bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of the protochromic green/red photocycle of the chromatic acclimation sensor RcaE
Authors: Nagae Takayuki , Unno Masashi , Koizumi Taiki , Miyanoiri Yohei , Fujisawa Tomotsumi , Masui Kento , Kamo Takanari , Wada Kei , Eki Toshihiko , Ito Yutaka , Hirose Yuu , Mishima Masaki 
Published: December 2020

AbstractCyanobacteriochromes (CBCRs) are bilin-binding photosensors of the phytochrome superfamily that show remarkable spectral diversity. The green/red CBCR subfamily is important for regulating chromatic acclimation of photosynthetic antenna in cyanobacteria and is applied for optogenetic control of gene expression in synthetic biology. They are suggested to combine the bilin C15-Z/C15-Ephotoisomerization with a change in the bilin protonation state to drive their absorption changes. However, structural information and direct evidence of the bilin protonation state are lacking. Here we report a high-resolution (1.63Å) crystal structure of the bilin-binding domain of the chromatic acclimation sensor RcaE in the red-absorbing photoproduct state. The bilin is buried within a “pan” consisting of hydrophobic residues, where the bilin configuration/conformation is C5-Z,syn/C10-Z,syn/C15-E,synwith the A–C rings co-planar and the D-ring tilted. Three pyrrole nitrogens of the A–C rings are covered in the α-face with a hydrophobic lid of Leu249 influencing the bilin pKa, whereas they are directly hydrogen-bonded in the β-face with the carboxyl group of Glu217. Glu217 is further connected to a cluster of waters forming a hole in the pan, which are in exchange with solvent waters in molecular dynamics simulation. We propose that the “holey pan” structure functions as a proton-exit/influx pathway upon photoconversion. NMR analysis demonstrated that the four pyrrole nitrogen atoms are indeed fully protonated in the red-absorbing state, but one of them, most likely the B-ring nitrogen, is deprotonated in the green-absorbing state. These findings deepen our understanding of the diverse spectral tuning mechanisms present in CBCRs.Significance StatementGreen/red CBCRs are one of the most important CBCR subfamilies owing to their physiological roles in cyanobacteria phylum and optogenetic applications. They are known to utilize a change in the bilin protonation state to drive the marked change in green/red absorption, but the structural basis of the protochromic green/red photocycle are not well understood. Here, we have determined the crystal structure of the chromatic acclimation sensor RcaE of this subfamily in the photoproduct state, demonstrating a unique conformation of the bilin and its interacting residues. In addition, we provide direct evidence of the protonation state of the bilin via NMR analysis. These findings bring insight to our understanding of the molecular mechanisms underlying the spectral diversity of CBCRs.
Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses
Authors: Tan Cedric C.S. , Owen Christopher J. , Tham Christine Y.L. , Bertoletti Antonio , van Dorp Lucy , Balloux Francois 
Published: December 2020

AbstractSeveral studies have reported the presence of pre-existing humoral or cell-mediated cross-reactivity to SARS-CoV-2 peptides in healthy individuals unexposed to SARS-CoV-2. In particular, the current literature suggests that this pre-existing cross-reactivity could, in part, derive from prior exposure to ‘common cold’ endemic human coronaviruses (HCoVs). In this study, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the entire diversity of theCoronaviridaefamily. Slightly over half (54.8%) of the tested epitopes did not have noticeable homology to any of the human endemic coronaviruses (HKU1, OC43, NL63 and 229E), suggesting prior exposure to these viruses cannot explain the full cross-reactive profiles observed in healthy unexposed individuals. Further, we find that the proportion of cross-reactive SARS-CoV-2 epitopes with noticeable sequence homology is extremely well predicted by the phylogenetic distance to SARS-CoV-2 (R2= 96.6%). None of the coronaviruses sequenced to date showed a statistically significant excess of T-cell epitope homology relative to the proportion of expected random matches given the sequence similarity of their core genome to SARS-CoV-2. Taken together, our results suggest that the repertoire of cross-reactive epitopes reported in healthy adults cannot be primarily explained by prior exposure to any coronavirus known to date, or any related yet-uncharacterised coronavirus.
DIAproteomics: A multi-functional data analysis pipeline for data-independent-acquisition proteomics and peptidomics
Authors: Bichmann Leon , Gupta Shubham , Rosenberger George , Kuchenbecker Leon , Sachsenberg Timo , Alka Oliver , Pfeuffer Julianus , Kohlbacher Oliver , Röst Hannes 
Published: December 2020

