bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of selective isolation media for detecting Actinomyces and Schaalia genera from oral specimens containing indigenous bacteria
Authors: Aoki Sadao , Yahara Hiroko , Nakao Ryoma , Tsuzukibashi Osamu , Yahara Koji 
Published: March 2024

To isolate specific bacteria from samples constituting the microbiota, it is essential to employ selective media that suppress the growth of resident bacteria other than specific target bacteria. Selective media for clinically important Actinomyces (including Schaalia, which was previously taxonomically classified as part of the Actinomyces genus) have been limited because they have been designed for a limited range of species within the genus and require ingredients which are difficult to prepare and handle. This study aimed to develop a selective medium (referred to as Actinomyces and Schaalia Selective Medium (ASSM)) for the isolation of a broad range of Actinomyces and Schaalia species from samples mixed with resident bacteria. The composition of ASSM includes yeast extract, agar, brain heart infusion (BHI), levofloxacin (LVFX), fosfomycin (FOM), colistin (CL), and metronidazole (MNZ). Evaluation of the medium using 24 swab samples serially collected from the roots of the teeth of a healthy individual for whom metagenome sequencing data of a saliva sample are publicly available revealed that ASSM adjusted to concentrations of LVFX 0.5 mg/L, FOM 5 mg/L, CL 1 mg/L, and MNZ 2 mg/L and cultured anaerobically at 35°C for 7 days enabled the isolation of Actinomyces species from 37.5% of the samples. The inclusion of CL and MNZ in ASSM can also be useful for samples suspected of harbouring other bacterial species. The selective isolation medium is expected to contribute to studies investigating the relationship between these bacteria and their pathogenesis or disease.
PVN-mPFC OT projections modulates pup-directed pup care or attacking in virgin mandarin voles
Authors: Li Lu , Li Yin , Huang Caihong , Hou Wenjuan , Lv Zijian , Zhang Lizi , Qu Yishan , Sun Yahan , Huang Kaizhe , Han Xiao , He Zhixiong , Tai Fadao 
Published: March 2024

AbstractIn many species, adult animals may exhibit caregiving or aggression towards conspecific offspring. The neural mechanisms underlying the infanticide and pup care remain poorly understood. Here, using monogamous virgin mandarin voles (Microtus mandarinus) that may exhibit pup care or infanticide, we found that more oxytocin (OT) neurons in the paraventricular nucleus (PVN) were activated during pup caring than infanticide. Optogenetic activation of OT neurons in the PVN facilitated pup-caring in male and female mandarin voles. In infanticide voles, optogenetic activation of PVN OT cells prolonged latency to approach and attack pups, whereas inhibition of these OT neurons facilitated approach and infanticide. In addition, OT release in the medial prefrontal cortex (mPFC) in pup-care voles increased upon approaching and retrieving pups, and decreased in infanticide voles upon attacking pups. Optogenetic activation of PVN OT neuron projections to the mPFC shortened the latency to approach and retrieve pups and facilitated the initiation of pup care, whereas inhibition of these projections had little effect. For pup-care females, neither activation nor inhibition of the fibers affected their behavior towards pups. In infanticide male and female voles, optogenetic activation of PVN-mPFC OT projection fibers prolonged the latency to approach and attack pups and suppressed the initiation of infanticide, whereas inhibition of these projections promoted approach and infanticide. Finally, we found that intraperitoneal injection of OT promoted pup care and inhibited infanticide behavior. It is suggested that the OT system, especially PVN OT neurons projecting to mPFC, modulates pup-directed behaviors and OT can be used to treat abnormal behavioral responses associated with some psychological diseases such as depression and psychosis.
Air-liquid interface exposure of A549 human lung cells to characterize the hazard potential of a gaseous bio-hybrid fuel blend
Authors: Daniel Jonas , Schönberger Alvarez Ariel A. , te Heesen Pia , Lehrheuer Bastian , Pischinger Stefan , Hollert Henner , Roß-Nickoll Martina , Du Miaomiao 
Published: March 2024

