bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple lineages of Monkeypox virus detected in the United States, 2021- 2022
Authors: Gigante Crystal M. , Korber Bette , Seabolt Matthew H. , Wilkins Kimberly , Davidson Whitni , Rao Agam K. , Zhao Hui , Hughes Christine M. , Minhaj Faisal , Waltenburg Michelle A. , Theiler James , Smole Sandra , Gallagher Glen R. , Blythe David , Myers Robert , Schulte Joann , Stringer Joey , Lee Philip , Mendoza Rafael M. , Griffin-Thomas LaToya A. , Crain Jenny , Murray Jade , Atkinson Annette , Gonzalez Anthony H. , Nash June , Batra Dhwani , Damon Inger , McQuiston Jennifer , Hutson Christina L. , McCollum Andrea M. , Li Yu 
Published: June 2022

AbstractMonkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of Monkeypox virus (MPXV) among nine 2021 and 2022 U.S. monkeypox cases. A 2021 case was highly similar to the 2022 MPXV outbreak variant, suggesting a common ancestor. Analysis of mutations among these two lineages revealed an extreme preference for GA-to-AA mutations indicative of APOBEC3 cytosine deaminase activity that was shared among West African MPXV since 2017 but absent from Congo Basin lineages. Poxviruses are not thought to be subject to APOBEC3 editing; however, these findings suggest APOBEC3 activity has been recurrent and dominant in recent West African MPXV evolution.
Robustness and reproducibility of simple and complex synthetic logic circuit designs using a DBTL loop
Authors: Cummins Breschine , Vrana Justin , Moseley Robert C. , Eramian Hamed , Deckard Anastasia , Fontanarrosa Pedro , Bryce Daniel , Weston Mark , Zheng George , Nowak Joshua , Motta Francis C. , Eslami Mohammed , Johnson Kara Layne , Goldman Robert P. , Myers Chris J. , Johnson Tessa , Vaughn Matthew W. , Gaffney Niall , Urrutia Joshua , Gopaulakrishnan Shweta , Biggers Vanessa , Higa Trissha R. , Mosqueda Lorraine A. , Gameiro Marcio , Gedeon Tomáš , Mischaikow Konstantin , Beal Jacob , Bartley Bryan , Mitchell Tom , Nguyen Tramy T. , Roehner Nicholas , Haase Steven B. 
Published: June 2022

AbstractComputational tools addressing various components of design-build-test-learn loops (DBTL) for the construction of synthetic genetic networks exist, but do not generally cover the entire DBTL loop. This manuscript introduces an end-to-end sequence of tools that together form a DBTL loop called DART (Design Assemble Round Trip). DART provides rational selection and refinement of genetic parts to construct and test a circuit. Computational support for experimental process, metadata management, standardized data collection, and reproducible data analysis is provided via the previously published Round Trip (RT) test-learn loop. The primary focus of this work is on the Design Assemble (DA) part of the tool chain, which improves on previous techniques by screening up to thousands of network topologies for robust performance using a novel robustness score derived from dynamical behavior based on circuit topology only. In addition, novel experimental support software is introduced for the assembly of genetic circuits. A complete design-through-analysis sequence is presented using several OR and NOR circuit designs, with and without structural redundancy, that are implemented in budding yeast. The execution of DART tested the predictions of the design tools, specifically with regard to robust and reproducible performance under different experimental conditions. The data analysis depended on a novel application of machine learning techniques to segment bimodal flow cytometry distributions. Evidence is presented that, in some cases, a more complex build may impart more robustness and reproducibility across experimental conditions.
LSD1 controls a nuclear checkpoint in Wnt/β-Catenin signaling to regulate muscle stem cell self-renewal
Authors: Mouradian Sandrine , Cicciarello Delia , Lacoste Nicolas , Risson Valérie , Berretta Francesca , Grand Fabien Le , Rose Nicolas , Simonet Thomas , Schaeffer Laurent , Scionti Isabella 
Published: June 2022

