bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation
Authors: Arosio Paolo , Michaels Thomas C. T. , Linse Sara , Månsson Cecilia , Emanuelsson Cecilia , Presto Jenny , Johansson Jan , Vendruscolo Michele , Dobson Christopher M. , Knowles Tuomas P. J. 
Published: March 2016

AbstractIt is increasingly recognized that molecular chaperones play a key role in modulating the formation of amyloid fibrils, a process associated with a wide range of human disorders. Understanding the detailed mechanisms by which they perform this function, however, has been challenging because of the great complexity of the protein aggregation process itself. In this work, we build on a previous kinetic approach and develop a model that considers pairwise interactions between molecular chaperones and different protein species to identify the protein components targeted by the chaperones and the corresponding microscopic reaction steps that are inhibited. We show that these interactions conserve the topology of the unperturbed reaction network but modify the connectivity weights between the different microscopic steps. Moreover, by analysing several protein-molecular chaperone systems, we reveal the striking diversity in the microscopic mechanisms by which molecular chaperones act to suppress amyloid formation.
Fish optimize sensing and respiration during undulatory swimming
Authors: Akanyeti O. , Thornycroft P. J. M. , Lauder G. V. , Yanagitsuru Y. R. , Peterson A. N. , Liao J. C. 
Published: March 2016

AbstractPrevious work in fishes considers undulation as a means of propulsion without addressing how it may affect other functions such as sensing and respiration. Here we show that undulation can optimize propulsion, flow sensing and respiration concurrently without any apparent tradeoffs when head movements are coupled correctly with the movements of the body. This finding challenges a long-held assumption that head movements are simply an unintended consequence of undulation, existing only because of the recoil of an oscillating tail. We use a combination of theoretical, biological and physical experiments to reveal the hydrodynamic mechanisms underlying this concerted optimization. Based on our results we develop a parsimonious control architecture that can be used by both undulatory animals and machines in dynamic environments.
ELL targets c-Myc for proteasomal degradation and suppresses tumour growth
Authors: Chen Yu , Zhou Chi , Ji Wei , Mei Zhichao , Hu Bo , Zhang Wei , Zhang Dawei , Wang Jing , Liu Xing , Ouyang Gang , Zhou Jiangang , Xiao Wuhan 
Published: March 2016

AbstractIncreasing evidence supports that ELL (eleven–nineteen lysine-rich leukaemia) is a key regulator of transcriptional elongation, but the physiological function of Ell in mammals remains elusive. Here we show that ELL functions as an E3 ubiquitin ligase and targets c-Myc for proteasomal degradation. In addition, we identify that UbcH8 serves as a ubiquitin-conjugating enzyme in this pathway. Cysteine 595 of ELL is an active site of the enzyme; its mutation to alanine (C595A) renders the protein unable to promote the ubiquitination and degradation of c-Myc. ELL-mediated c-Myc degradation inhibits c-Myc-dependent transcriptional activity and cell proliferation, and also suppresses c-Myc-dependent xenograft tumour growth. In contrast, the ELL(C595A) mutant not only loses the ability to inhibit cell proliferation and xenograft tumour growth, but also promotes tumour metastasis. Thus, our work reveals a previously unrecognized function for ELL as an E3 ubiquitin ligase for c-Myc and a potential tumour suppressor.
Disentanglement of growth dynamic and thermodynamic effects in LaAlO3/SrTiO3 heterostructures
Authors: Xu Chencheng , Bäumer Christoph , Heinen Ronja Anika , Hoffmann-Eifert Susanne , Gunkel Felix , Dittmann Regina 
Published: March 2016

AbstractThe influence of non-equilibrium and equilibrium processes during growth of LaAlO3/SrTiO3 (LAO/STO) heterostructures is analyzed. We investigate the electronic properties of LAO/STO heterostructures obtained at constant growth conditions after annealing in different oxygen atmospheres within the typical growth window (1 × 10−4 mbar –1 × 10−2 mbar). The variation of annealing conditions is found to cause a similar change of electronic properties as observed for samples grown in different oxygen pressure. The results indicate that equilibrium defect formation is the dominant process for establishing the properties of the two-dimensional electron gas (2DEG), while growth dynamics play a minor role in the typical LAO/STO growth regime. Furthermore, the effects of non-equilibrium processes occurring during growth are investigated in detail by quenching just-grown LAO/STO heterostructures directly after growth. We show that during growth the sample is pushed into a non-equilibrium state. After growth, the sample then relaxes towards equilibrium, while the relaxation rate strongly depends on the ambient pressure. The observed relaxation behavior is mainly associated with a reoxidation of the STO bulk, while the 2DEG is formed immediately after the growth.
Genome-Wide Identification of R2R3-MYB Genes and Expression Analyses During Abiotic Stress in Gossypium raimondii
Authors: He Qiuling , Jones Don C. , Li Wei , Xie Fuliang , Ma Jun , Sun Runrun , Wang Qinglian , Zhu Shuijin , Zhang Baohong 
Published: March 2016

