bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-specific signatures of intra-individual mitochondrial DNA heteroplasmy and their potential evolutionary advantages
Authors: Tikochinski Yaron , Carreras Carlos , Tikochinski Gili , Vilaça Sibelle T. 
Published: January 2020

AbstractHeteroplasmy is the existence of more than one mitochondrial DNA (mtDNA) variant within a cell. The evolutionary mechanisms of heteroplasmy are not fully understood, despite being a very common phenomenon. Here we combined heteroplasmy measurements using high throughput sequencing on green turtles (Chelonia mydas) with simulations to understand how heteroplasmy modulates population diversity across generations and under different demographic scenarios. We found heteroplasmy to be widespread in all individuals analysed, with consistent signal in individuals across time and tissue. Significant shifts in haplotype composition were found from mother to offspring, signalling the effect of the cellular bottleneck during oogenesis as included in the model. Our model of mtDNA inheritance indicated that heteroplasmy favoured the increase of population diversity through time and buffered against population bottlenecks, thus indicating the importance of this phenomenon in species with reduced population sizes and frequent population bottlenecks like marine turtles. Individuals with recent haplotypes showed higher levels of heteroplasmy than the individuals with ancient haplotypes, suggesting a potential advantage of maintaining established copies when new mutations arise. We recommend using heteroplasmy through high throughput sequencing in marine turtles, as well as other wildlife populations, for diversity assessment, population genetics, and mixed stock analysis.
Superdirective dimers of coupled self-resonant split ring resonators: Analytical modelling and numerical and experimental validation
Authors: Vallecchi A. , Radkovskaya A. , Li L. , Faulkner G. , Stevens C. J. , Shamonina E. 
Published: January 2020

AbstractSuperdirective antennas developed over the last century have received renewed interest in recent years from the development of metamaterials. These arrays of electromagnetic resonators (or meta-atoms) carrying short wavelength electro- and/or magneto-inductive waves support current distributions with very high spatial frequency as required by the classical conditions for superdirectivity. As meta-atoms can have both electric and magnetic dipole characteristics (and hence radiation properties), developing antennas exploiting these distributions can challenge conventional intuitions regarding the optimal configurations required. In this work we are reporting the development of a genuinely superdirective array using split ring resonators (SRRs). We provide a comprehensive analytical model characterizing the radiation from SRR dimers in which excitation of only one split ring leads to superdirective radiation via mutually coupled modes. Our model exploits simple circuit descriptions of coupled resonant circuits, combined with standard radiation formulae for curvilinear current distributions. Using this simple model we are able to map directivity against possible SRR locations and orientations in two dimensions and identify the unique optimal configuration which meets the requirements for superdirective emission. We validate the theoretical findings by comparison to both full wave simulations and experiments showing that our SRR dimer achieves endfire directivity very close to the maximum theoretical value.
Impact of BH3-mimetics on Human and Mouse Blood Leukocytes: A Comparative Study
Authors: Rohner Lionel , Reinhart Ramona , Iype Joseena , Bachmann Sofia , Kaufmann Thomas , Fux Michaela 
Published: January 2020

AbstractBH3-mimetics are small molecule inhibitors that neutralize the function of anti-apoptotic BCL-2 family members. BH3-mimetics have recently gained a lot of popularity in oncology because of their success in cancer treatment. However, BH3-mimetics might have a broader clinical application. Here, we established an ex vivo flow cytometric assay allowing the comparison of the impact of BH3-mimetics (ABT-199, ABT-263, WEHI-539, and S63845) on leukocyte populations of both, healthy human subjects and C57BL/6 J wild type mice. BH3-mimetics were added to freshly drawn blood that was diluted 1/2 in cell medium, and BH3-mimetics-mediated impact on leukocyte count was assessed by flow cytometry. Our results demonstrate that responses towards 1μM of BH3-mimetics can be identical as well as considerably different in leukocytes of humans and mice. For instance, the inhibition of BCL-2 by ABT-199 caused cell death in all types of lymphocytes in mice but was exclusively specific for B cells in humans. Moreover, inhibition of BCL-XL by WEHI-539 affected solely mouse leukocytes while targeting MCL-1 by S63845 resulted in efficient induction of cell death in human neutrophils but not in their mouse counterparts. Our ex vivo assay enables initial identification of analogies and differences between human and mouse leukocytes in response towards BH3-mimetics.
Unraveling the Role of Interfaces on the Spall Failure of Cu/Ta Multilayered Systems
Authors: Chen Jie , Mathaudhu Suveen N. , Thadhani Naresh , Dongare Avinash M. 
Published: January 2020

