bluuebunny/crossref_metadata_2025 huggingface dataset:
Science Explains “Rough and Chaotic” Cloud Feature
Authors: Kornei Katherine
Published: June 2017

Research on the newest entry in the International Cloud Atlas produces insights into what these cloud features are made of and how they form.
The bZIP transcription factor MdHY5 regulates anthocyanin accumulation and nitrate assimilation in apple
Authors: An Jian-Ping , Qu Feng-Jia , Yao Ji-Fang , Wang Xiao-Na , You Chun-Xiang , Wang Xiao-Fei , Hao Yu-Jin
Published: June 2017

The basic leucine zipper (bZIP) transcription factor HY5 plays a multifaceted role in plant growth and development. Here the apple MdHY5 gene was cloned based on its homology with Arabidopsis HY5. Expression analysis demonstrated that MdHY5 transcription was induced by light and abscisic acid treatments. Electrophoretic mobility shift assays and transient expression assays subsequently showed that MdHY5 positively regulated both its own transcription and that of MdMYB10 by binding to E-box and G-box motifs, respectively. Furthermore, we obtained transgenic apple calli that overexpressed the MdHY5 gene, and apple calli coloration assays showed that MdHY5 promoted anthocyanin accumulation by regulating expression of the MdMYB10 gene and downstream anthocyanin biosynthesis genes. In addition, the transcript levels of a series of nitrate reductase genes and nitrate uptake genes in both wild-type and transgenic apple calli were detected. In association with increased nitrate reductase activities and nitrate contents, the results indicated that MdHY5 might be an important regulator in nutrient assimilation. Taken together, these results indicate that MdHY5 plays a vital role in anthocyanin accumulation and nitrate assimilation in apple.
Erratum: Adiposity and blood pressure among 55 000 relatively lean rural adults in southwest of China
Authors: Chen X , Du H , Zhang J , Chen X , Luo G , Que X , Zhang N , Bian Z , Guo Y , Li L , Chen Z , Wu X
Published: June 2017

Correction to: Journal of Human Hypertension (2015) 29, 522–529; doi:10.1038/jhh.2014.129; published online 5 February 2015 This article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.
Contrasting mechanisms of growth in two model rod-shaped bacteria
Authors: Billaudeau Cyrille , Chastanet Arnaud , Yao Zhizhong , Cornilleau Charlène , Mirouze Nicolas , Fromion Vincent , Carballido-López Rut
Published: June 2017

How cells control their shape and size is a long-standing question in cell biology. Many rod-shaped bacteria elongate their sidewalls by the action of cell wall synthesizing machineries that are associated to actin-like MreB cortical patches. However, little is known about how elongation is regulated to enable varied growth rates and sizes. Here we use total internal reflection fluorescence microscopy and single-particle tracking to visualize MreB isoforms, as a proxy for cell wall synthesis, in Bacillus subtilis and Escherichia coli cells growing in different media and during nutrient upshift. We find that these two model organisms appear to use orthogonal strategies to adapt to growth regime variations: B. subtilis regulates MreB patch speed, while E. coli may mainly regulate the production capacity of MreB-associated cell wall machineries. We present numerical models that link MreB-mediated sidewall synthesis and cell elongation, and argue that the distinct regulatory mechanism employed might reflect the different cell wall integrity constraints in Gram-positive and Gram-negative bacteria.
River plastic emissions to the world’s oceans
Authors: Lebreton Laurent C. M. , van der Zwet Joost , Damsteeg Jan-Willem , Slat Boyan , Andrady Anthony , Reisser Julia
Published: June 2017

Plastics in the marine environment have become a major concern because of their persistence at sea, and adverse consequences to marine life and potentially human health. Implementing mitigation strategies requires an understanding and quantification of marine plastic sources, taking spatial and temporal variability into account. Here we present a global model of plastic inputs from rivers into oceans based on waste management, population density and hydrological information. Our model is calibrated against measurements available in the literature. We estimate that between 1.15 and 2.41 million tonnes of plastic waste currently enters the ocean every year from rivers, with over 74% of emissions occurring between May and October. The top 20 polluting rivers, mostly located in Asia, account for 67% of the global total. The findings of this study provide baseline data for ocean plastic mass balance exercises, and assist in prioritizing future plastic debris monitoring and mitigation strategies.
Dendro-dendritic cholinergic excitation controls dendritic spike initiation in retinal ganglion cells
Authors: Brombas A. , Kalita-de Croft S. , Cooper-Williams E. J. , Williams S. R.
Published: June 2017