AbstractThe Wnt/β-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve profound gene expression and epigenome remodeling and linking Wnt/β-Catenin signaling to chromatin modifications has been a challenge over the past decades. Functional studies of the histone demethylase LSD1/KDM1A converge to indicate that this epigenetic regulator is a key regulator of cell fate, although the extracellular cues controlling LSD1 action remain largely unknown. Here we show that β-Catenin is a substrate of LSD1. Demethylation by LSD1 prevents β-Catenin degradation thereby maintaining its nuclear levels. Consistently, in absence of LSD1, β-Catenin transcriptional activity is reduced in both MuSCs and ESCs. Moreover, inactivation of LSD1 in mouse muscle stem cells and embryonic stem cells shows that LSD1 promotes mitotic spindle orientation via β-Catenin protein stabilization. Altogether, by inscribing LSD1 and β-Catenin in the same molecular cascade linking extracellular factors to gene expression, our results provide a mechanistic explanation to the similarity of action of canonical Wnt/β-Catenin signaling and LSD1 on stem cell fate.
The role of diets in maternal vaccinations against typhoid toxin
Authors: Neupane Durga P. , Ahn Changhwan , Yang Yi-An , Lee Gi Young , Song Jeongmin 
Published: June 2022

AbstractChildren are particularly susceptible to typhoid fever caused by the bacterial pathogenSalmonellaTyphi. Typhoid fever is prevalent in developing countries where diets can be less well-balanced. Here, using a murine model, we investigated the role of the macronutrient composition of the diet in maternal vaccination efficacies of two subunit vaccines targeting typhoid toxin: ToxoidVac and PltBVac. We found that maternal vaccinations protected all offspring against a lethal-dose typhoid toxin challenge in a balanced, normal diet (ND) condition, but the declined protection in a malnourished diet (MD) condition was observed in the PltBVac group. Despite the comparable antibody titers in both MD and ND mothers, MD offspring had a significantly lower level of typhoid toxin neutralizing antibodies than their ND counterparts. We observed a lower expression of the neonatal Fc receptor on the yolk sac of MD mothers than in ND mothers, agreeing with the observed lower antibody titers in MD offspring. Protein supplementation to MD diets, but not fat supplementation, increased FcRn expression and protected all MD offspring from the toxin challenge. Similarly, providing additional typhoid toxin-neutralizing antibodies to MD offspring was sufficient to protect all MD offspring from the toxin challenge. These results emphasize the significance of balanced/normal diets for a more effective maternal vaccination transfer to their offspring.Author summaryTyphoid fever is a life-threatening systemic infectious disease caused bySalmonellaTyphi, which is prevalent in developing countries where diets can be less well-balanced. Here, we used mice to study the role of nutrition in maternal vaccination efficacies of two subunit vaccines targetingSalmonella’s typhoid toxin. We found maternal vaccinations protected all offspring from a lethal-dose typhoid toxin challenge in a balanced/normal diet (ND) condition, but the lack of protection in a malnourished diet (MD) condition was observed in the PltBVac group. Our data indicate that the difference in maternal vaccination outcomes between ND and MD offspring was due to the less effective maternal antibody transfer from MD mothers to their offspring. Providing additional proteins to MD mothers or additional toxin-neutralizing antibodies to MD offspring saved all malnourished offspring from a lethal-dose typhoid toxin challenge, highlighting the importance of balanced/normal diets for effective maternal vaccination outcomes.
Spatial variation in population genomic responses to over a century of anthropogenic change within a tidal marsh songbird
Authors: Benham Phred M. , Walsh Jennifer , Bowie Rauri C. K. 
Published: June 2022

ABSTRACTCombating the current biodiversity crisis requires the accurate documentation of population responses to human-induced ecological change. To this end, museum collections preserve a record of population responses to anthropogenic change that can provide critical baseline data on patterns of genetic diversity, connectivity, and population structure. We leveraged spatially-replicated time series of specimens to document population genomic responses to the destruction of nearly 90% of coastal habitats occupied by the Savannah sparrow (Passerculus sandwichensis) in California. Spatial-temporal analyses of genetic diversity from 219 sparrows collected between 1889-2017 showed that the amount of habitat lost was not predictive of genetic diversity loss. Despite experiencing the greatest levels of habitat loss, we found that genetic diversity in the San Francisco Bay Area remained relatively high. Over the past century, immigration into the Bay Area from interior populations has also increased. This may have minimized genetic diversity declines, but likely led to the erosion of divergence at loci associated with tidal marsh adaptation. Tracing the genomic trajectories of multiple populations over time provided unique insights into how shifting patterns of gene flow through time in response to human-induced habitat loss may contribute to negative fitness consequences.
Mapping Protein Dynamics at High Spatial Resolution with Temperature-Jump X-ray Crystallography
Authors: Wolff Alexander M. , Nango Eriko , Young Iris D. , Brewster Aaron S. , Kubo Minoru , Nomura Takashi , Sugahara Michihiro , Owada Shigeki , Barad Benjamin A. , Ito Kazutaka , Bhowmick Asmit , Carbajo Sergio , Hino Tomoya , Holton James M. , Im Dohyun , O’Riordan Lee J. , Tanaka Tomoyuki , Tanaka Rie , Sierra Raymond G. , Yumoto Fumiaki , Tono Kensuke , Iwata So , Sauter Nicholas K. , Fraser James S. , Thompson Michael C. 
Published: June 2022

