bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of flavone-based wooly fibres by glandular trichomes ofDionysia tapetodes
Authors: Bourdon Matthieu , Gaynord Josephine , Müller Karin , Evans Gareth , Wallis Simon , Aston Paul , Spring David R. , Wightman Raymond 
Published: October 2020

AbstractDionysia tapetodes, a small cushion-forming mountainous evergreen in the Primulaceae, possesses a vast surface-covering of long silky fibres forming the characteristic “wooly” farina. This contrasts with some relatedPrimulawhich instead possess a powdery farina. Using a combination of cell biology and analytical chemical techniques, we provide a detailed insight of wooly farina formation by glandular trichomes that produce a mixture of flavone and substituted flavone derivatives, including hydroxyflavones. Conversely, our analysis show that the powdery form consist almost entirely of flavone. The wooly farina inD. tapetodesis extruded through specific sites at the surface of the glandular head cell, characterised by a small complete gap in the plasma membrane, cell wall and cuticle. The data is consistent with formation and thread elongation occurring from within the cell. The putative mechanism of wool thread formation and its stability is discussed.
The sandarazols are cryptic and structurally unique plasmid encoded toxins from a rare myxobacterium
Authors: Panter Fabian , Bader Chantal D. , Müller Rolf 
Published: October 2020

AbstractSoil dwelling bacteria such as myxobacteria defend themselves by using secondary metabolites to inhibit growth of competing microorganisms. In this work we describe a new plasmid found inSandaracinussp. MSr10575 named pSa001 spanning 209.7 kbp that harbors a cryptic secondary metabolite biosynthesis gene cluster (BGC). Activation of this BGC by homologous recombination mediated exchange of the native promoter sequence against a vanillate inducible system led to production and subsequent isolation and structure elucidation of novel secondary metabolites, the sandarazols A-G. The sandarazol structure contains intriguing features such as an α-chlorinated ketone, an epoxyketone and a (2R)-2-amino-3- (N,N-dimethylamino)-propionic acid building block. In depth investigation of the underlying biosynthetic machinery led to a concise biosynthetic model for the new compound family, including several uncommon biosynthesis steps. The chlorinated congener sandarazol C shows an IC50value of 0.5 µM against HCT 116 cells and a MIC of 14 µM againstMycobacterium smegmatis, which points at the sandarazol’s potential function as defensive secondary metabolites or toxins. The sandara-zols’ BGC location on pSa001 is one of the very few example of large multimodular BGCs on a replicative plasmid, whose existence points at the mechanism of horizontal gene transfer events of entire multimodular BGCs to exchange chemical warfare capabilities between bacterial species.
The mouse cortico-basal ganglia-thalamic network
Authors: Foster Nicholas N. , Korobkova Laura , Garcia Luis , Gao Lei , Becerra Marlene , Sherafat Yasmine , Peng Bo , Li Xiangning , Choi Jun-Hyeok , Gou Lin , Zingg Brian , Azam Sana , Lo Darrick , Khanjani Neda , Zhang Bin , Stanis Jim , Bowman Ian , Cotter Kaelan , Cao Chunru , Yamashita Seita , Tugangui Amanda , Li Anan , Jiang Tao , Jia Xueyan , Feng Zhao , Aquino Sarvia , Dan Gordon , Fayzullina Marina , Mun Hyun-Seung , Ustrell Sarah , Boesen Tyler , Santarelli Anthony , Zhu Muye , Benavidez Nora L. , Song Monica , Johnson David L. , Xu Hanpeng , Bienkowski Michael S. , Yang X. William , Gong Hui , Wickersham Ian , Luo Qingming , Lim Byung Kook , Zhang Li I. , Hintiryan Houri , Dong Hongwei 
Published: October 2020

ABSTRACTThe cortico-basal ganglia-thalamic loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behavior, and the natural history of many neurological and neuropsychiatric diseases. Classically, the basal ganglia is conceptualized to contain three primary information output channels: motor, limbic, and associative. However, given the roughly 65 cortical areas and two dozen thalamic nuclei that feed into the dorsal striatum, a three-channel view is overly simplistic for explaining the myriad functions of the basal ganglia. Recent works from our lab and others have subdivided the dorsal striatum into numerous functional domains based on convergent and divergent inputs from the cortex and thalamus. To complete this work, we generated a comprehensive data pool of ∼700 injections placed across the striatum, external globus pallidus (GPe), substantia nigra pars reticulata (SNr), thalamic nuclei, and cortex. We identify 14 domains of SNr, 36 in the GPe, and 6 in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify 6 parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information with complex patterns of convergence and divergence through every elemental node of the entire cortico-basal ganglia loop. These experiments reveal multiple important novel features of the cortico-basal ganglia network motif. The prototypical sub-network structure is characterized by a highly interconnected nature, with cortical information processing through one or more striatal nodes, which send a convergent output to the SNr and a more parallelized output to the GPe; the GPe output then converges with the SNr. A domain of the thalamus receives the nigral output, and is interconnected with both the striatal domains and the cortical areas that filter into its nigral input source. This study provides conceptual advancement of our understanding of the structural and functional organization of the classic cortico-basal ganglia network.
Environmental stressors induced strong small-scale phenotypic differentiation in a wide-dispersing marine snail
Authors: Bonel Nicolás , Pointier Jean-Pierre , Alda Pilar 
Published: October 2020

