bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mathematical model of tumor regression and recurrence after therapeutic oncogene inactivation
Authors: Hori Sharon S. , Tong Ling , Swaminathan Srividya , Liebersbach Mariola , Wang Jingjing , Gambhir Sanjiv S. , Felsher Dean W. 
Published: January 2021

AbstractThe targeted inactivation of individual oncogenes can elicit regression of cancers through a phenomenon called oncogene addiction. Oncogene addiction is mediated by cell-autonomous and immune-dependent mechanisms. Therapeutic resistance to oncogene inactivation leads to recurrence but can be counteracted by immune surveillance. Predicting the timing of resistance will provide valuable insights in developing effective cancer treatments. To provide a quantitative understanding of cancer response to oncogene inactivation, we developed a new 3-compartment mathematical model of oncogene-driven tumor growth, regression and recurrence, and validated the model using a MYC-driven transgenic mouse model of T-cell acute lymphoblastic leukemia. Our mathematical model uses imaging-based measurements of tumor burden to predict the relative number of drug-sensitive and drug-resistant cancer cells in MYC-dependent states. We show natural killer (NK) cell adoptive therapy can delay cancer recurrence by reducing the net-growth rate of drug-resistant cells. Our studies provide a novel way to evaluate combination therapy for personalized cancer treatment.
A study of the dopamine transporter using the TRACT assay, a novel in vitro tool for solute carrier drug discovery
Authors: Sijben Hubert J. , van den Berg Julie J. E. , Broekhuis Jeremy D. , IJzerman Adriaan P. , Heitman Laura H. 
Published: January 2021

AbstractMembers of the solute carrier (SLC) transporter protein family are increasingly recognized as therapeutic drug targets. The majority of drug screening assays for SLCs are based on the uptake of radiolabeled or fluorescent substrates. Thus, these approaches often have limitations that compromise on throughput or the physiological environment of the SLC. In this study, we report a novel application of an impedance-based biosensor, xCELLigence, to investigate dopamine transporter (DAT) activity via substrate-induced activation of G protein-coupled receptors (GPCRs). The resulting assay, which is coined the ‘transporter activity through receptor activation’ (TRACT) assay, is based on the hypothesis that DAT-mediated removal of extracellular dopamine directly affects the ability of dopamine to activate cognate membrane-bound GPCRs. In two human cell lines with heterologous DAT expression, dopamine-induced GPCR signaling was attenuated. Pharmacological inhibition or the absence of DAT restored the apparent potency of dopamine for GPCR activation. The inhibitory potencies for DAT inhibitors GBR12909 (pIC50 = 6.2, 6.6) and cocaine (pIC50 = 6.3) were in line with values from reported orthogonal transport assays. Conclusively, this study demonstrates the novel use of label-free whole-cell biosensors to investigate DAT activity using GPCR activation as a readout. This holds promise for other SLCs that share their substrate with a GPCR.
Identifying of biomarkers associated with gastric cancer based on 11 topological analysis methods of CytoHubba
Authors: Ma Hua , He Zhihui , Chen Jing , Zhang Xu , Song Pingping 
Published: January 2021

AbstractGastric cancer (GC) is one of the most common types of malignancy. Its potential molecular mechanism has not been clarified. In this study, we aimed to explore potential biomarkers and prognosis-related hub genes associated with GC. The gene chip dataset GSE79973 was downloaded from the GEO datasets and limma package was used to identify the differentially expressed genes (DEGs). A total of 1269 up-regulated and 330 down-regulated genes were identified. The protein-protein interactions (PPI) network of DEGs was constructed by STRING V11 database, and 11 hub genes were selected through intersection of 11 topological analysis methods of CytoHubba in Cytoscape plug-in. All the 11 selected hub genes were found in the module with the highest score from PPI network of all DEGs by the molecular complex detection (MCODE) clustering algorithm. In order to explore the role of the 11 hub genes, we performed GO function and KEGG pathway analysis for them and found that the genes were enriched in a variety of functions and pathways among which cellular senescence, cell cycle, viral carcinogenesis and p53 signaling pathway were the most associated with GC. Kaplan-Meier analysis revealed that 10 out of the 11 hub genes were related to the overall survival of GC patients. Further, seven of the 11 selected hub genes were verified significantly correlated with GC by uni- or multivariable Cox model and LASSO regression analysis including C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1. C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1 may serve as potential prognostic biomarkers and therapeutic targets for GC.
Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes
Authors: Moretti Isabele F. , Lerario Antonio M. , Trombetta-Lima Marina , Sola Paula R. , da Silva Soares Roseli , Oba-Shinjo Sueli M. , Marie Suely K. N. 
Published: January 2021

