bluuebunny/crossref_metadata_2025 huggingface dataset:
Expected Performances of the Copernicus Imaging Microwave Radiometer (CIMR) for an All‐Weather and High Spatial Resolution Estimation of Ocean and Sea Ice Parameters
Authors: Kilic Lise , Prigent Catherine , Aires Filipe , Boutin Jacqueline , Heygster Georg , Tonboe Rasmus T. , Roquet Hervé , Jimenez Carlos , Donlon Craig
Published: October 2018

Climate change resulting in ocean warming, sea level rise, and sea ice melting has consequences for the global economy, navigation, and security. The Copernicus Imaging Microwave Radiometer (CIMR) mission is a high priority candidate mission within the European Copernicus Expansion program. CIMR is designed to observe the ocean and sea ice and more particularly the Arctic environment. Sea surface temperature (SST), ocean wind speed, sea surface salinity (SSS), and sea ice concentration (SIC) are fundamental variables for understanding, monitoring, and predicting the state of the ocean and sea ice. CIMR is a conically scanning microwave radiometer imager that includes channels at 1.4, 6.9, 10.65, 18.7, and 36.5 GHz, in a Sun‐synchronous polar orbit, to provide SST, ocean wind speed, SSS, and SIC with an increased accuracy and/or spatial resolution. Here we analyze the performances of the CIMR mission in terms of theoretical retrieval precision and spatial resolution on the SST, SSS, and SIC products. A careful information content analysis is conducted. The CIMR performances are compared with the Advanced Microwave Scanning Radiometer 2 and the Soil Moisture Active Passive current missions. Maps of the retrieval precision based on realistic conditions are computed. CIMR will provide SST, SSS, and SIC with a spatial resolution of 15, 55, and 5 km and a precision of 0.2 K, 0.3 psu, and 5%, respectively. The SST and SIC will be retrieved at better than 30 km from the coast. CIMR is currently in preparatory phase, and if selected, it is for a launch in the 2025+ time frame.
Investigation of Liquid Cloud Microphysical Properties of Deep Convective Systems: 2. Parameterization of Raindrop Size Distribution and its Application for Convective Rain Estimation
Authors: Wang Jingyu , Dong Xiquan , Xi Baike
Published: October 2018

The liquid cloud microphysical properties for stratiform rain (SR) have been investigated in Part 1 of this series. Since convective rain (CR) has characteristics in raindrop size distribution (DSD) and precipitation that are distinct from SR, we investigate the CR properties in this study by using 20 hr of CR samples collected by 17 Automatic Parsivel Units disdrometers during the Midlatitude Continental Convective Clouds Experiment over the Atmospheric Radiation Measurement Southern Great Plains site. A full spectrum of DSD is constructed based on a total of 23 size channels (0.321 to 9.785 mm), and both Gamma and Exponential fitted functions are applied to extract the DSD shape parameters. Compared to SR properties, CR has distinct features including broader size range and narrower exponential slope parameter (λE). These results indicate that the assumption of constant exponential intercept parameter (N0E) is inappropriate for CR rain rate estimates. Additionally, the subsetting scheme of the CR DSD spectra also has a strong impact on the Gamma/Exponential functions. Therefore, a new CR DSD parameterization scheme is developed by choosing the appropriate spectra subset with the constraint of rain rate and using the constant λE instead of constant N0E. With the input of the radar reflectivity at the lowest observed height, the newly calculated CR rain rates match well with the collocated surface rain gauge measurements (127 Mesonet stations and 17 Automatic Parsivel Units), while the rain rates calculated using traditional Z‐R relationship are 3–4 times larger, indicating that constant λE is a better assumption for CR DSD.
Using AIRS and ARM SGP Clear‐Sky Observations to Evaluate Meteorological Reanalyses: A Hyperspectral Radiance Closure Approach
Authors: Chen Xiuhong , Huang Xianglei , Dong Xiquan , Xi Baike , Dolinar Erica K. , Loeb Norman G. , Kato Seiji , Stackhouse Paul W. , Bosilovich Michael G.
Published: October 2018

Using the ground‐based measurements from the Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site and spectral radiance from the Atmospheric Infrared Sounder (AIRS) on National Aeronautics and Space Administration Aqua, we evaluate the temperature and humidity profiles from European Center for Medium Range Weather Forecasting ERA‐Interim and Modern‐Era Retrospective analysis for Research and Applications Version 2 reanalyses. Four sets of synthetic AIRS spectra are calculated using 51 clear‐sky sounding profiles from the ARM SGP observations, the collocated AIRS L2 retrievals and the two reanalyses, respectively. A subset of AIRS channels sensitive to temperature, CO2, or H2O but not to other trace gases is chosen and further categorized into different groups according to the peak altitudes of their weighting functions. Synthetic radiances are then compared to the observed AIRS radiances for each group. For all groups, the observed AIRS radiances agree well with the synthetic ones based on the ARM SGP soundings or the AIRS L2 retrievals. The brightness temperature (BT) differences are within ±0.5 K. For two reanalyses, BT differences in all temperature‐sensitive groups are generally within ±0.5 K; but the mean BT differences in all groups sensitive to both T and H2O are negative. Together, they suggest a wet bias in the free troposphere in both reanalyses. Moreover, such BT differences can be seen in the analysis of AIRS clear‐sky radiances over the entire 30–40°N zone. A grid‐search retrieval suggests that 9–30% reduction for reanalysis humidity between 200 and 800 hPa is needed to correct such wet bias.
Using Machine Learning to Parameterize Moist Convection: Potential for Modeling of Climate, Climate Change, and Extreme Events
Authors: O'Gorman Paul A. , Dwyer John G.
Published: October 2018

