bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Using 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

Several 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

Cathepsin 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

Neuroblastoma 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

Heavy 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

Severely 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

Reactive 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

As 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

Oxidative 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.
Process optimization for biosynthesis of mono and bimetallic alloy nanoparticle catalysts for degradation of dyes in individual and ternary mixture
Authors: Ghosh Sabyasachi , Roy Swarup , Naskar Jishu , Kole Ramen Kumar
Published: January 2020

Nanoparticle (NP) catalysts are widely used for removal of dyes for single use, but there is an acute need for developing catalysts with high efficiency and reusability for mixed dyes. Here we first optimized the process (reactant proportion, temperature, time, and pH) for biosynthesis of monometallic Ag, Au and bimetallic Au–Ag alloy NP catalysts using Polyalthia longifolia leaf extract. The biosynthesized NP catalysts were characterized by UV-vis, DLS, Zeta potential, TEM and EDX study while the probable biomolecules responsible for biosynthesis were identified by FTIR and GC-MS/MS analysis. The NPs are found to be mostly spherical in shape (size 5–20 nm) with prolonged stability. We evaluated their chemo-catalytic performance through degradation of dyes (methyl orange, methyl violet, methylene blue) in individual and ternary mixture in presence of NaBH4. The degradation percentage (80.06–96.59% within 5 min), degradation kinetics (k = 0.361–1.518 min–1), half-life (T50 = 0.457–1.920 min) and 80% degradation (T80 = 1.060–4.458 min) of dyes indicated highest catalytic activity of alloy in ternary mixture. Here we report a unique vacuum filtration system using alloy coated beads with excellent catalytic activity which could be reused thrice for removal of hazardous ternary mixed dyes with great promise for environmental remediation.
Canopy hyperspectral characteristics and yield estimation of winter wheat (Triticum aestivum) under low temperature injury
Authors: Xie Yongkai , Wang Chao , Yang Wude , Feng Meichen , Qiao Xingxing , Song Jinyao
Published: January 2020

To evaluate the effect of low-temperature stress in winter wheat during the early growth stages, the response regularity of the canopy spectral reflectance was evaluated. Besides, winter wheat yield during the maturation stage and the relationship between yield and canopy spectral reflectance were also analyzed. Two multivariate methods, namely, the successive projections algorithm (SPA) and multiple linear regression (MLR), were combined to explore the relationship between the spectral reflectance and yield. Our results showed that the green peak and red valley in visible wavelengths altered obviously and the red edge gradually moved towards blue wavebands. The canopy spectral reflectance in the near-infrared wavebands increased with an increase in low-temperature stress intensity. Moreover, the reflectance proved that the red edge region under low-temperature stress is related to winter wheat yield, and approximately 38% of extracted wavebands were concentrated in the red edge region (680–780 nm). Compared with the predictive MLR models, the model calibrated during the flowering period of winter wheat (25 days post low-temperature treatment) had better performance in predicting crop yield. Whole-spectrum predictive models based on the principle component regression (PCR) method and Normalized Difference Vegetation Index (NDVI) models based on MLR were also established. Moreover, the performance of three kinds of calibration methods and the validation result of the field test were compared to select the optimal monitoring stage and technique to estimate the yield in the early growth stage of winter wheat under low-temperature stress. This study could provide a theoretical basis and practical reference for hyperspectral assessment of yield in winter wheat during low-temperature stress.
Single-cell transcriptional profiles in human skeletal muscle
Authors: Rubenstein Aliza B. , Smith Gregory R. , Raue Ulrika , Begue Gwénaëlle , Minchev Kiril , Ruf-Zamojski Frederique , Nair Venugopalan D. , Wang Xingyu , Zhou Lan , Zaslavsky Elena , Trappe Todd A. , Trappe Scott , Sealfon Stuart C.
Published: January 2020

