bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic analyses of two Alteromonas stellipolaris strains reveal traits with potential biotechnological applications
Authors: Torres Marta , Hong Kar-Wai , Chong Teik-Min , Reina José Carlos , Chan Kok-Gan , Dessaux Yves , Llamas Inmaculada
Published: February 2019

The Alteromonas stellipolaris strains PQQ-42 and PQQ-44, previously isolated from a fish hatchery, have been selected on the basis of their strong quorum quenching (QQ) activity, as well as their ability to reduce Vibrio-induced mortality on the coral Oculina patagonica. In this study, the genome sequences of both strains were determined and analyzed in order to identify the mechanism responsible for QQ activity. Both PQQ-42 and PQQ-44 were found to degrade a wide range of N-acylhomoserine lactone (AHL) QS signals, possibly due to the presence of an aac gene which encodes an AHL amidohydrolase. In addition, the different colony morphologies exhibited by the strains could be related to the differences observed in genes encoding cell wall biosynthesis and exopolysaccharide (EPS) production. The PQQ-42 strain produces more EPS (0.36 g l−1) than the PQQ-44 strain (0.15 g l−1), whose chemical compositions also differ. Remarkably, PQQ-44 EPS contains large amounts of fucose, a sugar used in high-value biotechnological applications. Furthermore, the genome of strain PQQ-42 contained a large non-ribosomal peptide synthase (NRPS) cluster with a previously unknown genetic structure. The synthesis of enzymes and other bioactive compounds were also identified, indicating that PQQ-42 and PQQ-44 could have biotechnological applications.
Correlative cryo super-resolution light and electron microscopy on mammalian cells using fluorescent proteins
Authors: Tuijtel Maarten W. , Koster Abraham J. , Jakobs Stefan , Faas Frank G. A. , Sharp Thomas H.
Published: February 2019

Sample fixation by vitrification is critical for the optimal structural preservation of biomolecules and subsequent high-resolution imaging by cryo-correlative light and electron microscopy (cryoCLEM). There is a large resolution gap between cryo fluorescence microscopy (cryoFLM), ~400-nm, and the sub-nanometre resolution achievable with cryo-electron microscopy (cryoEM), which hinders interpretation of cryoCLEM data. Here, we present a general approach to increase the resolution of cryoFLM using cryo-super-resolution (cryoSR) microscopy that is compatible with successive cryoEM investigation in the same region. We determined imaging parameters to avoid devitrification of the cryosamples without the necessity for cryoprotectants. Next, we examined the applicability of various fluorescent proteins (FPs) for single-molecule localisation cryoSR microscopy and found that all investigated FPs display reversible photoswitchable behaviour, and demonstrated cryoSR on lipid nanotubes labelled with rsEGFP2 and rsFastLime. Finally, we performed SR-cryoCLEM on mammalian cells expressing microtubule-associated protein-2 fused to rsEGFP2 and performed 3D cryo-electron tomography on the localised areas. The method we describe exclusively uses commercially available equipment to achieve a localisation precision of 30-nm. Furthermore, all investigated FPs displayed behaviour compatible with cryoSR microscopy, making this technique broadly available without requiring specialised equipment and will improve the applicability of this emerging technique for cellular and structural biology.
Immediate anterior open reduction and plate fixation in the management of lower cervical dislocation with facet interlocking
Authors: Li Yuwei , Zhou Peng , Cui Wei , Li Cheng , Xiao Wei , Wen Yan , Wang Haoran , Wang Haijiao
Published: February 2019

Lower cervical dislocation with facet interlocking is one of the most drastic injuries to the cervical spine. The early reduction is thought critical in preventing progressive secondary spinal cord injury. The authors report a new surgical procedure in the management of lower cervical dislocation with facet interlocking. A total of twenty-one cases received immediate single-staged anterior open reduction, realignment and plate fixation under general anesthesia. After the procedures, most cases exhibited improved neurological function. All patients showed stable fusion at 1-year follow-up. Loss of spinal alignment or kyphotic deformity was not found in any case. Hardware failure including screw loosening or penetrating was not observed. In conclusion, the immediate anterior open reduction and plate fixation is a safe and effective procedure in the management of lower cervical dislocation with facet interlocking.
Baryon decays to purely baryonic final states
Authors: Hsiao Y. K. , Geng C. Q. , Rodrigues Eduardo
Published: February 2019

The LHCb collaboration has presented first experimental evidence that spin-carrying matter and antimatter differ. The study looked at four-body decays of the $${{\boldsymbol{\Lambda }}}_{{\boldsymbol{b}}}^{{\bf{0}}}$$

Λ

b

0

baryon. Differences in the behaviour of matter and antimatter are associated with the non-invariance of fundamental interactions under the combined charge-conjugation and parity transformations, known as CP violation. We discuss purely baryonic decay processes, i.e. decay processes involving only spin-carrying particles. They are yet unexplored elementary processes. Their study opens a new chapter of flavour physics in the route towards a better understanding of CP violation. It may help us understand the observed matter and antimatter asymmetry of the Universe.
Reference assembly and gene expression analysis of Apostichopus japonicus larval development
Authors: Boyko Alexey V. , Girich Alexander S. , Eliseikina Marina G. , Maslennikov Sergey I. , Dolmatov Igor Yu.
Published: February 2019