The parameterization of moist convection contributes to uncertainty in climate modeling and numerical weather prediction. Machine learning (ML) can be used to learn new parameterizations directly from high‐resolution model output, but it remains poorly understood how such parameterizations behave when fully coupled in a general circulation model (GCM) and whether they are useful for simulations of climate change or extreme events. Here we focus on these issues using idealized tests in which an ML‐based parameterization is trained on output from a conventional parameterization and its performance is assessed in simulations with a GCM. We use an ensemble of decision trees (random forest) as the ML algorithm, and this has the advantage that it automatically ensures conservation of energy and nonnegativity of surface precipitation. The GCM with the ML convective parameterization runs stably and accurately captures important climate statistics including precipitation extremes without the need for special training on extremes. Climate change between a control climate and a warm climate is not captured if the ML parameterization is only trained on the control climate, but it is captured if the training includes samples from both climates. Remarkably, climate change is also captured when training only on the warm climate, and this is because the extratropics of the warm climate provides training samples for the tropics of the control climate. In addition to being potentially useful for the simulation of climate, we show that ML parameterizations can be interrogated to provide diagnostics of the interaction between convection and the large‐scale environment.
Pangenomic comparison of globally distributed Poribacteria associated with sponge hosts and marine particles
Authors: Podell Sheila , Blanton Jessica M , Neu Alexander , Agarwal Vinayak , Biggs Jason S , Moore Bradley S , Allen Eric E
Published: October 2018

Candidatus Poribacteria is a little-known bacterial phylum, previously characterized by partial genomes from a single sponge host, but never isolated in culture. We have reconstructed multiple genome sequences from four different sponge genera and compared them to recently reported, uncharacterized Poribacteria genomes from the open ocean, discovering shared and unique functional characteristics. Two distinct, habitat-linked taxonomic lineages were identified, designated Entoporibacteria (sponge-associated) and Pelagiporibacteria (free-living). These lineages differed in flagellar motility and chemotaxis genes unique to Pelagiporibacteria, and highly expanded families of restriction endonucleases, DNA methylases, transposases, CRISPR repeats, and toxin–antitoxin gene pairs in Entoporibacteria. Both lineages shared pathways for facultative anaerobic metabolism, denitrification, fermentation, organosulfur compound utilization, type IV pili, cellulosomes, and bacterial proteosomes. Unexpectedly, many features characteristic of eukaryotic host association were also shared, including genes encoding the synthesis of eukaryotic-like cell adhesion molecules, extracellular matrix digestive enzymes, phosphoinositol-linked membrane glycolipids, and exopolysaccharide capsules. Complete Poribacteria 16S rRNA gene sequences were found to contain multiple mismatches to “universal” 16S rRNA gene primer sets, substantiating concerns about potential amplification failures in previous studies. A newly designed primer set corrects these mismatches, enabling more accurate assessment of Poribacteria abundance in diverse marine habitats where it may have previously been overlooked.
Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA
Authors: Wei Chao , Han Xiao , Weng Danwei , Feng Qiru , Qi Xiangbing , Li Jin , Luo Minmin
Published: October 2018

Heroin, nicotine, cocaine, and MDMA are abused by billions of people. They are believed to target midbrain dopamine neurons and/or serotonin neurons, but their effects on the dynamic neuronal activity remain unclear in behaving states. By combining cell-type-specific fiber photometry of Ca2+ signals and intravenous drug infusion, here we show that these four drugs of abuse profoundly modulate the activity of mouse midbrain dopamine neurons and serotonin neurons with distinct potency and kinetics. Heroin strongly activates dopamine neurons, and only excites serotonin neurons at higher doses. Nicotine activates dopamine neurons in merely a few seconds, but produces minimal effects on serotonin neurons. Cocaine and MDMA cause long-lasting suppression of both dopamine neurons and serotonin neurons, although MDMA inhibits serotonin neurons more profoundly. Moreover, these inhibitory effects are mediated through the activity of dopamine and serotonin autoreceptors. These results suggest that the activity of dopamine neurons and that of serotonin neurons are more closely associated with the drug's reinforcing property and the drug's euphorigenic property, respectively. This study also shows that our methodology may facilitate further in-vivo interrogation of neural dynamics using animal models of drug addiction.
Exonic deletions in GALC are frequent in Japanese globoid-cell leukodystrophy patients
Authors: Irahara-Miyana Kaori , Enokizono Takashi , Ozono Keiichi , Sakai Norio
Published: October 2018