Skeletal muscle is a heterogeneous tissue comprised of muscle fiber and mononuclear cell types that, in addition to movement, influences immunity, metabolism and cognition. We investigated the gene expression patterns of skeletal muscle cells using RNA-seq of subtype-pooled single human muscle fibers and single cell RNA-seq of mononuclear cells from human vastus lateralis, mouse quadriceps, and mouse diaphragm. We identified 11 human skeletal muscle mononuclear cell types, including two fibro-adipogenic progenitor (FAP) cell subtypes. The human FBN1+ FAP cell subtype is novel and a corresponding FBN1+ FAP cell type was also found in single cell RNA-seq analysis in mouse. Transcriptome exercise studies using bulk tissue analysis do not resolve changes in individual cell-type proportion or gene expression. The cell-type gene signatures provide the means to use computational methods to identify cell-type level changes in bulk studies. As an example, we analyzed public transcriptome data from an exercise training study and revealed significant changes in specific mononuclear cell-type proportions related to age, sex, acute exercise and training. Our single-cell expression map of skeletal muscle cell types will further the understanding of the diverse effects of exercise and the pathophysiology of muscle disease.
CD8 infiltration is associated with disease control and tobacco exposure in intermediate-risk oropharyngeal cancer
Authors: Kemnade J. O. , Elhalawani H. , Castro P. , Yu J. , Lai S. , Ittmann M. , Mohamed A. S. R. , Lai S. Y. , Fuller C. D. , Sikora A. G. , Sandulache V. C.
Published: January 2020

Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing at a nearly epidemic rate, largely driven by the human papillomavirus (HPV). Despite the generally favorable clinical outcomes of patients with HPV driven (HPV+) OPSCC, a significant subset of HPV tumors associated with tobacco exposure have diminished treatment response and worse survival. The tumor immune microenvironment (TIME) has been shown to be a critical driver of treatment response and oncologic outcomes in OPSCC generally and HPV+ OPSCC more specifically. However, the impact of tobacco exposure on the TIME in OPSCC patients remains unclear. We analyzed the relationship between TIME, tobacco exposure and clinical outcomes in OPSCC patients (n = 143) with extensive tobacco exposure (median pack-years = 40). P16 overexpression, a surrogate marker of HPV association, was a strong predictor of relapse-free (RFS) and overall survival (OS) (p < 0.001, p < 0.001 respectively) regardless of tobacco exposure and associated strongly with differential infiltration of the tumor by both CD3 and CD8 lymphocytes measured via immunohistochemistry (p < 001, p < 0.001 respectively). CD3 and CD8 infiltration was a strong predictor of RFS and OS and associated strongly with disease stage (AJCC 8th Edition Staging Manual). Tobacco exposure correlated significantly (p < 0.001) with decreased CD8 infiltration in p16+ OPSCC tumors. Our findings demonstrate that the HPV+ OPSCC clinical outcomes are strongly correlated with the TIME, which is potentially modulated by tobacco exposure. Immunomodulatory strategies targeting this disease in smokers must take into consideration the potential modifying effects of tobacco exposure on treatment effectiveness and clinical outcomes.
Coherent intradimer dynamics in reaction centers of photosynthetic green bacterium Chloroflexus aurantiacus
Authors: Yakovlev Andrei G. , Shuvalov Vladimir A.
Published: January 2020

Early-time dynamics of absorbance changes (light minus dark) in the long-wavelength Qy absorption band of bacteriochlorophyll dimer P of isolated reaction centers (RCs) from thermophilic green bacterium Chloroflexus (Cfx.) aurantiacus was studied by difference pump-probe spectroscopy with 18-fs resolution at cryogenic temperature. It was found that the stimulated emission spectrum gradually moves to the red on the ~100-fs time scale and subsequently oscillates with a major frequency of ~140 cm−1. By applying the non-secular Redfield theory and linear susceptibility theory, the coherent dynamics of the stimulated emission from the excited state of the primary electron donor, bacteriochlorophyll dimer P*, was modeled. The model showed the possibility of an extremely fast transition from the locally excited state P1* to the spectrally different excited state P2*. This transition is clearly seen in the kinetics of the stimulated emission at 880 and 945 nm, where mostly P1* and P2* states emit, respectively. These findings are similar to those obtained previously in RCs of the purple bacterium Rhodobacter (Rba.) sphaeroides. The assumption about the existence of the second excited state P2* helps to explain the complicated temporal behavior of the ΔA spectrum measured by pump-probe spectroscopy. It is interesting that, in spite of the strong coupling between the P1* and P2* states assumed in our model, the form of the coherent oscillations is mainly defined by pure vibrational coherence in the excited states. A possible nature of the P2* state is discussed.
Investigation of The Cellular Response to Bone Fractures: Evidence for Flexoelectricity
Authors: Núñez-Toldrà Raquel , Vasquez-Sancho Fabian , Barroca Nathalie , Catalan Gustau
Published: January 2020

