bluuebunny/crossref_metadata_2025 huggingface dataset:
Flumioxazin effects on soybean canopy formation and soil-borne pathogen presence
Authors: Priess Grant L , Norsworthy Jason K , Roberts Trenton L , Spurlock Terry N
Published: April 2020

Rapid crop canopy formation is important to reduce weed emergence and selection for herbicide resistance. Field experiments were conducted in 2017 and 2018 in Fayetteville, AR, to evaluate the impacts of PRE applications of flumioxazin on soybean injury, soybean density, canopy formation, and incidence of soil-borne pathogens. Flumioxazin was applied at 0, 70, and 105 g ai ha−1to predetermined flumioxazin-tolerant and -sensitive soybean varieties. Flumioxazin at 70 g ha−1injured the tolerant and sensitive varieties from 0% to 4% and 14% to 15%, respectively. When averaged over flumioxazin rates, density of the sensitive variety was only reduced in 2017 when activation of flumioxazin was delayed 7 d. Compared to the tolerant soybean variety, flumioxazin at 70 g ha−1delayed the sensitive variety from reaching 20%, 40%, 60%, and 80% groundcover by 15, 16, 11, and 5 d, respectively. No delay in canopy closure (95% groundcover) was observed with either variety. Consequently, no yield loss occurred for either variety following a flumioxazin application. Flumioxazin did not impact root colonization ofDidymella, Fusarium, Macrophomina, orRhizoctonia.Pythiumcolonization of the soybean stem was increased by flumioxazin in 2017, but not in 2018. Increased injury, delays in percent groundcover, and an increase inPythiumcolonization of soybean following a flumioxazin application may warrant the need for other soil-applied herbicides at soybean planting. Alternatively, soybean injury and delays in percent groundcover following flumioxazin applications can be mitigated through appropriate variety selection; however, comprehensive screening is needed to determine which varieties are most tolerant to flumioxazin.
Fatty acids of human milk – a review
Authors: Bobiński Rafał , Bobińska Jagna
Published: April 2020

Abstract. The composition of human milk is the result of the evolution of mammals over millions of years. Among the most important components of milk are fatty acids. Approximately 85% are saturated and monounsaturated fatty acids – the rest are polyunsaturated one. Their role is to provide energy and immunity and to serve as buildings blocks, as well as assisting the hormonal system and the metabolism of fats, carbohydrates and proteins. The structural differences between fatty acids determine their biodiversity and give them particular physiological importance. Correct development of the nervous system, retina and other structures depend on an adequate supply of both these fatty acids during intrauterine development and in the newborn and infant stages. The fats present in milk form milk fat globules – structures that do not appear in milk formula prepared using vegetable oils. Apart from the mother’s diet, other sources of fatty acids are endogenous biosynthesis in the mammary gland and the fat deposits from which the fatty acids are released. Evolution of the mother’s body has also created adaptive mechanisms that adjust the amount of fatty acids in milk to the state of health and needs of the child. These mechanisms go some way to creating a buffer with regard to dietary shortages experienced by pregnant/breastfeeding women, and optimalise the composition of milk fatty acids depending on the age of the pregnant woman, the birth weight of the infant and the efficiency of the placenta during pregnancy.
Multimodel Future Projections of the Regional Vegetation‐Climate System Over East Asia: Comparison Between Two Ensemble Approaches
Authors: Liu Weiguang , Wang Guiling , Yu Miao , Chen Haishan , Jiang Yelin
Published: April 2020

This study compares two ensemble methods, pseudo global warming (PGW) and multimodel ensemble (MME) mean in evaluating future vegetation‐climate changes and feedback over East Asia using a regional model driven with boundary conditions derived from historical and RCP8.5 runs of four global models. Over most of the domain, MME and PGW produce similar future climate changes, except for two regions: over Northeast Asia, MME projects less winter warming and less increase of summer precipitation than PGW, and over North China Plain, MME projects greater increase of summer precipitation than PGW. Both PGW and MME project greater leaf area index (LAI) and expansion of tree coverage at the expense of grass over most of the domain due to elevated CO2 concentration and climate change. However, over Northeast China, PGW and three ensemble members project an increase of temperate trees at the expense of boreal trees or grass and a decrease of LAI, and one ensemble member projects a loss of forest to grassland. Both PGW and MME identify two hotspots of vegetation‐temperature feedback, including the Northeast China where the projected loss of boreal evergreen forest causes a significant winter cooling (which offsets a major portion of greenhouse gas‐induced warming) and the Tibetan Plateau where the projected LAI increase and vegetation expansion lead to a significant winter warming through reduced albedo. The vegetation feedback impact on precipitation is similar between the two approaches, including a significant wet signal in a belt between 30°N and 40°N during winter and over the Tibetan Plateau during summer.
Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrin α2β1
Authors: Huang Wenjing , Yan Yanyan , Liu Yun , Lin Minting , Ma Jinxiang , Zhang Wei , Dai Jianwei , Li Jiajun , Guo Qiaoru , Chen Hubiao , Makabel Bolat , Liu Hong , Su Chaoyue , Bi Hong , Zhang Jianye
Published: April 2020