ABSTRACTHeterogeneous environments pose a particular challenge for organisms because the same phenotype is unlikely to perform best regardless of the variety of encountered stressors. To understand how species meet this challenge, we investigated the extent to which contrasting environmental pressures induced ecological and phenotypic responses in a natural population of a wide-dispersing marine snail at a small spatial scale. We analyzed several traits ofHeleobia australis(Rissooidea: Cochliopidae) collected from heterogeneous, but highly connected, habitats from the intertidal area of the Bahía Blanca estuary, Argentina. We also conducted molecular analyses by amplifying the COI gene in individuals sampled from each habitat. We found that sympatric subpopulations ofH. australisexhibited a strong phenotypic divergence in shell characters and body weight in response to thermal, saline, and dehydration stress, crab predation risk, and parasitic castrators. We proved that this differentiation occurred even early in life as most of the characters observed in juveniles mirrored those found in adults. We also found a divergence in penis size in snails collected from each habitat and raised in common garden laboratory conditions. The molecular analyses confirmed that the individuals studied constituted a single species despite the strong phenotypic differences among subpopulations. The small-scale phenotypic differentiation suggests thatH.australisexperienced a fine-grained environment where conditions imposed by different sources of stress favored the expression of beneficial traits. We discuss the role of plasticity in shaping adaptive phenotypic responses that increase the likelihood of persistence of subpopulations facing environmental stress conditions.
A triresidue motif in the GLUTAMATE RECEPTOR-LIKE 3.3 C-tail interacts with IMPAIRED SUCROSE INDUCTION 1 and controls long distance wound signaling
Authors: Wu Qian , Stolz Stéphanie , Kumari Archana , Glauser Gaétan , Farmer Edward E. 
Published: October 2020

AbstractArabidopsisClade 3GLUTAMATE RECEPTOR-LIKE(GLRs) genes are primary players in wound-induced electrical signaling and jasmonate-activated defense responses. As cation-permeable ion channels, previous studies have focused on resolving their gating properties and structures. However, little is known regarding to the regulatory mechanism of these channel proteins. Here, we report that the C-tail of GLR3.3 contains key elements that control its function in long distance wound signaling. GLR3.3 without its C-tail failed to rescue theglr3.3amutant. To further investigate the underlying mechanism, we performed a yeast two-hybrid screen. IMPAIRED SUCROSE INDUCTION 1 (ISI1) was identified as an interactor with both the C-tail and the full-length GLR3.3in planta. Reduced functionisi1mutants had enhanced electrical activity and jasmonate-regulated defense responses. Furthermore, we found that a triresidue motif RFL (R884, F885 and L886) in the GLR3.3 C-tail is essential for interacting with ISI1. RFL mutation abolished GLR3.3 function in electrical signaling and jasmonate-mediated defense gene activation. Our study shows the importance of the C-tail in GLR3.3 function, and reveals parallels with the ipnotropic glutamate receptor regulation in animal cells.
Extinct species identification from Upper Pleistocene bone fragments not identifiable from their osteomorphological studies by proteomics analysis
Authors: Bray Fabrice , Flament Stéphanie , Abrams Grégory , Bonjean Dominique , Modica Kévin Di , Rolando Christian , Tokarski Caroline , Auguste Patrick 
Published: October 2020

AbstractThe ancient preserved molecules offer the opportunity to gain a better knowledge on the biological past. In recent years, bones proteomics has become an attractive method to study the animal biological origin, extinct species and species evolution as an alternative to DNA analysis which is limited by DNA amplification present in ancient samples and its contamination. However, the development of a proteomic workflow remains a challenge. The analysis of fossils must consume a low quantity of material to avoid damaging the samples. Another difficulty is the absence of genomic data for most of the extinct species. In this study, a proteomic methodology was applied to mammalian bones of 130,000 years old from the earlier Upper Pleistocene site of Scladina Cave (Belgium). Starting from 5 milligram samples, our results show a large majority of detected peptides matching collagen I alpha 1 and alpha 2 proteins with a sequence coverage up to 60%. Using sequence homology with modern sequences, a biological classification was successfully achieved and the associated taxonomic ranks to each bone were identified consistently with the information gained from osteomorphological studies and palaeoenvironmental and palaeodietary data. Among the taxa identified are the Felidae family, Bovinae subfamily, Elephantidae family and the Ursus genus. Amino acid substitutions on the collagens were identified providing new information on extinct species sequences and also helping in taxonomy-based clustering. Considering samples with no osteomorphological information, such as two bone retouchers, proteomics successfully identified the bovidae and ursidae families providing new information to the paleontologists on these objects. Combining osteomorphology studies and amino acid variations identified by proteomics, one retoucher was identified to be potentially from theUrsus spelaeusspecies.
Uncertainty is Maintained and Used in Working Memory
Authors: Yoo Aspen H. , Acerbi Luigi , Ma Wei ji 
Published: October 2020