AbstractThe R2R3-MYB is one of the largest families of transcription factors, which have been implicated in multiple biological processes. There is great diversity in the number of R2R3-MYB genes in different plants. However, there is no report on genome-wide characterization of this gene family in cotton. In the present study, a total of 205 putative R2R3-MYB genes were identified in cotton D genome (Gossypium raimondii), that are much larger than that found in other cash crops with fully sequenced genomes. These GrMYBs were classified into 13 groups with the R2R3-MYB genes from Arabidopsis and rice. The amino acid motifs and phylogenetic tree were predicted and analyzed. The sequences of GrMYBs were distributed across 13 chromosomes at various densities. The results showed that the expansion of the G. Raimondii R2R3-MYB family was mainly attributable to whole genome duplication and segmental duplication. Moreover, the expression pattern of 52 selected GrMYBs and 46 GaMYBs were tested in roots and leaves under different abiotic stress conditions. The results revealed that the MYB genes in cotton were differentially expressed under salt and drought stress treatment. Our results will be useful for determining the precise role of the MYB genes during stress responses with crop improvement.
Thermal erosion of cratonic lithosphere as a potential trigger for mass-extinction
Authors: Guex Jean , Pilet Sebastien , Müntener Othmar , Bartolini Annachiara , Spangenberg Jorge , Schoene Blair , Sell Bryan , Schaltegger Urs 
Published: March 2016

AbstractThe temporal coincidence between large igneous provinces (LIPs) and mass extinctions has led many to pose a causal relationship between the two. However, there is still no consensus on a mechanistic model that explains how magmatism leads to the turnover of terrestrial and marine plants, invertebrates and vertebrates. Here we present a synthesis of ammonite biostratigraphy, isotopic data and high precision U-Pb zircon dates from the Triassic-Jurassic (T-J) and Pliensbachian-Toarcian (Pl-To) boundaries demonstrating that these biotic crises are both associated with rapid change from an initial cool period to greenhouse conditions. We explain these transitions as a result of changing gas species emitted during the progressive thermal erosion of cratonic lithosphere by plume activity or internal heating of the lithosphere. Our petrological model for LIP magmatism argues that initial gas emission was dominated by sulfur liberated from sulfide-bearing cratonic lithosphere before CO2became the dominant gas. This model offers an explanation of why LIPs erupted through oceanic lithosphere are not associated with climatic and biotic crises comparable to LIPs emitted through cratonic lithosphere.
A model to assess the efficacy of vaccines for control of liver fluke infection
Authors: Turner Joanne , Howell Alison , McCann Cathy , Caminade Cyril , Bowers Roger G. , Williams Diana , Baylis Matthew 
Published: March 2016

AbstractFasciola hepatica, common liver fluke, infects cattle and sheep causing disease and production losses costing approximately $3billion annually. Current control relies on drugs designed to kill the parasite. However, resistance is evident worldwide and widespread in some areas. Work towards a vaccine has identified several antigens of F. hepatica that show partial efficacy in terms of reducing worm burden and egg output. A critical question is what level of efficacy is required for such a vaccine to be useful? We have created the first mathematical model to assess the effectiveness of liver fluke vaccines under simulated field conditions. The model describes development of fluke within a group of animals and includes heterogeneity in host susceptibility, seasonal exposure to metacercariae and seasonal changes in temperature affecting metacercarial survival. Our analysis suggests that the potential vaccine candidates could reduce total fluke burden and egg output by up to 43% and 99%, respectively, on average under field conditions. It also suggests that for a vaccine to be effective, it must protect at least 90% of animals for the whole season. In conclusion, novel, partial, vaccines could contribute substantially towards fasciolosis control, reducing usage of anthelmintics and thus delaying the spread of anthelmintic resistance.
Trace fossil evidence of coral-inhabiting crabs (Cryptochiridae) and its implications for growth and paleobiogeography
Authors: Klompmaker Adiël A. , Portell Roger W. , van der Meij Sancia E.T. 
Published: March 2016