Exosomes play critical roles in regulating various physiological and pathological processes, including immune stimulation, immune suppression, cardiovascular diseases, and cancers. Recent studies show that exosomes that transport specific microRNAs (miRNAs) are involved in tumor development. However, the molecular mechanism by which tumor invasion and migration are regulated by exosomes from non-small cell lung cancer (NSCLC) is not well understood. Here, we show that exosomes shuttling low levels of miR-34c-3p are involved in NSCLC progression. Our results showed that exosomes derived from NSCLC cells carrying low levels of miR-34c-3p could be transported into the cytoplasm of NSCLC cells and accelerate NSCLC invasion and migration by upregulating integrin α2β1. A luciferase assay revealed that integrin α2β1 was the direct target of miR-34c-3p, and overexpression of integrin α2β1 could promote the invasion and migration of NSCLC cells. The analysis of exosomes derived from clinical serum samples indicated that the expression of miR-34c-3p was significantly downregulated in exosomes from NSCLC patients compared with that of normal controls. A549-derived exosomes promoted NSCLC cells lung metastases in vivo. Exosomes shuttling low levels of miR-34c-3p were associated with the progression of NSCLC in vitro and in vivo. Our data demonstrate that exosomes shuttling low levels of miR-34c-3p can accelerate the invasion and migration of NSCLC by upregulating integrin α2β1. MiR-34c-3p can be a diagnostic and prognostic marker for NSCLC. High expression of integrin α2β1 is positively related to the migration and metastasis of NSCLC cells.
Facilitating translational science in anxiety disorders by adjusting extinction training in the laboratory to exposure-based therapy procedures
Authors: Hollandt Maike , Wroblewski Adrian , Yang Yunbo , Ridderbusch Isabelle C. , Kircher Tilo , Hamm Alfons O. , Straube Benjamin , Richter Jan
Published: April 2020

Extinction learning is suggested to be a central mechanism during exposure-based cognitive behavioral psychotherapy. A positive association between the patients’ pretreatment extinction learning performance and treatment outcome would corroborate the hypothesis. Indeed, there is first correlational evidence between reduced extinction learning and therapy efficacy. However, the results of these association studies may be hampered by extinction-training protocols that do not match treatment procedures. Therefore, we developed an extinction-training protocol highly tailored to the procedure of exposure therapy and tested it in two samples of 46 subjects in total. By using instructed fear acquisition training, including a consolidation period overnight, we wanted to ensure that the conditioned fear response was well established prior to extinction training, which is the case in patients with anxiety disorders prior to treatment. Moreover, the extinction learning process was analyzed on multiple response levels, comprising unconditioned stimulus (US) expectancy ratings, autonomic responses, defensive brain stem reflexes, and neural activation using functional magnetic resonance imaging. Using this protocol, we found robust fear conditioning and slow-speed extinction learning. We also observed within-group heterogeneity in extinction learning, albeit a stable fear response at the beginning of the extinction training. Finally, we found discordance between different response systems, suggesting that multiple processes are involved in extinction learning. The paradigm presented here might help to ameliorate the association between extinction learning performance assessed in the laboratory and therapy outcomes and thus facilitate translational science in anxiety disorders.
Engineering nanomedicines through boosting immunogenic cell death for improved cancer immunotherapy
Authors: Gao Jing , Wang Wei-qi , Pei Qing , Lord Megan S. , Yu Hai-jun
Published: April 2020

Current cancer immunotherapy has limited response rates in a large variety of solid tumors partly due to the low immunogenicity of the tumor cells and the immunosuppressive tumor microenvironment (ITM). A number of clinical cancer treatment modalities, including radiotherapy, chemotherapy, photothermal and photodynamic therapy, have been shown to elicit immunogenicity by inducing immunogenic cell death (ICD). However, ICD-based immunotherapy is restricted by the ITM limiting its efficacy in eliciting a long-term antitumor immune response, and by severe systemic toxicity. To address these challenges, nanomedicine-based drug delivery strategies have been exploited for improving cancer immunotherapy by boosting ICD of the tumor cells. Nanosized drug delivery systems are promising for increasing drug accumulation at the tumor site and codelivering ICD inducers and immune inhibitors to simultaneously elicit the immune response and relieve the ITM. This review highlights the recent advances in nanomedicine-based immunotherapy utilizing ICD-based approaches. A perspective on the clinical translation of nanomedicine-based cancer immunotherapy is also provided.
BCL-w: apoptotic and non-apoptotic role in health and disease
Authors: Hartman Mariusz L. , Czyz Malgorzata
Published: April 2020

The BCL-2 family of proteins integrates signals that trigger either cell survival or apoptosis. The balance between pro-survival and pro-apoptotic proteins is important for tissue development and homeostasis, while impaired apoptosis contributes to several pathologies and can be a barrier against effective treatment. BCL-w is an anti-apoptotic protein that shares a sequence similarity with BCL-XL, and exhibits a high conformational flexibility. BCL-w level is controlled by a number of signaling pathways, and the repertoire of transcriptional regulators largely depends on the cellular and developmental context. As only a few disease-relevant genetic alterations of BCL2L2 have been identified, increased levels of BCL-w might be a consequence of abnormal activation of signaling cascades involved in the regulation of BCL-w expression. In addition, BCL-w transcript is a target of a plethora of miRNAs. Besides its originally recognized pro-survival function during spermatogenesis, BCL-w has been envisaged in different types of normal and diseased cells as an anti-apoptotic protein. BCL-w contributes to survival of senescent and drug-resistant cells. Its non-apoptotic role in the promotion of cell migration and invasion has also been elucidated. Growing evidence indicates that a high BCL-w level can be therapeutically relevant in neurodegenerative disorders, neuron dysfunctions and after small intestinal resection, whereas BCL-w inhibition can be beneficial for cancer patients. Although several drugs and natural compounds can bi-directionally affect BCL-w level, agents that selectively target BCL-w are not yet available. This review discusses current knowledge on the role of BCL-w in health, non-cancerous diseases and cancer.
Mismatched and wobble base pairs govern primary microRNA processing by human Microprocessor
Authors: Li Shaohua , Nguyen Trung Duc , Nguyen Thuy Linh , Nguyen Tuan Anh
Published: April 2020

