bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating cytotoxicity and genotoxicity of oil extracted from visceral fat ofCaiman yacare(Daudin, 1802) in chinese hamster lung fibroblastin vitro
Authors: Azevedo Lucas P. , Rios-Santos Fabricio , Branco Carmen L. B. , Pressinotti Leandro N. , de M. Reis Érica , Filho Samuel V. , de O. Martins Domingos T. , de Arruda Silva Willian , de Vasconcelos Leonardo G. , Santos Ferraz Rosa Helena dos , Mesquita Fernanda Vieira , Junior Paulo T. S. 
Published: July 2023

ABSTRACTIn previous studies, the oil extracted from the visceral fat ofCaiman yacare(Daudin, 1802) demonstrated a wound-healing effect on the skin of Wistar rats. To enhance knowledge our about the mechanism underlying this effect, we analysed the oil’s toxicological potentialin vitro. Cytotoxicity, genotoxicity, pro-oxidant, and antioxidant activities were evaluated in a V79-4 cell line. The oil was obtained using the Soxhlet method, and the proportions of the fatty acid profile was previously identified 43.74 % saturated and 34.65 % unsaturated fatty acids. Protocol 487 of the Organisation for Economic Co-operation and Development (OECD) was employed for cell line selection and concentrations. Cytotoxicity was determined using the MTT assay and clonogenic survival. Pro-oxidant and antioxidant activities were analysed using flow cytometry. Genotoxicity was evaluated using comet and micronucleus assays. The oil did not demonstrate cytotoxicity up to a concentration of 500 µg/mL. At concentrations of 250 and 500 µg/mL, the oil exerted a protective effect against oxidative stress and showed genotoxic effects only at the highest concentration (2000 µg/mL). Like other oils of interest for human health, the oil extracted from the visceral fat ofC. yacaredemonstrated low toxicological potentialin vitro.SUMMARY STATEMENTThe oil fromCaiman yacarevisceral fat presents low cytotoxicity and genotoxicity, highlighting its potential for therapeutic applications without adverse effects.
Distribution of carbon monoxide (CO) in several tissues from Atlantic bottlenose dolphins (Tursiops truncatus)
Authors: Tift Michael S. , Litzenberg Kerryanne , Herrmann Kayleigh M. , Cotoia Alicia T. , Jackson Olivia N. , Keenan Tiffany F. , Kezar Kristi M. , Pearson Anna B. , McLellan William A. , Pabst D. Ann 
Published: July 2023

AbstractCarbon monoxide (CO) is known as “The Silent Killer” due to its toxic effect at high concentrations, leading to an impairment in oxygen storage, delivery, and use. The cytotoxicity of CO is due to its high affinity for transition metals, such as iron, where CO outcompetes oxygen for the heme binding sites on hemoproteins in the body. CO is madein vivoin most organisms as a byproduct of heme degradation via heme oxygenase enzymes. Certain species of deep-diving marine mammals with high quantities of hemoproteins in blood and skeletal muscle have naturally elevated concentrations of CO in these tissues. To date, there exist few data on extravascular tissue CO content in wild animals. This study aims to characterize CO concentrations in nine different tissues from stranded Atlantic bottlenose dolphins (Tursiops truncatus). We found three tissues (liver, skeletal muscle, and spleen) have higher CO concentrations than other tissues. In a subset of samples from animals that tested positive for dolphin morbillivirus, the CO content in their kidney and liver was lower when compared to animals that tested negative. The mean CO concentration found in every tissue from dolphins was higher than those previously reported in healthy rodents. However, the skeletal muscle CO concentrations in dolphins from this study were much lower than those of deep-diving elephant seals. These results highlight the diversity and pattern of CO found in different tissues from bottlenose dolphins and continues to show that the heme oxygenase/carbon monoxide pathway appears to be critical for air-breathing divers.
DCLRE1B/hSNM1B (Apollo) is not acutely required for human pluripotent stem cell survival
Authors: Bartke Rebecca , Hockemeyer Dirk 
Published: July 2023

