bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA Stabilizes Transcription-Dependent Chromatin Loops Induced By Nuclear Hormones
Authors: Pezone Antonio , Zuchegna Candida , Tramontano Alfonso , Romano Antonella , Russo Giusi , de Rosa Mariarosaria , Vinciguerra Maria , Porcellini Antonio , Gottesman Max E. , Avvedimento Enrico Vittorio 
Published: March 2019

AbstractWe show that transcription induced by nuclear receptors for estrogen (E2) or retinoic acid (RA) is associated with formation of chromatin loops that juxtapose the 5’ end (containing the promoter) with the enhancer and the 3′ polyA addition site of the target gene. We find three loop configurations which change as a function of time after induction: 1. RA or E2-induced loops which connect the 5′ end, the enhancer and the 3′ end of the gene, and are stabilized by RNA early after induction; 2. E2-independent loops whose stability does not require RNA; 3. Loops detected only by treatment of chromatin with RNAse H1 prior to hormonal induction. RNAse H1 digests RNA that occludes the relevant restriction sites, thus preventing detection of these loops. R-loops at the 5′ and 3′ ends of the RA or E2-target genes were demonstrated by immunoprecipitation with anti-DNA-RNA hybrid antibodies as well as by sensitivity to RNAse H1. The cohesin RAD21 subunit is preferentially recruited to the target sites upon RA or E2 induction of transcription. RAD21 binding to chromatin is eliminated by RNAse H1. We identified E2-induced and RNase H1-sensitive antisense RNAs located at the 5′ and 3′ ends of the E2-induced transcription unit which stabilize the loops and RAD21 binding to chromatin. This is the first report of chromatin loops that form after gene induction that are maintained by RNA:DNA hybrids.
Magnetically guided non-invasive CRISPR-Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection
Authors: Kaushik Ajeet , Yndart Adriana , Atluri Venkata , Tiwari Sneham , Tomitaka Asahi , Gupta Purnima , Jayant Rahul Dev , Alvarez-Carbonell David , Khalili Kamel , Nair Madhavan 
Published: March 2019

AbstractCRISPR-Cas9/gRNA exhibits therapeutic efficacy against latent human immunodeficiency virus (HIV) genome but the delivery of this therapeutic cargo to the brain remains as a challenge. In this research, for the first time, we demonstrated magnetically guided non-invasive delivery of a nano-formulation (NF), composed of Cas9/gRNA bound with magneto-electric nanoparticles (MENPs), across the blood-brain barrier (BBB) to inhibit latent HIV-1 infection in microglial (hμglia)/HIV (HC69) cells. An optimized ac-magnetic field of 60 Oe was applied on NF to release Cas9/gRNA from MENPs surface and to facilitate NF cell uptake resulting in intracellular release and inhibition of HIV. The outcomes suggested that developed NF reduced HIV-LTR expression significantly in comparison to unbound Cas9/gRNA in HIV latent hμglia/HIV (HC69) cells. These findings were also validated qualitatively using fluorescence microscopy to assess NF efficacy against latent HIV in the microglia cells. We believe that CNS delivery of NF (CRISPR/Cas9-gRNA-MENPs) across the BBB certainly will have clinical utility as future personalized nanomedicine to manage neuroHIV/AIDS.
Global response of diacylglycerol kinase towards substrate binding observed by 2D and 3D MAS NMR
Authors: Möbius Kristin , Kazemi Sina , Güntert Peter , Jakob Andreas , Heckel Alexander , Becker-Baldus Johanna , Glaubitz Clemens 
Published: March 2019

AbstractEscherichia coli diacylglycerol kinase (DGK) is an integral membrane protein, which catalyses the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatic acid (PA). It is a unique trimeric enzyme, which does not share sequence homology with typical kinases. It exhibits a notable complexity in structure and function despite of its small size. Here, chemical shift assignment of wild-type DGK within lipid bilayers was carried out based on 3D MAS NMR, utilizing manual and automatic analysis protocols. Upon nucleotide binding, extensive chemical shift perturbations could be observed. These data provide evidence for a symmetric DGK trimer with all of its three active sites concurrently occupied. Additionally, we could detect that the nucleotide substrate induces a substantial conformational change, most likely directing DGK into its catalytic active form. Furthermore, functionally relevant interprotomer interactions are identified by DNP-enhanced MAS NMR in combination with site-directed mutagenesis and functional assays.
miRNA analysis with Prost! reveals evolutionary conservation of organ-enriched expression and post-transcriptional modifications in three-spined stickleback and zebrafish
Authors: Desvignes Thomas , Batzel Peter , Sydes Jason , Eames B. Frank , Postlethwait John H. 
Published: March 2019

