bluuebunny/crossref_metadata_2025_split huggingface dataset:
US nativity and dietary acculturation impact the gut microbiome in a diverse US population
Authors: Peters Brandilyn A , Yi Stella S , Beasley Jeannette M , Cobbs Emilia N , Choi Hee Sun , Beggs Dia B , Hayes Richard B , Ahn Jiyoung 
Published: March 2020

Abstract
Little is known regarding the impact of immigrant acculturation on the gut microbiome. We characterized differences in the gut microbiome between racially/ethnically diverse US immigrant and US-born groups, and determined the impact of dietary acculturation on the microbiome. Stool samples were collected from 863 US residents, including US-born (315 White, 93 Black, 40 Hispanic) and foreign-born (105 Hispanic, 264 Korean) groups. We determined dietary acculturation from dissimilarities based on food frequency questionnaires, and used 16S rRNA gene sequencing to characterize the microbiome. Gut microbiome composition differed across study groups, with the largest difference between foreign-born Koreans and US-born Whites, and significant differences also observed between foreign-born and US-born Hispanics. Differences in sub-operational taxonomic unit (s-OTU) abundance between foreign-born and US-born groups tended to be distinct from differences between US-born groups. Bacteroides plebeius, a seaweed-degrading bacterium, was strongly enriched in foreign-born Koreans, while Prevotella copri and Bifidobacterium adolescentis were strongly enriched in foreign-born Koreans and Hispanics, compared with US-born Whites. Dietary acculturation in foreign-born participants was associated with specific s-OTUs, resembling abundance in US-born Whites; e.g., a Bacteroides plebeius s-OTU was depleted in highly diet-acculturated Koreans. In summary, we observed that US nativity is a determinant of the gut microbiome in a US resident population. Dietary acculturation may result in loss of native species in immigrants, though further research is necessary to explore whether acculturation-related microbiome alterations have consequences for immigrant health.
Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics
Authors: Leonard Anne , Möhlis Kevin , Schlüter Rabea , Taylor Edward , Lalk Michael , Methling Karen 
Published: March 2020

AbstractThe Gram-positive bacterium Streptococcus pneumoniae is one of the common causes of community acquired pneumonia, meningitis, and otitis media. Analyzing the metabolic adaptation toward environmental stress conditions improves our understanding of its pathophysiology and its dependency on host-derived nutrients. In this study, extra- and intracellular metabolic profiles were evaluated to investigate the impact of antimicrobial compounds targeting different pathways of the metabolome of S. pneumoniae TIGR4Δcps. For the metabolomics approach, we analyzed the complex variety of metabolites by using 1H NMR, HPLC-MS, and GC–MS as different analytical techniques. Through this combination, we detected nearly 120 metabolites. For each antimicrobial compound, individual metabolic effects were detected that often comprised global biosynthetic pathways. Cefotaxime altered amino acids metabolism and carbon metabolism. The purine and pyrimidine metabolic pathways were mostly affected by moxifloxacin treatment. The combination of cefotaxime and azithromycin intensified the stress response compared with the use of the single antibiotic. However, we observed that three cell wall metabolites were altered only by treatment with the combination of the two antibiotics. Only moxifloxacin stress-induced alternation in CDP-ribitol concentration. Teixobactin-Arg10 resulted in global changes of pneumococcal metabolism. To meet the growing requirements for new antibiotics, our metabolomics approach has shown to be a promising complement to other OMICs investigations allowing insights into the mode of action of novel antimicrobial compounds.
The cardiac work-loop technique: An in vitro model for identifying and profiling drug-induced changes in inotropy using rat papillary muscles
Authors: Fletcher Sophie , Maddock Helen , James Rob S. , Wallis Rob , Gharanei Mayel 
Published: March 2020