Globoid-cell leukodystrophy is an autosomal-recessive lysosomal storage disorder. Single-base substitutions and small indel mutations in the GALC gene are common in Japanese patients. In this study, we identified three novel deletions, in exons 1, 8, and 11–12, in three patients using Multiplex Ligation-dependent Probe Amplification. We suggest that some patients in whom no or only a single pathogenic mutation is detected by Sanger sequencing may have exon deletions.
A transportome-scale amiRNA-based screen identifies redundant roles of Arabidopsis ABCB6 and ABCB20 in auxin transport
Authors: Zhang Yuqin , Nasser Victoria , Pisanty Odelia , Omary Moutasem , Wulff Nikolai , Di Donato Martin , Tal Iris , Hauser Felix , Hao Pengchao , Roth Ohad , Fromm Hillel , Schroeder Julian I. , Geisler Markus , Nour-Eldin Hussam Hassan , Shani Eilon
Published: October 2018

Transport of signaling molecules is of major importance for regulating plant growth, development, and responses to the environment. A prime example is the spatial-distribution of auxin, which is regulated via transporters to govern developmental patterning. A critical limitation in our ability to identify transporters by forward genetic screens is their potential functional redundancy. Here, we overcome part of this functional redundancy via a transportome, multi-targeted forward-genetic screen using artificial-microRNAs (amiRNAs). We generate a library of 3000 plant lines expressing 1777 amiRNAs, designed to target closely homologous genes within subclades of transporter families and identify, genotype and quantitatively phenotype, 80 lines showing reproducible shoot growth phenotypes. Within this population, we discover and characterize a strong redundant role for the unstudied ABCB6 and ABCB20 genes in auxin transport and response. The unique multi-targeted lines generated in this study could serve as a genetic resource that is expected to reveal additional transporters.
Author Correction: Large intrinsic anomalous Hall effect in half-metallic ferromagnet Co3Sn2S2 with magnetic Weyl fermions
Authors: Wang Qi , Xu Yuanfeng , Lou Rui , Liu Zhonghao , Li Man , Huang Yaobo , Shen Dawei , Weng Hongming , Wang Shancai , Lei Hechang
Published: October 2018

The original version of this Article incorrectly omitted an affiliation of Hongming Weng: “Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, 100190, Beijing, China”

This has been corrected in both the PDF and HTML versions of the Article.
Broad phylogenetic analysis of cation/proton antiporters reveals transport determinants
Authors: Masrati Gal , Dwivedi Manish , Rimon Abraham , Gluck-Margolin Yael , Kessel Amit , Ashkenazy Haim , Mayrose Itay , Padan Etana , Ben-Tal Nir
Published: October 2018

Cation/proton antiporters (CPAs) play a major role in maintaining living cells’ homeostasis. CPAs are commonly divided into two main groups, CPA1 and CPA2, and are further characterized by two main phenotypes: ion selectivity and electrogenicity. However, tracing the evolutionary relationships of these transporters is challenging because of the high diversity within CPAs. Here, we conduct comprehensive evolutionary analysis of 6537 representative CPAs, describing the full complexity of their phylogeny, and revealing a sequence motif that appears to determine central phenotypic characteristics. In contrast to previous suggestions, we show that the CPA1/CPA2 division only partially correlates with electrogenicity. Our analysis further indicates two acidic residues in the binding site that carry the protons in electrogenic CPAs, and a polar residue in the unwound transmembrane helix 4 that determines ion selectivity. A rationally designed triple mutant successfully converted the electrogenic CPA, EcNhaA, to be electroneutral.
An efficient and compact switch for quantum circuits
Authors: Wu Yulin , Yang Li-Ping , Gong Ming , Zheng Yarui , Deng Hui , Yan Zhiguang , Zhao Yanjun , Huang Keqiang , Clark Juno , Munro William J. , Nemoto Kae , Zheng Dong-Ning , Sun C. P. , Liu Yu-xi , Zhu Xiaobo , Lu Li
Published: October 2018

The engineering of quantum devices has reached the stage where we now have small-scale quantum processors containing multiple interacting qubits within them. Simple quantum circuits have been demonstrated and scaling up to larger numbers is underway. However, as the number of qubits in these processors increases, it becomes challenging to implement switchable or tunable coherent coupling among them. The typical approach has been to detune each qubit from others or the quantum bus it connected to, but as the number of qubits increases this becomes problematic to achieve in practice due to frequency crowding issues. Here, we demonstrate that by applying a fast longitudinal control field to the target qubit, we can turn off its couplings to other qubits or buses. This has important implications in superconducting circuits as it means we can keep the qubits at their optimal points, where the coherence properties are greatest, during coupling/decoupling process. Our approach suggests another way to control coupling among qubits and data buses that can be naturally scaled up to large quantum processors.
Trends in clinical trials for articular cartilage repair by cell therapy
Authors: Negoro Takaharu , Takagaki Yuri , Okura Hanayuki , Matsuyama Akifumi
Published: October 2018

