bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Money: Parental Perspectives About Finances and Type 1 Diabetes in Youth
Authors: Eshtehardi Sahar S. , Anderson Barbara J. , Cao Viena T. , McKinney Brett M. , Thompson Deborah I. , Marrero David G. , Hilliard Marisa E.
Published: September 2020

Objective: Given the costs of diabetes care, finances may be a source of stress for parents of youth with type 1 diabetes. The purpose of this study was to characterize the perspectives of parents of youth with type 1 diabetes about diabetes-related expenses and any potential relationship with quality of life. Methods: Parents ( n = 23, 96% mothers) of youth with type 1 diabetes (aged 5–17 years; 35% female, mean HbA1c = 8.7%) each completed a semistructured qualitative interview. Verbatim transcripts were coded using thematic analysis to derive central themes related to diabetes-related finances. Results: Two primary themes emerged: (a) sacrifices and hardships—Parents described making decisions about household finances to accommodate diabetes-related expenses and employment choices based on salary and benefits; many described prioritizing spending for diabetes supplies, healthy foods, and medical bills and forgoing spending related to family vacations, recreation, and personal needs; and (b) gratitude—Parents discussed feeling thankful for employment and insurance coverage, which help reduce diabetes-related financial stressors or hardships. Conclusions: Care of families of youth with type 1 diabetes should consider parents’ financial experiences and effects on family. Routinely asking about diabetes-specific financial issues in relation to family stress and coping may help inform behavioral and medical care and can facilitate referrals to social work.

Implications for Impact Statement

Type 1 diabetes care is expensive, and finances can be a significant source of distress for families. Consideration of how parents may need to make sacrifices to afford diabetes expenses and their gratitude for the resources they are able to access can inform pediatric psychologists’ care of families living with type 1 diabetes.
Chitinase-3 like-protein-1 function and its role in diseases
Authors: Zhao Ting , Su Zhongping , Li Yingchang , Zhang Xiaoren , You Qiang
Published: September 2020

Non-enzymatic chitinase-3 like-protein-1 (CHI3L1) belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is regulated by extracellular matrix changes, cytokines, growth factors, drugs, and stress. CHI3L1 is synthesized and secreted by a multitude of cells including macrophages, neutrophils, synoviocytes, chondrocytes, fibroblast-like cells, smooth muscle cells, and tumor cells. It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses. CHI3L1 has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, and coronary artery disease. Moreover, following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line, CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models. To date, interleukin-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, chemo-attractant receptor-homologous 2, and CD44 have been identified as CHI3L1 receptors. CHI3L1 signaling plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4+T cells. Interestingly, CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis. This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis, then posits investigational strategies for targeted therapies.
Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis
Authors: Li Bo , Lee Carol , O’Connell Joshua S. , Antounians Lina , Ganji Niloofar , Alganabi Mashriq , Cadete Marissa , Nascimben Francesca , Koike Yuhki , Hock Alison , Botts Steven R. , Wu Richard Y. , Miyake Hiromu , Minich Adam , Maalouf Michael F. , Zani-Ruttenstock Elke , Chen Yong , Johnson-Henry Kathene C. , De Coppi Paolo , Eaton Simon , Maattanen Pekka , Delgado Olguin Paul , Zani Augusto , Sherman Philip M. , Pierro Agostino
Published: September 2020

Necrotizing enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society. The treatment and the outcome of the disease have not changed in recent decades. Emerging evidence has shown that stimulating the Wnt/β-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment. Amniotic fluid stem cells (AFSC) and AFSC-derived extracellular vesicles (EV) can be used to improve intestinal injury in experimental NEC. However, the mechanisms by which they affect the Wnt/β-catenin pathway and intestinal regeneration are unknown. In our current study, we demonstrated that AFSC and EV attenuate NEC intestinal injury by activating the Wnt signaling pathway. AFSC and EV stimulate intestinal recovery from NEC by increasing cellular proliferation, reducing inflammation and ultimately regenerating a normal intestinal epithelium. EV administration has a rescuing effect on intestinal injury when given during NEC induction; however, it failed to prevent injury when given prior to NEC induction. AFSC-derived EV administration is thus a potential emergent novel treatment strategy for NEC.
Compound heterozygous variants in the ABCG8 gene in a Japanese girl with sitosterolemia
Authors: Hashimoto Nobuhiro , Dateki Sumito , Suzuki Eri , Tsuchihashi Takatoshi , Isobe Aiko , Banno Sari , Kageyama Tomoka , Maeda Naonori , Hatabu Naomi , Sato Rieko , Miharu Masashi , Fujita Hisayo , Komiyama Osamu , Shimizu Hitomi , Hasegawa Tomonobu , Yamazawa Kazuki
Published: September 2020

