bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strobilurin biosynthesis in Basidiomycete fungi
Authors: Nofiani Risa , de Mattos-Shipley Kate , Lebe Karen E. , Han Li-Chen , Iqbal Zafar , Bailey Andrew M. , Willis Christine L. , Simpson Thomas J. , Cox Russell J. 
Published: September 2018

AbstractStrobilurins from fungi are the inspiration for the creation of the β-methoxyacrylate class of agricultural fungicides. However, molecular details of the biosynthesis of strobilurins have remained cryptic. Here we report the sequence of genomes of two fungi that produce strobilurins and show that each contains a biosynthetic gene cluster, which encodes a highly reducing polyketide synthase with very unusual C-terminal hydrolase and methyltransferase domains. Expression of stpks1 in Aspergillus oryzae leads to the production of prestrobilurin A when the fermentation is supplemented with a benzoyl coenzyme A (CoA) analogue. This enables the discovery of a previously unobserved route to benzoyl CoA. Reconstruction of the gene cluster in A. oryzae leads to the formation of prestrobilurin A, and addition of the gene str9 encoding an FAD-dependent oxygenase leads to the key oxidative rearrangement responsible for the creation of the β-methoxyacrylate toxophore. Finally, two methyltransferases are required to complete the synthesis.
Asymmetric remote C-H borylation of internal alkenes via alkene isomerization
Authors: Chen Xu , Cheng Zhaoyang , Guo Jun , Lu Zhan 
Published: September 2018

AbstractRecent years have witnessed the growing interest in the remote functionalization of alkenes for it offers a strategy to activate the challenging C–H bonds distant from the initiation point via alkene isomerization/functionalization. However, the catalytic enantioselective isomerization/functionalization with one single transition metal catalyst remains rare. Here we report a highly regio- and enantioselective cobalt-catalyzed remote C–H bond borylation of internal alkenes via sequential alkene isomerization/hydroboration. A chiral ligand featured twisted pincer, anionic, and non-rigid characters is designed and used for this transformation. This methodology, which is operationally simple using low catalyst loading without additional activator, shows excellent enantioselectivity and can be used to convert various internal alkenes with regio- and stereoisomers to valuable chiral secondary organoboronates with good functional group tolerance.
Mapping protein selectivity landscapes using multi-target selective screening and next-generation sequencing of combinatorial libraries
Authors: Naftaly Si , Cohen Itay , Shahar Anat , Hockla Alexandra , Radisky Evette S. , Papo Niv 
Published: September 2018

AbstractCharacterizing the binding selectivity landscape of interacting proteins is crucial both for elucidating the underlying mechanisms of their interaction and for developing selective inhibitors. However, current mapping methods are laborious and cannot provide a sufficiently comprehensive description of the landscape. Here, we introduce a novel and efficient strategy for comprehensively mapping the binding landscape of proteins using a combination of experimental multi-target selective library screening and in silico next-generation sequencing analysis. We map the binding landscape of a non-selective trypsin inhibitor, the amyloid protein precursor inhibitor (APPI), to each of the four human serine proteases (kallikrein-6, mesotrypsin, and anionic and cationic trypsins). We then use this map to dissect and improve the affinity and selectivity of APPI variants toward each of the four proteases. Our strategy can be used as a platform for the development of a new generation of target-selective probes and therapeutic agents based on selective protein–protein interactions.
Identification of small-molecule ion channel modulators in C. elegans channelopathy models
Authors: Jiang Qiang , Li Kai , Lu Wen-Jing , Li Shuang , Chen Xin , Liu Xi-Juan , Yuan Jie , Ding Qiurong , Lan Feng , Cai Shi-Qing 
Published: September 2018

AbstractIon channels are important therapeutic targets, but the discovery of ion channel drugs remains challenging due to a lack of assays that allow high-throughput screening in the physiological context. Here we report C. elegans phenotype-based methods for screening ion channel drugs. Expression of modified human ether-a-go-go-related gene (hERG) potassium channels in C. elegans results in egg-laying and locomotive defects, which offer indicators for screening small-molecule channel modulators. Screening in worms expressing hERGA561V, which carries a trafficking-defective mutation A561V known to associate with long-QT syndrome, identifies two functional correctors Prostratin and ingenol-3,20-dibenzoate. These compounds activate PKCε signaling and consequently phosphorylate S606 at the pore region of the channel to promote hERGA561V trafficking to the plasma membrane. Importantly, the compounds correct electrophysiological abnormalities in hiPSC-derived cardiomyocytes bearing a heterozygous CRISPR/Cas9-edited hERGA561V. Thus, we have developed an in vivo high-throughput method for screening compounds that have therapeutic potential in treating channelopathies.
Acoustic communities reflects lateral hydrological connectivity in riverine floodplain similarly to macroinvertebrate communities
Authors: Desjonquères Camille , Rybak Fanny , Castella Emmanuel , Llusia Diego , Sueur Jérôme 
Published: September 2018