AbstractMolecular dynamics (MD) simulations are carried out to investigate the effects of the type and spacing of FCC/BCC interfaces on the deformation and spall behavior. The simulations are carried out using model Cu/Ta multilayers with six different types of interfaces. The results suggest that interface type can significantly affect the structure and intensity of the incoming shock wave, change the activated slip systems, alter dislocation slip and twinning behavior, affect where and how voids are nucleated during spallation and the resulting spall strength. Moreover, the above aspects are significantly affected by the interface spacing. A transition from homogeneous to heterogeneous dislocation nucleation occurs as the interface spacing is decreased to 6 nm. Depending on interface type and spacing, damage (voids) nucleation and spall failure is observed to occur not only at the Cu/Ta interfaces, but also in the weaker Cu layer interior, or even in the stronger Ta layer interior, although different mechanisms underlie each of these three distinct failure modes. These findings point to the fact that, depending on the combination of interface type and spacing, interfaces can lead to both strengthening and weakening of the Cu/Ta multilayered microstructures.
Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus
Authors: Sakamoto Kazuhito , Rädler Patrick D. , Wehde Barbara L. , Triplett Aleata A. , Shrestha Hridaya , Ferraiuolo Rosa-Maria , Amari Foued , Coppola Vincenzo , Klinakis Apostolos , Efstratiadis Argiris , Wagner Kay-Uwe 
Published: January 2020

AbstractUsing an efficient gene targeting approach, we developed a novel mouse line that expresses the tetracycline-controlled transactivator (tTA) from the constitutively active Eef1a1 locus in a Cre recombinase-inducible manner. The temporally and spatially controlled expression of the EF1-LSL-tTA knockin and activation of tTA-driven responder transgenes was tested using four transgenic lines that express Cre under tissue-specific promoters of the pancreas, mammary gland and other secretory tissues, as well as an interferon-inducible promoter. In all models, the endogenous Eef1a1 promoter facilitated a cell-type-specific activation of target genes at high levels without exogenous enhancer elements. The applicability of the EF1-LSL-tTA strain for biological experiments was tested in two studies related to mammary gland development and tumorigenesis. First, we validated the crucial role of active STAT5 as a survival factor for functionally differentiated epithelial cells by expressing a hyperactive STAT5 mutant in the mammary gland during postlactational remodeling. In a second experiment, we assessed the ability of the EF1-tTA to initiate tumor formation through upregulation of mutant KRAS. The collective results show that the EF1-LSL-tTA knockin line is a versatile genetic tool that can be applied to constitutively express transgenes in specific cell types to examine their biological functions at defined developmental stages.
Classifying superconductivity in Moiré graphene superlattices
Authors: Talantsev E. F. , Mataira R. C. , Crump W. P. 
Published: January 2020

AbstractSeveral research groups have reported on the observation of superconductivity in bilayer graphene structures where single atomic layers of graphene are stacked and then twisted at angles θ forming Moiré superlattices. The characterization of the superconducting state in these 2D materials is an ongoing task. Here we investigate the pairing symmetry of bilayer graphene Moiré superlattices twisted at θ = 1.05°, 1.10° and 1.16° for carrier doping states varied in the range of n = (0.5 − 1.5) · 1012 cm−2 (where superconductivity can be realized) by analyzing the temperature dependence of the upper critical field Bc2(T) and the self-field critical current Jc(sf,T) within currently available models – all of which start from phonon-mediated BCS theory – for single- and two-band s−, d−, p− and d + id-wave gap symmetries. Extracted superconducting parameters show that only s-wave and a specific kind of p-wave symmetries are likely to be dominant in bilayer graphene Moiré superlattices. More experimental data is required to distinguish between the s- and remaining p-wave symmetries as well as the suspected two-band superconductivity in these 2D superlattices.
Hyaluronan suppresses enhanced cathepsin K expression via activation of NF-κB with mechanical stress loading in a human chondrocytic HCS-2/8 cells
Authors: Suzuki Mochihito , Takahashi Nobunori , Sobue Yasumori , Ohashi Yoshifumi , Kishimoto Kenji , Hattori Kyosuke , Ishiguro Naoki , Kojima Toshihisa 
Published: January 2020

AbstractCathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to osteoarthritis (OA). Hyaluronan (HA) plays a pivotal role in maintaining homeostasis within articular chondrocytes. Intra-articular supplementation of high molecular weight hyaluronan (HMW-HA) has been widely used in OA treatment. However, its prospective mechanism of action is still unclear. In this study, we examined the suppressive effect of HA on enhanced cathepsin K expression induced by mechanical stress loading. A human chondrocytic HCS-2/8 cells were cultured in silicon chambers and subjected to cyclic tensile stress (CTS) loading. CTS loading significantly increased messenger ribonucleic acid and protein expression of cathepsin K, which appeared to be suppressed by pre-treatment with HMW-HA. Activation of nuclear factor-kappa B (NF-κB) was induced by CTS loading, and suppressed by pre-treatment with HMW-HA. Helenalin, a chemical inhibitor of NF-κB, clearly suppressed the enhanced expression of cathepsin K, as well as NF-κB activation induced by CTS loading. The suppressive effect of HMW-HA on enhanced cathepsin K expression via NF-κB inhibition impacts the effectiveness of HMW-HA in OA treatment. Our findings provide new evidence supporting the biological effectiveness of intra-articular HMW-HA injections for treatment of OA.
The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness
Authors: Mus Liselot M. , Lambertz Irina , Claeys Shana , Kumps Candy , Van Loocke Wouter , Van Neste Christophe , Umapathy Ganesh , Vaapil Marica , Bartenhagen Christoph , Laureys Genevieve , De Wever Olivier , Bexell Daniel , Fischer Matthias , Hallberg Bengt , Schulte Johannes , De Wilde Bram , Durinck Kaat , Denecker Geertrui , De Preter Katleen , Speleman Frank 
Published: January 2020

AbstractNeuroblastoma is an aggressive childhood cancer arising from sympatho-adrenergic neuronal progenitors. The low survival rates for high-risk disease point to an urgent need for novel targeted therapeutic approaches. Detailed molecular characterization of the neuroblastoma genomic landscape indicates that ALK-activating mutations are present in 10% of primary tumours. Together with other mutations causing RAS/MAPK pathway activation, ALK mutations are also enriched in relapsed cases and ALK activation was shown to accelerate MYCN-driven tumour formation through hitherto unknown ALK-driven target genes. To gain further insight into how ALK contributes to neuroblastoma aggressiveness, we searched for known oncogenes in our previously reported ALK-driven gene signature. We identified ETV5, a bona fide oncogene in prostate cancer, as robustly upregulated in neuroblastoma cells harbouring ALK mutations, and show high ETV5 levels downstream of the RAS/MAPK axis. Increased ETV5 expression significantly impacted migration, invasion and colony formation in vitro, and ETV5 knockdown reduced proliferation in a murine xenograft model. We also established a gene signature associated with ETV5 knockdown that correlates with poor patient survival. Taken together, our data highlight ETV5 as an intrinsic component of oncogenic ALK-driven signalling through the MAPK axis and propose that ETV5 upregulation in neuroblastoma may contribute to tumour aggressiveness.
Melt processing of polypropylene-grafted-maleic anhydride/Chitosan polymer blend functionalized with montmorillonite for the removal of lead ions from aqueous solutions
Authors: Moja T. N. , Bunekar N. , Mishra S. B. , Tsai T.-Y. , Hwang S. S. , Mishra A. K 
Published: January 2020

