bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA Transfection-Induced Activation of Primary Human Monocytes and Macrophages: Dependence on Carrier System and Nucleotide Modification
Authors: Moradian Hanieh , Roch Toralf , Lendlein Andreas , Gossen Manfred 
Published: March 2020

AbstractMonocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.
Molecular sexing and preliminary assessment of population sex ratio of the endangered Malayan tapir (Tapirus indicus) in Peninsular Malaysia
Authors: Lim Qi Luan , Tan Yoeng Leh , Ng Wei Lun , Yong Christina Seok Yien , Ismail Ahmad , Rovie-Ryan Jeffrine J. , Rosli Norsyamimi , Annavi Geetha 
Published: March 2020

AbstractA molecular sexing method by polymerase chain reaction (PCR) amplification of a portion of the sex-determining region Y (SRY) and the zinc finger (ZF) gene, as well as six equine Y-chromosome-specific microsatellite markers, were tested in the Malayan tapir (Tapirus indicus). While the microsatellite markers did not yield any male-specific amplicons for sex-typing, the SRY/ZF marker system produced reliable molecular sexing results by accurately sex-typing 31 reference Malayan tapirs, using whole blood, dried blood spot (DBS), or tissue samples as materials for DNA extraction. The marker system was also tested on 16 faecal samples, and the results were in general consistent with the pre-determined sexes of the animals, despite some amplification failures. A preliminary estimation of wild Malayan tapir population sex ratio was estimated from the Wildlife Genomic Resource Bank (WGRB) database of the Malaysian Department of Wildlife and National Parks (PERHILITAN), zoos, and the Sungai Dusun Wildlife Conservation Centre (WCC), as well as from the results of molecular sexing 12 samples of unknown sex. The overall sex ratio favoured females, but the deviation from parity was statistically not significant when tested using the binomial test (p > 0.05), which may be due to reduced statistical power caused by small sample sizes.
High-Throughput Screening to Predict Chemical-Assay Interference
Authors: Borrel Alexandre , Huang Ruili , Sakamuru Srilatha , Xia Menghang , Simeonov Anton , Mansouri Kamel , Houck Keith A. , Judson Richard S. , Kleinstreuer Nicole C. 
Published: March 2020

AbstractThe U.S. federal consortium on toxicology in the 21st century (Tox21) produces quantitative, high-throughput screening (HTS) data on thousands of chemicals across a wide range of assays covering critical biological targets and cellular pathways. Many of these assays, and those used in other in vitro screening programs, rely on luciferase and fluorescence-based readouts that can be susceptible to signal interference by certain chemical structures resulting in false positive outcomes. Included in the Tox21 portfolio are assays specifically designed to measure interference in the form of luciferase inhibition and autofluorescence via multiple wavelengths (red, blue, and green) and under various conditions (cell-free and cell-based, two cell types). Out of 8,305 chemicals tested in the Tox21 interference assays, percent actives ranged from 0.5% (red autofluorescence) to 9.9% (luciferase inhibition). Self-organizing maps and hierarchical clustering were used to relate chemical structural clusters to interference activity profiles. Multiple machine learning algorithms were applied to predict assay interference based on molecular descriptors and chemical properties. The best performing predictive models (accuracies of ~80%) have been included in a web-based tool called InterPred that will allow users to predict the likelihood of assay interference for any new chemical structure and thus increase confidence in HTS data by decreasing false positive testing results.
A competent bidrug loaded water soluble chitosan derivative for the effective inhibition of breast cancer
Authors: E A K Nivethaa , S Baskar , Martin Catherine Ann , J Ramana Ramya , A Stephen , V Narayanan , B S Lakshmi , Frank-Kamenetskaya Olga V. , Radhakrishnan Subathra , S Narayana Kalkura 
Published: March 2020