ABSTRACTData-independent acquisition (DIA) is becoming a leading analysis method in biomedical mass spectrometry. Main advantages include greater reproducibility, sensitivity and dynamic range compared to data-dependent acquisition (DDA). However, data analysis is complex and often requires expert knowledge when dealing with large-scale data sets. Here we present DIAproteomics a multi-functional, automated high-throughput pipeline implemented in Nextflow that allows to easily process proteomics and peptidomics DIA datasets on diverse compute infrastructures. Central components are well-established tools such as the OpenSwathWorkflow for DIA spectral library search and PyProphet for false discovery rate assessment. In addition, it provides options to generate spectral libraries from existing DDA data and carry out retention time and chromatogram alignment. The output includes annotated tables and diagnostic visualizations from statistical post-processing and computation of fold-changes across pairwise conditions, predefined in an experimental design. DIAproteomics is open-source software and available under a permissive license to the scientific community athttps://www.openms.de/diaproteomics/.
A broadly resolved molecular phylogeny of New Zealand cheilostome bryozoans as a framework for hypotheses of morphological evolution
Authors: Orr RJS , Di Martino E , Gordon DP , Ramsfjell MH , Mello HL , Smith AM , Liow LH 
Published: December 2020

AbstractLarger molecular phylogenies based on ever more genes are becoming commonplace with the advent of cheaper and more streamlined sequencing and bioinformatics pipelines. However, many groups of inconspicuous but no less evolutionarily or ecologically important marine invertebrates are still neglected in the quest for understanding species- and higher-level phylogenetic relationships. Here, we alleviate this issue by presenting the molecular sequences of 165 cheilostome bryozoan species from New Zealand waters. New Zealand is our geographic region of choice as its cheilostome fauna is taxonomically, functionally and ecologically diverse, and better characterized than many other such faunas in the world. Using this most taxonomically broadly-sampled and statistically-supported cheilostome phylogeny comprising 214 species, when including previously published sequences, we tested several existing systematic hypotheses based solely on morphological observations. We find that lower taxonomic level hypotheses (species and genera) are robust while our inferred trees did not reflect current higher-level systematics (family and above), illustrating a general need for the rethinking of current hypotheses. To illustrate the utility of our new phylogeny, we reconstruct the evolutionary history of frontal shields (i.e., a calcified bodywall layer in ascus-bearing cheilostomes) and asked if its presence has any bearing on the diversification rates of cheilostomes.
HDLs extract lipophilic drugs from cells
Authors: Zheng Adi , Dubuis Gilles , Ferreira Carla Susana Mendes , Mercier Thomas , Decosterd Laurent , Widmann Christian 
Published: December 2020

AbstractHigh-density lipoproteins (HDLs) prevent cell death induced by a variety of cytotoxic drugs. The underlying mechanisms are however still poorly understood. Here we present evidence that HDLs efficiently protect cells against thapsigargin (a SERCA inhibitor) by extracting the drug from cells. Drug efflux could also be triggered to some extent by low-density lipoproteins (LDLs) and serum, which contains lipoproteins. HDLs did not reverse the non-lethal mild endoplasmic reticulum (ER) stress response induced by low thapsigargin concentrations or by SERCA knock-down but HDLs inhibited the toxic SERCA-independent effects mediated by high thapsigargin concentrations. HDLs were also found to extract other lipophilic compounds, such as the anti-diabetic drug glibenclamide. In contrast, hydrophilic substances (doxorubicin hydrochloride, rhodamine 123) were not extracted from cells by HDLs. This work shows that HDLs utilize their capacity of loading themselves with lipophilic compounds, akin to their ability to extract cellular cholesterol, to reduce the cell content of hydrophobic drugs. Silencing of the P-glycoprotein/ABCB1 transporter reduced the capacity of cells to load thapsigargin on HDLs. This work suggests that HDL-mediated cell efflux of toxic lipophilic xenobiotic is beneficial but also that HDL-mediated efflux can be detrimental to the therapeutic benefit of lipophilic drugs such as glibenclamide. Lipoprotein-mediated drug efflux should therefore be considered when evaluating drug efficacy.
Genomic analyses reveal FoxG as an upstream regulator ofwnt1required for posterior identity specification in planarians
Authors: Pascual-Carreras E. , Marín-Barba M. , Castillo-Lara S. , Coronel-Córdoba P. , Magri M.S. , Wheeler G.N. , Abril J.F. , Gomez-Skarmeta J.L. , Saló E. , Adell T. 
Published: December 2020

