bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure determination of protein-peptide complexes from NMR chemical shift data using MELD
Authors: Mondal Arup , Swapna G.V.T. , Hao Jingzhou , Ma LiChung , Roth Monica J. , Montelione Gaetano T. , Perez Alberto 
Published: January 2022

ABSTRACTIntrinsically disordered regions of proteins often mediate important protein-protein interactions. However, the folding upon binding nature of many polypeptide-protein interactions limits the ability of modeling tools to predict structures of such complexes. To address this problem, we have taken a tandem approach combining NMR chemical shift data and molecular simulations to determine structures of peptide-protein complexes. Here, we demonstrate this approach for polypeptide complexes formed with the extraterminal (ET) domain of bromo and extraterminal domain (BET) proteins, which exhibit a high degree of binding plasticity. This system is particularly challenging as the binding process includes allosteric changes across the ET receptor upon binding, and the polypeptide binding partners can form different conformations (e.g., helices and hairpins) in the complex. In a blind study, the new approach successfully modeled bound-state conformations and binding poses, using only backbone chemical shift data, in excellent agreement with experimentally-determined structures. The approach also predicts relative binding affinities of different peptides. This hybrid MELD-NMR approach provides a powerful new tool for structural analysis of protein-polypeptide complexes in the low NMR information content regime, which can be used successfully for flexible systems where one polypeptide binding partner folds upon complex formation.
SpotLink enables sensitive and precise identification of site non-specific cross-links at the proteome scale
Authors: Zhang Weijie , Gong Pengyun , Shan Yichu , Zhao Lili , Hu Hongke , Wei Qiushi , Liang Zhen , Liu Chao , Zhang Lihua , Zhang Yukui 
Published: January 2022

AbstractWe developed SpotLink software for identifying site non-specific cross-links at the proteome scale. Contributed by the dual pointer dynamic pruning (DPDP) algorithm and the quality control of cross-linking sites, SpotLink identified more than 3000 cross-links from human proteome database with rich site information in a few days. We demonstrated that SpotLink outperformed other approaches in terms of sensitivity and precision on a simulated dataset and a protein complexes dataset with known structures. Additionally, we discovered some valuable protein-protein interaction (PPI) information contained in the protein complexes dataset and HeLa dataset, indicating the unique identification advantages of site non-specific cross-linking. The excellent performance of SpotLink will increase the usage of site non-specific cross-linking in the near future. SpotLink is publicly available on GitHub [https://github.com/DICP1810/SpotLink].
Pachytene karyotypes of 17 species of birds
Authors: Slobodchikova Anastasia Y. , Malinovskaya Lyubov P. , Grishko Ekaterina O. , Pristyazhnyuk Inna E. , Torgasheva Anna A. , Borodin Pavel M. 
Published: January 2022

AbstractKaryotypes of less than 10% of bird species are known. Using immunolocalization of the synaptonemal complex, the core structure of meiotic chromosomes at the pachytene stage, and centromere proteins we described male pachytene karyotypes of seventeen species of birds. This method enables higher resolution than the conventional analyses of metaphase chromosomes. We provided the first descriptions of the karyotypes of three species (Rook, Blyth’s reed warbler and European pied flycatcher), corrected the published data on the karyotypes of ten species and confirmed them for four species. All passerine species examined have highly conservative karyotypes, 2n=80-82 with seven pairs of macrochromosomes and 33-34 pairs of microchromosomes. In all of them but not in the Common cuckoo we revealed single copies of the germline restricted chromosomes varying in size and morphology even between closely related species. This indicates a fast evolution of this additional chromosome. The interspecies differences concern the sizes of the macrochromosomes, morphology of the microchromosomes and sizes of the centromeres. The pachytene cells of the Gouldian finch, Brambling and Common linnet contained heteromorphic synaptonemal complexes indicating heterozygosity for inversions or centromere shifts. The European pied flycatcher, Gouldian finch and Domestic canary have extended centromeres in several macro- and microchromosomes.
Concerted expansion and contraction of immune receptor gene repertoires in plant genomes
Authors: Man Ngou Bruno Pok , Heal Robert , Wyler Michele , Schmid Marc W , Jones Jonathan DG 
Published: January 2022