Sitosterolemia is an autosomal recessive disorder that affects lipid metabolism and is characterized by elevated serum plant sterol levels, xanthomas, and accelerated atherosclerosis. In this study, we report a novel nonsense single-nucleotide variant, c.225G > A (p.Trp75*), and an East Asian population-specific missense multiple-nucleotide variant, c.1256_1257delTCinsAA (p.Ile419Lys), in the ABCG8 gene in a compound heterozygous state observed in a Japanese girl with sitosterolemia.
Vertical organic synapse expandable to 3D crossbar array
Authors: Choi Yongsuk , Oh Seyong , Qian Chuan , Park Jin-Hong , Cho Jeong Ho
Published: September 2020

Recently, three-terminal synaptic devices have attracted considerable attention owing to their nondestructive weight-update behavior, which is attributed to the completely separated terminals for reading and writing. However, the structural limitations of these devices, such as a low array density and complex line design, are predicted to result in low processing speeds and high energy consumption of the entire system. Here, we propose a vertical three-terminal synapse featuring a remote weight update via ion gel, which is also extendable to a crossbar array structure. This synaptic device exhibits excellent synaptic characteristics, which are achieved via precise control of ion penetration onto the vertical channel through the weight-control terminal. Especially, the applicability of the developed vertical organic synapse array to neuromorphic computing is demonstrated using a simple crossbar synapse array. The proposed synaptic device technology is expected to be an important steppingstone to the development of high-performance and high-density neural networks.
Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder
Authors: Egervari Gabor , Akpoyibo Diana , Rahman Tanni , Fullard John F. , Callens James E. , Landry Joseph A. , Ly Annie , Zhou Xianxiao , Warren Noël , Hauberg Mads E. , Hoffman Gabriel , Ellis Randy , Ferland Jacqueline-Marie N. , Miller Michael L. , Keller Eva , Zhang Bin , Roussos Panos , Hurd Yasmin L.
Published: September 2020

The current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches. Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls. Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase FYN as the most affected region in neurons. FYN expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro. Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents. Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder.
Caspase-8 mediates inflammation and disease in rodent malaria
Authors: Pereira Larissa M. N. , Assis Patrícia A. , de Araújo Natalia M. , Durso Danielle F. , Junqueira Caroline , Ataíde Marco Antônio , Pereira Dhelio B. , Lien Egil , Fitzgerald Katherine A. , Zamboni Dario S. , Golenbock Douglas T. , Gazzinelli Ricardo T.
Published: September 2020

Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFα and IL-1β and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human disease.
Gold catalysts containing interstitial carbon atoms boost hydrogenation activity
Authors: Sun Yafei , Cao Yueqiang , Wang Lili , Mu Xiaotong , Zhao Qingfei , Si Rui , Zhu Xiaojuan , Chen Shangjun , Zhang Bingsen , Chen De , Wan Ying
Published: September 2020

Supported gold nanoparticles are emerging catalysts for heterogeneous catalytic reactions, including selective hydrogenation. The traditionally used supports such as silica do not favor the heterolytic dissociation of hydrogen on the surface of gold, thus limiting its hydrogenation activity. Here we use gold catalyst particles partially embedded in the pore walls of mesoporous carbon with carbon atoms occupying interstitial sites in the gold lattice. This catalyst allows improved electron transfer from carbon to gold and, when used for the chemoselective hydrogenation of 3-nitrostyrene, gives a three times higher turn-over frequency (TOF) than that for the well-established Au/TiO2 system. The d electron gain of Au is linearly related to the activation entropy and TOF. The catalyst is stable, and can be recycled ten times with negligible loss of both reaction rate and overall conversion. This strategy paves the way for optimizing noble metal catalysts to give an enhanced hydrogenation catalytic performance.
An artificial sensory neuron with visual-haptic fusion
Authors: Wan Changjin , Cai Pingqiang , Guo Xintong , Wang Ming , Matsuhisa Naoji , Yang Le , Lv Zhisheng , Luo Yifei , Loh Xian Jun , Chen Xiaodong
Published: September 2020

Human behaviors are extremely sophisticated, relying on the adaptive, plastic and event-driven network of sensory neurons. Such neuronal system analyzes multiple sensory cues efficiently to establish accurate depiction of the environment. Here, we develop a bimodal artificial sensory neuron to implement the sensory fusion processes. Such a bimodal artificial sensory neuron collects optic and pressure information from the photodetector and pressure sensors respectively, transmits the bimodal information through an ionic cable, and integrates them into post-synaptic currents by a synaptic transistor. The sensory neuron can be excited in multiple levels by synchronizing the two sensory cues, which enables the manipulating of skeletal myotubes and a robotic hand. Furthermore, enhanced recognition capability achieved on fused visual/haptic cues is confirmed by simulation of a multi-transparency pattern recognition task. Our biomimetic design has the potential to advance technologies in cyborg and neuromorphic systems by endowing them with supramodal perceptual capabilities.
Random terpolymer based on thiophene-thiazolothiazole unit enabling efficient non-fullerene organic solar cells
Authors: Wu Jingnan , Li Guangwei , Fang Jin , Guo Xia , Zhu Lei , Guo Bing , Wang Yulong , Zhang Guangye , Arunagiri Lingeswaran , Liu Feng , Yan He , Zhang Maojie , Li Yongfang
Published: September 2020

