bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory B cells: the cutting edge of immune tolerance in kidney transplantation
Authors: Peng Bo , Ming Yingzi , Yang Cheng
Published: January 2018

Kidney transplantation is the optimal treatment for end-stage renal diseases. Although great improvement has been achieved, immune tolerance is still the Holy Grail that every organ transplant practitioner pursues. The role of B cells in transplantation has long been considered simply to serve as precursors of plasma cells, which produce alloantibodies and induce antibody-mediated rejection. Recent research indicates that a specialized subset of B cells plays an important role in immune regulation, which has been well demonstrated in autoimmune diseases, infections, and cancers. This category of regulatory B cells (Bregs) differs from conventional B cells, and they may help develop a novel immunomodulatory therapeutic strategy to achieve immune tolerance in transplantation. Here, we review the latest evidence regarding phenotypes, functions, and effectors of Bregs and discuss their diverse effects on kidney transplantation.
Givinostat reduces adverse cardiac remodeling through regulating fibroblasts activation
Authors: Milan Marika , Pace Valentina , Maiullari Fabio , Chirivì Maila , Baci Denisa , Maiullari Silvia , Madaro Luca , Maccari Sonia , Stati Tonino , Marano Giuseppe , Frati Giacomo , Puri Pier Lorenzo , De Falco Elena , Bearzi Claudia , Rizzi Roberto
Published: January 2018

Cardiovascular diseases (CVDs) are a major burden on the healthcare system: indeed, over two million new cases are diagnosed every year worldwide. Unfortunately, important drawbacks for the treatment of these patients derive from our current inability to stop the structural alterations that lead to heart failure, the common endpoint of many CVDs. In this scenario, a better understanding of the role of epigenetics – hereditable changes of chromatin that do not alter the DNA sequence itself – is warranted. To date, hyperacetylation of histones has been reported in hypertension and myocardial infarction, but the use of inhibitors for treating CVDs remains limited. Here, we studied the effect of the histone deacetylase inhibitor Givinostat on a mouse model of acute myocardial infarction. We found that it contributes to decrease endothelial-to-mesenchymal transition and inflammation, reducing cardiac fibrosis and improving heart performance and protecting the blood vessels from apoptosis through the modulatory effect of cardiac fibroblasts on endothelial cells. Therefore, Givinostat may have potential for the treatment of CVDs.
Energy use and life cycle greenhouse gas emissions of drones for commercial package delivery
Authors: Stolaroff Joshuah K. , Samaras Constantine , O’Neill Emma R. , Lubers Alia , Mitchell Alexandra S. , Ceperley Daniel
Published: January 2018

The use of automated, unmanned aerial vehicles (drones) to deliver commercial packages is poised to become a new industry, significantly shifting energy use in the freight sector. Here we find the current practical range of multi-copters to be about 4 km with current battery technology, requiring a new network of urban warehouses or waystations as support. We show that, although drones consume less energy per package-km than delivery trucks, the additional warehouse energy required and the longer distances traveled by drones per package greatly increase the life-cycle impacts. Still, in most cases examined, the impacts of package delivery by small drone are lower than ground-based delivery. Results suggest that, if carefully deployed, drone-based delivery could reduce greenhouse gas emissions and energy use in the freight sector. To realize the environmental benefits of drone delivery, regulators and firms should focus on minimizing extra warehousing and limiting the size of drones.
Joint coding of shape and blur in area V4
Authors: Oleskiw Timothy D. , Nowack Amy , Pasupathy Anitha
Published: January 2018

Edge blur, a prevalent feature of natural images, is believed to facilitate multiple visual processes including segmentation and depth perception. Furthermore, image descriptions that explicitly combine blur and shape information provide complete representations of naturalistic scenes. Here we report the first demonstration of blur encoding in primate visual cortex: neurons in macaque V4 exhibit tuning for both object shape and boundary blur, with observed blur tuning not explained by potential confounds including stimulus size, intensity, or curvature. A descriptive model wherein blur selectivity is cast as a distinct neural process that modulates the gain of shape-selective V4 neurons explains observed data, supporting the hypothesis that shape and blur are fundamental features of a sufficient neural code for natural image representation in V4.
Anderson light localization in biological nanostructures of native silk
Authors: Choi Seung Ho , Kim Seong-Wan , Ku Zahyun , Visbal-Onufrak Michelle A. , Kim Seong-Ryul , Choi Kwang-Ho , Ko Hakseok , Choi Wonshik , Urbas Augustine M. , Goo Tae-Won , Kim Young L.
Published: January 2018

Light in biological media is known as freely diffusing because interference is negligible. Here, we show Anderson light localization in quasi-two-dimensional protein nanostructures produced by silkworms (Bombyx mori). For transmission channels in native silk, the light flux is governed by a few localized modes. Relative spatial fluctuations in transmission quantities are proximal to the Anderson regime. The sizes of passive cavities (smaller than a single fibre) and the statistics of modes (decomposed from excitation at the gain–loss equilibrium) differentiate silk from other diffusive structures sharing microscopic morphological similarity. Because the strong reflectivity from Anderson localization is combined with the high emissivity of the biomolecules in infra-red radiation, silk radiates heat more than it absorbs for passive cooling. This collective evidence explains how a silkworm designs a nanoarchitectured optical window of resonant tunnelling in the physically closed structures, while suppressing most of transmission in the visible spectrum and emitting thermal radiation.
Adenoviral vector with shield and adapter increases tumor specificity and escapes liver and immune control
Authors: Schmid Markus , Ernst Patrick , Honegger Annemarie , Suomalainen Maarit , Zimmermann Martina , Braun Lukas , Stauffer Sarah , Thom Cristian , Dreier Birgit , Eibauer Matthias , Kipar Anja , Vogel Viola , Greber Urs F. , Medalia Ohad , Plückthun Andreas
Published: January 2018