1AbstractWhat are the contents of working memory? In both behavioral and neural computational models, a working memory representation is typically described by a single number, namely a point estimate of a stimulus. Here, we asked if people also maintain the uncertainty associated with a memory, and if people use this uncertainty in subsequent decisions. We collected data in a two-condition orientation change detection task; while both conditions measured whether people used memory uncertainty, only one required maintaining it. For each condition, we compared an optimal Bayesian observer model, in which the observer uses an accurate representation of uncertainty in their decision, to one in which the observer does not. We find that this “Use Uncertainty” model fits better for all participants in both conditions. In the first condition, this result suggests that people use uncertainty optimally in a working memory task when that uncertainty information is available at the time of decision, confirming earlier results. Critically, the results of the second condition suggest that this uncertainty information was maintained in working memory. We test model variants and find that our conclusions do not depend on our assumptions about the observer’s encoding process, inference process, or decision rule. Our results provide evidence that people have uncertainty that reflects their memory precision on an item-specific level, maintain this information over a working memory delay, and use it implicitly in a way consistent with an optimal observer. These results challenge existing computational models of working memory to update their frameworks to represent uncertainty.
The guidance and adhesion protein FLRT2 dimerizesin cisvia dual Small-X3-Small transmembrane motifs
Authors: Jackson Verity , Hermann Julia , Tynan Christopher J. , Rolfe Daniel J. , Corey Robin A. , Duncan Anna L. , Noriega Maxime , Chu Amy , Kalli Antreas C. , Yvonne Jones E. , Sansom Mark S. P. , Martin-Fernandez Marisa L. , Seiradake Elena , Chavent Matthieu 
Published: October 2020

AbstractFibronectin Leucine-rich Repeat Transmembrane (FLRT 1-3) proteins are a family of broadly expressed single-spanning transmembrane receptors that play key roles in development. Their extracellular domains mediate homotypic cell-cell adhesion and heterotypic protein interactions with other receptors to regulate cell adhesion and guidance. Thesein transFLRT interactions determine the formation of signaling complexes of varying complexity and function. Whether FLRTs also interact at the surface of the same cell,in cis, remains unknown. Here, molecular dynamics simulations reveal two dimerization motifs in the FLRT2 transmembrane helix. Single particle tracking experiments show that these ‘Small-X3-Small’ motifs synergize with a third dimerization motif encoded in the extracellular domain to permit thecisassociation and co-diffusion patterns of FLRT2 receptors on cells. These results may point to a competitive switching mechanism betweenin cisandin transinteractions which suggests that homotypic FLRT interaction mirrors the functionalities of classic adhesion molecules.FieldsStructural Biology and Biophysics / Computational Biology
Dominant monoallelic variant in the PAK2 gene causes Knobloch syndrome type 2
Authors: Antonarakis Stylianos E. , Holoubek Ales , Rapti Melivoia , Rademaker Jesse , Meylan Jenny , Iwaszkiewicz Justyna , Zoete Vincent , Ansar Muhammad , Borel Christelle , Menzel Olivier , Kuželová Kateřina , Santoni Federico A. 
Published: October 2020

AbstractKnobloch syndrome is an autosomal recessive phenotype mainly characterized by retinal detachment and encephalocele caused by biallelic pathogenic variants in theCOL18A1gene. However, there are patients clinically diagnosed as Knobloch syndrome with unknown molecular etiology not linked toCOL18A1. We studied an historical pedigree (published in 1998) designated as KNO2 (Knobloch type 2 syndrome with intellectual disability, autistic behavior, retinal degeneration, encephalocele). Whole exome sequencing of the two affected siblings and the normal parents resulted in the identification of a PAK2 non-synonymous substitution p.(Glu435Lys) as a causative variant. The variant was monoallelic and apparentlyde novoin both siblings indicating a likely germline mosaicism in one of the parents; the mosaicism however could not be observed after deep sequencing of blood parental DNA. PAK2 encodes a member of a small group of serine/threonine kinases; these P21-activating kinases (PAKs) are essential in signal transduction and cellular regulation (cytoskeletal dynamics, cell motility, death and survival signaling, and cell cycle progression). Structural analysis of the PAK2 p.(Glu435Lys) variant which is located in the kinase domain of the protein predicts a possible compromise in the kinase activity. Functional analysis of the p.(Glu435Lys) PAK2 variant in transfected HEK293T cells results in a partial loss of the kinase activity. PAK2 has been previously suggested as an autism related gene. Our results show that PAK2 induced phenotypic spectrum is broad and not fully understood. We conclude that the KNO2 syndrome in the studied family is dominant and caused by a deleterious variant in the PAK2 gene.
BiSulfite Bolt: A BiSulfite Sequencing Analysis Platform
Authors: Farrell Colin , Thompson Michael , Tosevska Anela , Oyetunde Adewale , Pellegrini Matteo 
Published: October 2020