AbstractDrug resistance and damage caused to the normal cells are the drawbacks which have limited the use of the existing effective anticancer drugs. Attainment of a steady and extended release by encapsulating dual drugs into biocompatible and biodegradable vehicles is the key to enable the use of these drugs for effective inhibition of cancer. In this study, carboxymethyl chitosan (CMCS), a proficient water-soluble derivative of chitosan has been synthesized using chemical route and used for the delivery of 5-Fluorouracil and doxorubicin individually as well as in combination. Carboxymethylation occuring at –NH2 and OH sites of chitosan, has been confirmed using FTIR. EDX and Fluorescence studies elucidate the encapsulation of 5-Fluorouracil and doxorubicin into CMCS. The capability of CMCS to release the drugs in a more sustained and prolonged manner is evident from the obtained release profiles. About 14.9 µg/ml is enough to cause 50% cell death by creating oxidative stress and effectuating DNA fragmentation. Amidst the existing reports, the uniqueness of this work lies in using this rare coalition of drugs for the suppression of breast cancer and in reducing the side effects of drugs by encapsulating them into CMCS, which is evidenced by the high hemocompatibilty of the samples.
Tuning electronic and optical properties of monolayer PdSe2 by introducing defects: first-principles calculations
Authors: Zhao X. W. , Yang Z. , Guo J. T. , Hu G. C. , Yue W. W. , Yuan X. B. , Ren J. F. 
Published: March 2020

AbstractBased on the density functional theory, the electronic and optical properties of pristine monolayer PdSe2 with Pd or Se vacancy-defect are investigated. Our results show that the Se defect is energetically more favorable than that of Pd defect. The band gap reduces, and some new midgap states appear after the Pd or Se defects are introduced. In terms of the optical properties, the prominent anisotropic characters are remained. The obvious new peaks of the dielectric constant appear after introducing defects. The light absorption in the visible energy range expands based on the appearance of the midgap states induced by the Pd or Se defects. The changes of the refractive index and reflectivity are similar with those of the dielectric constants and the light absorption. The energy loss spectrum of the PdSe2 with Pd or Se defects is obviously different, which can be used to identify different defects in PdSe2. These findings provide effective strategies to tune electronic and optical properties of monolayer PdSe2 by introducing defects.
A durable murine model of spleen transplantation with arterial and venous anastomoses
Authors: Figueiredo Jose-Luiz , Santa-Cruz Fernando , Lima-Filho José Luiz , Hilgendorf Ingo , Aikawa Masanori , Pittet Mikael J. , Nahrendorf Matthias , Weissleder Ralph , Swirski Filip K. , Robbins Clinton S. 
Published: March 2020

AbstractThe spleen is a large lymphoid organ located in the abdomen that filters blood and regulates the immune system. The extent of mobilization of splenic immune cells to peripheral tissues in health and disease, however, remains poorly understood. This is due, in large part, to a lack of in vivo, spleen-specific lineage tagging strategies. Here, we describe a detailed practical protocol of spleen transplantation and its evaluation for long-term graft survival. Unlike implantation of splenic morsels in the great omentum, our approach uses arterial and venous anastomoses which rapidly restores blood flow and facilitates long-term survival of the graft. The use of congenic mouse strains permits the use of immunofluorescence and flow cytometry-based methodologies to unambiguously track the migration of spleen-derived cells to peripheral tissues.
The Association of Diabetes with Knee Pain Severity and Distribution in People with Knee Osteoarthritis using Data from the Osteoarthritis Initiative
Authors: Alenazi Aqeel M. , Alshehri Mohammed M. , Alothman Shaima , Alqahtani Bader A. , Rucker Jason , Sharma Neena , Segal Neil A. , Bindawas Saad M. , Kluding Patricia M. 
Published: March 2020