AbstractGaseous and semi-volatile organic compounds emitted by the transport sector contribute to air pollution and have adverse effects on human health. To reduce harmful effects to the environment as well as to humans, renewable and sustainable bio-hybrid fuels are explored and investigated in the cluster of excellence “The Fuel Science Center” at RWTH Aachen University. However, data on the effects of bio-hybrid fuels on human health is scarce, leaving a data gap regarding their hazard potential. To help close this data gap, this study investigates potential toxic effects of a Ketone-Ester-Alcohol-Alkane (KEAA) fuel blend on A549 human lung cells. Experiments were performed using a commercially available air-liquid interface exposure system which was optimized beforehand. Then, cells were exposed at the air-liquid interface to 50-2000 ppm C3.7of gaseous KEAA for 1 h. After a 24 h recovery period in the incubator metabolic activity and cytotoxicity of cells were assessed. Our data support the international occupational exposure limits of the single KEAA constituents and moreover indicate no adverse effect to A549 cells when exposed to a fuel mixture. This finding applies only to the exposure scenario tested in this study and is difficult to extrapolate to the complexin vivosituation.
Changes in plant physiology during cultivation periods influence the hydrogen isotope ratio of the water-insect relationship
Authors: Fujii Tomohisa , Akiduki Gaku , Yabusaki Shiho , Tayasu Ichiro 
Published: March 2024

AbstractThe hydrogen stable isotope ratios (δ2H) in tissues of terrestrial insects are widely applied to estimate natal origins in field populations. The hydrogen isotopes of insect tissues incorporate those of environmental waters through the insects’ metabolic processes. Water sources and abiotic environmental factors reflect changes in plant physiology, as indicated by the δ2H values of plants. However, the influence of plant physiology on the assimilation of hydrogen in insect tissues derived from water through feeding diets is still unknown.We experimentally examined the influence of water on the δ2H values of maize leaf and of forewings ofMythimna separata(Lepidoptera: Noctuidae) andSpodoptera frugiperda(Noctuidae). We prepared five specific water samples for cultivating maize, aiming to replicate the gradient of δ2H values observed in environmental waters across the Japanese archipelago.The mean-percentage contribution of water to hydrogen in maize leaves was 17.6% (July-August) and 25.1% (September-October). Linear analyses indicated that 17.4% and 32.7% of hydrogen inM. separataandS. frugiperdaforewings were derived from water through the consumption of maize leaves. The slope values of linear regression between the insect forewings and the maize leaves supplied in the final instar were closest to 1.0. These results indicated that the δ2H values of maize leaves and insect forewings reflected those of water resources.This study presented the seasonal changes in climate conditions that affected the δ2H values of host plants and insect tissues. Changes in plant physiology with seasonal variations may influence the interpretation of the linear relationship between water and insect tissues on the estimation of natal origins.
Integrative Co-Registration of Elemental Imaging and Histopathology for Enhanced Spatial Multimodal Analysis of Tissue Sections through TRACE
Authors: Lu Yunrui , Steiner Ramsey , Han Serin , Srivastava Aruesha , Shaik Neha , Chan Matthew , Diallo Alos , Punshon Tracy , Jackson Brian , Kolling Fred , Vahdat Linda , Vaickus Louis , Marotti Jonathan , Ho Sunita , Levy Joshua 
Published: March 2024

AbstractSummaryElemental imaging provides detailed profiling of metal bioaccumulation, offering more precision than bulk analysis by targeting specific tissue areas. However, accurately identifying comparable tissue regions from elemental maps is challenging, requiring the integration of hematoxylin and eosin (H&E) slides for effective comparison. Facilitating the streamlined co-registration of Whole Slide Images (WSI) and elemental maps, TRACE enhances the analysis of tissue regions and elemental abundance in various pathological conditions. Through an interactive containerized web application, TRACE features real-time annotation editing, advanced statistical tools, and data export, supporting comprehensive spatial analysis. Notably, it allows for comparison of elemental abundances across annotated tissue structures and enables integration with other spatial data types through WSI co-registration.Availability and ImplementationAvailable on the following platforms– GitHub:jlevy44/trace_app, PyPI:trace_app, Docker:joshualevy44/trace_app, Singularity:joshualevy44/trace_app.Contactjoshua.levy@cshs.orgSupplementary informationSupplementary data are available.
Inference of Transcriptional Regulation From STARR-seq Data
Authors: Safaeesirat Amin , Taeb Hoda , Tekoglu Emirhan , Morova Tunc , Lack Nathan A. , Emberly Eldon 
Published: March 2024

