bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying drivers of sewage-associated pollutants in pollinators across urban landscapes
Authors: Meyer Michael F. , Brousil Matthew R. , Lee Benjamin W. , Armstrong Madison L. , Bloom Elias H. , Crowder David W. 
Published: January 2023

ABSTRACTHuman sewage can introduce pollutants into food webs and threaten ecosystem integrity. Among the many sewage-associated pollutants, pharmaceuticals and personal care products (PPCPs) are useful indicators of sewage in ecosystems and can also cause potent ecological consequences even at minute concentrations (e.g., ng/L). Despite increased study over the past three decades, PPCPs in terrestrial systems have been less studied than those in aquatic ecosystems. To evaluate PPCP prevalence and drivers in a terrestrial ecosystem, we analyzed managed and native bees collected from agroecosystems in Washington State (USA) for PPCPs. Caffeine, paraxanthine, cotinine, and acetaminophen were detected in all three evaluated taxa (Bombus vosnesenskii, Agapostemon texanus, andApis mellifera), withB. vosnesenskiiandA. texanushaving a higher probability of PPCP detection relative toA. mellifera. The probability for PPCP presence in all three taxa increased in landscapes with more human development or greater plant abundance, with significant but negative interactions among these factors. These results suggest that human activity, availability of resources, and species-specific traits affect the introduction and mobilization of PPCPs in terrestrial ecosystems. Consequently, monitoring PPCPs and their ecological responses in terrestrial ecosystems creates opportunities to synthesize consequences of sewage pollution across terrestrial and aquatic ecosystems and organism types.
Estimation of reproduction number of SARS-CoV-2 Omicron variant outbreak in Hong Kong
Authors: Allieta Mattia , Komloš Jelena , Sebastiano Davide Rossi 
Published: January 2023

AbstractWe present the evolution of time dependent reproduction number across the five different Hong Kong Special Administrative Region of the People’s Republic of China (HK) epidemic waves from January, 2020, to March, 2022. We provide reliable estimation of reproduction number of Omicron variant of concern (VOC) by analysing data related to fifth wave to determine its peculiar characteristics with respect to the other VOCs.HK could be considered as the optimal model for the calculation of the dynamics of Omicron VOC transmission in an environment representative of the fully populated cities of the Asian Pacific coast.On the basis of Rt calculated for Omicron VOC in our work, researchers could refine provisional data for the current outbreak which is affecting China
Sex differences in adolescent cannabis vapor self-administration mediate enduring effects on behavioral flexibility and prefrontal microglia activation in rats
Authors: Freels Timothy G. , Westbrook Sara R. , Wright Hayden R. , Kuyat Jacqulyn R. , Zamberletti Erica , Malena Alexandra M. , Melville Max W. , Brown Amanda M. , Glodosky Nicholas C. , Ginder Darren E. , Klappenbach Courtney M. , Delevich Kristen M. , Rubino Tiziana , McLaughlin Ryan J. 
Published: January 2023

ABSTRACTCannabis is the most used illicit drug in the United States. With many states passing legislation to permit its recreational use, there is concern that cannabis use among adolescents could increase dramatically in the coming years. Historically, it has been difficult to model real-world cannabis use to investigate the causal relationship between cannabis use in adolescence and behavioral and neurobiological effects in adulthood. To this end, we used a novel volitional vapor administration model to investigate long-term effects of cannabis use during adolescence on the medial prefrontal cortex (mPFC) and mPFC-dependent behaviors in male and female rats. Adolescent (35-55 day old) female rats had significantly higher rates of responding for vaporized Δ9-tetrahydrocannabinol (THC)-dominant cannabis extract (CANTHC) compared to adolescent males. In adulthood (70-110 day old), female, but not male, CANTHCrats also took more trials to reach criterion and made more regressive errors in an automated attentional set-shifting task compared to vehicle rats. Similar set-shifting deficits were observed in males when they were exposed to a non-contingent CANTHCvapor dosing regimen that approximated CANTHCself-administration rates in females. No differences were observed in effort-based decision making in either sex. In the mPFC, female (but not male) CANTHCrats displayed more reactive microglia with no significant changes in myelin basic protein expression or dendritic spine density. Together, these data reveal important sex differences in rates of cannabis vapor self-administration in adolescence that confer enduring alterations to mPFC structure and function. Importantly, female-specific deficits in behavioral flexibility appear to be driven by elevated rates of CANTHCself-administration as opposed to a sex difference in the effects of CANTHCvaporper se.
A new cheese population inPenicillium roquefortiand adaptation of the five populations to their ecological niche
Authors: Crequer Ewen , Ropars Jeanne , Jany Jean-Luc , Caron Thibault , Coton Monika , Snirc Alodie , Vernadet Jean-Philippe , Branca Antoine , Giraud Tatiana , Coton Emmanuel 
Published: January 2023

