bluuebunny/crossref_metadata_2025_split huggingface dataset:
LectinOracle – A Generalizable Deep Learning Model for Lectin-Glycan Binding Prediction
Authors: Lundstrøm Jon , Korhonen Emma , Lisacek Frédérique , Bojar Daniel 
Published: August 2021

AbstractRanging from bacterial cell adhesion over viral cell entry to human innate immunity, glycan-binding proteins or lectins abound in nature. Widely used as staining and characterization reagents in cell biology, and crucial for understanding the interactions in biological systems, lectins are a focal point of study in glycobiology. Yet the sheer breadth and depth of specificity for diverse oligosaccharide motifs has made studying lectins a largely piecemeal approach, with few options to generalize. Here, we present LectinOracle, a model combining transformer-based representations for proteins and graph convolutional neural networks for glycans to predict their interaction. Using a curated dataset of 564,647 unique protein-glycan interactions, we show that LectinOracle predictions agree with literature-annotated specificities for a wide range of lectins. We further identify clusters of lectins with related binding specificity that are not clustered based on sequence similarity. Using a range of specialized glycan arrays, we show that LectinOracle predictions generalize to new glycans and lectins, with qualitative and quantitative agreement with experimental data. We further demonstrate that LectinOracle can analyze whole lectomes and their role in host-microbe interactions. We envision that the herein presented platform will advance both the study of lectins and their role in (glyco)biology.
Interannual climate variability data improves niche estimates in species distribution models
Authors: Karger Dirk Nikolaus , Saladin Bianca , Wüest-Karpati Rafael O. , Graham Catherine H. , Zurell Damaris , Mo Lidong , Zimmermann Niklaus E. 
Published: August 2021

AbstractAimClimate is an essential element of species’ niche estimates in many current ecological applications such as species distribution models (SDMs). Climate predictors are often used in the form of long-term mean values. Yet, climate can also be described as spatial or temporal variability for variables like temperature or precipitation. Such variability, spatial or temporal, offers additional insights into niche properties. Here, we test to what degree spatial variability and long-term temporal variability in temperature and precipitation improve SDM predictions globally.LocationGlobal.Time period1979-2013Major taxa studiesMammal, Amphibians, ReptilesMethodsWe use three different SDM algorithms, and a set of 833 amphibian, 779 reptile, and 2211 mammal species to quantify the effect of spatial and temporal climate variability in SDMs. All SDMs were cross-validated and accessed for their performance using the Area under the Curve (AUC) and the True Skill Statistic (TSS).ResultsMean performance of SDMs with climatic means as predictors was TSS=0.71 and AUC=0.90. The inclusion of spatial variability offers a significant gain in SDM performance (mean TSS=0.74, mean AUC=0.92), as does the inclusion of temporal variability (mean TSS=0.80, mean AUC=0.94). Including both spatial and temporal variability in SDMs shows similarly high TSS and AUC scores.Main conclusionsAccounting for temporal rather than spatial variability in climate improved the SDM prediction especially in exotherm groups such as amphibians and reptiles, while for endotermic mammals no such improvement was observed. These results indicate that more detailed information about temporal climate variability offers a highly promising avenue for improving niche estimates and calls for a new set of standard bioclimatic predictors in SDM research.
Microstructural Properties of Human Brain Revealed by Fractional Anisotropy can Predict the After-effect of Intermittent Theta Burst Stimulation
Authors: Kimura Ikko , Oishi Hiroki , Hayashi Masamichi J , Amano Kaoru 
Published: August 2021

AbstractIntermittent theta burst stimulation (iTBS) delivered by transcranial magnetic stimulation (TMS) produces a long term potentiation (LTP)-like after-effect useful for investigations of cortical function and of potential therapeutic value. However, the iTBS-evoked after-effect over the primary motor cortex (M1) as measured by changes in motor evoked potential (MEP) amplitude exhibits a largely unexplained variability across individuals. Here, we present evidence that individual differences in white and grey matter microstructural properties revealed by fractional anisotropy (FA) predict the magnitude of the iTBS-induced after-effect over M1. The MEP amplitude change in the early phase (5–10 min) post-iTBS was associated with FA values in white matter tracts such as right superior longitudinal fasciculus and corpus callosum. In contrast, the MEP amplitude change in the late phase (15–30 min) post-iTBS was associated with FA in grey matter, primarily in right frontal cortex. These results suggest that the microstructural properties of regions connected directly or indirectly to the target region (M1) are crucial determinants of the iTBS after-effect. FA values indicative of these microstructural differences can predict the potential effectiveness of rTMS for both investigational use and clinical application.
Mutationathon: towards standardization in estimates of pedigree-based germline mutation rates
Authors: Bergeron Lucie A. , Besenbacher Søren , Turner Tychele N. , Versoza Cyril J. , Wang Richard J. , Price Alivia Lee , Armstrong Ellie , Riera Meritxell , Carlson Jedidiah , Chen Hwei-yen , Hahn Matthew W. , Harris Kelley , Snøfrid Lo Natalie M Kleppe April , López-Nandam Elora H. , Moorjani Priya , Pfeifer Susanne P. , Tiley George P. , Yoder Anne D. , Zhang Guojie , Schierup Mikkel H. 
Published: August 2021