AbstractGlioblastoma (GBM) is the most aggressive brain primary malignancy. Toll-like receptor 4 (TLR4) has a dual role in cell fate, promoting cell survival or death depending on the context. Here, we analyzed TLR4 expression in different grades of astrocytoma, and observed increased expression in tumors, mainly in GBM, compared to non-neoplastic brain tissue. TLR4 role was investigated in U87MG, a GBM mesenchymal subtype cell line, upon LPS stimulation. p65 nuclear translocation was observed in late phase, suggesting TLR4-non-canonical pathway activation. In fact, components of ripoptosome and inflammasome cascades were upregulated and they were significantly correlated in GBMs of the TCGA-RNASeq dataset. Moreover, an increased apoptotic rate was observed when the GBM-derived U87MG cells were co-treated with LPS and Temozolomide (TMZ) in comparison to TMZ alone. Increased TLR4 immunostaining was detected in nuclei of U87MG cells 12 h after LPS treatment, concomitant to activation of DNA repair genes. Time-dependent increased RAD51, FEN1 and UNG expression levels were confirmed after LPS stimulation, which may contribute to tumor cell fitness. Moreover, the combined treatment with the RAD51 inhibitor, Amuvatinib in combination with, TMZ after LPS stimulation reduced tumor cell viability more than with each treatment alone. In conclusion, our results suggest that stimulation of TLR4 combined with pharmacological inhibition of the DNA repair pathway may be an alternative treatment for GBM patients.
Seagrasses provide a novel ecosystem service by trapping marine plastics
Authors: Sanchez-Vidal Anna , Canals Miquel , de Haan William P. , Romero Javier , Veny Marta 
Published: January 2021

AbstractThere is strong evidence that the seafloor constitutes a final sink for plastics from land sources. There is also evidence that part of the plastics lying on the shallow seafloor are washed up back to the shoreline. However, little is known on the natural trapping processes leading to such landwards return. Here we investigate microplastics and larger plastic debris within beached seagrass remains including balls (aegagropilae) made of natural aggregates of vegetal fibers intertwined by seawater motion. We found up to 1470 plastic items per kg of plant material, which were mainly composed of negatively buoyant polymer filaments and fibers. Our findings show that seagrass meadows promote plastic debris trapping and aggregation with natural lignocellulosic fibers, which are then ejected and escape the coastal ocean. Our results show how seagrasses, one of the key ecosystems on Earth in terms of provision of goods and services, also counteract marine plastic pollution. In view of our findings, the regression of seagrass meadows in some marine regions acquires a new dimension.
Laparoscopic sleeve gastrectomy alters 1H-NMR-measured lipoprotein and glycoprotein profile in patients with severe obesity and nonalcoholic fatty liver disease
Authors: Cabré Noemí , Gil Míriam , Amigó Núria , Luciano-Mateo Fedra , Baiges-Gaya Gerard , Fernández-Arroyo Salvador , Rodríguez-Tomàs Elisabet , Hernández-Aguilera Anna , Castañé Helena , París Marta , Sabench Fàtima , Del Castillo Daniel , Camps Jordi , Joven Jorge 
Published: January 2021

