bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of operational conditions on drinking water biofilm dynamics and coliform invasion potential
Authors: Waegenaar Fien , García-Timermans Cristina , Van Landuyt Josefien , De Gusseme Bart , Boon Nico 
Published: September 2023

AbstractBiofilms within drinking water distribution systems serve as a habitat for drinking water microorganisms. However, biofilms can negatively impact drinking water quality by causing water discoloration and deterioration and can be a reservoir for unwanted microorganisms. In this study, we investigated whether indicator organisms for drinking water quality, such as coliforms, can settle in mature drinking water biofilms. Therefore, a biofilm monitor consisting of glass rings was used to grow and sample drinking water biofilms. Two mature drinking water biofilms were characterized by flow cytometry, ATP measurements, confocal laser scanning microscopy and 16S rRNA sequencing. Biofilms developed under treated chlorinated surface water supply exhibited lower cell densities in comparison with biofilms resulting from treated groundwater. Overall, the phenotypic as well as the genotypic characteristics were significantly different between both biofilms. In addition, the response of the biofilm microbiome and possible biofilm detachment after minor water quality changes were investigated. Limited changes in pH and free chlorine addition, to simulate operational changes that are relevant for practice, were evaluated. It was shown that both biofilms remained resilient. Finally, mature biofilms were prone to invasion of the coliform,Serratia fonticola. After spiking low concentrations (i.e. ± 100 cells/100 mL) of the coliform to the corresponding bulk water samples, the coliforms were able to attach and get established within the mature biofilms. These outcomes are emphasizing the need for continued research on biofilm detachment and its implications for water contamination in distribution networks.ImportanceThe revelation that even low concentrations of coliforms can infiltrate into mature drinking water biofilms highlights a potential public health concern. Nowadays, the measurement of coliform bacteria is used as an indicator for fecal contamination and to control the effectiveness of disinfection processes and the cleanliness and integrity of distribution systems. In Flanders (Belgium), 533 out of 18840 measurements exceeded the established norm for the coliform indicator parameter in 2021, however, the source of microbial contamination is mostly unknown. Here, we showed that mature biofilms, are susceptible to invasion ofSerratia fonticola. These findings emphasize the importance of understanding and managing biofilms in drinking water distribution systems, not only for their potential to influence water quality, but also for their role in harboring and potentially disseminating pathogens. Further research into biofilm detachment, long-term responses to operational changes, and pathogen persistence within biofilms is crucial to inform strategies for safeguarding drinking water quality.
Exploring Neural Dynamics in Self-Voice Processing and Perception: Implications for Hallucination Proneness
Authors: Duggirala Suvarnalata Xanthate , Honcamp Hanna , Schwartze Michael , van Amelsvoort Therese , Pinheiro Ana P. , Linden David E. J. , Kotz Sonja A. 
Published: September 2023

AbstractAltered sensory feedback processing and attention control are assumed to contribute to auditory verbal hallucinations, which are experienced by the general population and patients with psychosis, implying a continuum of hallucination proneness (HP). However, the interaction of altered sensory feedback processing and attention control along this HP continuum remains unclear. Manipulating the level of certainty of sensory feedback by changing self-voice quality (100% neutral, 60-40% neutral-angry, 50-50% neutral-angry, 40-60% neutral-angry, 100% angry) in individuals varying in HP, we tested this interaction using electroencephalography while participants self-generated or passively listened to their voices. Regardless of voice quality, HP modulated the N100 and P200 suppression effects. High HP individuals showed an increased N100 response to the self-generated voices and an increased P200 response for externally-generated voices. This may indicate increased error awareness and attention allocation in high HP individuals for self-voice generation stemming from altered sensory feedback processing, and/or attentional control. The current findings suggest that alterations of the sensory feedback processing in self-voice production are a fundamental characteristic of the continuum of HP, regardless of the clinical status of voice hearers.HighlightsAltered N100 voice suppression in high HP, regardless of the clinical status.High HP associated with altered sensory feedback processing and attentional control.Current findings support a ‘neurophysiological’ continuum of HP.
Sparse and distributed cortical populations mediate sensorimotor integration
Authors: Pancholi Ravi , Sun-Yan Andrew , Laughton Maya , Peron Simon 
Published: September 2023