AbstractMembers of the Cryptochiridae are small, fragile, symbiotic crabs that live in domiciles in modern corals. Despite their worldwide occurrence with over 50 species known today, their fossil record is unknown. We provide the first unambiguous evidence of cryptochirids in the fossil record through their crescentic pits, typical for certain cryptochirids, in Western Atlantic fossil corals, while the Eocene genus Montemagrechirus is excluded from the Cryptochiridae and referred to Montemagrechiridae fam. nov. Nine Pleistocene corals with crescentic pits originate from Florida (USA) and single specimens with pits come from the late Pleistocene of Cuba and the late Pliocene of Florida, all of which are measured for growth analyses. These pits represent trace fossils named Galacticus duerri igen. nov., isp. nov. A study of modern cryptochirid domicile shape (crescentic pit, circular-oval pit, or a true gall) shows that species within crab genera tend to inhabit the same pit shape. Crescentic pits in corals occur not only in the Western Atlantic today, but also in the Indo-West Pacific and in the Eastern Pacific. Thus, examination of Cenozoic fossil coral collections from these regions should yield further examples of cryptochirid pits, which would help to constrain the antiquity of this cryptic crab family.
Insects for breakfast and whales for dinner: the diet and body condition of dingoes on Fraser Island (K’gari)
Authors: Behrendorff Linda , Leung Luke K.-P. , McKinnon Allan , Hanger Jon , Belonje Grant , Tapply Jenna , Jones Darryl , Allen Benjamin L. 
Published: March 2016

AbstractTop-predators play stabilising roles in island food webs, including Fraser Island, Australia. Subsidising generalist predators with human-sourced food could disrupt this balance, but has been proposed to improve the overall health of the island’s dingo (Canis lupus dingo) population, which is allegedly ‘starving’ or in ‘poor condition’. We assess this hypothesis by describing the diet and health of dingoes on Fraser Island from datasets collected between 2001 and 2015. Medium-sized mammals (such as bandicoots) and fish were the most common food items detected in dingo scat records. Stomach contents records revealed additional information on diet, such as the occurrence of human-sourced foods. Trail camera records highlighted dingo utilisation of stranded marine fauna, particularly turtles and whales. Mean adult body weights were higher than the national average, body condition scores and abundant-excessive fat reserves indicated a generally ideal-heavy physical condition, and parasite loads were low and comparable to other dingo populations. These data do not support hypotheses that Fraser Island dingoes have restricted diets or are in poor physical condition. Rather, they indicate that dingoes on Fraser Island are capable of exploiting a diverse array of food sources which contributes to the vast majority of dingoes being of good-excellent physical condition.
Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods
Authors: Serag Ahmed , Blesa Manuel , Moore Emma J. , Pataky Rozalia , Sparrow Sarah A. , Wilkinson A. G. , Macnaught Gillian , Semple Scott I. , Boardman James P. 
Published: March 2016

AbstractAccurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases ‘uniformly’ distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.
Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury
Authors: Lee Se-Yeon , Lee Seahyoung , Choi Eunhyun , Ham Onju , Lee Chang Youn , Lee Jiyun , Seo Hyang-Hee , Cha Min-Ji , Mun Bohyun , Lee Yunmi , Yoon Cheesoon , Hwang Ki-Chul 
Published: March 2016

AbstractGenetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death.
Artificial Synaptic Devices Based on Natural Chicken Albumen Coupled Electric-Double-Layer Transistors
Authors: Wu Guodong , Feng Ping , Wan Xiang , Zhu Liqiang , Shi Yi , Wan Qing 
Published: March 2016

AbstractRecent progress in using biomaterials to fabricate functional electronics has got growing attention for the new generation of environmentally friendly and biocompatible electronic devices. As a kind of biological material with rich source, proteins are essential natural component of all organisms. At the same time, artificial synaptic devices are of great significance for neuromorphic systems because they can emulate the signal process and memory behaviors of biological synapses. In this report, natural chicken albumen with high proton conductivity was used as the coupling electrolyte film for organic/inorganic hybrid synaptic devices fabrication. Some important synaptic functions including paired-pulse facilitation, dynamic filtering, short-term to long-term memory transition and spatial summation and shunting inhibition were successfully mimicked. Our results are very interesting for biological friendly artificial neuron networks and neuromorphic systems.
WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion
Authors: García Esther , Ragazzini Chiara , Yu Xinzi , Cuesta-García Elena , Bernardino de la Serna Jorge , Zech Tobias , Sarrió David , Machesky Laura M. , Antón Inés M. 
Published: March 2016

