bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atmospheric Electron Spatial Range Extended by Thundercloud Electric Field Below the Relativistic Runaway Electron Avalanche Threshold
Authors: Diniz G. , Wada Y. , Ohira Y. , Nakazawa K. , Enoto T. 
Published: January 2022

AbstractCosmic‐ray shower, hitting the atmosphere all the time, includes high‐energy electrons. Electric fields in thunderstorms accelerate these electrons so that they can reach farther distances with producing secondary electrons. The strong field above 0.284 MV m−1 causes the Relativistic Runaway Electron Avalanches (RREA) process with an exponential increase of electrons. Even with lower electric fields below this RREA threshold which are usually measured in thunderstorms, an increase in electrons' kinetic energy and production of secondary electrons can occur without avalanche processes, known as Modification Of Spectra (MOS) of the cosmic‐ray shower. Both phenomena are related to observed gamma ray glow, which is bremsstrahlung emission from accelerated electrons in thunderstorms. We calculate an extended range and kinetic energy of electrons below the RREA threshold using an analytical evaluation and Geant4 Monte Carlo simulations. For example, at 0.280 MV m−1 slightly below the RREA threshold, 3 MeV electrons gain 100% of their original kinetic energy through the passage of the continuous slowing down approximation (CSDA) range defined at the null electric field, which is consistent with results in previous studies as the transition to the RREA process. Even at a lower field of 0.260 MV m−1, the energy recovery by the field allows an injected 20 MeV electron beam to extend its average electron range from 73 m, in the null field configuration, to 562 m. We have performed analytical calculation and Geant4 simulations of atmospheric electron behavior for initial electron energy of 0.1–100 MeV and an electric field below 0.290 MV m−1.
The ubiquitin E3 ligase ARIH1 regulates hnRNP E1 protein stability, EMT and breast cancer progression
Authors: Howley Breege V. , Mohanty Bidyut , Dalton Annamarie , Grelet Simon , Karam Joseph , Dincman Toros , Howe Philip H. 
Published: January 2022

AbstractThe epithelial to mesenchymal transition (EMT), a process that is aberrantly activated in cancer and facilitates metastasis to distant organs, requires coordinated transcriptional and post-transcriptional control of gene expression. The tumor-suppressive RNA binding protein, hnRNP-E1, regulates splicing and translation of EMT-associated transcripts and it is thought that it plays a major role in the control of epithelial cell plasticity during cancer progression. We have utilized yeast 2 hybrid screening to identify novel hnRNP-E1 interactors that play a role in regulating hnRNP-E1; this approach led to the identification of the E3 ubiquitin ligase ARIH1. Here, we demonstrate that hnRNP-E1 protein stability is increased upon ARIH1 silencing, whereas, overexpression of ARIH1 leads to a reduction in hnRNP-E1. Reduced ubiquitination of hnRNP-E1 detected in ARIH1 knockdown (KD) cells compared to control suggests a role for ARIH1 in hnRNP-E1 degradation. The identification of hnRNP-E1 as a candidate substrate of ARIH1 led to the characterization of a novel function for this ubiquitin ligase in EMT induction and cancer progression. We demonstrate a delayed induction of EMT and reduced invasion in mammary epithelial cells silenced for ARIH1. Conversely, ARIH1 overexpression promoted EMT induction and invasion. ARIH1 silencing in breast cancer cells significantly attenuated cancer cell stemness in vitro and tumor formation in vivo. Finally, we utilized miniTurboID proximity labeling to identify novel ARIH1 interactors that may contribute to ARIH1’s function in EMT induction and cancer progression.
LncRNAs LCETRL3 and LCETRL4 at chromosome 4q12 diminish EGFR-TKIs efficiency in NSCLC through stabilizing TDP43 and EIF2S1
Authors: Li Yankang , Shen Yue , Xie Mengyu , Wang Bowen , Wang Teng , Zeng Jiajia , Hua Hui , Yu Jinming , Yang Ming 
Published: January 2022

AbstractEpidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective targeted therapy drugs for advanced non-small cell lung cancer (NSCLC) patients carrying sensitized EGFR mutations. The rapid development of EGFR-TKIs resistance represents a major clinical challenge for managing NSCLC. The chromosome 4q12 is the first genome-wide association study (GWAS)-reported locus associated with progression-free survival (PFS) of NSCLC patients treated with EGFR-TKIs. However, the biological significance of the noncoding transcripts at 4q12 in NSCLC remains elusive. In the present study, we identified two 4q12 long noncoding RNAs (lncRNAs) LCETRL3 and LCETRL4 which could significantly dimmish EGFR-TKIs efficiency. In line with their oncogenic role, evidently higher LCETRL3 and LCETRL4 levels were observed in NSCLC tissues as compared with normal specimens. Importantly, lncRNA LCETRL3 can interact with oncoprotein TDP43 and inhibit ubiquitination and degradation of TDP43. Similarly, lncRNA LCETRL4 can bind and stabilize oncoprotein EIF2S1 through reducing ubiquitin-proteasome degradation of EIF2S1. In particular, elevated levels of LCETRL3 or LCETRL4 in NSCLC cells resulted in stabilization of TDP43 or EIF2S1, increased levels of NOTCH1 or phosphorylated PDK1, activated AKT signaling and, thus, EGFR-TKIs resistance. Taken together, our data revealed a novel model that integrates two lncRNAs transcribed from the 4q12 locus into the regulation of EGFR-TKIs resistance in NSCLC. These findings shed new light on the importance of functionally annotating lncRNAs in the GWAS loci and provided insights to declare novel druggable targets, i.e., lncRNAs, which may unlock the therapeutic potential of EGFR-TKIs resistant NSCLC in the clinic.
Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota
Authors: Lopes Guilherme S. , Lopes Jaime L. , Bielinski Suzette J. , Armasu Sebastian M. , Zhu Ye , Cavanaugh Dana C. , Moyer Ann M. , Jacobson Debra J. , Wang Liwei , Jiang Ruoxiang , St. Sauver Jennifer L. , Larson Nicholas B. 
Published: January 2022

AbstractThe study of sex-specific genetic associations with opioid response may improve the understanding of inter-individual variability in pain treatments. We investigated sex-specific associations between genetic variation and opioid response. We identified participants in the RIGHT Study prescribed codeine, tramadol, hydrocodone, and oxycodone between 01/01/2005 and 12/31/2017. Prescriptions were collapsed into codeine/tramadol and hydrocodone/oxycodone. Outcomes included poor pain control and adverse reactions within six weeks after prescription date. We performed gene-level and single-variant association analyses stratified by sex. We included 7169 non-Hispanic white participants and a total of 1940 common and low-frequency variants (MAF > 0.01). Common variants in MACROD2 (rs76026520), CYP1B1 (rs1056837, rs1056836), and CYP2D6 (rs35742686) were associated with outcomes. At the gene level, FAAH, SCN1A, and TYMS had associations for men and women, and NAT2, CYP3A4, CYP1A2, and SLC22A2 had associations for men only. Our findings highlight the importance of considering sex in association studies on opioid response.
Evaluation of the EMPAR study population on the basis of metabolic phenotypes of selected pharmacogenes
Authors: Fracowiak Jochen , Huebner Tatjana , Heß Steffen , Roethlein Christoph , Langner Daria , Schneider Udo , Falkenberg Felix , Scholl Catharina , Linder Roland , Stingl Julia , Haenisch Britta , Steffens Michael 
Published: January 2022

AbstractThe impact of genetic variability of pharmacogenes as a possible risk factor for adverse drug reactions is elucidated in the EMPAR (Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung/English: influence of metabolic profiles on the safety of drug therapy in routine care) study. EMPAR evaluates possible associations of pharmacogenetically predicted metabolic profiles relevant for the metabolism of frequently prescribed cardiovascular drugs. Based on a German study population of 10,748 participants providing access to healthcare claims data and DNA samples for pharmacogenetic assessment, first analyses were performed and evaluated. The aim of this first evaluation was the characterization of the study population with regard to general parameters such as age, gender, comorbidity, and polypharmacy at baseline (baseline year) as well as important combinations of cardiovascular drugs with relevant genetic variants and predicted metabolic phenotypes. The study was registered in the German Clinical Trials Register (DRKS) on July 6, 2018 (DRKS00013909).
Estimating heritability using family-pooled phenotypic and genotypic data: a simulation study applied to aquaculture
Authors: Khalilisamani Nima , Thomson Peter Campbell , Raadsma Herman Willem , Khatkar Mehar Singh 
Published: January 2022

