bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement Receptor 1 availability on red blood cell surface modulates Plasmodium vivax invasion of human reticulocytes
Authors: Prajapati Surendra Kumar , Borlon Céline , Rovira-Vallbona Eduard , Gruszczyk Jakub , Menant Sebastien , Tham Wai-Hong , Kattenberg Johanna Helena , Villasis Elizabeth , De Meulenaere Katlijn , Gamboa Dionicia , Vinetz Joseph , Fujita Ricardo , Xuan Xa Nguyen , Urbano Ferreira Marcelo , Niño Carlos H. , Patarroyo Manuel A. , Spanakos Gregory , Kestens Luc , Abbeele Jan Van Den , Rosanas-Urgell Anna
Published: June 2019

Plasmodium vivaxparasites preferentially invade reticulocyte cells in a multistep process that is still poorly understood. In this study, we usedex vivoinvasion assays and population genetic analyses to investigate the involvement of complement receptor 1 (CR1) inP.vivaxinvasion. First, we observed thatP.vivaxinvasion of reticulocytes was consistently reduced when CR1 surface expression was reduced through enzymatic cleavage, in the presence of naturally low-CR1-expressing cells compared with high-CR1-expressing cells, and with the addition of soluble CR1, a known inhibitor ofP.falciparuminvasion. Immuno-precipitation experiments withP.vivaxReticulocyte Binding Proteins showed no evidence of complex formation. In addition, analysis of CR1 genetic data for worldwide human populations with different exposure to malaria parasites show significantly higher frequency of CR1 alleles associated with low receptor expression on the surface of RBCs and higher linkage disequilibrium in human populations exposed toP.vivaxmalaria compared with unexposed populations. These results are consistent with a positive selection of low-CR1-expressing alleles in vivax-endemic areas. Collectively, our findings demonstrate that CR1 availability on the surface of RBCs modulatesP.vivaxinvasion. The identification of new molecular interactions is crucial to guiding the rational development of new therapeutic interventions against vivax malaria.
From basic perception deficits to facial affect recognition impairments in schizophrenia
Authors: Marosi Csilla , Fodor Zsuzsanna , Csukly Gábor
Published: June 2019

While impaired facial emotion recognition and magnocellular deficits in visual perception are core features of schizophrenia, their relationship is still unclear. Our aim was to analyze the oscillatory background of these processes and to investigate the connection between the magnocellular pathway deficit and the abnormal facial affect processing. Thirty-nine subjects with schizophrenia and forty socially matched healthy controls subjects were enrolled. A 128 channel EEG was recorded in three experimental tasks: first, participants viewed magnocellular biased low-spatial frequency (LSF) and parvocellular biased high-spatial frequency (HSF) Gabor-patches, then faces and houses were presented and in the third task a facial affect recognition task was presented with happy, sad and neutral faces. Event-related theta (4–7 Hz) synchronization (ERS) (i.e. an increase in theta power) by magnocellular biased stimuli was decreased in patients relative to controls, while no similar differences were found between groups in the parvocellular biased condition. ERS was significantly lower in patients compared to healthy controls both in the face and in the emotion recognition task. Theta ERS to magnocellular biased stimuli, but not to parvocellular biased stimuli, were correlated with emotion recognition performance. These findings indicate a bottom up disruption of face perception and emotion recognition in schizophrenia.
In-silico Prediction of Synergistic Anti-Cancer Drug Combinations Using Multi-omics Data
Authors: Celebi Remzi , Bear Don’t Walk Oliver , Movva Rajiv , Alpsoy Semih , Dumontier Michel
Published: June 2019

Chemotherapy is a routine treatment approach for early-stage cancers, but the effectiveness of such treatments is often limited by drug resistance, toxicity, and tumor heterogeneity. Combination chemotherapy, in which two or more drugs are applied simultaneously, offers one promising approach to address these concerns, since two single-target drugs may synergize with one another through interconnected biological processes. However, the identification of effective dual therapies has been particularly challenging; because the search space is large, combination success rates are low. Here, we present our method for DREAM AstraZeneca-Sanger Drug Combination Prediction Challenge to predict synergistic drug combinations. Our approach involves using biologically relevant drug and cell line features with machine learning. Our machine learning model obtained the primary metric = 0.36 and the tie-breaker metric = 0.37 in the extension round of the challenge which was ranked in top 15 out of 76 submissions. Our approach also achieves a mean primary metric of 0.39 with ten repetitions of 10-fold cross-validation. Further, we analyzed our model’s predictions to better understand the molecular processes underlying synergy and discovered that key regulators of tumorigenesis such as TNFA and BRAF are often targets in synergistic interactions, while MYC is often duplicated. Through further analysis of our predictions, we were also ble to gain insight into mechanisms and potential biomarkers of synergistic drug pairs.
The effect of trait anxiety on attentional mechanisms in combined context and cue conditioning and extinction learning
Authors: Stegmann Yannik , Reicherts Philipp , Andreatta Marta , Pauli Paul , Wieser Matthias J.
Published: June 2019