AbstractTelomeric DNA ends in a 3’ single stranded overhang that is implicated in the protective function of telomeres ensuring genomic stability in mammals. Telomere overhang formation relies on the coordinated interplay between DNA synthesis and exonuclease activity. DCLRE1B/hSNM1B/Apollo generates an initial resection at the newly synthesized, blunt-ended leading strand telomere. This resection is thought to be required for further nucleolytic processing at the leading strand telomere. Here, we investigated the functional relevance of Apollo in human pluripotent stem cells (hPSCs) by generating Apollo deficient cells. Leveraging CRISPR/Cas9 technology, we generated locally haploid hPSCs (loHAPs) that lack one allele of Apollo. Subsequently, we mutated the remaining Apollo allele and monitored the resultant allele spectrum over 3 weeks. Surprisingly, cells survived regardless of Apollo status. These results suggest that, in hPSCs, Apollo is not acutely essential for cellular survival.
Data-driven modeling of core gene regulatory network underlying leukemogenesis in IDH mutant AML
Authors: Katebi Ataur , Chen Xiaowen , Li Sheng , Lu Mingyang 
Published: July 2023

ABSTRACTAcute myeloid leukemia (AML) is characterized by uncontrolled proliferation of poorly differentiated myeloid cells, with a heterogenous mutational landscape. Mutations in IDH1 and IDH2 are found in 20% of the AML cases. Although much effort has been made to identify genes associated with leukemogenesis, the regulatory mechanism of AML state transition is still not fully understood. To alleviate this issue, here we develop a new computational approach that integrates genomic data from diverse sources, including gene expression and ATAC-seq datasets, curated gene regulatory interaction databases, and mathematical modeling to establish models of context-specific core gene regulatory networks (GRNs) for a mechanistic understanding of tumorigenesis of AML with IDH mutations. The approach adopts a novel optimization procedure to identify the optimal network according to its accuracy in capturing gene expression states and its flexibility to allow sufficient control of state transitions. From GRN modeling, we identify key regulators associated with the function of IDH mutations, such as DNA methyltransferase DNMT1, and network destabilizers, such as E2F1. The constructed core regulatory network and outcomes of in-silico network perturbations are supported by survival data from AML patients. We expect that the combined bioinformatics and systems-biology modeling approach will be generally applicable to elucidate the gene regulation of disease progression.SignificanceA combined bioinformatics and systems-biology modeling approach is designed to model a transcriptional regulatory network for AML with IDH mutations. Network modeling identifies key regulators DNMT1 and E2F1, which is supported by patient survival data.
microRNA-22 displaces ITAFs from the 5’UTR and inhibit the translation of Coxsackievirus B3 RNA
Authors: Rani Priya , George Biju , Sabarishree V , Biswas Somarghya , Rajmani Raju S , Pal Apala , Das Saumitra 
Published: July 2023

ABSTRACTmicroRNAs play an essential role in gene regulation during virus infections and have major consequences on viral pathogenesis. During RNA virus infections, the host miRNAs can target both host mRNAs and the virus genomic RNA. Using the CVB3 virus as a model, we have investigated how a host miRNA can target viral genomic RNA and act as an antiviral factor limiting the growth of the virus. CVB3 is an RNA virus whose infection causes myocarditis and, eventually, dilated cardiomyopathy. We shortlisted miRNAs with a potential binding site in the CVB3 genomic RNA. Among these, miR-22 was picked for further studies as its binding site was putatively located in a region in the CVB3 5’ UTR, important for recruiting ITAFs and ribosomes for IRES-mediated translation. Using mutational analysis and pull-down assays, we first confirmed the binding of miR-22 on the 5’UTR. This binding negatively regulated the translation of CVB3 RNA. However, miR-22 binding-defective mutant of CVB3 RNA had no effect of miR-22 overexpression and could translate normally. Moreover, cells from which miR-22 was knocked out, showed a higher level of CVB3 infection as compared to the wild type. We have further demonstrated that the binding of miR-22 interferes with the recruitment of several ITAFs (La, PSF, and PTB) on viral mRNA. This abrogates the spatial structure necessary for ribosome recruitment on the CVB3 RNA, ultimately inhibiting its translation. Also, the level of miR-22 increases 4 hours post-infection, presumably after the synthesis of viral 2A protease, to regulate infection in the host cell more effectively. Along with the direct effect on viral RNA, the altered level of miR-22 affects the level of its cellular targets which might contribute to CVB3 infection. To identify the possible players, we obtained a list of miR-22 targets and performed pathway analysis. Several targets were shortlisted among the top hits and their levels upon CVB3 infection were checked. Protocadherin-1 (PCDH-1), a single-pass transmembrane protein, followed an expected trend, and its levels were significantly downregulated upon CVB3 infection in miR-22 dependent manner. miR-22 mediated suppression of PCDH1 levels during CVB3 infection points towards the possible role of miR-22 in either modulating antiviral signaling or in virus entry, in addition to regulating the viral translation.
STING/RANTES Pathway in Airway Epithelium Stimulates Sensitization toDer p1in an Asthma Model
Authors: Tsuji Mayoko , Kondo Mitsuko , Nishiyama Akira , Tamura Tomohiko , Nakamura-Ishizu Ayako , Tagaya Etsuko 
Published: July 2023