Focal and degenerative lesions of articular cartilage greatly reduce the patient’s quality of life. Various therapies including surgical treatment have been developed, but a definitive therapy is not yet known. Several cell therapy products have already been developed and are available in the market. In this study, we examined the clinical research trends related to cell therapy products in the cartilage repair field based on data obtained from the ClinicalTrial.gov website. Although this website does not provide comprehensive results of clinical trials, it offers information on prospective clinical trials, including work in progress, and thus allows for chronological analysis of the data. We selected 203 studies related to the field of cartilage regeneration from ClinicalTrial.gov. The results showed a shift in the clinical translational trend in utilized cells from cartilage- and bone marrow- to adipose tissue-based cells. Whereas the studies that used cartilage as the cell source included many phase III trials, fewer studies using bone marrow and adipose tissue cells progressed to phase III, suggesting that most clinical developments using the latter sources have not been successful so far. One product covered the entire period from the start of phase I to the completion of phase III, with a time to completion of more than 100 months. Translational trends in autologous chondrocyte implantation were also discussed. The use of ClinicalTrials.gov as the sole data source can yield a perspective view of the global clinical translational trends, which has been difficult to observe up to this point.
Male-specific association between subclinical hypothyroidism and the risk of non-alcoholic fatty liver disease estimated by hepatic steatosis index: Korea National Health and Nutrition Examination Survey 2013 to 2015
Authors: Lee Jeongmin , Ha Jeonghoon , Jo Kwanhoon , Lim Dong-Jun , Lee Jung-Min , Chang Sang-Ah , Kang Moo-Il , Cha Bong-Yun , Kim Min-Hee
Published: October 2018

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease encompassing a broad spectrum of pathologic changes in the liver. Metabolic derangements are suggested to be main causes of NAFLD. As thyroid hormone is a main regulator of energy metabolism, there may be a link between NAFLD and thyroid function. In previous studies, the association between NAFLD and thyroid function was not conclusive. The aim of this study was to clarify the relationship between NAFLD and thyroid function, focusing on subclinical hypothyroidism, using nationwide survey data representing the Korean population. NAFLD was defined as a hepatic steatosis index of 36 or higher. Based on the analysis of nationwide representative data, subclinical hypothyroidism was related to a high risk of NAFLD in males, but not in females. Our study showed that thyroid function might play a substantial role in the development of NAFLD, especially in males. Further study to elucidate the underlying mechanism of gender specific association of mild thyroid dysfunction and NAFLD would be required.
Bayesian spatiotemporal analysis for association of environmental factors with hand, foot, and mouth disease in Guangdong, China
Authors: Du Zhicheng , Lawrence Wayne R. , Zhang Wangjian , Zhang Dingmei , Yu Shicheng , Hao Yuantao
Published: October 2018

Hand, foot, and mouth disease (HFMD) remains a significant public health and economic burden in parts of China, particularly Guangdong Province. Although the association between meteorological factors and HFMD has been well documented, significant gaps remain in our understanding of the potential impact of environmental factors. Using county-level monthly HFMD data from China CDC and environmental data from multiple sources, we used spatiotemporal Bayesian models to evaluate the association between HFMD and environmental factors including vegetation index, proportion of artificial surface, road capacity, temperature and humidity, and assessed the spatial and temporal dynamic of the association. Statistically significant correlation coefficients from −0.056 to 0.36 (all P < 0.05) were found between HFMD incidence and all environmental factors. The contributions of these factors for HFMD incidence were estimated to be 16.32%, 12.31%, 14.61%, 13.53%, and 2.63%. All environmental factors including vegetation index (Relative Risk: 0.889; Credible Interval: 0.883–0.895), artificial surface (1.028; 1.022–1.034), road capacity (1.033; 1.028–1.038), temperature (1.039; 1.028–1.05), and relative humidity (1.015; 1.01–1.021) were statistically retained in the final spatiotemporal model. More comprehensive environmental factors were identified as associating with HFMD incidence. Taking these environmental factors into consideration for prevention and control strategy might be of great practical significance.
Heat-stress triggers MAPK crosstalk to turn on the hyperosmotic response pathway
Authors: Dunayevich Paula , Baltanás Rodrigo , Clemente José Antonio , Couto Alicia , Sapochnik Daiana , Vasen Gustavo , Colman-Lerner Alejandro
Published: October 2018

Cells make decisions based on a combination of external and internal signals. In yeast, the high osmolarity response (HOG) is a mitogen-activated protein kinase (MAPK) pathway that responds to a variety of stimuli, and it is central to the general stress response. Here we studied the effect of heat-stress (HS) on HOG. Using live-cell reporters and genetics, we show that HS promotes Hog1 phosphorylation and Hog1-dependent gene expression, exclusively via the Sln1 phosphorelay branch, and that the strength of the activation is larger in yeast adapted to high external osmolarity. HS stimulation of HOG is indirect. First, we show that HS causes glycerol loss, necessary for HOG activation. Preventing glycerol efflux by deleting the glyceroporin FPS1 or its regulators RGC1 and ASK10/RGC2, or by increasing external glycerol, greatly reduced HOG activation. Second, we found that HOG stimulation by HS depended on the operation of a second MAPK pathway, the cell-wall integrity (CWI), a well-known mediator of HS, since inactivating Pkc1 or deleting the MAPK SLT2 greatly reduced HOG activation. Our data suggest that the main role of the CWI in this process is to stimulate glycerol loss. We found that in yeast expressing the constitutively open channel mutant (Fps1-Δ11), HOG activity was independent of Slt2. In summary, we suggest that HS causes a reduction in turgor due to the loss of glycerol and the accompanying water, and that this is what actually stimulates HOG. Thus, taken together, our findings highlight a central role for Fps1, and the metabolism of glycerol, in the communication between the yeast MAPK pathways, essential for survival and reproduction in changing environments.
PAR-1 is a novel mechano-sensor transducing laminar flow-mediated endothelial signaling
Authors: Kim Suji , Han Jung-Hwa , Nam Dae-Hwan , Kim Geun-Young , Lim Jae Hyang , Kim Jae-Ryong , Woo Chang-Hoon
Published: October 2018