AbstractLimited research has examined the association between diabetes mellitus (DM) and knee pain in people with osteoarthritis (OA). Therefore, this study aimed at examining the association between DM and knee pain severity, and to explore the association between DM and knee pain distribution (unilateral or bilateral versus no pain) in subjects with knee OA. This is a cross-sectional analysis of the baseline visit of individuals who were enrolled in the Osteoarthritis Initiative. Data of participants with knee OA were used for this analysis (n = 1319), and grouped into subjects with both knee OA and DM (n = 148) or knee OA only without DM (n = 1171). Pain severity was measured using a numeric rating scale from 0 to 10 over the past 7 and 30 days for each knee, and the more symptomatic knee with higher pain severity was chosen for analysis. DM was significantly associated with increased knee pain severity over 7 days (B 0.68; 95% CI 0.25–1.11) and over 30 days (B 0.59; 95% CI 0.17–1.01) after adjustments for all covariates, including age, gender, BMI, race, depression symptoms, composite OA score, use of pain medications, and knee injections. Multinomial regression showed that participants with knee OA and DM had 2.45 (95% CI 1.07–5.61) to 2.55 (95% CI 1.12–5.79) times higher likelihood of having unilateral and bilateral knee pain than those without DM and without knee pain. This study found that DM was associated with higher pain severity and unilateral and bilateral knee pain distribution.
Paclitaxel-induced peripheral neuropathy is caused by epidermal ROS and mitochondrial damage through conserved MMP-13 activation
Authors: Cirrincione Anthony M. , Pellegrini Adriana D. , Dominy Jessica R. , Benjamin Marisa E. , Utkina-Sosunova Irina , Lotti Francesco , Jergova Stanislava , Sagen Jacqueline , Rieger Sandra 
Published: March 2020

AbstractPaclitaxel induces peripheral neuropathy as a side effect of cancer treatment. The underlying causes are unclear, but epidermal, unmyelinated axons have been shown to be the first to degenerate. We previously utilized an in vivo zebrafish model to show that the epidermal matrix-metalloproteinase 13 (MMP-13) induces degeneration of unmyelinated axons, whereas pharmacological inhibition of MMP-13 prevented axon degeneration. However, the precise functions by which MMP-13 is regulated and affects axons remained elusive. In this study, we assessed mitochondrial damage and reactive oxygen species (ROS) formation as possible inducers of MMP-13, and we analyzed MMP-13-dependent damage. We show that the small ROS, H2O2, is increased in basal keratinocytes following treatment with paclitaxel. Cytoplasmic H2O2 appears to derive, at least in part, from mitochondrial damage, leading to upregulation of MMP-13, which in turn underlies increased epidermal extracellular matrix degradation. Intriguingly, also axonal mitochondria show signs of damage, such as fusion/fission defects and vacuolation, but axons do not show increased levels of H2O2. Since MMP-13 inhibition prevents axon degeneration but does not prevent mitochondrial vacuolation, we suggest that vacuolization occurs independently of axonal damage. Finally, we show that MMP-13 dysregulation also underlies paclitaxel-induced peripheral neuropathy in mammals, indicating that epidermal mitochondrial H2O2 and its effectors could be targeted for therapeutic interventions.
Indirect regulation of TFPI-2 expression by miR-494 in breast cancer cells
Authors: Andresen Marianne S. , Stavik Benedicte , Sletten Marit , Tinholt Mari , Sandset Per Morten , Iversen Nina , Skretting Grethe 
Published: March 2020

AbstractTFPI-2 has been shown to be involved in breast cancer pathogenesis by inhibiting extracellular matrix degradation, and low levels are associated with disease progression. As microRNA-494 (miR-494) protects against breast cancer progression, we investigated whether miR-494 is involved in the regulation of TFPI-2 in MCF-7 breast cancer cells. TFPI-2 mRNA and protein levels increased after transfection with miR-494 mimic, and TFPI-2 mRNA and miR-494 levels correlated positively in tumors from breast cancer patients. No specific binding sites for miR-494 in the 3′-untranslated region (UTR) of TFPI2 were identified; however, miR-494 was predicted in silico to bind 3′-UTR of the transcription factors AHR and ELF-1, which have potential binding sites in the TFPI2 promoter. ELF-1 mRNA was downregulated whereas AHR mRNA levels were upregulated after transfection with miR-494 mimic. Knockdown of ELF-1 and AHR increased and reduced TFPI-2 mRNA levels, respectively. Increased luciferase activity was seen when TFPI-2 promoter constructs containing the potential AHR or ELF-1 binding sites were co-transfected with miR-494 mimic. In conclusion, TFPI-2 mRNA levels were upregulated by miR-494 in MCF-7 breast cancer cells most likely by an indirect association where miR-494 targeted the transcription factors AHR and ELF-1. This association was supported in a breast cancer cohort.
Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide
Authors: Tateno Shumpei , Iida Midori , Fujii Satoshi , Suwa Tetsufumi , Katayama Miki , Tokuyama Haruka , Yamamoto Junichi , Ito Takumi , Sakamoto Satoshi , Handa Hiroshi , Yamaguchi Yuki 
Published: March 2020