Developing a high-performance donor polymer is critical for achieving efficient non-fullerene organic solar cells (OSCs). Currently, most high-efficiency OSCs are based on a donor polymer named PM6, unfortunately, whose performance is highly sensitive to its molecular weight and thus has significant batch-to-batch variations. Here we report a donor polymer (named PM1) based on a random ternary polymerization strategy that enables highly efficient non-fullerene OSCs with efficiencies reaching 17.6%. Importantly, the PM1 polymer exhibits excellent batch-to-batch reproducibility. By including 20% of a weak electron-withdrawing thiophene-thiazolothiazole (TTz) into the PM6 polymer backbone, the resulting polymer (PM1) can maintain the positive effects (such as downshifted energy level and reduced miscibility) while minimize the negative ones (including reduced temperature-dependent aggregation property). With higher performance and greater synthesis reproducibility, the PM1 polymer has the promise to become the work-horse material for the non-fullerene OSC community.
Precise allele-specific genome editing by spatiotemporal control of CRISPR-Cas9 via pronuclear transplantation
Authors: Li Yanhe , Weng Yuteng , Bai Dandan , Jia Yanping , Liu Yingdong , Zhang Yalin , Kou Xiaochen , Zhao Yanhong , Ruan Jingling , Chen Jiayu , Yin Jiqing , Wang Hong , Teng Xiaoming , Wang Zuolin , Liu Wenqiang , Gao Shaorong
Published: September 2020

Gene-targeted animal models that are generated by injecting Cas9 and sgRNAs into zygotes are often accompanied by undesired double-strand break (DSB)-induced byproducts and random biallelic targeting due to uncontrollable Cas9 targeting activity. Here, we establish a parental allele-specific gene-targeting (Past-CRISPR) method, based on the detailed observation that pronuclear transfer-mediated cytoplasmic dilution can effectively terminate Cas9 activity. We apply this method in embryos to efficiently target the given parental alleles of a gene of interest and observed little genomic mosaicism because of the spatiotemporal control of Cas9 activity. This method allows us to rapidly explore the function of individual parent-of-origin effects and to construct animal models with a single genomic change. More importantly, Past-CRISPR could also be used for therapeutic applications or disease model construction.
Stabilization of a molecular water oxidation catalyst on a dye−sensitized photoanode by a pyridyl anchor
Authors: Zhu Yong , Wang Degao , Huang Qing , Du Jian , Sun Licheng , Li Fei , Meyer Thomas J.
Published: September 2020

Understanding and controlling the properties of water-splitting assemblies in dye-sensitized photoelectrosynthesis cells is a key to the exploitation of their properties. We demonstrate here that, following surface loading of a [Ru(bpy)3]2+ (bpy = 2,2′-bipyridine) chromophore on nanoparticle electrodes, addition of the molecular catalysts, Ru(bda)(L)2 (bda  =  2,2′-bipyridine-6,6′-dicarboxylate) with phosphonate or pyridyl sites for water oxidation, gives surfaces with a 5:1 chromophore to catalyst ratio. Addition of the surface-bound phosphonate derivatives with L = 4-pyridyl phosphonic acid or diethyl 3-(pyridin-4-yloxy)decyl-phosphonic acid, leads to well-defined surfaces but, following oxidation to Ru(III), they undergo facile, on-surface dimerization to give surface-bound, oxo-bridged dimers. The dimers have a diminished reactivity toward water oxidation compared to related monomers in solution. By contrast, immobilization of the Ru-bda catalyst on TiO2 with the 4,4′-dipyridyl anchoring ligand can maintain the monomeric structure of catalyst and gives relatively stable photoanodes with photocurrents that reach to 1.7 mA cm−2 with an optimized, applied bias photon-to-current efficiency of 1.5%.
Chemical entrapment and killing of insects by bacteria
Authors: Ho Louis K. , Daniel-Ivad Martin , Jeedigunta Swathi P. , Li Jing , Iliadi Konstantin G. , Boulianne Gabrielle L. , Hurd Thomas R. , Smibert Craig A. , Nodwell Justin R.
Published: September 2020