AbstractRecent studies revealed that information on ecological patterns and processes can be investigated using sounds emanating from animal communities. In freshwater environments, animal communities are strongly shaped by key ecological factors such as lateral connectivity and temperature. We predict that those ecological factors are linked to acoustic communities formed by the collection of sounds emitted underwater. To test this prediction, we deployed a passive acoustic monitoring during 15 days in six floodplain channels of the European river Rhône. The six channels differed in their temperature and level of lateral connectivity to the main river. In parallel, we assessed the macroinvertebrate communities of these six channels using classical net sampling methods. A total of 128 sound types and 142 animal taxa were inventoried revealing an important underwater diversity. This diversity, instead of being randomly distributed among the six floodplain channels, was site-specific. Generalized mixed-effects models demonstrated a strong effect of both temperature and lateral connectivity on acoustic community composition. These results, congruent with macroinvertebrate community composition, suggest that acoustic communities reflect the interactions between animal communities and their environment. Overall our study strongly supports the perspectives offered by acoustic monitoring to describe and understand ecological patterns in freshwater environments.
The allergic response mediated by fire ant venom proteins
Authors: Zamith-Miranda Daniel , Fox Eduardo G. P. , Monteiro Ana Paula , Gama Diogo , Poublan Luiz E. , de Araujo Almair Ferreira , Araujo Maria F. C. , Atella Georgia C. , Machado Ednildo A. , Diaz Bruno L. 
Published: September 2018

AbstractFire ants are widely studied, invasive and venomous arthropod pests. There is significant biomedical interest in immunotherapy against fire ant stings. However, mainly due to practical reasons, the physiological effects of envenomation has remained poorly characterized. The present study takes advantage of a recently-described venom protein extract to delineate the immunological pathways underlying the allergic reaction to fire ant venom toxins. Mice were injected with controlled doses of venom protein extract. Following sensitization and a second exposure, a marked footpad swelling was observed. Based on eosinophil recruitment and production of Th2 cytokines, we hereby establish that fire ant proteins per se can lead to an allergic response, which casts a new light into the mechanism of action of these toxins.
Longitudinal Patterns in Clinical and Imaging Measurements Predict Residual Survival in Glioblastoma Patients
Authors: Smedley Nova F. , Ellingson Benjamin M. , Cloughesy Timothy F. , Hsu William 
Published: September 2018

AbstractThe growing amount of longitudinal data for a large population of patients has necessitated the application of algorithms that can discover patterns to inform patient management. This study demonstrates how temporal patterns generated from a combination of clinical and imaging measurements improve residual survival prediction in glioblastoma patients. Temporal patterns were identified with sequential pattern mining using data from 304 patients. Along with patient covariates, the patterns were incorporated as features in logistic regression models to predict 2-, 6-, or 9-month residual survival at each visit. The modeling approach that included temporal patterns achieved test performances of 0.820, 0.785, and 0.783 area under the receiver operating characteristic curve for predicting 2-, 6-, and 9-month residual survival, respectively. This approach significantly outperformed models that used tumor volume alone (p < 0.001) or tumor volume combined with patient covariates (p < 0.001) in training. Temporal patterns involving an increase in tumor volume above 122 mm3/day, a decrease in KPS across multiple visits, moderate neurologic symptoms, and worsening overall neurologic function suggested lower residual survival. These patterns are readily interpretable and found to be consistent with known prognostic indicators, suggesting they can provide early indicators to clinicians of changes in patient state and inform management decisions.
Community Structure, Dynamics and Interactions of Bacteria, Archaea and Fungi in Subtropical Coastal Wetland Sediments
Authors: Cheung Man Kit , Wong Chong Kim , Chu Ka Hou , Kwan Hoi Shan 
Published: September 2018