AbstractCancer cells form actin-rich degradative protrusions (invasive pseudopods and invadopodia), which allows their efficient dispersal during metastasis. Using biochemical and advanced imaging approaches, we demonstrate that the N-WASP-interactors WIP and WICH/WIRE play non-redundant roles in cancer cell invasion. WIP interacts with N-WASP and cortactin and is essential for invadopodium assembly, whereas WICH/WIRE regulates N-WASP activation to control invadopodium maturation and degradative activity. Our data also show that Nck interaction with WIP and WICH/WIRE modulates invadopodium maturation; changes in WIP and WICH/WIRE levels induce differential distribution of Nck. We show that WIP can replace WICH/WIRE functions and that elevated WIP levels correlate with high invasiveness. These findings identify a role for WICH/WIRE in invasiveness and highlight WIP as a hub for signaling molecule recruitment during invadopodium generation and cancer progression, as well as a potential diagnostic biomarker and an optimal target for therapeutic approaches.
Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment
Authors: Obonai Toshifumi , Fuchigami Hirobumi , Furuya Fumiaki , Kozuka Naoyuki , Yasunaga Masahiro , Matsumura Yasuhiro 
Published: March 2016

AbstractThe diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC) and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.
Morphotype-specific effector functions of Cryptococcus neoformans PUM1
Authors: Kaur Jan Naseer , Panepinto John C. 
Published: March 2016

AbstractThe basidiomycete fungal pathogen Cryptococcus neoformans requires the PUF protein, Pum1, for hyphal morphogenesis during sexual development. In this study we found that Pum1 was auto-repressive under growth as yeast, but that auto-repression was relieved during filamentous growth through utilization of an alternative transcription start site driven by the master filamentation regulator Znf2. In addition, Pum1 was required to stabilize the ZNF2 mRNA through an indirect mechanism suggesting that Znf2 and Pum1 each positively regulate the expression of the other to achieve the filamentous morphotype required for sexual development in Cryptococcus.
RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus
Authors: Drujont Lucile , Lemoine Aurélie , Moreau Aurélie , Bienvenu Géraldine , Lancien Mélanie , Cens Thierry , Guillot Flora , Bériou Gaëlle , Bouchet-Delbos Laurence , Fehling Hans Jörg , Chiffoleau Elise , Nicot Arnaud B. , Charnet Pierre , Martin Jérôme C. , Josien Régis , Cuturi Maria Cristina , Louvet Cédric 
Published: March 2016

AbstractRetinoid-related orphan receptor gamma t (RORγt) is a master transcription factor central to type 17 immunity involving cells such as T helper 17, group 3 innate lymphoid cells or IL-17-producing γδ T cells. Here we show that the intracellular ion channel TMEM176B and its homologue TMEM176A are strongly expressed in these RORγt+ cells. We demonstrate that TMEM176A and B exhibit a similar cation channel activity and mainly colocalise in close proximity to the trans-Golgi network. Strikingly, in the mouse, the loss of Tmem176b is systematically associated with a strong upregulation of Tmem176a. While Tmem176b single-deficiency has no effect on the course of experimental autoimmune encephalomyelitis, T cell or DSS-induced colitis, it significantly reduces imiquimod-induced psoriasis-like skin inflammation. These findings shed light on a potentially novel specific process linked to post-Golgi trafficking for modulating the function of RORγt+ cells and indicate that both homologues should be simultaneously targeted to clearly elucidate the role of this intracellular ion flow.
Microstructured Thin Film Nitinol for a Neurovascular Flow-Diverter
Authors: Chen Yanfei , Howe Connor , Lee Yongkuk , Cheon Seongsik , Yeo Woon-Hong , Chun Youngjae 
Published: March 2016

AbstractA cerebral aneurysm occurs as a result of a weakened blood vessel, which allows blood to flow into a sac or a ballooned section. Recent advancement shows that a new device, ‘flow-diverter’, can divert blood flow away from the aneurysm sac. People found that a flow-diverter based on thin film nitinol (TFN), works very effectively, however there are no studies proving the mechanical safety in irregular, curved blood vessels. Here, we study the mechanical behaviors and structural safety of a novel microstructured TFN membrane through the computational and experimental studies, which establish the fundamental aspects of stretching and bending mechanics of the structure. The result shows a hyper-elastic behavior of the TFN with a negligible strain change up to 180° in bending and over 500% in radial stretching, which is ideal in the use in neurovascular curved arteries. The simulation determines the optimal joint locations between the TFN and stent frame. In vitro experimental test qualitatively demonstrates the mechanical flexibility of the flow-diverter with multi-modal bending. In vivo micro X-ray and histopathology study demonstrate that the TFN can be conformally deployed in the curved blood vessel of a swine model without any significant complications or abnormalities.