bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainty and hotspots in 21st century projections of agricultural drought from CMIP5 models
Authors: Lu Junyu , Carbone Gregory J. , Grego John M. 
Published: March 2019

AbstractFuture climate changes could alter hydrometeorological patterns and change the nature of droughts at global to regional scales. However, there are considerable uncertainties in future drought projections. Here, we focus on agricultural drought by analyzing surface soil moisture outputs from CMIP5 multi-model ensembles (MMEs) under RCP2.6, RCP4.5, RCP6.0, and RCP8.5 scenarios. First, the annual mean soil moisture by the end of the 21st century shows statistically significant large-scale drying and limited areas of wetting for all scenarios, with stronger drying as the strength of radiative forcing increases. Second, the MME mean spatial extent of severe drought is projected to increase for all regions and all future RCP scenarios, and most notably in Central America (CAM), Europe and Mediterranean (EUM), Tropical South America (TSA), and South Africa (SAF). Third, the model uncertainty presents the largest source of uncertainty (over 80%) across the entire 21st century among the three sources of uncertainty: internal variability, model uncertainty, and scenario uncertainty. Finally, we find that the spatial pattern and magnitude of annual and seasonal signal to noise (S/N) in soil moisture anomalies do not change significantly by lead time, indicating that the spreads of uncertainties become larger as the signals become stronger.
Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish
Authors: Cianciolo Cosentino Chiara , Berto Alessandro , Pelletier Stéphane , Hari Michelle , Loffing Johannes , Neuhauss Stephan C. F. , Doye Valérie 
Published: March 2019

AbstractAlthough structural nuclear pore proteins (nucleoporins) are seemingly required in every cell type to assemble a functional nuclear transport machinery, mutations or deregulation of a subset of them have been associated with specific human hereditary diseases. In particular, previous genetic studies of patients with nephrotic syndrome identified mutations in Nup107 that impaired the expression or the localization of its direct partner at nuclear pores, Nup133. In the present study, we characterized the zebrafish nup133 orthologous gene and its expression pattern during larval development. Using a morpholino-mediated gene knockdown, we show that partial depletion of Nup133 in zebrafish larvae leads to the formation of kidney cysts, a phenotype that can be rescued by co-injection of wild type mRNA. Analysis of different markers for tubular and glomerular development shows that the overall kidney development is not affected by nup133 knockdown. Likewise, no gross defect in nuclear pore complex assembly was observed in these nup133 morphants. On the other hand, nup133 downregulation results in proteinuria and moderate foot process effacement, mimicking some of the abnormalities typically featured by patients with nephrotic syndrome. These data indicate that nup133 is a new gene required for proper glomerular structure and function in zebrafish.
Eco-physiological responses of copepods and pteropods to ocean warming and acidification
Authors: Engström-Öst J. , Glippa O. , Feely R. A. , Kanerva M. , Keister J. E. , Alin S. R. , Carter B. R. , McLaskey A. K. , Vuori K. A. , Bednaršek N. 
Published: March 2019

AbstractWe compare physiological responses of the crustacean copepod Calanus pacificus and pelagic pteropod mollusk Limacina helicina to ocean temperatures and pH by measuring biomarkers of oxidative stress, antioxidant defences, and the activity of the respiratory electron transport system in organisms collected on the 2016 West Coast Ocean Acidification cruise in the California Current System. Copepods and pteropods exhibited strong but divergent responses in the same habitat; copepods had higher oxygen-reactive absorbance capacity, glutathione-S-transferase, and total glutathione content. The ratio between reduced to oxidised glutathione was higher in copepods than in pteropods, indicating lower oxidative stress in copepods. Pteropods showed higher activities of glutathione reductase, catalase, and lipid peroxidation, indicating increased antioxidant defences and oxidative stress. Thus, the antioxidant defence system of the copepods has a greater capacity to respond to oxidative stress, while pteropods already face severe stress and show limited capacity to deal with further changes. The results suggest that copepods have higher adaptive potential, owing to their stronger vertical migration behaviour and efficient glutathione metabolism, whereas pteropods run the risk of oxidative stress and mortality under high CO2 conditions. Our results provide a unique dataset and evidence of stress-inducing mechanisms behind pteropod ocean acidification responses.
On a new crested pterodactyloid from the Early Cretaceous of the Iberian Peninsula and the radiation of the clade Anhangueria
Authors: Holgado Borja , Pêgas Rodrigo V. , Canudo José Ignacio , Fortuny Josep , Rodrigues Taissa , Company Julio , Kellner Alexander W. A. 
Published: March 2019