SUMMARYTouch information is central to sensorimotor integration, yet little is known about how cortical touch and movement representations interact. Touch- and movement-related activity is present in both somatosensory and motor cortices, making both candidate sites for touch-motor interactions. We studied touch-motor interactions in layer 2/3 of the primary vibrissal somatosensory and motor cortices of behaving mice. Volumetric two-photon calcium imaging revealed robust responses to whisker touch, whisking, and licking in both areas. Touch activity was dominated by a sparse population of broadly tuned neurons responsive to multiple whiskers that exhibited longitudinal stability and disproportionately influenced interareal communication. Movement representations were similarly dominated by sparse, stable, reciprocally projecting populations. In both areas, many broadly tuned touch cells also produced robust licking or whisking responses. These touch-licking and touch-whisking neurons showed distinct dynamics suggestive of specific roles in shaping movement. Cortical touch-motor interactions are thus mediated by specialized populations of highly responsive, broadly tuned neurons.
Fusion-negative rhabdomyosarcoma orthotopic tongue xenografts for study of invasion, intravasation and metastasis in live animals
Authors: Hammoudeh Sarah M. , Ng Yeap , Wei Bih-Rong , Madsen Thomas D. , Simpson R. Mark , Weigert Roberto , Randazzo Paul A. 
Published: September 2023

AbstractPAX3/7 Fusion-negative rhabdomyosarcoma (FN-RMS) is a childhood mesodermal lineage malignancy with a poor prognosis for metastatic or relapsed cases. Towards achieving a more complete understanding of advanced FN-RMS, we developed an orthotopic tongue xenograft model for studies of molecular basis of FN-RMS invasion and metastasis. The behavior of FN-RMS cells injected into murine tongue was examined using in vivo bioluminescence imaging, non-invasive intravital microscopy (IVM), and histopathology and compared to the prevailing hindlimb intramuscular and subcutaneous xenografts. FN-RMS cells were retained in the tongue and invaded locally into muscle mysial spaces and vascular lumen. While evidence of hematogenous dissemination to the lungs occurred in tongue and intramuscular xenografts, evidence of local invasion and lymphatic dissemination to lymph nodes only occurred in tongue xenografts. IVM and RNA-seq of tongue xenografts reveal shifts in cellular phenotype and differentiation state in tongue xenografts. IVM also shows homing to blood and lymphatic vessels, lymphatic intravasation, and dynamic membrane protrusions. Based on these findings, the tongue orthotopic xenograft of FN-RMS is a valuable model for tumor progression studies at the tissue, cellular and subcellular levels providing insight into kinetics and molecular bases of tumor invasion and metastasis and, hence, new therapeutic avenues for advanced FN-RMS.
Glutamate neurotransmission from leptin receptor cells is required for typical puberty and reproductive function in female mice
Authors: Sáenz de Miera Cristina , Bellefontaine Nicole , Allen Susan J. , Myers Martin G. , Elias Carol F. 
Published: September 2023