AbstractPatients with morbid obesity frequently present non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) associated with pro-atherogenic alterations. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for weight reduction, and for the remission of hepatic alterations. Using 1H-nuclear magnetic resonance (1H-NMR), we investigated the effects of LSG on lipoprotein and glycoprotein profile in patients with morbid obesity and liver disease. We included 154 patients with morbid obesity (49 non-NASH, 54 uncertain NASH, 51 definite NASH). A blood sample was obtained before surgery and, in patients with definite NASH, one year after surgery. Patients with NASH had increased concentrations of medium and small VLDL particles, VLDL and IDL cholesterol concentrations, IDL, LDL, and HDL triglyceride concentrations, and elevated glycoprotein levels. These changes were more marked in patients with type 2 diabetes mellitus. LSG produced significant decreases in the concentration of VLDL particles, VLDL cholesterol and triglycerides, an increase in the concentration LDL particles and LDL cholesterol concentrations, and a decrease in protein glycation. We conclude that patients with obesity and NASH had significant alterations in circulating levels of lipoproteins and glycoproteins that were associated with the severity of the disease. Most of these changes were reversed post-LSG.
Abundance, distribution, and growth characteristics of three keystone Vachellia trees in Gebel Elba National Park, south-eastern Egypt
Authors: Abbas Ahmed M. , Al-Kahtani Mohammed , Novak Stephen J. , Soliman Wagdi Saber 
Published: January 2021

AbstractThis study was conducted to evaluate the abundance and distribution pattern of three keystone Vachellia taxa in wadi Khoda and wadi Rahaba, Gebel Elba National Park, a protected area in south-eastern Egypt. These taxa included Vachellia tortilis subsp. tortilis, Vachellia tortilis subsp. raddiana, and Vachellia ehrenbergiana. In wadi Khoda, only two of these taxa were detected (V. tortilis subsp. raddiana and V. tortilis subsp. tortilis), while all three taxa were encountered in wadi Rahaba. The density of trees in wadi Khoda was 34.3 plant ha−1 compared to 26.3 plant ha−1 in wadi Rahaba. Vachellia tortilis subsp. raddiana was the most frequently observed tree, with an average of 47.93% and 68.25% in wadi Rahaba and wadi Khoda, respectively. Crown depth and tree height were mainly associated with elevation, indicating that elevation plays a key role in the growth of these Vachellia taxa. Our results suggest that human activities have had limited effect on the distribution of these three keystone taxa. Thus, management in Gebel Elba National Park should continue to limit the impact of human activities on these three keystone species.
Structural characterization of a GNAT family acetyltransferase from Elizabethkingia anophelis bound to acetyl-CoA reveals a new dimeric interface
Authors: Shirmast P. , Ghafoori S. M. , Irwin R. M. , Abendroth J. , Mayclin S. J. , Lorimer D. D. , Edwards Thomas E. , Forwood Jade K. 
Published: January 2021

AbstractGeneral control non-repressible 5 (GCN5)-related N-acetyltransferases (GNATs) catalyse the acetylation of a diverse range of substrates, thereby orchestrating a variety of biological processes within prokaryotes and eukaryotes. GNAT enzymes can catalyze the transfer of an acetyl group from acetyl coenzyme A to substrates such as aminoglycoside antibiotics, amino acids, polyamines, peptides, vitamins, catecholamines, and large macromolecules including proteins. Although GNATs generally exhibit low to moderate sequence identity, they share a conserved catalytic fold and conserved structural motifs. In this current study we characterize the high-resolution X-ray crystallographic structure of a GNAT enzyme bound with acetyl-CoA from Elizabethkingia anophelis, an important multi-drug resistant bacterium. The tertiary structure is comprised of six α-helices and nine β-strands, and is similar with other GNATs. We identify a new and uncharacterized GNAT dimer interface, which is conserved in at least two other unpublished GNAT structures. This suggests that GNAT enzymes can form at least five different types of dimers, in addition to a range of other oligomers including trimer, tetramer, hexamer, and dodecamer assemblies. The high-resolution structure presented in this study is suitable for future in-silico docking and structure–activity relationship studies.
A defined glycosylation regulatory network modulates total glycome dynamics during pluripotency state transition
Authors: Pecori Federico , Yokota Ikuko , Hanamatsu Hisatoshi , Miura Taichi , Ogura Chika , Ota Hayato , Furukawa Jun-ichi , Oki Shinya , Yamamoto Kazuo , Yoshie Osamu , Nishihara Shoko 
Published: January 2021

