bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Glycerol on Microbial Community in Industrial Wastewater Treatment Plant
Authors: Negara M A Prawira , Jayawardhana B , Euverink G J W 
Published: January 2023

ABSTRACTIn this paper, we developed and analyzed lab-scale reactors that model the industrial saline wastewater treatment plant (SWWTP) used in North Water SWWTP in Delfzijl, the Netherlands. This industrial wastewater treatment plant is different from a typical municipal wastewater treatment plant, where the wastewater has some recalcitrant chemicals that are hard to degrade and contains a high COD-to-nitrogen ratio and a high concentration of NaCl. The process also differs from other standard industrial wastewater plants where the anaerobic process precedes the aerobic process. The proposed lab-scale reactors are shown to be stable and able to represent the studied industrial SWWTP where glycerol is present in abundance, and there is no similar lab-scale model that has investigated the effect of glycerol on the process. The removal of COD (glycerol) and nitrogen in the system and the changes in the microbial community in both reactors was followed over time. Based on the data, we were able to study the growth of the microbial population that is present in the sludge. The result of the experiment showed that glycerol and ammonia were completely removed, and some nitrate was left in the effluent. At the end of the experiment, we determined that the order Actinomycetales dominated the anaerobic reactor since it is known as the organisms that use glycerol as the carbon source and is quite tolerant with a high salt concentration in the influent. On the other hand, the order Flavobacteriales dominated the aerobic reactor as it is correlated with the ammonia concentration.
The effects of social experience on host gut microbiome in male zebrafish (Danio rerio)
Authors: Scott Emily , Brewer Michael S , Peralta Ariane L , Issa Fadi A 
Published: January 2023

ABSTRACTAlthough the gut and the brain vastly differ in physiological function, they have been interlinked in a variety of different neurological and behavioral disorders. The bacteria that comprise the gut microbiome communicate and influence the function of various physiological processes within the body including nervous system function. However, the effects of social experience in the context of dominance and chronic stress on gut microbiome remain poorly understood. Here, we examined whether social experience impacts the host zebrafish (Danio rerio) gut microbiome. We studied how social dominance during the first two weeks of social interactions changed the composition of zebrafish gut microbiome by comparing gut bacterial composition, diversity and relative abundance among socially dominant, submissive, social isolates, and control group-housed communal fish. Using amplicon sequencing of the 16S rRNA gene, we report that social dominance significantly affects host gut bacterial community composition but not bacterial diversity. At the genus-level,Aeromonasand unclassified Enterobacteriaceae relative abundance decreased in dominant individuals while commensal bacteria (e.g.,ExiguobacteriumandCetobacterium)increased in relative abundance. Conversely, the relative abundance ofPsychrobacterandAcinetobacterwas increased in subordinates, isolates, and communal fish compared to dominant fish. The shift in commensal and pathogenic bacteria highlights the impact of social experience and the accompanying stress on gut microbiome with potentially similar effects in other social organisms.IMPORTANCEDisruptions in the gut microbiome negatively impact various systems in the body. Recently, the gut microbiome has been associated with neurological deficits in both behavioral and neurodegenerative disorders. Given the increasing prevalence in diagnosis of both neurological disease and behavioral disorders, researching the link between social behaviors and the gut microbiome is critical to better understand how the gut and the brain communicate during healthy and diseased states. Our research findings demonstrate the effects of social dominance and chronic stress on host gut microbiome composition. By identifying variations in bacterial relative abundance based on social experience and associated stress, a broader understanding ofpathogenic(e.g., Enterobacteriaceae,Aeromonas) versus commensal communities (e.g.,Exiguobacterium, Cetobacterium) and related host physiology can be inferred.
The association between academic pressure and adolescent mental health problems: A systematic review
Authors: Steare Thomas , Muñoz Carolina Gutiérrez , Sullivan Alice , Lewis Gemma 
Published: January 2023