The recent discovery of bone flexoelectricity (strain-gradient-induced electrical polarization) suggests that flexoelectricity could have physiological effects in bones, and specifically near bone fractures, where flexoelectricity is theoretically highest. Here, we report a cytological study of the interaction between crack stress and bone cells. We have cultured MC3T3-E1 mouse osteoblastic cells in biomimetic microcracked hydroxyapatite substrates, differentiated into osteocytes and applied a strain gradient to the samples. The results show a strong apoptotic cellular response, whereby mechanical stimulation causes those cells near the crack to die, as indicated by live-dead and caspase staining. In addition, analysis two weeks post-stimulation shows increased cell attachment and mineralization around microcracks and a higher expression of osteocalcin –an osteogenic protein known to be promoted by physical exercise. The results are consistent with flexoelectricity playing at least two different roles in bone remodelling: apoptotic trigger of the repair protocol, and electro-stimulant of the bone-building activity of osteoblasts.
Temporal Network Pattern Identification by Community Modelling
Authors: Gao Xubo , Zheng Qiusheng , Vega-Oliveros Didier A. , Anghinoni Leandro , Zhao Liang
Published: January 2020

Temporal network mining tasks are usually hard problems. This is because we need to face not only a large amount of data but also its non-stationary nature. In this paper, we propose a method for temporal network pattern representation and pattern change detection following the reductionist approach. The main idea is to model each stable (durable) state of a given temporal network as a community in a sampled static network and the temporal state change is represented by the transition from one community to another. For this purpose, a reduced static single-layer network, called a target network, is constructed by sampling and rearranging the original temporal network. Our approach provides a general way not only for temporal networks but also for data stream mining in topological space. Simulation results on artificial and real temporal networks show that the proposed method can group different temporal states into different communities with a very reduced amount of sampled nodes.
Integrative analysis of blood and gut microbiota data suggests a non-alcoholic fatty liver disease (NAFLD)-related disorder in French SLAdd minipigs
Authors: Moroldo Marco , Munyaka Peris Mumbi , Lecardonnel Jérôme , Lemonnier Gaëtan , Venturi Eric , Chevaleyre Claire , Oswald Isabelle P. , Estellé Jordi , Rogel-Gaillard Claire
Published: January 2020

Minipigs are a group of small-sized swine lines, which show a broad range of phenotype variation and which often tend to be obese. The SLAdd (DD) minipig line was created by the NIH and selected as homozygous at the SLA locus. It was brought to France more than 30 years ago and maintained inbred ever since. In this report, we characterized the physiological status of a herd of French DD pigs by measuring intermediate phenotypes from blood and faeces and by using Large White (LW) pigs as controls. Three datasets were produced, i.e. complete blood counts (CBCs), microarray-based blood transcriptome, and faecal microbiota obtained by 16S rRNA sequencing. CBCs and expression profiles suggested a non-alcoholic fatty liver disease (NAFLD)-related pathology associated to comorbid cardiac diseases. The characterization of 16S sequencing data was less straightforward, suggesting only a potential weak link to obesity. The integration of the datasets identified several fine-scale associations between CBCs, gene expression, and faecal microbiota composition. NAFLD is a common cause of chronic liver disease in Western countries and is linked to obesity, type 2 diabetes mellitus and cardiac pathologies. Here we show that the French DD herd is potentially affected by this syndrome.
ToF-SIMS 3D imaging unveils important insights on the cellular microenvironment during biomineralization of gold nanostructures
Authors: Singh Ajay Vikram , Jungnickel Harald , Leibrock Lars , Tentschert Jutta , Reichardt Philipp , Katz Aaron , Laux Peter , Luch Andreas
Published: January 2020

