bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of long-lasting insecticidal nets onPlasmodium falciparuminfection among women attending antenatal clinic at the Bonassama District Hospital, Littoral Region of Cameroon
Authors: Ajonina Marcelus U. , Ajonina-Ekoti Irene U. , Ngulefac John , Ade Nicholas , Awambeng Derick N. , Nfor Carine K. , Ayim Martin , Apinjoh Tobias O. 
Published: May 2024

AbstractMalaria during pregnancy continues to be a significant cause of morbidity and mortality for both infants and mothers, particularly in sub-Saharan African (SSA) countries, despite increased efforts to control it. The utilization of long-lasting insecticide-treated nets (LLINs) during pregnancy is a well-established strategy to reduce the prevalence of malaria. Nonetheless, inadequate adherence remains a persistent challenge in certain regions with high malaria endemicity. This research aimed to assess the effectiveness of long-lasting insecticidal nets in preventing asymptomatic malaria infections among pregnant women attending antenatal care at the Bonassama District Hospital in the Littoral Region of Cameroon. A hospital-based cross-sectional study was conducted from March to June 2022. Data on sociodemographic characteristics and LLIN usage were collected through a structured questionnaire, while asymptomatic malaria infections were identified using a PfHRP2/pLDH malaria qualitative rapid diagnostic kit. The relationship between categorical variables was analyzed using the chi-square test and logistic regression at a significance level of 5%. Out of the 411 pregnant women included in the study, 156 (35.4%) were diagnosed with malaria. The LLIN utilization rate was 65.1% (287). The risk of malaria infection was 2.7 times higher (AOR = 2.75, 95% CI = 1.83-4.14, p < 0.001) among women who did not consistently use LLINs compared to those who did. The majority (65.1%) of pregnant women always used LLINs, while 34.9% did not consistently use them. Pregnant women aged 20-29 were 3.5 times more likely to use LLINs (AOR = 3.53, 95% CI = 1.61-7.75, p = 0.002) compared to those in the 30-39 and >39 age groups. Furthermore, women practicing Christianity were 1.7 times more likely (AOR = 1.72, 95% CI = 1.01-2.96, p = 0.047) to consistently use LLINs than those of the Islamic faith. Pregnant women in their first trimester (AOR = 3.40, 95% CI = 1.24-4.64, p = 0.010) and second trimester (AOR = 1.90, 95%CI = 0.99 -3.62, p = 0.055) were more likely to sleep under net when compared to those in the third trimester. Among the reasons reported by participants for not frequently using LLINs were heat [55.2% (85)], suffocation [13.6% (21)] and the smell of nets [8.4% (13)]. The use of LLIN was moderately high among the participants in this study, though still below national target. Age group, occupation, religion and gestation period were the major factors determining the use of LLINs. Considering the proven effectiveness of LLINs in reducing malaria morbidity and mortality, it is imperative for the National Malaria Control Programme (NMCP) to remain focused in promoting both LLIN ownership and utilization to achieve the national target of 100% and 80%, respectively.
Function and interactions of a protein bridge between the inner membrane complex and subpellicular microtubules inToxoplasma gondii
Authors: Cheng Emily S. , Moon Andy S. , Barshop William D. , Wohlschlegel James A. , Bradley Peter J. 
Published: May 2024

AbstractToxoplasma gondiiis an obligate intracellular parasite that utilizes peripheral membrane and cytoskeletal structures for critical functions such as host cell invasion, replication, and maintaining cellular morphology. These structures include the inner membrane complex (IMC) as well as the underlying longitudinal subpellicular microtubules (SPMTs) that provide support for the IMC and give the parasite its distinctive crescent shape. While the IMC and SPMTs have been studied on their own, the mechanisms linking these adjacent structures remain largely unknown. This study identifies aT. gondiiprotein named IMT1 that localizes to the maternal IMC and SPMTs and thus appears to tether the IMC to the microtubules. We disrupt the IMT1 gene to assess function and then use deletion analyses and mutagenesis to reveal regions of the protein that are necessary for binding to the IMC cytoskeleton or SPMTs. Using proximity labelling with IMT1 as bait, we identify a series of candidate interactors in the IMC or SPMTs. Exploration of two of these candidates reveals that IMT1 regulates the levels of the microtubule associated protein TLAP2 and binds directly to the cytoskeletal IMC protein IMC1. Taken together, these interactions unveil the specific interactions linking two key cytoskeletal structures of the parasite and provides new insight into the organization of the structural backbone ofT. gondii.
Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome
Authors: Byrne Shane R , DeMott Michael S , Yuan Yifeng , Ghanegolmohammadi Farzan , Kaiser Stefanie , Fox James G. , Alm Eric J. , Dedon Peter C 
Published: May 2024

AbstractBackgroundEpigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically-reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed bydndandsspgene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications.ResultsExploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5-10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m6dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor’s Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Firmicutes, Actinobacteria, and Proteobacteria, which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies.ConclusionsThe results of our studies provide a benchmark for understanding the behavior of an abundant and chemically-reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.
Impact of variants and vaccination on nasal immunity across three waves of SARS-CoV-2
Authors: Long Jaclyn M. , Miao Vincent N. , Owings Anna H. , Tang Ying , Bromley Joshua D. , Kazer Samuel W. , Kimler Kyle , Asare Chelsea , Ziegler Carly G. K. , Ibrahim Samira , Jivanjee Tasneem , George Micayla , Navia Andrew W. , Drake Riley S. , Parker Adam , Billingsley Benjamin C. , Dotherow Paul , Tarugu Spurthi , Kota Sai K. , Laird Hannah , Wichman T. Grant , Davis Yesenia T. , Dhaliwal Neha S. , Pride Yilianys , Guo Yanglin , Senitko Michal , Harvey Jessie , Bates John T. , Diamond Gill , Garrett Michael R. , Robinson D. Ashley , Frame I.J. , Lyons Jonathan J. , Robinson Tanya O. , Shalek Alex K. , Horwitz Bruce H. , Glover Sarah C. , Ordovas-Montanes Jose 
Published: May 2024

AbstractSARS-CoV-2 infection and COVID-19 disease vary with respect to viral variant and host vaccination status. However, how vaccines, emergent variants, and their intersection shift host responses in the human nasal mucosa remains uncharacterized. We and others have shown during the first SARS-CoV-2 wave that a muted nasal epithelial interferon response at the site of infection underlies severe COVID-19. We sought to further understand how upper airway cell subsets and states associate with COVID-19 phenotypes across viral variants and vaccination. Here, we integrated new single-cell RNA-sequencing (scRNA-seq) data from nasopharyngeal swabs collected from 67 adult participants during the Delta and Omicron waves with data from 45 participants collected during the original (Ancestral) wave in our prior study. By characterizing detailed cellular states during infection, we identified changes in epithelial and immune cells that are both unique and shared across variants and vaccination status. By defining SARS-CoV-2 RNA+ cells for each variant, we found that Delta samples had a marked increase in the abundance of viral RNA+ cells. Despite this dramatic increase in viral RNA+ cells in Delta cases, the nasal cellular compositions of Delta and Omicron exhibit greater similarity, driven partly by myeloid subsets, than the Ancestral landscapes associated with specialized epithelial subsets. We found that vaccination prior to infection was surprisingly associated with nasal macrophage recruitment and activation rather than adaptive immune cell signatures. While patients with severe disease caused by Ancestral or Delta variants had muted interferon responses, Omicron-infected patients had equivalent interferon responses regardless of disease severity. Our study defines the evolution of cellular targets and signatures of disease severity in the upper respiratory tract across SARS-CoV-2 variants, and suggests that intramuscular vaccines shape myeloid responses in the nasal mucosa upon SARS-CoV-2 infection.
Cardiolipin remodeling maintains the inner mitochondrial membrane in cells with saturated lipidomes
Authors: Venkatraman Kailash , Budin Itay 
Published: May 2024