AbstractEmbryonic stem cells (ESCs) and epiblast-like cells (EpiLCs) recapitulate in vitro the epiblast first cell lineage decision, allowing characterization of the molecular mechanisms underlying pluripotent state transition. Here, we performed a comprehensive and comparative analysis of total glycomes of mouse ESCs and EpiLCs, revealing that overall glycosylation undergoes dramatic changes from early stages of development. Remarkably, we showed for the first time the presence of a developmentally regulated network orchestrating glycosylation changes and identified polycomb repressive complex 2 (PRC2) as a key component involved in this process. Collectively, our findings provide novel insights into the naïve-to-primed pluripotent state transition and advance the understanding of glycosylation complex regulation during early mouse embryonic development.
Intake of dairy products and associations with major atherosclerotic cardiovascular diseases: a systematic review and meta-analysis of cohort studies
Authors: Jakobsen Marianne Uhre , Trolle Ellen , Outzen Malene , Mejborn Heddie , Grønberg Manja G. , Lyndgaard Christian Bøge , Stockmarr Anders , Venø Stine K. , Bysted Anette 
Published: January 2021

AbstractSpecific types of dairy products may be differentially associated with atherosclerotic cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of cohort studies to summarize findings on the associations between total dairy product intake and intake of dairy product subgroups and the risk of major atherosclerotic CVDs in the general adult population. Our protocol was registered in PROSPERO (CRD42019125455). PubMed and Embase were systematically searched through 15 August 2019. For high versus low intake and dose–response meta-analysis, random-effects modelling was used to calculate summary risk ratios (RR). There were 13 cohort studies included for coronary heart disease (CHD), 7 for ischemic stroke and none for peripheral artery disease. High-fat milk was positively associated with CHD (RR 1.08 (95% confidence interval 1.00–1.16) per 200 g higher intake/day) and cheese was inversely associated with CHD (RR 0.96 (95% confidence interval 0.93–0.98) per 20 g higher intake/day). Heterogeneity, however, was observed in high versus low meta-analyses. Milk was inversely associated with ischemic stroke in high versus low meta-analysis only. In conclusion, this systematic review indicates a positive association of high-fat milk and an inverse association of cheese with CHD risk. The findings should be interpreted in the context of the observed heterogeneity.
Additive interactions of some reduced-risk biocides and two entomopathogenic nematodes suggest implications for integrated control of Spodoptera litura (Lepidoptera: Noctuidae)
Authors: Khan Rashad Rasool , Arshad Muhammad , Aslam Asad , Arshad Muhammad 
Published: January 2021

AbstractHigher volumes of conventional and novel chemical insecticides are applied by farmers to control resistant strains of armyworm (Spodoperta litura) in Pakistan without knowing their risks to the environment and to public health. Ten reduced-risk insecticides were tested for their compatibility with two entomopathogenic nematodes (EPNs);Heterorhabditis indicaandSteinernema carpocapsaeagainst S. litura. The insecticide emamectin benzoate was highly toxic (LC50 = 2.97 mg/l) against 3rdinstarS. lituralarvae when applied alone whereas, novaluron and methoxyfenozide were the least toxic (LC50 = 29.56 mg/l and 21.06 mg/l), respectively. All the insecticides proved harmless against the two EPNs even 96 h after treatment. Indoxacarb, flubendiamide and spinetoram produced the greatest mortalities (72–76%) ofS. lituralarvae after 72 h when applied in mixtures withH. indica. Lowest mortalities (44.00 ± 3.74% and 48.00 ± 2.89) were observed for mixtures ofH. indicawith methoxyfenozide and chlorfenapyr, respectively. The positive control treatments with both EPNs (S. carpocapsaeandH. indica) produced > 50% mortality 96 h after treatment. For insecticide mixtures withS. carpocapsae, only indoxacarb produced 90% mortality of larvae, whereas, indoxacarb, flubendiamide, emamectin benzoate, and spinetoram produced 90–92% mortality of larvae when applied in mixtures withH. indica. Additive interactions (Chi-square < 3.84) of EPN mixtures with reduced volumes of reduced-risk insecticides suggest opportunities to develop more environmentally favorable pest management programs forS. litura.
Seasonal variation in sex-specific immunity in wild birds
Authors: Valdebenito José O. , Halimubieke Naerhulan , Lendvai Ádám Z. , Figuerola Jordi , Eichhorn Götz , Székely Tamás 
Published: January 2021