MicroRNAs (miRNAs) are small RNAs that regulate gene expression. miRNAs are produced from primary miRNAs (pri-miRNAs), which are cleaved by Microprocessor. Microprocessor, therefore, plays a crucial role in determining the efficiency and precision of miRNA production, and thus the function of the final miRNA product. Here, we conducted high-throughput enzymatic assays to investigate the catalytic mechanism of Microprocessor cleaving randomized pri-miRNAs. We identified multiple mismatches and wobble base pairs in the upper stem of pri-miRNAs, which influence the efficiency and accuracy of their processing. The existence of these RNA elements helps to explain the alternative cleavage of Microprocessor for some human pri-miRNAs. We also demonstrated that miRNA biogenesis can be altered via modification of the RNA elements by RNA-editing events or single nucleotide polymorphisms (SNPs). These findings improve our understanding of pri-miRNA processing mechanisms and provide a foundation for interpreting differential miRNA expression due to RNA modifications and SNPs.
Solvent tuning of photochemistry upon excited-state symmetry breaking
Authors: Dereka Bogdan , Svechkarev Denis , Rosspeintner Arnulf , Aster Alexander , Lunzer Markus , Liska Robert , Mohs Aaron M. , Vauthey Eric
Published: April 2020

The nature of the electronic excited state of many symmetric multibranched donor–acceptor molecules varies from delocalized/multipolar to localized/dipolar depending on the environment. Solvent-driven localization breaks the symmetry and traps the exciton in one branch. Using a combination of ultrafast spectroscopies, we investigate how such excited-state symmetry breaking affects the photochemical reactivity of quadrupolar and octupolar A–(π-D)2,3 molecules with photoisomerizable A–π–D branches. Excited-state symmetry breaking is identified by monitoring several spectroscopic signatures of the multipolar delocalized exciton, including the S2 ← S1 electronic transition, whose energy reflects interbranch coupling. It occurs in all but nonpolar solvents. In polar media, it is rapidly followed by an alkyne–allene isomerization of the excited branch. In nonpolar solvents, slow and reversible isomerization corresponding to chemically-driven symmetry breaking, is observed. These findings reveal that the photoreactivity of large conjugated molecules can be tuned by controlling the localization of the excitation.
Structural basis for active single and double ring complexes in human mitochondrial Hsp60-Hsp10 chaperonin
Authors: Gomez-Llorente Yacob , Jebara Fady , Patra Malay , Malik Radhika , Nisemblat Shahar , Chomsky-Hecht Orna , Parnas Avital , Azem Abdussalam , Hirsch Joel A. , Ubarretxena-Belandia Iban
Published: April 2020

mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins without the negative ATP binding inter-ring cooperativity of GroEL-GroES. Here we report the crystal structure of an ATP (ADP:BeF3-bound) ground-state mimic double-ring mHsp6014-(mHsp107)2 football complex, and the cryo-EM structures of the ADP-bound successor mHsp6014-(mHsp107)2 complex, and a single-ring mHsp607-mHsp107 half-football. The structures explain the nucleotide dependence of mHsp60 ring formation, and reveal an inter-ring nucleotide symmetry consistent with the absence of negative cooperativity. In the ground-state a two-fold symmetric H-bond and a salt bridge stitch the double-rings together, whereas only the H-bond remains as the equatorial gap increases in an ADP football poised to split into half-footballs. Refolding assays demonstrate obligate single- and double-ring mHsp60 variants are active, and complementation analysis in bacteria shows the single-ring variant is as efficient as wild-type mHsp60. Our work provides a structural basis for active single- and double-ring complexes coexisting in the mHsp60-mHsp10 chaperonin reaction cycle.
Author Correction: A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2
Authors: Tamura Ryota , Fujioka Masato , Morimoto Yukina , Ohara Kentaro , Kosugi Kenzo , Oishi Yumiko , Sato Mizuto , Ueda Ryo , Fujiwara Hirokazu , Hikichi Tetsuro , Noji Shinobu , Oishi Naoki , Ogawa Kaoru , Kawakami Yutaka , Ohira Takayuki , Yoshida Kazunari , Toda Masahiro
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
FiCli, the Fish and Climate Change Database, informs climate adaptation and management for freshwater fishes
Authors: Krabbenhoft Trevor J. , Myers Bonnie J. E. , Wong Jesse P. , Chu Cindy , Tingley Ralph W. , Falke Jeffrey A. , Kwak Thomas J. , Paukert Craig P. , Lynch Abigail J.
Published: April 2020