SummaryUnderstanding and controlling protein motion at atomic resolution is a hallmark challenge for structural biologists and protein engineers because conformational dynamics are essential for complex functions such as enzyme catalysis and allosteric regulation. Time-resolved crystallography offers a window into protein motions, yet without a universal perturbation to initiate conformational changes the method has been limited in scope. Here we couple a solvent-based temperature jump with time-resolved crystallography to visualize structural motions in lysozyme, a dynamic enzyme. We observed widespread atomic vibrations on the nanosecond timescale, which evolve on the sub-millisecond timescale into localized structural fluctuations that are coupled to the active site. An orthogonal perturbation to the enzyme, inhibitor binding, altered these dynamics by blocking key motions that allow energy to dissipate from vibrations into functional movements linked to the catalytic cycle. Because temperature-jump is a universal method for perturbing molecular motion, the method demonstrated here is broadly applicable for studying protein dynamics.
‘Formation and function of the meninges arachnoid barrier around the developing brain’
Authors: Derk Julia , Como Christina N. , Jones Hannah E. , Joyce Luke R. , Bonney Stephanie , O’Rourke Rebecca , Pawlikowski Brad , Doran Kelly S. , Siegenthaler Julie A. 
Published: June 2022

AbstractBarriers at the level of the brain endothelium, choroid plexus, and meninges strictly regulate movement of molecules and cells into and out of the central nervous system (CNS). In contrast to the blood-brain barrier and choroid plexus epithelial barrier, developmental timing and function of the meningeal arachnoid barrier, a layer of epithelial-like cells connected by tight and adherens junctions, is largely unknown. To begin to address this, we mined our E14.5 mouse single cell transcriptomic (scRNA-seq) meningeal fibroblast data set and identified the repression of Wnt-β-catenin signaling as a key mechanism underlying the specification of epithelial-like arachnoid barrier cells from Collagen 1+ and Crabp2+ mesenchymal meningeal precursors. We show that elevating Wnt-β-catenin signaling in prenatal meningeal mesenchymal cells prevented the development of arachnoid barrier cells. In the absence of dorsal arachnoid barrier cells, the prenatal meninges and brain are penetrable to biocytin-TMR and Streptococcus agalactiae (Group B Streptococcus, GBS), the leading pathogen known to drive life-threatening neonatal meningitis. We show that a layer of Claudin 11 (tight junction) and E-cadherin (adherens junction) expressing arachnoid barrier cells appear around the mouse brain from E13-E15 and the emergence of a functional barrier by E17 coincides with junctional localization of Claudin 11. Postnatal growth of the arachnoid barrier is marked initially by proliferation and later re-organization of junctional domains. This work provides fundamental knowledge on development and prenatal function of a meningeal arachnoid barrier, and novel tools for future studies on regional functions of this CNS barrier in the meninges.
Nanoparticles targeted to fibroblast activation protein outperform PSMA for MRI delineation of primary prostate tumours
Authors: Dmochowska Nicole , Milanova Valentina , Mukkamala Ramesh , Chow Kwok Keung , Pham Nguyen T.H. , Srinivasarao Madduri , Ebert Lisa M. , Stait-Gardner Timothy , Le Hien , Shetty Anil , Nelson Melanie , Low Philip S. , Thierry Benjamin 
Published: June 2022