AbstractThe pterosaur record from the Iberian Peninsula is mostly scarce and undefined, but in the last few years some new taxa have been described from different Lower Cretaceous sites of Spain. Here we describe a new genus and species of toothed pterodactyloid pterosaur from the Barremian of the Iberian Peninsula, Iberodactylus andreui gen. et sp. nov., that shows a close and rather unexpected relationship with Hamipterus tianshanensis from China. A review of the phylogenetic relationships of the Anhangueria reveals a new family of pterodactyloid pterosaurs, the Hamipteridae fam. nov. being recovered as sister-group of the Anhangueridae. This latter clade can be in turn divided into the new clades Anhanguerinae and Coloborhynchinae. The close relationships of Iberodactylus and Hamipterus shows an interesting palaeobiogeographical correlation between the Chinese and Iberian pterosaur faunas during the Barremian (Lower Cretaceous). The discovery of Iberodactylus strongly suggests that the clade Anhangueria has clear ancestral ties in eastern Laurasia.
Comparison of supine or prone crawl photon or proton breast and regional lymph node radiation therapy including the internal mammary chain
Authors: Speleers Bruno A. , Belosi Francesca M. , De Gersem Werner R. , Deseyne Pieter R. , Paelinck Leen M. , Bolsi Alessandra , Lomax Antony J. , Boute Bert G. , Van Greveling Annick E. , Monten Christel M. , Van de Velde Joris J. , Vercauteren Tom H. , Veldeman Liv , Weber Damien C. , De Neve Wilfried C. 
Published: March 2019

AbstractWe report on a dosimetrical study comparing supine (S) and prone-crawl (P) position for radiotherapy of whole breast (WB) and loco-regional lymph node regions, including the internal mammary chain (LN_IM). Six left sided breast cancer patients were CT-simulated in S and P positions and four patients only in P position. Treatment plans were made using non-coplanar volumetric modulated arc photon therapy (VMAT) or pencil beam scanning intensity modulated proton therapy (IMPT). Dose prescription was 15*2.67 Gy(GyRBE). The average mean heart doses for S or P VMAT were 5.6 or 4.3 Gy, respectively (p = 0.16) and 1.02 or 1.08 GyRBE, respectively for IMPT (p = 0.8; p < 0.001 for IMPT versus VMAT). The average mean lung doses for S or P VMAT were 5.91 or 2.90 Gy, respectively (p = 0.002) and 1.56 or 1.09 GyRBE, respectively for IMPT (p = 0.016). In high-risk patients, average (range) thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 6.8(5.4–9.4)% or 3.8(2.8–5.1)% for S or P VMAT (p < 0.001), respectively, and 1.6(1.1–2.0)% or 1.2(0.8–1.6)% for S or P IMPT (p = 0.25), respectively. Radiation-related mortality risk could outweigh the ~8% disease-specific survival benefit of WB + LN_IM radiotherapy for S VMAT but not P VMAT. IMPT carries the lowest radiation-related mortality risks.
Non-canonical WNT-signaling controls differentiation of lymphatics and extension lymphangiogenesis via RAC and JNK signaling
Authors: Lutze Grit , Haarmann Anna , Demanou Toukam Jules A. , Buttler Kerstin , Wilting Jörg , Becker Jürgen 
Published: March 2019