Sensory processing and attention allocation are shaped by threat, but the role of trait-anxiety in sensory processing as a function of threat predictability remains incompletely understood. Therefore, we measured steady-state visual evoked potentials (ssVEPs) as an index of sensory processing of predictable and unpredictable threat cues in 29 low (LA) and 29 high (HA) trait-anxious participants during a modified NPU-paradigm followed by an extinction phase. Three different contextual cues indicated safety (N), predictable (P) or unpredictable threat (U), while foreground cues signalled shocks in the P-condition only. All participants allocated increased attentional resources to the central P-threat cue, replicating previous findings. Importantly, LA individuals exhibited larger ssVEP amplitudes to contextual threat (U and P) than to contextual safety cues, while HA individuals did not differentiate among contextual cues in general. Further, HA exhibited higher aversive ratings of all contexts compared to LA. These results suggest that high trait-anxious individuals might be worse at discriminating contextual threat stimuli and accordingly overestimate the probability and aversiveness of unpredictable threat. These findings support the notion of aberrant sensory processing of unpredictable threat in anxiety disorders, as this processing pattern is already evident in individuals at risk of these disorders.
Measuring the atomic spin-flip scattering rate by x-ray emission spectroscopy
Authors: Decker Régis , Born Artur , Büchner Robby , Ruotsalainen Kari , Stråhlman Christian , Neppl Stefan , Haverkamp Robert , Pietzsch Annette , Föhlisch Alexander
Published: June 2019

While extensive work has been dedicated to the measurement of the demagnetization time following an ultra-short laser pulse, experimental studies of its underlying microscopic mechanisms are still scarce. In transition metal ferromagnets, one of the main mechanism is the spin-flip of conduction electrons driven by electron-phonon scattering. Here, we present an original experimental method to monitor the electron-phonon mediated spin-flip scattering rate in nickel through the stringent atomic symmetry selection rules of x-ray emission spectroscopy. Increasing the phonon population leads to a waning of the 3d → 2p3/2 decay peak intensity, which reflects an increase of the angular momentum transfer scattering rate attributed to spin-flip. We find a spin relaxation time scale in the order of 50 fs in the 3d-band of nickel at room temperature, while consistantly, no such peak evolution is observed for the diamagnetic counterexample copper, using the same method.
Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis12
Authors: Abe-Kanoh Naomi , Kunisue Narumi , Myojin Takumi , Chino Ayako , Munemasa Shintaro , Murata Yoshiyuki , Satoh Ayano , Moriya Hisao , Nakamura Yoshimasa
Published: June 2019

Benzyl isothiocyanate (BITC) is a naturally-occurring isothiocyanate derived from cruciferous vegetables. BITC has been reported to inhibit the proliferation of various cancer cells, which is believed to be important for the inhibition of tumorigenesis. However, the detailed mechanisms of action remain unclear. In this study, we employed a budding yeast Saccharomyces cerevisiae as a model organism for screening. Twelve genes including MTW1 were identified as the overexpression suppressors for the antiproliferative effect of BITC using the genome-wide multi-copy plasmid collection for S. cerevisiae. Overexpression of the kinetochore protein Mtw1 counteracts the antiproliferative effect of BITC in yeast. The inhibitory effect of BITC on the proliferation of human colon cancer HCT-116 cells was consistently suppressed by the overexpression of Mis12, a human orthologue of Mtw1, and enhanced by the knockdown of Mis12. We also found that BITC increased the phosphorylated and ubiquitinated Mis12 level with consequent reduction of Mis12, suggesting that BITC degrades Mis12 through an ubiquitin-proteasome system. Furthermore, cell cycle analysis showed that the change in the Mis12 level affected the cell cycle distribution and the sensitivity to the BITC-induced apoptosis. These results provide evidence that BITC suppresses cell proliferation through the post-transcriptional regulation of the kinetochore protein Mis12.
Neuropeptide precursors and neuropeptides in the sea cucumber Apostichopus japonicus: a genomic, transcriptomic and proteomic analysis
Authors: Chen Muyan , Talarovicova Alzbeta , Zheng Yingqiu , Storey Kenneth B. , Elphick Maurice R.
Published: June 2019

The sea cucumber Apostichopus japonicus is a foodstuff with very high economic value in China, Japan and other countries in south-east Asia. It is at the heart of a multibillion-dollar industry and to meet demand for this product, aquaculture methods and facilities have been established. However, there are challenges associated with optimization of reproduction, feeding and growth in non-natural environments. Therefore, we need to learn more about the biology of A. japonicus, including processes such as aestivation, evisceration, regeneration and albinism. One of the major classes of molecules that regulate physiology and behaviour in animals are neuropeptides, and a few bioactive peptides have already been identified in A. japonicus. To facilitate more comprehensive investigations of neuropeptide function in A. japonicus, here we have analysed genomic and transcriptomic sequence data and proteomic data to identify neuropeptide precursors and neuropeptides in this species. We identified 44 transcripts encoding neuropeptide precursors or putative neuropeptide precursors, and in some instances neuropeptides derived from these precursors were confirmed by mass spectrometry. Furthermore, analysis of genomic sequence data enabled identification of the location of neuropeptide precursor genes on genomic scaffolds and linkage groups (chromosomes) and determination of gene structure. Many of the precursors identified contain homologs of neuropeptides that have been identified in other bilaterian animals. Precursors of neuropeptides that have thus far only been identified in echinoderms were identified, including L- and F-type SALMFamides, AN peptides and others. Precursors of several peptides that act as modulators of neuromuscular activity in A. japonicus were also identified. The discovery of a large repertoire of neuropeptide precursors and neuropeptides provides a basis for experimental studies that investigate the physiological roles of neuropeptide signaling systems in A. japonicus. Looking ahead, some of these neuropeptides may have effects that could be harnessed to enable improvements in the aquaculture of this economically important species.
Energy expenditure for isometric contractions of right and left ventricular trabeculae over a wide range of frequencies at body temperature
Authors: Pham Toan , Zgierski-Johnston Callum M. , Tran Kenneth , Taberner Andrew J. , Loiselle Denis S. , Han June-Chiew
Published: June 2019

