other serogroups using random-effects meta-analyses. Of serotyped isolates, we pooled the prevalence ofSalmonellaTyphimurium (member of serogroup O:4),SalmonellaEnteritidis (member of serogroup O:9), and other serovars. Of 82 studies yielding 24,258 serogrouped isolates, pooled prevalence (95% CI) was 44.7% (36.3%-48.3%) for serogroup O:4, 45.4% (36.9%-49.0%) for serogroup O:9, and 9.9% (6.1%-13.3%) for other serogroups. Pooled prevalence (95%CI) was 36.8% (29.9%-44.0%) forSalmonellaTyphimurium, 37.8% (33.2%-42.4%) forSalmonellaEnteritidis, and 18.4% (11.4%-22.9%) for other serovars. Of global serogrouped non-typhoidalSalmonellaisolates from normally sterile sites, serogroup O:4 and O:9 together accounted for 90%. Of global serotyped isolates, serovars Typhimurium and Enteritidis together accounted for 75%. Vaccine development strategies covering serogroups O:4 and O:9, or serovars Typhimurium and Enteritidis, have the potential to prevent the majority of non-typhoidalSalmonellainvasive disease.PROSPERO:CRD42022376658.Key resultsInvasive infections in normally sterile sites caused by non-typhoidalSalmonellahave a case fatality ratio of 15%.Vaccine products for human non-typhoidalSalmonellaare in currently in development.For future vaccine strategies, we provide global non-typhoidalSalmonellaserogroup and serovar coverage by region and by age groups.Serogroups O:4 and O:9 account for 90% of isolates of non-typhoidalSalmonella entericafrom normally sterile sites.Serovars Typhimurium and Enteritidis, members of serogroup O:4 and O:9, respectively, cover 75% of isolates of non-typhoidalSalmonella entericafrom normally sterile sites.
Modeling soybean growth: A mixed model approach
Authors: Delattre Maud , Toda Yusuke , Tressou Jessica , Iwata Hiroyoshi 
Published: June 2023

AbstractThe evaluation of plant and animal growth, separately for genetic and environmental effects, is necessary for genetic understanding and genetic improvement of environmental responses of plants and animals. We propose to extend an existing approach that combines nonlinear mixed-effects model (NLMEM) and the stochastic approximation of the Expectation-Maximization algorithm (SAEM) to analyze genetic and environmental effects on plant growth. These tools are widely used in many fields but very rarely in plant biology. During model formulation, a nonlinear function describes the shape of growth, and random effects describe genetic and environmental effects and their variability. Genetic relationships among the varieties were also integrated into the model using a genetic relationship matrix. The SAEM algorithm was chosen as an efficient alternative to MCMC methods, which are more commonly used in the domain. It was implemented to infer the expected growth patterns in the analyzed population and the expected curves for each variety through a maximum-likelihood and a maximum-a-posteriori approaches, respectively. The obtained estimates can be used to predict the growth curves for each variety. We illustrate the strengths of the proposed approach using simulated data and soybean plant growth data obtained from a soybean cultivation experiment conducted at the Arid Land Research Center, Tottori University. In this experiment, plant height was measured daily using drones, and the growth was monitored for approximately 200 soybean cultivars for which whole-genome sequence data were available. The NLMEM approach improved our understanding of the determinants of soybean growth and can be successfully used for the genomic prediction of growth pattern characteristics.Author summaryNonlinear models are useful for modeling animal and plant growth; however, their parameters are influenced by both genetic and environmental factors. If the same model can be applied to data with different genetic and environmental factors by allowing parameter variations, it can be used to understand, predict, and control the genetic and environmental influences of growth models based on parameter variation. In this study, we propose a statistical method based on nonlinear mixed-effects modeling. The simulation and real data analysis results show that the proposed method was effective in modeling the growth of genetically different soybean varieties under different drought conditions. The usefulness of the proposed method is expected to increase, as high-throughput measurements provide growth data for a large number of genotypes in various environments.
Novel joint enrichment test demonstrates high performance in simulations and identifies cell-types with enriched expression of inflammatory bowel disease risk loci
Authors: Voda Alexandru-Ioan , Jostins-Dean Luke 
Published: June 2023