AbstractEmbryonic specification of the first body axis requires the formation of an Organizer, a group of cells with the ability to instruct fates in the surrounding tissue. The existence of organizing regions in adults, i.e. during regeneration, which also requires patterning of new tissues, remains unstudied. To that aim, we study regeneration in planarians, flatworms that can regenerate any missing structure, even the head, in a few days. In planarians, as described in embryonic models, the cWNT pathway specifies the anterior-posterior axis. During the first 12-24h after amputation bothwnt1andnotum(a Wnt inhibitor) are expressed in any wound, but 48 hours later they become restricted to posterior or anterior facing wounds, forming the anterior and the posterior organizers, respectively. In this study we undertook a genomic approach to further understand the mechanism that triggers the early expression ofwnt1and the specification of the posterior identity. Through ATAC-sequencing and CHIPmentation techniques we uncovered Cis-Regulatory Elements ofSchmidtea mediterraneagenome and analyzed them innotumandwnt1(RNAi) animals. The result shows that already at 12 hours after amputation the chromatin structure of the wounds has changed its conformation according to the polarity of the pre-existing tissue. Analysing the DNA binding motives present in the proximal regulatory regions of genes down-regulated afterwnt1(RNAi) we found a few genes containing a TCF binding site, which include posterior Homeobox genes and chromatin remodelling proteins, suggesting that those are direct targets of the cWNT pathway and the responsible to trigger the expression of the posterior effectors. Furthermore, we have identified FoxG as an up-stream regulator ofwnt1transcription, probably though binding to an enhancer found in its first intron. Silencing offoxGinhibits the early phase ofwnt1expression and phenocopies thewnt1(RNAi) phenotype, indicating its early role in specifying posteriorversusanterior identity. Moreover, we have created a new open platform to interpret all transcriptomic and genomic results obtained (https://compgen.bio.ub.edu/PlanNET/planexp).
Pathway to Validate Gene Function in Key Bioenergy Crop,Sorghum bicolor
Authors: Aregawi K , Shen J , Pierroz G , Bucheli C , Sharma M , Dahlberg J , Owiti J , Lemaux PG 
Published: December 2020

AbstractDetermining gene function is an essential goal for the key bioenergy crop,Sorghum bicolor(L.) Moench - particularly for genes associated with its notable abiotic stress tolerances. However, detailed molecular understanding of the genes associated with those traits is limited. This was made clear in our in-depth transcriptome studies in sorghum, which indicated nearly 50% of its transcriptome is not annotated. In this report, we describe a full spectrum of tools needed to transform sorghum in order to validate and annotate genes. Efforts began with modifying a transformation method that uses the morphogenic genesBaby BoomandWuschel2(Ovule Development Protein2) to accelerate transformation speed and expand amenable genotypes. In our experience, transforming RTx430 without morphogenic genes requires ~18 to 21 weeks, compared with ~10 to 12 weeks to generate T0plants using methods with morphogenic genes. Utilizing morphogenic genes also allowed for the transformation of several sorghum genotypes not previously transformed or historically recalcitrant to transformation, i.e., rapid cycling SC187, stay-green BTx642, BTx623 and sweet sorghum Ramada. In order to validate candidate genes via engineering, while simultaneously introducing the morphogenic genes, a co-transformation strategy, termed altruistic transformation, was developed. To accomplish editing of the target gene, phytoene desaturase, novel constructs were created that also included morphogenic genes. To enable full characterization of transformed plants, we adapted techniques to determine copy number and independence of events at high-throughput levels. Through these efforts, we created a complete pathway from Agrobacterium infection to high-throughput molecular genotyping that can be used to ascertain gene function and expedite basic genetic research in this widely-grown bioenergy crop plant.
Microglia orchestrate neuronal activity in brain organoids
Authors: Fagerlund Ilkka , Dougalis Antonios , Shakirzyanova Anastasia , Gómez-Budia Mireia , Konttinen Henna , Ohtonen Sohvi , Feroze Fazaludeen , Koskuvi Marja , Kuusisto Johanna , Hernández Damián , Pebay Alice , Koistinaho Jari , Lehtonen Sarka , Korhonen Paula , Malm Tarja 
Published: December 2020

