bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Members 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

Gastric 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

Glioblastoma (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

There 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

Patients 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

This 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

General 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

Embryonic 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

Specific 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

Higher 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

Whilst 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

To 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

Ratio-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.
Gut microbiota derived trimethylamine N-oxide (TMAO) detection through molecularly imprinted polymer based sensor
Authors: Lakshmi G. B. V. S. , Yadav Amit K. , Mehlawat Neha , Jalandra Rekha , Solanki Pratima R. , Kumar Anil
Published: January 2021

Trimethylamine N-oxide (TMAO), a microbiota-derived metabolite has been implicated in human health and disease. Its early detection in body fluids has been presumed to be significant in understanding the pathogenesis and treatment of many diseases. Hence, the development of reliable and rapid technologies for TMAO detection may augment our understanding of pathogenesis and diagnosis of diseases that TMAO has implicated. The present work is the first report on the development of a molecularly imprinted polymer (MIP) based electrochemical sensor for sensitive and selective detection of TMAO in body fluids. The MIP developed was based on the polypyrrole (PPy), which was synthesized via chemical oxidation polymerization method, with and without the presence of TMAO. The MIP, NIP and the non-sonicated polymer (PPy-TMAO) were separately deposited electrophoretically onto the hydrolyzed indium tin oxide (ITO) coated glasses. The chemical, morphological, and electrochemical behavior of MIP, non-imprinted polymer (NIP), and PPy-TMAO were characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and electrochemical techniques. The detection response was recorded using differential pulse voltammetry (DPV), which revealed a decrease in the peak current with the increase in concentration of TMAO. The MIP sensor showed a dynamic detection range of 1–15 ppm with a sensitivity of 2.47 µA mL ppm−1 cm−2. The developed sensor is easy to construct and operate and is also highly selective to detect TMAO in body fluids such as urine. The present research provides a basis for innovative strategies to develop sensors based on MIP to detect other metabolites derived from gut microbiota that are implicated in human health and diseases.
Precision modification of the human gut microbiota targeting surface-associated proteins
Authors: Marcos-Fernández Raquel , Ruiz Lorena , Blanco-Míguez Aitor , Margolles Abelardo , Sánchez Borja
Published: January 2021

This work describes a new procedure that allows the targeted modification of the human gut microbiota by using antibodies raised against bacterial surface-associated proteins specific to the microorganism of interest. To this end, a polyclonal antibody recognising the surface-associated protein Surface Layer Protein A of Lactobacillus acidophilus DSM20079T was developed. By conjugating this antibody with fluorescent probes and magnetic particles, we were able to specifically identify this bacterium both in a synthetic, and in real gut microbiotas by means of a flow cytometry approach. Further, we demonstrated the applicability of this antibody to deplete complex human gut microbiotas from L. acidophilus in a single step. L. acidophilus was found to interact with other bacteria both in synthetic and in real microbiotas, as reflected by its concomitant depletion together with other species. Further optimization of the procedure including a trypsin step enabled to achieve the selective and complete isolation of this species. Depleting a single species from a gut microbiota, using antibodies recognizing specific cell surface elements of the target organism, will open up novel ways to tackle research on the specific immunomodulatory and metabolic contributions of a bacterium of interest in the context of a complex human gut microbiota, including the investigation into therapeutic applications by adding/depleting a key bacterium. This represents the first work in which an antibody/flow-cytometry based application enabled the targeted edition of human gut microbiotas, and represents the basis for the design of precision microbiome-based therapies.
Combined transcriptomic and lipidomic analysis reveals aberrant lipid metabolism in central nervous system hemangioblastomas
Authors: Wang Qiguang , Liu Wenke , Zhang Si , Liang Zuoyu , Jiang Linhong , Xue Aiqin , Cen Xiaobo , Bu Qian
Published: January 2021