Most systemic viral gene therapies have been limited by sequestration and degradation of virions, innate and adaptive immunity, and silencing of therapeutic genes within the target cells. Here we engineer a high-affinity protein coat, shielding the most commonly used vector in clinical gene therapy, human adenovirus type 5. Using electron microscopy and crystallography we demonstrate a massive coverage of the virion surface through the hexon-shielding scFv fragment, trimerized to exploit the hexon symmetry and gain avidity. The shield reduces virion clearance in the liver. When the shielded particles are equipped with adaptor proteins, the virions deliver their payload genes into human cancer cells expressing HER2 or EGFR. The combination of shield and adapter also increases viral gene delivery to xenografted tumors in vivo, reduces liver off-targeting and immune neutralization. Our study highlights the power of protein engineering for viral vectors overcoming the challenges of local and systemic viral gene therapies.
Continental shelves as a variable but increasing global sink for atmospheric carbon dioxide
Authors: Laruelle Goulven G. , Cai Wei-Jun , Hu Xinping , Gruber Nicolas , Mackenzie Fred T. , Regnier Pierre
Published: January 2018

It has been speculated that the partial pressure of carbon dioxide (pCO2) in shelf waters may lag the rise in atmospheric CO2. Here, we show that this is the case across many shelf regions, implying a tendency for enhanced shelf uptake of atmospheric CO2. This result is based on analysis of long-term trends in the air–sea pCO2 gradient (ΔpCO2) using a global surface ocean pCO2 database spanning a period of up to 35 years. Using wintertime data only, we find that ΔpCO2 increased in 653 of the 825 0.5° cells for which a trend could be calculated, with 325 of these cells showing a significant increase in excess of +0.5 μatm yr−1 (p < 0.05). Although noisier, the deseasonalized annual data suggest similar results. If this were a global trend, it would support the idea that shelves might have switched from a source to a sink of CO2 during the last century.
DNA-assisted swarm control in a biomolecular motor system
Authors: Keya Jakia Jannat , Suzuki Ryuhei , Kabir Arif Md. Rashedul , Inoue Daisuke , Asanuma Hiroyuki , Sada Kazuki , Hess Henry , Kuzuya Akinori , Kakugo Akira
Published: January 2018

In nature, swarming behavior has evolved repeatedly among motile organisms because it confers a variety of beneficial emergent properties. These include improved information gathering, protection from predators, and resource utilization. Some organisms, e.g., locusts, switch between solitary and swarm behavior in response to external stimuli. Aspects of swarming behavior have been demonstrated for motile supramolecular systems composed of biomolecular motors and cytoskeletal filaments, where cross-linkers induce large scale organization. The capabilities of such supramolecular systems may be further extended if the swarming behavior can be programmed and controlled. Here, we demonstrate that the swarming of DNA-functionalized microtubules (MTs) propelled by surface-adhered kinesin motors can be programmed and reversibly regulated by DNA signals. Emergent swarm behavior, such as translational and circular motion, can be selected by tuning the MT stiffness. Photoresponsive DNA containing azobenzene groups enables switching between solitary and swarm behavior in response to stimulation with visible or ultraviolet light.
Integrated circuits based on conjugated polymer monolayer
Authors: Li Mengmeng , Mangalore Deepthi Kamath , Zhao Jingbo , Carpenter Joshua H. , Yan Hongping , Ade Harald , Yan He , Müllen Klaus , Blom Paul W. M. , Pisula Wojciech , de Leeuw Dago M. , Asadi Kamal
Published: January 2018

It is still a great challenge to fabricate conjugated polymer monolayer field-effect transistors (PoM-FETs) due to intricate crystallization and film formation of conjugated polymers. Here we demonstrate PoM-FETs based on a single monolayer of a conjugated polymer. The resulting PoM-FETs are highly reproducible and exhibit charge carrier mobilities reaching 3 cm2 V−1 s−1. The high performance is attributed to the strong interactions of the polymer chains present already in solution leading to pronounced edge-on packing and well-defined microstructure in the monolayer. The high reproducibility enables the integration of discrete unipolar PoM-FETs into inverters and ring oscillators. Real logic functionality has been demonstrated by constructing a 15-bit code generator in which hundreds of self-assembled PoM-FETs are addressed simultaneously. Our results provide the state-of-the-art example of integrated circuits based on a conjugated polymer monolayer, opening prospective pathways for bottom-up organic electronics.
A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression
Authors: Velazquez-Torres Guermarie , Shoshan Einav , Ivan Cristina , Huang Li , Fuentes-Mattei Enrique , Paret Harrison , Kim Sun Jin , Rodriguez-Aguayo Cristian , Xie Victoria , Brooks Denise , Jones Steven J. M. , Robertson A. Gordon , Calin George , Lopez-Berenstein Gabriel , Sood Anil , Bar-Eli Menashe
Published: January 2018