AbstractRecent reports suggest that cell-surface and intracellular immune receptors function synergistically to activate robust defence against pathogens, but whether or not they co-evolve is unclear. Here we determined the copy numbers of cell-surface and intracellular immune receptors in 208 species. Surprisingly, these receptor gene families contract and/or expand together in plant genomes, suggesting the mutual potentiation of immunity initiated by cell-surface and intracellular receptors is reflected in the concerted co-evolution of the size of their repertoires across plant species.
A simple island biodiversity model is robust to trait dependence in diversification and colonization rates
Authors: Xie Shu , Valente Luis , Etienne Rampal S. 
Published: January 2022

AbstractThe application of state-dependent speciation and extinction (SSE) models to phylogenetic trees has revealed an important role for traits in diversification. However, this role remains comparatively unexplored on islands, which can include multiple independent clades resulting from different colonization events. Here, we perform a robustness study to identify how trait-dependence in rates of island colonization, extinction and speciation (CES rates) affects the estimation accuracy of a phylogenetic model that assumes no rate variation between trait states. We extend the DAISIE (Dynamic Assembly of Islands through Speciation, Immigration and Extinction) simulation model to include state-dependent rates, and evaluate the robustness of the DAISIE inference model using simulated data. Our results show that when the CES rate differences between trait states are moderate, DAISIE shows negligible error for a variety of island diversity metrics. However, for large differences in speciation rates, we find large errors when reconstructing clade size variation and non-endemic species diversity through time. We conclude that for many biologically realistic scenarios with trait-dependent speciation and colonization, island diversity dynamics can be accurately estimated without the need to explicitly model trait dynamics. Nonetheless, our new simulation model may provide a useful tool for studying patterns of trait variation.
oca2targeting using CRISPR/Cas9 in the Malawi cichlidAstatotilapia calliptera
Authors: Clark Bethan , Elkin Joel , Marconi Aleksandra , Turner George F. , Smith Alan M. , Joyce Domino , Miska Eric A. , Juntti Scott A. , Santos M. Emília 
Published: January 2022

AbstractIdentifying genetic loci underlying trait variation provides insights into the mechanisms of diversification, but demonstrating causality and characterising the role of genetic loci requires testing candidate gene function, often in non-model species. Here we establish CRISPR/Cas9 editing inAstatotilapia calliptera, a generalist cichlid of the remarkably diverse Lake Malawi radiation. By targeting the geneoca2required for melanin synthesis in other vertebrate species, we show efficient editing and germline transmission. Gene edits include indels in the coding region, likely a result of non-homologous end joining, and a large deletion in the 3′ UTR due to homology-directed repair. We find thatoca2knock-outA. callipteralack melanin, which may be useful for developmental imaging in embryos and studying colour pattern formation in adults. AsA. callipteraresembles the presumed generalist ancestor of the Lake Malawi cichlids radiation, establishing genome editing in this species will facilitate investigating speciation, adaptation and trait diversification in this textbook radiation.
Controlling critical mistag-associated false discoveries in metagenetic data
Authors: Richardson Rodney T. 
Published: January 2022