The transcriptome of the holothurian Apostichopus japonicus was sequenced at four developmental stages—blastula, gastrula, auricularia, pentactula—on an Illumina sequencer. Based on our RNA-seq data and the paired-end reads from 16 libraries obtained by other researchers earlier, we have achieved the currently most complete transcriptome assembly for A. japonicus with the best basic statistical parameters. An analysis of the obtained transcriptome has revealed 174 differentially expressed transcription factors, as well as stage-specific transcription factors that are most promising for further study. In addition, a total of 1,174,999 high-quality single nucleotide polymorphisms have been identified, including 58,932 indels. A GO enrichment analysis of contigs containing polymorphic loci shows the predominance of GO terms associated with immune response. The data obtained by us provide an additional basis for a deeper study of the mechanisms of the planktotrophic-type development in holothurians and can be used in commercial sea cucumber breeding programs.
Three-dimensional organization of transzonal projections and other cytoplasmic extensions in the mouse ovarian follicle
Authors: Baena Valentina , Terasaki Mark
Published: February 2019

Each mammalian oocyte is nurtured by its own multi-cellular structure, the ovarian follicle. We used new methods for serial section electron microscopy to examine entire cumulus and mural granulosa cells and their projections in mouse antral ovarian follicles. Transzonal projections (TZPs) are thin cytoplasmic projections that connect cumulus cells to the oocyte and are crucial for normal oocyte development. We studied these projections in detail and found that most TZPs do not reach the oocyte, and that they often branch and make gap junctions with each other. Furthermore, the TZPs that connect to the oocyte are usually contacted on their shaft by oocyte microvilli. Mural granulosa cells were found to possess randomly oriented cytoplasmic projections that are strikingly similar to the free-ended TZPs. We propose that granulosa cells use cytoplasmic projections to search for the oocyte, and cumulus cell differentiation results from a contact-mediated paracrine interaction with the oocyte.
Improvement of laryngoscopic view by hand-assisted elevation and caudad traction of the shoulder during tracheal intubation in pediatric patients
Authors: Ahn Jin Hee , Kim Doyeon , Gil Nam-su , Son Yong Hun , Seong Bong Gyu , Jeong Ji Seon
Published: February 2019

Pediatric patients have large heads and relatively small bodies, making it difficult to perform intubation even in the sniffing position. Therefore, this study was planned on the assumption that hand-assisted elevation and caudad traction of the shoulder (HA-ECTS) would compensate for the laryngoscopic view. In this observational study, 45 pediatric patients aged 0–36 months with an ASA physical status of I-III and scheduled for elective surgery under general anesthesia were enrolled. HA-ECTS was defined as hand-assisted personalized traction in the upper and caudad directions with both hands under the lower cervical area. The POGO (percentage of glottis opening) score, MO (mouth opening), and LHS (laryngoscopic handling score) were compared before and after HA-ECTS. The median [range] POGO score was 30[10–50]% and 60[15–80]% before and after HA-ECTS, respectively (median difference, 20; 95% confidence interval [CI] 10 to 25%; P = 0.002). MO was 1.0[0.8–1.9] cm and 1.8[1.3–2.0] cm before and after HA-ECTS, respectively (median difference, 0.45 cm; 95% CI 0.25 to 0.60; P < 0.001). The ease of laryngoscopic handling was improved after HA-ECTS(P < 0.001). The application of HA-ECTS to pediatric patients younger than 3 years improved POGO score, MO, and LHS and could prove to be an assistive technique for tracheal intubation.
Completely scrambled memory for quantum superposition
Authors: Mukai Tetsuya
Published: February 2019

Although constructing a quantum computation device with multiple qubits is arguably a difficult task, several seconds of coherence time with tens of thousands of quantum particles has been demonstrated with a trapped atomic ensemble. As a practical application, a security-enhanced quantum state memory using atoms has been demonstrated. It was shown that the quantum superposition preserved in an atomic ensemble was scrambled and faithfully descrambled; however, the scrambled phase ambiguity remained at 50%. To overcome this problem, we propose and demonstrate a scheme that achieves 100% phase ambiguity without introducing an extra Ramsey interferometer. Moreover, this scheme can be used as a direct application to keep the choice between two values secret without falsification.
Modeling spinocerebellar ataxias 2 and 3 with iPSCs reveals a role for glutamate in disease pathology
Authors: Chuang Ching-Yu , Yang Chih-Chao , Soong Bing-Wen , Yu Chun-Ying , Chen Shu-Hwa , Huang Hsiang-Po , Kuo Hung-Chih
Published: February 2019

Spinocerebellar ataxias 2 and 3 (SCA2 and SCA3) are dominantly inherited neurodegenerative diseases caused by expansion of polyglutamine-encoding CAG repeats in the affected genes. The etiology of these disorders is known to involve widespread loss of neuronal cells in the cerebellum, however, the mechanisms that contribute to cell death are still elusive. Here we established SCA2 and SCA3 induced pluripotent stem cells (iPSCs) and demonstrated that SCA-associated pathological features can be recapitulated in SCA-iPSC-derived neurons. Importantly, our results also revealed that glutamate stimulation promotes the development of disease-related phenotypes in SCA-iPSC-derived neurons, including altered composition of glutamatergic receptors, destabilized intracellular calcium, and eventual cell death. Furthermore, anti-glutamate drugs and calcium stabilizer treatment protected the SCA-iPSC-derived neurons and reduced cell death. Collectively, our study demonstrates that the SCA-iPSC-derived neurons can recapitulate SCA-associated pathological features, providing a valuable tool to explore SCA pathogenic mechanisms and screen drugs to identify potential SCA therapeutics.
Real-time analysis of quantum dot labeled single porcine epidemic diarrhea virus moving along the microtubules using single particle tracking
Authors: Hou Wei , Li Yangyang , Kang Wenjie , Wang Xin , Wu Xuping , Wang Shouyu , Liu Fei
Published: February 2019