The retina processes visual images to compute features such as the direction of image motion. Starburst amacrine cells (SACs), axonless feed-forward interneurons, are essential components of the retinal direction-selective circuitry. Recent work has highlighted that SAC-mediated dendro-dendritic inhibition controls the action potential output of direction-selective ganglion cells (DSGCs) by vetoing dendritic spike initiation. However, SACs co-release GABA and the excitatory neurotransmitter acetylcholine at dendritic sites. Here we use direct dendritic recordings to show that preferred direction light stimuli evoke SAC-mediated acetylcholine release, which powerfully controls the stimulus sensitivity, receptive field size and action potential output of ON-DSGCs by acting as an excitatory drive for the initiation of dendritic spikes. Consistent with this, paired recordings reveal that the activation of single ON-SACs drove dendritic spike generation, because of predominate cholinergic excitation received on the preferred side of ON-DSGCs. Thus, dendro-dendritic release of neurotransmitters from SACs bi-directionally gate dendritic spike initiation to control the directionally selective action potential output of retinal ganglion cells.
WASH maintains NKp46+ ILC3 cells by promoting AHR expression
Authors: Xia Pengyan , Liu Jing , Wang Shuo , Ye Buqing , Du Ying , Xiong Zhen , Han Ze-Guang , Tong Liang , Fan Zusen
Published: June 2017

Innate lymphoid cells (ILCs) communicate with other haematopoietic and non-haematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How these ILC lineages develop and are maintained is not clear. Here we show that WASH is highly expressed in the nucleus of group 3 ILCs (ILC3s). WASH deletion impairs the cell pool of NKp46+ ILC3s. In NKp46+ ILC3s, WASH recruits Arid1a to the Ahr promoter thus activating AHR expression. WASH deletion in ILC3s decreases the number of NKp46+ ILC3s. Moreover, Arid1a deletion impedes AHR expression and impairs the maintenance of NKp46+ ILC3s. Therefore, WASH-mediated AHR expression has a critical function in the maintenance of NKp46+ ILC3s.
The CaMKII holoenzyme structure in activation-competent conformations
Authors: Myers Janette B. , Zaegel Vincent , Coultrap Steven J. , Miller Adam P. , Bayer K. Ulrich , Reichow Steve L.
Published: June 2017

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) assembles into large 12-meric holoenzymes, which is thought to enable regulatory processes required for synaptic plasticity underlying learning, memory and cognition. Here we used single particle electron microscopy (EM) to determine a pseudoatomic model of the CaMKIIα holoenzyme in an extended and activation-competent conformation. The holoenzyme is organized by a rigid central hub complex, while positioning of the kinase domains is highly flexible, revealing dynamic holoenzymes ranging from 15–35 nm in diameter. While most kinase domains are ordered independently, ∼20% appear to form dimers and <3% are consistent with a compact conformation. An additional level of plasticity is revealed by a small fraction of bona-fide 14-mers (<4%) that may enable subunit exchange. Biochemical and cellular FRET studies confirm that the extended state of CaMKIIα resolved by EM is the predominant form of the holoenzyme, even under molecular crowding conditions.
Type-2 innate lymphoid cells control the development of atherosclerosis in mice
Authors: Newland Stephen A. , Mohanta Sarajo , Clément Marc , Taleb Soraya , Walker Jennifer A. , Nus Meritxell , Sage Andrew P. , Yin Changjun , Hu Desheng , Kitt Lauren L. , Finigan Alison J. , Rodewald Hans-Reimer , Binder Christoph J. , McKenzie Andrew N. J. , Habenicht Andreas J. , Mallat Ziad
Published: June 2017

Type-2 innate lymphoid cells (ILC2) are a prominent source of type II cytokines and are found constitutively at mucosal surfaces and in visceral adipose tissue. Despite their role in limiting obesity, how ILC2s respond to high fat feeding is poorly understood, and their direct influence on the development of atherosclerosis has not been explored. Here, we show that ILC2 are present in para-aortic adipose tissue and lymph nodes and display an inflammatory-like phenotype atypical of adipose resident ILC2. High fat feeding alters both the number of ILC2 and their type II cytokine production. Selective genetic ablation of ILC2 in Ldlr−/− mice accelerates the development of atherosclerosis, which is prevented by reconstitution with wild type but not Il5−/− or Il13−/− ILC2. We conclude that ILC2 represent a major innate cell source of IL-5 and IL-13 required for mounting atheroprotective immunity, which can be altered by high fat diet.
Chloroplast Genomic Resource of Paris for Species Discrimination
Authors: Song Yun , Wang Shaojun , Ding Yuanming , Xu Jin , Li Ming Fu , Zhu Shuifang , Chen Naizhong
Published: June 2017

Paris is famous in China for its medicinal value and has been included in the Chinese Pharmacopoeia. Inaccurate identification of these species could confound their effective exploration, conservation, and domestication. Due to the plasticity of the morphological characteristics, correct identification among Paris species remains problematic. In this regard, we report the complete chloroplast genome of P. thibetica and P. rugosa to develop highly variable molecular markers. Comparing three chloroplast genomes, we sought out the most variable regions to develop the best cpDNA barcodes for Paris. The size of Paris chloroplast genome ranged from 162,708 to 163,200 bp. A total of 134 genes comprising 81 protein coding genes, 45 tRNA genes and 8 rRNA genes were observed in all three chloroplast genomes. Eight rapidly evolving regions were detected, as well as the difference of simple sequence repeats (SSR) and repeat sequence. Two regions of the coding gene ycf1, ycf1a and ycf1b, evolved the quickest and were proposed as core barcodes for Paris. The complete chloroplast genome sequences provide more integrated and adequate information for better understanding the phylogenetic pattern and improving efficient discrimination during species identification.
FGF23 is synthesised locally by renal tubules and activates injury-primed fibroblasts
Authors: Smith Edward R. , Tan Sven-Jean , Holt Stephen G. , Hewitson Tim D.
Published: June 2017