Previously we have reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and consequently are impaired in their ability to perform A-to-I microRNA (miRNA) editing. The effects of A-to-I miRNAs editing on melanoma growth and metastasis are yet to be determined. Here we report that miR-378a–3p is undergoing A-to-I editing only in the non-metastatic but not in metastatic melanoma cells. The function of the edited form is different from its wild-type counterpart. The edited form of miR-378a-3p preferentially binds to the 3′-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotype. Indeed, edited miR-378a-3p but not its WT form inhibits melanoma metastasis in vivo. These results further emphasize the role of RNA editing in melanoma progression.
Structural basis of the molecular ruler mechanism of a bacterial glycosyltransferase
Authors: Ramírez Ana S. , Boilevin Jérémy , Mehdipour Ahmad Reza , Hummer Gerhard , Darbre Tamis , Reymond Jean-Louis , Locher Kaspar P.
Published: January 2018

The membrane-associated, processive and retaining glycosyltransferase PglH from Campylobacter jejuni is part of the biosynthetic pathway of the lipid-linked oligosaccharide (LLO) that serves as the glycan donor in bacterial protein N-glycosylation. Using an unknown counting mechanism, PglH catalyzes the transfer of exactly three α1,4 N-acetylgalactosamine (GalNAc) units to the growing LLO precursor, GalNAc-α1,4-GalNAc-α1,3-Bac-α1-PP-undecaprenyl. Here, we present crystal structures of PglH in three distinct states, including a binary complex with UDP-GalNAc and two ternary complexes containing a chemo-enzymatically generated LLO analog and either UDP or synthetic, nonhydrolyzable UDP-CH2-GalNAc. PglH contains an amphipathic helix (“ruler helix”) that has a dual role of facilitating membrane attachment and glycan counting. The ruler helix contains three positively charged side chains that can bind the pyrophosphate group of the LLO substrate and thus limit the addition of GalNAc units to three. These results, combined with molecular dynamics simulations, provide the mechanism of glycan counting by PglH.
Liquid crystal elastomer coatings with programmed response of surface profile
Authors: Babakhanova Greta , Turiv Taras , Guo Yubing , Hendrikx Matthew , Wei Qi-Huo , Schenning Albert P. H. J. , Broer Dirk J. , Lavrentovich Oleg D.
Published: January 2018

Stimuli-responsive liquid crystal elastomers with molecular orientation coupled to rubber-like elasticity show a great potential as elements in soft robotics, sensing, and transport systems. The orientational order defines their mechanical response to external stimuli, such as thermally activated muscle-like contraction. Here we demonstrate a dynamic thermal control of the surface topography of an elastomer prepared as a coating with a pattern of in-plane molecular orientation. The inscribed pattern determines whether the coating develops elevations, depressions, or in-plane deformations when the temperature changes. The deterministic dependence of the out-of-plane dynamic profile on the in-plane orientation is explained by activation forces. These forces are caused by stretching-contraction of the polymer networks and by spatially varying molecular orientation. The activation force concept brings the responsive liquid crystal elastomers into the domain of active matter. The demonstrated relationship can be used to design coatings with functionalities that mimic biological tissues such as skin.
Infliximab versus intravenous immunoglobulin for refractory Kawasaki disease: a phase 3, randomized, open-label, active-controlled, parallel-group, multicenter trial
Authors: Mori Masaaki , Hara Takuma , Kikuchi Masako , Shimizu Hiroyuki , Miyamoto Tomoyuki , Iwashima Satoru , Oonishi Tatsuya , Hashimoto Kunio , Kobayashi Norimoto , Waki Kenji , Suzuki Yasuo , Otsubo Yoshikazu , Yamada Hiroshi , Ishikawa Chikao , Kato Taichi , Fuse Shigeto
Published: January 2018

We compared the efficacy and safety of infliximab with intravenous immunoglobulin (IVIG), a standard therapy, in a phase 3 trial (NCT01596335) for Japanese patients with Kawasaki disease (KD) showing persistent fever after initial IVIG. Patients with initial IVIG-refractory KD, aged 1–10 years, received a single dose of IV infliximab 5 mg/kg or IV polyethylene glycol-treated human immunoglobulin (VGIH) 2 g/kg on day 0. Primary outcome was defervescence rate within 48 h after the start of treatment. Safety was evaluated through day 56. Overall, 31 patients were randomized (infliximab, n = 16; VGIH, n = 15); 31.3% and 60.0% patients discontinued due to worsening KD. Defervescence rate within 48 h was greater with infliximab (76.7%) than VGIH (37.0%) (p = 0.023), and defervescence was achieved earlier with infliximab (p = 0.0072). Coronary artery lesions occurred in 1 (6.3%) and 3 (20.0%) patients receiving infliximab and VGIH, respectively, up to day 21. Adverse events occurred in 15 (93.8%) and 15 (100.0%) patients in the infliximab and VGIH groups, respectively. No serious adverse events in the infliximab group and one in the VGIH group were observed. Infliximab improved the defervescence rate within 48 h and time to defervescence versus standard therapy, and was well tolerated in patients with IVIG-refractory KD.
The effect of PU.1 knockdown on gene expression and function of mast cells
Authors: Oda Yoshihito , Kasakura Kazumi , Fujigaki Izumi , Kageyama Azusa , Okumura Ko , Ogawa Hideoki , Yashiro Takuya , Nishiyama Chiharu
Published: January 2018