In order to study the infection mechanism of porcine epidemic diarrhea virus (PEDV), which causes porcine epidemic diarrhea, a highly contagious enteric disease, we combined quantum dot labeled method, which could hold intact infectivity of the labeled viruses to the largest extent, with the single particle tracking technique to dynamically and globally visualize the transport behaviors of PEDVs in live Vero cells. Our results were the first time to uncover the dynamic characteristics of PEDVs moving along the microtubules in the host cells. It is found that PEDVs kept restricted motion mode with a relatively stable speed in the cell membrane region; while performed a slow-fast-slow velocity pattern with different motion modes in the cell cytoplasm region and near the microtubule organizing center region. In addition, the return movements of small amount of PEDVs were also observed in the live cells. Collectively, our work is crucial for understanding the movement mechanisms of PEDV in the live cells, and the proposed work also provided important references for further analysis and study on the infection mechanism of PEDVs.
12,23-Dione dammarane triterpenes from Gynostemma longipes and their muscle cell proliferation activities via activation of the AMPK pathway
Authors: Ha Thi Kim Quy , Pham Ha Thanh Tung , Cho Hyo Moon , Tran Van On , Yang Jun-Li , Jung Da-Woon , Williams Darren R. , Oh Won Keun
Published: February 2019

The aging population is growing rapidly around the world and there is also an increase in sarcopenia, which is characterized by decreased muscle mass, strength and function in the elderly population. AMP-activated protein kinase (AMPK) is an essential sensor and regulator of glucose, lipid and energy metabolism throughout the body. Previous studies have shown that AMPK pathway activation by regular exercise and appropriate dietary control have beneficial effects on skeletal muscle. In the process of searching for new AMPK activators from medicinal plants, we isolated and characterized eight new 12,23-dione dammarane triterpenoids (1–3 and 5–9), as well as one known gypentonoside A from Gynostemma longipes. When all isolates were tested for their AMPK activation activities, seven compounds (1 and 3–8) were significantly activated AMPK phosphorylation in mouse C2C12 skeletal muscle cell lines. Since G. longipes contained a significant amount of active compound 1 (over 2.08% per dried raw plant), it suggested the potential of this plant to be developed as a functional food or botanical drug that enhances muscle proliferation by activating AMPK signaling pathways.
Using all-sky differential photometry to investigate how nocturnal clouds darken the night sky in rural areas
Authors: Jechow Andreas , Hölker Franz , Kyba Christopher C. M.
Published: February 2019

Artificial light at night has affected most of the natural nocturnal landscapes worldwide and the subsequent light pollution has diverse effects on flora, fauna and human well-being. To evaluate the environmental impacts of light pollution, it is crucial to understand both the natural and artificial components of light at night under all weather conditions. The night sky brightness for clear skies is relatively well understood and a reference point for a lower limit is defined. However, no such reference point exists for cloudy skies. While some studies have examined the brightening of the night sky by clouds in urban areas, the published data on the (natural) darkening by clouds is very sparse. Knowledge of reference points for the illumination of natural nocturnal environments however, is essential for experimental design and ecological modeling to assess the impacts of light pollution. Here we use differential all-sky photometry with a commercial digital camera to investigate how clouds darken sky brightness at two rural sites. The spatially resolved data enables us to identify and study the nearly unpolluted parts of the sky and to set an upper limit on ground illumination for overcast nights at sites without light pollution.
Structural and electronic properties of Mo6S3I6 nanowires by newly proposed theoretical compositional ordering
Authors: Chung You Kyoung , Lee Weon-Gyu , Chae Sudong , Choi Jae-Young , Huh Joonsuk
Published: February 2019

The structural, electronic, and magnetic properties of molybdenum-based nanowires have been actively investigated for their potential applications in nanodevices; however, further advancement is hindered by incomplete knowledge of the electronic and atomic structures of Mo6S3I6. To facilitate further development of Mo6S3I6 nanowire devices, we propose possible atomic structures and corresponding electronic properties of Mo6S3I6 nanowires based on density functional theory. We explored various combinations of atomic structures by changing the positions of sulfur and iodine atoms linked to the two Mo6 octahedra in the Mo6S3I6 unit cell. We found two stable local energy minima structures characterized by elongation of the wire length, and therefore propose 28 possible atomic configurations. We calculated band structures of the newly proposed atomic models and found three structures that behaved as conductors. According to our compositional ordering structural analysis, we concluded that (i) periodic distortion of the bond lengths influences the behavior of the electrons in the system, (ii) the role of sulfur atoms in the bridging plane is important for intramolecular charge transport due to delocalized charge differences, and (iii) the electronic band gap energy is proportional to the integrated Mo-S bonding orbital energy.
Fluorescent Fe Embedded Magnetic Nanodiamonds Made by Ion Implantation
Authors: Lin Bo-Rong , Kunuku Srinivasu , Chen Chien-Hsu , Chen Tzung-Yuang , Hsiao Tung-Yuan , Yu Hung-Kai , Chang Yu-Jen , Liao Li-Chuan , Niu Huan , Lee Chien-Ping
Published: February 2019