AbstractBackgroundAcademic pressure is a potential contributor to adolescent mental health problems, but international evidence on this association has never been synthesised.MethodsWe conducted the first systematic review on the association between academic pressure and adolescent depression, anxiety, self-harm, suicidality, suicide attempts and suicide. We searched MEDLINE, PsycINFO, ERIC and Web of Science (core collection) up to November 24, 2022, for studies of school-going children or adolescents, which measured academic pressure or timing within the school year as the exposure and depression, anxiety, self-harm, or suicidal ideation, attempts or suicide as outcomes. Risk of bias was assessed using the Mixed Methods Appraisal Tool. We used narrative synthesis to summarise the evidence. The review was prospectively registered with PROSPERO (CRD42021232702).ResultsWe included 52 studies primarily from Asia (n=26) and Europe (n=20). Most studies assessed mixed anxiety and depressive symptoms (n=20) or depressive symptoms (n=19). Forty-eight studies found evidence of a positive association between academic pressure or timing within the school year and at least one mental health outcome.LimitationsMost studies were cross-sectional (n=39), adjusted for a narrow range of confounders or had other limitations which limited the strength of causal inferences.ConclusionsWe found evidence that academic pressure is a potential candidate for public health interventions which could prevent adolescent mental health problems. Large population-based cohort studies are needed to investigate whether academic pressure is a causal risk factor that should be targeted in school- and policy-based interventions.FundingUCL Health of the Public; Wellcome Institutional Strategic Support Fund.
Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer
Authors: Pearce David R. , Akarca Ayse U. , De Maeyer Roel P. H. , Kostina Emily , Huebner Ariana , Sivakumar Monica , Karasaki Takahiro , Shah Kavina , Janes Sam M. , McGranahan Nicholas , Reddy Venkat , Akbar Arne N. , Moore David A. , Marafioti Teresa , Swanton Charles , Hynds Robert E. 
Published: January 2023

ABSTRACTPatient-derived xenograft (PDX) models involve the engraftment of tumour tissue in immunocompromised mice and represent an important pre-clinixtcal oncology research. A limitation of non-small cell lung cancer (NSCLC) PDX model derivation in NOD-scidIL2Rgammanull(NSG) mice is that a subset of initial engraftments are of lymphocytic, rather than tumour origin. In the lung TRACERx PDX pipeline, lymphoproliferations occurred in 17.8% of lung adenocarcinoma and 10% of lung squamous cell carcinoma transplantations, despite none of these patients having a prior or subsequent clinical history of lymphoproliferative disease. Lymphoproliferations were predominantly human CD20+ B cells and had the immunophenotype expected for post-transplantation diffuse large B cell lymphoma. All lymphoproliferations expressed Epstein-Barr-encoded RNAs (EBER). Analysis of immunoglobulin light chain gene rearrangements in three tumours where multiple tumour regions had resulted in lymphoproliferations suggested that each had independent clonal origins. Overall, these data suggest the presence of B cell clones with lymphoproliferative potential within primary NSCLC tumours that are under continuous immune surveillance. Since these cells can be expanded following transplantation into NSG mice, our data highlight the value of quality control measures to identify lymphoproliferations within xenograft pipelines and support the incorporation of strategies to minimise lymphoproliferations during the early stages of xenograft establishment pipelines. To present the histology data herein, we developed a Python-based tool for generating patient-level pathology overview figures from whole-slide image files; PATHOverview is available on GitHub (https://github.com/EpiCENTR-Lab/PATHOverview).
Thermoneutral housing does not accelerate metabolic dysfunction-associated fatty liver disease in male or female mice fed a Western diet
Authors: Nunes Julia R.C. , Smith Tyler K.T. , Ghorbani Peyman , O’Dwyer Conor , Trzaskalski Natasha A. , Dergham Habiba , Pember Ciara , Kilgour Marisa K. , Mulvihill Erin E. , Fullerton Morgan D. 
Published: January 2023