In kidney disease, higher circulating levels of the mineral-regulating hormone fibroblast growth factor (FGF)-23 are predictive of disease progression but direct pathogenic effects on the kidney are unknown. We sought evidence of local renal synthesis in response to unilateral ureteric obstruction in the mouse, and pro-fibrotic actions of FGF23 on the fibroblast in vitro. Acute tubulointerstitial injury due to unilateral ureteric obstruction stimulated renal FGF23 synthesis by tubules, and downregulated inactivating proprotein convertases, without effects on systemic mineral metabolism. In vitro, FGF23 had divergent effects on fibroblast activation in cells derived from normal and obstructed kidneys. While FGF23 failed to stimulate fibrogenesis in normal fibroblasts, in those primed by injury, FGF23 induced pro-fibrotic signalling cascades via activation of TGF-β pathways. Effects were independent of α-klotho. Tubule-derived FGF23 may amplify myofibroblast activation in acute renal injury, and might provide a novel therapeutic target in renal fibrosis.
The importance of naming cryptic species and the conservation of endemic subterranean amphipods
Authors: Delić Teo , Trontelj Peter , Rendoš Michal , Fišer Cene
Published: June 2017

Molecular taxonomy often uncovers cryptic species, reminding us that taxonomic incompleteness is even more severe than previous thought. The importance of cryptic species for conservation is poorly understood. Although some cryptic species may be seriously threatened or otherwise important, they are rarely included in conservation programs as most of them remain undescribed. We analysed the importance of cryptic species in conservation by scrutinizing the South European cryptic complex of the subterranean amphipod Niphargus stygius sensu lato. Using uni- and multilocus delineation methods we show that it consists of 15 parapatric and sympatric species, which we describe using molecular diagnoses. The new species are not mere “taxonomic inflation” as they originate from several distinct branches within the genus and coexist with no evidence of lineage sharing. They are as evolutionarily distinct as average nominal species of the same genus. Ignoring these cryptic species will underestimate the number of subterranean endemics in Slovenia by 12 and in Croatia by four species, although alpha diversity of single caves remains unchanged. The new taxonomy renders national Red Lists largely obsolete, as they list mostly large-ranged species but omit critically endangered single-site endemics. Formal naming of cryptic species is critical for them to be included in conservation policies and faunal listings.
Politeness and Compassion Differentially Predict Adherence to Fairness Norms and Interventions to Norm Violations in Economic Games
Authors: Zhao Kun , Ferguson Eamonn , Smillie Luke D.
Published: June 2017

Adherence to norms and interventions to norm violations are two important forms of social behaviour modelled in economic games. While both appear to serve a prosocial function, they may represent separate mechanisms corresponding with distinct emotional and psychological antecedents, and thus may be predicted by different personality traits. In this study, we compared adherence to fairness norms in the dictator game with responses to violations of the same norms in third-party punishment and recompensation games with respect to prosocial traits from the Big Five and HEXACO models of personality. The results revealed a pattern of differential relations between prosocial traits and game behaviours. While norm adherence in the dictator game was driven by traits reflecting good manners and non-aggression (the politeness aspect of Big Five agreeableness and HEXACO honesty-humility), third-party recompensation of victims—and to a lesser extent, punishment of offenders—was uniquely driven by traits reflecting emotional concern for others (the compassion aspect of Big Five agreeableness). These findings demonstrate the discriminant validity between similar prosocial constructs and highlight the different prosocial motivations underlying economic game behaviours.
Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
Authors: Truszkowska Grażyna T. , Bilińska Zofia T. , Muchowicz Angelika , Pollak Agnieszka , Biernacka Anna , Kozar-Kamińska Katarzyna , Stawiński Piotr , Gasperowicz Piotr , Kosińska Joanna , Zieliński Tomasz , Płoski Rafał
Published: June 2017

The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, and is involved in myofibrillar assembly in the foetal heart and in force transmission in the adult heart. The homozygous NRAP truncating variant (rs201084642), which is predicted to introduce premature stop codon into all NRAP isoforms, was revealed in the dilated cardiomyopathy patient using whole exome sequencing. The same genotype was detected in the asymptomatic proband’s brother. The expression of the NRAP protein was undetectable in the patient’s heart muscle by the Western blot. Genotyping for rs201084642 in the ethnically matched cohort of 231 dilated cardiomyopathy patients did not reveal any additional subjects with this variant. Our findings suggest that the biallelic loss-of-function mutation in NRAP could constitute a relatively rare, low-penetrance genetic risk factor for dilated cardiomyopathy.
Bone Fusion in Normal and Pathological Development is Constrained by the Network Architecture of the Human Skull
Authors: Esteve-Altava Borja , Vallès-Català Toni , Guimerà Roger , Sales-Pardo Marta , Rasskin-Gutman Diego
Published: June 2017