AbstractBackgroundAsthma development can be attributed to various factors, including viral infections. Several pathogen including viruses activate stimulators of interferon genes (STING), and a small amount of STING agonist functions as adjuvants for sensitization to house dust mite (HDM); however, the associated mechanism is unclear. We investigated the role of STING during sensitization to HDM in airway epithelial cells.MethodsAirway epithelial cell STING expression was analyzed using the GEO database. We delivered cyclic-GMP-AMP (cGAMP), a STING agonist to mice intranasally, and sorted epithelial cells and performed RNA-seq. Human airway epithelial cells (HBEpCs) were stimulated using cGAMPin vitro. Next, we sensitized mice with cGAMP and HDM,Der p1on Day 1, and challenged with HDM on Day 7, and on Day 8, analyzed cytokine/chemokine levels, bronchoalveolar lavage cell fraction, histology, and the number of group 2 innate lymphoid cells (ILC2s) and dendritic cells (DCs). Furthermore, we evaluated the effect of RANTES/CCL5 alone on sensitizing to HDM.ResultsRelative to other pattern recognition receptors,TMEM173, encoding STING, was highly expressed in HBEpCs, andRANTESexpression was remarkably upregulated in cGAMP-treated mice.RANTES, notIL-33orTSLP, was also activated by cGAMP in HBEpCs, especially in the presence of H2O2. Type 2 cytokine/chemokine, eosinophil, and goblet cell metaplasia increased with ILC2 and cDC2 accumulation in cGAMP-adjuvanted HDM-sensitized mice. RANTES alone functioned as an adjuvant for induction of type 2 inflammation in mice.ConclusionSTING was highly expressed in airway epithelial cells. STING/RANTES axis may be a crucial pathway for stimulating asthma sensitization.
Nutrient deprivation differentially affects gene expression, immunity, and pathogen susceptibility across symbiotic states in a model cnidarian
Authors: Valadez-Ingersoll Maria , Aguirre Carrión Pablo J. , Bodnar Caoimhe A. , Desai Niharika A. , Gilmore Thomas D. , Davies Sarah W. 
Published: July 2023

AbstractMutualistic symbioses between cnidarians and photosynthetic algae are modulated by complex interactions between host immunity and environmental conditions. Here, we investigate how symbiosis interacts with nutrient limitation to influence gene expression and stress response programming in the sea anemoneExaiptasia pallida(Aiptasia). Transcriptomic responses to starvation were similar between symbiotic and aposymbiotic Aiptasia; however, aposymbiotic anemone responses were stronger. Starved Aiptasia of both symbiotic states exhibited increased protein levels of immune-related transcription factor NF-κB, its associated gene pathways, and putative target genes. However, this starvation-induced increase in NF-κB only correlated with increased immunity in symbiotic anemones. Furthermore, starvation had opposite effects on Aiptasia susceptibility to pathogen and oxidative stress challenges, suggesting distinct energetic priorities under nutrient scarce conditions. Finally, when we compared starvation responses in Aiptasia to those of a facultative coral and nonsymbiotic anemone, “defense” responses were similarly regulated in Aiptasia and the facultative coral, but not in the nonsymbiotic anemone. This pattern suggests that capacity for symbiosis influences immune responses in cnidarians. In summary, expression of certain immune pathways – including NF-κB – does not necessarily predict susceptibility to pathogens, highlighting the complexities of cnidarian immunity and the influence of symbiosis under varying energetic demands.
Large-FOV 3D localization microscopy by spatially variant point spread function generation
Authors: Xiao Dafei , Kedem Orange Reut , Opatovski Nadav , Parizat Amit , Nehme Elias , Alalouf Onit , Shechtman Yoav 
Published: July 2023