Inland fishes provide important ecosystem services to communities worldwide and are especially vulnerable to the impacts of climate change. Fish respond to climate change in diverse and nuanced ways, which creates challenges for practitioners of fish conservation, climate change adaptation, and management. Although climate change is known to affect fish globally, a comprehensive online, public database of how climate change has impacted inland fishes worldwide and adaptation or management practices that may address these impacts does not exist. We conducted an extensive, systematic primary literature review to identify peer-reviewed journal publications describing projected and documented examples of climate change impacts on inland fishes. From this standardized Fish and Climate Change database, FiCli (pronounced fick-lee), researchers and managers can query fish families, species, response types, or geographic locations to obtain summary information on inland fish responses to climate change and recommended management actions. The FiCli database is updatable and provides access to comprehensive published information to inform inland fish conservation and adaptation planning in a changing climate.
Higher order photoprotection mutants reveal the importance of ΔpH-dependent photosynthesis-control in preventing light induced damage to both photosystem II and photosystem I
Authors: Barbato Roberto , Tadini Luca , Cannata Romina , Peracchio Carlotta , Jeran Nicolaj , Alboresi Alessandro , Morosinotto Tomas , Bajwa Azfar Ali , Paakkarinen Virpi , Suorsa Marjaana , Aro Eva-Mari , Pesaresi Paolo
Published: April 2020

Although light is essential for photosynthesis, when in excess, it may damage the photosynthetic apparatus, leading to a phenomenon known as photoinhibition. Photoinhibition was thought as a light-induced damage to photosystem II; however, it is now clear that even photosystem I may become very vulnerable to light. One main characteristic of light induced damage to photosystem II (PSII) is the increased turnover of the reaction center protein, D1: when rate of degradation exceeds the rate of synthesis, loss of PSII activity is observed. With respect to photosystem I (PSI), an excess of electrons, instead of an excess of light, may be very dangerous. Plants possess a number of mechanisms able to prevent, or limit, such damages by safe thermal dissipation of light energy (non-photochemical quenching, NPQ), slowing-down of electron transfer through the intersystem transport chain (photosynthesis-control, PSC) in co-operation with the Proton Gradient Regulation (PGR) proteins, PGR5 and PGRL1, collectively called as short-term photoprotection mechanisms, and the redistribution of light between photosystems, called state transitions (responsible of fluorescence quenching at PSII, qT), is superimposed to these short term photoprotective mechanisms. In this manuscript we have generated a number of higher order mutants by crossing genotypes carrying defects in each of the short-term photoprotection mechanisms, with the final aim to obtain a direct comparison of their role and efficiency in photoprotection. We found that mutants carrying a defect in the ΔpH-dependent photosynthesis-control are characterized by photoinhibition of both photosystems, irrespectively of whether PSBS-dependent NPQ or state transitions defects were present or not in the same individual, demonstrating the primary role of PSC in photoprotection. Moreover, mutants with a limited capability to develop a strong PSBS-dependent NPQ, were characterized by a high turnover of the D1 protein and high values of Y(NO), which might reflect energy quenching processes occurring within the PSII reaction center.
Clinical aspects of mCRPC management in patients treated with radium-223
Authors: Rizzini Elisa Lodi , Dionisi Valeria , Ghedini Pietro , Morganti Alessio Giuseppe , Fanti Stefano , Monari Fabio
Published: April 2020

Bone is the most common site of metastasis in metastatic castration-resistant prostate cancer (mCRPC), which is associated with pain and skeletal events. Radium-223 dichloride (Xofigo) is an alpha-emitting radioactive isotope that can specifically target bone lesions. Herein, we report the results of a retrospective analysis that documents our experience in the use of radium-223. Data from 63 patients (pts) with mCRPC who underwent radium-223 treatment from December 2015 to September 2017 were collected. Radium-223 (55 kBq/kg) was administered every 4 weeks for up to 6 cycles. The primary endpoint was OS. Radium-223 was administered as first line therapy in 11 pts, as second line in 19 pts, as third line in 16 pts and in successive lines in 17 pts; 42 pts out of 63 (67%) completed all six cycles. Within one month after the end of 6 cycles of radium-223, 15 pts out of 42 (35.7%) had achieved PR, 11 pts out of 42 (26.2%) had SD and 14 pts out of 42 (33.3%) had PD. Levels of pain decreased with progressive cycles of radium-223. After a minimum follow-up of 2 months and a maximum of 43 months, median OS was 15 months and median PFS was 8 months. The most frequent radium-223 related toxicity was low grade haematologic toxicity, predominantly G1-G2, that occurred halfway through treatment in about 75% of pts. The favourable results reported herein confirm that radium-223 can be considered well tolerated and effective in mCRPC, and is associated with significant decreases in pain.
Dysregulated EGFR pathway in serum in early-stage breast cancer patients: A case control study
Authors: Kjær Ina Mathilde , Olsen Dorte Aalund , Brandslund Ivan , Bechmann Troels , Jakobsen Erik Hugger , Bogh Søren Bie , Madsen Jonna Skov
Published: April 2020

The epidermal growth factor receptor (EGFR) and its ligands are involved in cancer pathogenesis and they might serve as circulating biomarkers. The current study aims to investigate if abnormal pre-treatment serum levels of EGFR and EGFR ligands are present in women with early-stage breast cancer and if up- or downregulation of EGFR and EGFR ligands occur in defined patient subgroups. Pre-treatment serum samples were obtained from 311 women with newly diagnosed early-stage breast cancer and from 419 healthy women and analysed for EGFR and the ligands: Epidermal growth factor (EGF), heparin-binding epidermal growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), and transforming growth factor α (TGF-α). Previously, age-dependent 95% reference intervals for EGFR and the EGFR ligands have been established based on the healthy women population. S-EGFR, S-EGF, S-HBEGF, S-AREG, and S-TGFα were all significantly different in women with breast cancer compared to healthy women (p < 0.05). Elevated S-EGFR, according to the reference intervals, was present in 11.3% of breast cancer patients, whereas decreased S-EGF was found in 11.6%. Elevated S-EGFR was associated with estrogen receptor positivity of tumor (ER+) and a subgroup of ER + breast cancer patients showed markedly elevated S-EGFR (>120 ng/mL).
gammaBOriS: Identification and Taxonomic Classification of Origins of Replication in Gammaproteobacteria using Motif-based Machine Learning
Authors: Sperlea Theodor , Muth Lea , Martin Roman , Weigel Christoph , Waldminghaus Torsten , Heider Dominik
Published: April 2020