Craniosynostosis, the premature fusion of cranial bones, affects the correct development of the skull producing morphological malformations in newborns. To assess the susceptibility of each craniofacial articulation to close prematurely, we used a network model of the skull to quantify the link reliability (an index based on stochastic block models and Bayesian inference) of each articulation. We show that, of the 93 human skull articulations at birth, the few articulations that are associated with non-syndromic craniosynostosis conditions have statistically significant lower reliability scores than the others. In a similar way, articulations that close during the normal postnatal development of the skull have also lower reliability scores than those articulations that persist through adult life. These results indicate a relationship between the architecture of the skull and the specific articulations that close during normal development as well as in pathological conditions. Our findings suggest that the topological arrangement of skull bones might act as a structural constraint, predisposing some articulations to closure, both in normal and pathological development, also affecting the long-term evolution of the skull.
A Diet Diverse in Bamboo Parts is Important for Giant Panda (Ailuropoda melanoleuca) Metabolism and Health
Authors: Wang Hairui , Zhong Heju , Hou Rong , Ayala James , Liu Guangmang , Yuan Shibin , Yan Zheng , Zhang Wenping , Liu Yuliang , Cai Kailai , Cai Zhigang , Huang He , Zhang Zhihe , Wu De
Published: June 2017

The aim of this study was to determine the metabolic response in giant pandas (Ailuropoda melanoleuca) to the consumption of certain parts of bamboo above ground growth. Giant pandas were provisioned with three species of bamboo: Phyllostachys bissetii, of which they only consume the culm (culm group); Bashania fargesii, of which they only consume the leaves (leaf group); and Qiongzhuea opienensis, of which they only consume the shoots (shoot group). The “culm” group absorbed the highest amount of calories and fiber, but was in short energy supply (depressed tricarboxylic acid cycle activity), and high fiber level diet might reduce the digestibility of protein. The “culm” and “leaf” groups absorbed less protein, and had a lower rate of body mass growth than the “shoot” group. Digestion of fiber requires energy input and yields low caloric extraction from the culm and leaf, and protein intake is important for increasing body mass. However, long-term consumption of shoots may have a potentially negative effect on the health because of high protein composition. Therefore, a balanced diet consisting of diverse plant parts of bamboo is important for the overall metabolic function and health of captive giant pandas.
EP4 inhibition attenuates the development of diabetic and non-diabetic experimental kidney disease
Authors: Thieme Karina , Majumder Syamantak , Brijmohan Angela S. , Batchu Sri N. , Bowskill Bridgit B. , Alghamdi Tamadher A. , Advani Suzanne L. , Kabir M. Golam , Liu Youan , Advani Andrew
Published: June 2017

The therapeutic targeting of prostanoid subtype receptors may slow the development of chronic kidney disease (CKD) through mechanisms that are distinct from those of upstream COX inhibition. Here, employing multiple experimental models of CKD, we studied the effects of inhibition of the EP4 receptor, one of four receptor subtypes for the prostanoid prostaglandin E2. In streptozotocin-diabetic endothelial nitric oxide synthase knockout mice, EP4 inhibition attenuated the development of albuminuria, whereas the COX inhibitor indomethacin did not. In Type 2 diabetic db/db mice, EP4 inhibition lowered albuminuria to a level comparable with that of the ACE inhibitor captopril. However, unlike captopril, EP4 inhibition had no effect on blood pressure or hyperfiltration although it did attenuate mesangial matrix accumulation. Indicating a glucose-independent mechanism of action, EP4 inhibition also attenuated proteinuria development and glomerular scarring in non-diabetic rats subjected to surgical renal mass ablation. Finally, in vitro, EP4 inhibition prevented transforming growth factor-ß1 induced dedifferentiation of glomerular podocytes. In rodent models of diabetic and non-diabetic CKD, EP4 inhibition attenuated renal injury through mechanisms that were distinct from either broadspectrum COX inhibition or “standard of care” renin angiotensin system blockade. EP4 inhibition may represent a viable repurposing opportunity for the treatment of CKD.
Abrupt p-n junction using ionic gating at zero-bias in bilayer graphene
Authors: Grover Sameer , Joshi Anupama , Tulapurkar Ashwin , Deshmukh Mandar M.
Published: June 2017