We demonstrate fluorescent Fe embedded magnetic nanodiamonds by ion implantation and two-step annealing. The diamond characteristics with a highly ordered core and a graphite surface layer are maintained after the implantation process. After the two-step annealing process, a bright red fluorescence associated with nitrogen-vacancy centers is observed. These new fluorescent magnetic nanodiamonds can be used as a dual-function in vivo tracer with both optical visibility and magnetic resonance imaging capabilities. They are potentially useful for the more advanced in vivo biological and medical applications.
Tracking perceptual decision mechanisms through changes in interhemispheric functional connectivity in human visual cortex
Authors: Sousa Teresa , Duarte João V. , Costa Gabriel N. , Kemper Valentin G. , Martins Ricardo , Goebel Rainer , Castelo-Branco Miguel
Published: February 2019

The role of long-range integration mechanisms underlying visual perceptual binding and their link to interhemispheric functional connectivity, as measured by fMRI, remains elusive. Only inferences on anatomical organization from resting state data paradigms not requiring coherent binding have been achieved. Here, we used a paradigm that allowed us to study such relation between perceptual interpretation and functional connectivity under bistable interhemispheric binding vs. non-binding of visual surfaces. Binding occurs by long-range perceptual integration of motion into a single object across hemifields and non-binding reflects opponent segregation of distinct moving surfaces into each hemifield. We hypothesized that perceptual integration vs. segregation of surface motion, which is achieved in visual area hMT+, is modulated by changes in interhemispheric connectivity in this region. Using 7T fMRI, we found that perceptual long-range integration of bistable motion can be tracked by changes in interhemispheric functional connectivity between left/right hMT+. Increased connectivity was tightly related with long-range perceptual integration. Our results indicate that hMT+ interhemispheric functional connectivity reflects perceptual decision, suggesting its pivotal role on long-range disambiguation of bistable physically constant surface motion. We reveal for the first time, at the scale of fMRI, a relation between interhemispheric functional connectivity and decision based perceptual binding.
Investigation of relationship between vitamin D status and reproductive fitness in Scottish hill sheep
Authors: Zhou Ping , McEvoy Thomas G. , Gill Andrew C. , Lambe Nicola R. , Morgan-Davies Claire R. , Hurst Emma , Sargison Neil D. , Mellanby Richard J.
Published: February 2019

There is a growing interest in the influence of vitamin D on ovine non-skeletal health. The aim of this study was to explore the relationship between pre-mating vitamin D status, as assessed by serum concentrations of 25-Hydroxyvitamin D [25(OH)D; comprising D2 and D3] and subsequent reproductive performance of genetically unimproved Scottish Blackface (UBF), genetically improved Scottish Blackface (IBF) and Lleyn ewes kept under Scottish hill conditions. 25-Hydroxyvitamin D2 (25(OH)D2) and 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were determined in serum samples harvested in November from ewes grazed outdoors. There were no significant differences in 25(OH)D2concentrations amongst the 3 genotypes. Lleyn ewes had significantly higher 25(OH)D3 and 25(OH)D concentrations than both Scottish Blackface ewe genotypes, whereas these vitamin D parameters did not differ significantly between the UBF and IBF ewes. Concentrations of 25(OH)D3 and 25(OH)D were positively associated with subsequent birth weights of singleton and of twin lamb litters. No significant associations between vitamin D status and number of lambs born or weaned per ewe were found. This study demonstrates that concentrations of cutaneously-derived 25(OH)D3, but not of orally consumed 25(OH)D2, differed between breeds. The positive association between ewe vitamin D status and offspring birth weight highlights the need for further investigations.
Preparation and characterization of homogeneous and enhanced casein protein-based composite films via incorporating cellulose microgel
Authors: Yao Yijun , Wang Hongru , Wang Ruirui , Chai Yong
Published: February 2019

Gelatin-coupled cellulose (GCC) microgel with whisker-like structure is prepared and used to incorporate into casein (CA) matrix to construct reinforced CA-based composite films by solution casting. The GCC microgel has excellent dispersibility and stability in water, which contributes to the hydrophobicity and significantly reduces the moisture absorption of the composite films, as well as a decrease in the water vapor permeability with an increase of GCC content at different relative humidity is also observed. Compared with pure casein material, the resultant CA-based composite films show more homogeneous and dense cross-sectional structure, and the cleavage temperature of the hydrogen bonds increases by 16 °C. In particular, their tensile strength and Young’s modulus increase by 6 and 3.5 times, respectively. These indicators are superior to that of the nanoparticle enhanced CA-based composite film. Moreover, the light transmittance of the CA-based films at 550 nm is about 88% when GCC content is higher than 9%. The above results could be attributed to the strong hydrogen bonds formed between GCC components and CA matrix, as further confirmed by fourier transform infrared spectra and X-ray diffraction analysis.
Autoimmune rheumatic disease IgG has differential effects upon neutrophil integrin activation that is modulated by the endothelium
Authors: Khawaja Akif A. , Pericleous Charis , Ripoll Vera M. , Porter Joanna C. , Giles Ian P.
Published: February 2019