AbstractThe cardiac work-loop technique closely mimics the intrinsicin vivomovement and characteristics of cardiac muscle function. In this study, six known inotropes were profiled using the work-loop technique to evaluate the potential of this method to predict inotropy. Papillary muscles from male Sprague-Dawley rats were mounted onto an organ bath perfused with Krebs-Henseleit buffer. Following optimisation, work-loop contractions were performed that included an initial stabilisation period followed by vehicle control or drug administration. Six known inotropes were tested: digoxin, dobutamine, isoprenaline, flecainide, verapamil and atenolol. Muscle performance was evaluated by calculating power output during work-loop contraction. Digoxin, dobutamine and isoprenaline caused a significant increase in power output of muscles when compared to vehicle control. Flecainide, verapamil and atenolol significantly reduced power output of muscles. These changes in power output were reflected in alterations in work loop shapes. This is the first study in which changes in work-loop shape detailing for example the activation, shortening or passive re-lengthening have been linked to the mechanism of action of a compound. This study has demonstrated that the work-loop technique can provide an important novel method with which to assess detailed mechanisms of drug-induced effects on cardiac muscle contractility.
Effects of Chlorhexidine mouthwash on the oral microbiome
Authors: Bescos Raul , Ashworth Ann , Cutler Craig , Brookes Zoe L. , Belfield Louise , Rodiles Ana , Casas-Agustench Patricia , Farnham Garry , Liddle Luke , Burleigh Mia , White Desley , Easton Chris , Hickson Mary 
Published: March 2020

AbstractFollowing a single blind, cross-over and non-randomized design we investigated the effect of 7-day use of chlorhexidine (CHX) mouthwash on the salivary microbiome as well as several saliva and plasma biomarkers in 36 healthy individuals. They rinsed their mouth (for 1 min) twice a day for seven days with a placebo mouthwash and then repeated this protocol with CHX mouthwash for a further seven days. Saliva and blood samples were taken at the end of each treatment to analyse the abundance and diversity of oral bacteria, and pH, lactate, glucose, nitrate and nitrite concentrations. CHX significantly increased the abundance of Firmicutes and Proteobacteria, and reduced the content of Bacteroidetes, TM7, SR1 and Fusobacteria. This shift was associated with a significant decrease in saliva pH and buffering capacity, accompanied by an increase in saliva lactate and glucose levels. Lower saliva and plasma nitrite concentrations were found after using CHX, followed by a trend of increased systolic blood pressure. Overall, this study demonstrates that mouthwash containing CHX is associated with a major shift in the salivary microbiome, leading to more acidic conditions and lower nitrite availability in healthy individuals.
The Human Lung Glycome Reveals Novel Glycan Ligands for Influenza A Virus
Authors: Jia Nan , Byrd-Leotis Lauren , Matsumoto Yasuyuki , Gao Chao , Wein Alexander N. , Lobby Jenna L. , Kohlmeier Jacob E. , Steinhauer David A. , Cummings Richard D. 
Published: March 2020

AbstractGlycans within human lungs are recognized by many pathogens such as influenza A virus (IAV), yet little is known about their structures. Here we present the first analysis of the N- and O- and glycosphingolipid-glycans from total human lungs, along with histological analyses of IAV binding. The N-glycome of human lung contains extremely large complex-type N-glycans with linear poly-N-acetyllactosamine (PL) [-3Galβ1–4GlcNAcβ1-]n extensions, which are predominantly terminated in α2,3-linked sialic acid. By contrast, smaller N-glycans lack PL and are enriched in α2,6-linked sialic acids. In addition, we observed large glycosphingolipid (GSL)-glycans, which also consists of linear PL, terminating in mainly α2,3-linked sialic acid. Histological staining revealed that IAV binds to sialylated and non-sialylated glycans and binding is not concordant with respect to binding by sialic acid-specific lectins. These results extend our understanding of the types of glycans that may serve as binding sites for human lung pathogens.
Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism
Authors: Schauer Nathan J. , Liu Xiaoxi , Magin Robert S. , Doherty Laura M. , Chan Wai Cheung , Ficarro Scott B. , Hu Wanyi , Roberts Rebekka M. , Iacob Roxana E. , Stolte Björn , Giacomelli Andrew O. , Perera Sumner , McKay Kyle , Boswell Sarah A. , Weisberg Ellen L. , Ray Arghya , Chauhan Dharminder , Dhe-Paganon Sirano , Anderson Ken C. , Griffin James D. , Li Jianing , Hahn William C. , Sorger Peter K. , Engen John R. , Stegmaier Kimberly , Marto Jarrod A. , Buhrlage Sara J. 
Published: March 2020

AbstractUbiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP7 has been proposed as a therapeutic target in several cancers because it has many reported substrates with a role in cancer progression, including FOXO4, MDM2, N-Myc, and PTEN. The multi-substrate nature of USP7, combined with the modest potency and selectivity of early generation USP7 inhibitors, has presented a challenge in defining predictors of response to USP7 and potential patient populations that would benefit most from USP7-targeted drugs. Here, we describe the structure-guided development of XL177A, which irreversibly inhibits USP7 with sub-nM potency and selectivity across the human proteome. Evaluation of the cellular effects of XL177A reveals that selective USP7 inhibition suppresses cancer cell growth predominantly through a p53-dependent mechanism: XL177A specifically upregulates p53 transcriptional targets transcriptome-wide, hotspot mutations in TP53 but not any other genes predict response to XL177A across a panel of ~500 cancer cell lines, and TP53 knockout rescues XL177A-mediated growth suppression of TP53 wild-type (WT) cells. Together, these findings suggest TP53 mutational status as a biomarker for response to USP7 inhibition. We find that Ewing sarcoma and malignant rhabdoid tumor (MRT), two pediatric cancers that are sensitive to other p53-dependent cytotoxic drugs, also display increased sensitivity to XL177A.
In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease
Authors: Mota Mânlio Tasso de Oliveira , Costa Vivian Vasconcelos , Sugimoto Michelle Amantéa , Guimarães Georgia de Freitas , Queiroz-Junior Celso Martins , Moreira Thaiane Pinto , de Sousa Carla Daiane , Santos Franciele Martins , Queiroz Victoria Fulgêncio , Passos Ingredy , Hubner Josy , Souza Danielle Gloria , Weaver Scott C. , Teixeira Mauro Martins , Nogueira Maurício Lacerda 
Published: March 2020

AbstractMayaro virus (MAYV) is endemic in South American countries where it is responsible for sporadic outbreaks of acute febrile illness. The hallmark of MAYV infection is a highly debilitating and chronic arthralgia. Although MAYV emergence is a potential threat, there are no specific therapies or licensed vaccine. In this study, we developed a murine model of MAYV infection that emulates many of the most relevant clinical features of the infection in humans and tested a live-attenuated MAYV vaccine candidate (MAYV/IRES). Intraplantar inoculation of a WT strain of MAYV into immunocompetent mice induced persistent hypernociception, transient viral replication in target organs, systemic production of inflammatory cytokines, chemokines and specific humoral IgM and IgG responses. Inoculation of MAYV/IRES in BALB/c mice induced strong specific cellular and humoral responses. Moreover, MAYV/IRES vaccination of immunocompetent and interferon receptor-defective mice resulted in protection from disease induced by the virulent wt MAYV strain. Thus, this study describes a novel model of MAYV infection in immunocompetent mice and highlights the potential role of a live-attenuated MAYV vaccine candidate in host’s protection from disease induced by a virulent MAYV strain.
Cold stress changes antioxidant defense system, phenylpropanoid contents and expression of genes involved in their biosynthesis in Ocimum basilicum L.
Authors: Rezaie Ramin , Abdollahi Mandoulakani Babak , Fattahi Mohammad 
Published: March 2020