We studied the energy expenditure of isometric contractions using both right-ventricular (RV) and left-ventricular (LV) trabeculae isolated from the rat heart. The energy expenditure under isometric contraction presents entirely as heat liberation. Preparations were challenged to perform at various rates of energy demand while accounting for their inevitable time-dependent decline of performance. They were electrically stimulated to contract at 37 °C with a frequency order (between 0.1 Hz and 10 Hz) dictated by a fully-balanced Latin-Square experimental design. We measured, simultaneously, their stress production and heat output. As functions of stimulus frequency, active stress and heat were not significantly different between RV and LV trabeculae. However, contraction kinetics, indexed as the maximal rate of rise and fall of twitch, were lower in the LV trabeculae. The ratio of heat to stress was greater in the LV trabeculae, suggesting that the economy of contraction of the LV trabeculae is lower. Their lower economy became more pronounced at high stimulus frequencies. Our results allow us to assess whether slowing of kinetics is a causative mechanism for improvement of economy of contraction.
Dual optical force plate for time resolved measurement of forces and pressure distributions beneath shoes and feet
Authors: Tompkins Christopher G. , Sharp James S.
Published: June 2019

Frustrated total internal reflection (FTIR) imaging was used to perform remote optical measurements of the forces/pressures exerted beneath shoes and feet during a number of different training activities including countermovement jumps, jogging and drop jumps. A single camera was used to simultaneously image two acrylic, FTIR waveguide imaging elements from below, at frame rates up to 200 frames per second. The images obtained using the camera were converted into pressure/force maps using a previously developed theory which combines the mechanics of contact of soft objects and the scattering of evanescent waves. The forces obtained from the optical measurements were shown to be in good agreement with measurements obtained from load cells placed beneath the FTIR imaging elements. The ability to produce accurate spatial maps of the force/pressure distribution beneath soft contacting objects such as feet and shoe outsoles at high frame rates has numerous potential applications in sports sciences and medicine.
EEG functional connectivity metrics wPLI and wSMI account for distinct types of brain functional interactions
Authors: Imperatori Laura Sophie , Betta Monica , Cecchetti Luca , Canales-Johnson Andrés , Ricciardi Emiliano , Siclari Francesca , Pietrini Pietro , Chennu Srivas , Bernardi Giulio
Published: June 2019

The weighted Phase Lag Index (wPLI) and the weighted Symbolic Mutual Information (wSMI) represent two robust and widely used methods for MEG/EEG functional connectivity estimation. Interestingly, both methods have been shown to detect relative alterations of brain functional connectivity in conditions associated with changes in the level of consciousness, such as following severe brain injury or under anaesthesia. Despite these promising findings, it was unclear whether wPLI and wSMI may account for distinct or similar types of functional interactions. Using simulated high-density (hd-)EEG data, we demonstrate that, while wPLI has high sensitivity for couplings presenting a mixture of linear and nonlinear interdependencies, only wSMI can detect purely nonlinear interaction dynamics. Moreover, we evaluated the potential impact of these differences on real experimental data by computing wPLI and wSMI connectivity in hd-EEG recordings of 12 healthy adults during wakefulness and deep (N3-)sleep, characterised by different levels of consciousness. In line with the simulation-based findings, this analysis revealed that both methods have different sensitivity for changes in brain connectivity across the two vigilance states. Our results indicate that the conjoint use of wPLI and wSMI may represent a powerful tool to study the functional bases of consciousness in physiological and pathological conditions.
Prophylactic inhibition of soluble epoxide hydrolase delays onset of nephritis and ameliorates kidney damage in NZB/W F1 mice
Authors: Klocke Jan , Ulu Arzu , Wu Kaiyin , Rudolph Birgit , Dragun Duska , Gollasch Maik , Schunck Wolf-Hagen , Hammock Bruce D. , Riemekasten Gabriela , Enghard Philipp
Published: June 2019