Actinobacteriaproduce antibacterial and antifungal specialized metabolites. Many insects harbour actinobacteria on their bodies or in their nests and use these metabolites for protection. However, some actinobacteria produce metabolites that are toxic to insects and the evolutionary relevance of this toxicity is unknown. Here we explore chemical interactions between streptomycetes and the fruit flyDrosophila melanogaster. We find that many streptomycetes produce specialized metabolites that have potent larvicidal effects against the fly; larvae that ingest spores of these species die. The mechanism of toxicity is specific to the bacterium’s chemical arsenal: cosmomycin D producing bacteria induce a cell death-like response in the larval digestive tract; avermectin producing bacteria induce paralysis. Furthermore, low concentrations of volatile terpenes like 2-methylisoborneol that are produced by streptomycetes attract fruit flies such that they preferentially deposit their eggs on contaminated food sources. The resulting larvae are killed during growth and development. The phenomenon of volatile-mediated attraction and specialized metabolite toxicity suggests that some streptomycetes pose an evolutionary risk to insects in nature.
Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide
Authors: Furihata Hirotake , Yamanaka Satoshi , Honda Toshiaki , Miyauchi Yumiko , Asano Atsuko , Shibata Norio , Tanokura Masaru , Sawasaki Tatsuya , Miyakawa Takuya
Published: September 2020

Thalidomide and its derivatives exert not only therapeutic effects as immunomodulatory drugs (IMiDs) but also adverse effects such as teratogenicity, which are due in part to different C2H2 zinc-finger (ZF) transcription factors, IKZF1 (or IKZF3) and SALL4, respectively. Here, we report the structural bases for the SALL4-specific proteasomal degradation induced by 5-hydroxythalidomide, a primary thalidomide metabolite generated by the enzymatic activity of cytochrome P450 isozymes, through the interaction with cereblon (CRBN). The crystal structure of the metabolite-mediated human SALL4-CRBN complex and mutagenesis studies elucidate the complex formation enhanced by the interaction between CRBN and an additional hydroxy group of (S)-5-hydroxythalidomide and the variation in the second residue of β-hairpin structure that underlies the C2H2 ZF-type neo-morphic substrate (neosubstrate) selectivity of 5-hydroxythalidomide. These findings deepen our understanding of the pharmaceutical action of IMiDs and provide structural evidence that the glue-type E3 ligase modulators cause altered neosubstrate specificities through their metabolism.
Author Correction: Understanding the genetic determinants of the brain with MOSTest
Authors: van der Meer Dennis , Frei Oleksandr , Kaufmann Tobias , Shadrin Alexey A. , Devor Anna , Smeland Olav B. , Thompson Wesley K. , Fan Chun Chieh , Holland Dominic , Westlye Lars T. , Andreassen Ole A. , Dale Anders M.
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Development and validation of the CHIRTS-daily quasi-global high-resolution daily temperature data set
Authors: Verdin Andrew , Funk Chris , Peterson Pete , Landsfeld Martin , Tuholske Cascade , Grace Kathryn
Published: September 2020

We present a high-resolution daily temperature data set, CHIRTS-daily, which is derived by merging the monthly Climate Hazards center InfraRed Temperature with Stations climate record with daily temperatures from version 5 of the European Centre for Medium-Range Weather Forecasts Re-Analysis. We demonstrate that remotely sensed temperature estimates may more closely represent true conditions than those that rely on interpolation, especially in regions with sparse in situ data. By leveraging remotely sensed infrared temperature observations, CHIRTS-daily provides estimates of 2-meter air temperature for 1983–2016 with a footprint covering 60°S-70°N. We describe this data set and perform a series of validations using station observations from two prominent climate data sources. The validations indicate high levels of accuracy, with CHIRTS-daily correlations with observations ranging from 0.7 to 0.9, and very good representation of heat wave trends.
On speeding up factoring with quantum SAT solvers
Authors: Mosca Michele , Basso Joao Marcos Vensi , Verschoor Sebastian R.
Published: September 2020

There have been several efforts to apply quantum SAT solving methods to factor large integers. While these methods may provide insight into quantum SAT solving, to date they have not led to a convincing path to integer factorization that is competitive with the best known classical method, the Number Field Sieve. Many of the techniques tried involved directly encoding multiplication to SAT or an equivalent NP-hard problem and looking for satisfying assignments of the variables representing the prime factors. The main challenge in these cases is that, to compete with the Number Field Sieve, the quantum SAT solver would need to be superpolynomially faster than classical SAT solvers. In this paper the use of SAT solvers is restricted to a smaller task related to factoring: finding smooth numbers, which is an essential step of the Number Field Sieve. We present a SAT circuit that can be given to quantum SAT solvers such as annealers in order to perform this step of factoring. If quantum SAT solvers achieve any asymptotic speedup over classical brute-force search for smooth numbers, then our factoring algorithm is faster than the classical NFS.
Higher cut-off values of non-invasive methods might be needed to detect moderate-to-severe steatosis in morbid obese patients: a pilot study
Authors: Parente Daniella Braz , Perazzo Hugo , Paiva Fernando Fernandes , Campos Carlos Frederico Ferreira , Saboya Carlos José , Pereira Silvia Elaine , Silva Felipe d’Almeida e , Rodrigues Rosana Souza , Perez Renata de Mello
Published: September 2020