AbstractPomalidomide, a derivative of thalidomide, is an effective treatment for multiple myeloma. The drug exerts its effects through CRBN, a component of the E3 ubiquitin ligase complex CRL4CRBN. To search for novel factors involved in the anti-cancer activity of pomalidomide, we performed a genome-wide shRNA library screen and identified 445 genes as those affecting pomalidomide sensitivity. Genes encoding components of the ubiquitin-proteasome pathway, such as subunits of the CRL4CRBN complex, the COP9 signalosome, and the 26S proteasome, were among the pomalidomide-affecting genes. Karyopherin beta 1 (KPNB1) was identified as a novel pomalidomide-affecting gene. KPNB1 was required for the nuclear import of CRBN and for the CRBN-directed, pomalidomide-dependent degradation of a clinically relevant substrate, the transcription factor Aiolos. By contrast, the cytoplasmic translation factor GSPT1 was degraded following treatment with the thalidomide derivative CC-885 only when CRBN was present in the cytoplasm, indicating that subcellular distribution of CRBN is critical for the efficacy of thalidomide-based medications.
The kinetics of inorganic phosphate excretion in the acidotic rabbit during intravenous phosphate loading: a pseudo-ruminant model
Authors: Walsh Patrick A. , O’Donovan Daniel J. 
Published: March 2020

AbstractThe rabbit is a much-used experimental animal in renal tubule physiology studies. Although a monogastric mammal, the rabbit is a known hindgut fermenter. That ruminant species excrete inorganic phosphate (Pi) mainly through the digestive system while non-ruminants eliminate surplus phosphate primarily through the renal system are acknowledged facts. To understand phosphate homeostasis in the acidotic rabbit, anaesthetized animals were infused with hydrochloric acid, after which they underwent intravenous phosphate loading. Biofluids were collected during the infusion process for analysis. Plasma Pi increased (7.9 ± 1.7 mmoles.Litre−1 (N = 5) vs 2.2 ± 0.4 mmoles.Litre−1 (N = 10) pre-infusion, (p < 0.001)), while urinary phosphate excretion was also enhanced (74.4 ± 15.3 from a control value of 4.7 ± 3 µmol.min−1 (N = 9), pre-infusion, p < 0.001)) over an 82.5 minute Pi loading period. However, the fractional excretion of Pi (FePi) only increased from 14.2 ± 5.4% to a maximum of 61.7 ± 19% (N = 5) over the infusion period. Furthermore, the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmPi/GFR) computed to 3.5 mmol.L−1, while a reading of 23.2 µmol.min−1.Kg.0.75 was obtained for the transport maximum for Pi (TmPi). The high reabsorptivity of the rabbit nephrons coupled with possibly a high secretory capacity of the salivary glands for Pi, may constitute a unique physiological mechanism that ensures the rabbit hindgut receives adequate phosphate to regulate caecal pH in favour of the resident metabolically - active microbiota. The handling of Pi by the rabbit is in keeping with the description of this animal as a monogastric, pseudo-ruminant herbivore.
Active inference under visuo-proprioceptive conflict: Simulation and empirical results
Authors: Limanowski Jakub , Friston Karl 
Published: March 2020