Graphene is a promising candidate for optoelectronic applications. In this report, a double gated bilayer graphene FET has been made using a combination of electrostatic and electrolytic gating in order to form an abrupt p-n junction. The presence of two Dirac peaks in the gating curve of the fabricated device confirms the formation of a p-n junction. At low temperatures, when the electrolyte is frozen intentionally, the photovoltage exhibits a six-fold pattern indicative of the hot electron induced photothermoelectric effect that has also been seen in graphene p-n junctions made using metallic gates. We have observed that the photovoltage increases with decreasing temperature indicating a dominant role of supercollision scattering. Our technique can also be extended to other 2D materials and to finer features that will lead to p-n junctions which span a large area, like a superlattice, that can generate a larger photoresponse. Our work creating abrupt p-n junctions is distinct from previous works that use a source–drain bias voltage with a single ionic gate creating a spatially graded p-n junction.
Single- and dual-band filtering-response power dividers embedded SIW filter with improved output isolation
Authors: Song Kaijun , Zhu Yu , Zhang Fan
Published: June 2017

Two filtering-response power dividers embedded substrate integrated waveguide (SIW) filter are presented in this paper. By employing different SIW resonators, single- and dual-band filtering response are achieved, respectively. The even- and odd-mode method and the coupled resonator theory are applied to analyze the presented power dividers. In addition, a novel isolation technique using multiple isolation resistors is proposed to improve the output isolation performance of the filtering-response power divider with multiple resonators. To verify the proposed circuits, the single- and dual-band filtering-response power dividers are designed, fabricated and measured. Reasonable agreement between the simulated and measured results is achieved. Moreover, the measured output isolation of the fabricated dual-band filtering-response power divider with multiple resonators is about 20 dB, which demonstrates the theoretical predication.
Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations?
Authors: Valente Umberto , Vinanzi Cinzia , Dipresa Savina , Selice Riccardo , Menegazzo Massimo , Iafrate Massimo , Foresta Carlo , Garolla Andrea
Published: June 2017

Klinefelter Syndrome (KS) is the most common chromosomal disorder in men leading to non-obstructive azoospermia. Spermatozoa can be found by TESE in about 50% of adults with KS despite severe testicular degeneration. We evaluated AR variations and polymorphism length in 135 non-mosaic KS patients, aimed to find possible correlation with clinical features, sex hormones and sperm retrieval. Among 135 KS patients we found AR variations in eight subjects (5.9%). All variations but one caused a single amino acid substitution. Four variations P392S, Q58L, L548F, A475V found in six patients had been previously described to be associated with different degrees of androgen insensitivity. Moreover we observed in two patients Y359F and D732D novel variations representing respectively a missense variation and a synonymous variation not leading to amino acid substitution. All the Klinefelter patients with AR gene variations were azoospermic. Spermatozoa were retrieved with TESE for two men (40%), sperm retrieval was unsuccessful in other 3 patients. This is the only study reporting AR variations in KS patients. Relevant clinical differences not emerged between AR mutated and not AR mutated KS patients, but does each variation play an important role in the trasmission to the offspring obtained by ART in this patients?
Estimating fish abundance at spawning aggregations from courtship sound levels
Authors: Rowell Timothy J. , Demer David A. , Aburto-Oropeza Octavio , Cota-Nieto Juan José , Hyde John R. , Erisman Brad E.
Published: June 2017

Sound produced by fish spawning aggregations (FSAs) permits the use of passive acoustic methods to identify the timing and location of spawning. However, difficulties in relating sound levels to abundance have impeded the use of passive acoustics to conduct quantitative assessments of biomass. Here we show that models of measured fish sound production versus independently measured fish density can be generated to estimate abundance and biomass from sound levels at FSAs. We compared sound levels produced by spawning Gulf Corvina (Cynoscion othonopterus) with simultaneous measurements of density from active acoustic surveys in the Colorado River Delta, Mexico. During the formation of FSAs, we estimated peak abundance at 1.53 to 1.55 million fish, which equated to a biomass of 2,133 to 2,145 metric tons. Sound levels ranged from 0.02 to 12,738 Pa2, with larger measurements observed on outgoing tides. The relationship between sound levels and densities was variable across the duration of surveys but stabilized during the peak spawning period after high tide to produce a linear relationship. Our results support the use of active acoustic methods to estimate density, abundance, and biomass of fish at FSAs; using appropriately scaled empirical relationships, sound levels can be used to infer these estimates.
Coupling neutron reflectivity with cell-free protein synthesis to probe membrane protein structure in supported bilayers
Authors: Soranzo Thomas , Martin Donald K. , Lenormand Jean-Luc , Watkins Erik B.
Published: June 2017