PU.1 is a hematopoietic cell-specific transcription factor. In the current study, we investigated the role of PU.1 in the gene expression and the function of mouse mast cells (MCs)in vitroandin vivo. When PU.1 siRNA was introduced into bone marrow-derived MCs (BMMCs), IgE-mediated activation was reduced, and the Syk and FcεRIβ mRNA levels were significantly decreased. As the regulatory mechanism of theSykgene is largely unknown, we performed promoter analysis and found that PU.1 transactivated theSykpromoter through direct binding to acis-element in the 5′-untranslated region. The involvement of PU.1 in theSykpromoter was also observed in mouse dendritic cells and human MCs, suggesting that the relationship between PU.1 and Syk is common in mammals and in hematopoietic lineages. When antigen was administrated intravenously after the transfusion of siRNA-transfected BMMCs in the mouse footpad, the footpad thickening was significantly suppressed by PU.1 knockdown. Finally, administration of the immunomodulator pomalidomide suppressed passive systemic anaphylaxis of mice. Taken together, these results indicate that PU.1 knockdown might be an efficacious strategy for the prevention of MC-mediated allergic diseases.
Human migration and the spread of malaria parasites to the New World
Authors: Rodrigues Priscila T. , Valdivia Hugo O. , de Oliveira Thais C. , Alves João Marcelo P. , Duarte Ana Maria R. C. , Cerutti-Junior Crispim , Buery Julyana C. , Brito Cristiana F. A. , de Souza Júlio César , Hirano Zelinda M. B. , Bueno Marina G. , Catão-Dias José Luiz , Malafronte Rosely S. , Ladeia-Andrade Simone , Mita Toshihiro , Santamaria Ana Maria , Calzada José E. , Tantular Indah S. , Kawamoto Fumihiko , Raijmakers Leonie R. J. , Mueller Ivo , Pacheco M. Andreina , Escalante Ananias A. , Felger Ingrid , Ferreira Marcelo U.
Published: January 2018

We examined the mitogenomes of a large global collection of human malaria parasites to explore how and when Plasmodium falciparum and P. vivax entered the Americas. We found evidence of a significant contribution of African and South Asian lineages to present-day New World malaria parasites with additional P. vivax lineages appearing to originate from Melanesia that were putatively carried by the Australasian peoples who contributed genes to Native Americans. Importantly, mitochondrial lineages of the P. vivax-like species P. simium are shared by platyrrhine monkeys and humans in the Atlantic Forest ecosystem, but not across the Amazon, which most likely resulted from one or a few recent human-to-monkey transfers. While enslaved Africans were likely the main carriers of P. falciparum mitochondrial lineages into the Americas after the conquest, additional parasites carried by Australasian peoples in pre-Columbian times may have contributed to the extensive diversity of extant local populations of P. vivax.
Differences in the mechanical unfolding pathways of apo- and copper-bound azurins
Authors: Yadav Anju , Paul Sanjoy , Venkatramani Ravindra , Ainavarapu Sri Rama Koti
Published: January 2018

Metalloproteins carry out diverse biological functions including metal transport, electron transfer, and catalysis. At present, the influence of metal cofactors on metalloprotein stability is not well understood. Here, we report the mechanical stability and unfolding pathway of azurin, a cupredoxin family protein with β-barrel topology and type I copper-binding centre. Single-molecule force spectroscopy (SMFS) experiments reveal 2-state and 3-state unfolding pathways for apo-azurin. The intermediate in the 3-state pathway occurs at an unfolding contour length of 7.5 nm from the native state. Steered molecular dynamics (SMD) simulations show that apo-azurin unfolds via a first transition state (TS) where β2Β–β8 and β7–β8 strand pairs rupture to form the intermediate, which subsequently unfolds by the collective rupture of remaining strands. SMFS experiments on holo-azurin exhibit an additional 4-state pathway besides the 2-state and 3-state pathways. The unfolding contour length leading to the first intermediate is 6.7 nm suggesting a sequestration of ~1 nm polypeptide chain length by the copper. SMD simulations reveal atomistic details of the copper sequestration and predict a combined β4–β7 pair and copper coordination sphere rupture to create the third TS in the 4-state pathway. Our systematic studies provide detailed mechanistic insights on modulation of protein mechanical properties by metal-cofactors.
Establishment and analysis of a novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation
Authors: Ikenoue Tsuneo , Terakado Yumi , Zhu Chi , Liu Xun , Ohsugi Tomoyuki , Matsubara Daisuke , Fujii Tomoki , Kakuta Shigeru , Kubo Sachiko , Shibata Takuma , Yamaguchi Kiyoshi , Iwakura Yoichiro , Furukawa Yoichi
Published: January 2018

F-box and WD40 domain protein 7 (FBXW7) is a component of the SKP1-CUL1-F-box protein (SCF) complex that mediates the ubiquitination of diverse oncogenic target proteins. The exploration of FBXW7 mutations in human primary cancer has revealed three mutation hotspots at conserved arginine residues (Arg465, Arg479, and Arg505) in the WD40 domain, which are critical for substrate recognition. To study the function of human FBXW7
R465C
, the most frequent mutation in human malignancies, we generated a novel conditional knockin mouse line of murine Fbxw7
R468C
corresponding to human FBXW7
R465C
. Systemic heterozygous knockin of the Fbxw7
R468C
mutation resulted in perinatal lethality due to defects in lung development, and occasionally caused an eyes-open at birth phenotype and cleft palate. Furthermore, mice carrying liver-specific heterozygous and homozygous Fbxw7
R468C
alleles cooperated with an oncogenic Kras mutation to exhibit bile duct hyperplasia within 8 months of birth and cholangiocarcinoma-like lesions within 8 weeks of birth, respectively. In addition, the substrates affected by the mutant Fbxw7 differed between the embryos, embryonic fibroblasts, and adult liver. This novel conditional knockin Fbxw7
R468C
line should be useful to gain a more profound understanding of carcinogenesis associated with mutation of FBXW7.
Ultrathin graphene oxide membranes on freestanding carbon nanotube supports for enhanced selective permeation in organic solvents
Authors: Kim Seon Joon , Kim Dae Woo , Cho Kyeong Min , Kang Kyoung Min , Choi Junghoon , Kim Daeok , Jung Hee-Tae
Published: January 2018