AbstractOne of the primary regulatory processes in cells is transcription, during which RNA polymerase II (Pol-II) transcribes DNA into RNA. The binding of Pol-II to its site is regulated through interactions with transcription factors (TFs) that bind to DNA at enhancer cis-regulatory elements. Measuring the enhancer activity of large libraries of distinct DNA sequences is now possible using Massively Parallel Reporter Assays (MPRAs), and computational methods have been developed to identify the dominant statistical patterns of TF binding within these large datasets. Such methods are global in their approach and may overlook important regulatory sites which function only within the local context. Here we introduce a method for inferring functional regulatory sites (their number, location and width) within an enhancer sequence based on measurements of its transcriptional activity from an MPRA method such as STARR-seq. The model is based on a mean-field thermodynamic description of Pol-II binding that includes interactions with bound TFs. Our method applied to simulated STARR-seq data for a variety of enhancer architectures shows how data quality impacts the inference and also how it can find local regulatory sites that may be missed in a global approach. We also apply the method to recently measured STARR-seq data on androgen receptor (AR) bound sequences, a TF that plays an important role in the regulation of prostate cancer. The method identifies key regulatory sites within these sequences which are found to overlap with binding sites of known co-regulators of AR.1Author SummaryWe present an inference method for identifying regulatory sites within a putative DNA enhancer sequence, given only the measured transcriptional output of a set of overlapping sequences using an assay like STARR-seq. It is based on a mean-field thermodynamic model that calculates the binding probability of Pol-II to its promoter and includes interactions with sites in the DNA sequence of interest. By maximizing the likelihood of the data given the model, we can infer the number of regulatory sites, their locations, and their widths. Since it is a local model, it can in principle find regulatory sites that are important within a local context that may get missed in a global fit. We test our method on simulated data of simple enhancer architectures and show that it is able to find only the functional sites. We also apply our method to experimental STARR-seq data from 36 androgen receptor bound DNA sequences from a prostate cancer cell line. The inferred regulatory sites overlap known important regulatory motifs and their ChIP-seq data in these regions. Our method shows potential at identifying locally important functional regulatory sites within an enhancer given only its measured transcriptional output.
Masitinib limits neuronal damage, as measured by serum neurofilament light chain concentration, in a model of neuroimmune-driven neurodegenerative disease
Authors: Hermine Olivier , Gros Laurent , Tran Truong-An , Loussaief Lamya , Flosseau Kathleen , Moussy Alain , Mansfield Colin D. , Vermersch Patrick 
Published: March 2024

ABSTRACTBackgroundMasitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the innate neuroimmune system. We have studied the neuroprotective action of masitinib on the manifestations of experimental autoimmune encephalitis (EAE) induced axonal and neuronal damage. EAE is a model of neuroimmune-driven chronic neuroinflammation and therefore highly relevant to masitinib’s mechanism of action in neurodegenerative diseases. Importantly, neuronal damage, or prevention thereof, can be rapidly assessed by measuring serum neurofilament light chain (NfL) concentration in EAE-induced mice.MethodsEAE induction was performed in healthy female C57BL/6 mice via active MOG35-55peptide immunization. Treatments were initiated 14 days post EAE induction. On day-0, 39 mice with established EAE symptoms were randomly assigned to 3 treatment groups (n=13): EAE control, masitinib 50 mg/kg/day (M50), and masitinib 100 mg/kg/day (M100). Treatment started on day-1 and ended on day-15. Blood samples were collected at day-1, day-8 (via tail vein sampling) and day-15 (via intracardiac puncture). Assessments included quantification of serum NfL levels along the disease duration, cytokine quantification at day-15, and clinical assessments.ResultsMasitinib treatment significantly (p<0.0001) limited NfL production with respect to control; specifically, relative change in serum NfL concentration at day-8 was 43% and 60% lower for the M50 and M100 groups, respectively. Likewise, for the assessment of absolute serum NfL at day-8 and day-15, there was a significantly lower NfL concentration for masitinib treatment as compared with control. Furthermore, EAE mice treated with masitinib showed significantly lower concentrations of several well-established pro-inflammatory cytokines relative to control at day-15. A beneficial effect of masitinib on functional performance was also observed, with both M50 and M100 groups showing significantly less relative deterioration in grip strength at day-15 as compared with control (p<0.001).ConclusionThis study is the first demonstration that masitinib, a drug that targets the innate as opposed to the adaptive neuroimmune system, can lower serum NfL levels, and by extension therefore, neuronal damage, in a neuroimmune-driven neurodegenerative disease model. Overall, findings indicate that masitinib has a neuroprotective effect under conditions of chronic neuroinflammation and therefore plausible disease-modifying activity across a broad range of neurodegenerative diseases.
Bridging fungal resistance and plant growth through constitutive overexpression ofThchit42gene inPelargonium graveolens
Authors: Khatoon Kahkashan , Warsi Zafar Iqbal , Singh Akanksha , Singh Kajal , Khan Feroz , Singh Palak , Shukla Rakesh Kumar , Verma Ram Swaroop , Singh Munmun K. , Verma Sanjeet K. , Husain Zakir , Parween Gazala , Singh Pooja , Afroz Shama , Rahman Laiq Ur 
Published: March 2024

SummaryPelargonium graveolensessential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidableColletotrichum gloeosporioidesandFusarium oxysporum. Additionally, phenotypic analysis revealed ∼2fold increase in leaf size and ∼2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause,De novotranscriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and ZF RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism ofThchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand.
Beyond functional connectivity: deep learning applied to resting-state fMRI time series in the prediction of 58 human traits in the HCP
Authors: Vieira Bruno Hebling , Schöttner Mikkel , Calhoun Vince D , Salmon Carlos Ernesto Garrido 
Published: March 2024

AbstractMachine learning has made several inroads into the study of brain-behavior relations based on in vivo imaging. While the advent of deep neural networks was expected to further improve predictions, the current literature based on resting-state functional connectivity presents mixed results. We hypothesize that the representation of the data,i.e.in the form of functional connectivity, could restrict an advantage of deep learning techniques, namely that of learning complex representations directly from the data. Thus, we investigated if bypassing this feature extraction resulted in improved performance in the prediction of 58 widely studied behavioral traits from a large sample of Human Connectome Project subjects, using deep learning techniques. For this task, we adapted the InceptionTime architecture, which jointly predicts traits directly from regional time series through representation learning, and compared results with a strong kernel-based baseline. Results revealed that both models achieve comparable performance in most traits. Eleven significant differences in mean squared error were detected, however, with seven favoring the neural network approach, and this number increased when accounting for covariates. We additionally show that contrary to the expectation, the neural network approach was more robust to reductions in the training set size. On the other hand, it was more sensitive to reductions in the length of the time series at test time. Our results present a more nuanced view of the potential of deep learning for the prediction of behavior from neuroimaging, which allows learning features directly from the data.
Two opposing roles for Bmp signalling in the development of electrosensory lateral line organs
Authors: Campbell Alexander S. , Minařík Martin , Franěk Roman , Vazačová Michaela , Havelka Miloš , Gela David , Pšenička Martin , Baker Clare V. H. 
Published: March 2024