AbstractHeavy metals such as lead ions Pb (II) are a primary concern in the aquatic environment. These is because Pb (II) is poisonous at a threshold limit above 0.01 mg/L, when consumed over a long period of time. Pb (II) poisoning is very harmful to various organs viz. heart, intestine and kidneys. Besides, it affects bones, tissues, nervous and reproductive systems. Hence, it is important to remove Pb (II) from aquatic environment. Polypropylene (PP) and polypropylene grafted-maleic-anhydride (PP-g-MA) based nanocomposites reinforced with Chitosan (CS) and modified montmorillonite clay nanofiller (CL120DT) were successfully fabricated using twin screw melt extrusion for adsorption of Pb (II). The resulting nanocomposites were characterized by XRD to analyze the dispersion properties of the material, TEM and SEM for surface morphology, FTIR analysis for the functional groups and TGA for thermal stability. Pure PP showed two sharp peaks, but there was decreased in the intensity upon adding of CS and CL120DT. Among series of nanocomposites 2.0 phr and 4.0 phr loaded samples shows better storage module than that of pure PP. The uptake of Pb (II) from lead nitrate aqueous solution by PP + PP-g-MA/CL120DT-CS 2.0 phr nanocomposites followed the Langmuir isotherm model, with a remediation of 90.9% at pH 8 and was verified by pseudo-second order kinetic model. These results indicate that PP + PP-g-MA//CL120DT-CS 2.0 phr nanocomposites performed as a superabsorbent for the Pb (II) ion removal from aqueous solution.
Early Recognition of Burn- and Trauma-Related Acute Kidney Injury: A Pilot Comparison of Machine Learning Techniques
Authors: Rashidi Hooman H. , Sen Soman , Palmieri Tina L. , Blackmon Thomas , Wajda Jeffery , Tran Nam K. 
Published: January 2020

AbstractSeverely burned and non-burned trauma patients are at risk for acute kidney injury (AKI). The study objective was to assess the theoretical performance of artificial intelligence (AI)/machine learning (ML) algorithms to augment AKI recognition using the novel biomarker, neutrophil gelatinase associated lipocalin (NGAL), combined with contemporary biomarkers such as N-terminal pro B-type natriuretic peptide (NT-proBNP), urine output (UOP), and plasma creatinine. Machine learning approaches including logistic regression (LR), k-nearest neighbor (k-NN), support vector machine (SVM), random forest (RF), and deep neural networks (DNN) were used in this study. The AI/ML algorithm helped predict AKI 61.8 (32.5) hours faster than the Kidney Disease and Improving Global Disease Outcomes (KDIGO) criteria for burn and non-burned trauma patients. NGAL was analytically superior to traditional AKI biomarkers such as creatinine and UOP. With ML, the AKI predictive capability of NGAL was further enhanced when combined with NT-proBNP or creatinine. The use of AI/ML could be employed with NGAL to accelerate detection of AKI in at-risk burn and non-burned trauma patients.
Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics
Authors: Emam Mehdi , Cánovas Angela , Islas-Trejo Alma D. , Fonseca Pablo A. S. , Medrano Juan. F. , Mallard Bonnie 
Published: January 2020

AbstractReactive Nitrogen Species (RNS) are a group of bactericidal molecules produced by macrophages in response to pathogens in a process called oxidative burst. Nitric oxide (NO−) is a member of RNS produced from arginine by inducible Nitric Oxide Synthase (iNOS) enzyme. The activity of iNOS and production of NO−by macrophages following stimulation is one of the indicators of macrophage polarization towards M1/proinflammatory. Production of NO−by bovine monocyte-derived macrophage (MDM) and mouse peritoneal macrophages has been shown to be strongly associated with host genetic with the heritability of 0.776 in bovine MDM and 0.8 in mouse peritoneal macrophages. However, the mechanism of genetic regulation of macrophage response has remained less explored. In the current study, the transcriptome of bovine MDMs was compared between two extreme phenotypes that had been classified as high and low responder based on NO−production. The results showed that 179 and 392 genes were differentially expressed (DE) between high and low responder groups at 3 and 18 hours after exposure toEscherichia coli, respectively. A set of 11 Transcription Factors (TFs) (STAT1,IRF7,SPI1,STAT4,IRF1,HIF1A,FOXO3,REL,NFAT5, HIC1, andIRF4) at 3 hours and a set of 13 TFs (STAT1,IRF1,HIF1A,STAT4,ATF4,TP63,EGR1,CDKN2A,RBL1, E2F1, PRDM1, GATA3, andIRF4) at 18 hours after exposure toE. coliwere identified to be differentially regulated between the high and low responder phenotypes. These TFs were found to be divided into two clusters of inflammatory- and hypoxia-related TFs. Functional analysis revealed that some key canonical pathways such as phagocytosis, chemotaxis, antigen presentation, and cell-to-cell signalling are enriched among the over-expressed genes by high responder phenotype. Based on the results of this study, it was inferred that the functional characteristics of bovine MDMs are associated with NO-based classification. Since NO−production is strongly associated with host genetics, this study for the first time shows the distinct proinflammatory profiles of macrophages are controlled by the natural genetic polymorphism in an outbred population. In addition, the results suggest that genetics can be considered as a new dimension in the current model of macrophage polarization which is currently described by the combination of stimulants, only.
The prognostic and predictive potential of Ki-67 in triple-negative breast cancer
Authors: Zhu Xiuzhi , Chen Li , Huang Binhao , Wang Yue , Ji Lei , Wu Jiong , Di Genhong , Liu Guangyu , Yu Keda , Shao Zhimin , Wang Zhonghua 
Published: January 2020

