bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of metabarcoding taxonomic markers to describe fungal communities in fermented foods
Authors: Rué Olivier , Coton Monika , Dugat-Bony Eric , Howell Kate , Irlinger Françoise , Legras Jean-Luc , Loux Valentin , Michel Elisa , Mounier Jérôme , Neuvéglise Cécile , Sicard Delphine 
Published: January 2023

AbstractNext generation sequencing offers several ways to study microbial communities. For agri-food sciences, identifying species in diverse food ecosystems is key for both food sustainability and food security. The aim of this study was to compare metabarcoding pipelines and markers to determine fungal diversity in food ecosystems, from Illumina short reads. We built mock communities combining the most representative fungal species in fermented meat, cheese, wine and bread. Four barcodes (ITS1, ITS2, D1/D2 and RPB2) were tested for each mock and on real fermented products. We created a database, including all mock species sequences for each barcode to compensate for the lack of curated data in available databases. Four bioinformatics tools (DADA2, QIIME, FROGS and a combination of DADA2 and FROGS) were compared. Our results clearly showed that the combined DADA2 and FROGS tool gave the most accurate results. Most mock community species were not identified by the RPB2 barcode due to unsuccessful barcode amplification. When comparing the three rDNA markers, ITS markers performed better than D1D2, as they are better represented in public databases and have better specificity to distinguish species. Between ITS1 and ITS2, differences in the best marker were observed according to the studied ecosystem. While ITS2 is best suited to characterize cheese, wine and fermented meat communities, ITS1 performs better for sourdough bread communities. Our results also emphasized the need for a dedicated database and enriched fungal-specific public databases with novel barcode sequences for 118 major species in food ecosystems.
Can we sort states of environmental DNA (eDNA) from a single sample?
Authors: Kirtane Anish , Kleyer Hannah , Deiner Kristy 
Published: January 2023

AbstractEnvironmental DNA (eDNA) once shed can exist in numerous states with varying behaviors including degradation rates and transport potential. In this study we consider three states of eDNA: 1) a membrane-bound state referring to DNA enveloped in a cellular or organellar membrane, 2) a dissolved state defined as the extracellular DNA molecule in the environment without any interaction with other particles, and 3) an adsorbed state defined as extracellular DNA adsorbed to a particle surface in the environment. Capturing, isolating, and analyzing a target state of eDNA provides utility for better interpretation of eDNA degradation rates and transport potential. While methods for separating different states of DNA have been developed, they remain poorly evaluated due to the lack of state-controlled experimentation. We evaluated the methods for separating states of eDNA from a single sample by spiking DNA from three different species to represent the three states of eDNA as state-specific controls. We used chicken DNA to represent the dissolved state, cultured mouse cells for the membrane-bound state, and salmon DNA adsorbed to clay particles as the adsorbed state. We performed the separation in three water matrices, two environmental and one synthetic, spiked with the three eDNA states. The membrane-bound state was the only state that was isolated with minimal contamination from non-target states. The membrane-bound state also had the highest recovery (54.11 ± 19.24 %), followed by the adsorbed state (5.08 ± 2.28 %), and the dissolved state had the lowest total recovery (2.21 ± 2.36 %). This study highlights the potential to sort the states of eDNA from a single sample and independently analyze them for more informed biodiversity assessments. However, further method development is needed to improve recovery and reduce cross-contamination.
The apicoplast is important for the viability and persistence ofToxoplasma gondiibradyzoites
Authors: Sanchez Syrian G. , Bassot Emilie , Cerutti Aude , Nguyen Hoa Mai , Aïda Amel , Blanchard Nicolas , Besteiro Sébastien 
Published: January 2023