ABSTRACTThe hypothalamic ventral premammillary nucleus (PMv) is a glutamatergic nucleus essential for the metabolic control of reproduction. However, conditional deletion of leptin receptor (LepRb) in vesicular glutamate transporter 2 (Vglut2) expressing neurons results in virtually no reproductive deficits. In this study, we determine the role of glutamatergic signaling from leptin responsive PMv neurons on puberty and fertility. We first assessed if stimulation of PMv neurons induces LH release in fed adult females. We used the stimulatory form of designer receptor exclusively activated by designer drugs (DREADDs) in LepRb-Cre mice. We collected blood sequentially before and for 1h after iv. clozapine-N-oxide injection. LH level increased in animals correctly targeted to the PMv, and LH level was correlated to the number of cFos immunoreactive neurons in the PMv. Next, females with deletion ofVglut2in LepRb neurons (LepRΔVGlut2) showed delayed age of puberty, disrupted estrous cycles, increased GnRH concentration in the axon terminals and disrupted LH responses, suggesting impaired GnRH release. To assess if glutamate is required for PMv actions in pubertal development, we generated a Cre-induced reexpression of endogenous LepRb (LepRloxTB)with concomitant deletion of Vglut2 (Vglut2-floxed) mice. Rescue of Lepr and deletion of Vglut2 in the PMv was obtained by stereotaxic injection of an adeno-associated virus vector expressing Cre recombinase. Control LepRloxTBmice with PMv LepRb rescue showed vaginal opening, follicle maturation and became pregnant, while LepRloxTB;Vglut2floxmice showed no pubertal development. Our results indicate that glutamatergic signaling from leptin sensitive neurons regulates the reproductive axis, and that leptin action on pubertal development via PMv neurons requires Vglut2.SIGNIFICANCE STATEMENTAge of puberty and reproductive function are strongly influenced by energy balance. Leptin is the primary metabolic hormone in reproductive control, but the neural circuitry involved is not fully understood. Previous studies have suggested that GABAergic but not glutamatergic neurotransmission is required for leptin action on reproduction. However, the PMv, a nucleus essential for the metabolic control of the reproductive function, densely expressesLeprand is essentially glutamatergic. Here we show that remote activation of leptin-responsive neurons in the PMv induces LH secretion, while deletion of glutamatergic neurotransmission in LepR (or PMv) neurons disrupts pubertal development and impairs the reproductive function in female mice. Our findings indicate that glutamate in LepR, and specifically in PMv, neurons is required for reproductive maturation and function.
KRAS inhibition activates an actionable CD24 ‘don’t eat me’ signal in pancreas cancer
Authors: Wei Yongkun , Liu Minghui , Yen Er-Yen , Yao Jun , Nguyen Phuoc T , Wang Xiaofei , Yang Zecheng , Yousef Abdelrahman , Pan Dean , Jin Yanqing , Theady Madelaine S. , Park Jungho , Cai Yiming , Takeda Mitsunobu , Vasquez Matthew , Zhou Yong , Zhao Hong , Viale Andrea , Wang Huamin , Zhao Dan , DePinho Ronald A. , Yao Wantong , Ying Haoqiang 
Published: September 2023

AbstractKRASG12Cinhibitor (G12Ci) has produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the tumor biology of the KRASG12Callele and possible bypass mechanisms, we developed a novel autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12DPDAC model, the G12C model exhibit slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12Ctumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘do-not-eat-me’ signal, is significantly upregulated on cancer cells upon G12Ci treatment. Blocking CD24 enhanced macrophage phagocytosis of cancer cells and significantly sensitized tumors to G12Ci treatment. Similar findings were observed in KRASG12D-driven PDAC. Our study reveals common and distinct oncogenic KRAS allele-specific biology and identifies a clinically actionable adaptive mechanism that may improve the efficacy of oncogenic KRAS inhibitor therapy in PDAC.SignificanceLack of faithful preclinical models limits the exploration of resistance mechanisms to KRASG12Cinhibitor in PDAC. We generated an autochthonous KRASG12C-driven PDAC model, which revealed allele-specific biology of the KRASG12Cduring PDAC development. We identified CD24 as an actionable adaptive mechanisms in cancer cells induced upon KRASG12Cinhibition and blocking CD24 sensitizes PDAC to KRAS inhibitors in preclinical models.
Inter-organellar nucleic acid communication by a mitochondrial tRNA regulates nuclear metabolic transcription
Authors: Rouya Christopher , Yambire King Faisal , Derbyshire Mark L. , Alwaseem Hanan , Tavazoie Sohail F. 
Published: September 2023

SUMMARYEfficient communication between mitochondria and the nucleus underlies homoeostatic metabolic control, though the involved mitochondrial factors and their mechanisms are poorly defined. Here, we report the surprising detection of multiple mitochondrial-derived transfer RNAs (mito-tRNAs) within the nuclei of human cells. Focused studies of nuclear-transported mito-tRNA-asparagine (mtAsn) revealed that its cognate charging enzyme (NARS2) is also present in the nucleus. MtAsn promoted interaction of NARS2 with histone deacetylase 2 (HDAC2), and repressed HDAC2 association with specific chromatin loci. Perturbation of this axis using antisense oligonucleotides promoted nucleotide biogenesis and enhanced breast cancer growth, and RNA and nascent transcript sequencing demonstrated specific alterations in the transcription of nuclear genes. These findings uncover nucleic-acid mediated communication between two organelles and the existence of a machinery for nuclear gene regulation by a mito-tRNA that restricts tumor growth through metabolic control.HighlightsMultiple mitochondrial-derived tRNAs are detected in human cell nucleiMtAsn promotes binding between NARS2 and HDAC2Metabolic alterations driven by mtAsn impact cell proliferationMtAsn inhibition releases HDAC2 to bind and transcriptionally regulate multiple nuclear genes
Benchmarking long-read sequencing strategies for obtaining ASV-resolved rRNA operons from environmental microeukaryotes
Authors: Overgaard Christina Karmisholt , Jamy Mahwash , Radutoiu Simona , Burki Fabien , Dueholm Morten Kam Dahl 
Published: September 2023