The biology of bacterial cells is, in general, based on information encoded on circular chromosomes. Regulation of chromosome replication is an essential process that mostly takes place at the origin of replication (oriC), a locus unique per chromosome. Identification of high numbers oforiCis a prerequisite for systematic studies that could lead to insights intooriCfunctioning as well as the identification of novel drug targets for antibiotic development. Current methods for identifyingoriCsequences rely on chromosome-wide nucleotide disparities and are therefore limited to fully sequenced genomes, leaving a large number of genomic fragments unstudied. Here, we present gammaBOriS (GammaproteobacterialoriCSearcher), which identifiesoriCsequences on gammaproteobacterial chromosomal fragments. It does so by employing motif-based machine learning methods. Using gammaBOriS, we created BOriS DB, which currently contains 25,827 gammaproteobacterialoriCsequences from 1,217 species, thus making it the largest available database fororiCsequences to date. Furthermore, we present gammaBOriTax, a machine-learning based approach for taxonomic classification oforiCsequences, which was trained on the sequences in BOriS DB. Finally, we extracted the motifs relevant for identification and classification decisions of the models. Our results suggest that machine learning sequence classification approaches can offer great support in functional motif identification.
MG132 exerts anti-viral activity against HSV-1 by overcoming virus-mediated suppression of the ERK signaling pathway
Authors: Ishimaru Hanako , Hosokawa Kohei , Sugimoto Atsuko , Tanaka Riho , Watanabe Tadashi , Fujimuro Masahiro
Published: April 2020

Herpes simplex virus 1 (HSV-1) causes a number of clinical manifestations including cold sores, keratitis, meningitis and encephalitis. Although current drugs are available to treat HSV-1 infection, they can cause side effects such as nephrotoxicity. Moreover, owing to the emergence of drug-resistant HSV-1 strains, new anti-HSV-1 compounds are needed. Because many viruses exploit cellular host proteases and encode their own viral proteases for survival, we investigated the inhibitory effects of a panel of protease inhibitors (TLCK, TPCK, E64, bortezomib, or MG132) on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection suppressed c-Raf-MEK1/2-ERK1/2-p90RSK signaling in host cells, which facilitated viral replication. The mechanism by which HSV-1 inhibited ERK signaling was mediated through the polyubiquitination and proteasomal degradation of Ras-guanine nucleotide-releasing factor 2 (Ras-GRF2). Importantly, the proteasome inhibitor MG132 inhibited HSV-1 replication by reversing ERK suppression in infected cells, inhibiting lytic genes (ICP5, ICP27 and UL42) expression, and overcoming the downregulation of Ras-GRF2. These results indicate that the suppression of ERK signaling via proteasomal degradation of Ras-GRF2 is necessary for HSV-1 infection and replication. Given that ERK activation by MG132 exhibits anti-HSV-1 activity, these results suggest that the proteasome inhibitor could serve as a novel therapeutic agent against HSV-1 infection.
Cadmium and Mercury phytostabilization from soil using Miscanthus × giganteus
Authors: Zgorelec Zeljka , Bilandzija Nikola , Knez Kristina , Galic Marija , Zuzul Silva
Published: April 2020

The determination of the effects of cadmium and mercury on the growth, biomass productivity and phytoremediation potential of Miscanthus × giganteus (MxG) grown on contaminated soil was the main aim of this paper. The use of bioenergy plants as an innovative strategy in phytotechnology gives additional benefits, including mitigation and adaptation to climate change, and soil remediation without affecting soil fertility. An experiment was set up as a randomized complete block design with the treatments varied in concentrations of Cd (0, 10 and 100 mg kg−1 soil) and Hg (0, 2 and 20 mg kg−1 soil) added to the soil. Three vegetative years were studied. Yield values ranged from 6.3–15.5 tDM ha−1, cadmium concentration in plants varied from 45–6758 µg kg−1 and Hg varied from 8.7–108.9 µg kg−1. Values between treatments and years were significantly different. MxG can accumulate and remove very modest amount (up to 293.8 µg Cd and 4.7 µg Hg) per pot per year in aboveground biomass. Based on this data it can be concluded that MxG, as a valuable energy crop, is a potential candidate for the phytostabilization and biomass production on soils contaminated with Cd and Hg moderately.
Insight on thermal stability of magnetite magnetosomes: implications for the fossil record and biotechnology
Authors: Cypriano Jefferson , Bahri Mounib , Dembelé Kassiogé , Baaziz Walid , Leão Pedro , Bazylinski Dennis A. , Abreu Fernanda , Ersen Ovidiu , Farina Marcos , Werckmann Jacques
Published: April 2020