The biomolecular imaging of cell-nanoparticle (NP) interactions using time-of-flight secondary ion mass spectrometry (ToF-SIMS) represents an evolving tool in nanotoxicology. In this study we present the three dimensional (3D) distribution of nanomaterials within biomolecular agglomerates using ToF-SIMS imaging. This novel approach was used to model the resistance of human alveolar A549 cells against gold (Au) ion toxicity through intra- and extracellular biomineralization. At low Au concentrations (≤1 mM HAuCl4) 3D-ToF-SIMS imaging reveals a homogenous intracellular distribution of Au-NPs in combination with polydisperse spherical NPs biomineralized in different layers on the cell surface. However, at higher precursor concentrations (≥2 mM) supplemented with biogenic spherical NPs as seeds, cells start to biosynthesize partially embedded long aspect ratio fiber-like Au nanostructures. Most interestingly, A549 cells seem to be able to sense the enhanced Au concentration. They change the chemical composition of the extracellular NP agglomerates from threonine-O-3-phosphate aureate to an arginine-Au(I)-imine. Furthermore they adopt the extracellular mineralization process from spheres to irregular structures to nanoribbons in a dose-dependent manner with increasing Au concentrations. The results achieved regarding size, shape and chemical specificity were cross checked by SEM-EDX and single particle (sp-)ICP-MS. Our findings demonstrate the potential of ToF-SIMS 3D imaging to better understand cell-NP interactions and their impact in nanotoxicology.
Cryogenic Memory Architecture Integrating Spin Hall Effect based Magnetic Memory and Superconductive Cryotron Devices
Authors: Nguyen Minh-Hai , Ribeill Guilhem J. , Gustafsson Martin V. , Shi Shengjie , Aradhya Sriharsha V. , Wagner Andrew P. , Ranzani Leonardo M. , Zhu Lijun , Baghdadi Reza , Butters Brenden , Toomey Emily , Colangelo Marco , Truitt Patrick A. , Jafari-Salim Amir , McAllister David , Yohannes Daniel , Cheng Sean R. , Lazarus Rich , Mukhanov Oleg , Berggren Karl K. , Buhrman Robert A. , Rowlands Graham E. , Ohki Thomas A.
Published: January 2020

One of the most challenging obstacles to realizing exascale computing is minimizing the energy consumption of L2 cache, main memory, and interconnects to that memory. For promising cryogenic computing schemes utilizing Josephson junction superconducting logic, this obstacle is exacerbated by the cryogenic system requirements that expose the technology’s lack of high-density, high-speed and power-efficient memory. Here we demonstrate an array of cryogenic memory cells consisting of a non-volatile three-terminal magnetic tunnel junction element driven by the spin Hall effect, combined with a superconducting heater-cryotron bit-select element. The write energy of these memory elements is roughly 8 pJ with a bit-select element, designed to achieve a minimum overhead power consumption of about 30%. Individual magnetic memory cells measured at 4 K show reliable switching with write error rates below 10−6, and a 4 × 4 array can be fully addressed with bit select error rates of 10−6. This demonstration is a first step towards a full cryogenic memory architecture targeting energy and performance specifications appropriate for applications in superconducting high performance and quantum computing control systems, which require significant memory resources operating at 4 K.
High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain
Authors: Abelein Axel , Chen Gefei , Kitoka Kristīne , Aleksis Rihards , Oleskovs Filips , Sarr Médoune , Landreh Michael , Pahnke Jens , Nordling Kerstin , Kronqvist Nina , Jaudzems Kristaps , Rising Anna , Johansson Jan , Biverstål Henrik
Published: January 2020