AbstractObjectiveMetabolic dysfunction-associated fatty liver disease (MAFLD) represents a growing cause of mortality and morbidity and encompasses a spectrum of liver pathologies. Potential therapeutic targets have been identified and are currently being pre-clinically and clinically tested. However, while dozens of preclinical models have been developed to recapitulate various stages of MAFLD, few achieve fibrosis using an experimental design that mimics human pathogenesis. We sought to clarify whether the combination of thermoneutral (TN) housing and consumption of a classical Western diet (WD) would accelerate the onset of MAFLD and progression in male and female mice.MethodsMale and female C57Bl/6J mice were fed a nutrient-matched low-fat control or Western diet (41% Kcal from fat, 43% carbohydrate and 0.2% cholesterol; WD) starting at ∼12 wk of age for a further 16 wk. Mice were divided and housed with littermates at either standard temperature (TS; 22°C) or thermoneutral conditions (TN; ∼29°C). Mice underwent tests for glucose tolerance, insulin sensitivity and body composition, as well as intestinal permeability. Following tissue harvest, circulating and liver markers of hepatic disease progression toward steatosis and fibrosis were determined.ResultsWhile male mice housed at TNand fed a WD were significantly heavier than TS-housed control animals, no other differences in body weight or composition were observed. WD-fed females housed under TNconditions had higher circulating LDL-cholesterol; however, there were no other significant differences between TNand TS-housing in circulating or hepatic lipid levels. While WD-fed TNmales had higher ALT levels, no other differences in markers of liver injury or disease progression were observed. Moreover, females housed at TNconditions and fed a WD remained significantly protected against the induction of fibrosis compared to male counterparts. Interestingly, sex-specific differences were observed in markers of glucose and insulin tolerance, where TNhousing and WD feeding resulted in hyperglycemia and impaired insulin responsiveness in both sexes, but glucose intolerance only in male mice.ConclusionsWhile TNhousing has been demonstrated to exacerbate high fat-induced hepatic steatosis and inflammation in male and female mice, coupling TNhousing with a WD for 16 wk was not sufficient to augment fatty liver progression in male or female mice.HighlightsThermoneutral housing and Western diet feeding does not progress to NASHFemale mice are not more susceptible to obesity induced fatty liver under these conditionsTemperature and diet had sex-specific effects on glucose tolerance and insulin sensitivity
SynBa: Improved estimation of drug combination synergies with uncertainty quantification
Authors: Zhang Haoting , Ek Carl Henrik , Rattray Magnus , Milo Marta 
Published: January 2023

AbstractMotivationThere exists a range of different quantification frameworks to estimate the synergistic effect of drug combinations. The diversity and disagreement in estimates make it challenging to determine which combinations from a large drug screening should be proceeded with. Furthermore, the lack of accurate uncertainty quantification for those estimates precludes the choice of optimal drug combinations based on the most favourable synergistic effect.ResultsIn this work, we propose SynBa, a flexible Bayesian approach to estimate the uncertainty of the synergistic efficacy and potency of drug combinations, so that actionable decisions can be derived from the model outputs. The actionability is enabled by incorporating the Hill equation into SynBa, so that the parameters representing the potency and the efficacy can be preserved. Existing knowledge may be conveniently inserted due to the flexibility of the prior, as shown by the empirical Beta prior defined for the normalised maximal inhibition. Through experiments on large combination screenings and comparison against benchmark methods, we show that SynBa provides improved accuracy of dose-response predictions and better-calibrated uncertainty estimation for the parameters and the predictions.AvailabilityThe code for SynBa is available athttps://github.com/HaotingZhang1/SynBa. The datasets are publicly available (DOI of DREAM: 10.7303/syn4231880; DOI of the NCI-ALMANAC subset: 10.5281/zenodo.4135059).Contacthz381@cam.ac.uk
KDM6 demethylases mediate EWSR1-FLI1-driven oncogenic transformation in Ewing Sarcoma
Authors: Figuerola-Bou Elisabet , Rios-Astorch Carla , Blanco Enrique , Sánchez-Jiménez María , Táboas Pablo , Fernández Guerau , Gómez Soledad , Muñoz Oscar , Castellano-Escuder Pol , Pérez-Jaume Sara , Prada Estela , Mateo-Lozano Silvia , Riggi Nicolo , Avgustinova Alexandra , Lavarino Cinzia , Di Croce Luciano , Sánchez-Molina Sara , Mora Jaume 
Published: January 2023