AbstractBackgroundBisulfite sequencing is commonly employed to measure DNA methylation. Processing bisulfite sequencing data is often challenging due to the computational demands of mapping a low complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis ready methylation matrix from read alignments. To address these shortcomings, we have developed BiSulfite Bolt (BSBolt); a fast and scalable bisulfite sequencing analysis platform. BSBolt performs a pre-alignment sequencing read assessment step to improve efficiency when handling asymmetrical bisulfite sequencing libraries.FindingsWe evaluated BSBolt against simulated and real bisulfite sequencing libraries. We found that BSBolt provides accurate and fast bisulfite sequencing alignments and methylation calls. We also compared BSBolt to several existing bisulfite alignment tools and found BSBolt outperforms Bismark, BSSeeker2, BISCUIT, and BWA-Meth based on alignment accuracy and methylation calling accuracy.ConclusionBSBolt offers streamlined processing of bisulfite sequencing data through an integrated toolset that offers support for simulation, alignment, methylation calling, and data aggregation. BSBolt is implemented as a python package and command line utility for flexibility when building informatics pipelines. BSBolt is available athttps://github.com/NuttyLogic/BSBoltunder an MIT license.
Clustering-based positive feedback between a kinase and its substrate enables effective T-cell receptor signaling
Authors: Dine Elliot , Reed Ellen H. , Toettcher Jared E. 
Published: October 2020

AbstractProtein clusters and condensates are pervasive in mammalian signaling. Yet how the signaling capacity of higher-order assemblies differs from simpler forms of molecular organization is still poorly understood. Here, we present an optogenetic approach to switch between light-induced clusters and simple protein heterodimers with a single point mutation. We apply this system to study how clustering affects signaling from the kinase Zap70 and its substrate LAT, proteins that normally form membrane-localized clusters during T cell activation. We find that light-induced clusters of LAT and Zap70 trigger potent activation of downstream signaling pathways even in non-T cells, whereas one-to-one dimers do not. We provide evidence that clusters harbor a local positive feedback loop between three components: Zap70, LAT, and Src-family kinases that bind to phosphorylated LAT and further activate Zap70. Overall, our study provides evidence for a specific role of protein condensates in cell signaling, and identifies a simple biochemical circuit that can robustly sense protein oligomerization state.Highlights-A general system for studying the role of protein clusters versus dimers.-Membrane clusters of the kinase Zap70 and its substrate LAT trigger potent downstream signaling.-Clustering Zap70 with LAT is required for full activation of Zap70 kinase activity.-A positive feedback loop connects phosphorylated LAT to Zap70 activation via Src-family kinases.
Detection of a historic reservoir of bedaquiline / clofazimine resistance associated variants inMycobacterium tuberculosis
Authors: Nimmo Camus , Ortiz Arturo Torres , Pang Juanita , Acman Mislav , Tan Cedric C.S. , Millard James , Padayatchi Nesri , Grant Alison , O’Donnell Max , Pym Alex , Brynildsrud Ola B , Eldholm Vegard , Grandjean Louis , Didelot Xavier , Balloux François , van Dorp Lucy 
Published: October 2020

AbstractDrug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains ofMycobacterium tuberculosis(Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in themmpR5gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug. We compiled a dataset of 3,682Mtbgenomes, including 150 carrying variants inmmpR5that have been associated to borderline (henceforth intermediate) or confirmed resistance to bedaquiline. We identified eight cases where RAVs were present in the genomes of strains collected prior to the use of bedaquiline in TB treatment regimes. Phylogenetic reconstruction points to multiple emergence events and circulation of RAVs inmmpR5, some estimated to predate the introduction of bedaquiline. However, epistatic interactions can complicate bedaquiline drug-susceptibility prediction from genetic sequence data. Indeed, in one clade of isolates where the RAV Ile67fs is estimated to have emerged prior to the antibiotic era, co-occurrence of mutations inmmpL5are found to neutralise bedaquiline resistance. The presence of a pre-existing reservoir ofMtbstrains carrying bedaquiline RAVs prior to its clinical use augments the need for rapid drug susceptibility testing and individualised regimen selection to safeguard the use of bedaquiline in TB care and control.