Epoxy-fatty-acids (EpFAs), cytochrome P450 dependent arachidonic acid derivatives, have been suggested to have anti-inflammatory properties, though their effects on autoimmune diseases like systemic lupus erythematosus (SLE) have yet to be investigated. We assessed the influence of EpFAs and their metabolites in lupus prone NZB/W F1 mice by pharmacological inhibition of soluble epoxide hydrolase (sEH, EPHX2). The sEH inhibitor 1770 was administered to lupus prone NZB/W F1 mice in a prophylactic and a therapeutic setting. Prophylactic inhibition of sEH significantly improved survival and reduced proteinuria. By contrast, sEH inhibitor-treated nephritic mice had no survival benefit; however, histological changes were reduced when compared to controls. In humans, urinary EpFA levels were significantly different in 47 SLE patients when compared to 10 healthy controls. Gene expression of EPHX2 was significantly reduced in the kidneys of both NZB/W F1 mice and lupus nephritis (LN) patients. Correlation of EpFAs with SLE disease activity and reduced renal EPHX gene expression in LN suggest roles for these components in human disease.
Structure-preserving visualisation of high dimensional single-cell datasets
Authors: Szubert Benjamin , Cole Jennifer E. , Monaco Claudia , Drozdov Ignat
Published: June 2019

Single-cell technologies offer an unprecedented opportunity to effectively characterize cellular heterogeneity in health and disease. Nevertheless, visualisation and interpretation of these multi-dimensional datasets remains a challenge. We present a novel framework, ivis, for dimensionality reduction of single-cell expression data. ivis utilizes a siamese neural network architecture that is trained using a novel triplet loss function. Results on simulated and real datasets demonstrate that ivis preserves global data structures in a low-dimensional space, adds new data points to existing embeddings using a parametric mapping function, and scales linearly to hundreds of thousands of cells. ivis is made publicly available through Python and R interfaces on https://github.com/beringresearch/ivis.
Coro2b, a podocyte protein downregulated in human diabetic nephropathy, is involved in the development of protamine sulphate-induced foot process effacement
Authors: Schwarz Angelina , Möller-Hackbarth Katja , Ebarasi Lwaki , Unnersjö Jess David , Zambrano Sonia , Blom Hans , Wernerson Annika , Lal Mark , Patrakka Jaakko
Published: June 2019

Podocytes have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte foot process effacement, mediated largely by the actin-based cytoskeleton of foot processes, is commonly detected in DN and is believed to be a key pathogenic event in the development of proteinuria. In this study, we identified coronin 2b (Coro2b), a member of known actin-regulating proteins, the coronins, as a highly podocyte-enriched molecule located at the cytoplasmic side of the apical plasma membrane. Studies in human renal biopsies show that glomerular Coro2b expression is significantly down-regulated in patients with DN. Studies in knockout mice indicate that Coro2b is not required for the development or maintenance of the glomerular filtration barrier. Moreover, inactivation of Coro2b specifically in podocytes does not affect the outcome of nephropathy in a streptozotocin-induced diabetes model. However, Coro2b seems to modulate the reorganization of foot processes under pathological conditions as Coro2b knockout podocytes are partially protected from protamine sulfate perfusion-induced foot process effacement. Taken together, our study suggests a role for Coro2b in the pathogenesis of glomerulopathies. Further studies regarding the involvement of Coro2b in podocyte health and diseases are warranted.
Two-step closure of the Miocene Indian Ocean Gateway to the Mediterranean
Authors: Bialik Or M. , Frank Martin , Betzler Christian , Zammit Ray , Waldmann Nicolas D.
Published: June 2019

The Tethys Ocean was compartmentalized into the Mediterranean Sea and Indian Ocean during the early Miocene, yet the exact nature and timing of this disconnection are not well understood. Here we present two new neodymium isotope records from isolated carbonate platforms on both sides of the closing seaway, Malta (outcrop sampling) and the Maldives (IODP Site U1468), to constrain the evolution of past water mass exchange between the present day Mediterranean Sea and Indian Ocean via the Mesopotamian Seaway. Combining these data with box modeling results indicates that water mass exchange was reduced by ~90% in a first step at ca. 20 Ma. The terminal closure of the seaway then coincided with the sea level drop caused by the onset of permanent glaciation of Antarctica at ca. 13.8 Ma. The termination of meridional water mass exchange through the Tethyan Seaway resulted in a global reorganization of currents, paved the way to the development of upwelling in the Arabian Sea and possibly led to a strengthening of South Asian Monsoon.
Bidirectional regulatory potentials of short-chain fatty acids and their G-protein-coupled receptors in autoimmune neuroinflammation
Authors: Park Jeongho , Wang Qin , Wu Qi , Mao-Draayer Yang , Kim Chang H.
Published: June 2019

Microbial metabolites, produced in the intestine, have significant effects on inflammatory diseases throughout the body. Short-chain fatty acids (SCFAs) have protective effects on experimental autoimmune encephalitis (EAE) responses but the detailed roles of SCFAs and their receptors in regulating autoimmune CNS inflammation have been unclear. SCFAs metabolically regulate T cells and change the phenotype of antigen presenting cells to efficiently induce IL-10+regulatory T cells. In line with the overall protective effect, blood levels of major SCFAs, such as acetate, propionate and butyrate, are significantly decreased in long-term active progressive multiple sclerosis (MS) patients. Importantly, SCFAs can induce CD4+effector T cells, which are highly inflammatory when transferred into mice, suggesting that the direct effect of SCFAs on T cells can even be pro-inflammatory in the CNS. In contrast to the moderate protective effect of SCFAs, mice deficient in GPR41 or GPR43 are more resistant to EAE pathogenesis. Thus, despite the overall protective function of SCFAs, SCFAs and their receptors have the potential to regulate autoimmune CNS inflammation both positively and negatively.
Delimiting a species’ geographic range using posterior sampling and computational geometry
Authors: Keith Jonathan M. , Spring Daniel , Kompas Tom
Published: June 2019