Peritumoral cysts are commonly detected in the central nervous system tumors, especially hemangioblastomas (HBs). However, the molecular mechanisms driving their formation and propagation are still unknown. We conducted an integrated lipidomics and transcriptomics analysis on solid and cystic HB samples in order to elucidate the changes in the lipid profile and expression of lipid metabolism-related genes during cyst formation. Transcriptomic analysis revealed differential expression of several genes between the solid and cystic HBs, and those associated with lipid metabolism, such as ADCY4, MGLL, ACOT2, DGKG, SHC1 and LPAR2, were markedly dysregulated in the cystic HBs. The lipidomic analysis further showed a significant reduction in the abundance of triacylglycerol, ceramide, lysophosphatidylcholine and lysophosphatidylethanolamine, and an increase in phosphatidylcholine and phosphatidylethanolamine levels in the cystic HBs. Furthermore, bioinformatics analysis revealed altered lipid biosynthesis, glycerophospholipid metabolism and phospholipase activity in the cystic HBs. Taken together, our findings indicate that cyst formation in HBs is related with aberrant lipid metabolism.
Sewage sludge application enhances soil properties and rice growth in a salt-affected mudflat soil
Authors: Shan Yuhua , Lv Min , Zuo Wengang , Tang Zehui , Ding Cheng , Yu Zhixuan , Shen Ziyi , Gu Chuanhui , Bai Yanchao
Published: January 2021

The most important measures for salt-affected mudflat soil reclamation are to reduce salinity and to increase soil organic carbon (OC) content and thus soil fertility. Salinity reduction is often accomplished through costly freshwater irrigation by special engineering measures. Whether fertility enhancement only through one-off application of a great amount of OC can improve soil properties and promote plant growth in salt-affected mudflat soil remains unclear. Therefore, the objective of our indoor pot experiment was to study the effects of OC amendment at 0, 0.5%, 1.0%, 1.5%, and 2.5%, calculated from carbon content, by one-off application of sewage sludge on soil properties, rice yield, and root growth in salt-affected mudflat soil under waterlogged conditions. The results showed that the application of sewage sludge promoted soil fertility by reducing soil pH and increasing content of OC, nitrogen and phosphorus in salt-affected mudflat soil, while soil electric conductivity (EC) increased with increasing sewage sludge (SS) application rates under waterlogged conditions. In this study, the rice growth was not inhibited by the highest EC of 4.43 dS m−1 even at high doses of SS application. The SS application increased yield of rice, promoted root growth, enhanced root activity and root flux activity, and increased the soluble sugar and amino acid content in the bleeding sap of rice plants at the tillering, jointing, and maturity stages. In conclusion, fertility enhancement through organic carbon amendment can “offset” the adverse effects of increased salinity and promote plant growth in salt-affected mudflat soil under waterlogged conditions.
Electrical percolation in extrinsically conducting, poly(ε-decalactone) composite neural interface materials
Authors: Krukiewicz Katarzyna , Britton James , Więcławska Daria , Skorupa Małgorzata , Fernandez Jorge , Sarasua Jose-Ramon , Biggs Manus J. P.
Published: January 2021

By providing a bidirectional communication channel between neural tissues and a biomedical device, it is envisaged that neural interfaces will be fundamental in the future diagnosis and treatment of neurological disorders. Due to the mechanical mismatch between neural tissue and metallic neural electrodes, soft electrically conducting materials are of great benefit in promoting chronic device functionality. In this study, carbon nanotubes (CNT), silver nanowires (AgNW) and poly(hydroxymethyl 3,4-ethylenedioxythiophene) microspheres (MSP) were employed as conducting fillers within a poly(ε-decalactone) (EDL) matrix, to form a soft and electrically conducting composite. The effect of a filler type on the electrical percolation threshold, and composite biocompatibility was investigated in vitro. EDL-based composites exhibited favourable electrochemical characteristics: EDL/CNT—the lowest film resistance (1.2 ± 0.3 kΩ), EDL/AgNW—the highest charge storage capacity (10.7 ± 0.3 mC cm− 2), and EDL/MSP—the highest interphase capacitance (1478.4 ± 92.4 µF cm−2). All investigated composite surfaces were found to be biocompatible, and to reduce the presence of reactive astrocytes relative to control electrodes. The results of this work clearly demonstrated the ability of high aspect ratio structures to form an extended percolation network within a polyester matrix, resulting in the formulation of composites with advantageous mechanical, electrochemical and biocompatibility properties.
Maternal and offspring high-fat diet leads to platelet hyperactivation in male mice offspring
Authors: Gaspar Renato S. , Unsworth Amanda J. , Al-Dibouni Alaa , Bye Alexander P. , Sage Tanya , Stewart Michelle , Wells Sara , Cox Roger D. , Gibbins Jonathan M. , Sellayah Dyan , E. Hughes Craig
Published: January 2021

Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. While prominent effects on cardiovascular health are observed, the impact on platelet physiology has not been studied. Here, we examined whether maternal high-fat diet (HF) ingestion affects the platelet function in lean and obese offspring. C57BL6/N mice dams were given a HF or control (C) diet for 8 weeks before and during pregnancy. Male and female offspring received C or HF diets for 26 weeks. Experimental groups were: C/C, dam and offspring fed standard laboratory diet; C/HF dam fed standard laboratory diet and offspring fed HF diet; HF/C and HF/HF. Phenotypic and metabolic tests were performed and blood collected for platelet studies. Compared to C/C, offspring HF groups were obese, with fat accumulation, hyperglycaemia and insulin resistance. Female offspring did not present platelet hyperactivity, hence we focused on male offspring. Platelets from HF/HF mice were larger, hyperactive and presented oxidative stress when compared to C/C. Maternal and offspring HF diet results in platelet hyperactivation in male mouse offspring, suggesting a novel ‘double-hit’ effect.
In vivo tracking of 14C thymidine labeled mesenchymal stem cells using ultra-sensitive accelerator mass spectrometry
Authors: Oh Min-Seok , Lee Seul-Gi , Lee Gwan-Ho , Kim C-Yoon , Kim Eun-Young , Song Jong Han , Yu Byung-Yong , Chung Hyung Min
Published: January 2021

Despite the tremendous advancements made in cell tracking, in vivo imaging and volumetric analysis, it remains difficult to accurately quantify the number of infused cells following stem cell therapy, especially at the single cell level, mainly due to the sensitivity of cells. In this study, we demonstrate the utility of both liquid scintillator counter (LSC) and accelerator mass spectrometry (AMS) in investigating the distribution and quantification of radioisotope labeled adipocyte derived mesenchymal stem cells (AD-MSCs) at the single cell level after intravenous (IV) transplantation. We first show the incorporation of 14C-thymidine (5 nCi/ml, 24.2 ng/ml) into AD-MSCs without affecting key biological characteristics. These cells were then utilized to track and quantify the distribution of AD-MSCs delivered through the tail vein by AMS, revealing the number of AD-MSCs existing within different organs per mg and per organ at different time points. Notably, the results show that this highly sensitive approach can quantify one cell per mg which effectively means that AD-MSCs can be detected in various tissues at the single cell level. While the significance of these cells is yet to be elucidated, we show that it is possible to accurately depict the pattern of distribution and quantify AD-MSCs in living tissue. This approach can serve to incrementally build profiles of biodistribution for stem cells such as MSCs which is essential for both research and therapeutic purposes.
Profiling of human burned bones: oxidising versus reducing conditions
Authors: Marques M. P. M. , Gonçalves D. , Mamede A. P. , Coutinho T. , Cunha E. , Kockelmann W. , Parker S. F. , Batista de Carvalho L. A. E.
Published: January 2021

Complementary optical and neutron-based vibrational spectroscopy techniques (Infrared, Raman and inelastic neutron scattering) were applied to the study of human bones (femur and humerus) burned simultaneously under either aerobic or anaerobic conditions, in a wide range of temperatures (400 to 1000 °C). This is the first INS study of human skeletal remains heated in an oxygen-deprived atmosphere. Clear differences were observed between both types of samples, namely the absence of hydroxyapatite’s OH vibrational bands in bone burned anaerobically (in unsealed containers), coupled to the presence of cyanamide (NCNH2) and portlandite (Ca(OH)2) in these reductive conditions. These results are expected to allow a better understanding of the heat effect on bone´s constituents in distinct environmental settings, thus contributing for an accurate characterisation of both forensic and archaeological human skeletal remains found in distinct scenarios regarding oxygen availability.
Estimation and correction of instrument artefacts in dynamic impedance spectra
Authors: Erinmwingbovo Collins , La Mantia Fabio
Published: January 2021