The structure of the p7 viroporin, an oligomeric membrane protein ion channel involved in the assembly and release of the hepatitis C virus, was determined from proteins expressed and inserted directly into supported model lipid membranes using cell-free protein expression. Cell-free protein expression allowed (i ) high protein concentration in the membrane, (ii ) control of the protein’s isotopic constitution, and (iii ) control over the lipid environment available to the protein. Here, we used cell-free protein synthesis to directly incorporate the hepatitis C virus (HCV) p7 protein into supported lipid bilayers formed from physiologically relevant lipids (POPC or asolectin) for both direct structural measurements using neutron reflectivity (NR) and conductance measurements using electrical impedance spectroscopy (EIS). We report that HCV p7 from genotype 1a strain H77 adopts a conical shape within lipid bilayers and forms a viroporin upon oligomerization, confirmed by EIS conductance measurements. This combination of techniques represents a novel approach to the study of membrane proteins and, through the use of selective deuteration of particular amino acids to enhance neutron scattering contrast, has the promise to become a powerful tool for characterizing the protein conformation in physiologically relevant environments and for the development of biosensor applications.
Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
Authors: Kim Tae Sung , Shin Yern-Hyerk , Lee Hye-Mi , Kim Jin Kyung , Choe Jin Ho , Jang Ji-Chan , Um Soohyun , Jin Hyo Sun , Komatsu Masaaki , Cha Guang-Ho , Chae Han-Jung , Oh Dong-Chan , Jo Eun-Kyeong
Published: June 2017

The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster–Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.
Fuel loads acquired at a stopover site influence the pace of intercontinental migration in a boreal songbird
Authors: Gómez Camila , Bayly Nicholas J. , Norris D. Ryan , Mackenzie Stuart A. , Rosenberg Kenneth V. , Taylor Philip D. , Hobson Keith A. , Daniel Cadena Carlos
Published: June 2017

Long-distance migratory organisms are under strong selection to migrate quickly. Stopovers demand more time than flying and are used by individuals to refuel during migration, but the effect of fuel loads (fat) acquired at stopover sites on the subsequent pace of migration has not been quantified. We studied stopover behaviour of Grey-cheeked Thrush (Catharus minimus) at a site in northern Colombia and then tracked their migration using an intercontinental radio-telemetry array. Tracking confirmed long-distance flights of more than 3000 km, highlighting the key importance of a single stopover site to the migration strategy of this species. Our results suggest that these songbirds behave as time-minimizers as predicted by optimal migration theory, and that fuel loads acquired at this South American stopover site, together with departure date, carry-over to influence the pace of migration, contributing to differences in travel time of up to 30 days in birds subsequently detected in the U. S. and Canada. Such variation in the pace of migration arising from a single stopover site, likely has important fitness consequences and suggests that identifying important fuelling sites will be essential to effectively conserve migratory species.
The Hippocampus Sparing Volume Modulated Arc Therapy does not Influence Plan Quality on Locally Advanced Nasopharyngeal Carcinoma Patients
Authors: Gu Wendong , Li Qilin , Xi Dan , Tian Ye , Mo Juncong , Pei Honglei
Published: June 2017

Irradiation on hippocampus would lead to neuro-cognitive dysfunction in locally advanced nasopharyneal carcinoma (LA-NPC) patients accepting radiotherapy. Our study here aimed to investigate if undergoing hippocampus sparing (HS) volume modulated arc therapy (VMAT) would influence the plan quality in LA NPC patients. We designed three kinds of radiotherapeutic plans for 11 LA NPC patients: conventional VMAT (C-VMAT), HS-VMAT and HS intensity modulated radiation therapy with dynamic multileaf collimator (HS-dMLC). And the dose distribution on targets and surrounding organs at risk (OAR) were carefully evaluated. We found out that the expected doses on hippocampus were significantly lowered in HS-VMAT (899 ± 378 cGy) and HS-dMLC (896 ± 321 cGy) as compared to C-VMAT (1518 ± 337 cGy, p < 0.05), but meaningless difference was presented on plan quality of targets (p > 0.05). Moreover, lower radiation doses on brain stem were observed in HS-VMAT plan in comparison with C-VMAT plan (p < 0.05). However, there were no statistically meaningful diversities in the doses received by other OARs among all plans. Here we concluded that HS-VMAT presented promising advantages on protecting hipppcampus and brain stem as compared to C-VMAT and HS-dMLC, but enthusiastically had no effects on plan quality in LA-NPC patients.
Identification of postsynaptic phosphatidylinositol-4,5-bisphosphate (PIP2) roles for synaptic plasticity using chemically induced dimerization
Authors: Kim Su-Jeong , Jeong Min-Jae , Jo Hee-Jung , Jung Jung Hoon , Kaang Bong-Kiun , Choi Yun-Beom , Kim Joung-Hun
Published: June 2017

