bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between clonal hematopoiesis driver mutations, immune cell function and the vasculometabolic complications of obesity
Authors: Tercan Helin , Cossins Benjamin , van Deuren Rosanne , Rutten Joost H.W. , Joosten Prof. Leo A.B. , Netea Prof. Mihai G. , Hoischen Alexander , Bekkering Siroon , Riksen Prof. Niels P. 
Published: July 2023

AbstractBackgroundObesity is accompanied by dysregulated inflammation, which can contribute to vasculometabolic complications, including metabolic syndrome and atherosclerosis. Recently, clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a risk factor for cardiovascular diseases. We aimed to determine how CHIP related to immune cell function, systemic inflammation, and vasculometabolic complications in obese individuals.Methods297 individuals with overweight and obesity, between the ages of 54 and 81, were recruited in a cross-sectional study. Clonal Hematopoiesis Driver Mutations (CHDMs) were identified with an ultrasensitive targeted assay. Assesment of carotid artery atherosclerosis was performed with ultrasound. Detailed immunological parameters were studied. Adipose tissue inflammation was determined in subcutenous fat biopsies.ResultsIndividuals with CHIP had higher concentrations of circulating IL-6. Total number of leukocytes and neutrophils were higher in individuals with CHIP. In contrast,ex vivocytokine production capacity of PBMCs was significantly lower in individuals with CHIP. Sex stratified analysis showed that men with CHDMs had significantly higher leukocyte and neutrophil counts andex vivocytokine production capacity was lower in women with CHDMs. Surprisingly, the presence of atherosclerotic plaques was significantly lower in individuals with CHDMs. There was no relation between CHIP and metabolic syndrome.ConclusionIn individuals with overweight or obesity, CHDMs are not associated with vasculometabolic complications, but rather with a lower presence of carotid plaques. CHDMs associate with increased circulating inflammatory markers and leukocyte numbers, but a lower PBMC cytokine production capacity.
Balloon guide catheter versus different sizes of non-balloon guide catheter; a MR CLEAN Registry analysis
Authors: Knapen Robrecht R.M.M. , Goldhoorn Robert-Jan B. , Hofmeijer Jeannette , Lycklamaà Nijeholt Geert J. , van den Berg René , van den Wijngaard Ido R. , van Oostenbrugge Robert J. , van Zwam Wim H. , van der Leij Christiaan 
Published: July 2023

AbstractIntroductionBalloon guide catheters (BGC) are used to prevent distal emboli during endovascular treatment (EVT) for acute ischemic stroke. Although literature reports benefit of BGC, these are not universally used and randomized head-to-head comparisons are lacking. This study compared functional, safety, and technical outcomes between patients treated with different sizes non-BGC and with BGC during EVT in a nationwide prospective multicenter registry.MethodsPatients from the MR CLEAN Registry (2014–2018), who underwent EVT with a 5-7French (Fr) non-BGC, a 8-9Fr non-BGC, or a 8-9Fr BGC were included. Primary outcome was the modified Rankin Scale (mRS) score at 90 days, secondary outcomes included procedure time and first-attempt successful reperfusion (eTICI ≥ 2C). Treatment-effect modification and subgroups were analyzed according to first-line thrombectomy technique: stent retriever (SR) or direct aspiration (ASP).ResultsIn total 2808 patients were included, and 1671 (60%) were treated with 8-9Fr BGC. Overall, no significant differences in clinical outcome were seen between non-BGC and BGC groups. The 8-9Fr non-BGC was associated with lower first-attempt successful revascularization rates compared to BGC (aOR:0.76, 95%CI:0.59-0.998), the 5-7 Fr non-BCG was not. Regression analysis showed a significant interaction between BGC use and device type. In the subgroup with SR as first-line technique, 90 day mRS scores were significantly higher in the 8-9Fr non-BGC group compared with BCG (acOR:0.77; 95%CI:0.59-0.996), but not in the 5-7Fr non-BCG. Direct aspiration combined with 5-7Fr non-BGC resulted in higher first-attempt rates compared to BGC (aOR:1.75; 95%CI:1.16-2.63).ConclusionThis large prospective multicenter registry showed no differences in clinical outcome between patients treated with 5-7Fr non-BGC, 8-9Fr non-BGC, and 8-9Fr BGC. Subgroup analyses, however, suggest that BCG outperforms the non-BGC when SR is used as first-line technique.
Plasma Oxylipin Profiling by High Resolution Mass Spectrometry Reveal Signatures of Inflammation and Hypermetabolism in Amyotrophic Lateral Sclerosis
Authors: Chaves-Filho Adriano B. , Diniz Larissa S. , Santos Rosangela S. , Lima Rodrigo S. , Oreliana Hector , Pinto Isabella F.D. , Dantas Lucas S. , Inague Alex , Faria Rodrigo L. , Medeiros Marisa H.G. , Glezer Isaías , Festuccia William T. , Yoshinaga Marcos Y. , Miyamoto Sayuri 
Published: July 2023