AbstractCardiolipin (CL) is a unique, four-chain phospholipid synthesized in the inner mitochondrial membrane (IMM). The acyl chain composition of CL is regulated through a remodeling pathway, whose loss causes mitochondrial dysfunction in Barth syndrome. Yeast has been used extensively as a model system to characterize CL metabolism, but mutants lacking its two remodeling enzymes, Cld1p and Taz1p, have not recapitulated the structural and respiratory phenotypes observed in other systems. Here we show the essential role of CL remodeling in the structure and function of the IMM in yeast grown under reduced oxygenation. Microaerobic fermentation, which mimics natural yeast environments, caused the accumulation of saturated fatty acids and, under these conditions, remodeling mutants showed a loss of IMM ultrastructure. We extended this observation to HEK293 cells, where iPLA2inhibition by bromoenol lactone resulted in respiratory dysfunction and cristae loss upon mild treatment with exogenous saturated fatty acids. In microaerobic yeast, remodeling mutants accumulated unremodeled, saturated CL, but also displayed reduced total CL levels, highlighting the interplay between saturation and CL biosynthesis and breakdown. We identified the mitochondrial phospholipase A1Ddl1p as a regulator of CL levels, and those of its precursors phosphatidylglycerol and phosphatidic acid, under these conditions. Loss ofDDL1partially rescued IMM structure in cells unable to initiate CL remodeling and had differing lipidomic effects depending on oxygenation. These results introduce a revised yeast model for investigating CL remodeling and suggest that its structural functions are dependent on the overall lipid environment in the mitochondrion.
Fragmentation of genomic DNA using Covaris g-Tubes prior to library preparation for sequencing
Authors: Crang Nick , Contreras-López Orlando 
Published: May 2024

AbstractCovaris g-TUBEs can be used to fragment DNA to pre-determined sizes based on the relative centrifugal force that they are run at. They are recommended for use while preparing Oxford Nanopore Technology libraries by the manufacturer. However, the volumes and DNA concentration typically used for ONT libraries are outside the range of the example data provided by Covaris. Here, we ran g-TUBEs at three different relative centrifugal forces and determined the effect on DNA fragmentation in the range 0.5 - 4 µg. This dataset can be used to inform the effective fragmentation of DNA for creating Oxford Nanopore libraries of an optimal size.
Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia
Authors: Galvão Isabella C. , Lemoine Manuela , Messias Lauana A. , Araújo Patrícia A.O.R.A. , Geraldis Jaqueline C. , Yasuda Clarissa L. , Alvim Marina K. M. , Ghizoni Enrico , Tedeschi Helder , Cendes Fernando , Rogerio Fabio , Lopes-Cendes Iscia , Veiga Diogo F. T. 
Published: May 2024

ABSTRACTFocal Cortical Dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-cell profiling to map the chromatin accessibility and transcriptome landscapes of FCD type II, generating a comprehensive multimodal single-cell dataset comprising 61,525 cells from 11 clinical samples of lesions and controls. Our findings revealed profound chromatin, transcriptomic, and cellular alterations affecting neuronal and glial cells in FCD lesions, including the selective loss of upper-layer excitatory neurons, significant expansion of oligodendrocytes and immature astrocytic populations, and a unique neuronal subpopulation harboring dysmorphic neurons. Furthermore, we uncovered activated microglia subsets, particularly in FCD IIb cases. This comprehensive study unveils neuronal and glial cell states driving FCD development and epileptogenicity, enhancing our understanding of FCD and offering new directions for targeted therapy development.
Structural and functional analysis of the Nipah virus polymerase complex
Authors: Hu Side , Kim Heesu , Yang Pan , Yu Zishuo , Ludeke Barbara , Mobilia Shawna , Pan Junhua , Stratton Margaret , Bian Yuemin , Fearns Rachel , Abraham Jonathan 
Published: May 2024