Phosphatidylinositol-4,5-bisphosphate (PIP2), one of the key phospholipids, directly interacts with several membrane and cytosolic proteins at neuronal plasma membranes, leading to changes in neuronal properties including the feature and surface expression of ionotropic receptors. Although PIP2 is also concentrated at the dendritic spines, little is known about the direct physiological functions of PIP2 at postsynaptic as opposed to presynaptic sites. Most previous studies used genetic and pharmacological methods to modulate enzymes that alter PIP2 levels, making it difficult to delineate time- or region-specific roles of PIP2. We used chemically-induced dimerization to translocate inositol polyphosphate 5-phosphatase (Inp54p) to plasma membranes in the presence of rapamycin. Upon redistribution of Inp54p, long-term depression (LTD) induced by low-frequency stimulation was blocked in the mouse hippocampal CA3-CA1 pathway, but the catalytically-dead mutant did not affect LTD induction. Collectively, PIP2 is critically required for induction of LTD whereas translocation of Inp54p to plasma membranes has no effect on the intrinsic properties of the neurons, basal synaptic transmission, long-term potentiation or expression of LTD.
Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail
Authors: Mahmoud Marwa M. , Serbanovic-Canic Jovana , Feng Shuang , Souilhol Celine , Xing Rouyu , Hsiao Sarah , Mammoto Akiko , Chen Jing , Ariaans Markus , Francis Sheila E. , Van der Heiden Kim , Ridger Victoria , Evans Paul C.
Published: June 2017

Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress. Gene silencing also revealed that Snail enhanced the permeability of endothelial monolayers to macromolecules by promoting EC proliferation and migration. En face staining of the murine aorta or carotid arteries modified with flow-altering cuffs demonstrated that Snail was expressed preferentially at low shear stress sites that are predisposed to atherosclerosis. Snail was also expressed in EC overlying atherosclerotic plaques in coronary arteries from patients with ischemic heart disease implying a role in human arterial disease. We conclude that Snail is an essential driver of EndMT under low shear stress conditions and may promote early atherogenesis by enhancing vascular permeability.
Orbital Angular Momentum (OAM) of Rotating Modes Driven by Electrons in Electron Cyclotron Masers
Authors: Sawant Ashwini , Choe Mun Seok , Thumm Manfred , Choi EunMi
Published: June 2017

The well-defined orbital angular momentum (OAM) of rotating cavity modes operating near the cutoff frequency excited by gyrating electrons in a high-power electron cyclotron maser (ECM)—a gyrotron—has been derived by photonic and electromagnetic wave approaches. A mode generator was built with a high-precision 3D printing technique to mimic the rotating gyrotron modes for precise low-power measurements and shows clear natural production of higher-order OAM modes. Cold-test measurements of higher-order OAM mode generation promise the realization towards wireless long-range communications using high-power ECMs.
Geometric quantum discords of interacting qubits in thermal reservoir
Authors: Li Zhao , Wang Xiao-Min , Zhou Wu , Hu Ming-Liang
Published: June 2017

We examined decay dynamics of various geometric quantum discords (GQDs) for two interacting qubits described by the Heisenberg XY model and further coupled independently to their respective thermal reservoirs. Compared to the case of noninteracting qubits, our results showed that decay rates of the GQDs can be retarded apparently by properly choosing system parameters of the interaction term. In the long-time limit, the asymptotic values of the GQDs are enhanced evidently by tuning anisotropy of the model and strength of the transverse magnetic field. We further illuminated the relations between different GQDs on characterizing quantum correlations, and observed multiple sudden change behaviors of their dynamics.
Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
Authors: Tripathi Amit Kumar , Kumari Tripti , Harioudh Munesh Kumar , Yadav Pranjal Kumar , Kathuria Manoj , Shukla P. K. , Mitra Kalyan , Ghosh Jimut Kanti
Published: June 2017

Marine fish antimicrobial peptide, chrysophsin-1 possesses versatile biological activities but its non-selective nature restricts its therapeutic possibilities. Often small alterations in structural motifs result in significant changes in the properties of concerned proteins/peptides. We have identified GXXXXG motif in chrysophsin-1. Glycine residue(s) of this motif in Chrysophsin-1 was/were replaced with alanine, valine and proline residue(s). Of these, proline-substituted Chrysophsin-1 analogs exhibited significantly reduced cytotoxicity towards mammalian cells. Further, these analogs showed broad-spectrum activity against Gram-positive, Gram-negative bacteria, Methicillin-resistant Staphylococcus aureus strains and fungi and also retained antibacterial activity in presence of physiological salts, serum and at elevated temperatures indicative of their therapeutic potential. These Chrysophsin-1 analogs also inhibited lipopolysaccharide (LPS) induced pro-inflammatory responses in THP-1 cells and in murine primary macrophages. One of these single proline-substituted Chrysophsin-1 analogs inhibited LPS-stimulated pro-inflammatory cytokine production in BALB/c mice and elicited appreciable survival of mice administered with a lethal dose of LPS in a model of severe sepsis. The data for the first time showed the implication of GXXXXG motifs in functional and biological properties of an antimicrobial peptide and could be useful to design novel anti-microbial and anti-endotoxin peptides by employing this motif.
Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs
Authors: Legendre Florence , Ollitrault David , Gomez-Leduc Tangni , Bouyoucef Mouloud , Hervieu Magalie , Gruchy Nicolas , Mallein-Gerin Frédéric , Leclercq Sylvain , Demoor Magali , Galéra Philippe
Published: June 2017

Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages. The chondrogenic lineage of BM-MSCs was induced in collagen scaffolds, under normoxia or hypoxia, by BMP-2 and/or TGF-β1. The best chondrogenic induction, with the least hypertrophic induction, was obtained with the combination of BMP-2 and TGF-β1 under hypoxia. Differentiated BM-MSCs were then transfected with siRNAs targeting two markers overexpressed in OA chondrocytes, type I collagen and/or HtrA1 protease. siRNAs significantly decreased mRNA and protein levels of type I collagen and HtrA1, resulting in a more typical chondrocyte phenotype, but with frequent calcification of the subcutaneously implanted constructs in a nude mouse model. Our 3D culture model with BMP-2/TGF-β1 andCOL1A1/HtrA1siRNAs was not effective in producing a cartilage-like matrixin vivo. Further optimization is needed to stabilize the chondrocyte phenotype of differentiated BM-MSCs. Nevertheless, this study offers the opportunity to develop a combinatory cellular therapy strategy for cartilage tissue engineering.
Raman micro-spectroscopy as a viable tool to monitor and estimate the ionic transport in epithelial cells
Authors: Puppulin Leonardo , Pezzotti Giuseppe , Sun Hongxin , Hosogi Shigekuni , Nakahari Takashi , Inui Toshio , Kumamoto Yasuaki , Tanaka Hideo , Marunaka Yoshinori
Published: June 2017

The typical response to the lowering of plasma Na+ concentration and blood pressure in our body involves the release of aldosterone from the adrenal glands, which triggers the reabsorption of sodium in the kidney. Although the effects of aldosterone on this physiological mechanism were extensively studied in the past decades, there are still some aspects to be fully elucidated. In the present study, we propose for the first time a new approach based on Raman spectroscopy to monitor the ionic activity in aldosterone-treated A6 renal epithelial cells. This spectroscopic technique is capable of probing the cells through their thickness in a non-destructive and nimble way. The spectroscopic variations of the Raman bands associated to the O-H stretching of water were correlated to the variations of ionic concentration in the intracellular and extracellular fluids. The increase of Na+ concentration gradients was clearly visualized in the cytosol of aldosterone-treated cells. The enhancement of the Na+ current density induced by aldosterone was estimated from the variation of the ionic chemical potential across the intracellular space. In addition, the variation of the O-H Raman bands of water was used to quantify the cell thickness, which was not affected by aldosterone.
Temporal trends in initiation of VKA, rivaroxaban, apixaban and dabigatran for the treatment of venous thromboembolism - A Danish nationwide cohort study
Authors: Sindet-Pedersen Caroline , Pallisgaard Jannik Langtved , Staerk Laila , Berger Jeffrey S. , Lamberts Morten , Torp-Pedersen Christian , Gislason Gunnar H. , Olesen Jonas Bjerring
Published: June 2017

Danish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). Temporal trends showed a decrease in the initiation of VKA (p-value for decreasing trend, p < 0001) and an increase in the initiation of rivaroxaban and apixaban (p-value for increasing trend, p < 0001). By September 2016, 12%, 70%, 16%, and 2% of patients with VTE were initiated on VKA, rivaroxaban, apixaban, and dabigatran. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with one of the NOACs. In conclusion the initiation of rivaroxaban and apixaban is increasing significantly over time in patients with VTE. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with rivaroxaban or apixaban.
3D ultra-high resolution seismic imaging of shallow Solfatara crater in Campi Flegrei (Italy): New insights on deep hydrothermal fluid circulation processes
Authors: De Landro Grazia , Serlenga Vincenzo , Russo Guido , Amoroso Ortensia , Festa Gaetano , Bruno Pier Paolo , Gresse Marceau , Vandemeulebrouck Jean , Zollo Aldo
Published: June 2017

Seismic tomography can be used to image the spatial variation of rock properties within complex geological media such as volcanoes. Solfatara is a volcano located within the Campi Flegrei, a still active caldera, so it is of major importance to characterize its level of activity and potential danger. In this light, a 3D tomographic high-resolution P-wave velocity image of the shallow central part of Solfatara crater is obtained using first arrival times and amultiscaleapproach. The retrieved images, integrated with the resistivity section and temperature and the CO2flux measurements, define the following characteristics: 1. A depth-dependent P-wave velocity layer down to 14 m, with Vp < 700 m/s typical of poorly-consolidated tephra and affected by CO2degassing; 2. An intermediate layer, deepening towards the mineralized liquid-saturated area (Fangaia), interpreted as permeable deposits saturated with condensed water; 3. A deep, confined high velocity anomaly associated with a CO2reservoir. These features are expression of an area located between the Fangaia, water saturated and replenished from deep aquifers, and the main fumaroles, superficial relief of the deep rising CO2flux. Therefore, the changes in the outgassing rate greatly affect the shallow hydrothermal system, which can be used as a “mirror” of fluid migration processes occurring at depth.