AbstractMetagenetic methods are commonplace within ecological and environmental research. One concern with these methods is the phenomenon of critical mistagging, where sequences from one sample are erroneously inferred to have originated from another sample due to errors in the attachment, PCR replication or sequencing of sample-specific dual-index tags. For studies using PCR-based library preparation on large sample sizes, the most cost-effective approach to limiting mistag-associated false detections involves using an unsaturated Latin square dual-indexing design. This allows researchers to estimate mistagging rates during sequencing but the statistical procedures for filtering out detections using this mistag rate have received little attention.We propose a straightforward method to limit mistag-associated false discoveries during metabarcoding applications. We analyzed two Illumina metabarcoding datasets produced using unsaturated Latin square designs to explore the distribution of mistagged sequences across dual-index combinations on a per taxon basis. We tested these data for conformity to the assumptions that 1) mistagging follows a binomial distribution [i.e.,X~B(n, p)] wherep, the probability of a sequence being mistagged, varies minimally across taxa and 2) mistags are distributed uniformly across dual-index combinations. We provide R functions that estimate the 95thpercentile of expected mistags per dual-index combination for each taxon under these assumptions.We show that mistagging rates were consistent across taxa within the datasets analyzed and that modelling mistagging as a binomial process with uniform distribution across dual-index combinations enabled robust control of mistag-associated false discoveries.We propose that this method of taxon-specific filtering of detections based on the maximum mistags expected per dual-index combination should be broadly accepted during metagenetic analysis, provided that experimental and control sequence abundances per taxon are strongly correlated. When this assumption is violated, data may be better fit by assuming that the distribution of mistags across combinations follows Poisson characteristics [i.e.,X~ Pois(λ)], withλempirically estimated from the abundance distribution of mistags among control samples. We provide a second R function for this case, though we have yet to observe such a dataset. Both functions and demonstrations associated with this work are freely available athttps://github.com/RTRichar/ModellingCriticalMistags.
Meta-analysis of the genetic loci of pigment pattern evolution in vertebrates
Authors: Elkin Joel , Martin Arnaud , Courtier-Orgogozo Virginie , Santos M. Emília 
Published: January 2022

AbstractVertebrate pigmentation patterns are amongst the best characterised model systems for studying the genetic basis of adaptive evolution. The wealth of available data on the genetic basis for pigmentation evolution allows for meta-analysis of trends and quantitative testing of evolutionary hypotheses. We employed Gephebase, a database of genetic variants associated with natural and domesticated trait variation, to examine trends in howcis-regulatory and coding mutations contribute to vertebrate pigmentation phenotypes, as well as factors that favour one mutation type over the other. We found that studies with lower ascertainment bias identified higher proportions ofcis-regulatory mutations, and thatcis-regulatory mutations were more common amongst animals harboring a higher number of pigment cell classes. We classified pigmentation traits firstly according to their physiological basis and secondly according to whether they affect colour or pattern, and identified that carotenoid-based pigmentation and variation in pattern boundaries are preferentially associated withcis-regulatory change. We also classified genes according to their developmental, cellular, and molecular functions. We found that genes implicated in upstream developmental processes had greatercis-regulatory proportions than downstream cellular function genes, and that ligands were associated with highercis-regulatory proportions than their respective receptors. Based on these trends, we discuss future directions for research in vertebrate pigmentation evolution.
Investigating neurotrophin genetics and hippocampal volume
Authors: de Frutos Lucas Jaisalmer , Vacher Michael , Porter Tenielle , Brown Belinda , Laws Simon 
Published: January 2022

AbstractAs individuals get older, the structural integrity of brain regions becomes progressively diminished. Neurotrophic function might aid in preventing such losses through increased synaptogenesis and neurogenesis, particularly in the hippocampus, a brain structure relevant for cognitive function. However, the carriage of certain genetic alleles for genes involved in neurotrophic function might restrain the effectiveness of neurotrophin signalling, hindering neuroprotection. Yet, research on the contribution of single nucleotide polymorphisms (SNPs) within genes coding for neurotrophins and their receptors to hippocampal volumes is scarce, with the exception of rs6265 within the brain-derived neurotrophic factor gene. Therefore, the aim of this study was to identify SNPs within genes involved neurotrophic function that are associated with hippocampal volume in a sample of 23,776 cognitively normal older adults from the UK Biobank. We found that, in individuals older than 50, homozygote carriage of the major alleles rs4839435-A within nerve growth factor gene and rs56405676-T within the neurotrophic receptor tyrosine kinase 2 gene, were associated with increase hippocampal volumes, compared to carriage of 1 or 2 copies of the minor alleles. However, only rs56405676-T was significantly associated with greater hippocampal volumes in individuals older than 60. Hence this study might serve to identify populations at higher risk of hippocampal attrition and cognitive decline.
Phase tracking algorithms detect both real and imaginary components of outer hair cell nonlinear membrane capacitance that exhibits dielectric loss
Authors: Santos-Sacchi Joseph 
Published: January 2022