AbstractEstimating heritability based on individual phenotypic and genotypic measurements can be expensive and labour-intensive in commercial aquaculture breeding. Here, the feasibility of estimating heritability using within-family means of phenotypes and allelic frequencies was investigated. Different numbers of full-sib families and family sizes across ten generations with phenotypic and genotypic information on 10 K SNPs were analysed in ten replicates. Three scenarios, representing differing numbers of pools per family (one, two and five) were considered. The results showed that using one pool per family did not reliably estimate the heritability of family means. Using simulation parameters appropriate for aquaculture, at least 200 families of 60 progeny per family divided equally in two pools per family was required to estimate the heritability of family means effectively. Although application of five pools generated more within- and between- family relationships, it reduced the number of individuals per pool and increased within-family residual variation, hence, decreased the heritability of family means. Moreover, increasing the size of pools resulted in increasing the heritability of family means towards one. In addition, heritability of family mean estimates were higher than family heritabilities obtained from Falconer’s formula due to lower intraclass correlation estimate compared to the coefficient of relationship.
Rare transmission of commensal and pathogenic bacteria in the gut microbiome of hospitalized adults
Authors: Siranosian Benjamin A. , Brooks Erin F. , Andermann Tessa , Rezvani Andrew R. , Banaei Niaz , Tang Hua , Bhatt Ami S. 
Published: January 2022

AbstractBacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT). Although previous research has demonstrated that pathogens may translocate from the gut microbiome into the bloodstream to cause infections, the mechanisms by which HCT patients acquire pathogens in their microbiome have not yet been described. Here, we use linked-read and short-read metagenomic sequencing to analyze 401 stool samples collected from 149 adults undergoing HCT and hospitalized in the same unit over three years, many of whom were roommates. We use metagenomic assembly and strain-specific comparison methods to search for high-identity bacterial strains, which may indicate transmission between the gut microbiomes of patients. Overall, the microbiomes of patients who share time and space in the hospital do not converge in taxonomic composition. However, we do observe six pairs of patients who harbor identical or nearly identical strains of the pathogen Enterococcus faecium, or the gut commensals Akkermansia muciniphila and Hungatella hathewayi. These shared strains may result from direct transmission between patients who shared a room and bathroom, acquisition from a common hospital source, or transmission from an unsampled intermediate. We also identify multiple patients with identical strains of species commonly found in commercial probiotics, including Lactobacillus rhamnosus and Streptococcus thermophilus. In summary, our findings indicate that sharing of identical pathogens between the gut microbiomes of multiple patients is a rare phenomenon. Furthermore, the observed potential transmission of commensal, immunomodulatory microbes suggests that exposure to other humans may contribute to microbiome reassembly post-HCT.
Heterogeneity within and among co-occurring foundation species increases biodiversity
Authors: Thomsen Mads S. , Altieri Andrew H. , Angelini Christine , Bishop Melanie J. , Bulleri Fabio , Farhan Roxanne , Frühling Viktoria M. M. , Gribben Paul E. , Harrison Seamus B. , He Qiang , Klinghardt Moritz , Langeneck Joachim , Lanham Brendan S. , Mondardini Luca , Mulders Yannick , Oleksyn Semonn , Ramus Aaron P. , Schiel David R. , Schneider Tristan , Siciliano Alfonso , Silliman Brian R. , Smale Dan A. , South Paul M. , Wernberg Thomas , Zhang Stacy , Zotz Gerhard 
Published: January 2022

AbstractHabitat heterogeneity is considered a primary causal driver underpinning patterns of diversity, yet the universal role of heterogeneity in structuring biodiversity is unclear due to a lack of coordinated experiments testing its effects across geographic scales and habitat types. Furthermore, key species interactions that can enhance heterogeneity, such as facilitation cascades of foundation species, have been largely overlooked in general biodiversity models. Here, we performed 22 geographically distributed experiments in different ecosystems and biogeographical regions to assess the extent to which variation in biodiversity is explained by three axes of habitat heterogeneity: the amount of habitat, its morphological complexity, and capacity to provide ecological resources (e.g. food) within and between co-occurring foundation species. We show that positive and additive effects across the three axes of heterogeneity are common, providing a compelling mechanistic insight into the universal importance of habitat heterogeneity in promoting biodiversity via cascades of facilitative interactions. Because many aspects of habitat heterogeneity can be controlled through restoration and management interventions, our findings are directly relevant to biodiversity conservation.
Mobilisation of deep crustal sulfide melts as a first order control on upper lithospheric metallogeny
Authors: Holwell David A. , Fiorentini Marco L. , Knott Thomas R. , McDonald Iain , Blanks Daryl E. , Campbell McCuaig T. , Gorczyk Weronika 
Published: January 2022