AbstractBacteria, archaea and fungi play crucial roles in wetland biogeochemical processes. However, little is known about their community structure, dynamics and interactions in subtropical coastal wetlands. Here, we examined communities of the three kingdoms in mangrove and mudflat sediments of a subtropical coastal wetland using Ion Torrent amplicon sequencing and co-occurrence network analysis. Bacterial, archaeal and fungal communities comprised mainly of members from the phyla Proteobacteria and Bacteroidetes, Bathyarchaeota and Euryarchaeota, and Ascomycota, respectively. Species richness and Shannon diversity were highest in bacteria, followed by archaea and were lowest in fungi. Distinct spatiotemporal patterns were observed, with bacterial and fungal communities varying, to different extent, between wet and dry seasons and between mangrove and mudflat, and archaeal community remaining relatively stable between seasons and regions. Redundancy analysis revealed temperature as the major driver of the seasonal patterns of bacterial and fungal communities but also highlighted the importance of interkingdom biotic factors in shaping the community structure of all three kingdoms. Potential ecological interactions and putative keystone taxa were identified based on co-occurrence network analysis. These findings facilitate current understanding of the microbial ecology of subtropical coastal wetlands and provide a basis for better modelling of ecological processes in this important ecosystem.
Modelling realistic microgels in an explicit solvent
Authors: Camerin F. , Gnan N. , Rovigatti L. , Zaccarelli E. 
Published: September 2018

AbstractThermoresponsive microgels are polymeric colloidal networks that can change their size in response to a temperature variation. This peculiar feature is driven by the nature of the solvent-polymer interactions, which triggers the so-called volume phase transition from a swollen to a collapsed state above a characteristic temperature. Recently, an advanced modelling protocol to assemble realistic, disordered microgels has been shown to reproduce experimental swelling behavior and form factors. In the original framework, the solvent was taken into account in an implicit way, condensing solvent-polymer interactions in an effective attraction between monomers. To go one step further, in this work we perform simulations of realistic microgels in an explicit solvent. We identify a suitable model which fully captures the main features of the implicit model and further provides information on the solvent uptake by the interior of the microgel network and on its role in the collapse kinetics. These results pave the way for addressing problems where solvent effects are dominant, such as the case of microgels at liquid-liquid interfaces.
First insight into microbiome profile of fungivorous thrips Hoplothrips carpathicus (Insecta: Thysanoptera) at different developmental stages: molecular evidence of Wolbachia endosymbiosis
Authors: Kaczmarczyk Agnieszka , Kucharczyk Halina , Kucharczyk Marek , Kapusta Przemysław , Sell Jerzy , Zielińska Sylwia 
Published: September 2018

AbstractInsects’ exoskeleton, gut, hemocoel, and cells are colonized by various microorganisms that often play important roles in their host life. Moreover, insects are frequently infected by vertically transmitted symbionts that can manipulate their reproduction. The aims of this study were the characterization of bacterial communities of four developmental stages of the fungivorous species Hoplothrips carpathicus (Thysanoptera: Phlaeothripidae), verification of the presence of Wolbachia, in silico prediction of metabolic potentials of the microorganisms, and sequencing its mitochondrial COI barcode. Taxonomy-based analysis indicated that the bacterial community of H. carpathicus contained 21 bacterial phyla. The most abundant phyla were Proteobacteria, Actinobacteria, Bacterioidetes and Firmicutes, and the most abundant classes were Alphaproteobacteria, Actinobacteria, Gammaproteobacteria and Betaproteobacteria, with different proportions in the total share. For pupa and imago (adult) the most abundant genus was Wolbachia, which comprised 69.95% and 56.11% of total bacterial population respectively. Moreover, similarity analysis of bacterial communities showed that changes in microbiome composition are congruent with the successive stages of H. carpathicus development. PICRUSt analysis predicted that each bacterial community should be rich in genes involved in membrane transport, amino acid metabolism, carbohydrate metabolism, replication and repair processes.
Heterocyclic sterol probes for live monitoring of sterol trafficking and lysosomal storage disorders
Authors: Králová Jarmila , Jurášek Michal , Krčová Lucie , Dolenský Bohumil , Novotný Ivan , Dušek Michal , Rottnerová Zdeňka , Kahle Michal , Drašar Pavel , Bartůněk Petr , Král Vladimír 
Published: September 2018