AbstractAccurate characterization of the microscopic point spread function (PSF) is crucial for achieving high-performance localization microscopy (LM). Traditionally, LM assumes a spatially-invariant PSF to simplify the modeling of the imaging system. However, for large fields of view (FOV) imaging, it becomes important to account for the spatially variant nature of the PSF. In this work, we propose an accurate and fast principal component analysis (PCA)-based field-dependent 3D PSF generator (PPG3D) and localizer for LM. Through simulations and experimental 3D single molecule localization microscopy (SMLM), we demonstrate the effectiveness of PPG3D, enabling super-resolution imaging of mitochondria and microtubules with high fidelity over a large FOV. A comparison of PPG3D with three other shift-invariant and shift-variant PSF generators for 3D LM reveals a three-fold improvement in accuracy and an operation speed approximately one hundred times faster. Given its user-friendliness and conciseness, we believe that PPG3D holds great potential for widespread application in SMLM and other imaging modalities.
Cell membranes sustain phospholipid imbalance via cholesterol asymmetry
Authors: Doktorova Milka , Symons Jessica L. , Zhang Xiaoxuan , Wang Hong-Yin , Schlegel Jan , Lorent Joseph H. , Heberle Frederick A. , Sezgin Erdinc , Lyman Edward , Levental Kandice R. , Levental Ilya 
Published: July 2023

SummaryMembranes are molecular interfaces that compartmentalize cells to control the flow of nutrients and information. These functions are facilitated by diverse collections of lipids, nearly all of which are distributed asymmetrically between the two bilayer leaflets. Most models of biomembrane structure and function often include the implicit assumption that these leaflets have similar abundances of phospholipids. Here, we show that this assumption is generally invalid and investigate the consequences of lipid abundance imbalances in mammalian plasma membranes (PM). Using quantitative lipidomics, we discovered that cytoplasmic leaflets of human erythrocyte membranes have >50% overabundance of phospholipids compared to exoplasmic leaflets. This imbalance is enabled by an asymmetric interleaflet distribution of cholesterol, which regulates cellular cholesterol homeostasis. These features produce unique functional characteristics, including low PM permeability and resting tension in the cytoplasmic leaflet that regulates protein localization. These largely overlooked aspects of membrane asymmetry represent an evolution of classic paradigms of biomembrane structure and physiology.
Veni, vidi, vici? Future spread and ecological impacts of a rapidly-expanding invasive predator population
Authors: David Nelsen R. , Aaron Corbit G. , Angela Chuang , John Deitsch F. , Michael Sitvarin I. , David Coyle R. 
Published: July 2023

AbstractEconomic and ecological consequences of invasive species make biological invasions an influential driver of global change. Monitoring the spread and impacts of non-native species is essential, but often difficult, especially during the initial stages of invasion. The Joro spider,Trichonephila clavata(L. Koch, 1878, Araneae: Araneidae), is a large-bodied orb weaver native to Asia, likely introduced to northern Georgia, U.S. around 2010. We investigated the nascent invasion ofT. clavataby constructing species distribution models (SDMs) from crowdsourced data to compare the climateT. clavataexperiences in its native range to its introduced range. We found evidence that the climate ofT. clavata’s native range differs significantly from its introduced range and that the most similar climate in North America to its native range is to the north of its current introduced range. We then compared the SDM predictions to current observations of spread. Consistent with predictions,T. clavataappears to be spreading faster to the north than to the south. Lastly, we conducted surveys to investigate potential ecological impacts ofT. clavataon the diversity of native orb weaving spiders. Importantly,Trichonephila clavatawas the most common and abundant species observed in the survey, and was numerically dominant at half of the sites it was present in. Our models also suggest that there is lower native orb weaver species richness and diversity closer to whereT. clavatawas initially found and where it has been established the longest, though human population density complicates this finding. This early study is the first to forecast how widely this spider may spread in its introduced range and explore potential ecological impacts ofT. clavata, and we call for continued investigation of this invasion’s effects.
Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn
Authors: Liebhoff Anna-Maria , Venkataraman Thiagarajan , Morgenlander William R , Na Miso , Kula Tomasz , Waugh Kathleen , Morrison Charles , Rewers Marian , Longman Randy , Round June , Elledge Stephen , Ruczinski Ingo , Langmead Ben , Larman H Benjamin 
Published: July 2023