During storage in the silk gland, the N-terminal domain (NT) of spider silk proteins (spidroins) keeps the aggregation-prone repetitive region in solution at extreme concentrations. We observe that NTs from different spidroins have co-evolved with their respective repeat region, and now use an NT that is distantly related to previously used NTs, for efficient recombinant production of the amyloid-β peptide (Aβ) implicated in Alzheimer’s disease. A designed variant of NT from Nephila clavipes flagelliform spidroin, which in nature allows production and storage of β-hairpin repeat segments, gives exceptionally high yields of different human Aβ variants as a solubility tag. This tool enables efficient production of target peptides also in minimal medium and gives up to 10 times more isotope-labeled monomeric Aβ peptides per liter bacterial culture than previously reported.
Climate change or irrigated agriculture – what drives the water level decline of Lake Urmia
Authors: Schulz Stephan , Darehshouri Sahand , Hassanzadeh Elmira , Tajrishy Massoud , Schüth Christoph
Published: January 2020

Lake Urmia is one of the largest hypersaline lakes on earth with a unique biodiversity. Over the past two decades the lake water level declined dramatically, threatening the functionality of the lake’s ecosystems. There is a controversial debate about the reasons for this decline, with either mismanagement of the water resources, or climatic changes assumed to be the main cause. In this study we quantified the water budget components of Lake Urmia and analyzed their temporal evolution and interplay over the last five decades. With this we can show that variations of Lake Urmia’s water level during the analyzed period were mainly triggered by climatic changes. However, under the current climatic conditions agricultural water extraction volumes are significant compared to the remaining surface water inflow volumes. Changes in agricultural water withdrawal would have a significant impact on the lake volume and could either stabilize the lake, or lead to its complete collapse.
Heavy metals bioconcentration in Crassostrea rhizophorae: A site-to-site transplant experiment at the Potengi estuary, Rio Grande do Norte, Brazil
Authors: Senez-Mello T. M. , Crapez M. A. C. , Ramos e Silva C. A. , Silva E. T. , Fonseca E. M.
Published: January 2020

In this study, we analyzed the bioconcentration of Cd, Cr, Cu, Pb, Ni, and Zn in the soft tissue of transplanted oysters in two sites in the Potengi estuary for six months. Native oysters collected before and after the transplantation experiment provided the background for statistical analyses. Cd, Cr, and Ni showed a strong inverse correlation with oyster weight in both sites. Transplantation upstream of the estuary presented increasing concentrations of Zn, Cu, and Pb and condition index (CI) and decreasing trends for Cd and Ni, whereas Cr oscillated significantly. In the downstream transplantation, Cu, Pb, and Zn and the CI tended to decrease, whereas for Ni, Cd, and Cr, the concentrations increased. Spatiotemporal principal component analysis correlated these results mainly with proximity to the polluting source, seasonality, and previous exposure to heavy metals. These results helped interpret the responses provided by these biomonitors to environmental changes, whether they are natural or anthropogenic.
Treatment of human skeletal muscle cells with inhibitors of diacylglycerol acyltransferases 1 and 2 to explore isozyme-specific roles on lipid metabolism
Authors: Løvsletten Nils G. , Vu Helene , Skagen Christine , Lund Jenny , Kase Eili T. , Thoresen G. Hege , Zammit Victor A. , Rustan Arild C.
Published: January 2020