Dynamic impedance spectroscopy is one of the most powerful techniques in the qualitative and quantitative mechanistic studies of electrochemical systems, as it allows for time-resolved investigation and dissection of various physicochemical processes occurring at different time scales. However, due to high-frequency artefacts connected to the non-ideal behaviour of the instrumental setup, dynamic impedance spectra can lead to wrong interpretation and/or extraction of wrong kinetic parameters. These artefacts arise from the non-ideal behaviour of the voltage and current amplifier (I/E converters) and stray capacitance. In this paper, a method for the estimation and correction of high-frequency artefacts arising from non-ideal behaviour of instrumental setup will be discussed. Using resistors, $$[\hbox {Fe(CN)}_6]^{3-/4-}$$

[

Fe(CN)
6

]

3
-
/
4
-

redox couple and nickel hexacyanoferrate nanoparticles, the effect of high-frequency artefacts will be investigated and the extraction of the impedance of the system from the measured dynamic impedance is proposed. It is shown that the correction allows acquiring proper dynamic impedance spectra at frequencies higher than the bandwidth of the potentiostat, and simultaneously acquire high precision cyclic voltammetry.
Isolation and purification of glycoglycerolipids to induce apoptosis in breast cancer cells
Authors: Abedin Muhammad Raisul , Barua Sutapa
Published: January 2021

Monogalactosyldiacylglycerol (MGDG) is the most abundant type of glycoglycerolipid found in the plant cell membrane and mostly in the chloroplast thylakoid membrane. The amphiphilic nature of MGDG is attractive in pharmaceutical fields for interaction with other biological molecules and hence exerting therapeutic anti-cancer, anti-viral, and anti-inflammatory activities. In this study, we investigated the therapeutic efficacy of cyanobacteria derived MGDG to inhibit breast cancer cell growth. MGDG was extracted from a cyanobacteria Synechocystis sp. PCC 6803 followed by a subsequent fractionation by column chromatographic technique. The purity and molecular structure of MGDG were analyzed by nuclear magnetic resonance (NMR) spectroscopy analysis. The presence of MGDG in the extracted fraction was further confirmed and quantified by high-performance liquid chromatography (HPLC). The anti-proliferation activity of the extracted MGDG molecule was tested against BT-474 and MDA-MB-231 breast cancer cell lines. The in vitro study showed that MGDG extracted from Synechocystis sp. PCC 6803 induced apoptosis in (70 ± 8) % of BT-474 (p < 0.001) and (58 ± 5) % of MDA-MB-231 cells (p < 0.001) using ~ 60 and 200 ng/ml of concentrations, respectively. The half-maximal inhibitory concentration, IC50 of MGDG extracted from Synechocystis sp. PCC 6803 were (27.2 ± 7.6) and (150 ± 70) ng/ml in BT-474 and MDA-MB-231 cell lines, respectively. Quantification of caspase-3/7 activity using flow cytometry showed (3.0 ± 0.4) and (2.1 ± 0.04)-fold (p < 0.001) higher protein expressions in the MGDG treated BT-474 and MDA-MB-231 cells, respectively than untreated controls conferring to the caspase-dependent apoptosis. The MGDG did not show any significant cytotoxic side effects in human dermal fibroblasts cells. A commercially available MGDG control did not induce any apoptotic cell death in cancer cells substantiating the potential of the MGDG extracted from Synechocystis sp. PCC 6803 for the treatment of breast cancer cells through the apoptosis-mediated pathway.
Reproduction of melting behavior for vitrified hillforts based on amphibolite, granite, and basalt lithologies
Authors: McCloy John S. , Marcial José , Clarke Jack S. , Ahmadzadeh Mostafa , Wolff John A. , Vicenzi Edward P. , Bollinger David L. , Ogenhall Erik , Englund Mia , Pearce Carolyn I. , Sjöblom Rolf , Kruger Albert A.
Published: January 2021