AbstractThe use of short-read metabarcoding for classifying microeukaryotes is challenged by the lack of comprehensive 18S rRNA reference databases. While recent advances in high-throughput long-read sequencing provide the potential to greatly increase the phylogenetic coverage of these databases, the performance of different sequencing technologies and subsequent bioinformatics processing remain to be evaluated, primarily because of the absence of well-defined eukaryotic mock communities. To address this challenge, we created a eukaryotic rRNA operons clone-library and turned it into a precisely defined synthetic eukaryotic mock community. This mock community was then used to evaluate the performance of three long-read sequencing techniques (PacBio HiFi, and Nanopore UMI with/without clonal pre-amplification) and three tools for resolving amplicons sequence variants (ASVs) (Uchime3, Unoise3, and DADA2). We investigated the sensitivity of the sequencing techniques based on the number of detected mock taxa, and the accuracy of the different ASV-calling tools with a specific focus on the presence of chimera among the final rRNA operon ASVs. Based on our findings, we provide recommendations and best practice protocols for how to cost-effectively obtain essential error-free rRNA operons in high-throughput. An agricultural soil sample was used to demonstrate that the sequencing and bioinformatic results from the mock community also translates to highly diverse natural samples.
Targeted hypermutation of putative antigen sensors in multicellular bacteria
Authors: Doré H. , Eisenberg A. R. , Junkins E. N. , Leventhal G. E. , Ganesh Anakha , Cordero O. X. , Paul B. G. , Valentine D. , O’Malley M. A. , Wilbanks E. G. 
Published: September 2023

AbstractDiversity-generating retroelements (DGRs) are used by bacteria, archaea and viruses as a targeted mutagenesis tool. Through error-prone reverse transcription, DGRs introduce random mutations at specific genomic loci, enabling rapid evolution of these targeted genes. However, the function and benefits of DGR-diversified proteins in cellular hosts remains elusive. We find that 85% of DGRs from one of the major monophyletic lineages of DGR reverse transcriptases are encoded by multicellular bacteria, which often have two or more DGR loci in their genomes. Using the multicellular purple sulfur bacteriumThiohalocapsasp. PB-PSB1 as an example, we characterized nine distinct DGR loci that cumulatively lead to more than 10294possible different combinations of target polypeptides. With environmental metagenomes from individualThiohalocapsaaggregates, we show that most of PB-PSB1’s DGR targets are diversified across its biogeographic range, with spatial heterogeneity in the diversity of each locus. In PSB1 and other members of this lineage of cellular DGRs, diversified target genes are associated with NACHT-domain anti-phage defenses and putative ternary conflict systems previously shown to be enriched in multicellular bacteria. We propose that these DGR-diversified target genes act as antigen sensors that confer a form of adaptive immunity to their multicellular consortia. These findings have implications for the emergence of multicellularity, as the NACHT-domain anti-phage systems and ternary systems share both domain homology and conceptual similarities with the innate immune and programmed cell death pathways of plants and metazoans.SignificanceTo defend themselves against predators, bacteria employ a wide range of conflict systems, some of which are enriched in multicellular bacteria. Here, we show that numerous multicellular bacteria use related diversity-generating retroelements (DGRs) to diversify such conflict systems. Error-prone reverse transcription in DGRs introduces random, targeted mutations and rapid diversification. We usedThiohalocapsaPB-PSB1, a member of multicellular bacterial consortia, as a model to study this association between conflict systems and DGRs. We characterized the natural diversity of PB-PSB1 DGRs and propose they function as hypervariable antigen sensors. The accumulation of such DGR-diversified defense systems in multicellular bacteria emphasizes the fitness advantage of a rapidly diversifying immune system for the evolution of multicellularity.
Epileptic responses in marmosets induced by knockdown of CREB Regulated Transcription Coactivator 1 (CRTC1)
Authors: Nakagami Yuki , Komatsu Misako , Nakae Ken , Otsuka Masanari , Hata Junichi , Mizukami Hiroaki , Takemori Hiroshi , Ishii Shin , Okano Hideyuki , Watakabe Akiya , Yamamori Tetsuo 
Published: September 2023