Diacylglycerol acyltransferases (DGAT) 1 and 2 catalyse the final step in triacylglycerol (TAG) synthesis, the esterification of fatty acyl-CoA to diacylglycerol. Despite catalysing the same reaction and being present in the same cell types, they exhibit different functions on lipid metabolism in various tissues. Yet, their roles in skeletal muscle remain poorly defined. In this study, we investigated how selective inhibitors of DGAT1 and DGAT2 affected lipid metabolism in human primary skeletal muscle cells. The results showed that DGAT1 was dominant in human skeletal muscle cells utilizing fatty acids (FAs) derived from various sources, both exogenously supplied FA, de novo synthesised FA, or FA derived from lipolysis, to generate TAG, as well as being involved in de novo synthesis of TAG. On the other hand, DGAT2 seemed to be specialised for de novo synthesis of TAG from glycerol-3-posphate only. Interestingly, DGAT activities were also important for regulating FA oxidation, indicating a key role in balancing FAs between storage in TAG and efficient utilization through oxidation. Finally, we observed that inhibition of DGAT enzymes could potentially alter glucose–FA interactions in skeletal muscle. In summary, treatment with DGAT1 or DGAT2 specific inhibitors resulted in different responses on lipid metabolism in human myotubes, indicating that the two enzymes play distinct roles in TAG metabolism in skeletal muscle.
D-tyrosine adds an anti-melanogenic effect to cosmetic peptides
Authors: Park Jisu , Jung Hyejung , Jang Bohee , Song Hyun-Kuk , Han Inn-Oc , Oh Eok-Soo
Published: January 2020

D-tyrosine is known to negatively regulate melanin synthesis by inhibiting tyrosinase activity. Here, we further reveal that peptides containing terminal D-tyrosine can reduce the melanin contents of human melanocytes. The addition of D-tyrosine to the terminus of the commercial anti-wrinkle peptide, pentapeptide-18 endowed the peptide with the ability to reduce the melanin content and tyrosinase activity in human MNT-1 melanoma cells and primary melanocytes. Consistently, terminal D-tyrosine-containing pentapeptide-18 inhibited the melanogenesis induced by α-MSH treatment or UV irradiation of MNT-1 cells and reduced melanin synthesis in the epidermal basal layer of a 3D human skin model. Furthermore, the addition of D-tyrosine to an anti-aging peptide (GEKG) or an anti-inflammatory peptide (GHK) endowed these short peptides with anti-melanogenic effects without altering their intrinsic effects. Together, these data suggest that the addition of D-tyrosine at the terminus of a short cosmetic peptide adds an anti-melanogenic effect to its intrinsic cosmetic effect. Our work offers a novel means of generating dual-function cosmetic peptides.
A machine learning based prediction system for the Indian Ocean Dipole
Authors: Ratnam J. V. , Dijkstra H. A. , Behera Swadhin K.
Published: January 2020

The Indian Ocean Dipole (IOD) is a mode of climate variability observed in the Indian Ocean sea surface temperature anomalies with one pole off Sumatra and the other pole near East Africa. An IOD event starts sometime in May-June, peaks in September-October and ends in November. Through atmospheric teleconnections, it affects the climate of many parts of the world, especially that of East Africa, Australia, India, Japan, and Europe. Owing to its large impacts, previous studies have addressed the predictability of the IOD using state of the art coupled climate models. Here, for the first-time, we predict the IOD using machine learning techniques, in particular artificial neural networks (ANNs). The IOD forecasts are generated for May to November from February-April conditions. The attributes for the ANNs are derived from sea surface temperature, 850 hPa and 200 hPa geopotential height anomalies, using a correlation analysis for the period 1949–2018. An ensemble of ANN forecasts is generated using 500 samples with replacement using jackknife approach. The ensemble mean of the IOD forecasts indicates the machine learning based ANN models to be capable of forecasting the IOD index well in advance with excellent skills. The forecast skills are much superior to the skills obtained from the persistence forecasts that one would guess from the observed data. The ANN models also perform far better than the models of the North American Multi-Model Ensemble (NMME) with higher correlation coefficients and lower root mean square errors (RMSE) for all the target months of May-November.
Metabolomic networks and pathways associated with feed efficiency and related-traits in Duroc and Landrace pigs
Authors: Carmelo Victor Adriano Okstoft , Banerjee Priyanka , da Silva Diniz Wellison Jarles , Kadarmideen Haja N.
Published: January 2020