AbstractDevelopment of lymphatics takes place during embryogenesis, wound healing, inflammation, and cancer. We previously showed that Wnt5a is an essential regulator of lymphatic development in the dermis of mice, however, the mechanisms of action remained unclear. Here, whole-mount immunostaining shows that embryonic day (ED) 18.5 Wnt5a-null mice possess non-functional, cyst-like and often blood-filled lymphatics, in contrast to slender, interconnected lymphatic networks of Wnt5a+/−and wild-type (wt) mice. We then compared lymphatic endothelial cell (LEC) proliferation during ED 12.5, 14.5, 16.5 and 18.5 between Wnt5a−/−, Wnt5a+/−and wt-mice. We did not observe any differences, clearly showing that Wnt5a acts independently of proliferation. Transmission electron microscopy revealed multiple defects of LECs in Wnt5a-null mice, such as malformed inter-endothelial junctions, ruffled cell membrane, intra-luminal bulging of nuclei and cytoplasmic processes. Application of WNT5A protein toex vivocultures of dorsal thoracic dermis from ED 15.5 Wnt5a-null mice induced flow-independent development of slender, elongated lymphatic networks after 2 days, in contrast to controls showing an immature lymphatic plexus. Reversely, the application of the WNT-secretion inhibitor LGK974 on ED 15.5 wt-mouse dermis significantly prevented lymphatic network elongation. Correspondingly, tube formation assays with human dermal LECsin vitrorevealed increased tube length after WNT5A application. To study the intracellular signaling of WNT5A we used LEC scratch assays. Thereby, inhibition of autocrine WNTs suppressed horizontal migration, whereas application of WNT5A to inhibitor-treated LECs promoted migration. Inhibition of the RHO-GTPase RAC, or the c-Jun N-terminal kinase JNK significantly reduced migration, whereas inhibitors of the protein kinase ROCK did not. WNT5A induced transient phosphorylation of JNK in LECs, which could be inhibited by RAC- and JNK-inhibitors. Our data show that WNT5A induces formation of elongated lymphatic networks through proliferation-independent WNT-signaling via RAC and JNK. Non-canonical WNT-signaling is a major mechanism of extension lymphangiogenesis, and also controls differentiation of lymphatics.
Adipocyte lipolysis affects Perilipin 5 and cristae organization at the cardiac lipid droplet-mitochondrial interface
Authors: Varghese Mita , Kimler Victoria A. , Ghazi Fariha R. , Rathore Gurnoor K. , Perkins Guy A. , Ellisman Mark H. , Granneman James G. 
Published: March 2019

AbstractThis study investigated the effects of elevated fatty acid (FA) supply from adipose tissue on the ultrastructure of cardiac lipid droplets (LDs) and the expression and organization of LD scaffold proteins perilipin-2 (PLIN2) and perilipin-5 (PLIN5). Stimulation of adipocyte lipolysis by fasting (24 h) or β3-adrenergic receptor activation by CL316, 243 (CL) increased cardiac triacylglycerol (TAG) levels and LD size, whereas CL treatment also increased LD number. LDs were tightly associated with mitochondria, which was maintained during LD expansion. Electron tomography (ET) studies revealed continuity of LD and smooth endoplasmic reticulum (SER), suggesting interconnections among LDs. Under fed ad libitum conditions, the cristae of mitochondria that apposed LD were mostly organized perpendicularly to the tangent of the LD surface. Fasting significantly reduced, whereas CL treatment greatly increased, the perpendicular alignment of mitochondrial cristae. Fasting and CL treatment strongly upregulated PLIN5 protein and PLIN2 to a lesser extent. Immunofluorescence and immuno-electron microscopy demonstrated strong targeting of PLIN5 to the cardiac LD-mitochondrial interface, but not to the mitochondrial matrix. CL treatment augmented PLIN5 targeting to the LD-mitochondrial interface, whereas PLIN2 was not significantly affected. Together, our results support the concept that the interface between LD and cardiac mitochondria represents an organized and dynamic “metabolic synapse” that is highly responsive to FA trafficking.
Plasma ATG5 is increased in Alzheimer’s disease
Authors: Cho Sun-Jung , Lim Hyun Joung , Jo Chulman , Park Moon Ho , Han Changsu , Koh Young Ho 
Published: March 2019

AbstractAlzheimer’s disease (AD) is a major cause of dementia. Growing evidence suggests that dysregulation of autophagy, a cellular mechanism essential for self-digestion of damaged proteins and organelles, is involved in neurological degenerative diseases including AD. Previously, we reported that autophagosomes are increased in the brains of AD mouse model. However, the plasma levels of autophagic markers have not yet been investigated in patients with AD. In this study, we investigated the expression of autophagy-related genes 5 and 12 (ATG5 and ATG12, respectively) in cells in vitro upon amyloid-beta (Aβ) treatment and in the plasma of AD patients. ATG5-ATG12 complex levels were increased in primary rat cortical neurons and human umbilical vein endothelial cells after Aβ treatment. Furthermore, we compared plasma from 69 patients with dementia, 82 patients with mild cognitive impairment (MCI), and 127 cognitively normal control participants. Plasma levels of ATG5 were significantly elevated in patients with dementia (149.3 ± 7.5 ng/mL) or MCI (152.9 ± 6.9 ng/mL) compared with the control subjects (129.0 ± 4.1 ng/mL) (p = 0.034, p = 0.016, respectively). Our results indicate that alterations in the plasma ATG5 levels might be a potential biomarker in patients at risk for AD.
Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor
Authors: Guevara Tibisay , Rodríguez-Banqueri Arturo , Lasica Anna M. , Ksiazek Miroslaw , Potempa Barbara A. , Potempa Jan , Gomis-Rüth F. Xavier 
Published: March 2019