SUMMARYEwing Sarcoma (EwS) is an aggressive bone and soft tissue tumor driven by the fusion oncoprotein EWSR1-FLI1. This aberrant transcription factor binds to GGAA microsatellites, causing epigenetic reprogramming through the formation of active neo-enhancers in a permissive cellular context. Inhibition of the oncogene remains challenging and current efforts instead seek to exploit emergent epigenetic treatments targeting EWSR1-FLI1 cofactors. Here, stemming from the genome-wide redistribution of H3K27me3 upon expression of EWSR1-FLI1 in pediatric hMSC, we unravel the contribution of the H3K27me3 demethylases KDM6A and KDM6B in transcriptional activation at EWSR1-FLI1 enhancers. We found that KDM6A has a demethylase-independent role in recruiting the SWI/SNF member BRG1 at EWSR1-FLI1-primed enhancers containing single GGAA motif, which is critical for EwS tumor growth. Conversely, KDM6B demethylates H3K27me3 at EWSR1-FLI1-active enhancers containing multimeric GGAA repeats and its deletion synergizes with EZH2 inhibitors. Our results highlight KDM6 demethylases as EWSR1-FLI1 cofactors with potential for future targeted therapies.
Amino acid transporter SLC7A5 regulates Paneth cell function to affect the intestinal inflammatory response
Authors: Bao Lingyu , Fu Liezhen , Su Yijun , Chen Zuojia , Peng Zhaoyi , Sun Lulu , Gonzalez Frank J. , Wu Chuan , Zhang Hongen , Shi Bingyin , Shi Yun-Bo 
Published: January 2023

AbstractThe intestine is critical for not only processing and resorbing nutrients but also protecting the organism from the environment. These functions are mainly carried out by the epithelium, which is constantly being self-renewed. Many genes and pathways can influence intestinal epithelial cell proliferation. Among them is mTORC1, whose activation increases cell proliferation. Here, we report the first intestinal epithelial cell-specific knockout (ΔIEC) of an amino acid transporter capable of activating mTORC1. We show that the transporter, SLC7A5, is highly expressed in mouse intestinal crypt andSlc7a5ΔIECreduces mTORC1 signaling. Surprisingly,Slc7a5ΔIECmice have increased cell proliferation but reduced secretory cells, particularly mature Paneth cells. scRNA-seq and electron microscopic analyses revealed dedifferentiation of Paneth cells inSlc7a5ΔIECmice, leading to markedly reduced secretory granules with little effect on Paneth cell number. We further show thatSlc7a5ΔIECmice are prone to experimental colitis. Thus, SLC7A5 regulates secretory cell differentiation to affect stem cell niche and/or inflammatory response to regulate cell proliferation.
Nuclease-dead S.aureusCas9 downregulates alpha-synuclein and reduces mtDNA damage and oxidative stress levels in patient-derived stem cell model of Parkinson’s disease
Authors: Sastre Danuta , Zafar Faria , Torres C. Alejandra Morato , Piper Desiree , Kirik Deniz , Sanders Laurie H. , Qi Stanley , Schüle Birgitt 
Published: January 2023

AbstractParkinson’s disease (PD) is one of the most common neurodegenerative diseases, but no disease modifying therapies have been successful in clinical translation presenting a major unmet medical need. A promising target is alpha-synuclein or its aggregated form, which accumulates in the brain of PD patients as Lewy bodies. While it is not entirely clear which alpha-synuclein protein species is disease relevant, mere overexpression of alpha-synuclein in hereditary forms leads to neurodegeneration.To specifically address gene regulation of alpha-synuclein, we developed a CRISPR interference (CRISPRi) system based on the nuclease deadS. aureusCas9 (SadCas9) fused with the transcriptional repressor domain Krueppel-associated box to controllably repress alpha-synuclein expression at the transcriptional level. We screened single guide (sg)RNAs across theSNCApromoter and identified several sgRNAs that mediate downregulation of alpha-synuclein at varying levels. CRISPRi downregulation of alpha-synuclein in iPSC-derived neuronal cultures from a patient with anSNCAgenomic triplication showed functional recovery by reduction of oxidative stress and mitochondrial DNA damage.Our results are proof-of-conceptin vitrofor precision medicine by targeting theSNCAgene promoter. TheSNCACRISPRi approach presents a new model to understand safe levels of alpha-synuclein downregulation and a novel therapeutic strategy for PD and related alpha-synucleinopathies.
Spatially Resolved Transcriptomic Analysis of the Germinating Barley Grain
Authors: Peirats-Llobet Marta , Yi Changyu , Liew Lim Chee , Berkowitz Oliver , Narsai Reena , Lewsey Mathew G. , Whelan James 
Published: January 2023