AbstractThe monitoring of intracellular cholesterol homeostasis and trafficking is of great importance because their imbalance leads to many pathologies. Reliable tools for cholesterol detection are in demand. This study presents the design and synthesis of fluorescent probes for cholesterol recognition and demonstrates their selectivity by a variety of methods. The construction of dedicated library of 14 probes was based on heterocyclic (pyridine)-sterol derivatives with various attached fluorophores. The most promising probe, a P1-BODIPY conjugate FP-5, was analysed in detail and showed an intensive labelling of cellular membranes followed by intracellular redistribution into various cholesterol rich organelles and vesicles. FP-5 displayed a stronger signal, with faster kinetics, than the commercial TF-Chol probe. In addition, cells with pharmacologically disrupted cholesterol transport, or with a genetic mutation of cholesterol transporting protein NPC1, exhibited strong and fast FP-5 signal in the endo/lysosomal compartment, co-localizing with filipin staining of cholesterol. Hence, FP-5 has high potential as a new probe for monitoring cholesterol trafficking and its disorders.
NKX2-1-AS1 negatively regulates CD274/PD-L1, cell-cell interaction genes, and limits human lung carcinoma cell migration
Authors: Kathuria Hasmeena , Millien Guetchyn , McNally Liam , Gower Adam C. , Tagne Jean-Bosco , Cao Yuxia , Ramirez Maria I. 
Published: September 2018

AbstractThe function of most long noncoding RNAs (lncRNAs) is unknown. However, recent studies reveal important roles of lncRNAs in regulating cancer-related pathways. Human antisense lncRNA-NKX2-1-AS1 partially overlaps the NKX2-1/TTF1 gene within chromosomal region 14q13.3. Amplification of this region and/or differential expression of genes therein are associated with cancer progression. Herein we show higher levels of NKX2-AS1 and NKX2-1 in lung adenocarcinomas relative to non-tumor controls but no correlation between NKX2-1-AS1 and NKX2-1 levels across specimens, or with amplification of the 14q13.3 region, suggesting that NKX2-1-AS1 and NKX2-1 are independently regulated. Loss-and-gain of function experiments showed that NKX2-1-AS1 does not regulate NKX2-1 expression, or nearby genes, but controls genes in trans. Genes up-regulated by NKX2-1-AS1-knockdown belong to cell adhesion and PD-L1/PD-1 checkpoint pathways. NKX2-1-AS1 negatively regulates endogenous CD274/PD-L1, a known target of NKX2-1, and the transcriptional activity of -1kb-CD274 promoter-reporter construct. Furthermore, NKX2-1-AS1 interferes with NKX2-1 protein binding to the CD274-promoter, likely by NKX2-1 protein-NKX2-1-AS1 interactions. Finally, NKX2-1-AS1 negatively regulates cell migration and wound healing, but not proliferation or apoptosis. These findings support potential roles of NKX2-1-AS1 in limiting motility and immune system evasion of lung carcinoma cells, highlighting a novel mechanism that may influence tumorigenic capabilities of lung epithelial cells.
Biomimetic matrices for rapidly forming mineralized bone tissue based on stem cell-mediated osteogenesis
Authors: Carvalho Marta S. , Poundarik Atharva A. , Cabral Joaquim M. S. , da Silva Cláudia L. , Vashishth Deepak 
Published: September 2018

AbstractBone regeneration, following fracture, relies on autologous and allogenic bone grafts. However, majority of fracture population consists of older individuals with poor quality bone associated with loss and/or modification of matrix proteins critical for bone formation and mineralization. Allografts suffer from same limitations and carry the risk of delayed healing, infection, immune rejection and eventual fracture. In this work, we apply a synergistic biomimetic strategy to develop matrices that rapidly form bone tissue - a critical aspect of fracture healing of weight bearing bones. Collagen matrices, enhanced with two selected key matrix proteins, osteocalcin (OC) and/or osteopontin (OPN), increased the rate and quantity of synthesized bone matrix by increasing mesenchymal stem/stromal cell (MSC) proliferation, accelerating osteogenic differentiation, enhancing angiogenesis and showing a sustained bone formation response from MSC obtained from a variety of human tissue sources (marrow, fat and umbilical cord).In vivoassessment of OC/OPN mineralized scaffolds in a critical sized-defect rabbit long-bone model did not reveal any foreign body reaction while bone tissue was being formed. We demonstrate a new biomimetic strategy to rapidly form mineralized bone tissue and secure a sustained bone formation response by MSC from multiple sources, thus facilitating faster patient recovery and treatment of non-union fractures in aging and diseased population. Acellular biomimetic matrices elicit bone regeneration response from MSC, obtained from multiple tissue sources, and can be used in variety of scaffolds and made widely available.
Evolution, and functional analysis of Natural Resistance-Associated Macrophage Proteins (NRAMPs) from Theobroma cacao and their role in cadmium accumulation
Authors: Ullah Ihsan , Wang Yirong , Eide David J. , Dunwell Jim M. 
Published: September 2018

