bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing cross-species transmission of hemoplasmas at the wild-domestic felid interface in Chile using genetic and landscape variables analysis
Authors: Sacristán I. , Acuña F. , Aguilar E. , García S. , López M. J. , Cevidanes A. , Cabello J. , Hidalgo-Hermoso E. , Johnson W. E. , Poulin E. , Millán J. , Napolitano C. 
Published: November 2019

AbstractThe co-occurrence of domestic cats (Felis silvestris catus) and wild felids in rural landscapes can facilitate pathogen transmission. However, in the relatively-isolated regions of southern South America there have been no comprehensive studies to assess disease transmission risks between domestic cats and forest-dwelling wild felids such as guigna (Leopardus guigna). We evaluated hemoplasma infection and the possibility of transmission between domestic cats and guignas by comparing spatial and phylogenetic patterns of pathogen prevalence. Blood/spleen samples were collected from 102 wild guignas and 262 co-occurring rural domestic cats across the entire distribution range of guigna in Chile. Hemoplasma infection was assessed by direct sequencing of the 16S RNA gene. Infection with hemoplasmas was common and geographically widespread across different bioclimatic areas for both species. The most common felineMycoplasmaspecies in guigna and domestic cats wereCandidatusM. haemominutum (CMhm) (15.7% guigna; 10.3% domestic cat) andMycoplasma haemofelis(Mhf) (9.8% guigna, 6.1% domestic cat). A previously undescribedMycoplasmasp. sequence was found in two guignas and one cat. Continuous forest-landscapes were associated with higher hemoplasma-prevalence in guignas. Shared hemoplasma nucleotide sequence types between guigna and domestic cats were rare, suggesting that cross-species transmission between guignas and domestic cats may occur, but is probably uncommon. Ectoparasites, which have been linked with hemoplasma transmission, were not found on guignas and were infrequent on domestic cats. Our results suggest that transmission pathways vary among hemoplasma species and, contrary to our predictions, domestic cats did not appear to be the main driver of hemoplasma infection in guignas in these human-dominated landscapes.
Data-driven spectral analysis for coordinative structures in periodic human locomotion
Authors: Fujii Keisuke , Takeishi Naoya , Kibushi Benio , Kouzaki Motoki , Kawahara Yoshinobu 
Published: November 2019

AbstractLiving organisms dynamically and flexibly operate a great number of components. As one of such redundant control mechanisms, low-dimensional coordinative structures among multiple components have been investigated. However, structures extracted from the conventional statistical dimensionality reduction methods do not reflect dynamical properties in principle. Here we regard coordinative structures in biological periodic systems with unknown and redundant dynamics as a nonlinear limit-cycle oscillation, and apply a data-driven operator-theoretic spectral analysis, which obtains dynamical properties of coordinative structures such as frequency and phase from the estimated eigenvalues and eigenfunctions of a composition operator. Using segmental angle series during human walking as an example, we first extracted the coordinative structures based on dynamics; e.g. the speed-independent coordinative structures in the harmonics of gait frequency. Second, we discovered the speed-dependent time-evolving behaviours of the phase by estimating the eigenfunctions via our approach on the conventional low-dimensional structures. We also verified our approach using the double pendulum and walking model simulation data. Our results of locomotion analysis suggest that our approach can be useful to analyse biological periodic phenomena from the perspective of nonlinear dynamical systems.
The positive correlation of TIPRL with LC3 and CD133 contributes to cancer aggressiveness: potential biomarkers for early liver cancer
Authors: Jun Soo Young , Jeon Su-Jin , Yoon Ji-Yong , Lee Jeong-Ju , Yoon Hyang Ran , Choi Min-Hyuk , Halder Debasish , Lee Kwangho , Kim Nam-Soon 
Published: November 2019