AbstractToxoplasma gondiiis responsible for toxoplasmosis, a disease that can be serious when contracted during pregnancy, but can also be a threat for immunocompromised individuals. Acute infection is associated with the tachyzoite form that spreads rapidly within the host. However, under stress conditions, some parasites can differentiate into cyst-forming bradyzoites, residing mainly in the central nervous system, retina and muscle. Because this latent form of the parasite is resistant to all currently available treatments, and is central to persistence and transmission of the parasite, new specific therapeutic strategies targeting this developmental stage need to be discovered.T. gondiicontains a plastid of endosymbiotic origin called the apicoplast, which is an appealing drug target because it is essential for tachyzoite viability and contains several key metabolic pathways that are largely absent from the mammalian host. Its function in bradyzoites, however, is unknown. Our objective was thus to study the contribution of the apicoplast to the viability and persistence of bradyzoites during chronic toxoplasmosis.We have used complementary strategies based on stage-specific promoters to generate conditional bradyzoite mutants of essential apicoplast genes. Our results show that specifically targeting the apicoplast in bothin vitroorin vivo-differentiated bradyzoites leads to a loss of long-term bradyzoite viability, highlighting the importance of this organelle for this developmental stage. This validates the apicoplast as a potential area to look for new therapeutic targets in bradyzoites, with the aim to interfere with this currently incurable parasite stage.Significance StatementIn its intermediate hosts, the parasiteToxoplasma gondiican persist as a cyst-contained developmental form that might reactivate and cause severe pathologies. Importantly, this form is resistant to current anti-parasitic drugs.T. gondiiharbors a plastid of endosymbiotic origin called the apicoplast, containing important and potentially druggable metabolic pathways, but whose contribution to the fitness and viability of persistent parasites has never been assessed. We have generated conditional mutants specifically affected for the homeostasis of the apicoplast in cyst-contained parasites and showed that this organelle is important for persistence of these particular developmental forms. Our work thus validates the apicoplast as a relevant drug target in the context of chronicT. gondiiinfection.
Single-dose YF17D-vectored Ebola vaccine candidate protects mice against both lethal surrogate Ebola and yellow fever virus challenge
Authors: Lemmens Viktor , Kelchtermans Lara , Debaveye Sarah , Chiu Winston , Vercruysse Thomas , Ma Ji , Thibaut Hendrik Jan , Neyts Johan , Sanchez-Felipe Lorena , Dallmeier Kai 
Published: January 2023

AbstractEbola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vectored dual-target vaccine candidate expressing EBOV-glycoprotein (GP) as protective antigen. Safety of YF-EBO in mice was further improved over that of parental YF17D vaccine. A single dose of YF-EBO was sufficient to induce high levels of EBOV-GP specific antibodies and cellular immune responses, that protected against lethal infection using EBOV-GP-pseudotyped recombinant vesicular stomatitis virus (rVSV-EBOV) in interferon-deficient (Ifnar-/-) mice as surrogate challenge model. Concomitantly induced yellow fever virus (YFV)-specific immunity protectedIfnar-/-mice against intracranial YFV challenge. YF-EBO could thus help to simultaneously combat both EBOV and YFV epidemics. Finally, we demonstrate how to target other highly pathogenic filoviruses such as SUDV at the root of a current outbreak in Uganda.
The role of the 5’ sensing function of ribonuclease E in cyanobacteria
Authors: Hoffmann Ute A. , Lichtenberg Elisabeth , Rogh Said N. , Bilger Raphael , Reimann Viktoria , Heyl Florian , Backofen Rolf , Steglich Claudia , Hess Wolfgang R. , Wilde Annegret 
Published: January 2023

AbstractRNA degradation is crucial for many processes in pro- and eukaryotic organisms. In bacteria, the preference of the central ribonucleases RNase E, RNase J and RNase Y towards 5’-monophosphorylated RNAs is considered important for RNA degradation. For RNase E, the underlying mechanism is termed 5’ sensing. Cyanobacteria, such asSynechocystissp. PCC 6803 (Synechocystis), encode RNase E and RNase J homologs. Here, we constructed aSynechocystisstrain lacking the 5’ sensing function of RNase E and mapped on a transcriptome-wide level 292 5’-sensing-dependent cleavage sites. These included so far unknown targets such as the 5’ untranslated region of the response regulator genelsiR;trxA, apcEandatpImRNAs, encoding proteins related to energy metabolism; as well assbtBandrbcLXSencoding proteins relevant for carbon fixation. Cyanobacterial 5’ sensing is important for the maturation of rRNA and several tRNAs, including tRNAGluUUC. This tRNA activates glutamate for tetrapyrrole biosynthesis in plant chloroplasts and most prokaryotes. We found that increased RNase activities leads to a higher copy number of the majorSynechocystisplasmids pSYSA and pSYSM. The results provide a first step towards understanding the relative importance of different target mechanisms of RNase E outsideEscherichia coli.
A tachykinin precursor 1 medullary circuit promoting rhythmic breathing
Authors: Rousseau Jean-Philippe , Furdui Andreea , da Silveira Scarpellini Carolina , Horner Richard L. , Montandon Gaspard 
Published: January 2023