AbstractAccurate and precise delineation of gross tumour volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumours, such as prostate cancer. Magnetic resonance imaging of tumour molecular targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-LINAC. Fibroblast activation protein (FAP) is a transmembrane protein overexpressed in stromal components of >90% of epithelial carcinomas. Herein we compare targeted MRI of gold standard PSMA with FAP in the delineation of orthotopic tumours in a mouse model of prostate cancer. Control (no ligand), FAP and PSMA-targeting iron oxide nanoparticles were prepared with modification of an MRI agent (FerroTrace). Mice with orthotopic LNCaP tumours underwent T2-weighted 3D MRI 24 hours after intravenous injection of contrast agents. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles, which was most pronounced on the tumour periphery. FAP-targeted MRI increased the proportion of tumour contrast enhancing black pixels by 13.37% when compared to PSMA. Furthermore, analysis of changes in R2 values between healthy prostates and LNCaP tumours indicated an increase in contrast enhancing pixels in the tumour border of 15%, when targeting FAP, in contrast to PSMA This study demonstrates preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.
Lipid transport by Candida albicans Dnf2 is required for hyphal growth and virulence
Authors: Jain Bhawik K. , Wagner Andrew S. , Reynolds Todd B. , Graham Todd R. 
Published: June 2022

AbstractCandida albicans is a common cause of human mucosal yeast infections, and invasive candidiasis can be fatal. Antifungal medications are limited, but those targeting the pathogen cell wall or plasma membrane have been effective. Therefore, virulence factors controlling membrane biogenesis are potential targets for drug development. P4-ATPases contribute to membrane biogenesis by selecting and transporting specific lipids from the extracellular leaflet to the cytoplasmic leaflet of the bilayer to generate lipid asymmetry. A subset of heterodimeric P4-ATPases, including Dnf1-Lem3 and Dnf2-Lem3 from Saccharomyces cerevisiae, transport phosphatidylcholine (PC), phosphatidylethanolamine (PE), and the sphingolipid glucosylceramide (GlcCer). GlcCer is a critical lipid for Candida albicans polarized growth and virulence, but the role of GlcCer transporters in virulence has not been explored. Here we show that the Candida albicans Dnf2 (CaDnf2) requires association with CaLem3 to form a functional transporter and flip fluorescent derivatives of GlcCer, PC and PE across the plasma membrane. Mutation of conserved substrate-selective residues in the membrane domain strongly abrogates GlcCer transport and partially disrupts PC transport by CaDnf2. Candida strains harboring dnf2 null alleles (dnf2ΔΔ) or point mutations that disrupt substrate recognition exhibit defects in the yeast to hyphal growth transition, filamentous growth and virulence in systemically infected mice. The influence of CaDNF1 deletion on the morphological phenotypes is negligible although the dnf1ΔΔ dnf2ΔΔ strain was less virulent than the dnf2ΔΔ strain. These results indicate that the transport of GlcCer and/or PC by plasma membrane P4-ATPases is important for pathogenicity of Candida albicans.
Mettl14-mediated m6A modification ensures the cell cycle progression of late-born retinal progenitor cells
Authors: Li Liang , Sun Yue , Davis Alexander E. , Wu Man-Ru , Lin Cheng-Hui , Ding Jun B. , Wang Sui 
Published: June 2022

AbstractNeural progenitor cells lengthen their cell cycle to prime themselves for differentiation as development proceeds. It is currently not clear how they counter this lengthening and avoid being halted in the cell cycle. Here, we show that m6A (N6-methyladenosine) methylation of cell cycle-related mRNAs ensures the proper cell cycle progression of late-born retinal progenitor cells (RPCs), which are born towards the end of retinogenesis and have long cell cycle durations. Conditional deletion ofMettl14, which is required for depositing m6A on mRNAs, significantly reduced the level of m6A modification in the developing mouse retina. This led to delayed cell cycle exit of late-born RPCs and neuronal cell death in mature retina, but appeared to have no effect on retinal development prior to birth. M6A-seq, which maps m6A modified mRNAs, and single cell transcriptomic analyses revealed that mRNAs involved in slowing down cell cycle progression were highly enriched for m6A modification, which could target them for degradation and guarantee proper cell cycle progression of late-born RPCs. In addition, we identifiedZfp292as a novel target of m6A and potent inhibitor of RPC cell cycle progression. Overall, our work establishes m6A modification as an important mechanism countering cell cycle lengthening in late-born retinal progenitor cells.
Benzidine Induces Proliferation of UMUC3 Bladder Cancer Cells Through Activation of ERK5 Pathway
Authors: Sun Xin , Zhang Tao , Tang Liang , Min Jie , Wang Yi , Yu De-Xin 
Published: June 2022