AbstractNipah virus (NiV) is a bat-borne, zoonotic RNA virus that is among the most pathogenic viruses known to humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a drug target. However, NiV polymerase structures were previously unavailable. We determined the cryo-EM structure of the NiV polymerase complex, comprising the large protein (L) and its associated co-factor (P), and performed structural, biophysical, and functional analyses of the NiV polymerase. The complex assembles with a long P tetrameric coiled-coil that is capped by a bundle of ⍺-helices that we show are likely dynamic in solution. Highly conserved zinc-binding modules in the capping domain and a large insert in the RdRp palm domain that is short or absent in most other non-segmented negative strand RNA viruses are critical for replication and transcription. Our findings have the potential to aid in the rational development of drugs to combat NiV infection.
Maintenance of haematopoietic stem cells by JAK inhibition and increased tyrosine-unphosphorylated STAT5
Authors: Williams Matthew J , Wang Xiaonan , Bastos Hugo P , Grondys-Kotarba Gabriela , Johnson Carys , Mende Nicole , Calderbank Emily F , Wantoch Michelle , Park Hyun Jung , Wu Qin , Jin Shucheng , Mantica Giovanna , Hannah Rebecca , Wilson Nicola K , Pask Dean C , Hamilton Tina L , Kinston Sarah J , Asby Ryan , Sneade Rachel , Baxter Joanna , Campbell Peter , Vassiliou George S , Laurenti Elisa , Li Juan , Göttgens Berthold , Green Anthony R 
Published: May 2024

AbstractNormal and malignant hematopoietic stem cells (HSCs) are controlled by extracellular cues including cytokine signalling through the JAK/STAT pathway. Here, we show that STAT5-deficient HSCs exhibit an unusual phenotype: while reduced multi-lineage repopulation and reduced self-renewal are commonly associated with overproliferation and exhaustion, they are instead associated with reduced cell-cycle progression and increased differentiation in STAT5-deficient HSCs. Mechanistic studies show that unphosphorylated-STAT5 (uSTAT5) contributes to this phenotype by constraining HSC differentiation, promoting HSC maintenance and upregulating transcriptional programs associated with stemness. The JAK1/2 inhibitor ruxolitinib increases levels of uSTAT5, constrains differentiation and proliferation of murine HSCs, promotes their maintenance and upregulates transcriptional programs associated with stemness. Ruxolitinib also enhances clonogenicity of normal human HSPCs, CALR-mutant murine HSCs and HSPCs from patients with myelofibrosis. Our results therefore reveal a previously unrecognized role for uSTAT5 in controlling HSC function, highlight JAK inhibition as a strategy for enhancing HSC function and provide insights into the failure of JAK inhibitors to eradicate myeloproliferative neoplasms.
Dissecting the ocular impact of SARS-CoV-2 variants: Analysis of eye globe and retina in animal models
Authors: da Silva José Igor Gomes , Kersten Victor , Munhóz Dati Livia M. , Lins Bruna B. , Tozzeto-Mendoza Tania R. , Rodrigues Daniela del R. F. , Barbosa Rodrigo J. V. , Lima Silvia H. , Villas Boas Lucy S. , da Silva Alexandre dos Santos , Chaim Khallil T. , Mendes-Corrêa Maria Cássia , Russo Momtchilo , Mirotti Luciana , Pinto Marcelo A. , Martins Rodrigo A. P. 
Published: May 2024

AbstractNeurological and ocular manifestations were reported in COVID-19 patients and in SARS-CoV-2 infected animal models. However, the effects of SARS-CoV-2 variants of concern (VoC) on the eyes and the retina remain unclear. Here, we investigate the cellular and molecular consequences of SARS-CoV-2 VoC infection on the eye and retina in mice and hamsters. Infection with the ancestral SARS-CoV-2 and the Gamma VoC induced a subtle increase in the eye volume of K18-hAce2 mice, but no morphological alteration was observed in hamsters’ eyes. Evaluation of the ocular tropism revealed that distinct SARS-CoV-2 VoC reached the eye globe, but not the retina of K18-hAce2 mice. In contrast, SARS-CoV-2 variants are detected in the hamsters’ retina during both acute infection and after disease recovery. Despite the presence of viral RNA, no inflammation was observed in the hamster retina, as evidenced by unchanged microglial cell density and unaltered gene expression of several immune mediators. Altogether, these findings indicate a limited impact of SARS-CoV-2 variants on the eye and retina.
Clubroot disease in soil: An examination of its occurrence in chemical and organic environments
Authors: Islam Zakirul , Tran Quoc Thinh , Kubo Motoki 
Published: May 2024