AbstractStudies have reported dysregulation of TIPRL, LC3 and CD133 in liver cancer tissues. However, their respective relationships to liver cancer and roles as biomarkers for prognosis and diagnosis of liver cancer have never been studied. Here we report that the level of TIPRL is significantly correlated with levels of LC3 (Spearman r = 0.9) and CD133 (r = 0.7) in liver cancer tissues. We observed significant upregulations of TIPRL, LC3 and CD133 in hepatocellular carcinomas (HCCs) compared with adjacent normal tissues. Importantly, TIPRL, tested among additional variables, showed a significant impact on the prognosis of HCC patients. TIPRL knockdown significantly reduced expressions of LC3, CD133, stemness-related genes, as well as viability and stemness of liver cancer cell-lines, which were promoted by ectopic TIPRL expression. Either alone or as a combination, TIPRL, LC3 and CD133 showed significant values of area under the curve (AUC) and sensitivity/specificity in early liver cancer tissues. Furthermore, the statistical association and the diagnostic efficacies of TIPRL, LC3 and CD133 in HCC tissues were confirmed in a different IHC cohort. This data demonstrates that the complex involvement of TIPRL/LC3/CD133 in liver cancer aggressiveness can together or individually serve as potential biomarkers for the early detection of liver cancer.
Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human Factor VIII
Authors: Chen Hainan , Shi Mi , Gilam Avital , Zheng Qi , Zhang Yin , Afrikanova Ivka , Li Jinling , Gluzman Zoya , Jiang Ruhong , Kong Ling-Jie , Chen-Tsai Ruby Yanru 
Published: November 2019

AbstractHemophilia A is a monogenic disease with a blood clotting factor VIII (FVIII) deficiency caused by mutation in the factor VIII (F8) gene. Current and emerging treatments such as FVIII protein injection and gene therapies via AAV-delivered F8 transgene in an episome are costly and nonpermanent. Here, we describe a CRISPR/Cas9-based in vivo genome editing method, combined with non-homologous end joining, enabling permanent chromosomal integration of a modified human B domain deleted-F8 (BDD-F8) at the albumin (Alb) locus in liver cells. To test the approach in mice, C57BL/6 mice received tail vein injections of two vectors, AAV8-SaCas9-gRNA, targeting Alb intron 13, and AAV8-BDD-F8. This resulted in BDD-F8 insertion at the Alb locus and FVIII protein expression in the liver of vector-, but not vehicle-, treated mice. Using this approach in hemophilic mice, BDD-F8 was expressed in liver cells as functional human FVIII, leading to increased plasma levels of FVIII and restoration of blood clotting properties in a dose-dependent manor for at least 7 months, with no detectable liver toxicity or meaningful off-target effects. Based on these findings, our BDD-F8 genome editing approach may offer an efficacious, long-term and safe treatment for patients with hemophilia A.
Engineering a Virus-Like Particle as an Antigenic Platform for a Pfs47-Targeted Malaria Transmission-Blocking Vaccine
Authors: Yenkoidiok-Douti Lampouguin , Williams Adeline E. , Canepa Gaspar E. , Molina-Cruz Alvaro , Barillas-Mury Carolina 
Published: November 2019

AbstractWe recently characterized Pfs47, a protein expressed on the surface of sexual stages and ookinetes of Plasmodium falciparum, as a malaria transmission-blocking vaccine (TBV) target. Mice immunization induced antibodies that conferred strong transmission-reducing activity (TRA) at a concentration of 200 μg/mL. Here, we sought to optimize the Pfs47 vaccine to elicit higher titers of high-affinity antibodies, capable of inducing strong TRA at a lower concentration. We report the development and evaluation of a Pfs47-based virus-like particle (VLP) vaccine generated by conjugating our 58 amino acid Pfs47 antigen to Acinetobacter phage AP205-VLP using the SpyCatcher:SpyTag adaptor system. AP205-Pfs47 complexes (VLP-P47) formed particles of ~22 nm diameter that reacted with polyclonal anti-Pfs47 antibodies, indicating that the antigen was accessible on the surface of the particle. Mice immunized with VLP-P47 followed by a boost with Pfs47 monomer induced significantly higher antibody titers, with higher binding affinity to Pfs47, than mice that received two immunizations with either VLP-P47 (VLP-P47/VLP-P47) or the Pfs47 monomer (P47/P47). Purified IgG from VLP-P47/P47 mice had strong TRA (83–98%) at concentrations as low as 5 μg/mL. These results indicate that conjugating the Pfs47 antigen to AP205-VLP significantly enhanced antigenicity and confirm the potential of Pfs47 as a TBV candidate.
Two Hybrid Au-ZnO Heterostructures with Different Hierarchical Structures: Towards Highly Efficient Photocatalysts
Authors: Yang Shuo , Wang Lijing , Yan Yongsheng , Yang Lili , Li Xin , Lu Ziyang , Zhai Hongju , Han Donglai , Huo Pengwei 
Published: November 2019