Recent studies have indicated that protease-activated receptor-1 (PAR-1) is involved in cytoprotective and anti-inflammatory responses in endothelial cells (ECs). However, the role of PAR-1 in laminar flow-mediated atheroprotective responses remains unknown. Herein, we investigated whether PAR-1 regulates laminar flow-mediated mechanotransduction in ECs. Confocal analysis showed that PAR-1 was internalized into early endosomes in response to laminar flow. In addition, flow cytometry analysis showed that cell surface expression of PAR-1 was reduced by laminar flow, suggesting that PAR-1 was activated in response to laminar flow. Depletion of PAR-1 using human PAR-1 siRNA inhibited unidirectional laminar flow-mediated actin stress fiber formation and cellular alignment as well as atheroprotective gene expressions in HUVECs. Moreover, PAR-1 knockdown inhibited laminar flow-stimulated eNOS phosphorylation, and inhibited the phosphorylations of Src, AMPK, ERK5 and HDAC5. Furthermore, PAR-1 depletion inhibited laminar flow-mediated anti-inflammatory responses as demonstrated by reduced TNFα-induced VCAM-1 expression and by monocyte adhesion to HUVECs, and prevented laminar flow-mediated anti-apoptotic response. An investigation of the role of PAR-1 in vasomotor modulation using mouse aortic rings revealed that acetylcholine-induced vasorelaxation was diminished in PAR-1 deficient mice compared to littermate controls. Taken together, these findings suggest that PAR-1 be viewed as a novel pharmacologic target for the treatment of vascular diseases, including atherosclerosis.
A break in parental interaction does not affect the temporal dependency of infant social engagement, but disrupts non-social engagement
Authors: Mattson Whitney I. , Messinger Daniel S. , Gangi Devon N. , Myers Nicholas D.
Published: October 2018

Infant looking patterns during interaction offer an early window into social and nonsocial engagement. Recent evidence indicates that infant looks exhibit temporal dependency—one look duration predicts the next look duration. It is unknown, however, whether temporal dependency emerges as infants structure their own looking or whether it is influenced by interaction. We examined whether a perturbation of social interaction affected temporal dependency. Using the Face-to-Face/Still-Face procedure, we compared temporal dependency during parental interaction (the Face-to-Face & Reunion episodes) to parental non-responsiveness (the Still-Face episode). Overall, the durations of successive infant looks were predictable; past behavior constrained current behavior. The duration of one look at the parent (Face Look) predicted the duration of the next Face Look. Likewise, the duration of a look at any place that was not the parent’s face (Away Look) predicted the duration of the next Away Look. The temporal dependency of Face Looks (social engagement) was unaffected by the Still-Face perturbation, but the temporal dependency of Away Looks (nonsocial engagement) declined during the Still-Face. Infant temporal structuring of engagement during social looking is not dependent on parental interaction while the disruption of interaction affects infants’ structuring of their own non-social engagement.
Antibiotic export by efflux pumps affects growth of neighboring bacteria
Authors: Wen Xi , Langevin Ariel M. , Dunlop Mary J.
Published: October 2018

Cell-cell interactions play an important role in bacterial antibiotic resistance. Here, we asked whether neighbor proximity is sufficient to generate single-cell variation in antibiotic resistance due to local differences in antibiotic concentrations. To test this, we focused on multidrug efflux pumps because recent studies have revealed that expression of pumps is heterogeneous across populations. Efflux pumps can export antibiotics, leading to elevated resistance relative to cells with low or no pump expression. In this study, we co-cultured cells with and without AcrAB-TolC pump expression and used single-cell time-lapse microscopy to quantify growth rate as a function of a cell’s neighbors. In inhibitory concentrations of chloramphenicol, we found that cells lacking functional efflux pumps (ΔacrB) grow more slowly when they are surrounded by cells with AcrAB-TolC pumps than when surrounded by ΔacrB cells. To help explain our experimental results, we developed an agent-based mathematical model, which demonstrates the impact of neighbors based on efflux efficiency. Our findings hold true for co-cultures of Escherichia coli with and without pump expression and also in co-cultures of E. coli and Salmonella typhumirium. These results show how drug export and local microenvironments play a key role in defining single-cell level antibiotic resistance.
Quantitative B-lymphocyte deficiency and increased TCRγδ T-lymphocytes in acute infectious spondylodiscitis
Authors: Haugaard Anna K. , Marquart Hanne V. , Kolte Lilian , Ryder Lars Peter , Kehrer Michala , Krogstrup Maria , Dragsted Ulrik B. , Dahl Benny , Gjørup Ida E. , Andersen Åse B. , Garred Peter , Nielsen Susanne D.
Published: October 2018

Acute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3–6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.
The effects of aquarium culture on coral oocyte ultrastructure
Authors: Lin Chiahsin , Zhuo Jian-Ming , Chong Gabriella , Wang Li-Hsueh , Meng Pei-Jie , Tsai Sujune
Published: October 2018