SummaryAnimal models have contributed greatly to the development of anticonvulsant drugs. However, 20-30% of epilepsy patients still do not achieve adequate seizure control. It is important to understand the biological mechanisms of epilepsy in order to develop treatments and novel anticonvulsant drugs. Here we reportCRTC1knockdown (KD) induced abnormalcFOSexpression beyond the injection sites followed by epileptic response by three local injections of short hairpin RNA (shRNA) in marmoset V1. Longitudinal monitoring of cortical-wide neural activity revealed transient changes in high frequency oscillations by cortical electrocorticography throughout the cortex, and a lesion in the temporal lobe was observed by MRI and postmortem histology.shCRTC1KD marmosets showed severe lesions surrounding the injection site several months after injection. Glial cell activation may occur simultaneously or prior to IEG induction aftershCRTC1injection. Thus, the epileptic process from seizure onset to remission can be studied in this animal model.
Diet composition drives tissue-specific intensity of murine enteric infections
Authors: Israelsen Helene , Vedsted-Jakobsen Amalie , Zhu Ling , Gagnaire Aurelie , von Munchow Alexandra , Polakovicova Nina , Valente Angela H. , Raza Ali , Andersen-Civil Audrey I.S. , Olsen John E. , Myhill Laura J. , Geldhof Peter , Williams Andrew R. 
Published: September 2023

AbstractDiet composition plays a large role in regulating of gut health and enteric infection. In particular, synthetic ‘Western-style’ diets may predispose to disease, whilst whole-grain diets containing high levels of crude fiber are thought to promote gut health. Here we show that, in contrast to this paradigm, mice fed unrefined chow are significantly more susceptible to infection withTrichuris muris, a caecum-dwelling nematode, than mice given refined, semi-synthetic diets (SSD). Moreover, mice fed SSD supplemented with inulin, a fermentable fiber, developed chronicT. murisburdens whereas mice given SSD efficiently cleared the infection. Diet composition significantly impacted infection-induced changes in the host gut microbiome. Mice infected with the bacteriumCitrobacter rodentiumwere also more susceptible to pathogen colonization when fed either chow or inulin-enriched SSD. However, transcriptomic analysis of tissues from mice fed either SSD or inulin-enriched SSD revealed that, in contrast toT. muris, increasedC. rodentiuminfection appeared to be independent of the host immune response. Accordingly, exogenous treatment with IL-25 partially reducedT. murisburdens in inulin-fed mice, whereas IL-22 treatment was unable to restore resistance toC. rodentiumcolonization. Diet-mediated effects on pathogen burden were more pronounced for large intestine-dwelling pathogens, as effects on small intestinal helminth (Heligmosomoides polygyrus) were less evident, and protozoan (Giardia muris) infection burdens were equivalent in mice fed chow, inulin-enriched SSD, or SSD, despite higher cyst excretion in chow-fed mice. Collectively, our results point to a tissue- and pathogen-restricted effect of dietary fiber levels on enteric infection intensity.ImportanceEnteric infections induce dysbiosis and inflammation and are a major public health burden. As the gut environment is strongly shaped by diet, the role of different dietary components in promoting resistance to infection is of interest. Whilst diets rich in fiber or whole grain are normally associated with improved gut health, we show here that these components predispose the host to higher levels of pathogen infection. Thus, our results have significance for interpreting how different dietary interventions may impact on gastrointestinal infections. Moreover, our results may shed light on our understanding of how gut flora and musical immune function is influenced by the food that we eat.