AbstractOuter hair cell (OHC) nonlinear membrane capacitance (NLC) represents voltage-dependent sensor charge movements within prestin (SLC26a5) that drive OHC electromotility. Dielectric loss, a shift in charge movement phase from purely “capacitive” to “resistive”, is likely indicative of prestin’s interaction with the viscous lipid bilayer and has been suggested to correspond to prestin power output. The frequency response of NLC in OHC membrane patches has been measured with phase tracking and complex capacitance methodologies. While the latter approach can directly determine the presence of dielectric loss by assessing charge movement both in and out of phase with driving voltage, the former has been suggested to fail in this regard. Here we show that standard phase tracking in the presence of dielectric loss does indeed register this loss. Such estimates of NLC correspond to the absolute magnitude of complex NLC, indicating that total charge movement regardless of phase is assessed, thereby validating past and present measures of NLC frequency response that limits its effectiveness at high frequencies. This observation has important implications for understanding prestin’s role in cochlear amplification.
Bacterial composition and inferring function profiles in the biofloc system rearing Litopenaeus vannamei postlarvae at a low salinity
Authors: Huang Hai-Hong , Li Chao-Yun , Lei Yan-Ju , Kuang Wei-Qi , Zou Wan-Sheng , Yang Pin-Hong 
Published: January 2022

AbstractThis study aimed to investigate the bacterial composition and inferring function profiles in the biofloc system rearing Litopenaeus vannamei postlarvae (PL) at a low salinity condition. PL (~ stage 15) were stocked in four parallel tanks filled in water with a salinity of 5.0‰ at a density of 4000 individuals per m3 for a 28-days culture experiment, during which glucose was added as carbon source with a C:N of 20:1. At the end of experiment, water was sampled from each tank and pooled to extract microbial DNA for high-throughput sequencing of V3-V4 region of 16S rRNA gene. Results showed that the bacterial community at 28 d was dominated by phyla of Proteobacteria (45.8%), Bacteroidetes (21.1%), Planctomycetes (13.5%), Chlamydiae (10.3%) and Firmicutes (6.8%). A proportion of 81% inferring KEGG functions of this bacterial community associated with metabolism. Among functions relating to nitrogen metabolism, 48.5% were involved in the conversion of ammonia to glutamate, but the proportion of those involved in transformation among ammonia, nitrite and nitrate was 18.0% in total, inferring higher protein-synthesis but lower inorganic nitrogen-transformation capacities of the bacterial community. At the same time (28 d), high levels of total nitrogen (231.3±6.0 mg L-1) and biofloc (127.0±63.0 mL L-1), but low concentrations of ammonia (0.04±0.01 mg L-1), nitrite (0.2±0.1 mg L-1) and nitrate (12.9±2.5 mg L-1) were observed. The results supply a novel insight for understanding the function of bacterial community in the biofloc system nursing L. vannamei PL at a low salinity.
Cooperative regulation of C1-domain membrane recruitment polarizes atypical Protein Kinase C
Authors: Jones Kimberly A. , Drummond Michael L. , Penkert Rhiannon R. , Prehoda Kenneth E. 
Published: January 2022

AbstractRecruitment of the Par complex protein atypical Protein Kinase C (aPKC) to a specific membrane domain is a key step in the polarization of animal cells. While numerous proteins and phospholipids interact with aPKC, how these interactions cooperate to control its membrane recruitment has been unknown. Here we identify aPKC’s C1 domain as a phospholipid interaction module that targets aPKC to the membrane ofDrosophilaneural stem cells (NSCs). The isolated C1 binds the NSC membrane in an unpolarized manner during interphase and mitosis and is uniquely sufficient among aPKC domains for targeting. Other domains, including the catalytic module and those that bind the upstream regulators Par-6 and Bazooka, restrict C1’s membrane targeting activity – spatially and temporally – to the apical NSC membrane during mitosis. Our results suggest that aPKC polarity results from cooperative activation of autoinhibited C1-mediated membrane binding activity.
Development, Structure, and Mechanism of Synthetic Antibodies that Target Claudin and Clostridium perfringens Enterotoxin Complexes
Authors: Orlando Benjamin J. , Dominik Pawel K. , Roy Sourav , Ogbu Chinemerem , Erramilli Satchal K. , Kossiakoff Anthony A. , Vecchio Alex J. 
Published: January 2022