As the world’s oceans are currently threatened by anthropogenic pollution and climate change, coral breeding has become an important conservation method, since it can limit marine organisms’ exposure to sub-optimal environment conditions. However, the aquarium environment is inherently different from the ocean, and this could manifest in physiological changes in the reared organisms, particularly with respect to their reproduction. Therefore, the aim of this study was to observe and compare the ultrastructure of the oocytes from wild Oxypora lacera and Echinopora gemmacea with the oocytes from cultured corals using transmission electron microscope. The oocytes from Wild O. lacera and E. gemmacea were larger than cultured ones, though their microvillus layers were significantly thiner. Internally, lipid granule areas and yolk material density in the oocytes of wild O. lacera and E. gemmacea were ~25% lower than in their cultured counterparts. Food availability and the presence and availability of symbiotic dinoflagellates (genus Symbiodinium) may have played a role in driving these lipid-based differences, in particular, as cultured corals had limited potential for heterotrophic feeding. These data will aid in future coral husbandry efforts.
Glutamate alleviates intestinal injury, maintains mTOR and suppresses TLR4 and NOD signaling pathways in weanling pigs challenged with lipopolysaccharide
Authors: Qin Qin , Xu Xiao , Wang Xiuying , Wu Huanting , Zhu Huiling , Hou Yongqing , Dai Bing , Liu Xiuting , Liu Yulan
Published: October 2018

This experiment aimed to explore whether glutamate (Glu) had beneficial effects on intestinal injury caused by Escherichia coli LPS challenge via regulating mTOR, TLRs, as well as NODs signaling pathways. Twenty-four piglets were allotted to 4 treatments including: (1) control group; (2) LPS group; (3) LPS + 1.0% Glu group; (4) LPS + 2.0% Glu group. Supplementation with Glu increased jejunal villus height/crypt depth ratio, ileal activities of lactase, maltase and sucrase, and RNA/DNA ratio and protein abundance of claudin-1 in jejunum and ileum. In addition, the piglets fed Glu diets had higher phosphorylated mTOR (Ser2448)/total mTOR ratio in jejunum and ileum. Moreover, Glu decreased TNF-α concentration in plasma. Supplementation with Glu also decreased mRNA abundance of jejunal TLR4, MyD88, IRAK1, TRAF6, NOD2 and increased mRNA abundance of ileal Tollip. These results indicate that Glu supplementation may be closely related to maintaining mTOR and inhibiting TLR4 and NOD signaling pathways, and concomitant improvement of intestinal integrity under an inflammatory condition.
Floristic diversity in different urban ecological niches of a southern European city
Authors: Salinitro Mirko , Alessandrini Alessandro , Zappi Alessandro , Melucci Dora , Tassoni Annalisa
Published: October 2018

The present paper aimed at studying the vertical and horizontal spatial distribution, species richness and diversity of vascular plants in different urban ecological niches (urban habitats) by means of the case study of Bologna (Italy), a typical densely populated southern European city. A total of 477 species were found in the study area of the historical city centre, 30% of which were alien species. Alien plant species were mainly present among phanerophytes, while native plants were mainly therophytes and hemicryptophytes. The habitats that mostly contributed to the species total richness were semi-natural soils, followed by paved areas, walls, rooftops and manholes. The number of exclusive species decreased according to the selectiveness of the habitat, with manholes and rooftops being the most selective. The presence of hemicryptophytes constant decreased going from 27% of more humid habitats to 5% of more arid habitats, so that they can be considered a water availability biomarker. Urban habitat quality, measured by the number of native species, was directly proportional to the strength of selective factors and inversely proportional to the rate of disturbance, with roofs and semi-natural soils having, respectively, the highest and lowest quality. Finally, a relation between species richness and street characteristics, like width, orientation and type of flooring, was demonstrated.
Placental FKBP51 mediates a link between second trimester maternal anxiety and birthweight in female infants
Authors: Togher Katie L. , O’Keeffe Gerard W. , Khashan Ali S. , Clarke Gerard , Kenny Louise C.
Published: October 2018

Prenatal distress is associated with adverse outcomes in affected offspring. Alterations in placental glucocorticoid signalling and subsequent foetal overexposure to glucocorticoids have been implicated as an underlying mechanism. Infant sex is emerging as an important factor in disease susceptibility. This study aimed to examine the effects of maternal distress across pregnancy on birth outcomes and placental glucocorticoid genes in a sex-dependent manner. Participants completed psychological distress questionnaires throughout pregnancy. Placental HSD11B2, NR3C1 and FKBP51 were analysed by real time PCR and cortisol was measured in new-born hair. Second trimester stress was negatively correlated with birthweight in males and positively correlated with placental NR3C1 mRNA in females. Second trimester anxiety was negatively correlated with birthweight and placental FKBP51 mRNA in females. In mediation analysis, placental FKBP51 mRNA expression was found to mediate the link between prenatal anxiety and birthweight. New-born cortisol was negatively correlated with second trimester anxiety and positively correlated with female placental FKBP51 mRNA levels. Again, FKBP51 mRNA was found to mediate the link between anxiety and new-born cortisol. These results highlight a role for FKBP51 in the placental response to prenatal distress in females. The precise role that placental FKBP51 has in foetal and infant development has not been extensively studied and warrants further investigations.
2.0 Å resolution crystal structure of human polκ reveals a new catalytic function of N-clasp in DNA replication
Authors: Jha Vikash , Ling Hong
Published: October 2018