AbstractMounting evidences have revealed that benzidine, a known human carcinogen, is a pivotal risk factor for bladder cancer (BC). Dysregulated cell proliferation serves as a pivotal pathophysiological step in BC development. The potential mechanisms of MAPK pathways, particularly extracellular regulated protein kinases 5 (ERK5), regarding the modulation of benzidine-elicited cell proliferation are still elusive. Herein, human BC cells UMUC-3 were exposed to indicated levels of benzidine for 5 days. Cell growth, cell cycle progression, cell cycle-related, MAPK genetic expression, and related protein contents were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, flow cytometry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and western blotting (WB), respectively. XMD8-92 (a specific suppressor of ERK5) and small interfering RNA (siRNA) were utilized to identify the roles of ERK5. Our results illustrated that benzidine elevated the proliferative ability of UMUC3 cells and accelerated the cell cycle transition from G1 to S phase, and it increased the expressions of cyclin D1 and proliferating cell nuclear antigen (PCNA) and reduced the expression of p21. Meanwhile, benzidine treatment resulted in the activation of ERK5 pathway and activator protein 1 (AP-1) proteins. In addition, benzidine-elicited cell proliferation and ERK5 stimulation were fully inhibited by XMD8-92 and siRNAs specific to ERK5. Taken together, these results demonstrated that ERK5-mediated cell proliferation was tightly related to benzidine-assoicated BC development, which established the foundation for targeting the ERK5 pathway in BC treatment.
Denaturation resistant P2 tetramer is required to import fatty acids into intraerythrocytic Plasmodium falciparum
Authors: Das Sudipta , Majumder Kaustav , Bhattacharjya Anwesha , Roy Bhaskar 
Published: June 2022

AbstractThe initiation of asymmetric karyokinesis of intraerythrocytic Plasmodium falciparum (Pf) begins without dismantling the nuclear envelope showing the hallmark feature of closed mitosis (1-10). In Pf, karyokinesis precedes cytokinesis and cell body formation (6, 8-10). Regulation at the beginning of nuclear division either through checkpoints or by importing serum components was largely unknown. At the trophozoite stage, PfP2 tetramer trafficked to the infected erythrocyte (IE) surface and the inaccessibility of IE surface PfP2 to its bonafide ligand led to the arrest of nuclear division (11-13). Here we show that PfP2 tetramer localization on the IE surface and the beginning of nuclear division are concomitant in nature. Synthetically induced denaturation resistant PfP2 tetramer interacts with human serum fatty acids and phospholipids for its import into IEs at the beginning of karyokinesis. In the natively folded denaturation resistant PfP2 tetramer cage, the Cys-Cys redox switch regulates the binding and subsequent release of fatty acids on the IE surface. This mechanistic insight of fatty acids import inside IEs using synthetically induced denaturation resistant PfP2 tetramer provides an unique drug screening platform for novel small molecule screening against malaria.
The application of mixed linear models for the estimation of functional effects on bovine stature based on SNP summary statistics from a whole-genome association study
Authors: Kotlarz Krzysztof , Kosinska-Selbi Barbara , Cai Zexi , Sahana Goutam , Szyda Joanna 
Published: June 2022

AbstractGenome-Wide Association Studies (GWAS) help identify polymorphic sites or genes linked to phenotypic variance, but a few identified genes / Single Nucleotide Polymorphisms are unlikely to explain a large part of the phenotypic variability of complex traits. In this study, the focus was moved from single loci to functional units, expressed by the metabolic pathways: Kyoto Encyclopaedia of Genes and Genomes (KEGG). Consequently, this study aimed to estimate KEGG effects on stature in three Nordic dairy cattle breeds using SNPs effects from GWAS as the dependent variable. The SNPs were annotated to genes, then the genes to KEGG pathways. The effects of KEGG were estimated separately for each breed using a mixed linear model incorporating the similarity between pathways expressed by common genes. The KEGG pathway D-amino acid metabolism (map00473) was estimated as significant on stature in two of the analysed breeds and revealed a borderline significance in the third breed. Interestingly, biological evidence exists that described the importance of D-amino acids for growth in experimental organisms as well as in cattle.