Among the various factors required for membranes in organic solvent separations, the stability of membrane supports is critical in the preparation of membranes with universal chemical stability, mechanical flexibility, and high flux. In this study, nanoporous freestanding carbon nanotube (CNT) films were fabricated and utilized as supports for enhanced permeation in organic solvents. The excellent chemical stability of the CNT support allowed it to withstand various organic solvents such as toluene, acetone, and dimethylformamide. In addition, the structural stability and high pore density of CNT supports allowed the deposition of an ultrathin selective layer for an enhanced-flux membrane. Membrane performance was demonstrated by depositing a thin graphene oxide (GO) layer on the CNT support; GO was selected because of its high chemical stability. CNT-supported GO membranes effectively blocked molecules with molecular weight larger than ~800 g mol−1 while allowing the fast permeation of small molecules such as naphthalene (permeation was 50 times faster than that through thick GO membranes) and maintaining selective permeation in harsh solvents even after 72 hours of operation. We believe that the developed CNT support can provide fundamental insights in utilizing selective materials toward organic solvent membranes.
Molecular interaction of 1-aminocyclopropane-1-carboxylate deaminase (ACCD)-producing endophytic Streptomyces sp. GMKU 336 towards salt-stress resistance of Oryza sativa L. cv. KDML105
Authors: Jaemsaeng Ratchaniwan , Jantasuriyarat Chatchawan , Thamchaipenet Arinthip
Published: January 2018

1-aminocyclopropane-1-carboxylate deaminase (ACCD)-producing endophytic Streptomyces sp. GMKU 336 and its ACCD-deficient mutant were inoculated into Thai jasmine rice Khao Dok Mali 105 cultivar (Oryza sativa L. cv. KDML105) under salt stress (150 mM NaCl) conditions. The results clearly indicated that Streptomyces sp. GMKU 336 significantly increased plant growth, chlorophyll, proline, K+, Ca+, and water contents; but decreased ethylene, reactive oxygen species (ROS), Na+, and Na+/K+ ratio when compared to plants not inoculated and those inoculated with the ACCD-deficient mutant. Expression profiles of stress responsive genes in rice in association with strain GMKU 336 were correlated to plant physiological characteristics. Genes involved in the ethylene pathway, ACO1 and EREBP1, were significantly down-regulated; while acdS encoding ACCD in Streptomyces sp. GMKU 336 was up-regulated in vivo. Furthermore, genes involved in osmotic balance (BADH1), Na+ transporters (NHX1 and SOS1), calmodulin (Cam1-1), and antioxidant enzymes (CuZn-SOD1 and CATb) were up-regulated; whereas, a gene implicated in a signaling cascade, MAPK5, was down-regulated. This work demonstrates the first time that ACCD-producing Streptomyces sp. GMKU 336 enhances growth of rice and increases salt tolerance by reduction of ethylene via the action of ACCD and further assists plants to scavenge ROS, balance ion content and osmotic pressure.
Social status shapes the bacterial and fungal gut communities of the honey bee
Authors: Yun Ji-Hyun , Jung Mi-Ja , Kim Pil Soo , Bae Jin-Woo
Published: January 2018

Despite the fungal abundance in honey and bee bread, little is known about the fungal gut community of the honey bee and its effect on host fitness. Using pyrosequencing of the16S rRNAgene and ITS2 region amplicons, we analysed the bacterial and fungal gut communities of the honey bee as affected by the host social status. Both communities were significantly affected by the host social status. The bacterial gut community was similar to those characterised in previous studies. The fungal gut communities of most worker bees were highly dominated bySaccharomycesbut foraging bees and queens were colonised by diverse fungal species andZygosaccharomyces, respectively. The high fungal density and positive correlation betweenSaccharomycesspecies andLactobacillusspecies, known yeast antagonists, were only observed in the nurse bee; this suggested that the conflict betweenSaccharomycesandLactobacilluswas compromised by the metabolism of the host and/or other gut microbes. PICRUSt analysis revealed significant differences in enriched gene clusters of the bacterial gut communities of the nurse and foraging bees, suggesting that different host social status might induce changes in the gut microbiota, and, that consequently, gut microbial community shifts to adapt to the gut environment.
Crystal structure of a Ca2+-dependent regulator of flagellar motility reveals the open-closed structural transition
Authors: Shojima Tomoki , Hou Feng , Takahashi Yusuke , Matsumura Yoshitaka , Okai Masahiko , Nakamura Akira , Mizuno Katsutoshi , Inaba Kazuo , Kojima Masaki , Miyakawa Takuya , Tanokura Masaru
Published: January 2018