Accurate delimitation of the geographic range of a species is important for control of biological invasions, conservation of threatened species, and understanding species range dynamics under environmental change. However, estimating range boundaries is challenging because monitoring methods are imperfect, the area that might contain individuals is often incompletely surveyed, and species may have patchy distributions. In these circumstances, large areas can be surveyed without finding individuals despite occupancy extending beyond surveyed areas, resulting in underestimation of range limits. We developed a delimitation method that can be applied with imperfect survey data and patchy distributions. The approach is to construct polygons indicative of the geographic range of a species. Each polygon is associated with a specific probability such that each interior point of the polygon has at least that posterior probability of being interior to the true boundary according to a Bayesian model. The method uses the posterior distribution of latent quantities derived from an agent-based Bayesian model and calculates the posterior distribution of the range as a derived quantity from Markov chain Monte Carlo samples. An application of this method described here informed the Australian campaign to eradicate red imported fire ants (Solenopsis invicta).
Fin whale (Balaenoptera physalus) migration in Australian waters using passive acoustic monitoring
Authors: Aulich Meghan G. , McCauley Robert D. , Saunders Benjamin J. , Parsons Miles J. G.
Published: June 2019

The fin whale is a globally endangered species and is listed as threatened in Australia, however no peer-reviewed studies are available to indicate the migratory movements of the species in Australian waters. This study uses passive acoustic monitoring as a tool to identify the migratory movements of fin whales in Australian waters. Sampling was conducted from eight locations around Australia between 2009 and 2017, providing a total of 37 annual migratory records. Taken together, our observations provide evidence of fin whale migration through Australian waters, with earliest arrival of the animals recorded on the Western Australian coast, at Cape Leeuwin in April. The whales travel through Cape Leeuwin, migrating northward along the Western Australian coast to the Perth Canyon (May to October), which likely acts as a way-station for feeding. Some whales continue migrating as far north as Dampier (19°S). On Australia’s east coast, at Tuncurry, fin whale seasonal presence each year occurred later, from June to late September/October. A total of only 8,024 fin whale pulses were recorded on the east coast, compared to 177,328 pulses recorded at the Perth Canyon. We suggest these differences, as well as the spatial separation between coasts, provide preliminary evidence that the fin whales present on the east and west coasts constitute separate sub-populations.
An improved method for the heterologous production of soluble human ribosomal proteins in Escherichia coli
Authors: Correddu Danilo , Montaño López José de Jesús , Vadakkedath Praveen G. , Lai Amy , Pernes Jane I. , Watson Paris R. , Leung Ivanhoe K. H.
Published: June 2019

Human ribosomal proteins play important structural and functional roles in the ribosome and in protein synthesis. An efficient method to recombinantly produce and purify these proteins would enable their full characterisation. However, the production of human ribosomal proteins can be challenging. The only published method about the recombinant production of human ribosomal proteins involved the recovery of proteins from inclusion bodies, a process that is tedious and may lead to significant loss of yield. Herein, we explored the use of different Escherichia coli competent cells and fusion protein tags for the recombinant production of human ribosomal proteins. We found that, by using thioredoxin as a fusion protein, soluble ribosomal protein could be obtained directly from cell lysates, thus leading to an improved method to recombinantly produce these proteins.
Soybean (Glycine max L.) triacylglycerol lipase GmSDP1 regulates the quality and quantity of seed oil
Authors: Kanai Masatake , Yamada Tetsuya , Hayashi Makoto , Mano Shoji , Nishimura Mikio
Published: June 2019

Seeds of soybean (Glycine max L.) are a major source of plant-derived oils. In the past, improvements have been made in the quantity and quality of seed oil. Triacylglycerols (TAGs) are the principal components of soybean seed oil, and understanding the metabolic regulation of TAGs in soybean seeds is essential. Here, we identified four soybean genes encoding TAG lipases, designated as SUGAR DEPENDENT1-1 (GmSDP1-1), GmSDP1-2, GmSDP1-3 and GmSDP1-4; these are homologous to Arabidopsis thaliana SDP1 (AtSDP1). To characterize the function of these genes during grain filling, transgenic lines of soybean were generated via RNA interference to knockdown the expression of all four GmSDP1 genes. The seed oil content of the transgenic soybean lines was significantly increased compared with the wild type (WT). Additionally, fatty acid profiles of the WT and transgenic soybean lines were altered; the content of linoleic acid, a major fatty acid in soybean seeds, was significantly reduced, whereas that of oleic acid was increased in transgenic soybean seeds compared with the WT. Substrate specificity experiments showed that TAG lipase preferentially cleaved oleic acid than linoleic acid in the oil body membrane in WT soybean. This study demonstrates that the GmSDP1 proteins regulate both the TAG content and fatty acid composition of soybean seeds during grain filling. These results provide a novel strategy for improving both the quantity and quality of soybean seed oil.
Quantitative analysis of the macula with optical coherence tomography angiography in normal Japanese subjects: The Taiwa Study
Authors: Sato Risa , Kunikata Hiroshi , Asano Toshifumi , Aizawa Naoko , Kiyota Naoki , Shiga Yukihiro , Nishiguchi Koji M. , Kato Keiichi , Nakazawa Toru
Published: June 2019