AbstractMicroRNAs (miRNAs) can have organ-specific expression and functions; they can originate from dedicated miRNA genes, from non-canonical miRNA genes, or from mirror-miRNA genes and can also experience post-transcriptional variation. It remains unclear, however, which mechanisms of miRNA production or modification are organ-specific and the extent of their evolutionary conservation. To address these issues, we developed the software Prost! (PRocessing Of Short Transcripts), which, among other features, helps quantify mature miRNAs, accounts for post-transcriptional processing, such as nucleotide editing, and identifies mirror-miRNAs. Here, we applied Prost! to annotate and analyze miRNAs in three-spined stickleback (Gasterosteus aculeatus), a model fish for evolutionary biology reported to have a miRNome larger than most teleost fish. Zebrafish (Danio rerio), a distantly related teleost with a well-known miRNome, served as comparator. Our results provided evidence for the existence of 286 miRNA genes and 382 unique mature miRNAs (excluding mir430 gene duplicates and the vaultRNA-derived mir733), which doesn’t represent a miRNAome larger than other teleost miRNomes. In addition, small RNA sequencing data from brain, heart, testis, and ovary in both stickleback and zebrafish identified suites of mature miRNAs that display organ-specific enrichment, many of which are evolutionarily-conserved in the brain and heart in both species. These data also supported the hypothesis that evolutionarily-conserved, organ-specific mechanisms may regulate post-transcriptional variations in miRNA sequence. In both stickleback and zebrafish, miR2188-5p was edited frequently with similar nucleotide changes in the seed sequence with organ specific editing rates, highest in the brain. In summary, Prost! is a new tool to identify and understand small RNAs, to help clarify a species’ miRNA biology as shown here for an important model for the evolution of developmental mechanisms, and to provide insight into organ-enriched expression and the evolutionary conservation of miRNA post-transcriptional modifications.
Physicochemical, cytotoxicity and in vivo biocompatibility of a high-plasticity calcium-silicate based material
Authors: Ferreira Cláudio M. A. , Sassone Luciana M. , Gonçalves Alexia S. , de Carvalho Jorge José , Tomás-Catalá Christopher J. , García-Bernal David , Oñate-Sánchez Ricardo E. , Rodríguez-Lozano Francisco J. , Silva Emmanuel João Nogueira Leal 
Published: March 2019

AbstractThe purpose of this work was to evaluate the physicochemical properties, the cytotoxicity and in vivo biocompatibility of MTA Repair HP (MTA HP) and White MTA (WMTA). The setting time, flow, radiopacity and water solubility were assessed. To the cytotoxicity assay, primary human osteoblast cells were exposed to several dilutions of both materials eluates. MTT assay, apoptosis assay and cell adhesion assay were performed. The in vivo biocompatibility was evaluated through histological analysis using different staining techniques. No differences were observed between MTA HP and WMTA for setting time, radiopacity, solubility and water absorption (P > 0.05). However, MTA HP showed a significantly higher flow when compared to WMTA (P < 0.05). Cell viability results revealed that the extracts of WMTA and MTA HP promoted the viability of osteoblasts. After incubation of cells with the endodontic cement extracts, the percentage of apoptotic or necrotic cells was very low (<3%). Furthermore, SEM results showed a high degree of cell proliferation and adhesion on both groups. MTA HP showed similar in vivo biocompatibility to the WMTA and the control group in all time-points. The MTA HP presented adequate physicochemical and biological properties with improved flow ability when compared to WMTA. Such improved flow ability may be a result of the addition of a plasticizing agent and should be related to an improvement in the handling of MTA HP.
Impact of Wuyiencin Application on the Soil Microbial Community and Fate of Typical Antibiotic Resistance Genes
Authors: Shi Liming , Ge Beibei , Liu Binghua , Liu Xingang , Jiang Mingguo , Zhang Kecheng 
Published: March 2019