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized not only by progressive loss of motor neurons, but also linked to systemic hypermetabolism, oxidative stress, and inflammation. In this context, oxylipins have been investigated as signaling molecules linked to neurodegeneration. However, the nature and role of major oxylipins involved in ALS disease progression remain unclear. Importantly, most methods focused on oxylipin analysis are based on low resolution mass spectrometry (LRMS), which usually confers high sensitivity, but not great accuracy for lipid identification, as provided by high-resolution MS (HRMS). Here, we established an ultra-high performance liquid chromatography coupled HRMS (LC-HRMS) method for simultaneous analysis of 126 oxylipins in plasma, including lipid hydroxides, ketones, epoxides, prostaglandins, leukotrienes, and others in a 15-minute run. Intra- and inter-day method validation showed high sensitivity (0.3 – 25 pg), accuracy and precision for more than 90 % of quality controls. This method was applied for the analysis of oxylipins in plasma of ALS rats overexpressing the mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A) at asymptomatic (ALS 70 days old) and symptomatic stages (ALS 120 days old), and their respective age-matched wild type controls (WT 70 days old and WT 120 days old). From the 56 oxylipins identified in plasma, 17 species were significantly altered. Remarkably, most of oxylipins linked to inflammation and oxidative stress derived from arachidonic acid, such as, prostaglandins, lipoxins, mono-hydroxides, and isoprostane, were increased in ALS 120d rats. In contrast, the linoleic acid diols involved in fatty acid uptake and β-oxidation, 9(10)-DiHOME and 12(13)-DiHOME, were strongly decreased in the ALS 120d. In summary, we developed and validated a high-throughput LC-HRMS method for oxylipin analysis and provided a comprehensive overview of plasma oxylipins involved in ALS disease progression. Noteworthy, the oxylipins altered in plasma of ALS 120d rats have potential to be investigated and used as biomarkers for inflammation and hypermetabolism in ALS.GRAPHICAL ABSTRACT
DeepNeuropePred: a robust and universal tool to predict cleavage sites from neuropeptide precursors by protein language model
Authors: Wang Lei , Zeng Zilu , Xue Zhidong , Wang Yan 
Published: July 2023

AbstractNeuropeptides play critical roles in many biological processes such as growth, learning, memory, metabolism, and neuronal differentiation. A few approaches have been reported for predicting neuropeptides that are cleaved from precursor protein sequences. However, these models for cleavage site prediction of precursors were developed using a limited number of neuropeptide precursor datasets and simple precursors representation models. In addition, a universal method for predicting neuropeptide cleavage sites that can be applied to all species is still lacking. In this paper, we proposed a novel deep learning method called DeepNeuropePred, using a combination of pretrained language model and Convolutional Neural Networks for feature extraction and predicting the neuropeptide cleavage sites from precursors. To demonstrate the model’s effectiveness and robustness, we evaluated the performance of DeepNeuropePred and four models from the NeuroPred server in the independent dataset and our model achieved the highest AUC score (0.916), which are 6.9%, 7.8%, 8.8%, and 10.9% higher than Mammalian (0.857), insects (0.850), Mollusc (0.842) and Motif (0.826), respectively. For the convenience of researchers, we provide an easy-to-install GitHub package (https://github.com/ISYSLAB-HUST/DeepNeuropePred) and a web server (http://isyslab.info/NeuroPepV2/deepNeuropePred.jsp).Key PointsDeepNeuropePred uses a deep learning algorithm based on protein language model to accurately predict neuropeptide cleavage sites from neuropeptide precursors.Independent test experiments show that DeepNeuropePred achieves significantly better performance than existing methods.DeepNeuropePred could capture meaningful patterns between neuro-peptide and non-neuropeptide cleavage sites.We further provide an easy-to-install GitHub package and a web server.
Colonization during a key developmental window reveals microbiota-dependent shifts in growth and immunity during undernutrition
Authors: Serrano Matos Yadeliz A. , Cano Jasmine , Shafiq Hamna , Williams Claire , Sunny Julee , Cowardin Carrie A. 
Published: July 2023