AbstractIt has been suggested that the brain controls hand movements via internal models that rely on visual and proprioceptive cues about the state of the hand. In active inference formulations of such models, the relative influence of each modality on action and perception is determined by how precise (reliable) it is expected to be. The ‘top-down’ affordance of expected precision to a particular sensory modality is associated with attention. Here, we asked whether increasing attention to (i.e., the precision of) vision or proprioception would enhance performance in a hand-target phase matching task, in which visual and proprioceptive cues about hand posture were incongruent. We show that in a simple simulated agent—based on predictive coding formulations of active inference—increasing the expected precision of vision or proprioception improved task performance (target matching with the seen or felt hand, respectively) under visuo-proprioceptive conflict. Moreover, we show that this formulation captured the behaviour and self-reported attentional allocation of human participants performing the same task in a virtual reality environment. Together, our results show that selective attention can balance the impact of (conflicting) visual and proprioceptive cues on action—rendering attention a key mechanism for a flexible body representation for action.
Lanthanum Prolongs Vase Life of Cut Tulip Flowers by Increasing Water Consumption and Concentrations of Sugars, Proteins and Chlorophylls
Authors: Gómez-Merino Fernando Carlos , Ramírez-Martínez Maribel , Castillo-González Ana María , Trejo-Téllez Libia Iris 
Published: March 2020

AbstractWe evaluated the effect of separately adding two sources of lanthanum (La), LaCl3 and La(NO3)3 × 6H2O at a concentration of 40 µM each, to the preservative solution of 15 cut tulip flower varieties. Ascorbic acid (AsA; 0.2 g/L) was used as a reference solution, while distilled water was used as control. The variety Laura Fygi recorded the longest vase life with 13 days. The highest water consumption per gram of stem fresh biomass weight (FBW) (2.5 mL) was observed in the variety Violet Beauty, whereas the lowest (1.098 mL) was recorded in Pink Impression. At the end of the vase life period, higher concentrations of total soluble sugars in petals and total soluble proteins in leaves were recorded in La-treated stems, compared to the AsA treatment and the control. Additionally, La(NO3)3 × 6H2O supply increased the fresh weight of stems in vase and prolonged vase life. Moreover, this treatment resulted in the highest foliar concentration of chlorophylls at the end of vase life. Therefore, La increases tulip flower vase life as a consequence of improving the concentrations of some vital biomolecules.
Estimating the photo-fission yield of the Trinity Test
Authors: Khan F. A. 
Published: March 2020

AbstractIn the Trinity Test, the energy was released not only from the fission of Pu-239 core but also from the fast neutron fission of tamper surrounding it. The high energy photons produced from the fissioning core can also induce fission in U-238 tamper. In this work, an effort has been made, for the first time, to develop an approach to investigate the possibility of photon-induced fission in U-238 tamper used in Trinity Test nuclear weapon. GEF nuclear reaction code, version 2018/1.1 is used to calculate the prompt γ-spectrum from the fast fission of Pu-239 core of the device. It is estimated that 14.3 ton (t) of TNT of the total 21 kT yield of the Trinity nuclear device is contributed by the photo-fission of U-238 tamper.
Transcriptomic analysis identifies novel genes and pathways for salt stress responses in Suaeda salsa leaves
Authors: Zhang Xuejie , Yao Yan , Li Xiaotong , Zhang Luoyan , Fan Shoujin 
Published: March 2020

AbstractSalinity is a critical abiotic stress, which significantly impacts the agricultural yield worldwide. Identification of the molecular mechanisms underlying the salt tolerance in euhalophyte Suaeda salsa is conducive to the development of salt-resistant crops. In the present study, high-throughput RNA sequencing was performed after S. salsa leaves were exposed to 300 mM NaCl for 7 days, and 7,753 unigenes were identified as differently expressed genes (DEGs) in S. salsa, including 3,638 increased and 4,115 decreased unigenes. Moreover, hundreds of pathways were predicted to participate in salt stress response in S. salsa by Gene Ontology (GO), MapMan and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, including ion transport and sequestration as well as photoprotection of photosystem (PS) II. The GO enrichment analysis indicated that genes related to ion transport, reactive oxygen species (ROS) scavenging and transcriptional factors were highly expressed upon NaCl treatment. The excessive Na+ and Cl− ions were supposed to be absorbed into the vacuole for ion sequestration and balance adjustment by potassium transporters (such as KEA3) with high expressions. Moreover, we predicted that mutiple candidate genes associated with photosynthesis (such as PSB33 and ABA4), ROS (such as TAU9 and PHI8) and transcriptional regulation (HB-7 and MYB78) pathways could mitigate salt stress-caused damage in S. salsa.