Sperm chemotaxis toward a chemoattractant is very important for the success of fertilization. Calaxin, a member of the neuronal calcium sensor protein family, directly acts on outer-arm dynein and regulates specific flagellar movement during sperm chemotaxis of ascidian, Ciona intestinalis. Here, we present the crystal structures of calaxin both in the open and closed states upon Ca2+ and Mg2+ binding. The crystal structures revealed that three of the four EF-hands of a calaxin molecule bound Ca2+ ions and that EF2 and EF3 played a critical role in the conformational transition between the open and closed states. The rotation of α7 and α8 helices induces a significant conformational change of a part of the α10 helix into the loop. The structural differences between the Ca2+- and Mg2+-bound forms indicates that EF3 in the closed state has a lower affinity for Mg2+, suggesting that calaxin tends to adopt the open state in Mg2+-bound form. SAXS data supports that Ca2+-binding causes the structural transition toward the closed state. The changes in the structural transition of the C-terminal domain may be required to bind outer-arm dynein. These results provide a novel mechanism for recognizing a target protein using a calcium sensor protein.
Body size is more important than diet in determining stable-isotope estimates of trophic position in crocodilians
Authors: Villamarín Francisco , Jardine Timothy D. , Bunn Stuart E. , Marioni Boris , Magnusson William E.
Published: January 2018

The trophic position of a top predator, synonymous with food-chain length, is one of the most fundamental attributes of ecosystems. Stable isotope ratios of nitrogen (δ15N) have been used to estimate trophic position of organisms due to the predictable enrichment of15N in consumer tissues relative to their diet. Previous studies in crocodilians have found upward ontogenetic shifts in their ‘trophic position’. However, such increases are not expected from what is known about crocodilian diets because ontogenetic shifts in diet relate to taxonomic categories of prey rather than shifts to prey from higher trophic levels. When we analysed dietary information from the literature on the four Amazonian crocodilians, ontogenetic shifts in dietary-based trophic position (TPdiet) were minimal, and differed from those estimated usingδ15N data (TPSIA). Thus, ontogenetic shifts in TPSIAmay result not only from dietary assimilation but also from trophic discrimination factors (TDF orΔ15N) associated with body size. Using a unique TDF value to estimate trophic position of crocodilians of all sizes might obscure conclusions about ontogenetic shifts in trophic position. Our findings may change the way that researchers estimate trophic position of organisms that show orders of magnitude differences in size across their life span.
Nonlinear mixed-modelling discriminates the effect of chemicals and their mixtures on zebrafish behavior
Authors: Gauthier Patrick T. , Vijayan Mathilakath M.
Published: January 2018

Zebrafish (Danio rerio) early-life stage behavior has the potential for high-throughput screening of neurotoxic environmental contaminants. However, zebrafish embryo and larval behavioral assessments typically utilize linear analyses of mean activity that may not capture the complexity of the behavioral response. Here we tested the hypothesis that nonlinear mixed-modelling of zebrafish embryo and larval behavior provides a better assessment of the impact of chemicals and their mixtures. We demonstrate that zebrafish embryo photomotor responses (PMRs) and larval light/dark locomotor activities can be fit by asymmetric Lorentzian and Ricker-beta functions, respectively, which estimate the magnitude of activity (e.g., maximum and total activities) and temporal aspects (e.g., duration of the responses and its excitatory periods) characterizing early life-stage zebrafish behavior. We exposed zebrafish embryos and larvae to neuroactive chemicals, including isoproterenol, serotonin, and ethanol, as well as their mixtures, to assess the feasibility of using the nonlinear mixed-modelling to assess behavioral modulation. Exposure to chemicals led to distinct effects on specific behavioral characteristics, and interactive effects on temporal characteristics of the behavioral response that were overlooked by the linear analyses of mean activity. Overall, nonlinear mixed-modelling is a more comprehensive approach for screening the impact of chemicals and chemical mixtures on zebrafish behavior.
Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling
Authors: Tobita Takashige , Nomura Seitaro , Fujita Takanori , Morita Hiroyuki , Asano Yoshihiro , Onoue Kenji , Ito Masamichi , Imai Yasushi , Suzuki Atsushi , Ko Toshiyuki , Satoh Masahiro , Fujita Kanna , Naito Atsuhiko T , Furutani Yoshiyuki , Toko Haruhiro , Harada Mutsuo , Amiya Eisuke , Hatano Masaru , Takimoto Eiki , Shiga Tsuyoshi , Nakanishi Toshio , Sakata Yasushi , Ono Minoru , Saito Yoshihiko , Takashima Seiji , Hagiwara Nobuhisa , Aburatani Hiroyuki , Komuro Issei
Published: January 2018

Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically heterogeneous. Cardiac function is improved after treatment in some cardiomyopathy patients, but little is known about genetic predictors of long-term outcomes and myocardial recovery following medical treatment. To elucidate the genetic basis of cardiomyopathy in Japan and the genotypes involved in prognosis and left ventricular reverse remodeling (LVRR), we performed targeted sequencing on 120 DCM (70 sporadic and 50 familial) and 52 HCM (15 sporadic and 37 familial) patients and integrated their genotypes with clinical phenotypes. Among the 120 DCM patients, 20 (16.7%) had TTN truncating variants and 13 (10.8%) had LMNA variants. TTN truncating variants were the major cause of sporadic DCM (21.4% of sporadic cases) as with Caucasians, whereas LMNA variants, which include a novel recurrent LMNA E115M variant, were the most frequent in familial DCM (24.0% of familial cases) unlike Caucasians. Of the 52 HCM patients, MYH7 and MYBPC3 variants were the most common (12 (23.1%) had MYH7 variants and 11 (21.2%) had MYBPC3 variants) as with Caucasians. DCM patients harboring TTN truncating variants had better prognosis than those with LMNA variants. Most patients with TTN truncating variants achieved LVRR, unlike most patients with LMNA variants.
In vivo photoacoustic monitoring using 700-nm region Raman source for targeting Prussian blue nanoparticles in mouse tumor model
Authors: Bui Nhat Quang , Cho Soon-Woo , Moorthy Madhappan Santha , Park Sang Min , Piao Zhonglie , Nam Seung Yun , Kang Hyun Wook , Kim Chang-Seok , Oh Junghwan
Published: January 2018