AbstractAntibiotic resistance genes (ARGs) have raised numerous concerns in recent years as emerging environmental contaminants. At present, research on environmental contamination by antibiotics focuses on medical, animal husbandry, and aquaculture fields, with few studies on environmental contamination by agricultural antibiotics in the field of plant protection. Wuyiencin is a low toxicity, high efficiency, and broad-spectrum agricultural antibiotic. It has been widely used in agricultural production and it effectively controls crop fungal diseases. In the present study, pot experiments with four soil treatments (A, B, C and D) were set up in a greenhouse to investigate the effect of the application of wuyiencin on the fate of typical ARGs and microbial community. Eight typical ARGs were detected by real-time PCR and the microbial communities were analyzed using high-throughput sequencing. The results showed that wuyiencin neither significantly influenced ARG abundance and absolute gene copy numbers, nor significantly varied microbial community among treatments. Since it only was short-term results, and the detection number of ARGs was limited, whether wuyiencin is safe or not to ecological environment when using for long-term will need further deep research.
A Universal Stamping Method of Graphene Transfer for Conducting Flexible and Transparent Polymers
Authors: Chandrashekar Bananakere Nanjegowda , Smitha Ankanahalli Shankaregowda , Wu Yingchun , Cai Nianduo , Li Yunlong , Huang Ziyu , Wang Weijun , Shi Run , Wang Jingwei , Liu Shiyuan , Krishnaveni S. , Wang Fei , Cheng Chun 
Published: March 2019

AbstractTransfer method of chemically vapor deposition graphene is an appealing issue to realize its application as flexible and transparent electrodes. A universal stamping method to transfer as grown graphene from copper onto different flexible and transparent polymers (FTPs) reported here ensures simple, robust, rapid, clean and low-cost. This method relies on coating ethylene vinyl acetate (EVA) onto the as grown graphene, binding EVA coated graphene/Cu with FTPs and delamination by hydrogen bubbling process, which is analogous to the method used by stamping process where ink carries the imprint of the object onto any materials. The fate of the stamping method depends on how strongly the adhesion of EVA coated graphene/Cu with target FTPs. Interestingly, we have found that the thin film of EVA/graphene/Cu can only bind strongly with the FTPs of less than 25 µm in thickness and lower glass transition temperature value to the EVA while wide range of other FTPs are considered upon surface engineering to enhance the binding strength between FTPs and EVA. What’s more, the electrical performance was investigated with a demonstration of triboelectric nanogenerators which confirmed the reliability of graphene transfer onto the FTPs and prospect for the development of flexible and transparent electronics.
Collective influencers in protein interaction networks
Authors: Boltz T. A. , Devkota P. , Wuchty Stefan 
Published: March 2019

AbstractRecent research increasingly shows the relevance of network based approaches for our understanding of biological systems. Analyzing human protein interaction networks, we determined collective influencers (CI), defined as network nodes that damage the integrity of the underlying networks to the utmost degree. We found that CI proteins were enriched with essential, regulatory, signaling and disease genes as well as drug targets, indicating their biological significance. Also by focusing on different organisms, we found that CI proteins had a penchant to be evolutionarily conserved as CI proteins, indicating the fundamental role that collective influencers in protein interaction networks plays for our understanding of regulation, diseases and evolution.
Structure guided design of an antibacterial peptide that targets UDP-N-acetylglucosamine acyltransferase
Authors: Dangkulwanich Manchuta , Raetz Christian R. H. , Williams Allison H. 
Published: March 2019

AbstractUDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of anR-3-hydroxyacyl chain from its acyl carrier protein (ACP) to the 3-OH group of UDP-GlcNAc. Essential in the growth of Gram-negative bacteria, LpxA is a logical target for antibiotics design. A pentadecapeptide (Peptide 920) with high affinity towards LpxA was previously identified in a phage display library. Here we created a small library of systematically designed peptides with the length of four to thirteen amino acids using Peptide 920 as a scaffold. The concentrations of these peptides at which 50% of LpxA is inhibited (IC50) range from 50 nM to >100 μM. We determined the crystal structure ofE. coliLpxA in a complex with a potent inhibitor. LpxA-inhibitor interaction, solvent model and all contributing factors to inhibitor efficacy were well resolved. The peptide primarily occludes the ACP binding site of LpxA. Interactions between LpxA and the inhibitor are different from those in the structure of Peptide 920. The inhibitory peptide library and the crystal structure of inhibitor-bound LpxA described here may further assist in the rational design of inhibitors with antimicrobial activity that target LpxA and potentially other acyltransferases.
Mathematical modelling indicates that lower activity of the haemostatic system in neonates is primarily due to lower prothrombin concentration
Authors: Siekmann Ivo , Bjelosevic Stefan , Landman Kerry , Monagle Paul , Ignjatovic Vera , Crampin Edmund J. 
Published: March 2019

AbstractHaemostasis is governed by a highly complex system of interacting proteins. Due to the central role of thrombin, thrombin generation and specifically the thrombin generation curve (TGC) is commonly used as an indicator of haemostatic activity. Functional characteristics of the haemostatic system in neonates and children are significantly different compared with adults; at the same time plasma levels of haemostatic proteins vary considerably with age. However, relating one to the other has been difficult, both due to significant inter-individual differences for individuals of similar age and the complexity of the biochemical reactions underlying haemostasis. Mathematical modelling has been very successful at representing the biochemistry of blood clotting. In this study we address the challenge of large inter-individual variability by parameterising the Hockin-Mann model with data from individual patients, across different age groups from neonates to adults. Calculating TGCs for each patient of a specific age group provides us with insight into the variability of haemostatic activity across that age group. From our model we observe that two commonly used metrics for haemostatic activity are significantly lower in neonates than in older patients. Because both metrics are strongly determined by prothrombin and prothrombin levels are considerably lower in neonates we conclude that decreased haemostatic activity in neonates is due to lower prothrombin availability.
Infrared-sensing snakes select ambush orientation based on thermal backgrounds
Authors: Schraft Hannes A. , Bakken George S. , Clark Rulon W. 
Published: March 2019

AbstractSensory information drives the ecology and behaviour of animals, and some animals are able to detect environmental cues unavailable to us. For example, rattlesnakes use infrared (IR) radiation to detect warm prey at night when visual cues are reduced. Until recently these sensory worlds have been inaccessible to human observers; now technology can allow us to “eavesdrop” on these species and understand how sensory perception drives ecology and behaviour. We used thermography and computer simulations to examine how prey-background temperature contrast and areas of temperature transitions influence the angular orientation of free-ranging rattlesnakes once they have selected an ambush site. We tracked free-ranging sidewinder rattlesnakes Crotalus cerastes to their selected ambush sites and recorded 360° near-ground thermographic panoramas from the centre of the ambush site. A computer simulation then moved a simulated prey item across the panorama and computed a contrast index for all directions. Rattlesnakes did not face ambush directions that offered stronger contrast than average, but they demonstrated a striking tendency to face directions with strong thermal transitions. Background transitions likely create a readily detected, rapidly changing stimulus when a prey animal passes. Quantifications of sensory environments like this one can boost our comprehension of how sensory function impacts the ecology, behaviour, and evolution of animals.
RNA-seq of Isolated Chromaffin Cells Highlights the Role of Sex-Linked and Imprinted Genes in Adrenal Medulla Development
Authors: Chan Wing Hei , Komada Masayuki , Fukushima Toshiaki , Southard-Smith E. Michelle , Anderson Colin R. , Wakefield Matthew J. 
Published: March 2019