AbstractSeeds, which provide a major source of calories for humans, are a unique stage of a flowering plant ‘s lifecycle. During seed germination the embryo reactivates rapidly and goes through major developmental transitions to become a seedling. This requires extensive and complex spatiotemporal coordination of cell and tissue activity. Existing gene expression profiling methods, such as laser capture microdissection followed by RNA-seq and single-cell RNA-seq, suffer from either low throughput or the loss of spatial information about the cells analysed. Spatial transcriptomics methods couple high throughput analysis of gene expression simultaneously with the ability to record the spatial location of each individual region analysed. We developed a spatial transcriptomics workflow for germinating barley grain to better understand the spatiotemporal control of gene expression within individual seed cell types. More than 14,000 genes were differentially regulated across 0, 1, 3, 6 and 24 hours after imbibition. This approach enabled us to observe that many functional categories displayed specific spatial expression patterns that could be resolved at a sub-tissue level. Individual aquaporin gene family members, important for water and ion transport, had specific spatial expression patterns over time, as well as genes related to cell wall modification, membrane transport and transcription factors. Using spatial autocorrelation algorithms, we were able to identify auxin transport genes that had increasingly focused expression within subdomains of the embryo over germination time, suggestive of a role in establishment of the embryo axis. Together, our data provides an unprecedented spatially resolved cellular map for barley grain germination and specific genes to target for functional genomics to define cellular restricted processes in tissues during germination. The data can be viewed athttps://spatial.latrobe.edu.au/.
Deep Learning Assisted Smartphone-based Quantitative Microscopy for Label-free Hematological Analysis
Authors: Huang Bingxin , Kang Lei , Tsang Victor T. C. , Lo Claudia T. K. , Wong Terence T. W. 
Published: January 2023

AbstractHematologists evaluate alterations in blood cell enumeration and morphology to confirm the peripheral blood smear findings through manual microscopic examination. However, routine peripheral blood smear analysis is both time-consuming and labor-intensive. Here, we propose a smartphone-based autofluorescence microscopy (Smart-AM) system for imaging label-free blood smears at sub-cellular resolution and performing hematological analysis. Smart-AM enables rapid, high-quality, and label-free visualization of morphological features of different blood cells (leukocytes, erythrocytes, and thrombocytes) and abnormal variations in blood cells. Moreover, assisted with deep learning algorithms, this technique can automatically detect and classify different leukocytes with high accuracy, and transform the autofluorescence images into virtual Giemsa-stained images maintaining significant cellular features. The proposed technique is portable, cost-effective, and user-friendly, making it significant for broad point-of-care applications.
A time- and space-resolved nuclear receptor atlas in mouse liver
Authors: Zummo Francesco Paolo , Berthier Alexandre , Gheeraert Céline , Vinod Manjula , Bobowski-Gérard Marie , Molendi-Coste Olivier , Pineau Laurent , Jung Matthieu , Guille Loic , Chevalier-Dubois Julie , Dombrowicz David , Staels Bart , Eeckhoute Jérôme , Lefebvre Philippe 
Published: January 2023

ABSTRACTThe unique functional versatility of the liver is paramount for organismal homeostasis. Both liver development and adult functions are controlled by tightly regulated transcription factor networks, within which nuclear receptors regulate essential functions of parenchymal and non-parenchymal cells. Acting as transcription factors sensitive to extracellular cues such as steroidal hormones, lipid metabolites, xenobiotics… and modulated by intracellular signaling pathways, nuclear receptors orchestrate many aspects of hepatic physiology. While liver functional zonation and adaptability to fluctuating conditions are known to rely on a sophisticated cellular architecture, a comprehensive knowledge of nuclear receptor functions in the different liver cell types is still lacking. As a first step toward the accurate mapping of nuclear receptor functions in mouse liver, we characterized their levels of expression in whole liver as a function of time and diet, and explored nuclear receptor isoform expression in hepatocytes, cholangiocytes, Kupffer cells, hepatic stellate cells and liver sinusoidal cells. In addition, we leveraged liver single cell RNAseq studies to provide here an up-to-date compendium of nuclear receptor expression in mouse liver in space and time.