AbstractPorphyromonas gingivalis is a member of the dysbiotic oral microbiome and a “keystone pathogen” that causes severe periodontal disease, which is among the most prevalent infectious diseases. Part of the virulence factors secreted by P. gingivalis are the essential cysteine peptidases gingipain K (Kgp) and R (RgpA and RgpB), which account for 85% of the extracellular proteolytic activity of the pathogen and are thus prime targets for inhibition. We report the high-resolution (1.20 Å) complex structure of Kgp with KYT-36, a peptide-derived, potent, bioavailable and highly selective inhibitor, which is widely used for studies in vitro, in cells and in vivo. Sub-nanomolar inhibition of Kgp is achieved by tight binding to the active-site cleft, which is covered for its sub-sites S3 through S1’ under establishment of nine hydrophobic interactions, 14 hydrogen bonds and one salt bridge. In addition, an inhibitor carbonyl carbon that mimics the scissile carbonyl of substrates is pyramidalized and just 2.02 Å away from the catalytic nucleophile of Kgp, C477Sγ. Thus, the crystal structure emulates a reaction intermediate of the first nucleophilic attack during catalysis of cysteine peptidases. The present study sets the pace for the development of tailored next-generation drugs to tackle P. gingivalis.
Development of a 13C Stable Isotope Assay for Dipeptidyl Peptidase-4 Enzyme Activity A New Breath Test for Dipeptidyl Peptidase Activity
Authors: Yazbeck Roger , Jaenisch Simone , Squire Michelle , Abbott Catherine A. , Parkinson-Lawrence Emma , Brooks Douglas A. , Butler Ross N. 
Published: March 2019

AbstractDipeptidyl peptidase-4 inhibitors (DPP4i) are a class of orally available, small molecule inhibitors for the management of Type-II diabetes. A rapid, real-time, functional breath test for DPP4 enzyme activity could help to define DPP4i efficacy in patients that are refractory to treatment. We aimed to develop a selective, non-invasive, stable-isotope 13C-breath test for DPP4. In vitro experiments were performed using high (Caco-2) and low (HeLa) DPP4 expressing cells. DPP gene expression was determined in cell lines by qRT-PCR. A DPP4 selective 13C-tripeptide was added to cells in the presence and absence of the DPP4 inhibitor Sitagliptin. Gas samples were collected from the cell headspace and 13CO2 content quantified by isotope ratio mass spectrometry (IRMS). DPP4 was highly expressed in Caco-2 cells compared to HeLa cells and using the 13C-tripeptide, we detected a high 13CO2 signal from Caco2 cells. Addition of Sitaglitpin to Caco2 cells significantly inhibited this 13CO2 signal. 13C-assay DPP4 activity correlated positively with the enzyme activity detected using a colorimetric substrate. We have developed a selective, non-invasive, 13C-assay for DPP4 that could have broad translational applications in diabetes and gastrointestinal disease.
Oligomeric self-association contributes to E2A-PBX1-mediated oncogenesis
Authors: Lin Chiou-Hong , Wang Zhong , Duque-Afonso Jesús , Wong Stephen Hon-Kit , Demeter Janos , Loktev Alexander V. , Somervaille Tim C. P. , Jackson Peter K. , Cleary Michael L. 
Published: March 2019

AbstractThe PBX1 homeodomain transcription factor is converted by t(1;19) chromosomal translocations in acute leukemia into the chimeric E2A-PBX1 oncoprotein. Fusion with E2A confers potent transcriptional activation and constitutive nuclear localization, bypassing the need for dimerization with protein partners that normally stabilize and regulate import of PBX1 into the nucleus, but the mechanisms underlying its oncogenic activation are incompletely defined. We demonstrate here that E2A-PBX1 self-associates through the PBX1 PBC-B domain of the chimeric protein to form higher-order oligomers in t(1;19) human leukemia cells, and that this property is required for oncogenic activity. Structural and functional studies indicate that self-association facilitates the binding of E2A-PBX1 to DNA. Mutants unable to self-associate are transformation defective, however their oncogenic activity is rescued by the synthetic oligomerization domain of FKBP, which confers conditional transformation properties on E2A-PBX1. In contrast to self-association, PBX1 protein domains that mediate interactions with HOX DNA-binding partners are dispensable. These studies suggest that oligomeric self-association may compensate for the inability of monomeric E2A-PBX1 to stably bind DNA and circumvents protein interactions that otherwise modulate PBX1 stability, nuclear localization, DNA binding, and transcriptional activity. The unique dependence on self-association for E2A-PBX1 oncogenic activity suggests potential approaches for mechanism-based targeted therapies.
A Wide-Area Coverage 35 Gb/s Visible Light Communications Link for Indoor Wireless Applications
Authors: Chun Hyunchae , Gomez Ariel , Quintana Crisanto , Zhang Weida , Faulkner Grahame , O’Brien Dominic 
Published: March 2019