AbstractAdrenal chromaffin cells and sympathetic neurons synthesize and release catecholamines, and both cell types are derived from neural crest precursors. However, they have different developmental histories, with sympathetic neurons derived directly from neural crest precursors while adrenal chromaffin cells arise from neural crest-derived cells that express Schwann cell markers. We have sought to identify the genes, including imprinted genes, which regulate the development of the two cell types in mice. We developed a method of separating the two cell types as early as E12.5, using differences in expression of enhanced yellow fluorescent protein driven from the tyrosine hydroxylase gene, and then used RNA sequencing to confirm the characteristic molecular signatures of the two cell types. We identified genes differentially expressed by adrenal chromaffin cells and sympathetic neurons. Deletion of a gene highly expressed by adrenal chromaffin cells, NIK-related kinase, a gene on the X-chromosome, results in reduced expression of adrenaline-synthesizing enzyme, phenyl-N-methyl transferase, by adrenal chromaffin cells and changes in cell cycle dynamics. Finally, many imprinted genes are up-regulated in chromaffin cells and may play key roles in their development.
Bloodmeal host identification with inferences to feeding habits of a fish-fed mosquito, Aedes baisasi
Authors: Miyake Takashi , Aihara Natsuki , Maeda Ken , Shinzato Chuya , Koyanagi Ryo , Kobayashi Hirozumi , Yamahira Kazunori 
Published: March 2019

AbstractThe mosquito, Aedes baisasi, which inhabits brackish mangrove swamps, is known to feed on fish. However, its host assemblage has not been investigated at the species level. We amplified and sequenced the cytochrome oxidase subunit I barcoding regions as well as some other regions from blood-fed females to identify host assemblages in the natural populations from four islands in the Ryukyu Archipelago. Hosts were identified from 230 females. We identified 15 host fish species belonging to eight families and four orders. Contrary to expectations from previous observations, mudskippers were detected from only 3% of blood-engorged females. The dominant host was a four-eyed sleeper, Bostrychus sinensis (Butidae, Gobiiformes), in Iriomote-jima Island (61%), while it was a snake eel, Pisodonophis boro (Ophichthidae, Anguilliformes), in Amami-oshima and Okinawa-jima islands (78% and 79%, respectively). Most of the identified hosts were known as air-breathing or amphibious fishes that inhabit mangroves or lagoons. Our results suggest that A. baisasi females locate the bloodmeal hosts within the mangrove forests and sometimes in the adjacent lagoons and land on the surface of available amphibious or other air-breathing fishes exposed in the air to feed on their blood.
Increased expression of Toll-like receptors 2, 3, 4 and 7 mRNA in the kidney and intestine of a septic mouse model
Authors: Krivan Sylvia , Kapelouzou Alkistis , Vagios Stylianos , Tsilimigras Diamantis I. , Katsimpoulas Michalis , Moris Demetrios , Aravanis Chrysostomos V. , Demesticha Theano D. , Schizas Dimitrios , Mavroidis Manolis , Pavlakis Kitty , Machairas Anastasios , Misiakos Evangelos , Liakakos Theodore 
Published: March 2019

AbstractToll-like receptors (TLRs) are the key regulators of innate and adaptive immunity and are highly expressed during sepsis. Thus, studying the expression of TLRs in an animal septic model might indicate their possible association with acute kidney injury in sepsis. Seventy-two male C57BL/6J mice were used for this study. Randomly, these animals were divided into 6 groups (N = 12/group): 3 control and 3 septic groups depending on the euthanasia time (24 h, 48 h, 72 h). Septic groups underwent cecal ligation and puncture (CLP) to induce peritonitis, while control groups had a sham operation. Hematological tests were performed in serum for immune biomarkers; immunohistochemistry, morphometry and qRT-PCR analysis were used on both kidney and intestine tissues to evaluate the expression of TLR 2, 3, 4 and 7 in a septic process. At the end of each experimental period, we found that TLRs 2, 3, 4 and 7 were expressed in both tissues but there were differences between those at various time points. Also, we found that mRNA levels were significantly higher in qRT-PCR evaluation in septic groups than control groups in both kidney and intestinal tissues (p < 0.05); showing a steady increase in the septic groups as the time to euthanasia was prolonged (p < 0.05). Overall, our study provides a suggestion that TLRs 2, 3, 4 and 7 are highly expressed in the kidneys of septic mice and especially that these TLRs are sensitive and specific markers for sepsis. Finally, our study supports the diagnostic importance of TLRs in AKI and provides an insight on the contribution of septic mice models in the study of multi organ dysfunction syndrome in general.