Photoacoustic imaging (PAI) is a noninvasive imaging tool to visualize optical absorbing contrast agents. Due to high ultrasonic resolution and superior optical sensitivity, PAI can be used to monitor nanoparticle-mediated cancer therapy. The current study synthesized Food and Drug Administration-approved Prussian blue (PB) in the form of nanoparticles (NPs) with the peak absorption at 712 nm for photoacoustically imaging tumor-bearing mouse models. To monitor PB NPs from the background tissue in vivo, we also developed a new 700-nm-region stimulated Raman scattering (SRS) source (pulse energy up to 200 nJ and repetition rate up to 50 kHz) and implemented optical-resolution photoacoustic microscopy (OR-PAM). The SRS-assisted OR-PAM system was able to monitor PB NPs in the tumor model with micrometer resolution. Due to strong light absorption at 712 nm, the developed SRS light yielded a two-fold higher contrast from PB NPs, in comparison with a 532-nm pumping source. The proposed laser source involved cost-effective and simple system implementation along with high compatibility with the fiber-based OR-PAM system. The study highlights the OR-PAM system in conjunction with the tunable-color SRS light source as a feasible tool to assist NP-mediated cancer therapy.
A model species for agricultural pest genomics: the genome of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)
Authors: Schoville Sean D. , Chen Yolanda H. , Andersson Martin N. , Benoit Joshua B. , Bhandari Anita , Bowsher Julia H. , Brevik Kristian , Cappelle Kaat , Chen Mei-Ju M. , Childers Anna K. , Childers Christopher , Christiaens Olivier , Clements Justin , Didion Elise M. , Elpidina Elena N. , Engsontia Patamarerk , Friedrich Markus , García-Robles Inmaculada , Gibbs Richard A. , Goswami Chandan , Grapputo Alessandro , Gruden Kristina , Grynberg Marcin , Henrissat Bernard , Jennings Emily C. , Jones Jeffery W. , Kalsi Megha , Khan Sher A. , Kumar Abhishek , Li Fei , Lombard Vincent , Ma Xingzhou , Martynov Alexander , Miller Nicholas J. , Mitchell Robert F. , Munoz-Torres Monica , Muszewska Anna , Oppert Brenda , Palli Subba Reddy , Panfilio Kristen A. , Pauchet Yannick , Perkin Lindsey C. , Petek Marko , Poelchau Monica F. , Record Éric , Rinehart Joseph P. , Robertson Hugh M. , Rosendale Andrew J. , Ruiz-Arroyo Victor M. , Smagghe Guy , Szendrei Zsofia , Thomas Gregg W.C. , Torson Alex S. , Vargas Jentzsch Iris M. , Weirauch Matthew T. , Yates Ashley D. , Yocum George D. , Yoon June-Sun , Richards Stephen
Published: January 2018

The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain whyLeptinotarsa decemlineatahas high sensitivity to dsRNA. TheL.decemlineatagenome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.
A comparative study of low energy radiation response of AlAs, GaAs and GaAs/AlAs superlattice and the damage effects on their electronic structures
Authors: Jiang M. , Xiao H. Y. , Peng S. M. , Yang G. X. , Liu Z. J. , Zu X. T.
Published: January 2018

In this study, the low energy radiation responses of AlAs, GaAs and GaAs/AlAs superlattice are simulated and the radiation damage effects on their electronic structures are investigated. It is found that the threshold displacement energies for AlAs are generally larger than those for GaAs, i.e., the atoms in AlAs are more difficult to be displaced than those in GaAs under radiation environment. As for GaAs/AlAs superlattice, the Ga and Al atoms are more susceptible to the radiation than those in the bulk AlAs and GaAs, whereas the As atoms need comparable or much larger energies to be displaced than those in the bulk states. The created defects are generally Frenkel pairs, and a few antisite defects are also created in the superlattice structure. The created defects are found to have profound effects on the electronic properties of GaAs/AlAs superlattice, in which charge transfer, redistribution and even accumulation take place, and band gap narrowing and even metallicity are induced in some cases. This study shows that it is necessary to enhance the radiation tolerance of GaAs/AlAs superlattice to improve their performance under irradiation.
Hemojuvelin Predicts Acute Kidney Injury and Poor Outcomes Following Cardiac Surgery
Authors: Ko Sheng-Wen , Chi Nai-Hsin , Wu Che-Hsiung , Huang Tao-Min , Chueh Shih-Chieh Jeff , Wang Chih-Hsien , Lin Jui-Hsiang , Wang Wei-Jie , Ting Jui-Tsung , Chang Huang-Ming , Connolly Rory , Lai Chien-Heng , Tseng Li-Jung , Wu Vin-Cent , Chu Tzong-Shinn
Published: January 2018