AbstractA new paradigm for photocatalysts based on two different hierarchically structured honeycomb and porous cylindrical Au-ZnO heterostructures was successfully developed via a straightforward and cost-effective hydrothermal method under different preparation conditions, which can be promising for industrial applications. The photocatalytic performance of all as-prepared samples under the illumination of sunlight was evaluated by the photocatalytic degradation of rhodamine B (RhB) and malachite green (MG) aqueous solutions. The results show that the photocatalytic degradation efficiency of RhB and MG was 55.3% and 40.7% for ZnO, 95.3% and 93.4% for the porous cylindrical Au-ZnO heterostructure, and 98.6% and 99.5% for the honeycomb Au-ZnO heterostructure, respectively. Compared with those from the ZnO, the results herein demonstrate an excellent reduction in the photoluminescence and improvement in the photocatalysis for the Au-ZnO hybrids with different morphologies. These results were attributed not only to the greatly improved sunlight utilization efficiency due to the surface plasmon resonance (SPR) absorption of Au nanoparticles in the visible region coupled with the UV light utilization by the ZnO nanostructures and multi-reflections of the incident light in the pore structures of their interior cavities but also to the high charge separation efficiency and low Schottky barrier generated by the combination of Au nanoparticles and ZnO micromaterials. Moreover, the honeycomb Au-ZnO heterostructure had a high Au content, surface area and surface oxygen vacancy (OV), which enabled photocatalytic properties that were higher than those of the porous cylindrical Au-ZnO heterostructures. In addition, two different formation mechanisms for the morphology and possible photocatalytic mechanisms are proposed in this paper.
High arrhythmic risk in antero-septal acute myocardial ischemia is explained by increased transmural reentry occurrence
Authors: Martinez-Navarro Hector , Mincholé Ana , Bueno-Orovio Alfonso , Rodriguez Blanca 
Published: November 2019

AbstractAcute myocardial ischemia is a precursor of sudden arrhythmic death. Variability in its manifestation hampers understanding of arrhythmia mechanisms and challenges risk stratification. Our aim is to unravel the mechanisms underlying how size, transmural extent and location of ischemia determine arrhythmia vulnerability and ECG alterations. High performance computing simulations using a human torso/biventricular biophysically-detailed model were conducted to quantify the impact of varying ischemic region properties, including location (LAD/LCX occlusion), transmural/subendocardial ischemia, size, and normal/slow myocardial propagation. ECG biomarkers and vulnerability window for reentry were computed in over 400 simulations for 18 cases evaluated. Two distinct mechanisms explained larger vulnerability to reentry in transmural versus subendocardial ischemia. Macro-reentry around the ischemic region was the primary mechanism increasing arrhythmic risk in transmural versus subendocardial ischemia, for both LAD and LCX occlusion. Transmural micro-reentry at the ischemic border zone explained arrhythmic vulnerability in subendocardial ischemia, especially in LAD occlusion, as reentries were favoured by the ischemic region intersecting the septo-apical region. ST elevation reflected ischemic extent in transmural ischemia for LCX and LAD occlusion but not in subendocardial ischemia (associated with mild ST depression). The technology and results presented can inform safety and efficacy evaluation of anti-arrhythmic therapy in acute myocardial ischemia.
Nitrogen enrichment leads to changing fatty acid composition of phytoplankton and negatively affects zooplankton in a natural lake community
Authors: Trommer Gabriele , Lorenz Patrick , Lentz Ameli , Fink Patrick , Stibor Herwig 
Published: November 2019