This study evaluated age-related changes in the superficial and deep retinal capillary plexus (SCP and DCP, respectively) and in the foveal avascular zone (FAZ). SCP and DCP perfusion density (PD) were measured in optical coherence tomography angiography (OCTA) macular scans of 145 eyes of 145 healthy Japanese subjects, and findings were compared with SCP FAZ and clinical data. We found that age was negatively correlated with SCP and DCP PD (r = −0.17, P = 0.04 and r = −0.20, P = 0.02, respectively) and positively correlated with FAZ area (r = 0.18, P = 0.03). SCP and DCP PD were correlated with each other (r = 0.67, P < 0.001). FAZ area was negatively correlated with SCP PD, DCP PD and central macular thickness (CMT) (r = −0.18, P = 0.03; r = −0.25, P < 0.01; and r = −0.39, P < 0.001, respectively). FAZ was larger and CMT was lower (P = 0.01 and P < 0.001, respectively) in women than men. SCP and DCP PD were positively correlated with estimated glomerular filtration rate (r = 0.17, P = 0.03 and r = 0.24, P < 0.01, respectively). Multiple regression analysis confirmed that age independently affected DCP PD and FAZ (P = 0.02 and P < 0.01, respectively) and that CMT independently affected FAZ area (P < 0.001). Thus, normal subjects showed age-related decreases in macular PD and renal function. FAZ and CMT were related, suggesting that age-related changes in macular thickness also affect capillary vasculature.
The importance of side branches in modeling 3D hemodynamics from angiograms for patients with coronary artery disease
Authors: Vardhan Madhurima , Gounley John , Chen S. James , Kahn Andrew M. , Leopold Jane A. , Randles Amanda
Published: June 2019

Genesis of atherosclerotic lesions in the human arterial system is critically influenced by the fluid mechanics. Applying computational fluid dynamic tools based on accurate coronary physiology derived from conventional biplane angiogram data may be useful in guiding percutaneous coronary interventions. The primary objective of this study is to build and validate a computational framework for accurate personalized 3-dimensional hemodynamic simulation across the complete coronary arterial tree and demonstrate the influence of side branches on coronary hemodynamics by comparing shear stress between coronary models with and without these included. The proposed novel computational framework based on biplane angiography enables significant arterial circulation analysis. This study shows that models that take into account flow through all side branches are required for precise computation of shear stress and pressure gradient whereas models that have only a subset of side branches are inadequate for biomechanical studies as they may overestimate volumetric outflow and shear stress. This study extends the ongoing computational efforts and demonstrates that models based on accurate coronary physiology can improve overall fidelity of biomechanical studies to compute hemodynamic risk-factors.
Effects of local climate on loggerhead hatchling production in Brazil: Implications from climate change
Authors: Montero Natalie , Tomillo Pilar Santidrian , Saba Vincent S. , dei Marcovaldi Maria A. G. , López-Mendilaharsu Milagros , Santos Alexsandro S. , Fuentes Mariana M. P. B.
Published: June 2019

Sea turtle eggs are heavily influenced by the environment in which they incubate, including effects on hatching success and hatchling viability (hatchling production). It is crucial to understand how the hatchling production of sea turtles is influenced by local climate and how potential changes in climate may impact future hatchling production. Generalized Additive Models were used to determine the relationship of six climatic variables at different temporal scales on loggerhead turtle (Caretta caretta) hatchling production at seventeen nesting beaches in Bahia, Espirito Santo, and Rio de Janeiro, Brazil. Using extreme and conservative climate change scenarios throughout the 21st century, potential impacts on future hatching success (the number of hatched eggs in a nest) were predicted using the climatic variable(s) that best described hatchling production at each nesting beach. Air temperature and precipitation were found to be the main drivers of hatchling production throughout Brazil. CMIP5 climate projections are for a warming of air temperature at all sites throughout the 21st century, while projections for precipitation vary regionally. The more tropical nesting beaches in Brazil, such as those in Bahia, are projected to experience declines in hatchling production, while the more temperate nesting beaches, such as those in Rio de Janeiro, are projected to experience increases in hatchling production by the end of the 21st century.
Microbial communities in top- and subsoil of repacked soil columns respond differently to amendments but their diversity is negatively correlated with plant productivity
Authors: Celestina Corinne , Wood Jennifer L. , Manson James B. , Wang Xiaojuan , Sale Peter W. G. , Tang Caixian , Franks Ashley E.
Published: June 2019