Acute kidney injury (AKI) is detrimental after cardiac surgery. In this multicenter study, the novel biomarker hemojuvelin (HJV) was evaluated for AKI prediction following cardiac surgery. Urinary HJV, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine were measured in 151 patients after surgery. The outcomes of advanced AKI (KDIGO stages 2 and 3) and all causes of in-hospital mortality as the composite outcome were recorded. Areas under the receiver operator characteristic curves (AUC) and a multivariate generalized additive model (GAM) were applied to predict these outcomes of interest. Urinary HJV differentiated patients with/without AKI, advanced AKI or composite outcome after surgery (p < 0.001, by a generalized estimating equation) in this study. At three hours post-surgery, urinary HJV predicted advanced AKI (p < 0.001) and composite outcome (p < 0.001) with corresponding AUC values of 0.768 and 0.828, respectively. The performance of creatinine-adjusted HJV was also superior to NGAL in predicting advanced AKI (AUC = 0.784 and 0.694; p = 0.037) and composite outcome (AUC = 0.842 and 0.676; p = 0.002). The integration of HJV into the Cleveland Clinic score for advanced AKI led to a significant increase in risk stratification (net reclassification improvement [NRI] = 0.598; p < 0.001).
Construction of two whole genome radiation hybrid panels for dromedary (Camelus dromedarius): 5000RAD and 15000RAD
Authors: Perelman Polina L. , Pichler Rudolf , Gaggl Anna , Larkin Denis M. , Raudsepp Terje , Alshanbari Fahad , Holl Heather M. , Brooks Samantha A. , Burger Pamela A. , Periasamy Kathiravan
Published: January 2018

The availability of genomic resources including linkage information for camelids has been very limited. Here, we describe the construction of a set of two radiation hybrid (RH) panels (5000RAD and 15000RAD) for the dromedary (Camelus dromedarius) as a permanent genetic resource for camel genome researchers worldwide. For the 5000RAD panel, a total of 245 female camel-hamster radiation hybrid clones were collected, of which 186 were screened with 44 custom designed marker loci distributed throughout camel genome. The overall mean retention frequency (RF) of the final set of 93 hybrids was 47.7%. For the 15000RAD panel, 238 male dromedary-hamster radiation hybrid clones were collected, of which 93 were tested using 44 PCR markers. The final set of 90 clones had a mean RF of 39.9%. This 15000RAD panel is an important high-resolution complement to the main 5000RAD panel and an indispensable tool for resolving complex genomic regions. This valuable genetic resource of dromedary RH panels is expected to be instrumental for constructing a high resolution camel genome map. Construction of the set of RH panels is essential step toward chromosome level reference quality genome assembly that is critical for advancing camelid genomics and the development of custom genomic tools.
Electrostatic Variation of Haemagglutinin as a Hallmark of the Evolution of Avian Influenza Viruses
Authors: Heidari Alireza , Righetto Irene , Filippini Francesco
Published: January 2018

Avian influenza virus is a zoonotic agent that significantly impacts public health and the poultry industry. Monitoring viral evolution and spread is crucial for surveillance and tracing programmes, which are currently based on serological or DNA sequencing-phylogenetics analysis. However, virus-host interactions, antigenic drift and spreading of viral clades strongly depend on variation in the surface features of capsid proteins. We report here that in silico comparative structural analysis of haemagglutinin can reveal relevant evolutionary fingerprints, particularly when integrated with sequence-based analyses. Phylogenetic analyses of H9 viral strains from wild birds and poultry, performed with different methods, reliably led to clustering of viruses into five main groups. Subsequent comparison of structural features showed congruence between such clustering and surface electrostatic fingerprints. These latter fingerprints relate group-specific variations in electrostatic charges and isocontours to well-known haemagglutinin sites involved in the modulation of immune escape and host specificity. This work suggests that the integration of structural and sequence comparisons may enhance investigations of trends and relevant mechanisms in viral evolution.
Lectin-mediated protocell crosslinking to mimic cell-cell junctions and adhesion
Authors: Villringer Sarah , Madl Josef , Sych Taras , Manner Christina , Imberty Anne , Römer Winfried
Published: January 2018

Cell adhesion is a crucial feature of all multicellular organisms, as it allows cells to organise themselves into tissues to carry out specific functions. Here, we present a mimetic approach that uses multivalent lectins with opposing binding sites to crosslink glycan-functionalised giant unilamellar vesicles. The crosslinking process drives the progression from contact puncta into elongated protocellular junctions, which form the vesicles into polygonal clusters resembling tissues. Due to their carbohydrate specificity, different lectins can be engaged in parallel with both natural and synthetic glycoconjugates to generate complex interfaces with distinct lectin domains. In addition, the formation of protocellular junctions can be combined with adhesion to a functionalised support by other ligand-receptor interactions to render increased stability against fluid flow. Furthermore, we consider that adhesion is a complex process of attraction and repulsion by doping the vesicles with a PEG-modified lipid, and demonstrate a dose-dependent decrease of lectin binding and formation of protocellular junctions. We suggest that the engineering of prototissues through lectin-glycan interactions is an important step towards synthetic minimal tissues and in designing artificial systems to reconstruct the fundamental functions of biology.
Serendipitous Discovery of a Guanine-rich DNA Molecule with a Highly Stable Structure in Urea
Authors: Zhang Wenqing , Liu Meng , Lee Christine , Salena Bruno J. , Li Yingfu
Published: January 2018

We have made an accidental discovery of an unusual, single-stranded, guanine-rich DNA molecule that is capable of adopting a folded structure in 7 M urea (7MU) known to denature nucleic acid structures. The folding of this molecule requires Na+ and Mg2+ and the folded structure remains stable when subjected to denaturing (7MU) polyacrylamide gel electrophoresis. Results from sequence mutagenesis, DNA methylation, and circular dichroism spectroscopy studies suggest that this molecule adopts an intramolecular guanine-quadruplex structure with 5 layers of guanine tetrads. Our finding indicates that DNA has the ability to create extremely stable structural folds despite its limited chemical repertoire, making it possible to develop DNA-based systems for unconventional applications.