AbstractDomestication is an excellent case study for understanding adaptation and multiple fungal lineages have been domesticated for fermenting food products. Studying domestication in fungi has thus both fundamental and applied interest. Genomic studies have revealed the existence of four populations within the blue-cheese-making fungusPenicillium roqueforti. The two cheese populations show footprints of domestication, but the adaptation of the two non-cheese populations to their ecological niches (i.e. silage/spoiled food and lumber/spoiled food) has not been investigated yet. Here, we reveal the existence of a newP. roquefortipopulation, specific to French Termignon cheeses, produced using small-scale traditional practices, with spontaneous blue mould colonisation. This Termignon population is genetically differentiated from the four previously identified populations, providing a novel source of genetic diversity for cheese making. Phenotypically, the non-Roquefort cheese population was the most differentiated, with specific traits beneficial for cheese making, in particular higher tolerance to salt, to acidic pH and to lactic acid. Our results support the view that this clonal population, used for many cheese types in multiple countries, is a domesticated lineage on which humans exerted strong selection. The Termignon population displayed substantial genetic diversity, both mating types, horizontally transferred regions previously detected in the non-Roquefort population, and intermediate phenotypes between cheese and non-cheese populations. The lumber/spoiled food and silage/spoiled food populations were not more tolerant to crop fungicides but showed faster growth in various carbon sources (e.g. dextrose, pectin, sucrose, xylose and/or lactose), which can be beneficial in their ecological niches. Such contrasted phenotypes betweenP. roquefortipopulations, with beneficial traits for cheese-making in the cheese populations and enhanced ability to metabolise sugars in the lumber/spoiled food population, support the inference of domestication in cheese fungi and more generally of adaptation to anthropized environments.
The modular biochemical reaction network structure of cellular translation
Authors: Cuevas-Zuviría Bruno , Fer Evrim , Adam Zachary R. , Kaçar Betül 
Published: January 2023

AbstractTranslation is an essential attribute of all living cells. At the heart of cellular operation, it is a chemical information decoding process that begins with an input string of nucleotides and ends with the synthesis of a specific output string of peptides. The translation process is interconnected with gene expression, physiological regulation, transcription, and responses to signaling molecules, among other cellular functions. Foundational efforts have uncovered a wealth of knowledge about the mechanistic functions of and many interactions between components of translation, but the broader biochemical connections between translation, metabolism and polymer biosynthesis that enable translation to occur have not been comprehensively mapped. Here we present a multilayer graph of biochemical reactions describing the translation, polymer biosynthesis and metabolism networks of anEscherichia colicell. Intriguingly, the compounds that compose these three layers are distinctly aggregated into three modes regardless of their layer categorization. Multimodal mass distributions are well-known in ecosystems, but this is the first such distribution reported at the biochemical level. The degree distributions of the translation and metabolic networks are each likely to be heavy-tailed, but the polymer biosynthesis network is not. A multimodal mass-degree distribution indicates that the translation and metabolism networks are each distinct, adaptive biochemical modules, and that the gaps between the modes reflect evolved responses to the functional use of metabolite, polypeptide and polynucleotide compounds. The chemical reaction network of cellular translation opens new avenues for exploring complex adaptive phenomena such as percolation and phase changes in biochemical contexts.
CompCorona: A Web Portal for Comparative Analysis of the Host Transcriptome of PBMC and Lung SARS-CoV-2, SARS-CoV, and MERS-CoV
Authors: Salihoğlu Rana , Saraçoğlu Fatih , Sibai Mustafa , Zengin Talip , Masud Başak Abak , Karasoy Onur , Önal-Süzek Tuğba 
Published: January 2023

AbstractMotivationUnderstanding the host response to SARS-CoV-2 infection is crucial for deciding on the correct treatment of this epidemic disease. Although several recent studies reported the comparative transcriptome analyses of the three coronaviridae (CoV) members; namely SARS-CoV, MERS-CoV, and SARS-CoV-2, there is yet to exist a web-tool to compare increasing number of host transcriptome response datasets against the pre-processed CoV member datasets. Therefore, we developed a web application called CompCorona, which allows users to compare their own transcriptome data of infected host cells with our pre-built datasets of the three epidemic CoVs, as well as perform functional enrichment and principal component analyses (PCA).ResultsComparative analyses of the transcriptome profiles of the three CoVs revealed that numerous differentially regulated genes directly or indirectly related to several diseases (e.g., hypertension, male fertility, ALS, and epithelial dysfunction) are altered in response to CoV infections. Transcriptome similarities and differences between the host PBMC and lung tissue infected by SARS-CoV-2 are presented. Most of our findings are congruent with the clinical cases recorded in the literature. Hence, we anticipate that our results will significantly contribute to ongoing studies investigating the pre-and/or post-implications of SARS-CoV-2 infection. In addition, we implemented a user-friendly public website, CompCorona for biomedical researchers to compare users own CoV-infected host transcriptome data against the built-in CoV datasets and visualize their results via interactive PCA, UpSet and Pathway plots.AvailabilityCompCorona is freely available on the web athttp://compcorona.mu.edu.trContacttugbasuzek@mu.edu.tr
Calculation of Protein Folding Thermodynamics using Molecular Dynamics Simulations
Authors: Galano-Frutos Juan José , Nerín-Fonz Francho , Sancho Javier 
Published: January 2023