AbstractWhilst the immune system often varies seasonally and exhibits differences between males and females, the general patterns in seasonality and sex differences across taxa have remained controversial. Birds are excellent model organisms to assess these patterns, because the immune system of many species is well characterised. We conducted a meta-analysis using 41 wild bird species from 24 avian families to investigate sex differences and seasonal (breeding/non-breeding) variations in immune status, including white blood cell counts, phytohaemagglutinin (PHA) test, bacteria-killing ability (BKA), haemolysis and haemagglutination assays. We found male-biased macrophage concentration, BKA and haemolysis titers, but only during the breeding season. Sex-specific heterophil concentrations, heterophil/lymphocyte ratios and PHA responses differed between breeding and non-breeding, suggesting larger changes in males than in females. Importantly, sex differences in immune status are stronger during the breeding period than during the non-breeding period. Taken together, our study suggests that both seasonal variation and sex differences in immune system are common in birds, although their associations are more complex than previously thought.
Modified-release of encapsulated bioactive compounds from annatto seeds produced by optimized ionic gelation techniques
Authors: Naranjo-Durán Ana María , Quintero-Quiroz Julián , Rojas-Camargo John , Ciro-Gómez Gelmy Luz 
Published: January 2021

AbstractTo compare the encapsulation of annatto extract by external gelation (EG) and internal gelation (IG) and to maximize process yield (% Y), two central composite designs were proposed. Calcium chloride (CaCl2) concentration (0.3–3.5%), alginate to gelling solution ratio (1:2–1:6); acetic acid (CH3COOH) concentration (0.2–5.0%) and alginate to gelling solution ratio (1:2–1:6) were taken as independent variables for EG and IG respectively. Release studies were conducted under different conditions; morphology, particle size, the encapsulation efficiency (EE), and release mechanism were evaluated under optimized conditions. The optimized EG conditions were 0.3% CaCl2and 1:1.2 alginate to gelling solution ratio, whereas a 0.3% CH3COOH and 1:5 alginate to gelling solution ratio were optimized conditions for IG. When 20% extract was employed, the highest EE was achieved, and the largest release was obtained at a pH 6.5 buffer. The Peppas–Sahlin model presented the best fit to experimental data. Polyphenol release was driven by diffusion, whereas bixin showed anomalous release. These results are promising for application as modulated release agents in food matrices.
Ratio-based multi-level resistive memory cells
Authors: Lastras-Montaño Miguel Angel , Del Pozo-Zamudio Osvaldo , Glebsky Lev , Zhao Meiran , Wu Huaqiang , Cheng Kwang-Ting 
Published: January 2021

AbstractRatio-based encoding has recently been proposed for single-level resistive memory cells, in which the resistance ratio of a pair of resistance-switching devices, rather than the resistance of a single device (i.e. resistance-based encoding), is used for encoding single-bit information, which significantly reduces the bit error probability. Generalizing this concept for multi-level cells, we propose a ratio-based information encoding mechanism and demonstrate its advantages over the resistance-based encoding for designing multi-level memory systems. We derive a closed-form expression for the bit error probability of ratio-based and resistance-based encodings as a function of the number of levels of the memory cell, the variance of the distribution of the resistive states, and the ON/OFF ratio of the resistive device, from which we prove that for a multi-level memory system using resistance-based encoding with bit error probability x, its corresponding bit error probability using ratio-based encoding will be reduced to $$x^2$$

x
2

at the best case and $$x^{\sqrt{2}}$$

x

2

at the worst case. We experimentally validated these findings on multiple resistance-switching devices and show that, compared to the resistance-based encoding on the same resistive devices, our approach achieves up to 3 orders of magnitude lower bit error probability, or alternatively it could reduce the cell’s programming time and programming energy by up 5–10$$\times$$
×
, while achieving the same bit error probability.