To evaluate the diagnostic value of described thresholds of controlled attenuation parameter (CAP) and biomarker scores for liver steatosis and to evaluate new cut-offs to detect moderate-to-severe steatosis (S2–3) in patients with morbid obesity. In this prospective study, 32 patients with morbid obesity with indications for bariatric surgery (15 women and 17 men, mean age = 36 years, median BMI = 40.2 kg/m2) underwent CAP, magnetic resonance spectroscopy (MRS), three biomarker scores (Steato-ELSA, Fatty Liver Index (FLI), and Hepatic Steatosis Index (HSI)), and liver biopsy. Subjects were divided into an exploratory cohort (reliable CAP and liver biopsy) and a confirmatory cohort (reliable CAP and MRS) to evaluate new thresholds for CAP and biomarker scores to detect S2–3. Receiver operator characteristic (ROC) curves analyses were performed and the optimal cut-off points were identified using the maximal Youden index. A total of 22 patients had CAP measure and liver biopsy (exploratory cohort) and 24 patients had CAP measure with MRS (confirmatory cohort). New cut-offs were identified for detection of S2–3 by the non-invasive tests using liver biopsy as the reference standard (exploratory cohort). Considering the new proposed cut-offs for detection of S2–3 for CAP (≥ 314 dB/m), Steato-ELSA (≥ 0.832), FLI (≥ 96), and HSI (≥ 53), for the exploratory and confirmatory cohorts sensitivities were: 71–75%, 86–81%, 85–81%, and 71–69% and specificities were: 94–89%, 75–63%, 63–63%, and 75–88%, respectively. Higher cut-offs for CAP and biomarker scores may be better to diagnose moderate-to-severe steatosis in patients with morbid obesity.
Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition
Authors: Grant Oliver C. , Montgomery David , Ito Keigo , Woods Robert J.
Published: September 2020

Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the innate and adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the notable exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight of the S trimer (17% for the HEK293 glycoform) they shield approximately 40% of the protein surface.
Investigating the influence of perinatal nicotine and alcohol exposure on the genetic profiles of dopaminergic neurons in the VTA using miRNA–mRNA analysis
Authors: Kazemi Tina , Huang Shuyan , Avci Naze G. , Waits Charlotte Mae K. , Akay Yasemin M. , Akay Metin
Published: September 2020

Nicotine and alcohol are two of the most commonly used and abused recreational drugs, are often used simultaneously, and have been linked to significant health hazards. Furthermore, patients diagnosed with dependence on one drug are highly likely to be dependent on the other. Several studies have shown the effects of each drug independently on gene expression within many brain regions, including the ventral tegmental area (VTA). Dopaminergic (DA) neurons of the dopamine reward pathway originate from the VTA, which is believed to be central to the mechanism of addiction and drug reinforcement. Using a well-established rat model for both nicotine and alcohol perinatal exposure, we investigated miRNA and mRNA expression of dopaminergic (DA) neurons of the VTA in rat pups following perinatal alcohol and joint nicotine–alcohol exposure. Microarray analysis was then used to profile the differential expression of both miRNAs and mRNAs from DA neurons of each treatment group to further explore the altered genes and related biological pathways modulated. Predicted and validated miRNA-gene target pairs were analyzed to further understand the roles of miRNAs within these networks following each treatment, along with their post transcription regulation points affecting gene expression throughout development. This study suggested that glutamatergic synapse and axon guidance pathways were specifically enriched and many miRNAs and genes were significantly altered following alcohol or nicotine–alcohol perinatal exposure when compared to saline control. These results provide more detailed insight into the cell proliferation, neuronal migration, neuronal axon guidance during the infancy in rats in response to perinatal alcohol/ or nicotine–alcohol exposure.
Evaluation of whole genome amplification and bioinformatic methods for the characterization of Leishmania genomes at a single cell level
Authors: Imamura Hideo , Monsieurs Pieter , Jara Marlene , Sanders Mandy , Maes Ilse , Vanaerschot Manu , Berriman Matthew , Cotton James A. , Dujardin Jean-Claude , Domagalska Malgorzata A.
Published: September 2020