European Bronze and Iron Age vitrified hillforts have been known since the 1700s, but archaeological interpretations regarding their function and use are still debated. We carried out a series of experiments to constrain conditions that led to the vitrification of the inner wall rocks in the hillfort at Broborg, Sweden. Potential source rocks were collected locally and heat treated in the laboratory, varying maximum temperature, cooling rate, and starting particle size. Crystalline and amorphous phases were quantified using X-ray diffraction both in situ, during heating and cooling, and ex situ, after heating and quenching. Textures, phases, and glass compositions obtained were compared with those for rock samples from the vitrified part of the wall, as well as with equilibrium crystallization calculations. ‘Dark glass’ and its associated minerals formed from amphibolite or dolerite rocks melted at 1000–1200 °C under reducing atmosphere then slow cooled. ‘Clear glass’ formed from non-equilibrium partial melting of feldspar in granitoid rocks. This study aids archaeological forensic investigation of vitrified hillforts and interpretation of source rock material by mapping mineralogical changes and glass production under various heating conditions.
Effects of climatic factors on the net primary productivity in the source region of Yangtze River, China
Authors: Yuan Zhe , Wang Yongqiang , Xu Jijun , Wu Zhiguang
Published: January 2021

The ecosystem of the Source Region of Yangtze River (SRYR) is highly susceptible to climate change. In this study, the spatial–temporal variation of NPP from 2000 to 2014 was analyzed, using outputs of Carnegie–Ames–Stanford Approach model. Then the correlation characteristics of NPP and climatic factors were evaluated. The results indicate that: (1) The average NPP in the SRYR is 100.0 gC/m2 from 2000 to 2014, and it shows an increasing trend from northwest to southeast. The responses of NPP to altitude varied among the regions with the altitude below 3500 m, between 3500 to 4500 m and above 4500 m, which could be attributed to the altitude associated variations of climatic factors and vegetation types; (2) The total NPP of SRYR increased by 0.18 TgC per year in the context of the warmer and wetter climate during 2000–2014. The NPP was significantly and positively correlated with annual temperature and precipitation at interannual time scales. Temperature in February, March, May and September make greater contribution to NPP than that in other months. And precipitation in July played a more crucial role in influencing NPP than that in other months; (3) Climatic factors caused the NPP to increase in most of the SRYR. Impacts of human activities were concentrated mainly in downstream region and is the primary reason for declines in NPP.
The glutaminase (CgGLS-1) mediates anti-bacterial immunity by prompting cytokine synthesis and hemocyte apoptosis in Pacific oyster Crassostrea gigas
Authors: Liang Yage , Li Meijia , Liu Zhaoqun , Li Yuanmei , Wang Lingling , Song Linsheng
Published: January 2021

Glutaminase, an amidohydrolase enzyme that hydrolyzes glutamine to glutamate, plays crucial roles in various immunomodulatory processes such as cell apoptosis, proliferation, migration, and secretion of cytokines. In the present study, a glutaminase homologue (designated as CgGLS-1) was identified from Pacific oyster Crassostrea gigas, whose open reading frame was of 1836 bp. CgGLS-1 exhibited high sequence identity with vertebrate kidney-type GLS, and closely clustered with their homologues from mollusc C. virginica. The enzyme activity of recombinant CgGLS-1 protein (rCgGLS-1) was estimated to be 1.705 U/mg. CgGLS-1 mRNA was constitutively expressed in all the tested tissues of oysters, with the highest expression level in hemocytes. CgGLS-1 mRNA expression in hemocytes was significantly up-regulated and peaked at 6 h (2.07-fold, p < 0.01) after lipopolysaccharide (LPS) stimulation. The CgGLS-1 protein was mainly distributed in the cytoplasm with a significant co-location with mitochondria in oyster hemocytes. The content of Glu in the oyster serum was significantly decreased after the inhibition of CgGLS-1 using specific inhibitor Bis-2- [5-(phenyl acetamido)-1,3,4-thiadiazol-2-yl] ethyl sulfide (BPTES), and the expression levels of CgmGluR6, CgAP-1, cytokines CgIL17-5 and CgTNF-1 were significantly decreased after BPTES and LPS stimulation. The transcripts of CgCaspase3 as well as the apoptosis index of hemocytes were also decreased. These results collectively suggest that CgGLS-1 is the enzyme to synthesize Glu in oyster, which can modulate anti-bacterial immunity by regulating the secretion of pro-inflammatory cytokines CgIL17-5 and CgTNF-1, as well as hemocyte apoptosis.
Machine learning predicts lymph node metastasis of poorly differentiated-type intramucosal gastric cancer
Authors: Zhou Cheng-Mao , Wang Ying , Ye Hao-Tian , Yan Shuping , Ji Muhuo , Liu Panmiao , Yang Jian-Jun
Published: January 2021