The importance of neutrophils in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), is increasingly recognised. Generation of reactive oxygen species (ROS) and release of neutrophil extracellular traps (NETs) by activated neutrophils are both thought to contribute to pathology; although the underlying mechanisms, particularly the effects of IgG autoantibodies upon neutrophil function, are not fully understood. Therefore, we determined whether purified IgG from patients with SLE or RA have differential effects upon neutrophil activation and function. We found that SLE- and RA-IgG both bound human neutrophils but differentially regulated neutrophil function. RA- and SLE-IgG both increased PMA-induced β1integrin-mediated adhesion to fibronectin, whilst only SLE-IgG enhanced αMβ2integrin-mediated adhesion to fibrinogen. Interestingly, only SLE-IgG modulated neutrophil adhesion to endothelial cells. Both SLE- and RA-IgG increased ROS generation and DNA externalisation by unstimulated neutrophils. Only SLE-IgG however, drove DNA externalisation following neutrophil activation. Co-culture of neutrophils with resting endothelium prevented IgG-mediated increase of extracellular DNA, but this inhibition was overcome for SLE-IgG when the endothelium was stimulated with TNF-α. This differential pattern of neutrophil activation has implications for understanding SLE and RA pathogenesis and may highlight avenues for development of novel therapeutic strategies.
Segmented Echo Planar Imaging Improves Detection of Subcortical Functional Connectivity Networks in the Rat Brain
Authors: Tambalo Stefano , Scuppa Giulia , Bifone Angelo
Published: February 2019

Susceptibility artifacts in the vicinity of aural and nasal cavities result in significant signal drop-out and image distortion in echo planar imaging of the rat brain. These effects may limit the study of resting state functional connectivity in deep brain regions. Here, we explore the use of segmented EPI for resting state fMRI studies in the rat, and assess the relative merits of this method compared to single shot EPI. Sequences were evaluated in terms of signal-to-noise ratio, geometric distortions, data driven detection of resting state networks and group level correlations of time series. Multishot imaging provided improved SNR, temporal SNR and reduced geometric distortion in deep areas, while maintaining acceptable overall image quality in cortical regions. Resting state networks identified by independent component analysis were consistent across methods, but multishot EPI provided a more robust and accurate delineation of connectivity patterns involving deep regions typically affected by susceptibility artifacts. Importantly, segmented EPI showed reduced between-subject variability and stronger statistical significance of pairwise correlations at group level over the whole brain and in particular in subcortical regions. Multishot EPI may represent a valid alternative to snapshot methods in functional connectivity studies, particularly for the investigation of subcortical regions and deep gray matter nuclei.
Azolla pinnata, Aspergillus terreus and Eisenia fetida for enhancing agronomic value of paddy straw
Authors: Arora Manveen , Kaur Arvinder
Published: February 2019

In the present study rice straw (R, control) was mixed with Cowdung (C), Azolla (A) and cellulolytic fungus Aspergillus terreus (F) in different combinations viz. RC, RA, RF, RCF, RCA, RFA and RCFA and subjected to aerobic composting (Acom) and vermicomposting (Vcom - with Eisenia fetida). It was found that addition of azolla and cattledung to two parts straw(RCA-666: 314:20 g) caused fastest degradation (105 days), gave maximum population buildup of E. fetida (cocoons, hatchlings and worm biomass), highest decline in pH, EC, TOC and C/N ratio and maximum increase over control in N(17.72%), P(44.64%), K(43.17%), H (7.93%), S (14.85%), Ca(10.16%), Na(145.97%), Fe(68.56%), Zn(12.10%) and Cu(32.24%). Rice straw (R) took longest time for degradation i.e. 120 and 140 days and had lowest content of nutrients in Vcom as well as Acom group. RCFA was also converted into Vcom at the same time but other parameters were less than RCA except for highest content of B (19.87%), Mg(21.27%) and Mn (5.58%). Bioconversion of three parts straw (RCA-735:245:20 g) was also faster (110 days) with vermicomposting than all the mixtures of Acom group (130–140 days) but nutrient content was slightly less than RCA with 2 parts straw. The results show that azolla reduces dependence on cattledung for recycling the carbon rich rice straw and enhances its agronomic value.
A novel immunogenic mouse model of melanoma for the preclinical assessment of combination targeted and immune-based therapy
Authors: Lelliott Emily J. , Cullinane Carleen , Martin Claire A. , Walker Rachael , Ramsbottom Kelly M. , Souza-Fonseca-Guimaraes Fernando , Abuhammad Shatha , Michie Jessica , Kirby Laura , Young Richard J. , Slater Alison , Lau Peter , Meeth Katrina , Oliaro Jane , Haynes Nicole , McArthur Grant A. , Sheppard Karen E.
Published: February 2019

Both targeted therapy and immunotherapy have been used successfully to treat melanoma, but the development of resistance and poor response rates to the individual therapies has limited their success. Designing rational combinations of targeted therapy and immunotherapy may overcome these obstacles, but requires assessment in preclinical models with the capacity to respond to both therapeutic classes. Herein, we describe the development and characterization of a novel, immunogenic variant of the BrafV600ECdkn2a−/−Pten−/− YUMM1.1 tumor model that expresses the immunogen, ovalbumin (YOVAL1.1). We demonstrate that, unlike parental tumors, YOVAL1.1 tumors are immunogenic in vivo and can be controlled by immunotherapy. Importantly, YOVAL1.1 tumors are sensitive to targeted inhibitors of BRAFV600E and MEK, responding in a manner consistent with human BRAFV600E melanoma. The YOVAL1.1 melanoma model is transplantable, immunogenic and sensitive to clinical therapies, making it a valuable platform to guide strategic development of combined targeted therapy and immunotherapy approaches in BRAFV600E melanoma.
Remotely constraining the temporal evolution of offshore oil systems
Authors: Corrick Alexander J. , Selby David , McKirdy David M. , Hall Philip A. , Gong Se , Trefry Christine , Ross Andrew S.
Published: February 2019