Organic and inorganic amendments with equivalent nutrient content may have comparable fertilizer effects on crop yield, but their effects on the soil microbial community and subsequent plant-soil-microbe interactions in this context are unknown. This experiment aimed to understand the relationship between soil microbial communities, soil physicochemical characteristics and crop performance after addition of amendments to soil. Poultry litter and synthetic fertilizer with balanced total nitrogen (N) content equivalent to 1,200 kg ha−1 were added to the topsoil (0–10 cm) or subsoil layer (20–30 cm) of repacked soil columns. Wheat plants were grown until maturity. Soil samples were taken at Zadoks 87–91 (76 days after sowing) for analysis of bacterial and fungal communities using 16S and ITS amplicon sequencing. The interaction between amendment type and placement depth had significant effects on bacterial and fungal community structure and diversity in the two soil layers. Addition of poultry litter and fertilizer stimulated or suppressed different taxa in the topsoil and subsoil leading to divergence of these layers from the untreated control. Both amendments reduced microbial community richness, diversity and evenness in the topsoil and subsoil compared to the nil-amendment control, with these reductions in diversity being consistently negatively correlated with plant biomass (root and shoot weight, root length, grain weight) and soil fertility (soil NH4+, shoot N). These results indicate that in this experimental system, the soil microbial diversity was correlated negatively with plant productivity.
Room-temperature Operation of Low-voltage, Non-volatile, Compound-semiconductor Memory Cells
Authors: Tizno Ofogh , Marshall Andrew R. J. , Fernández-Delgado Natalia , Herrera Miriam , Molina Sergio I. , Hayne Manus
Published: June 2019

Whilst the different forms of conventional (charge-based) memories are well suited to their individual roles in computers and other electronic devices, flaws in their properties mean that intensive research into alternative, or emerging, memories continues. In particular, the goal of simultaneously achieving the contradictory requirements of non-volatility and fast, low-voltage (low-energy) switching has proved challenging. Here, we report an oxide-free, floating-gate memory cell based on III-V semiconductor heterostructures with a junctionless channel and non-destructive read of the stored data. Non-volatile data retention of at least 104 s in combination with switching at ≤2.6 V is achieved by use of the extraordinary 2.1 eV conduction band offsets of InAs/AlSb and a triple-barrier resonant tunnelling structure. The combination of low-voltage operation and small capacitance implies intrinsic switching energy per unit area that is 100 and 1000 times smaller than dynamic random access memory and Flash respectively. The device may thus be considered as a new emerging memory with considerable potential.
Characterization of C-nucleoside Antimicrobials from Streptomyces albus DSM 40763: Strepturidin is Pseudouridimycin
Authors: Rosenqvist Petja , Palmu Kaisa , Prajapati Ranjit Kumar , Yamada Keith , Niemi Jarmo , Belogurov Georgiy A. , Metsä-Ketelä Mikko , Virta Pasi
Published: June 2019

Pseudouridimycin (PUM), a selective inhibitor of bacterial RNA polymerase has been previously detected in microbial-extracts of two strains of Streptomyces species (strain ID38640 and ID38673). Here, we isolated PUM and its deoxygenated analogue desoxy-pseudouridimycin (dPUM) from Streptomyces albus DSM 40763, previously reported to produce the metabolite strepturidin (STU). The isolated compounds were characterized by HRMS and spectroscopic techniques and they selectively inhibited transcription by bacterial RNA polymerase as previously reported for PUM. In contrast, STU could not be detected in the cultures of S. albus DSM 40763. As the reported characteristics reported for STU are almost identical with that of PUM, the existence of STU was questioned. We further sequenced the genome of S. albus DSM 40763 and identified a gene cluster that contains orthologs of all PUM biosynthesis enzymes but lacks the enzymes that would conceivably allow biosynthesis of STU as an additional product.
Reducing Campylobacter jejuni colonization in broiler chickens by in-feed supplementation with hyperimmune egg yolk antibodies
Authors: Vandeputte Jasmien , Martel An , Canessa Stefano , Van Rysselberghe Nathalie , De Zutter Lieven , Heyndrickx Marc , Haesebrouck Freddy , Pasmans Frank , Garmyn An
Published: June 2019

Campylobacterinfections sourced mainly to poultry products, are the most important bacterial foodborne zoonoses worldwide. No effective measures to control these infections in broiler production exist to date. Here, we used passive immunization with hyperimmune egg yolks to confer broad protection of broilers againstCampylobacterinfection. Two novel vaccines, a bacterin of thirteenCampylobacter jejuni(C.jejuni) andC.colistrains and a subunit vaccine of six immunodominantCampylobacterantigens, were used for the immunization of layers, resulting in high and prolonged levels of specific immunoglobulin Y (IgY) in the hens’ yolks. In the firstin vivotrial, yolks (sham, bacterin or subunit vaccine derived) were administered prophylactically in the broiler feed. Both the bacterin- and subunit vaccine-induced IgY significantly reduced the number ofCampylobacter-colonized broilers. In the secondin vivotrial, the yolks were administered therapeutically during three days before euthanasia. The bacterin IgY resulted in a significant decrease inC.jejunicounts per infected bird. The hyperimmune yolks showed strong reactivity to a broad representation ofC.jejuniandC.coliclonal complexes. These results indicate that passive immunization with hyperimmune yolks, especially bacterin derived, offers possibilities to controlCampylobactercolonization in poultry.
Opening a new window on MR-based Electrical Properties Tomography with deep learning
Authors: Mandija Stefano , Meliadò Ettore F. , Huttinga Niek R. F. , Luijten Peter R. , van den Berg Cornelis A. T.
Published: June 2019

