bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory B cells: the cutting edge of immune tolerance in kidney transplantation
Authors: Peng Bo , Ming Yingzi , Yang Cheng 
Published: January 2018

AbstractKidney 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

AbstractCardiovascular 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

AbstractThe 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

AbstractEdge 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

AbstractLight 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

AbstractMost 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

AbstractIt 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

AbstractIn 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

AbstractIt 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

AbstractPreviously 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

AbstractThe 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

AbstractStimuli-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

AbstractWe 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

AbstractPU.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

AbstractWe 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

AbstractMetalloproteins 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

AbstractF-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.