AbstractHuman stem cell-derived brain organoids provide a physiologically relevantin vitro3D brain model for studies of neurological development that are unique to the human nervous system. Prior studies have reported protocols that support the maturation of microglia from mesodermal progenitors leading to innately developing microglia within the organoids. However, although microglia are known to support neuronal development in rodents, none of the previous studies have reported what is the impact of microglia on neuronal growth and maturation in human brain organoids. Here we show that incorporating microglial progenitors into the developing organoid supports neuronal maturation, the emergence of neurons capable of firing repetitive action potentials and the appearance of synaptic and neuronal bursting activity. Immunocompetent organoids enable experimental strategies for interrogating fundamental questions on microglial and neuronal diversity and function during human brain development.
Bioluminescence and fluorescence of three sea pens in the north-west Mediterranean sea
Authors: Francis Warren R , de Vilar Anaïs Sire 
Published: December 2020

AbstractBioluminescence of Mediterranean sea pens has been known for a long time, but basic parameters such as the emission spectra are unknown. Here we examined bioluminescence in three species of Pennatulacea,Pennatula rubra, Pteroeides griseum, andVeretillum cynomorium. Following dark adaptation, all three species could easily be stimulated to produce green light. All species were also fluorescent, with bioluminescence being produced at the same sites as the fluorescence. The shape of the fluorescence spectra indicates the presence of a GFP closely associated with light production, as seen inRenilla. Our videos show that light proceeds as waves along the colony from the point of stimulation for all three species, as observed in many other octocorals. Features of their bioluminescence are strongly suggestive of a “burglar alarm” function.
Mysterious disappearances of a large mammal in Neotropical forests
Authors: Fragoso J.M.V. , Antunes A.P. , Altrichter M. , Constantino P.A.L. , Zapata-Ríos G. , Camino M. , de Thoisy B. , Wallace R.B. , El Bizri H.R. , Morcatty T.Q. , Mayor P. , Richard-Hansen C. , Hallett M.T. , Reyna-Hurtado R.A. , Beck H. , de Bustos S. , Bodmer R.E. , Keuroghlian A. , Nava A. , Montenegro O.L. , Painkow Neto E. , Desbiez A.L.J. , Silvius K.M. 
Published: December 2020

SummaryThe drivers of periodic population cycling by some animal species in northern systems remain unresolved1. Mysterious disappearances of populations of the Neotropical, herdforming white-lipped peccary (Tayassu pecari, henceforth “WLP”) have been anecdotally documented and explained as local events resulting from migratory movements or overhunting2,3,4, or as disease outbreaks5,6, and have not been considered in the context of large-scale species-specific population dynamics. Here we present evidence that WLP disappearances represent troughs in population cycles that occur with regular periodicity and are synchronized at regional and perhaps continent-wide spatial scales. Analysis of 43 disappearance events and 88 years of commercial and subsistence harvesting data reveals boom – bust population cycles lasting from 20 to 30 years, in which a rapid population crash occurring over 1 to 5 years is followed by a period of absence of 7 to12 years and then a slow growth phase. Overhunting alone cannot explain the crashes, but as in northern systems dispersal during the growth phase appears to play a key role. This is the first documentation of population cycling in a tropical vertebrate.
Intranasal administration of SARS-CoV-2 neutralizing human antibody prevents infection in mice
Authors: Zhang Hongbing , Yang Zhiyuan , Xiang Jingyi , Cui Ziyou , Liu Jianying , Liu Cheng 
Published: December 2020