ABSTRACTStrains of the Gram-positive bacterium Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflict millions of humans and domesticated animals annually by causing prevalent gastrointestinal illnesses. CpE’s C-terminal domain (cCpE) binds cell surface receptors then its N-terminal domain restructures to form a membrane-penetrating β-barrel pore, which is toxic to epithelial cells of the gut. The claudin family of membrane proteins are the receptors for CpE, and also control the architecture and function of cell/cell contacts called tight junctions that create barriers to intercellular transport of solutes. CpE binding disables claudin and tight junction assembly and induces cytotoxicity via β-pore formation, disrupting gut homeostasis. Here, we aimed to develop probes of claudin/CpE assembly using a phage display library encoding synthetic antigen-binding fragments (sFabs) and discovered two that bound complexes between human claudin-4 and cCpE. We established each sFab’s unique modes of molecular recognition, their binding affinities and kinetics, and determined structures for each sFab bound to ~35 kDa claudin-4/cCpE in three-protein comprised complexes using cryogenic electron microscopy (cryoEM). The structures reveal a recognition epitope common to both sFabs but also that each sFab distinctly conforms to bind their antigen, which explain their unique binding equilibria. Mutagenesis of antigen/sFab interfaces observed therein result in further binding changes. Together, these findings validate the structures and uncover the mechanism of targeting claudin-4/cCpE complexes by these sFabs. Based on these structural insights we generate a model for CpE’s cytotoxic claudin-bound β-pore that predicted that these two sFabs would not prevent CpE cytotoxicity, which we verify in vivo with a cell-based assay. This work demonstrates the development and targeting mechanisms of sFabs against claudin/cCpE that enable rapid structural elucidation of these small membrane protein complexes using a cryoEM workflow. It further provides a structure-based framework and therapeutic strategies for utilizing these sFabs as molecular templates to target claudin/CpE assemblies, obstruct CpE cytotoxicity, and treat CpE-linked gastrointestinal diseases that cause substantial economic and quality of life losses throughout the world.
Role of vegetation characteristics on the distribution of three hornbill species in and around Pakke Tiger Reserve, Arunachal Pradesh, India
Authors: Dasgupta Soumya , Bhattacharya Tapajit , Kaul Rahul 
Published: January 2022

AbstractThe relationship between various vegetation characteristics and the relative abundance of three hornbill species [Great Pied Hornbill (Buceros bicornis), Wreathed Hornbill (Rhyticeros undulatus) and Oriental Pied Hornbill (Anthracoceros albirostris)] was studied in and around Pakke Tiger Reserve, Arunachal Pradesh. We walked transects (n=11; 22 walks) in three study sites to detect hornbills. Vegetation sampling was done using circular plots (n=33; 10 m radius) at every 400m interval along each transect. Encounter rate (1.5± 0.188/km) of Great Pied Hornbill (Buceros bicornis) was highest in the protected and undisturbed forest area where food and roosting tree density were also high (114/ha). Oriental Pied Hornbill was common in both the sites within Pakke Tiger reserve near riverine forests (0.75±0.25/km) and also in the dense undisturbed forest (0.875±0.226/km). Multivariate analysis revealed that tree density, presence of fruiting trees (utilized by hornbills), canopy cover, and tree diversity in a particular area are the major factors responsible for the assemblage of more than one species of hornbills. The study shows that protection of the forest patches to keep the diversity and density of the tree species intact is crucial for the survival and distribution of the hornbills in the landscape.