AbstractThe presence of the toxic metal cadmium (Cd2+) in certain foodstuffs is recognised as a global problem, and there is increasing legislative pressure to reduce the content of Cd in food. The present study was conducted on cacao (Theobroma cacao), the source of chocolate, and one of the crops known to accumulate Cd in certain conditions. There are a range of possible genetic and agronomic methods being tested as a route to such reduction. As part of a gene-based approach, we focused on the Natural Resistance-Associated Macrophage Proteins (NRAMPS), a family of proton/metal transporter proteins that are evolutionarily conserved across all species from bacteria to humans. The plant NRAMP gene family are of particular importance as they are responsible for uptake of the nutritionally vital divalent cations Fe2+, Mn2+, Zn2+, as well as Cd2+. We identified the five NRAMP genes in cacao, sequenced these genes and studied their expression in various organs. We then confirmed the expression patterns in response to variation in nutrient cation availability and addition of Cd2+. Functional analysis by expression in yeast provided evidence that NRAMP5 encoded a protein capable of Cd2+ transport, and suggested this gene as a target for genetic selection/modification.
Cell type-specific activation of mitogen-activated protein kinase in D1 receptor-expressing neurons of the nucleus accumbens potentiates stimulus-reward learning in mice
Authors: Bin Saifullah Md. Ali , Nagai Taku , Kuroda Keisuke , Wulaer Bolati , Nabeshima Toshitaka , Kaibuchi Kozo , Yamada Kiyofumi 
Published: September 2018

AbstractMedium spiny neurons (MSN) in the nucleus accumbens (NAc) are a fundamental component of various aspects of motivated behavior. Although mitogen-activated protein kinase (MAPK) signaling plays a crucial role in several types of learning, the cell type-specific role of MAPK pathway in stimulus-reward learning and motivation remains unclear. We herein investigated the role of MAPK in accumbal MSNs in reward-associated learning and memory. During the acquisition of Pavlovian conditioning, the number of phosphorylated MAPK1/3-positive cells was increased significantly and exclusively in the NAc core by 7-days of extensive training. MAPK signaling in the respective D1R- and D2R-MSNs was manipulated by transfecting an adeno-associated virus (AAV) plasmid into the NAc of Drd1a-Cre and Drd2-Cre transgenic mice. Potentiation of MAPK signaling shifted the learning curve of Pavlovian conditioning to the left only in Drd1a-Cre mice, whereas such manipulation in D2R-MSNs had negligible effects. In contrast, MAPK manipulation in D2R-MSNs of the NAc core significantly increased motivation for food rewards as found in Drd1a-Cre mice. These results suggest that MAPK signaling in the D1R-MSNs of NAc core plays an important role in stimulus-reward learning, while MAPK signaling in both D1R- and D2R-MSNs is involved in motivation for natural rewards.
Reversible two-state folding of the ultrafast protein gpW under mechanical force
Authors: Schönfelder Jörg , De Sancho David , Berkovich Ronen , Best Robert B. , Muñoz Victor , Perez-Jimenez Raul 
Published: September 2018

AbstractUltrafast folding proteins have limited cooperativity and thus are excellent models to resolve, via single-molecule experiments, the fleeting molecular events that proteins undergo during folding. Here we report single-molecule atomic force microscopy experiments on gpW, a protein that, in bulk, folds in a few microseconds over a marginal folding barrier (∼1 kBT). Applying pulling forces of only 5 pN, we maintain gpW in quasi-equilibrium near its mechanical unfolding midpoint and detect how it interconverts stochastically between the folded and an extended state. The interconversion pattern is distinctly binary, indicating that, under an external force, gpW (un)folds over a significant free-energy barrier. Using molecular simulations and a theoretical model we rationalize how force induces such barrier in an otherwise downhill free-energy surface. Force-induced folding barriers are likely a general occurrence for ultrafast folding biomolecules studied with single-molecule force spectroscopy.