SummaryChildhood undernutrition is a major global health challenge with devastating lifelong consequences. Linear growth stunting due to undernutrition has been linked to poor outcomes, and mothers who experience stunting are more likely to give birth to stunted children. Murine models that capture the intergenerational and multifactorial nature of undernutrition are critical to understanding the underlying biology of this disorder. Here we report a gnotobiotic mouse model of undernutrition using microbiota from human infants with healthy or stunted growth trajectories. Intergenerational transmission of microbiota from parents to offspring leads to the development of growth and immune features of undernutrition and enteropathy, including reduced linear growth, intestinal villus blunting and accumulation of intraepithelial lymphocytes. In contrast, colonization after weaning reduces sensitivity to detect changes driven by distinct microbial communities. Overall, these results suggest intergenerational colonization is a useful approach with which to investigate microbiota-dependent growth and immunity in early life.
First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer
Authors: Purves Kevin , Brown Hannah , Haverty Ruth , Ryan Andrew , Griffin Laura L. , McCormack Janet , O’Reilly Sophie , Mallon Patrick W. , Gautier Virginie , Cassidy Joseph P. , Fabre Aurelie , Carr Michael J. , Gonzalez Gabriel , Ciuti Simone , Fletcher Nicola F. 
Published: July 2023

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects wildlife. Recent studies highlighted that variants of concern (VOC) may expand into novel animal reservoirs with the potential for reverse zoonosis. North American white-tailed deer are the only deer species in which SARS-CoV-2 has been documented, raising the question whether further reservoir species exist as new VOC emerge. Here, we report the first cases of deer SARS-CoV-2 seropositivity in Eurasia, in a city population of fallow deer in Dublin, Ireland. Deer were seronegative in 2020 (circulating variant in humans: Alpha), one animal was seropositive in 2021 (Delta variant), and 57% of animals tested in 2022 were seropositive (Omicron variant). Ex vivo, a clinical isolate of Omicron BA.1 infected fallow deer precision cut lung slice type-2 pneumocytes, also a major target of infection in human lungs. Our findings suggest a change in host tropism as new variants emerged in the human reservoir, highlighting the importance of continued wildlife disease monitoring and limiting human-wildlife contacts.Teaser:This study is the first report of SARS-CoV-2 seropositivity in fallow deer, highlighting expansion of viral variants into new host reservoirs.
Complex Sphingolipid Profiling and Identification of an Inositol Phosphorylceramide Synthase inDictyostelium discoideum
Authors: Listian Stevanus A. , Kol Matthijs , Ufelmann Edwin , Eising Sebastian , Fröhlich Florian , Walter Stefan , Holthuis Joost C. M. , Barisch Caroline 
Published: July 2023

AbstractDictyostelium discoideumis a professional phagocyte frequently used as experimental model to study cellular processes underlying the recognition, engulfment and infection course of microbial pathogens. Sphingolipids are abundant components of the plasma membrane that bind cholesterol, control vital membrane properties, participate in signal transmission and serve as adhesion molecules in recognition processes relevant to immunity and infection. While the pathway of sphingolipid biosynthesis has been well characterized in plants, animals and fungi, the identity of sphingolipids produced inD. discoideum, an organism at the crossroads between uni- and multicellular life, is not known. Combining lipidomics with a bioinformatics-based cloning strategy for key sphingolipid biosynthetic enzymes, we show here thatD. discoideumproduces phosphoinositol-containing sphingolipids with predominantly phytoceramide backbones. Cell-free expression of candidate inositol-phosphorylceramide (IPC) synthases fromD. discoideumin defined lipid environments enabled identification of an enzyme that selectively catalyses the transfer of phosphoinositol from phosphatidylinositol onto ceramide. The corresponding IPC synthase,DdIPCS1, is non-homologous to but shares multiple sequence motifs with yeast IPC and human sphingomyelin synthases and localizes to the Golgi apparatus as well as the contractile vacuole ofD. discoideum. Collectively, these findings open up important opportunities for exploring a role of sphingolipids in phagocytosis and infection across major evolutionary boundaries.
Nuclear Localization of Argonaute is affected by Cell Density and May Relieve Repression by microRNAs
Authors: Johnson Krystal C. , Kilikevicius Audrius , Hofman Cristina , Hu Jiaxin , Liu Yang , Aguilar Selina , Graswich Jon , Han Yi , Wang Tao , Westcott Jill M. , Brekken Rolf A. , Peng Lan , Karagkounis Georgios , Corey David R. 
Published: July 2023