An understanding of the temporal evolution of a petroleum system is fundamental to interpreting where hydrocarbons may be trapped in the subsurface. However, traditional exploration methods provide few absolute constraints on the timing of petroleum generation. Here we show that 187Re/187Os geochronology may be applied to natural crude oil seepage to determine when petroleum generation occurred in offshore sedimentary basins. Using asphaltites collected from the South Australian coastline, our determined Re-Os age (68 ± 15 million years ago) is consistent with their derivation from a Late Cretaceous source rock in the nearby Bight Basin, an interpretation similarly favoured by source-specific biomarker constraints. Furthermore, the calculated initial 187Os/188Os composition of the asphaltites, a value inherited from the source rock at the time of oil generation, suggests that the source rock represents the later stage of Oceanic Anoxic Event 2. Our results demonstrate a new approach to identifying the origin of crude oils encountered in coastal environments by providing direct constraints on the timing of petroleum generation and potential source rock intervals in poorly characterised offshore sedimentary basins prior to exploratory drilling.
Interaction between NMDA Receptor- and Endocannabinoid-Mediated Modulation of Nociceptive Synapses
Authors: Yuan Sharleen , Burrell Brian D.
Published: February 2019

Nociceptors, sensory neurons that detect damage or potential damage to the body, are the first stage of communicating noxious stimuli from the periphery to central nervous system (CNS). In this study, long-term potentiation (LTP) in the CNS of the medicinal leech, Hirudo verbana, was examined, taking advantage of the ability to selectively record from nociceptive synapses in this model organism. High frequency stimulation (HFS) of nociceptors produced a persistent increase in synaptic transmission and this LTP was both NMDA receptor-mediated and synapse-specific. Surprisingly, inhibition of NMDA receptors during HFS “uncovered” a persistent form of depression. This long-term depression (LTD) was mediated by the endocannabinoid 2-arachidonoyl glycerol (2-AG) acting on a TRPV (transient receptor potential vanilloid) –like channel. These observations suggest that (1) NMDA receptor mediated LTP is observed in nociceptors across both vertebrate and invertebrate phyla and (2) there may be an interaction between NMDA receptor-mediated and endocannabinoid-mediated forms of synaptic plasticity in nociceptors. Specifically, the NMDA receptor mediated processes may suppress endocannabinoid signaling. Such findings could be significant for understanding cellular mechanisms behind nociceptive sensitization and perhaps their contribution to chronic pain.
Optimization of Pulmonary Vasculature Tridimensional Phenotyping in The Rat Fetus
Authors: Aydin Emrah , Levy Brittany , Oria Marc , Nachabe Hussam , Lim Foong-Yen , Peiro Jose L.
Published: February 2019

Comparative, functional, developmental, and some morphological studies on animal anatomy require accurate visualization of three-dimensional structures. Nowadays, several widely applicable methods exist for non-destructive whole-mount imaging of animal tissues. The purpose of this study was to optimize specimen preparation and develop a method for quantitative analysis of the total pulmonary vasculature in fetal rats. Tissues were harvested at E21 and fetuses fixed overnight in 4% paraformaldehyde/phosphate buffered saline. They were treated with 25% Lugol solution for 72 hours to ensure perfusion. Four different methods were used for fetal specimen preparation; isolated lung, upper torso, direct right ventricle contrast injection, and whole body with partial thoracic skin excision. The microCT scan was performed, and pulmonary vasculature was segmented. Vessels were analyzed for diameter, length, and branching. Of the four preparation methods, only whole body with partial thoracic skin excision resulted in adequate reconstruction of the pulmonary vasculature. In silico generated 3D images gathered by micro CT showed pulmonary vasculature distributed throughout the lung, which was representative of the shape and structure of the lungs. The mean number of vessels segmented in the pulmonary tree was 900 ± 24 with a mean diameter of 134.13 µm (range 40.72–265.69 µm). While up to the 30th generation of vessels could be segmented, both for arteries and veins, the majority of branching was between the 21st and 30th generations. Passive diffusion of contrast material enables quantitative analysis of the fetal pulmonary vasculature. This technique is a useful tool to analyze the characteristics and quantify the fetal pulmonary vasculature.
Encoding information into autonomously bursting neural network with pairs of time-delayed pulses
Authors: Kim June Hoan , Lee Ho Jun , Choi Wonshik , Lee Kyoung J.
Published: February 2019

Biological neural networks with many plastic synaptic connections can store external input information in the map of synaptic weights as a form of unsupervised learning. However, the same neural network often produces dramatic reverberating events in which many neurons fire almost simultaneously – a phenomenon coined as ‘population burst.’ The autonomous bursting activity is a consequence of the delicate balance between recurrent excitation and self-inhibition; as such, any periodic sequences of burst-generating stimuli delivered even at a low frequency (~1 Hz) can easily suppress the entire network connectivity. Here we demonstrate that ‘Δt paired-pulse stimulation’, can be a novel way for encoding spatially-distributed high-frequency (~10 Hz) information into such a system without causing a complete suppression. The encoded memory can be probed simply by delivering multiple probing pulses and then estimating the precision of the arrival times of the subsequent evoked recurrent bursts.
Independent Left Ventricular Morphometric Atlases Show Consistent Relationships with Cardiovascular Risk Factors: A UK Biobank Study
Authors: Gilbert Kathleen , Bai Wenjia , Mauger Charlene , Medrano-Gracia Pau , Suinesiaputra Avan , Lee Aaron M. , Sanghvi Mihir M. , Aung Nay , Piechnik Stefan K. , Neubauer Stefan , Petersen Steffen E. , Rueckert Daniel , Young Alistair A.
Published: February 2019