AbstractDespite impressive advances by AlphaFold2 in the field of computational biology, the protein folding problem remains an enigma to be solved. The continuous development of algorithms and methods to explore longer simulation timescales of biological systems, as well as the enhanced accuracy of potential functions (force fields and solvent models) have not yet led to significant progress in the calculation of the thermodynamics quantities associated to protein folding from first principles. Progress in this direction can help boost related fields such as protein engineering, drug design, or genetic interpretation, but the task seems not to have been addressed by the scientific community. Following an initial explorative study, we extend here the application of a Molecular Dynamics-based approach −with the most accurate force field/water model combination previously found (Charmm22-CMAP/Tip3p)− to computing the folding energetics of a set of two-state and three-state proteins that do or do not carry a bound cofactor. The proteins successfully computed are representative of the main protein structural classes, their sequences range from 84 to 169 residues, and their isoelectric points from 4.0 to 8.9. The devised approach enables accurate calculation of two essential magnitudes governing the stability of proteins −the changes in enthalpy and in heat capacity associated to protein unfolding−, which are used to obtain accurate values of the change in Gibbs free-energy, also known as the protein conformational stability. The method proves to be also suitable to obtain changes in stability due to changes in solution pH, or stability differences between a wild-type protein and a variant. The approach addresses the calculation by difference, a shortcut that avoids having to simulate the protein folding time, which is very often unfeasible computationally.
Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis
Authors: Mennillo Elvira , Kim Yang Joon , Lee Gyehyun , Rusu Iulia , Patel Ravi K. , Dorman Leah C. , Flynn Emily , Li Stephanie , Bain Jared L. , Andersen Christopher , Rao Arjun , Tamaki Stanley , Tsui Jessica , Shen Alan , Lotstein Madison L. , Rahim Maha , Naser Mohammad , Bernard-Vazquez Faviola , Eckalbar Walter , Cho Soo-jin , Beck Kendall , El-Nachef Najwa , Lewin Sara , Selvig Daniel R , Terdiman Jonathan P , Mahadevan Uma , Oh David Y. , Fragiadakis Gabriela K. , Pisco Angela , Combes Alexis J. , Kattah Michael G. 
Published: January 2023

ABSTRACTUlcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.
Hep3D: A 3D single-cell digital atlas of the liver to study spatio-temporal tissue architecture
Authors: Martínez Dilan , Maldonado Valentina , Pérez Cristian , Yañez Rodrigo , Candia Valeria , Kalaidzidis Yannis , Zerial Marino , Morales-Navarrete Hernán , Segovia-Miranda Fabián 
Published: January 2023

AbstractThree dimensional (3D) geometrical models are not only a powerful tool for quantitatively characterizing complex tissues but also useful for probing structure-function relationships in a tissue. However, these models are generally incomplete due to experimental limitations in acquiring multiple (>4) fluorescent channels simultaneously. Indeed, predictive geometrical and functional models of the liver have been restricted to few tissue and cellular components, excluding important cellular populations such as hepatic stellate cells (HSCs) and Kupffer cells (KCs). Here, we performed deep-tissue immunostaining, multiphoton microscopy, deeplearning techniques, and 3D image processing to computationally expand the number of simultaneously reconstructed tissue structures. We then generated a spatio-temporal singlecell atlas of hepatic architecture (Hep3D), including all main tissue and cellular components at different stages of post-natal development in mice. We used Hep3D to quantitatively study 1) hepatic morphodynamics from early post-natal development to adulthood, and 2) the structural role of KCs in the murine liver homeostasis. In addition to a complete description of bile canaliculi and sinusoidal network remodeling, our analysis uncovered unexpected spatiotemporal patterns of non-parenchymal cells and hepatocytes differing in size, number of nuclei, and DNA content. Surprisingly, we found that the specific depletion of KCs alters the number and morphology of the HSCs. These findings reveal novel characteristics of liver heterogeneity and have important implications for both the structural organization of liver tissue and its function. Our next-gen 3D single-cell atlas is a powerful tool to understand liver tissue architecture, under both physiological and pathological conditions.
Evolution of phenotypic plasticity during environmental fluctuations
Authors: Sekajova Zuzana , Fossen Erlend I. F. , Rosa Elena , Ratikainen Irja I. , Tourniaire-Blum Manon , Bolund Elisabeth , Lind Martin I. 
Published: January 2023