AbstractA number of methods have been developed to assess the enrichment of polygenic risk variants – from summary statistics of genome-wide association studies (GWAS) – within specific gene-sets, pathways, or cell-type signatures. The assumptions made by these methods vary, which leads to differences in results and performance across different genetic trait architectures and sample sizes. We devise a novel statistical test that combines independent signals from each of three commonly-used enrichment tests (LDSC, MAGMA & SNPsea) into a single P-value, called the block jackknife GWAS joint enrichment test (GWASJET). Through simulations, we show that this method has comparable or greater power than competing methods across a range of sample sizes and trait architectures. We use our new test in an extensive analysis of the cell-type specific enrichment of genetic risk for inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Counterintuitively, we find stronger enrichments of IBD risk genes in older gene expression data from bulk immune cell-types than in single-cell data from inflamed patient intestinal samples. We demonstrate that GWASJET removes many seemingly-spurious enriched cell-types identified by other methods, and identifies a core set of immune cells that express IBD risk genes, particularly myeloid cells that have been experimentally stimulated. We also demonstrate that many cell-types are differentially enriched for CD compared to UC risk genes, for example gamma-delta T cells show stronger enrichment for CD than UC risk genes.Author summaryGenetic association studies have discovered a number of DNA variations that are associated with heritable human diseases and traits. One method of investigating the functions of these variants is to test whether they are enriched in parts of the genome associated with specific cell-types or cell conditions – defined by gene expression data or other similar data types. However, there are a number of published statistical methods to test such enrichments; these methdos make different assumptions and their results can vary, sometimes dramatically. We present a novel consensus method, called GWASJET, that combines the results of these different methods to produce a single result. We show that GWASJET can outperform individual methods in simulations. We apply this method to gene expression data from a number of tissues and conditions relevant to inflammatory bowel diseases (IBD). Our method removes potentially false results based ona prioribiological knowledge, and reveals that IBD genes are generally clustered in a large number of immune cell-types, especially myeloid cells treated with specific stimulatory molecules.
Pain hypersensitivity is dependent on autophagy protein Beclin 1 in males but not females
Authors: Tam Theresa H. , Zhang Wenbo , Tu YuShan , Hicks Janice L. , Farcas Sophia , Salter Michael W. 
Published: June 2023

ABSTRACTChronic pain is a pervasive health, social, and economic problem affecting 1 in 5 individuals around the world. Increasingly, it is understood that alterations in fundamental cell biological processes are critical for chronic pain. A prominent cellular process is autophagy but whether it plays a role in pain is unknown. To investigate whether autophagy is involved in pain processing and is targetable for pain relief, we focused on Beclin 1, a component of the class III phosphatidylinositol 3-kinase (PI3K) complex necessary for initiating autophagy. Here, we found that inflammatory pain hypersensitivity in male mice lacking one allele ofBecn1is significantly greater than that in wild type mice. By contrast, in female mice, loss ofBecn1did not affect inflammation-induced pain hypersensitivity. Further, intrathecal delivery of an activator of Beclin 1, tat-beclin 1, reversed mechanical hypersensitivity induced by peripheral inflammation or peripheral nerve injury in males. Tat-beclin 1 also prevented mechanical hypersensitivity induced by exogenous brain-derived neurotrophic factor (BDNF), a core mediator of inflammatory and neuropathic pain in the spinal dorsal horn in males. Pain signaling pathways converge on enhancement ofN-methyl-D-aspartate receptors (NMDARs) in spinal dorsal horn neurons. We found that loss of Beclin 1 increases expression of the pain-critical NMDAR subunit, GluN2B, in the dorsal horn and upregulates synaptic NMDAR-mediated currents in dorsal horn neurons from males but not females. From our converging lines of evidence, we conclude that inhibition of Beclin 1 in the dorsal horn is critical in mediating inflammatory and neuropathic pain signaling pathways in males. Our findings provide the basis for sex-specific therapeutic approaches targeting pain with a new class of analgesics - activators of Beclin 1.
Does intellectual capital in Islamic banks outperform conventional banks? Evidence from GCC countries
Authors: Farooque Omar Al , AlObaid Rayed Obaid Hammoud , Khan Ashfaq Ahmad 
Published: June 2023

PurposeThis study explores, first, the performance effect (accounting- and market-based performance) of intellectual capital (IC), measured using the value-added intellectual coefficient (VAIC) and its modified version (MVAIC), on Islamic and conventional listed banks in Gulf Cooperation Council (GCC) countries and, second, whether Islamic banks outperform conventional banks in utilising IC.Design/methodology/approachUsing resource-based view theory and literature reviews, regression analyses are conducted on data for the period 2012–2019 on 26 Islamic and 42 conventional banks. For hypothesis testing, the generalised method of moments panel data regression analysis is applied after addressing endogeneity issues.FindingsResults, after controlling for corporate governance, indicate that the performance effects of IC (VAIC and MVAIC) on both bank types largely converge and Islamic banks do not outperform conventional banks in IC use. IC has a stronger effect on accounting performance measures for conventional banks than for Islamic banks, but IC has some effect on market performance measures for Islamic banks alone. Corporate governance variables do not play a significant role in the presence of VAIC and MVAIC although there are differences in corporate governance between the two bank types.Originality/valueThis study bridges the gap in GCC banking sector literature on the association between IC efficiency and performance measures of Islamic and conventional banks, from a comparative perspective. It enhances understanding, about the IC–financial performance nexus, of policymakers, regulators, bank managers and other stakeholders interested in the influence of different business models, financing/investment methods and governance structure on the performance of both bank types.