AbstractThe lateral line system enables all fishes and aquatic-stage amphibians to detect local water movement via mechanosensory hair cells in neuromasts, and many species to detect weak electric fields via electroreceptors (modified hair cells) in ampullary organs. Both neuromasts and ampullary organs develop from lateral line placodes. However, the molecular mechanisms underpinning ampullary organ formation are understudied relative to neuromasts, as the ancestral lineages of zebrafish (teleosts) andXenopus(frogs) independently lost electroreception. We identifiedBmp5as a promising candidate via differential RNA-seq in an electroreceptive ray-finned fish, the Mississippi paddlefish (Polyodon spathula; Modrell et al., 2017,eLife6: e24197). In an experimentally tractable relative, the sterlet sturgeon (Acipenser ruthenus), we found thatBmp5and four other Bmp pathway genes are expressed in the developing lateral line, and that Bmp signalling is active. Furthermore, CRISPR/Cas9-mediated mutagenesis targetingBmp5in G0-injected sterlet embryos resulted in fewer ampullary organs. Conversely, when Bmp signalling was inhibited by DMH1 treatment shortly before the formation of ampullary organ primordia, supernumerary ampullary organs developed. These data suggest that Bmp5 promotes ampullary organ development, whereas Bmp signalling via another ligand(s) prevents their overproduction. Taken together, this demonstrates two opposing roles for Bmp signalling during ampullary organ formation.
A perivascular niche supports endometrial epithelial regeneration
Authors: Li Shu-Yun , Whiteside Sarah , Li Bo , Sun Xiaofei , DeFalco Tony 
Published: March 2024

AbstractEndometrial regeneration is essential for reproductive cycles and pregnancies, allowing the endometrium to undergo repair and renewal after menstruation and parturition. Epithelial cells lining the uterine cavity are shed during each cycle, although remnant luminal and glandular epithelial cells can regenerate the lumen lining. It is presumed that adult stem/progenitor cells in the uterine stroma also contribute to this regeneration. However, the specific cell type(s) and the underlying mechanisms have not been determined. Herein, we use genetic lineage tracing assays in mice to identifyNestin+ perivascular cells as active contributors to epithelial regeneration. Notch signaling maintainsNestin+ perivascular cells in a quiescent state but these cells re-enter the cell cycle and differentiate into epithelial cells via estrogen-stimulated suppression of Notch signaling dependent on estrogen receptor alpha (ERα/ESR1). These findings demonstrate that perivascular cells support epithelial regeneration and reveal a mechanism regulating the quiescence and activation of uterine perivascular cells.
Scalable Isolation of Surface-Engineered Extracellular Vesicles and Separation of Free Proteins via Tangential Flow Filtration and Size Exclusion Chromatography (TFF-SEC)
Authors: Kawai-Harada Yuki , Nimmagadda Vasudha , Harada Masako 
Published: March 2024

AbstractBackgroundExtracellular vesicles (EVs) represent small lipid bilayer structures pivotal in mediating intercellular communication via biomolecular transfer. Their inherent characteristics, including packaging, non-immunogenicity, and biofluid stability, position EVs as promising drug delivery vectors. However, developing clinical quality EVs requires multifaceted technological advancement.MethodsIn this study, a method is introduced for engineering extracellular vesicles (eEVs) from cultured cells and their subsequent isolation using lab-scale tangential flow filtration (TFF). This is the first study to evaluate DNA loading efficacy into EVs isolated by TFF, marking a significant milestone in the field of targeted drug delivery. Initially, cells are transfected with EV-display constructs to facilitate the secretion of eEVs bearing the desired coding molecules. Following brief centrifugation, the cell culture media undergoes filtration using hollow fiber filters. TFF, by applying a constant flow, effectively segregates molecules based on designated molecular weight cut-off (MWCO), enriching particles between 50 nm and 650 nm.ResultsCompared to conventional methods like ultracentrifugation, TFF demonstrates higher efficiency in removing undesired molecules/aggregates while exerting less stress on EVs. Characterization of eEVs through various assays confirms TFF’s superiority in isolating pure EV populations. Additionally, the necessity of size-exclusion chromatography (SEC) after tangential flow filtration (TFF) becomes evident for effectively removing unbound protein contaminants.ConclusionIn conclusion, TFF-SEC emerges as a scalable and superior approach for eEV isolation, promising significant advancements in clinical applications.