ABSTRACTArgonaute protein is associated with post-transcriptional control of cytoplasmic gene expression through miRNA-induced silencing complexes (miRISC). Specific cellular and environmental conditions can trigger AGO protein to accumulate in the nucleus. Localization of AGO is central to understanding miRNA action, yet the consequences of AGO being in the nucleus are undefined. We show nuclear enrichment of AGO2 in HCT116 cells grown in two-dimensional culture to high density, HCT116 cells grown in three-dimensional tumor spheroid culture, and human colon tumors. The shift in localization of AGO2 from cytoplasm to nucleus de-represses cytoplasmic AGO2-eCLIP targets that were candidates for canonical regulation by miRISC. Constitutive nuclear localization of AGO2 using an engineered nuclear localization signal increases cell migration. Critical RNAi factors also affect the localization of AGO2. Knocking out an enzyme essential for miRNA biogenesis, DROSHA, depletes mature miRNAs and restricts AGO2 localization to the cytoplasm, while knocking out the miRISC scaffolding protein, TNRC6, results in nuclear localization of AGO2. These data suggest that AGO2 localization and miRNA activity can be regulated depending on environmental conditions, expression of mature miRNAs, and expression of miRISC cofactors. Localization and expression of core miRISC protein machinery should be considered when investigating the roles of miRNAs.
The global communication architecture of the human brain transcends the subcortical - cortical - cerebellar subdivisions
Authors: Schulte Julian , Senden Mario , Deco Gustavo , Kobeleva Xenia , Zamora-López Gorka 
Published: July 2023

ABSTRACTThe white matter is made of anatomical fibres that constitute the highway of long-range connections between different parts of the brain. This network is referred to as the brain’s structural connectivity and lays the foundation of network interaction between brain areas. When analysing the architectural principles of this global network most studies have mainly focused on cortico-cortical and partly on cortico-subcortical connections. Here we show, for the first time, how the integrated cortical, subcortical, and cerebellar brain areas shape the structural architecture of the whole brain. We find that dense clusters vertically transverse cortical, subcortical, and cerebellar brain areas, which are themselves centralised by a global rich-club consisting similarly of cortical and subcortical brain areas. Notably, the most prominent hubs can be found in subcortical brain regions, and their targeted in-silico lesions proved to be most harmful for global signal propagation. Individually, the cortical, subcortical, and cerebellar sub-networks manifest distinct network features despite some similarities, which underline their unique structural fingerprints. Our results, exposing the heterogeneity of internal organisation across cortex, subcortex, and cerebellum, and the crucial role of the subcortex for the integration of the global anatomical pathways, highlight the need to overcome the prevalent cortex-centric focus towards a global consideration of the structural connectivity.
Ablation ofOCT4function in cattle embryos by double electroporation of CRISPR-Cas for DNA and RNA targeting (CRISPR-DART)
Authors: Nix Jada L. , Schettini Gustavo P. , Speckhart Savannah L. , Ealy Alan D. , Biase Fernando H. 
Published: July 2023