Human polymerase kappa (polκ) is a distinct Y-family DNA polymerase with a unique N-terminal N-clasp domain. The N-clasp renders polκ’s high efficiency and accuracy in DNA replication and lesion bypass. How N-clasp empowers polκ in replication remains unclear due to the disordering of N-clasp. Here, we present a 2.0-Å resolution crystal structure of a polκ ternary complex with DNA and an incoming nucleotide. The structure-function study reveals an ordered N-clasp domain that brings conserved and functionally important residues in contact with the replicating basepair in the active site and contributes to the nucleotidyl transfer reaction. Particularly, a fully ordered Lys25 from the N-clasp domain is in H-bonding with the α- and γ-phosphates of the incoming nucleotide. K25A mutation reduces the polymerase activity of polκ significantly. This lysine is structurally analogous to a conserved lysine in the A-family DNA polymerases in the closed form. In contrast, Lys25 in the previous structures of polκ does not have any contacts with the incoming nucleotide, resembling an open form of a DNA polymerase. Based on structural and functional similarity, we propose a local open/closed mechanism for polκ in DNA replication catalysis, which mimics the common mechanism for all DNA polymerases.
Engineering a branching sucrase for flavonoid glucoside diversification
Authors: Malbert Yannick , Moulis Claire , Brison Yoann , Morel Sandrine , André Isabelle , Remaud-Simeon Magali
Published: October 2018

Enzymatic glycosylation of flavonoids is an efficient mean to protect aglycons against degradation while enhancing their solubility, life time and, by extension, their bioavailability which is critical for most of their applications in health care. To generate a valuable enzymatic platform for flavonoid glucosylation, an α-1,2 branching sucrase belonging to the family 70 of glycoside-hydrolases was selected as template and subsequently engineered. Two libraries of variants targeting pair-wise mutations inferred by molecular docking simulations were generated and screened for quercetin glucosylation using sucrose as a glucosyl donor. Only a limited number of variants (22) were retained on the basis of quercetin conversion and product profile. Their acceptor promiscuity towards five other flavonoids was subsequently assessed, and the automated screening effort revealed variants showing remarkable ability for luteolin, morin and naringenin glucosylation with conversion ranging from 30% to 90%. Notably, naringenin and morin, a priori considered as recalcitrant compounds to glucosylation using this α-transglucosylases, could also be modified. The approach reveals the potential of small platforms of engineered GH70 α-transglucosylases and opens up the diversity of flavonoid glucosides to molecular structures inaccessible yet.
Modeling the Transmission Dynamics of Clonorchiasis in Foshan, China
Authors: Yuan Ruixia , Huang Jicai , Zhang Xinan , Ruan Shigui
Published: October 2018

Clonorchiasis, known as the Chinese liver fluke disease, is caused by Clonorchis sinensis infection with food-borne liver fluke, which is transmitted via snails to freshwater fish and then to human beings or other piscivorous mammals. Clonorchis sinensis infection is mainly related to liver and biliary disorders, especially cholangiocarcinoma, and has an increased human-health impact due to the greater consumption of raw freshwater fish. In this article, we propose a deterministic model to describe the spread of clonorchiasis among human-snail-fish populations and use the model to simulate the data on the numbers of inspected and infected individuals of Foshan City, located in Guangdong Province in the southeast of P.R China, from 1980–2010. Mathematical and numerical analyses of the model are carried out to understand the transmission dynamics of clonorchiasis and explore effective control measures for the local outbreaks of the disease. We find that (i) the transmission of clonorchiasis from cercariae to fish plays a more important role than that from eggs to snails and from fish to humans; (ii) As the cycle of infection-treatment-reinfection continues, it is unlikely that treatment with drugs alone can control and eventually eradicate clonorchiasis. These strongly suggest that a more comprehensive approach needs to include environmental modification in order to break the cercariae-fish transmission cycle, to enhance awareness about the disease, and to improve prevention measures.
The Impact of Caesarean Section on the Risk of Childhood Overweight and Obesity: New Evidence from a Contemporary Cohort Study
Authors: Masukume Gwinyai , O’Neill Sinéad M. , Baker Philip N. , Kenny Louise C. , Morton Susan M. B. , Khashan Ali S.
Published: October 2018

Caesarean section (CS) rates are increasing globally and exceed 50% in some countries. Childhood obesity has been linked to CS via lack of exposure to vaginal microflora although the literature is inconsistent. We investigated the association between CS birth and the risk of childhood obesity using the nationally representative Growing-Up-in-Ireland (GUI) cohort. The GUI study recruited randomly 11134 infants. The exposure was categorised into normal vaginal birth (VD) [reference], assisted VD, elective (planned) CS and emergency (unplanned) CS. The primary outcome measure was obesity defined according to the International Obesity Taskforce criteria. Statistical analysis included multinomial logistic regression with adjustment for potential confounders. Infants delivered by elective CS had an adjusted relative risk ratio (aRRR) = 1.32; [95% confidence interval (CI) 1.01–1.74] of being obese at age three years. This association was attenuated when macrosomic children were excluded (aRRR = 0.99; [95% CI 0.67–1.45]). Infants delivered by emergency CS had an increased risk of obesity aRRR = 1.56; [95% CI 1.20–2.03]; this association remained after excluding macrosomic children. We found insufficient evidence to support a causal relationship between elective CS and childhood obesity. An increased risk of obesity in children born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora.
Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas and Other Glucose-lowering Therapies for Three Acute Outcomes
Authors: Gamble John-Michael , Donnan Jennifer R. , Chibrikov Eugene , Twells Laurie K. , Midodzi William K. , Majumdar Sumit R.
Published: October 2018