AbstractWe investigated a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To enhance this approach, we developed Dolphyn, a novel method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn improves the fraction of gut phage library peptides bound by antibodies from 10% to 31% in healthy individuals, while also reducing the number of synthesized peptides by 78%. In our study on gut phages, we discovered that the immune system develops antibodies to bacteria-infecting viruses in the human gut, particularlyE.coli-infectingMyoviridae. Cost-effective PhIP-Seq libraries designed with Dolphyn enable the assessment of a wider range of proteins in a single experiment, thus facilitating the study of the gut-immune axis.
Smith-Magenis syndrome protein RAI1 regulates body weight homeostasis through hypothalamic BDNF-producing neurons and neurotrophin downstream signalling
Authors: Javed Sehrish , Chang Ya-Ting , Cho Yoobin , Lee Yu-Ju , Chang Hao-Cheng , Haque Minza , Lin Yu Cheng , Huang Wei-Hsiang 
Published: July 2023

AbstractRetinoic acid-induced 1(RAI1) haploinsufficiency causes Smith-Magenis syndrome (SMS), a genetic disorder with symptoms including hyperphagia, hyperlipidemia, severe obesity, and autism phenotypes. RAI1 is a transcriptional regulator with a pan-neural expression pattern and hundreds of downstream targets. The mechanisms linking neuralRai1to body weight regulation remain unclear. Here we find that hypothalamic brain-derived neurotrophic factor (BDNF) and its downstream signalling are disrupted in SMS (Rai1+/-) mice. SelectiveRai1loss from all BDNF-producing cells or from BDNF-producing neurons in the paraventricular nucleus of the hypothalamus (PVH) induced obesity in mice. Electrophysiological recordings revealed thatRai1ablation decreased the intrinsic excitability of PVHBDNFneurons. Chronic treatment of SMS mice with LM22A-4 engages neurotrophin downstream signalling and delayed obesity onset. This treatment also partially rescued disrupted lipid profiles, insulin intolerance, and stereotypical repetitive behaviour in SMS mice. These data argue that RAI1 regulates body weight and metabolic function through hypothalamic BDNF-producing neurons and that targeting neurotrophin downstream signalling might improve associated SMS phenotypes.
Genetic reprogramming by brief inhibition of the renin-angiotensin system in spontaneously hypertensive rats leads to persistently reduced kidney renin and low blood pressure
Authors: Byars Sean G. , Prestes Priscilla , Suphapimol Vara , Takeuchi Fumihiko , De Vries Nathan , Maier Michelle C , Melo Mariana , Balding David , Samani Nilesh , Allen Andrew , Kato Norihiro , Wilkinson-Berka Jennifer L , Charchar Fadi , Harrap Stephen B 
Published: July 2023

ABSTRACTBACKGROUNDPrevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this reprogramming, but relevant genetic changes are unknown.METHODSIn SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme (ACE) inhibitor, perindopril (with controls for non-specific effects of lowering BP) on differential RNA expression, DNA methylation and renin immunolabelling in the kidney at 20 weeks of age.RESULTSRNA sequencing revealed a 6-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). At 20 weeks, six weeks after treatment cessation, mean arterial pressure remained lower in the treated SHR (P = 0.006), kidneyRenexpression was reduced by 23% (P = 0.03) and DNA methylation within theRenpromoter region was increased (P = 0.04). Experiments with the ACE inhibitor perindopril confirmed a long-term reduction in kidneyRenexpression of 43% (P = 1.4 x 10-6). Renin immunolabelling was also lower after losartan or perindopril treatment (P = 0.002). RNA sequencing identified differential expression of 13 candidate genes (Grhl1,Ammecr1l,Hs6st1,Nfil3,Fam221a,Lmo4,Adamts1,Cish,Hif3a,Bcl6,Rad54l2,Adap1,Dok4) and the miRNA miR-145-3p. We found correlations between expression of mRNAs, miRNAs and lncRNAs that we believe represent genetic networks underpinning the decreasedRenexpression and lower BP. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS and the kidneys.CONCLUSIONSEarly RAS inhibition in SHR reprograms genetic pathways and networks resulting in a legacy of reducedRenexpression and the persistent reduction in BP.