AbstractSecondary production in freshwater zooplankton is frequently limited by the food quality of phytoplankton. One important parameter of phytoplankton food quality are essential polyunsaturated fatty acids (PUFAs). Since the fatty acid composition of phytoplankton is variable and depends on the algae’s nutrient supply status, inorganic nutrient supply may affect the algal PUFA composition. Therefore, an indirect transfer of the effects of nutrient availability on zooplankton by changes in algal PUFA composition is conceivable. While the phosphorus (P) supply in lakes is largely decreasing, nitrogen (N) inputs continue to increase. This paper presents data from a mesocosm field experiment in which we exposed phytoplankton communities to increasing N enrichment. As a consequence, the PUFA composition of the phytoplankton community changed. With increasing nitrogen fertilisation, we observed lower quantities of essential PUFAs, together with a decrease in the abundances of the dominant herbivorous zooplanktonDaphnia sp. Their biomass was significantly correlated with phytoplankton PUFA content (C18:3 ω3, C20:5 ω3, C18:2 ω6). Our data therefore indicate that changes in nitrogen supply, together with the resultant changes in phytoplankton food quality, can negatively affect the secondary production of herbivorous zooplankton by reducing the availability of essential polyunsaturated fatty acids.
Musical imagery depends upon coordination of auditory and sensorimotor brain activity
Authors: Gelding Rebecca W. , Thompson William F. , Johnson Blake W. 
Published: November 2019

AbstractRecent magnetoencephalography (MEG) studies have established that sensorimotor brain rhythms are strongly modulated during mental imagery of musical beat and rhythm, suggesting that motor regions of the brain are important for temporal aspects of musical imagery. The present study examined whether these rhythms also play a role in non-temporal aspects of musical imagery including musical pitch. Brain function was measured with MEG from 19 healthy adults while they performed a validated musical pitch imagery task and two non-imagery control tasks with identical temporal characteristics. A 4-dipole source model probed activity in bilateral auditory and sensorimotor cortices. Significantly greater β-band modulation was found during imagery compared to control tasks of auditory perception and mental arithmetic. Imagery-induced β-modulation showed no significant differences between auditory and sensorimotor regions, which may reflect a tightly coordinated mode of communication between these areas. Directed connectivity analysis in the θ-band revealed that the left sensorimotor region drove left auditory region during imagery onset. These results add to the growing evidence that motor regions of the brain are involved in the top-down generation of musical imagery, and that imagery-like processes may be involved in musical perception.
Functional and topographic effects on DNA methylation in IDH1/2 mutant cancers
Authors: Bledea Ramona , Vasudevaraja Varshini , Patel Seema , Stafford James , Serrano Jonathan , Esposito Gianna , Tredwin Lilian M. , Goodman Nina , Kloetgen Andreas , Golfinos John G. , Zagzag David , Weigelt Britta , Iafrate A. John , Sulman Erik P. , Chi Andrew S. , Dogan Snjezana , Reis-Filho Jorge S. , Chiang Sarah , Placantonakis Dimitris , Tsirigos Aristotelis , Snuderl Matija 
Published: November 2019

AbstractIDH1/2 mutations are early drivers present in diverse human cancer types arising in various tissue sites. IDH1/2 mutation is known to induce a global hypermethylator phenotype. However, the effects on DNA methylation across IDH mutant cancers and functionally different genome regions, remain unknown. We analyzed DNA methylation data from IDH1/2 mutant acute myeloid leukemia, oligodendroglioma, astrocytoma, solid papillary breast carcinoma with reverse polarity, sinonasal undifferentiated carcinoma and cholangiocarcinoma, which clustered by their embryonal origin. Hypermethylated common probes affect predominantly gene bodies while promoters in IDH1/2 mutant cancers remain unmethylated. Enhancers showed global hypermethylation, however commonly hypomethylated enhancers were associated with tissue differentiation and cell fate determination. We demonstrate that some chromosomes, chromosomal arms and chromosomal regions are more affected by IDH1/2 mutations while others remain resistant to IDH1/2 mutation induced methylation changes. Therefore IDH1/2 mutations have different methylation effect on different parts of the genome, which may be regulated by different mechanisms.
Frequency and Clinical Associating Factors of Valvular Heart Disease in Asymptomatic Korean Adults
Authors: Kim Min Sun , Cho Soo Jin , Park Sung-Ji , Cho Sung Won , Choi Soo-Hee , Kim Hye Seung , Carriere Keumhee , Kim Eun Kyoung , Chang Sung-A , Lee Sang-Chol , Park Seung Woo 
Published: November 2019