Magnetosomes are intracellular magnetic nanocrystals composed of magnetite (Fe3O4) or greigite (Fe3S4), enveloped by a lipid bilayer membrane, produced by magnetotactic bacteria. Because of the stability of these structures in certain environments after cell death and lysis, magnetosome magnetite crystals contribute to the magnetization of sediments as well as providing a fossil record of ancient microbial ecosystems. The persistence or changes of the chemical and magnetic features of magnetosomes under certain conditions in different environments are important factors in biotechnology and paleomagnetism. Here we evaluated the thermal stability of magnetosomes in a temperature range between 150 and 500 °C subjected to oxidizing conditions by usingin situscanning transmission electron microscopy. Results showed that magnetosomes are stable and structurally and chemically unaffected at temperatures up to 300 °C. Interestingly, the membrane of magnetosomes was still observable after heating the samples to 300 °C. When heated between 300 °C and 500 °C cavity formation in the crystals was observed most probably associated to the partial transformation of magnetite into maghemite due to the Kirkendall effect at the nanoscale. This study provides some insight into the stability of magnetosomes in specific environments over geological periods and offers novel tools to investigate biogenic nanomaterials.
Environmental DNA survey captures patterns of fish and invertebrate diversity across a tropical seascape
Authors: Nguyen Bryan N. , Shen Elaine W. , Seemann Janina , Correa Adrienne M. S. , O’Donnell James L. , Altieri Andrew H. , Knowlton Nancy , Crandall Keith A. , Egan Scott P. , McMillan W. Owen , Leray Matthieu
Published: April 2020

Accurate, rapid, and comprehensive biodiversity assessments are critical for investigating ecological processes and supporting conservation efforts. Environmental DNA (eDNA) surveys show promise as a way to effectively characterize fine-scale patterns of community composition. We tested whether a single PCR survey of eDNA in seawater using a broad metazoan primer could identify differences in community composition between five adjacent habitats at 19 sites across a tropical Caribbean bay in Panama. We paired this effort with visual fish surveys to compare methods for a conspicuous taxonomic group. eDNA revealed a tremendous diversity of animals (8,586 operational taxonomic units), including many small taxa that would be undetected in traditional in situ surveys. Fish comprised only 0.07% of the taxa detected by a broad COI primer, yet included 43 species not observed in the visual survey. eDNA revealed significant differences in fish and invertebrate community composition across adjacent habitats and areas of the bay driven in part by taxa known to be habitat-specialists or tolerant to wave action. Our results demonstrate the ability of broad eDNA surveys to identify biodiversity patterns in the ocean.
Exploring phase contrast imaging with a laser-based Kα x-ray source up to relativistic laser intensity
Authors: Gambari M. , Clady R. , Stolidi A. , Utéza O. , Sentis M. , Ferré A.
Published: April 2020

This study explores the ability of a hard Kα x-ray source (17.48 keV) produced by a 10 TW class laser system operated at high temporal contrast ratio and high repetition rate for phase contrast imaging. For demonstration, a parametric study based on a known object (PET films) shows clear evidence of feasibility of phase contrast imaging over a large range of laser intensity on target (from ~1017 W/cm2 to 7.0 × 1018 W/cm2). To highlight this result, a comparison of raw phase contrast and retrieved phase images of a biological object (a wasp) is done at different laser intensities below the relativistic intensity regime and up to 1.3 × 1019 W/cm2. This brings out attractive imaging strategies by selecting suitable laser intensity for optimizing either high spatial resolution and high quality of image or short acquisition time.
Tracking respiratory mechanics around natural breathing rates via variable ventilation
Authors: Bou Jawde Samer , Walkey Allan J. , Majumdar Arnab , O’Connor George T. , Smith Bradford J. , Bates Jason H. T. , Lutchen Kenneth R. , Suki Béla
Published: April 2020

Measuring respiratory resistance and elastance as a function of time, tidal volume, respiratory rate, and positive end-expiratory pressure can guide mechanical ventilation. However, current measurement techniques are limited since they are assessed intermittently at non-physiological frequencies or involve specialized equipment. To this end, we introduce ZVV, a practical approach to continuously track resistance and elastance during Variable Ventilation (VV), in which frequency and tidal volume vary from breath-to-breath. ZVV segments airway pressure and flow recordings into individual breaths, calculates resistance and elastance for each breath, bins them according to frequency or tidal volume and plots the results against bin means. ZVV’s feasibility was assessed clinically in five human patients with acute lung injury, experimentally in five mice ventilated before and after lavage injury, and computationally using a viscoelastic respiratory model. ZVV provided continuous measurements in both settings, while the computational study revealed <2% estimation errors. Our findings support ZVV as a feasible technique to assess respiratory mechanics under physiological conditions. Additionally, in humans, ZVV detected a decrease in resistance and elastance with time by 12.8% and 6.2%, respectively, suggesting that VV can improve lung recruitment in some patients and can therefore potentially serve both as a dual diagnostic and therapeutic tool.
Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells
Authors: Herráez-Aguilar Diego , Madrazo Elena , López-Menéndez Horacio , Ramírez Manuel , Monroy Francisco , Redondo-Muñoz Javier
Published: April 2020

The nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis. By using multiple particle tracking (MPT) technique on chromatin granules, we designed a SURF (Speeded Up Robust Features)-based algorithm to study the mechanical properties of isolated nuclei and in living cells. We have determined the apparent shear stiffness, viscosity and optical density of the nucleus, and how the chromatin structure influences on these biophysical values. Moreover, we used our MPT-SURF analysis to study the apparent mechanical properties of isolated nuclei from patients of acute lymphoblastic leukemia. We found that leukemia cells exhibited mechanical differences compared to normal lymphocytes. Interestingly, isolated nuclei from high-risk leukemia cells showed increased viscosity than their counterparts from normal lymphocytes, whilst nuclei from relapsed-patient's cells presented higher density than those from normal lymphocytes or standard- and high-risk leukemia cells. Taken together, here we presented how MPT-SURF analysis of nuclear chromatin granules defines nuclear mechanical phenotypic features, which might be clinically relevant.
Drought stress modify cuticle of tender tea leaf and mature leaf for transpiration barrier enhancement through common and distinct modes
Authors: Chen Mingjie , Zhu Xiaofang , Zhang Yi , Du Zhenghua , Chen Xiaobing , Kong Xiangrui , Sun Weijiang , Chen Changsong
Published: April 2020

Cuticle is the major transpiration barrier that restricts non-stomatal water loss and is closely associated with plant drought tolerance. Although multiple efforts have been made, it remains controversial what factors shape up the cuticular transpiration barrier. Previously, we found that the cuticle from the tender tea leaf was mainly constituted by very-long-chain-fatty-acids and their derivatives while alicyclic compounds dominate the mature tea leaf cuticle. The presence of two contrasting cuticle within same branch offered a unique system to investigate this question. In this study, tea seedlings were subjected to water deprivation treatment, cuticle structures and wax compositions from the tender leaf and the mature leaf were extensively measured and compared. We found that cuticle wax coverage, thickness, and osmiophilicity were commonly increased from both leaves. New waxes species were specifically induced by drought; the composition of existing waxes was remodeled; the chain length distributions of alkanes, esters, glycols, and terpenoids were altered in complex manners. Drought treatment significantly reduced leaf water loss rates. Wax biosynthesis-related gene expression analysis revealed dynamic expression patterns dependent on leaf maturity and the severity of drought. These data suggested that drought stress-induced structural and compositional cuticular modifications improve cuticle water barrier property. In addition, we demonstrated that cuticle from the tender leaf and the mature leaf were modified through both common and distinct modes.
Modulation in phase and frequency of neural oscillations during epileptiform activity induced by neonatal Zika virus infection in mice
Authors: Pinheiro Daniel J. L. L. , Oliveira Leandro F. , Souza Isis N. O. , Brogin João A. Ferres , Bueno Douglas D. , Miranda Iranaia Assunção , Da Poian Andrea T. , Ferreira Sergio T. , Figueiredo Claudia P. , Clarke Julia R. , Cavalheiro Esper A. , Faber Jean
Published: April 2020

Modulation of brain activity is one of the main mechanisms capable of demonstrating the synchronization dynamics of neural oscillations. In epilepsy, modulation is a key concept since seizures essentially result from neural hypersynchronization and hyperexcitability. In this study, we have introduced a time-dependent index based on the Kullback-Leibler divergence to quantify the effects of phase and frequency modulations of neural oscillations in neonatal mice exhibiting epileptiform activity induced by Zika virus (ZIKV) infection. Through this index, we demonstrate that fast oscillations (gamma and beta 2) are the more susceptible modulated rhythms in terms of phase, during seizures, whereas slow waves (delta and theta) mainly undergo changes in frequency. The index also allowed detection of specific patterns associated with the interdependent modulation of phase and frequency in neural activity. Furthermore, by comparing ZIKV modulations with the general computational model Epileptors, we verify different signatures related to the brain rhythms modulation in phase and frequency. These findings instigate new studies on the effects of ZIKV infection on neuronal networks from electrophysiological activities, and how different mechanisms can trigger epilepsy.
Risk of metachronous gastric neoplasm occurrence during intermediate-term follow-up period after endoscopic submucosal dissection for gastric dysplasia
Authors: Kim Young-Il , Park Jae Yong , Kim Beom Jin , Hwang Hye Won , Hong Soon Auck , Kim Jae Gyu
Published: April 2020

After endoscopic resection (ER) of gastric dysplasia, metachronous gastric neoplasm (MGN) appears to have an incidence rate similar to that detected after ER of early gastric cancer (EGC). We investigated whether the risk of MGN after ER for gastric dysplasia is different between patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Between March 2011 and December 2016, 198 patients with LGD (LGD group) and 46 patients with HGD (HGD group) who underwent ER were included in the study. During a median follow-up of 2.5 years, MGNs developed in 21 patients (10.6%) in the LGD group and in 6 patients (13.0%) in the HGD group. Hazard ratios (HRs) for MGNs (HR, 1.45; P = 0.425) and for metachronous HGD or gastric cancer (HR, 2.41; P = 0.214) in the HGD group were not different than those of the LGD group. However, considering patients without Helicobacter pylori infection, those in the HGD group had a significantly increased risk of metachronous HGD or gastric cancer compared to those in the LGD group (HR in HGD-group, 5.23; P = 0.044). These results indicate that meticulous surveillance endoscopy is needed to detect MGNs after ER of gastric dysplasia, especially in patients with HGD, including those without H. pylori infection.
Refractory plasmonics enabling 20% efficient lead-free perovskite solar cells
Authors: Mohsen Ahmed A. , Zahran Mohamed , Habib S. E. D. , Allam Nageh K.
Published: April 2020