AbstractRhythmic breathing is generated by neural circuits located in the brainstem. At its core is the preBötzinger Complex (preBötC), a region of the medulla, necessary for the generation of rhythmic breathing in mammals. The preBötC is comprised of various neuronal populations expressing neurokinin-1 receptors, the cognate G-protein-coupled receptor of the neuropeptide substance P (encoded by the tachykinin precursor 1 orTac1). Neurokinin-1 receptors are highly expressed in the preBötC and destruction or deletion of neurokinin-1 receptor-expressing preBötC neurons severely impairs rhythmic breathing. Application of substance P to the preBötC stimulates breathing in rodents, however substance P is often associated with nociception and locomotion in various brain regions, suggesting thatTac1neurons found in the preBötC may have diverse functional roles. Here, we aim to characterize the role ofTac1-expressing preBötC neurons in the generation of rhythmic breathingin vivo, as well as motor behaviors. Using a cre-lox recombination approach, we injected adeno-associated virus containing the excitatory channelrhodopsin-2 ChETA in the preBötC region ofTac1-cre mice. Using a combination of histological, optogenetics, respiratory, and behavioral assays, we defined the identity and the role ofTac1preBötC neurons. These neurons are glutamatergic and their stimulation promotes rhythmic breathing in both anesthetized and freely moving/awake animals, but also triggers locomotion and overcomes respiratory depression by opioid drugs. Overall, our study identifies a new population of excitatory preBötC with major role in rhythmic breathing and behaviors.
A Role for Astrocytic Insulin-Like Growth Factor I Receptors in the Response to Ischemic Insult
Authors: Suda K. , Pignatelli J. , Genis L. , Fernandez A.M. , Fernandez de Sevilla E. , Fernandez de la Cruz I. , Pozo-Rodrigalvarez A. , de Ceballos M. L. , Díaz-Pacheco S. , Herrero-Labrador R. , Torres Aleman I. 
Published: January 2023

AbstractIncreased neurotrophic support, including insulin-like growth factor I (IGF-I), is an important aspect of the adaptive response to ischemic insult. However, recent findings indicate that the IGF-I receptor (IGF-IR) in neurons plays a detrimental role in the response to stroke. Thus, we investigated the role of astrocytic IGF-IR on ischemic insults by deleting it using tamoxifen-regulated Cre deletion in glial fibrillary acidic protein (GFAP) astrocytes, a major cellular component in the response to injury. Ablation of IGF-IR in astrocytes (GFAP-IGF-IR KO mice) resulted in larger ischemic lesions, greater blood-brain-barrier disruption and more deteriorated sensorimotor coordination. RNAseq detetected increases in inflammatory, cell adhesion and angiogenic pathways, while the expression of various classical biomarkers of response to ischemic lesion, including aquaporin 4, complement 1q subunit a, early growth response protein 1, and C-C motif chemokine ligand 2, were significantly increased at the lesion site compared to control littermates. While serum IGF-I levels after injury were decreased in both control and GFAP-IR KO mice, brain IGF-I mRNA expression show larger increases in the latter. Further, greater damage was also accompanied by altered glial reactivity as reflected by changes in the morphology of GFAP astrocytes, and relative abundance of ionized calcium binding adaptor molecule 1 microglia. These results suggest a protective role for astrocytic IGF-IR in the response to ischemic injury.
Biophysical modeling of the electric field magnitude and distribution induced by electrical stimulation with intracerebral electrodes
Authors: Alonso Fabiola , Mercadal Borja , Salvador Ricardo , Ruffini Giulio , Bartolomei Fabrice , Wendling Fabrice , Modolo Julien 
Published: January 2023