AbstractCRISPR-Cas ribonucleoproteins are important tools for gene editing in pre-implantation embryos. However, the inefficient production of biallelic deletions in cattle zygotes has hindered mechanistic studies of gene function. In addition, the presence of maternal RNAs that support embryo development until embryonic genome activation may cause confounding phenotypes. Here, we aimed to improve the efficiency of biallelic deletions and deplete specific maternal RNAs in cattle zygotes using CRISPR-Cas editing technology. Two electroporation sessions with Cas9D10A ribonucleoproteins targeting exon 1 and the promoter ofOCT4produced biallelic deletions in 91% of the embryos tested. In most cases, the deletions were longer than 1000 nucleotides long. Electroporation of Cas13a ribonucleoproteins prevents the production of the corresponding proteins. We electroporated Cas9D10A ribonucleoproteins targeting exon 1, including the promoter region, ofOCT4in two sessions with inclusion of Cas13a ribonucleoproteins targetingOCT4mRNAs in the second session to ablateOCT4function in cattle embryos. A lack ofOCT4resulted in embryos arresting development prior to blastocyst formation at a greater proportion (13%) than controls (31.6%, P<0.001). The few embryos that developed past the morula stage did not form a normal inner cell mass. Transcriptome analysis of single blastocysts, confirmed to lack exon 1 and promoter region ofOCT4, revealed a significant (FDR<0.1) reduction in transcript abundance of many genes functionally connected to stemness, including markers of pluripotency (CADHD1,DPPA4,GNL3,RRM2). The results confirm thatOCT4is key regulator of genes that modulate pluripotency and is required to form a functional blastocyst in cattle.Significance StatementCRISPR-Cas mediated DNA editing can revolutionize agriculture and biomedicine due to its simplicity of design and use. Modifications induced in embryos, though challenging to accomplish, are beneficial for the advancement of livestock production and the study of biological function. Here, we developed an approach using CRISPR-Cas enzymes to remove DNA segments of the cattle genome in one-cell embryos. Our results show major advancement in the efficiency of producing large deletions in the genome of cattle embryos. Using our approach, we removed the function of theOCT4gene. Our results confirmedOCT4as a major regulator of pluripotency genes during embryo development and its requirement for the formation of an inner cell mass in cattle.
The Prokaryotic and Eukaryotic Microbiome of Pacific Oyster Spat is Shaped by Ocean Warming but not Acidification
Authors: Zhong Kevin Xu , Chan Amy M. , Collicutt Brenna , Daspe Maxim , Finke Jan F. , Foss Megan , Green Timothy J. , Harley Christopher D.G. , Hesketh Amelia V. , Miller Kristina M. , Otto Sarah P. , Rolheiser Kate , Saunders Rob , Sutherland Ben J.G. , Suttle Curtis A. 
Published: July 2023

AbstractPacific oysters (Magallana gigas,also known asCrassostrea gigas), the most widely farmed oysters, are under threat from climate change and emerging pathogens. In part, their resilience may be affected by their microbiome, which, in turn, may be influenced by ocean warming and acidification. Consequently, for three weeks, we exposed early-development Pacific oyster spat to different temperatures (18 and 24 °C) andpCO2levels (800, 1600 and 2800µatm) in a fully crossed design. Under all conditions, the microbiome developed over time, with potentially pathogenic ciliates (Uronema marinum) greatly reduced in all treatments, suggesting that the spat’s microbiome undergoes adaptive shifts as the oysters age. The microbiome composition also differed significantly with temperature, but not acidification, indicating thatM. gigasspat microbiomes can be altered by ocean warming but resilient to ocean acidification in our experiments. These findings highlight the spat microbiome’s flexibility to environmental changes as well as its “protective” capability against potentially pathogenic microbes.
Viral enumeration using cost-effective wet-mount epifluorescence microscopy for aquatic ecosystems and modern microbialites
Authors: Bellanger Madeline , Visscher Pieter , White Richard Allen 
Published: July 2023

AbstractEnumeration is a fundamental measure of community ecology in which viruses represent the most numerous biological identities. Epifluorescence microscopy (EFM) has been the gold standard method for environmental viral enumeration for over 25 years. Currently, standard EFM methods using the Anodisc filters are no longer cost-effective (>$15 per slide) and have yet to be applied to modern microbialites. Microbialites are microbially driven benthic organosedimentary deposits that have been present for most of Earth’s history. We present a cost-effective method for environmental viral enumeration from aquatic samples, microbial mats, and exopolymeric substances (EPS) within modern microbialites using EFM. Our integrated approach, which includes filtration, differential centrifugation, chloroform treatment, glutaraldehyde fixation, benzonase nuclease treatment, probe sonication (EPS and mat only), SYBR Gold staining, wet-mounting, and imaging, provides a robust method for modern microbialites and aquatic samples. Viral abundances of modern microbialites and aquatic samples collected from Fayetteville Green Lake (FGL) and Great Salt Lake (GSL) did not differ across ecosystems by sample type. EPS and microbial mat samples had an order of magnitude higher viral-like particle (VLP) abundance when compared to water regardless of the ecosystem (107vs. 106). Viral enumeration allows for estimates of total viral numbers and weights. The entire weight of all the viruses in FGL and GSL are ∼598 g and ∼2.2 kg, respectively; this is equivalent to a loaf of bread for FGL and standard brick for GSL. Further development of EFM methods and software is needed for viral enumeration. Our method provides a robust and cost-effective (∼$0.75 per sample) viral enumeration within modern microbialites and aquatic ecosystems.