Although the glucose lowering effect of dipeptidyl peptidase-4 (DPP4) inhibitors is well established, several potential serious acute safety concerns have been raised including acute kidney injury, respiratory tract infections, and acute pancreatitis. Using the UK-based Clinical Practice Research Datalink (CPRD), we identified initiators (365-day washout period) of DPP4 inhibitors and relevant comparators including initiators of sulfonylureas, metformin, thiazolidinediones, and insulin between January 2007 and January 2016 to quantify the association between DPP4 inhibitors and three acute health events – acute kidney injury, respiratory tract infections, and acute pancreatitis. The associations between drug and study outcomes were estimated using Cox proportional hazard models adjusted for deciles of high-dimensional propensity scores and number of additional glucose lowering agents. After controlling for potential confounders, the risk was not significantly increased or decreased for initiators of DPP4 inhibitors compared to sulfonylureas (hazard ratio (HR) [95% confidence interval (CI)] for acute kidney injury: 0.81 [0.56–1.18]; HR for respiratory tract infections: 0.93 [0.84–1.04]; HR for acute pancreatitis 1.03 [0.42–2.52], metformin (HR for respiratory tract infection 0.91 [0.65–1.27]), thiazolidinediones (HR for acute kidney injury: 1.12 [0.60–2.10]; HR for respiratory tract infections: 1.02 [0.86–1.21]; HR for acute pancreatitis: 1.21 [0.25–5.72]), or insulin (HR for acute kidney injury: 1.40 [0.77–2.55]; HR for respiratory tract infections: 0.74 [0.60–0.92]; HR for acute pancreatitis: 1.01 [0.24–4.19]). Initiators of DPP4 inhibitors were associated with an increased risk of acute kidney injury when compared to metformin initiators (HR [95% CI] for acute kidney injury: 1.85 [1.10–3.12], although this association was attenuated when DPP4 inhibitor monotherapy was compared to metformin monotherapy exposure as a time-dependent variable (HR 1.39 [0.91–2.11]). Initiation of a DPP4 inhibitor was not associated with an increased risk of acute kidney injury, respiratory tract infections, or acute pancreatitis compared to sulfonylureas or other glucose-lowering therapies.
Development of lentiviral vectors for efficient glutamatergic-selective gene expression in cultured hippocampal neurons
Authors: Egashira Yoshihiro , Mori Yasunori , Yanagawa Yuchio , Takamori Shigeo
Published: October 2018

Targeting gene expression to a particular subset of neurons helps study the cellular function of the nervous system. Although neuron-specific promoters, such as the synapsin I promoter and the α-CaMKII promoter, are known to exhibit selectivity for excitatory glutamatergic neurons in vivo, the cell type-specificity of these promoters has not been thoroughly tested in culture preparations. Here, by using hippocampal culture preparation from the VGAT-Venus transgenic mice, we examined the ability of five putative promoter sequences of glutamatergic-selective markers including synapsin I, α-CaMKII, the vesicular glutamate transporter 1 (VGLUT1), Dock10 and Prox1. Among these, a genomic fragment containing a 2.1 kb segment upstream of the translation start site (TSS) of the VGLUT1 implemented in a lentiviral vector with the Tet-Off inducible system achieved the highest preferential gene expression in glutamatergic neurons. Analysis of various lengths of the VGLUT1 promoter regions identified a segment between −2.1 kb and −1.4 kb from the TSS as a responsible element for the glutamatergic selectivity. Consistently, expression of channelrhodopsin under this promoter sequence allowed for selective light-evoked activation of excitatory neurons. Thus, the lentiviral system carrying the VGLUT1 promoter fragment can be used to effectively target exogenous gene expression to excitatory glutamatergic neurons in cultures.
Anodal transcranial direct current stimulation prevents methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by modulating autophagy in an in vivo mouse model of Parkinson’s disease
Authors: Lee Sang-Bin , Kim Hee-Tae , Yang Hyun Ok , Jang Wooyoung
Published: October 2018

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the accumulation of protein inclusions and the loss of dopaminergic neurons. Transcranial direct current stimulation (tDCS) is a non-invasive brain-stimulating technique that has demonstrated promising results in clinical studies of PD. Despite accumulating evidence indicating that tDCS exerts a protective effect, the mechanism underlying its activity remains unknown. In the present study, we first investigated the neuroprotective effect of tDCS in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and then evaluated the effect of tDCS on the autophagy pathway. tDCS improved behavioral alterations, increased tyrosine hydroxylase protein levels and suppressed α-synuclein protein levels in MPTP-treated mice. MPTP-treated mice subjected to tDCS also had lower levels of autophagy-related proteins, such as microtubule-associated protein 1 light chain 3 and AMP-activated protein kinase, and higher levels of mechanistic target of rapamycin and p62. In addition, the protein levels of phosphoinositide 3-kinase and brain-derived neurotrophic factor were higher, and the levels of unc-51-like kinase 1 were lower in MPTP-treated mice subjected to tDCS. Our findings suggest that tDCS protected against MPTP-induced PD in a mouse model by modulating autophagy.