AbstractPrevention of SARS-CoV-2 infection at the point of nasal entry is a novel strategy that has the potential to help contain the ongoing pandemic. Using our proprietary technologies, we have engineered a human antibody that recognizes SARS-CoV-2 S1 spike protein with an enhanced affinity for mucin to improve the antibody’s retention in respiratory mucosa. The modified antibody, when administered into mouse nostrils, was shown to block infection in mice that were exposed to high titer SARS-CoV-2 pseudovirus 10 hours after the initial antibody treatment. Our data show that the protection against SARS-CoV-2 infection is effective in both nasal and lung areas 7 days after viral exposure. The modified antibody is stable in a nasal spray formulation and maintains its SARS-CoV-2 neutralizing activity. Nasal spray of the modified antibody can be developed as an affordable and effective prophylactic product to protect people from infection by exposure to SARS-CoV-2 virus in the air.One-sentence summaryA Fc-modified human antibody prevents SARS-CoV-2 viral infection via nasal administration
Mechanisms for Communicating in a Marmoset ‘Cocktail Party’
Authors: Jovanovic Vladimir , Miller Cory T 
Published: December 2020

AbstractA fundamental challenge for audition is parsing the voice of a single speaker amid a cacophony of other voices known as the Cocktail Party Problem (CPP). Despite its prevalence, relatively little remains known about how our simian cousins solve the CPP for active, natural communication. Here we employed an innovative, multi-speaker paradigm comprising five computer-generated Virtual Monkeys (VM) whose respective vocal behavior could be systematically varied to construct marmoset cocktail parties and tested the impact of specific acoustic scene manipulations on vocal behavior. Results indicate that marmosets not only employ auditory mechanisms – including attention – for speaker stream segregation, but also selectively change their own vocal behavior in response to the dynamics of the acoustic scene to overcome the challenges of the CPP. These findings suggest notable parallels between human and nonhuman primate audition and highlight the active role that speakers play to optimize communicative efficacy in complex real-world acoustic scenes.
Making the Most of Potential: Potential Games and Genotypic Convergence
Authors: Edhan OMER , Hellman ZIV , Nehama ILAN 
Published: December 2020

AbstractWe consider genotypic convergence of populations and show that under fixed fitness asexual and haploid sexual populations attain monomorphic convergence (even under genetic linkage between loci) to basins of attraction with locally exponential convergence rates; the same convergence obtains in single locus diploid sexual reproduction but to polymorphic populations. Furthermore, we show that there is a unified underlying theory underlying these convergences: all of them can be interpreted as instantiations of players in a potential game implementing a multiplicative weights updating algorithm to converge to equilibrium, making use of the Baum–Eagon Theorem. To analyse varying environments, we introduce the concept of ‘virtual convergence’, under which, even if fixation is not attained, the population nevertheless achieves the fitness growth rate it would have had under convergence to an optimal genotype. Virtual convergence is attained by asexual, haploid sexual, and multi-locus diploid reproducing populations, even if environments vary arbitrarily. We also study conditions for true monomorphic convergence in asexually reproducing populations in varying environments.
Structure of Human BCCIP and Implications for Binding and Modification of Partner Proteins
Authors: Choi Woo Suk , Liu Bochao , Shen Zhiyuan , Yang Wei 
Published: December 2020

AbstractBCCIP was isolated based on its interactions with tumor suppressors BRCA2 and p21. Knockdown or knockout of BCCIP causes embryonic lethality in mice. BCCIP deficient cells exhibit impaired cell proliferation and chromosome instability. BCCIP also plays a key role in biogenesis of ribosome 60S subunits. BCCIP is conserved from yeast to humans, but it has no discernible sequence similarity to proteins of known structures. Here we report two crystal structures of an N-terminal truncated human BCCIPβ, consisting of residues 61-314. Structurally BCCIP is similar to GCN5-related acetyltransferases (GNATs) but contains different sequence motifs. Moreover, both acetyl-CoA and substrate-binding grooves are altered in BCCIP. A large 19-residue flap over the putative CoA binding site adopts either an open or closed conformation in BCCIP. The substrate binding groove is significantly reduced in size and is positively charged despite the acidic isoelectric point of BCCIP. BCCIP has potential binding sites for partner proteins and may have enzymatic activity.