AbstractMagmatic arcs are terrestrial environments where lithospheric cycling and recycling of metals and volatiles is enhanced. However, the first-order mechanism permitting the episodic fluxing of these elements from the mantle through to the outer Earth’s spheres has been elusive. To address this knowledge gap, we focus on the textural and minero-chemical characteristics of metal-rich magmatic sulfides hosted in amphibole-olivine-pyroxene cumulates in the lowermost crust. We show that in cumulates that were subject to increasing temperature due to prolonged mafic magmatism, which only occurs episodically during the complex evolution of any magmatic arc, Cu-Au-rich sulfide can exist as liquid while Ni-Fe rich sulfide occurs as a solid phase. This scenario occurs within a ‘Goldilocks’ temperature zone at ~1100–1200 °C, typical of the base of the crust in arcs, which permits episodic fractionation and mobilisation of Cu-Au-rich sulfide liquid into permeable melt networks that may ascend through the lithosphere providing metals for porphyry and epithermal ore deposits.
Increased ENSO sea surface temperature variability under four IPCC emission scenarios
Authors: Cai Wenju , Ng Benjamin , Wang Guojian , Santoso Agus , Wu Lixin , Yang Kai 
Published: January 2022

AbstractSea surface temperature (SST) variability of El Niño–Southern Oscillation (ENSO) underpins its global impact, and its future change is a long-standing science issue. In its sixth assessment, the IPCC reports no systematic change in ENSO SST variability under any emission scenarios considered. However, comparison between the 20th and 21st century shows a robust increase in century-long ENSO SST variability under four IPCC plausible emission scenarios.
Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs
Authors: Bengtsson Rebecca J. , Simpkin Adam J. , Pulford Caisey V. , Low Ross , Rasko David A. , Rigden Daniel J. , Hall Neil , Barry Eileen M. , Tennant Sharon M. , Baker Kate S. 
Published: January 2022

AbstractShigella spp. are the leading bacterial cause of severe childhood diarrhoea in low- and middle-income countries (LMICs), are increasingly antimicrobial resistant and have no widely available licenced vaccine. We performed genomic analyses of 1,246 systematically collected shigellae sampled from seven countries in sub-Saharan Africa and South Asia as part of the Global Enteric Multicenter Study (GEMS) between 2007 and 2011, to inform control and identify factors that could limit the effectiveness of current approaches. Through contemporaneous comparison among major subgroups, we found that S. sonnei contributes ≥6-fold more disease than other Shigella species relative to its genomic diversity, and highlight existing diversity and adaptative capacity among S. flexneri that may generate vaccine escape variants in <6 months. Furthermore, we show convergent evolution of resistance against ciprofloxacin, the current WHO-recommended antimicrobial for the treatment of shigellosis, among Shigella isolates. This demonstrates the urgent need to integrate existing genomic diversity into vaccine and treatment plans for Shigella, providing a framework for the focused application of comparative genomics to guide vaccine development, and the optimization of control and prevention strategies for other pathogens relevant to public health policy considerations.
In vivo melanin 3D quantification and z-epidermal distribution by multiphoton FLIM, phasor and Pseudo-FLIM analyses
Authors: Pena Ana-Maria , Decencière Etienne , Brizion Sébastien , Sextius Peggy , Koudoro Serge , Baldeweck Thérèse , Tancrède-Bohin Emmanuelle 
Published: January 2022