Left ventricular (LV) mass and volume are important indicators of clinical and pre-clinical disease processes. However, much of the shape information present in modern imaging examinations is currently ignored. Morphometric atlases enable precise quantification of shape and function, but there has been no objective comparison of different atlases in the same cohort. We compared two independent LV atlases using MRI scans of 4547 UK Biobank participants: (i) a volume atlas derived by automatic non-rigid registration of image volumes to a common template, and (ii) a surface atlas derived from manually drawn epicardial and endocardial surface contours. The strength of associations between atlas principal components and cardiovascular risk factors (smoking, diabetes, high blood pressure, high cholesterol and angina) were quantified with logistic regression models and five-fold cross validation, using area under the ROC curve (AUC) and Akaike Information Criterion (AIC) metrics. Both atlases exhibited similar principal components, showed similar relationships with risk factors, and had stronger associations (higher AUC and lower AIC) than a reference model based on LV mass and volume, for all risk factors (DeLong p < 0.05). Morphometric variations associated with each risk factor could be quantified and visualized and were similar between atlases. UK Biobank LV shape atlases are robust to construction method and show stronger relationships with cardiovascular risk factors than mass and volume.
Comparison of different smartphone cameras to evaluate conjunctival hyperaemia in normal subjects
Authors: Otero Carles , García-Porta Nery , Tabernero Juan , Pardhan Shahina
Published: February 2019

Despite the significant advantages that smartphones’ cameras can provide in teleophthalmology and artificial intelligence applications, their use as black-box systems for clinical data acquisition, without adequate information of the quality of photographs can compromise data accuracy. The aim of this study is to compare the objective and subjective quantification of conjunctival redness in images obtained with calibrated and non-calibrated cameras, in different lighting conditions and optical magnifications. One hundred ninety-two pictures of the eye were taken in 4 subjects using 3 smartphone cameras{Bq, Iphone, Nexus}, 2 lighting levels{high 815 lx, low 122 lx} and 2 magnification levels{high 10x, low 6x}. Images were duplicated: one set was white balanced and color corrected (calibrated) and the other was left as it was. Each image was subjective and objectively evaluated. There were no significant differences in subjective evaluation in any of the conditions whereas many statistically significant main effects and interaction effects were shown for all the objective metrics. The clinician’s evaluation was not affected by different cameras, lighting conditions or optical magnifications, demonstrating the effectiveness of the human eye’s color constancy properties. However, calibration of a smartphone’s camera is essential when extracting objective data from images.
Identification of Novel Regulatory Genes in APAP Induced Hepatocyte Toxicity by a Genome-Wide CRISPR-Cas9 Screen
Authors: Shortt Katherine , Heruth Daniel P. , Zhang NiNi , Wu Weibin , Singh Shipra , Li Ding-You , Zhang Li Qin , Wyckoff Gerald J. , Qi Lei S. , Friesen Craig A. , Ye Shui Qing
Published: February 2019

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, and 3) predicted affected biological pathways. We further demonstrated the implementation of intermediate time points for the identification of early and late response genes. This study illustrated the power of a genome-wide CRISPR-Cas9 screen to systematically identify novel genes involved in APAP-induced hepatotoxicity and to provide potential targets to develop novel therapeutic modalities.
GPER activation protects against epithelial barrier disruption by Staphylococcus aureus α-toxin
Authors: Triplett Kathleen D. , Pokhrel Srijana , Castleman Moriah J. , Daly Seth M. , Elmore Bradley O. , Joyner Jason A. , Sharma Geetanjali , Herbert Guy , Campen Matthew J. , Hathaway Helen J. , Prossnitz Eric R. , Hall Pamela R.
Published: February 2019

Sex bias in innate defense against Staphylococcus aureus skin and soft tissue infection (SSTI) is dependent on both estrogen production by the host and S. aureus secretion of the virulence factor, α-hemolysin (Hla). The impact of estrogen signaling on the immune system is most often studied in terms of the nuclear estrogen receptors ERα and ERβ. However, the potential contribution of the G protein-coupled estrogen receptor (GPER) to innate defense against infectious disease, particularly with respect to skin infection, has not been addressed. Using a murine model of SSTI, we found that GPER activation with the highly selective agonist G-1 limits S. aureus SSTI and Hla-mediated pathogenesis, effects that were absent in GPER knockout mice. Specifically, G-1 reduced Hla-mediated skin lesion formation and pro-inflammatory cytokine production, while increasing bacterial clearance. In vitro, G-1 reduced surface expression of the Hla receptor, ADAM10, in a human keratinocyte cell line and increased resistance to Hla-mediated permeability barrier disruption. This novel role for GPER activation in skin innate defense against infectious disease suggests that G-1 may have clinical utility in patients with epithelial permeability barrier dysfunction or who are otherwise at increased risk of S. aureus infection, including those with atopic dermatitis or cancer.
Fatty acid profiles of muscle, liver, heart and kidney of Australian prime lambs fed different polyunsaturated fatty acids enriched pellets in a feedlot system
Authors: Van Le Hung , Nguyen Don Viet , Vu Nguyen Quang , Malau-Aduli Bunmi Sherifat , Nichols Peter David , Malau-Aduli Aduli Enoch Othniel
Published: February 2019