AbstractVisible Light Communications (VLC) can provide both illumination and communications and offers a means to alleviate the predicted spectrum crunch for radio-frequency wireless communications. In this paper, we report a laser diode based white-light communications link that operates over a wide area and supports high data rates. The proposed system is a four-colour multiplexed high-speed VLC system that uses a microelectromechanical system (MEMS) mirror-based beam-steering. The system operates at record data-rates of more than 35 Gb/s (Bit Error Rate(BER) < 3.8 × 10−3) with a coverage area of 39 m2 at a link distance of 4 m. To the best of our knowledge this is the fastest VLC demonstration reported thus far. The paper also addresses issues of eye-safety, showing data rates of more than 10 Gb/s are feasible.
Huge decrease of frost frequency in the Mont-Blanc Massif under climate change
Authors: Pohl Benjamin , Joly Daniel , Pergaud Julien , Buoncristiani Jean-François , Soare Paul , Berger Alexandre 
Published: March 2019

AbstractMountains are a sensitive indicator of climate change and these areas are an early glimpse of what could happen in lowland environments. Peaking at 4808 m asl, the Mont-Blanc summit, at the boundary between France and Italy, is the highest of the Alps, in Western Europe. Its Massif is world-famous for outdoor and extreme sport activities, especially since the 1924 Olympic games held in Chamonix. Here, we use a novel statistical downscaling approach to regionalize current and future climate change over the Mont-Blanc Massif at an unequalled spatial resolution of 200 m. The algorithm is applied to daily minimum and maximum temperature derived from global climate models used in the fifth assessment report of the International Panel on Climate Change (IPCC). This new high-resolution database allows for a precise quantification of frost occurrence and its evolution until 2100. In the winter season and by the end of the 21st century, under a pessimistic scenario (RCP8.5), frost frequency in the morning could decrease by 30–35 percentage points in the valley of Chamonix, and in the afternoon, similar changes could occur for elevations comprised between 2000 and 3000 m. In summertime, changes are even larger, reaching a huge drop of 45–50 points in the afternoon between 3500 and 4500 m. These changes are much reduced under an optimistic scenario. They could have huge impacts on the environment (glacier shrinking, permafrost degradation, floods, changes in the distribution of species and ecosystems) and societies (summer tourism for climbing and hiking, and winter tourism for skiing).
Aggregatibacter actinomycetemcomitans mediates protection of Porphyromonas gingivalis from Streptococcus sanguinis hydrogen peroxide production in multi-species biofilms
Authors: Zhu Bin , Macleod Lorna C. , Newsome Eric , Liu Jinlin , Xu Ping 
Published: March 2019

AbstractMixed species biofilms are shaped and influenced by interactions between species. In the oral cavity, dysbiosis of the microbiome leads to diseases such as periodontitis. Porphyromonas gingivalis is a keystone pathogen of periodontitis. In this study, we showed that polymicrobial biofilm formation promoted the tolerance of Porphyromonas gingivalis to oxidative stress under micro-aerobic conditions. The presence of Streptococcus sanguinis, an oral commensal bacterium, inhibited the survival of P. gingivalis in dual-species biofilms via the secretion of hydrogen peroxide (H2O2). Interestingly, this repression could be attenuated by the presence of Aggregatibacter actinomycetemcomitans in tri-species biofilms. It was also shown that the katA gene, encoding a cytoplasmic catalase in A. actinomycetemcomitans, was responsible for the reduction of H2O2 produced by S. sanguinis, which consequently increased the biomass of P. gingivalis in tri-species biofilms. Collectively, these findings reveal that polymicrobial interactions play important roles in shaping bacterial community in biofilm. The existence of catalase producers may support the colonization of pathogens vulnerable to H2O2, in the oral cavity. The catalase may be a potential drug target to aid in the prevention of periodontitis.