AbstractCharacterizing melanins in situ and determining their 3D z-epidermal distribution is paramount for understanding physiological/pathological processes of melanin neosynthesis, transfer, degradation or modulation with external UV exposure or cosmetic/pharmaceutical products. Multiphoton fluorescence intensity- and lifetime-based approaches have been shown to afford melanin detection, but how can one quantify melanin in vivo in 3D from multiphoton fluorescence lifetime (FLIM) data, especially since FLIM imaging requires long image acquisition times not compatible with 3D imaging in a clinical setup? We propose an approach combining (i) multiphoton FLIM, (ii) fast image acquisition times, and (iii) a melanin detection method called Pseudo-FLIM, based on slope analysis of autofluorescence intensity decays from temporally binned data. We compare Pseudo-FLIM to FLIM bi-exponential and phasor analyses of synthetic melanin, melanocytes/keratinocytes coculture and in vivo human skin. Using parameters of global 3D epidermal melanin density and z-epidermal distribution profile, we provide first insights into the in vivo knowledge of 3D melanin modulations with constitutive pigmentation versus ethnicity, with seasonality over 1 year and with topical application of retinoic acid or retinol on human skin. Applications of Pseudo-FLIM based melanin detection encompass physiological, pathological, or environmental factors-induced pigmentation modulations up to whitening, anti-photoaging, or photoprotection products evaluation.
Herbivorous fish (Medialuna ancietae) as a sustainable alternative for nutrition security in Northern Chile
Authors: Lozano-Muñoz Ivonne , Castellaro Giorgio , Bueno German , Wacyk Jurij 
Published: January 2022

AbstractSustainability in aquaculture is a necessity of the future, not only as the most promising means of supplying the protein that the world will require to feed its growing population but to offer needed conservation of the world’s ocean resources. The use of wild fish inputs in farm-raised fish outputs has been a primary concern of sustainability in aquaculture production. Herbivorous fish are more efficient converters of protein into fish flesh. Species of the genus Medialuna fish have been reported as a fast-growing, short-lived species. The native fish Acha (Medialuna ancietae Chirichigno 1987) in the Northern part of Chile is an over-exploited fish that has been associated with aquatic vegetation as a food source. We studied the feeding habits and nutritional composition of M. ancietae. For this, we developed a reference collection of marine macroalga (epidermis and nutritional composition) observed in the diet of individuals of this species for the study of digestive material. More than 90% of the components found were marine macroalgae, indicating that M. ancietae is an herbivorous fish. Compared to non-herbivorous fish our results showed that most of the nutrients present in the Medialuna diet are found at much lower levels including n-3 long-chain polyunsaturated fatty acids (49.7%) and protein (13–60%). M. ancietae meat provides essential components of human nutrition with a significant protein content (18.99 ± 0.26%) and 268 ± 5.9 mg/100 g of the essential n-3 long-chain polyunsaturated fatty acids. Most fed aquaculture non-herbivorous species rely on wild-captured fish for these essential nutrients, while M. ancietae can obtain and concentrate them from potentially cultivable macroalgae. M. ancietae has potential for sustainable aquaculture production as a contribution to nutrition security and the re-stocking of wild populations.
Fecal and soil microbiota composition of gardening and non-gardening families
Authors: Brown Marina D. , Shinn Leila M. , Reeser Ginger , Browning Matthew , Schwingel Andiara , Khan Naiman A. , Holscher Hannah D. 
Published: January 2022

AbstractHistorically, humans have interacted with soils, which contain a rich source of microorganisms. Fruit and vegetable gardening is the primary interaction humans have with soil today. Animal research reveals that soil microorganisms can be transferred to the rodent intestine. However, studies on fecal and soil microbial changes associated with gardening in humans are lacking. The current case-controlled cohort study aimed to characterize the fecal and soil microbiota of gardening families (n = 10) and non-gardening (control) families (n = 9). Families included two adults and one child (5–18 years) for a total of 56 participants. All participants provided a fecal sample, soil sample, and diet history questionnaires before the gardening season (April) and during the peak of the gardening season (August). Healthy Eating Index (HEI-2015) scores and nutrient analysis were performed. Fecal and soil DNA were extracted and amplified. Sequence data were then processed and analyzed. Peak season gardening families tended to have greater fecal operational features, a greater Faith's Phylogenetic Diversity score, greater fiber intake, and higher abundances of fiber fermenting bacteria than peak control families. Soil endemic microbes were also shared with gardening participant’s fecal samples. This study revealed that the fecal microbiota of gardening families differs from non-gardening families, and that there are detectable changes in the fecal microbial community of gardeners and their family members over the course of the gardening season. Additional research is necessary to determine if changes induced by gardening on the gut microbiota contribute to human health.