AbstractClubroot is a disease in cruciferous plants caused by the soil-borne pathogenPlasmodiophora brassicae. This pathogen rapidly spreads in soil, and plant growth is inhibited by infection with spores. In this study, the development of clubroot disease inBrassica rapavar. perviridis was investigated in different soil environments (chemical and organic soils). The bacterial biomass and diversity of the soil and roots were also analyzed in both chemical and organic soils. Bacterial biomass and diversity in the organic soil were higher than those in the chemical soil. The disease severity of plants cultivated in organic soil was lower than that in chemical soil. The number of endophytic bacteria in the roots decreased when the plants were infected withP. brassicaein both soil types. Higher bacterial biomass in the soils and roots appeared to reduce the infection ofP. brassicae.ImportancClubroot is a major disease of cruciferous plants caused by soil borne pathogenPlasmodiophora brassica.Pesticides are applied in the soil during cultivation for the inhibition of clubroot disease, which demise soil microbiome. Therefore, eco-friendly control methods are required for sustainable cultivation. Soil management is an important strategy to inhibit clubroot disease severity. In this study, the occurrence of clubroot disease inB.rapawere compared in two distinct soil environments (chemical and organic). Results show infection rate increased with the increase of spore number for both chemical and organic soil environments. However, the diseases severity was lower in plants cultivated in organic soil. The higher endophytic bacterial biomass and diversity seems to be linked for the disease inhibition in organic plants. These findings suggest a sustainable soil management process to reduce clubroot disease prevalence. Application of organic fertilizers in commented soils could substantially reduce clubroot disease severity in the plants.
The Cell Division Protein FzlA Performs a Conserved Function in Diverse Alphaproteobacteria
Authors: Payne Isaac P. , Aubry Brody , Barrows Jordan M. , Brown Pamela J.B. , Goley Erin D. 
Published: May 2024

AbstractIn almost all bacteria, the tubulin-like GTPase FtsZ polymerizes to form a “Z-ring” that marks the site of division. FtsZ recruits other proteins, collectively known as the divisome, that together remodel and constrict the envelope. Constriction is driven by peptidoglycan (PG) cell wall synthesis by the glycosyltransferase FtsW and the transpeptidase FtsI (FtsWI), but these enzymes require activation to function. How recruitment of FtsZ to the division site leads to FtsWI activation and constriction remains largely unknown. Previous work in our laboratory demonstrated that an FtsZ-binding protein, FzlA, is essential for activation of FtsWI in the alphaproteobacteriumCaulobacter crescentus. Additionally, we found that FzlA also binds to a DNA translocase called FtsK, suggesting that it may link constriction activation to chromosome segregation. FzlA is conserved throughout alphaproteobacteria but has only been examined in detail inC. crescentus. Here, we explored whether FzlA function is conserved in diverse alphaproteobacteria. We assessed FzlA homologs fromRickettsia parkeriandAgrobacterium tumefaciens, and found that, similar toC. crescentusFzlA, they bind directly to FtsZ and localize to midcell. The FtsZ-FzlA interaction interface is conserved, as we demonstrated that FzlA from each of the three species examined can bind to FtsZ from any of the threein vitro. Additionally, we determined thatA. tumefaciensFzlA can fulfill the essential function of FzlA when produced inC. crescentus, indicating conservation of function. These results suggest that FzlA serves as an important regulator that coordinates chromosome segregation with envelope constriction across diverse alphaproteobacteria.ImportanceCell division is essential for bacterial replication and must be highly regulated to ensure robust remodeling of the cell wall in coordination with segregation of the genome to daughter cells. InCaulobacter crescentus, FzlA plays a major role in regulating this process by activating cell wall synthesis in a manner that couples constriction to chromosome segregation. FzlA is broadly conserved in alphaproteobacteria suggesting it plays a similar function across this class of bacteria. Here we have shown that, indeed, FzlA biochemical interactions and function are conserved in diverse alphaproteobacteria. Because FzlA is conserved in alphaproteobacterial human pathogens, understanding this protein and its interactome could present therapeutic benefits by identifying potential antibiotic targets to treat infections.