To construct a machine learning algorithm model of lymph node metastasis (LNM) in patients with poorly differentiated-type intramucosal gastric cancer. 1169 patients with postoperative gastric cancer were divided into a training group and a test group at a ratio of 7:3. The model for lymph node metastasis was established with python machine learning. The Gbdt algorithm in the machine learning results finds that number of resected nodes, lymphovascular invasion and tumor size are the primary 3 factors that account for the weight of LNM. Effect of the LNM model of PDC gastric cancer patients in the training group: Among the 7 algorithm models, the highest accuracy rate was that of GBDT (0.955); The AUC values for the 7 algorithms were, from high to low, XGB (0.881), RF (0.802), GBDT (0.798), LR (0.778), XGB + LR (0.739), RF + LR (0.691) and GBDT + LR (0.626). Results of the LNM model of PDC gastric cancer patients in test group : Among the 7 algorithmic models, XGB had the highest accuracy rate (0.952); Among the 7 algorithms, the AUC values, from high to low, were GBDT (0.788), RF (0.765), XGB (0.762), LR (0.750), RF + LR (0.678), GBDT + LR (0.650) and XGB + LR (0.619). Single machine learning algorithm can predict LNM in poorly differentiated-type intramucosal gastric cancer, but fusion algorithm can not improve the effect of machine learning in predicting LNM.
Comparison of multi echo T2 relaxation and steady state approaches for myelin imaging in the central nervous system
Authors: Dvorak Adam V. , Ljungberg Emil , Vavasour Irene M. , Lee Lisa Eunyoung , Abel Shawna , Li David K. B. , Traboulsee Anthony , MacKay Alex L. , Kolind Shannon H.
Published: January 2021

The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T2relaxation data to calculate the myelin water fraction (MWF). A fundamentally different approach, abbreviated “mcDESPOT”, uses a more efficient steady-state acquisition to generate an equivalent metric (fM). Although previous studies have demonstrated inherent instability and bias in the complex mcDESPOT analysis procedure, fMhas often been used as a surrogate for MWF. We produced and compared multivariate atlases of MWF and fMin healthy human brain and cervical spinal cord (available online) and compared their ability to detect multiple sclerosis pathology. A significant bias was found in all regions (p < 10–5), albeit reversed for spinal cord (fM-MWF =  − 3.4%) compared to brain (+ 6.2%). MWF and fMfollowed an approximately linear relationship for regions with MWF <  ~ 10%. For MWF >  ~ 10%, the relationship broke down and fMno longer increased in tandem with MWF. For multiple sclerosis patients, MWF and fMZ score maps showed overlapping areas of low Z score and similar trends between patients and brain regions, although those of fMgenerally had greater spatial extent and magnitude of severity. These results will guide future choice of myelin-sensitive quantitative MRI and improve interpretation of studies using either myelin imaging approach.
Galápagos upwelling driven by localized wind–front interactions
Authors: Forryan Alexander , Naveira Garabato Alberto C. , Vic Clément , Nurser A. J. George , Hearn Alexander R.
Published: January 2021

The Galápagos archipelago, rising from the eastern equatorial Pacific Ocean some 900 km off the South American mainland, hosts an iconic and globally significant biological hotspot. The islands are renowned for their unique wealth of endemic species, which inspired Charles Darwin’s theory of evolution and today underpins one of the largest UNESCO World Heritage Sites and Marine Reserves on Earth. The regional ecosystem is sustained by strongly seasonal oceanic upwelling events—upward surges of cool, nutrient-rich deep waters that fuel the growth of the phytoplankton upon which the entire ecosystem thrives. Yet despite its critical life-supporting role, the upwelling’s controlling factors remain undetermined. Here, we use a realistic model of the regional ocean circulation to show that the intensity of upwelling is governed by local northward winds, which generate vigorous submesoscale circulations at upper-ocean fronts to the west of the islands. These submesoscale flows drive upwelling of interior waters into the surface mixed layer. Our findings thus demonstrate that Galápagos upwelling is controlled by highly localized atmosphere–ocean interactions, and call for a focus on these processes in assessing and mitigating the regional ecosystem’s vulnerability to 21st-century climate change.