Core-shell refractory plasmonic nanoparticles are used as excellent nanoantennas to improve the efficiency of lead-free perovskite solar cells (PSCs). SiO2 is used as the shell coating due to its high refractive index and low extinction coefficient, enabling the control over the sunlight directivity. An optoelectronic model is developed using 3D finite element method (FEM) as implemented in COMSOL Multiphysics to calculate the optical and electrical parameters of plain and ZrN/SiO2-modified PSCs. For a fair comparison, ZrN-decorated PSCs are also simulated. While the decoration with ZrN nanoparticles boosts the power conversion efficiency (PCE) of the PSC from 12.9% to 17%, the use of ZrN/SiO2 core/shell nanoparticles shows an unprecedented enhancement in the PCE to reach 20%. The enhancement in the PCE is discussed in details.
Urinary and serum oxysterols in children: developmental pattern and potential biomarker for pediatric liver disease
Authors: Takaki Yugo , Mizuochi Tatsuki , Takei Hajime , Eda Keisuke , Konishi Ken-ichiro , Ishihara Jun , Kinoshita Masahiro , Hashizume Naoki , Yamashita Yushiro , Nittono Hiroshi , Kimura Akihiko
Published: April 2020

Few reports describe oxysterols in healthy children or in children with liver disease. We aimed to determine whether developmental changes in urinary and serum oxysterols occur during childhood, and to assess whether oxysterols might be biomarkers for pediatric liver disease. Healthy children enrolled as subjects (36 and 35 for urine and serum analysis, respectively) included neonates, infants, preschoolers, and school-age children, studied along with 14 healthy adults and 8 children with liver disease. We quantitated 7 oxysterols including 4β-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol using liquid chromatography/electrospray ionization-tandem mass spectrometry. Urinary total oxysterols were significantly greater in neonates than in infants (P < 0.05), preschoolers (P < 0.001), school-age children (P < 0.001), or adults (P < 0.001), declining with age. Serum total oxysterols in neonates were significantly lower than in infants (P < 0.05), preschoolers (P < 0.001), school-age children (P < 0.05), or adults (P < 0.01). Compared with healthy children, total oxysterols and 24(S)-hydroxycholesterol in liver disease were significantly increased in both urine (P < 0.001 and P < 0.001, respectively) and serum (P < 0.001 and P < 0.05, respectively). Oxysterols in liver disease, particularly 24(S)-hydroxycholesterol, were greater in urine than serum. Oxysterols change developmentally and might serve as a biomarker for pediatric liver disease. To our knowledge, this is the first such report.
The Influence of the Variation in Sepsis Rate between Neonatal Intensive Care Units on Neonatal Outcomes in Very-Low-Birth-Weight Infants
Authors: Sung Tae-Jung , Sohn Jin A. , Oh Sohee , Lee Jin A.
Published: April 2020

Sepsis is commonly known to affect neonatal outcomes. We assessed how much center-to-center variability of the sepsis rate affects the outcomes of very-low-birth-weight infants (VLBWIs). 7,493 VLBWIs registered in the Korean Neonatal Network from 2013 to 2016 were classified into three groups according to the sepsis rate: low sepsis group (LS) < 25th percentile versus intermediate sepsis group (IS) 25th–75th versus high sepsis group (HS) ≥ 75th. The incidence density of sepsis for the LS, IS, and HS groups were 1.17, 3.17, and 8.88 cases/1,000 person-days. After propensity score matching was done for multiple antenatal and perinatal factors, the odds ratio of death, moderate to severe bronchopulmonary dysplasia and/or death, periventricular leukomalacia, and survival without major morbidities for the HS group were 2.0 (95% confidence interval 1.4–2.8), 1.9 (1.5–2.4), 1.5 (1.1–2.3) and 0.7 (0.5–0.8) when compared with the IS group, and 2.2 (1.6–3.2), 2.3 (1.8–2.9), 2.0 (1.3–2.9), and 0.7 (0.6–0.9) when compared with the LS group. There were no significant differences in those outcomes between the LS and IS groups. Hence, nationwide quality improvements to control the sepsis rate especially in units with a high sepsis rate will be helpful to improve the outcomes of VLBWIs.
Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity
Authors: Alshamsan Aws , Binkhathlan Ziyad , Kalam Mohd Abul , Qamar Wajhul , Kfouri Hala , Alghonaim Mohammed , Lavasanifar Afsaneh
Published: April 2020

The aim of this study was to assess the ability of PLGA nanoparticles (NPs) to reduce the tacrolimus (TAC)-associated nephrotoxicity following multiple dose administration. The mean diameter of prepared NPs was in the range of 227 to 263 nm with an 8.32% drug loading (w/w). Moreover, in vitro release profile of TAC-loaded NPs showed a sustained release of the drug with only less than 30% release within 12 days. Flow cytometry as well as fluorescence microscopy results confirmed the uptake of FITC-labelled PLGA NPs by dendritic cells. The ex vivo study showed that TAC-loaded NPs caused a significant suppression of the proliferation of CD4+ and CD8+ cells, which was comparable to the control formulation (Prograf). In vivo immunosuppressive activity as well as the kidney function were assessed following drug administration to mice. The animals received TAC subcutaneously at a daily dose of 1 mg/kg for 30 days delivered as the control formulation (Prograf) or TAC-loaded NPs. The results revealed significantly lower drug-associated toxicity with an activity comparable to Prograf for TAC-loaded PLGA NPs. These findings show a potential for PLGA NPs in reducing the nephrotoxicity of TAC while preserving the immunosuppressive activity.