Improving feed efficiency (FE) is a major goal of pig breeding, reducing production costs and providing sustainability to the pig industry. Reliable predictors for FE could assist pig producers. We carried out untargeted blood metabolite profiling in uncastrated males from Danbred Duroc (n = 59) and Danbred Landrace (n = 50) pigs at the beginning and end of a FE testing phase to identify biomarkers and biological processes underlying FE and related traits. By applying linear modeling and clustering analyses coupled with WGCNA framework, we identified 102 and 73 relevant metabolites in Duroc and Landrace based on two sampling time points. Among them, choline and pyridoxamine were hub metabolites in Duroc in early testing phase, while, acetoacetate, cholesterol sulfate, xanthine, and deoxyuridine were identified in the end of testing. In Landrace, cholesterol sulfate, thiamine, L-methionine, chenodeoxycholate were identified at early testing phase, while, D-glutamate, pyridoxamine, deoxycytidine, and L-2-aminoadipate were found at the end of testing. Validation of these results in larger populations could establish FE prediction using metabolomics biomarkers. We conclude that it is possible to identify a link between blood metabolite profiles and FE. These results could lead to improved nutrient utilization, reduced production costs, and increased FE.
Association of sarcopenia with phase angle and body mass index in kidney transplant recipients
Authors: Kosoku Akihiro , Uchida Junji , Nishide Shunji , Kabei Kazuya , Shimada Hisao , Iwai Tomoaki , Maeda Keiko , Hanayama Yoshiko , Ishihara Takuma , Naganuma Toshihide , Takemoto Yoshiaki , Nakatani Tatsuya
Published: January 2020

Malnutrition is an important risk factor for the development of sarcopenia. Recently, phase angle (PhA) obtained from the bioelectrical impedance analysis is increasingly becoming known as a nutritional status marker and may be considered a good indicator to identify elderly patients at risk of sarcopenia. In this study, we investigated the prevalence of sarcopenia and the relationship between sarcopenia and PhA or body mass index (BMI) as nutritional factors, and evaluated the discrimination performance of these nutritional factors for sarcopenia in 210 kidney transplant recipients. The median age was 55 years and 11.1% had sarcopenia. This prevalence of sarcopenia was lower than previous reports in kidney transplant recipients, maybe because of the differences in sarcopenia definitions and population demographics such as age, sex, race, and comorbidities. Both PhA and BMI were negatively correlated with sarcopenia after adjusting for age, sex, dialysis vintage, time after transplant, presence of diabetes mellitus, hemoglobin, estimated glomerular filtration rate, and the other nutritional factor. The discrimination performance for PhA and BMI had enough power to detect sarcopenia. These results suggest that PhA and BMI can be used in clinical practice to predict sarcopenia in kidney transplant patients.
Citizen Science, a promising tool for detecting and monitoring outbreaks of the crown-of-thorns starfish Acanthaster spp.
Authors: Dumas Pascal , Fiat Sylvie , Durbano Amaury , Peignon Christophe , Mou-Tham Gérard , Ham Jayven , Gereva Sompert , Kaku Rocky , Chateau Olivier , Wantiez Laurent , De Ramon N’Yeurt Antoine , Adjeroud Mehdi
Published: January 2020

Monitoring potentially devastating coral-eating crown-of-thorns starfish (COTS) populations at scales relevant to management is a challenging task. Here, we investigated a citizen science approach to detect COTS outbreaks and prioritize management responses. Between 2014 and 2018, 38 000 COTS were recorded through 641 online observation reports submitted across New Caledonia, Vanuatu and Fiji by private stakeholders (51%), NGOs (22%), business operator (11%), research/government agencies (16%). COTS were observed in multiple areas, including in remote/inhabited reefs where they had never been reported. A three-level classification was developed to discriminate risk areas and propose operational guidelines to streamline management actions. About two-thirds of reports had low abundances (<10 starfish sighted) and could be addressed with low priority. Verification surveys at 65 reef sites confirmed outbreaks in half of the cases, along with high peak densities (7 000 ind.ha−1). Combining professional and non-professional observers increased the detection range (+27%) and the number of COTS detections (+129%). Citizen reports were eventually followed by removal campaigns organized within diverse institutional frameworks. While citizen monitoring has intrinsic limitations, we advocate that it constitutes a complementary and promising approach to support the ongoing management efforts in all countries affected by COTS.