AbstractAs a cell proliferation biomarker, Ki-67 is principally used in ER+/HER2− breast cancer. However, the importance and the best cutoff point of Ki-67 in triple-negative breast cancer (TNBC) remains unclear and was evaluated in this study.A total of 1800 patients with early invasive TNBC between 2011 and 2016 at Fudan University Shanghai Cancer Center were consecutively recruited for this study. The optimal cutoff for Ki-67 was assessed by Cutoff Finder. Propensity score matching (PSM, ratio = 1:2) was performed to match the Ki-67low group with the Ki-67high group. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups using the Kaplan-Meier method and Cox regression model. The most relevant cutoff value for Ki-67 for prognosis was 30% (p = 0.008). At the cutoff point of 30%, worse DFS and OS were observed in the Ki-67high group. In multivariate analyses, N-stage (p < 0.001), T-stage (p = 0.038), and Ki-67 at the 30% threshold (p = 0.020) were independently linked to OS. In subgroup analysis, Ki-67 cutoff at 30% had prognostic and predictive potential for DFS with either tumor size ≤2 cm (p = 0.008) or lymph node-negative (N−) (p = 0.038) and especially with T1N0M0 (stage I) TNBCs. For 945 N− TNBC patients, adjuvant chemotherapy (CT) was associated with better OS in the Ki-67high group (p = 0.017) than in the Ki-67low group (p = 0.875). For stage I/Ki-67low patients, adjuvant CT did not affect DFS (p = 0.248). Thus, Ki-67 cutoff at 30% had early independent prognostic and predictive potential for OS and DFS in TNBCs, and Ki-67 > 30% was significantly associated with worse prognosis, especially for stage I patients. For stage I/Ki-67low TNBC patients, the advantage of CT is unclear, providing the basis for future de-escalation therapy.
Oxidised Met147 of human serum albumin is a biomarker of oxidative stress, reflecting glycaemic fluctuations and hypoglycaemia in diabetes
Authors: Momozono Akari , Kodera Yoshio , Sasaki Sayaka , Nakagawa Yuzuru , Konno Ryo , Shichiri Masayoshi 
Published: January 2020

AbstractOxidative stress has been linked to a number of chronic diseases, and this has aroused interest in the identification of clinical biomarkers that can accurately assess its severity. We used liquid chromatography-high resolution mass spectrometry (LC-MS) to show that oxidised and non-oxidised Met residues at position 147 of human serum albumin (Met147) can be accurately and reproducibly quantified with stable isotope-labelled peptides. Met147 oxidation was significantly higher in patients with diabetes than in controls. Least square multivariate analysis revealed that glycated haemoglobin (HbA1c) and glycated albumin (GA) did not significantly influence Met147 oxidation, but the GA/HbA1c ratio, which reflects glycaemic excursions, independently affected Met147 oxidation status. Continuous glucose monitoring revealed that Met147 oxidation strongly correlates with the standard deviation of sensor glucose concentrations and the time spent with hypoglycaemia or hyperglycaemia each day. Thus, glycaemic variability and hypoglycaemia in diabetes may be associated with greater oxidation of Met147. Renal function, high-density lipoprotein-cholesterol and serum bilirubin were also associated with the oxidation status of Met147. In conclusion, the quantification of oxidised and non-oxidised Met147 in serum albumin using our LC-MS methodology could be used to assess the degree of intravascular oxidative stress induced by hypoglycaemia and glycaemic fluctuations in diabetes.