AbstractEvolution in fluctuating environments is predicted to disfavor specialization and instead select for alternative strategies, such as phenotypic plasticity or possibly bet-hedging, depending on the accuracy of environmental cues and type of fluctuations. While these two alternatives are often contrasted in theoretical studies, their evolution are seldom studied together in empirical work.We used experimental evolution in the nematode wormCaenorhabditis remaneito simultaneously study the evolution of plasticity and bet-hedging in environments differing only in their temperature variability. We exposed worms for 30 generations to either fluctuating or slowly increasing temperature, these two environments had the same average temperature over evolutionary time. After experimental evolution, we scored size at sexual maturity and fitness in full siblings reared in two different temperatures, optimal 20°C and mildly stressful 25°C.Experimental evolution in the fluctuating environment resulted in the evolution of increased body size plasticity but not increased bet-hedging, compared to evolution in the slowly changing environment. Plasticity followed the temperature size rule as size decreased with increasing temperature and this plastic response was adaptive. In addition, we documented substantial standing genetic variation in body size, which represents a potential for further evolutionary change.
Mitochondrial diabetes in mice expressing a dominant-negative allele of nuclear respiratory factor-1 (Nrf1) in pancreatic β-cells
Authors: Morrish Fionnuala , Gingras Helene , Noonan Joanna , Huang Li , Sweet Ian R. , Kuok Iok Teng , Knoblaugh Sue E. , Hockenbery David M. 
Published: January 2023

SUMMARYGenetic polymorphisms in nuclear respiratory factor-1 (NRF1), a key transcriptional regulator of nuclear-encoded mitochondrial proteins, have been linked to diabetes. Homozygous deletion ofNrf1is embryonic lethal in mice. Our goal was to generate mice with β-cell-specific reduction in NRF1 function to investigate the relationship between NRF1 and diabetes. We report the generation of mice expressing a dominant-negative allele ofNrf1(DNNRF1) in pancreatic β-cells. Heterozygous transgenic mice had high fed blood glucose levels detected at 3 wks of age, which persisted through adulthood. Plasma insulin levels in DNNRF1 transgenic mice were reduced, while insulin sensitivity remained intact in young animals. Islet size was reduced with increased numbers of apoptotic cells, and insulin content in islets by immunohistochemistry was low. Glucose-stimulated insulin secretion in isolated islets was reduced in DNNRF1-mice, but partially rescued by KCl, suggesting that decreased mitochondrial function contributed to the insulin secretory defect. Electron micrographs demonstrated abnormal mitochondrial morphology in β- cells. Expression of NRF1 target genesTfam,T@1mandT@2m, and islet cytochrome c oxidase and succinate dehydrogenase activities were reduced in DNNRF1-mice. Rescue of mitochondrial function with low level activation of transgenic c-Myc in β-cells was sufficient to restore β-cell mass and prevent diabetes. This study demonstrates that reduced NRF1 function can lead to loss of β-cell function and establishes a model to study the interplay between regulators of bi- genomic gene transcription in diabetes.
Circadian regulation of Homologous Recombination by Cryptochrome1-mediated dampening of DNA end resection
Authors: Romero-Franco Amador , Checa-Rodríguez Cintia , Jimeno Sonia , Castellano-Pozo Maikel , Aguilera Paula , Miras Hector , Wals Amadeo , Jimeno-González Silvia , Lopez-Contreras Andres Joaquin , Huertas Pablo 
Published: January 2023

AbstractGenomic stability maintenance requires the repair of DNA breaks in the most accurate fashion. So, an exquisite regulatory network controls the choice between different repair mechanisms to maximize genome integrity. This relies mostly at the level of DNA end resection, the initial steps of the homologous recombination. On the other hand, most cellular activities follow a 24 h oscillation known as the circadian cycle. Here we explore the regulation of the choice between different DNA break repair pathways along the circadian cycle. We observed that in human cells DNA resection shows a circadian oscillation, with a peak at early morning followed by a progressive reduction until late afternoon. Such regulation depends on the circadian clock core component CRY1, which modulates the anti-resection activity of CCAR2 to limit CtIP at nightfall. Additionally, such regulation requires DNA-PK-mediated phosphorylation of CRY1. Finally, this circadian regulation impacts cancer progression and response to radiation therapy of specific tumours.One sentence summary:CCAR2-dependent inhibition of DNA end resection and homologous recombination is controlled by the intrinsic cellular circadian clock protein CRY1