We investigated the effect of various dietary polyunsaturated fatty acid (PUFA) sources on the fatty acid profiles of muscle, liver, heart and kidney of Australian prime lambs. Seventy-two White Suffolk x Corriedale first-cross lambs weaned at 6 months of age were randomly allocated to the following six treatments: (1) Control: Lucerne hay only; wheat-based pellets infused with 50 ml/kg dry matter (DM) of oil from (2) rice bran (RBO); (3) canola (CO); (4) rumen-protected (RPO), (5) flaxseed (FSO) and (6) safflower (SO) sources in a completely randomized experimental design. Lambs in CO, FSO, SO and RPO treatments achieved contents of eicosapentaenoic acid (EPA, 22:5n-3) plus docosahexaenoic acid (DHA, 22:6n-3) in the longissimus dorsi muscle ranging from 31.1 to 57.1 mg/135 g, over and above the 30 mg per standard serve (135 g) threshold for “source” claim under the Australian guidelines. There was no difference in n-3 LC-PUFA contents in longissimus dorsi muscle of lambs fed dietary oils of plant origin. The highest 18:3n-3 (ALA) contents achieved with FSO diet in the muscle, liver and heart were 45.6, 128.1 and 51.3 mg/100 g, respectively. Liver and kidney contained high contents of n-3 LC-PUFA (ranging from 306.7 to 598.2 mg/100 g and 134.0 to 300.4 mg/100 g, respectively), with all values readily exceeding the ‘good source’ status (60 mg per serve under Australian guidelines). The liver and kidney of PUFA fed lambs can be labelled as ‘good source’ of n-3 LC-PUFA based on EPA and DHA contents stipulated by the Food Standards of Australia and New Zealand guidelines. Therefore, if lamb consumers consider eating the liver and kidney as their dietary protein sources, they can adequately obtain the associated health benefits of n-3 LC-PUFA.
Correlation of systemic arterial stiffness with changes in retinal and choroidal microvasculature in type 2 diabetes
Authors: Kim Mirinae , Kim Rae-Young , Kim Joo-Young , Park Young-Hoon
Published: February 2019

This study was conducted to assess whether systemic arterial stiffness, indicated by cardio-ankle vascular index (CAVI), is related to changes in the microvasculature of the retina and choroid in diabetes mellitus (DM). This study included 113 patients with a confirmed diagnosis of type-2 DM. Among them, 18 patients did not have diabetic retinopathy (DR), 71 had non-proliferative DR (NPDR), and 24 had proliferative DR (PDR). The mean CAVI was 7.58 ± 1.41 in no DR, 8.72 ± 1.47 in NPDR, and 8.43 ± 1.25 in PDR group. Of the 113 eyes, 42 (37.2%) were classified as abnormal CAVI group (CAVI ≥ 9). This group had significantly higher cardiac autonomic neuropathy risk index score, decreased central choroidal thickness, and decreased choroidal vascularity index (CVI). Deep foveal avascular zone area was higher in the abnormal CAVI group. After adjustment for possible confounding factors, CAVI showed negative correlation with the CVI (r = −0.247, P = 0.013). In conclusion, there was a significant correlation between arteriosclerosis and choroidal vascular changes in DR. We suggest prompt ophthalmic evaluation in patients with systemic arteriosclerosis. If the ophthalmologist notes advanced DR, the patient should be referred to a cardiovascular clinic for detailed evaluation of systemic arteriosclerosis.
Patterns of cardiovascular variability after long-term sino-aortic denervation in unanesthetized adult rats
Authors: Radaelli Alberto , Mancia Giuseppe , De Carlini Caterina , Soriano Francesco , Castiglioni Paolo
Published: February 2019

Baroreflex dysfunction is a diffuse chronic condition that is expected to be followed by a profound loss of organization of BP and HR variability. Nevertheless, long-term effects of baroreflex withdrawal are still debated. Aim of our work was to study BP and HR changes long term after sino-aortic denervation (SAD). Inter-beat-interval (IBI) and intra-arterial BP were recorded beat-by-beat in 43 Wistar-Kyoto rats (Controls, n = 33; SAD rats, n = 10). Power spectra were calculated in controls and in SAD rats within three days and at seven months from denervation. Compared to controls, chronic SAD rats showed 1) similar mean BP (control vs SAD: 95 ± 16 vs 87 ± 22 mmHg) and IBI (171 ± 22 vs 181 ± 15 ms) values, 2) dramatically higher values of BP variance (12 ± 2 vs 64 ± 2 mmHg2, p < 0.01) and of ultra- (ULF) and very-low-frequency (VLF) BP oscillations, 3) dramatically higher values of IBI variability (24 ± 2 vs 71 ± 4 ms2, p < 0.01) and of ULF-IBI oscillations that were synchronized with BP oscillations. Chronic SAD rats reveal a marked change in the pattern of cardiovascular variability characterized by the appearance of synchronized slower oscillations of BP and HR. The cardiovascular system, therefore, retains a high level of organization despite the absence of a reflex control mechanism.