AbstractLimited information is available on the prevalence and clinical determinants of valvular heart disease (VHD) in apparently healthy people. This study sought to assess the frequency and clinical associating factors of aortic stenosis (AS), aortic regurgitation (AR), mitral stenosis (MS), mitral regurgitation (MR), tricuspid regurgitation (TR) in asymptomatic individuals with health check-up examination. We included 23,254 subjects ≥50 years of age who underwent a health check-up examination with transthoracic echocardiography (TTE) between 2012 and 2016 in a single tertiary-care hospital in Korea. Among a total of 23,254 subjects, 15,358 men (66.0%) and 7,896 women (34.0%) underwent TTE. Newly identified (predominantly mild) VHD was detected in 9.4% of subjects. The most common VHD were TR (4.6%), AR (3.0%) and MR (2.4%). Clinically significant (more than moderate) VHD was identified in 176 subjects (0.8%). Age ≥75 years was associated with all clinically significant VHD, and female gender was associated with AR, MS and TR. Korea has been very active in the health check-up examination including echocardiography. We find that VHD in apparently healthy people is not uncommon than believed; all VHD except MS were more frequent in elderly over 75 years of age in a large population-based study.
Taxane-based Chemotherapy Induced Androgen Receptor Splice Variant 7 in Patients with Castration-Resistant Prostate Cancer: A Tissue-based Analysis
Authors: Shim Myungsun , Kim Yunlim , Park Yangsoon , Ahn Hanjong 
Published: November 2019

AbstractIn total, 95 prostate cancer (Pca) patients who underwent transurethral resection of the prostate from 2000 to 2013 were assigned to four groups: Group 1, hormone-naïve and T1a or T1b Pca (n = 17); Group 2, hormone-sensitive and metastatic Pca (n = 33); Group 3, chemo-naïve castration-resistant Pca (CRPC), (n = 18); and Group 4, CRPC with chemotherapy (n = 27). Full-length androgen receptor (ARfl) transcript levels significantly increased from Group 1 through to Group 3 (p = 0.045), but decreased from Group 3 through to Group 4. AR splice variant 7 (ARV7) and glucocorticoid receptor (GR) transcript levels significantly increased from Group 1 through to Group 4 (p = 0.002 and 0.049, respectively). Kaplan–Meier curve revealed that the high transcript level of these three receptors resulted in significantly poorer cancer-specific survival (CSS) than that by low transcript level, although Cox regression analysis revealed that the ARV7 level alone was an independent prognostic factor for CSS in CRPC patients (high vs. low: hazard ratio, 1.897; 95% confidence interval, 1.102–3.625; p = 0.042). In conclusion, ARV7 and GR transcript levels significantly increase as Pca progresses to CRPC.
Mebendazole for Differentiation Therapy of Acute Myeloid Leukemia Identified by a Lineage Maturation Index
Authors: Li Yulin , Thomas Daniel , Deutzmann Anja , Majeti Ravindra , Felsher Dean W. , Dill David L. 
Published: November 2019

AbstractAccurate assessment of changes in cellular differentiation status in response to drug treatments or genetic perturbations is crucial for understanding tumorigenesis and developing novel therapeutics for human cancer. We have developed a novel computational approach, the Lineage Maturation Index (LMI), to define the changes in differentiation state of hematopoietic malignancies based on their gene expression profiles. We have confirmed that the LMI approach can detect known changes of differentiation state in both normal and malignant hematopoietic cells. To discover novel differentiation therapies, we applied this approach to analyze the gene expression profiles of HL-60 leukemia cells treated with a small molecule drug library. Among multiple drugs that significantly increased the LMIs, we identified mebendazole, an anti-helminthic clinically used for decades with no known significant toxicity. We tested the differentiation activity of mebendazole using primary leukemia blast cells isolated from human acute myeloid leukemia (AML) patients. We determined that treatment with mebendazole induces dramatic differentiation of leukemia blast cells as shown by cellular morphology and cell surface markers. Furthermore, mebendazole treatment significantly extended the survival of leukemia-bearing mice in a xenograft model. These findings suggest that mebendazole may be utilized as a low toxicity therapeutic for human acute myeloid leukemia and confirm the LMI approach as a robust tool for the discovery of novel differentiation therapies for cancer.