Here, we report a pilot study paving the way for further single cell genomics studies in Leishmania. First, the performances of two commercially available kits for Whole Genome Amplification (WGA), PicoPLEX and RepliG were compared on small amounts of Leishmania donovani DNA, testing their ability to preserve specific genetic variations, including aneuploidy levels and SNPs. We show here that the choice of WGA method should be determined by the planned downstream genetic analysis, PicoPLEX and RepliG performing better for aneuploidy and SNP calling, respectively. This comparison allowed us to evaluate and optimize corresponding bio-informatic methods. As PicoPLEX was shown to be the preferred method for studying single cell aneuploidy, this method was applied in a second step, on single cells of L. braziliensis, which were sorted by fluorescence activated cell sorting (FACS). Even sequencing depth was achieved in 28 single cells, allowing accurate somy estimation. A dominant karyotype with three aneuploid chromosomes was observed in 25 cells, while two different minor karyotypes were observed in the other cells. Our method thus allowed the detection of aneuploidy mosaicism, and provides a solid basis which can be further refined to concur with higher-throughput single cell genomic methods.
Validation of reference genes for expression analysis in a murine trauma model combining traumatic brain injury and femoral fracture
Authors: Otto Ellen , Köhli Paul , Appelt Jessika , Menzel Stefanie , Fuchs Melanie , Bahn Alina , Graef Frank , Duda Georg N. , Tsitsilonis Serafeim , Keller Johannes , Jahn Denise
Published: September 2020

Systemic and local posttraumatic responses are often monitored on mRNA expression level using quantitative real-time PCR (qRT-PCR), which requires normalisation to adjust for confounding sources of variability. Normalisation requests reference (housekeeping) genes stable throughout time and divergent experimental conditions in the tissue of interest, which are crucial for a reliable and reproducible gene expression analysis. Although previous animal studies analysed reference genes following isolated trauma, this multiple-trauma gene expression analysis provides a notable study analysing reference genes in primarily affected (i.e. bone/fracture callus and hypothalamus) and secondarily affected organs (i.e. white adipose tissue, liver, muscle and spleen), following experimental long bone fracture and traumatic brain injury. We considered tissue-specific and commonly used top-ranked reference candidates from different functional groups that were evaluated applying the established expression stability analysis tools NormFinder, GeNorm, BestKeeper and RefFinder. In conclusion, reference gene expression in primary organs is highly time point as well as tissue-specific, and therefore requires careful evaluation for qRT-PCR analysis. Furthermore, the general application of Ppia, particularly in combination with a second reference gene, is strongly recommended for the analysis of systemic effects in the case of indirect trauma affecting secondary organs through local and systemic pathophysiological responses.
Gene polymorphisms and serum levels of sVEGFR-1 in patients with systemic lupus erythematosus
Authors: Yuan Zhi-Chao , Xu Wang-Dong , Wang Jia-Min , Wu Qian , Zhou Jie , Huang An-Fang
Published: September 2020

Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case–control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.
Response of vertebrate scavengers to power line and road rights-of-way and its implications for bird fatality estimates
Authors: Bernardino Joana , Bispo Regina , Martins Ricardo C. , Santos Sara , Moreira Francisco
Published: September 2020

Linear infrastructures, such as power lines and roads, are an important source of bird mortality. However, little is known on the potential effect of these infrastructures on local scavenger guilds, their foraging activity and the resulting bird carcass removal patterns. This is an important source of bias in studies aiming to quantify bird fatalities due to linear infrastructures. We used camera-traps to record scavenger identity and persistence patterns of bird carcasses placed close to linear infrastructure and nearby controls in two Mediterranean agricultural regions. We found that linear infrastructure influence on scavenger identity varied depending on the region. Contrary to expectations, linear infrastructure presence had either none or a positive effect on carcass persistence, meaning that carcasses placed within power line or road rights-of-way were not removed faster than the ones placed in controls. We conclude that linear infrastructure effect on vertebrate scavenging patterns is likely to be region-specific, and that reliable correction factors for carcass removal-bias in bird fatality estimates require site-specific experiments to characterize local scavenging processes.
Environmental impact of utilization of “produced water” from oil and gas operations in turfgrass systems
Authors: Shaikh Sameera S. , Abu-Dieyeh Mohammed H. , Al Naemi Fatima A. , Ahmed Talaat , Al-Ghouti Mohammad A.
Published: September 2020

This study attempted to use produced water (PW) to irrigate turfgrass species, Cynodon dactylon and Paspalum sp. Assessment on established grasses, heavy metal accumulation and germination tests for weeds and turf grass seeds were conducted to evaluate the impact of PW irrigation. C. dactylon depicted lower tolerance while Paspalum sp. showed better tolerance capacity towards PW. C. dactylon grown from seeds under greenhouse conditions were not able to tolerate more than 30% concentration of PW (4.5% salinity). In comparison to tap water irrigated turf grass, Paspalum sp. was found to accumulate higher concentrations of V and Pb in shoots and Cr, Ni and As in roots. The results of seed germination tests recommended that irrigation with PW is to be performed after turfgrass establishment. Germination tests also revealed that PW could encourage growth of the weed—Chloris virgata while it could discourage growth of Amaranthus viridis and Launaea mucronata. This study suggests that PW could be used for turfgrass as an alternative water resource but only after further research on the long-term scale.
Integrative genomic analysis of salivary duct carcinoma
Authors: Kim Youngwook , Song Sanghoon , Lee Miran , Swatloski Teresa , Kang Joon Ho , Ko Young-Hyeh , Park Woong-Yang , Jeong Han-Sin , Park Keunchil
Published: September 2020

Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally applicable except in very limited cases, and there exists a strong need for the development of treatment against this unique tumor type. To further interrogate genomic features of SDC, we have conducted multi-omic profiling of the SDC to describe the genomic alterations prevalent in this disease. Whole-genome sequencing, whole exome-sequencing and transcriptome sequencing were performed on a discovery cohort of 10 SDC samples. Targeted genomic profiling was performed in additional 32 SDC samples to support the findings obtained from the original discovery cohort. The cancer cohort was characterized by an average mutation burden of 85 somatic exonic mutations per tumor sample. The cohort harbored a mutational signature of BRCA and APOBEC/AID. Several genes, including TP53, RB1, SMAD4, HRAS, APC, PIK3CA and GNAQ were recurrently somatically altered in SDC. A novel fusion gene, generated by genomic rearrangement, MYB-NHSL1, was also noted. Our findings represent a significant layer in the systematic understanding of potentially clinically useful genomic and molecular targets for a subset of recurrent/metastatic SDC.
UQCRH downregulation promotes Warburg effect in renal cell carcinoma cells
Authors: Luo Yanting , Medina Bengtsson Louise , Wang Xuechun , Huang Tianhe , Liu Guoqiang , Murphy Sean , Wang Caiqin , Koren John , Schafer Zachary , Lu Xin
Published: September 2020

Ubiquinol-cytochrome c reductase hinge protein (UQCRH) is the hinge protein for the multi-subunit complex III of the mitochondrial electron transport chain and is involved in the electron transfer reaction between cytochrome c1 and c. Recent genome-wide transcriptomic and epigenomic profiling of clear cell renal cell carcinoma (ccRCC) by The Cancer Genome Atlas (TCGA) identified UQCRH as the top-ranked gene showing inverse correlation between DNA hypermethylation and mRNA downregulation. The function and underlying mechanism of UQCRH in the Warburg effect metabolism of ccRCC have not been characterized. Here, we verified the clinical association of low UQCRH expression and shorter survival of ccRCC patients through in silico analysis and identified KMRC2 as a highly relevant ccRCC cell line that displays hypermethylation-induced UQCRH extinction. Ectopic overexpression of UQCRH in KMRC2 restored mitochondrial membrane potential, increased oxygen consumption, and attenuated the Warburg effect at the cellular level. UQCRH overexpression in KMRC2 induced higher apoptosis and slowed down in vitro and in vivo tumor growth. UQCRH knockout by CRISPR/Cas9 had little impact on the metabolism and proliferation of 786O ccRCC cell line, suggesting the dispensable role of UQCRH in cells that have entered a Warburg-like state through other mechanisms. Together, our study suggests that loss of UQCRH expression by hypermethylation may promote kidney carcinogenesis through exacerbating the functional decline of mitochondria thus reinforcing the Warburg effect.
Breath methane to hydrogen ratio as a surrogate marker of intestinal dysbiosis in head and neck cancer
Authors: Dharmawardana Nuwan , Goddard Thomas , Woods Charmaine , Watson David I. , Butler Ross , Ooi Eng H. , Yazbeck Roger
Published: September 2020

Exhaled breath compounds can non-invasively detect head and neck squamous cell carcinoma (HNSCC). Here we investigated exhaled compounds related to intestinal bacterial carbohydrate fermentation. Fasting breath samples were collected into 3 litre FlexFoil PLUS bags from patients awaiting a biopsy procedure for suspected HNSCC. Samples were analysed using a Syft selected ion flow-tube mass spectrometer and a Quintron BreathTracker. Two tailed non-parametric significance testing was conducted with corrections for multiple imputations. 74 patients were diagnosed (histological) with HNSCC and 61 patients were benign (controls). The methane to hydrogen ratio was significantly different between cancer and non-cancer controls (p = 0.0440). This ratio increased with tumour stage with a significant difference between T1 and T4 tumours (p = 0.0259). Hydrogen levels were significantly higher in controls who were smokers (p = 0.0129), with no smoking dependent methane changes. There were no differences in short chain fatty acids between groups. Exhaled compounds of intestinal carbohydrate fermentation can detect HNSCC patients. These findings suggest a modified carbohydrate fermentation profile in HNSCC patients that is tumour stage and smoking status dependent.
Overexpression of ATP sulfurylase improves the sulfur amino acid content, enhances the accumulation of Bowman–Birk protease inhibitor and suppresses the accumulation of the β-subunit of β-conglycinin in soybean seeds
Authors: Kim Won-Seok , Sun-Hyung Jeong , Oehrle Nathan W. , Jez Joseph M. , Krishnan Hari B.
Published: September 2020

