bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCL-w: apoptotic and non-apoptotic role in health and disease
Authors: Hartman Mariusz L. , Czyz Malgorzata 
Published: April 2020

AbstractThe 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

AbstractMicroRNAs (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

AbstractThe 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

AbstractmHsp60-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.
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

AbstractInland 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

AbstractAlthough 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

AbstractBone 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

AbstractThe 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

AbstractThe 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

AbstractHerpes 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

AbstractThe 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

AbstractMagnetosomes 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

AbstractAccurate, 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

AbstractThis 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

AbstractMeasuring 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.