In the radiofrequency (RF) range, the electrical properties of tissues (EPs: conductivity and permittivity) are modulated by the ionic and water content, which change for pathological conditions. Information on tissues EPs can be used e.g. in oncology as a biomarker. The inability of MR-Electrical Properties Tomography techniques (MR-EPT) to accurately reconstruct tissue EPs by relating MR measurements of the transmit RF field to the EPs limits their clinical applicability. Instead of employing electromagnetic models posing strict requirements on the measured MRI quantities, we propose a data driven approach where the electrical properties reconstruction problem can be casted as a supervised deep learning task (DL-EPT). DL-EPT reconstructions for simulations and MR measurements at 3 Tesla on phantoms and human brains using a conditional generative adversarial network demonstrate high quality EPs reconstructions and greatly improved precision compared to conventional MR-EPT. The supervised learning approach leverages the strength of electromagnetic simulations, allowing circumvention of inaccessible MR electromagnetic quantities. Since DL-EPT is more noise-robust than MR-EPT, the requirements for MR acquisitions can be relaxed. This could be a major step forward to turn electrical properties tomography into a reliable biomarker where pathological conditions can be revealed and characterized by abnormalities in tissue electrical properties.
Epithelial-mesenchymal transition of cancer cells using bioengineered hybrid scaffold composed of hydrogel/3D-fibrous framework
Authors: Pal Mintu , Chen Huizhi , Lee Bae Hoon , Lee Justin Yin Hao , Yip Yun Sheng , Tan Nguan Soon , Tan Lay Poh
Published: June 2019

Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D) in-vitro culture models of tumorigenesis are inadequate to replicate the complexity of in-vivo microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.
Anti-aging effects of long-term space missions, estimated by heart rate variability
Authors: Otsuka Kuniaki , Cornelissen Germaine , Kubo Yutaka , Shibata Koichi , Mizuno Koh , Ohshima Hiroshi , Furukawa Satoshi , Mukai Chiaki
Published: June 2019

Reports that aging slows down in space prompted this investigation of anti-aging effects in humans by analyzing astronauts’ heart rate variability (HRV). Ambulatory 48-hour electrocardiograms from 7 astronauts (42.1 ± 6.8 years; 6 men) 20.6 ± 2.7 days (ISS01) and 138.6 ± 21.8 days (ISS02) after launch were divided into 24-hour spans of relative lower or higher magnetic disturbance, based on geomagnetic measures in Tromso, Norway. Magnetic disturbances were significantly higher on disturbed than on quiet days (ISS01: 72.01 ± 33.82 versus 33.96 ± 17.90 nT, P = 0.0307; ISS02: 71.06 ± 51.52 versus 32.53 ± 27.27 nT, P = 0.0308). SDNNIDX was increased on disturbed days (by 5.5% during ISS01, P = 0.0110), as were other HRV indices during ISS02 (SDANN, 12.5%, P = 0.0243; Triangular Index, 8.4%, P = 0.0469; and TF-component, 17.2%, P = 0.0054), suggesting the action of an anti-aging or longevity effect. The effect on TF was stronger during light (12:00–17:00) than during darkness (0:00–05:00) (P = 0.0268). The brain default mode network (DMN) was activated, gauged by increases in the LF-band (9.7%, P = 0.0730) and MF1-band (9.9%, P = 0.0281). Magnetic changes in the magnetosphere can affect and enhance HRV indices in space, involving an anti-aging or longevity effect, probably in association with the brain DMN, in a light-dependent manner and/or with help from the circadian clock.
Associations of mortality with own blood pressure using
son’s blood pressure as an instrumental variable
Authors: Carslake David , Fraser Abigail , May Margaret T. , Palmer Tom , Silventoinen Karri , Tynelius Per , Lawlor Debbie A. , Davey Smith George
Published: June 2019

High systolic blood pressure (SBP) causes cardiovascular disease (CVD)
and is associated with mortality from other causes, but conventional
multivariably-adjusted results may be confounded. Here we used a son’s SBP (>1
million Swedish men) as an instrumental variable for parental SBP and examined
associations with parents’ cause-specific mortality, avoiding reverse causation. The
hazard ratio for CVD mortality per SD (10.80 mmHg) of SBP was 1.49 (95% CI: 1.43,
1.56); SBP was positively associated with coronary heart disease and stroke. SBP was
also associated positively with all-cause, diabetes and kidney cancer mortality, and
negatively with external causes. Negative associations with respiratory-related
mortality were probably confounded by smoking. Hazard ratios for other causes were
imprecise or null. Diastolic blood pressure gave similar results to SBP. CVD hazard
ratios were intermediate between those from conventional multivariable studies and
Mendelian randomization and stronger than those from clinical trials, approximately
consistent with an effect of exposure duration on effect sizes. Plots of parental
mortality against offspring SBP were approximately linear, supporting calls for
lower SBP targets. Results suggest that conventional multivariable analyses of
mortality and SBP are not substantially confounded by reverse causation and confirm
positive effects of SBP on all-cause, CVD and diabetes mortality.