AbstractIntracranial electrodes are used clinically for diagnostic or therapeutic purposes, notably in drug-refractory epilepsy (DRE) among others. Visualization and quantification of the energy delivered through such electrodes is key to understanding how the resulting electric fields modulate neuronal excitability, i.e. the ratio between excitation and inhibition. Quantifying the electric field induced by electrical stimulation in a patient-specific manner is challenging, because these electric fields depend on a number of factors: electrode trajectory with respect to folded brain anatomy, biophysical (electrical conductivity / permittivity) properties of brain tissue and stimulation parameters such as electrode contacts position and intensity.Here, we aimed to evaluate various biophysical models for characterizing the electric fields induced by electrical stimulation in DRE patients undergoing stereoelectroencephalography (SEEG) recordings in the context of pre-surgical evaluation. This stimulation was performed with multiple-contact intracranial electrodes used in routine clinical practice. We introduced realistic 3D models of electrode geometry and trajectory in the neocortex. For the electrodes, we compared point (0D) and line (1D) sources approximations. For brain tissue, we considered three configurations of increasing complexity: a 6-layer spherical model, a toy model with a sulcus representation, replicating results from previous approaches; and went beyond the state-of-the-art by using a realistic head model geometry.Electrode geometry influenced the electric field distribution at close distances (~3 mm) from the electrode axis. For larger distances, the volume conductor geometry and electrical conductivity dominated electric field distribution. These results are the first step towards accurate and computationally tractable patient-specific models of electric fields induced by neuromodulation and neurostimulation procedures.
Age-dependent loss of cohesion protection in human oocytes
Authors: Mihalas Bettina P , Pieper Gerard H , Currie Cerys E , Kelly David A , Hartshorne Geraldine M , McAinsh Andrew D , Anderson Richard A , Marston Adele L 
Published: January 2023

AbstractAneuploid human eggs (oocytes) are a major cause of infertility, miscarriage and chromosomal disorders. Such aneuploidies increase greatly as women age, originating from defective linkages between sister-chromatids (cohesion) in meiosis. We found evidence that loss of a specific pool of the cohesin protector protein, shugoshin 2 (Sgo2) contributes to this phenomenon. Our data indicate that Sgo2 preserves sister chromatid cohesion in meiosis by protecting a ‘cohesin bridge’ between sister chromatids. In human oocytes, Sgo2 localizes to both sub-centromere cups and the pericentromeric bridge which spans the sister chromatid junction. Sgo2 normally colocalizes with cohesin, however, in oocytes from older women, Sgo2 is frequently lost specifically from the pericentromeric bridge and sister chromatid cohesion is weakened. Mps1 and Bub1 kinase activities maintain Sgo2 at sub-centromeres and the pericentromeric bridge. Removal of Sgo2 throughout meiosis I by Mps1 inhibition reduces cohesion protection, increasing the incidence of single chromatids at meiosis II. Therefore, Sgo2 deficiency in human oocytes can exacerbate the effects of maternal age by rendering residual cohesin at pericentromeres vulnerable to loss in anaphase I. Our data show that maternal age-dependent loss of Sgo2 at the pericentromere bridge in human oocytes impairs cohesion integrity and contributes to the increased incidence of aneuploidy observed in human oocytes with advanced maternal age.
The effect ofDnaaf5gene dosage on primary ciliary dyskinesia phenotypes
Authors: Horani Amjad , Gupta Deepesh Kumar , Xu Jian , Xu Huihui , Carmen Puga-Molina Lis del , Santi Celia M. , Ramagiri Sruthi , Brennen Steven K. , Pan Jiehong , Huang Tao , Hyland Rachael M. , Gunsten Sean P. , Tzeng Shin-Cheng , Strahle Jennifer M. , Mill Pleasantine , Mahjoub Moe R. , Dutcher Susan K. , Brody Steven L. 
Published: January 2023

AbstractDNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift null deletion inDnaaf5. Litters withDnaaf5heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the nullDnaaf5alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals homozygous for the missense mutation had improved survival, with partial preserved cilia function and motor assembly observed by ultrastructure analysis. Notably, the same variant alleles exhibited divergent cilia function across different multiciliated tissues. Proteomic analysis of isolated airway cilia from mutant mice revealed reduction in some axonemal regulatory and structural proteins not previously reported inDNAAF5variants. While transcriptional analysis of mouse and human mutant cells showed increased expression of genes coding for axonemal proteins. Together, these findings suggest allele-specific and tissue-specific molecular requirements for cilia motor assembly that may affect disease phenotypes and clinical trajectory in motile ciliopathies.Brief SummaryA mouse model of human DNAAF5 primary ciliary dyskinesia variants reveals gene dosage effects of mutant alleles and tissue-specific molecular requirements for cilia motor assembly.
Genotypic and phenotypic differences among phase-variable colony variants conserved acrossGardnerellaspp
Authors: Garcia Erin M. , Klimowicz Amy K. , Edupuganti Laahirie , Topf Madeline A. , Bhide Shraddha R. , Slusser Dawson J. , Leib Samantha M. , Buck Gregory A. , Jefferson Kimberly K. , Pepperell Caitlin S. , Dillard Joseph P. 
Published: January 2023

AbstractTheGardnerellagenus, now made up of more than 13 species, is associated with the polymicrobial disorder bacterial vaginosis (BV). However, the details of BV pathogenesis are poorly defined, and the contributions made by individual species are largely unknown. We report here that colony phenotypes characterized by size (large and small) and opacity (opaque and translucent) are phase variable and are conserved among all testedGardnerellastrains, representing at least ten different species. With the hypothesis that these different variants could be an important missing piece to the enigma of how BV develops in vivo, we characterized their differences. Beyond increased colony size, large colony variants (Lg) showed reduced vaginolysin secretion and faster growth rate relative to small colony variants (Sm). The ability to inhibit growth ofNeisseria gonorrhoeaeand commensal lactobacillus species varied by strain and in some instances differed between variants. Proteomics analyses indicate that 127-173 proteins are differentially expressed between variants. Further, whole genome sequencing analyses revealed an abundance of genes associated with variable poly-guanine tracts, implicating slipped strand mispairing inGardnerellaphase variation, and illuminating the potential for previously unrecognized variability within clonal populations. Collectively, these results suggest that colony variants may be primed to serve different roles in BV pathogenesis.
Histopathology: Deep machine learning based semantic segmentation features predict patient survival
Authors: Ramachandra Vikas 
Published: January 2023

AbstractIn this paper, we use deep learning techniques to segment different regions from breast cancer histopathology images, such as tumor nucleus, epithelium and stromal areas. Then, in the second stage, the deep segmentation features learned by the neural network are used to predict individual patient survival, using random forest based classification. We show that the deep segmentation network features can predict survival very well, and outperform classical computer vision based shape, texture and other feature descriptors used in earlier research for the same survival prediction task.
Effect of abnormal increase in credit supply on economic growth in Nigeria
Authors: Ozili Peterson K. , Oladipo Olajide , Iorember Paul Terhemba 
Published: January 2023

PurposeThis paper investigates the effect of abnormal increase in credit supply on economic growth in Nigeria after controlling for the quality of the legal system, size of central bank asset, banking sector cost efficiency and bank insolvency risk.Design/methodology/approachThe authors employ the generalised method of moments (GMM) regression methodology to estimate the effect of abnormal increase in credit supply on two measures of economic growth in Nigeria.FindingsThe abnormal increase in credit supply has a significant effect on economic growth. Abnormal increase in credit supply increases real gross domestic product (GDP) growth. The abnormal increase in credit supply decreases real GDP per capita during the global financial crisis. The abnormal increase in domestic credit to the private sector has a significant positive effect on GDP per capita when there is strong legal system quality in Nigeria. In contrast, the abnormal increase in domestic credit to the private sector has a significant negative effect on real GDP growth when there is strong legal system quality in Nigeria.Practical implicationsThe abnormal increase in credit supply is ineffective in increasing GDP per capita during crisis years. Policymakers should be cautious in pressuring financial institutions to release an abnormally large amount of credit into the economy particularly during financial crises. Rather, policymakers should encourage financial institutions to supply credit in a sustained manner – not in an abnormal manner –and in a way that supports growth.Originality/valueThe present study contributes to the literature by analysing the effect of abnormal increase in credit supply on economic growth in a developing country context.