AbstractEnvironmental stresses might alter the activity of antioxidant defense system and both quantity and quality of the essential oil constituents in aromatic plants. In the current study, a greenhouse experiment was designed to assess the influence of cold stress on total phenolic (TPC) and flavonoid contents (TFC), DPPH radical scavenging, antioxidant and phenylalanine ammonia-lyase (PAL) enzymes activity and content of phenylpropanoid compounds inOcimum basilicumL. The genes expression levels of chavicolO-methyl transferase (CVOMT), cinnamate 4-hydroxylase (C4H), eugenol synthase 1 (EGS1) and eugenolO-methyl transferase (EOMT) were also investigated. Results revealed the highest TPC, TFC and DPPH at 4 °C for 12 h. Positive significant correlation was observed between TFC and DPPH, as well as TPC and PAL enzyme activity. The highest activity of superoxide dismutase and guaiacol peroxidase was recorded in 4 °C for 48 h, while this treatment caused the highest reduction in the activities of ascorbate peroxidase and catalase. In plants exposed to 10 °C for 48 h, the contents of methyleugenol and methylchavicol was positively associated with the expression levels ofEGS1 and EOMT. A positive correlation was also found betweenC4Hexpression and eugenol, methyleugenol and methylchavicol contents under 4 °C for 12 h.
A New Nanocomposite Copolymer Based On Functionalised Graphene Oxide for Development of Heart Valves
Authors: Ovcharenko Evgeny A. , Seifalian Amelia , Rezvova Maria A. , Klyshnikov Kirill Yu. , Glushkova Tatiana V. , Akenteva Tatyana N. , Antonova Larisa V. , Velikanova Elena A. , Chernonosova Vera S. , Shevelev Georgy Yu. , Shishkova Darya K. , Krivkina Evgeniya O. , Kudryavceva Yuliya A. , Seifalian Alexander M. , Barbarash Leonid S. 
Published: March 2020

AbstractPolymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name “Hastalex” in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p < 0.05). The contact angles of Hastalex surfaces (85.2 ± 1.1°) significantly (p < 0.05) are lower than those of GORE-TEX (127.1 ± 6.8°). The highest number of viable cells Ea.hy 926 is on the Hastalex surface exceeding 7.5-fold when compared with the GORE-TEX surface (p < 0.001). The platelet deformation index for GORE-TEX is 2-fold higher than that of Hastalex polymer (p < 0.05). Calcium content is greater for GORE-TEX (8.4 mg/g) in comparison with Hastalex (0.55 mg/g). The results of this study have proven that Hastalex meets the main standards required for manufacturing artificial heart valves and has superior mechanical, hemocompatibility and calcific resistance properties in comparison with GORE-TEX.
Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Authors: Lande Asgeir , Fluge Øystein , Strand Elin B. , Flåm Siri T. , Sosa Daysi D. , Mella Olav , Egeland Torstein , Saugstad Ola D. , Lie Benedicte A. , Viken Marte K. 
Published: March 2020

AbstractThe etiology and pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are unknown, and autoimmunity is one of many proposed underlying mechanisms. Human Leukocyte Antigen (HLA) associations are hallmarks of autoimmune disease, and have not been thoroughly investigated in a large ME/CFS patient cohort. We performed high resolution HLA -A, -B, -C, -DRB1, -DQB1 and -DPB1 genotyping by next generation sequencing in 426 adult, Norwegian ME/CFS patients, diagnosed according to the Canadian Consensus Criteria. HLA associations were assessed by comparing to 4511 healthy and ethnically matched controls. Clinical information was collected through questionnaires completed by patients or relatives. We discovered two independent HLA associations, tagged by the alleles HLA-C*07:04 (OR 2.1 [95% CI 1.4–3.1]) and HLA-DQB1*03:03 (OR 1.5 [95% CI 1.1–2.0]). These alleles were carried by 7.7% and 12.7% of ME/CFS patients, respectively. The proportion of individuals carrying one or both of these alleles was 19.2% in the patient group and 12.2% in the control group (OR 1.7 [95% CI 1.3–2.2], pnc = 0.00003). ME/CFS is a complex disease, potentially with a substantial heterogeneity. We report novel HLA associations pointing toward the involvement of the immune system in ME/CFS pathogenesis.
GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats
Authors: Li Chunzhu , Yan Jia , Tang Dewei , Zhu Jidong , Huang Chen , Sun Yu , Hu Rong , Wang Hao , Fu Chaoying , Chen Yelin , Jiang Hong 
Published: March 2020