ATP sulfurylase, an enzyme which catalyzes the conversion of sulfate to adenosine 5′-phosphosulfate (APS), plays a significant role in controlling sulfur metabolism in plants. In this study, we have expressed soybean plastid ATP sulfurylase isoform 1 in transgenic soybean without its transit peptide under the control of the 35S CaMV promoter. Subcellular fractionation and immunoblot analysis revealed that ATP sulfurylase isoform 1 was predominantly expressed in the cell cytoplasm. Compared with that of untransformed plants, the ATP sulfurylase activity was about 2.5-fold higher in developing seeds. High-resolution 2-D gel electrophoresis and immunoblot analyses revealed that transgenic soybean seeds overexpressing ATP sulfurylase accumulated very low levels of the β-subunit of β-conglycinin. In contrast, the accumulation of the cysteine-rich Bowman–Birk protease inhibitor was several fold higher in transgenic soybean plants when compared to the non-transgenic wild-type seeds. The overall protein content of the transgenic seeds was lowered by about 3% when compared to the wild-type seeds. Metabolite profiling by LC–MS and GC–MS quantified 124 seed metabolites out of which 84 were present in higher amounts and 40 were present in lower amounts in ATP sulfurylase overexpressing seeds compared to the wild-type seeds. Sulfate, cysteine, and some sulfur-containing secondary metabolites accumulated in higher amounts in ATP sulfurylase transgenic seeds. Additionally, ATP sulfurylase overexpressing seeds contained significantly higher amounts of phospholipids, lysophospholipids, diacylglycerols, sterols, and sulfolipids. Importantly, over expression of ATP sulfurylase resulted in 37–52% and 15–19% increases in the protein-bound cysteine and methionine content of transgenic seeds, respectively. Our results demonstrate that manipulating the expression levels of key sulfur assimilatory enzymes could be exploited to improve the nutritive value of soybean seeds.
Effects of SF6 decomposition components and concentrations on the discharge faults and insulation defects in GIS equipment
Authors: Zhuang Yuan , Hu Xiaotong , Tang Bin , Wang Siwei , Cui Anyang , Hou Keyong , He Yunhua , Zhu Liangqing , Li Wenwu , Chu Junhao
Published: September 2020

Gas-insulated switchgear (GIS) is widely used across multiple electric stages and different power grid levels. However, the threat from several inevitable faults in the GIS system surrounds us for the safety of electricity use. In order to improve the evaluation ability of GIS system safety, we propose an efficient strategy by using machine learning to conduct SF6 decomposed components analysis (DCA) for further diagnosing discharge fault types in GIS. Note that the empirical probability function of different faults fitted by the Arrhenius chemical reaction model has been investigated into the robust feature engineering for machine learning based GIS diagnosing model. Six machine learning algorithms were used to establish models for the severity of discharge fault and main insulation defects, where identification algorithms were trained by learning the collection dataset composing the concentration of the different gas types (SO2, SOF2, SO2F2, CF4, and CO2, etc.) in the system and their ratios. Notably, multiple discharge fault types coexisting in GIS can be effectively identified based on a probability model. This work would provide a great insight into the development of evaluation and optimization on solving discharge fault in GIS.
Norepinephrine depleting toxin DSP-4 and LPS alter gut microbiota and induce neurotoxicity in α-synuclein mutant mice
Authors: Song Sheng , Liu Jie , Zhang Feng , Hong Jau-Shyong
Published: September 2020

This study examined the genetic mutation and toxicant exposure in producing gut microbiota alteration and neurotoxicity. Homozygous α-synuclein mutant (SNCA) mice that overexpress human A53T protein and littermate wild-type mice received a single injection of LPS (2 mg/kg) or a selective norepinephrine depleting toxin DSP-4 (50 mg/kg), then the motor activity, dopaminergic neuron loss, colon gene expression and gut microbiome were examined 13 months later. LPS and DSP-4 decreased rotarod and wirehang activity, reduced dopaminergic neurons in substantia nigra pars compacta (SNpc), and SNCA mice were more vulnerable. SNCA mice had 1,000-fold higher human SNCA mRNA expression in the gut, and twofold higher gut expression of NADPH oxidase (NOX2) and translocator protein (TSPO). LPS further increased expression of TSPO and IL-6 in SNCA mice. Both LPS and DSP-4 caused microbiome alterations, and SNCA mice were more susceptible. The altered colon microbiome approximated clinical findings in PD patients, characterized by increased abundance of Verrucomicrobiaceae, and decreased abundance of Prevotellaceae, as evidenced by qPCR with 16S rRNA primers. The Firmicutes/Bacteroidetes ratio was increased by LPS in SNCA mice. This study demonstrated a critical role of α-synuclein and toxins interactions in producing gut microbiota disruption, aberrant gut pro-inflammatory gene expression, and dopaminergic neuron loss.