AbstractAnesthetics are used to produce hypnosis and analgesic effects during surgery, but anesthesia for a long time after the operation is not conducive to the recovery of animals or patients. Therefore, finding appropriate treatments to counter the effects of anesthetics could enhance postoperative recovery. In the current study, we discovered the novel role of a GluN2A-selective positive allosteric modulator (PAM) in ketamine-induced anesthesia and investigated the effects of the PAM combined with nalmefene and flumazenil (PNF) in reversing the actions of an anesthetic combination (ketamine-fentanyl-dexmedetomidine, KFD). PAM treatment dose-dependently decreased the duration of the ketamine-induced loss of righting reflex (LORR). Compared with those in the KFD group, the duration of LORR and the analgesic effect of the KFD + PNF group were obviously decreased. Meanwhile, successive administration of PNF and KFD had no adverse effects on the cardiovascular and respiratory systems. Both the KFD group and the KFD + PNF group showed no changes in hepatic and renal function or cognitive function in rats. Moreover, the recovery of motor coordination of the KFD + PNF group was faster than that of the KFD group. In summary, our results suggest the potential application of the PNF combination as an antagonistic treatment strategy for anesthesia.
Interference with SRF expression in skeletal muscles reduces peripheral nerve regeneration in mice
Authors: Wanner Renate , Knöll Bernd 
Published: March 2020

AbstractTraumatic injury of peripheral nerves typically also damages nerve surrounding tissue including muscles. Hence, molecular and cellular interactions of neighboring damaged tissues might be decisive for successful axonal regeneration of injured nerves. So far, the contribution of muscles and muscle-derived molecules to peripheral nerve regeneration has only poorly been studied. Herein, we conditionally ablated SRF (serum response factor), an important myofiber transcription factor, in skeletal muscles of mice. Subsequently, the impact of this myofiber-restricted SRF deletion on peripheral nerve regeneration, i.e. facial nerve injury was analyzed. Quantification of facial nerve regeneration by retrograde tracer transport, inspection of neuromuscular junctions (NMJs) and recovery of whisker movement revealed reduced axonal regeneration upon muscle specific Srf deletion. In contrast, responses in brainstem facial motor neuron cell bodies such as regeneration-associated gene (RAG) induction of Atf3, synaptic stripping and neuroinflammation were not overly affected by SRF deficiency. Mechanistically, SRF in myofibers appears to stimulate nerve regeneration through regulation of muscular satellite cell (SC) proliferation. In summary, our data suggest a role of muscle cells and SRF expression within muscles for regeneration of injured peripheral nerves.
Hoechst-tagged Fluorescein Diacetate for the Fluorescence Imaging-based Assessment of Stomatal Dynamics in Arabidopsis thaliana
Authors: Takaoka Yousuke , Miyagawa Saki , Nakamura Akinobu , Egoshi Syusuke , Tsukiji Shinya , Ueda Minoru 
Published: March 2020

AbstractIn plants, stomata regulate water loss through transpiration for plant growth and survival in response to various environmental stressors; and simple methods to assess stomatal dynamics are needed for physiological studies. Herein, we report a fluorescence-imaging-based method using fluorescein diacetate tagged with Hoechst 33342, a nuclear staining chemical probe (HoeAc2Fl) for the qualitative assessment of stomatal dynamics. In our method, the stomatal movement is inferred by simple monitoring of the fluorescence intensity in the nucleus of the stomata.
Achieving sub-wavelength imaging through a flat hyperlens in a modified anodic aluminum oxide template
Authors: Tao Chung-Wei , Yen Ta-Jen , Huang Tsung-Yu 
Published: March 2020

AbstractConstrained by the diffraction limit, a lens can only resolve features larger than half of the incident wavelength owing to the decaying nature of evanescent waves. Several novel devices have been proposed, for example, superlenses and hyperlenses to break this limit. In this work, we present a flat hyperlens composed of silver nanowires embedded in a modified anodic aluminum oxide (AAO) template to demonstrate subwavelength imaging. Measurement conducted by the near-field scanning optical microscope at 633 nm suggests that our proposed flat hyperlens can indeed achieve sub-wavelength imaging with a resolution down to 0.34λ and 0.25λ along two orthogonal directions. Furthermore, to confirm the resolution limit of the flat hyperlens, numerical simulations were performed at the incident wavelengths of 633 and 365 nm, and the corresponding resolution were 0.19λ and 0.3λ, respectively, thus paving a route for sub-wavelength photolithography.