AbstractIn the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various non-human species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and how to appropriately account for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a “Mutationathon”, a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a two-fold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees.
Evidence for Free Radical Drug Ligands in class A G-protein Coupled Receptors
Authors: Gehrckens Angela S , Horsfield Andrew P , Skoulakis Efthimios M C , Turin Luca 
Published: August 2021

AbstractWe analyse the conformation of 22 cationic ligands bound to G-protein coupled receptors of known structure and find three ligands that are present inside receptors not in their closed shell cation form, but as neutral radicals, i.e. after addition of an electron to the ligand. The implications of this finding for GPCR function are discussed and a possible experimental test is proposed.
A Jacalin-like lectin-domain-containing protein of Sclerospora graminicola act as an apoplastic virulence effector in plant–oomycete interactions
Authors: Kobayashi Michie , Utsushi Hiroe , Fujisaki Koki , Takeda Takumi , Yamashita Tetsuro , Terauchi Ryohei 
Published: August 2021

SUMMARYThe plant extracellular space, including the apoplast and plasma membrane, is the initial site of plant– pathogen interactions. Pathogens deliver numerous secreted proteins, called effectors, into this region to suppress plant immunity and establish infection. Downy mildew caused by the oomycete pathogen Sclerospora graminicola (Sg) is an economically important disease of Poaceae crops including foxtail millet (Setaria italica). We previously reported the genome sequence of Sg and showed that the Jacalin-related lectin (JRL) gene family has significantly expanded in this lineage. However, the biological functions of JRL proteins remained unknown. Here, we show that JRL from S. graminicola (SgJRL) functions as an apoplastic virulence effector. We identified eight SgJRLs via protein mass spectrometry analysis of extracellular fluid from S. graminicola-inoculated foxtail millet leaves. SgJRLs consist of a Jacalin-like lectin domain and an N-terminal putative secretion signal, and SgJRL expression is induced by Sg infection. Heterologous expression of three SgJRLs with N-terminal secretion signal peptides in Nicotiana benthamiana enhanced the virulence of the pathogen Phytophthora palmivora inoculated onto the same leaves. Of the three SgJRLs, SG06536 fused with GFP localized to the apoplastic space in N. benthamiana leaves. INF1-mediated induction of defense-related genes was suppressed by co-expression of SG06536-GFP. These findings suggest that JRLs are novel apoplastic effectors that contribute to pathogenicity by suppressing plant defense responses.
Intrinsic variation in the vertically transmitted insect-specific core virome of Aedes aegypti
Authors: Coatsworth H. , Bozic J , Carrillo J. , Buckner E.A. , Rivers A.R. , Dinglasan R.R. , Mathias D.K. 
Published: August 2021

AbstractSince 2009, local outbreaks of dengue (serotypes 1-3) mediated by Aedes aegypti mosquitoes have occurred in the United States, particularly in Florida (FL). In 2016 and 2017, dengue virus serotype 4 was found alongside several insect-specific viruses (ISVs) in pools of A. aegypti from sites in Manatee County, FL, in the absence of an index case. Although ISVs have been characterized in A. aegypti globally, the constitution of a core virome in natural populations remains unclear. Using mosquitoes sampled from the same area in 2018, we compared baseline ovary viromes of field (G0) and lab (Orlando) A. aegypti via metagenomic RNA sequencing. Across all samples, virome composition varied by sample type (field- or colony-derived). Four ISVs comprised >97% of virus sequences: a novel partiti-like virus (Partitiviridae), a previously described toti-like virus (Totiviridae), unclassified Riboviria, and four previously described orthomyxo-like viruses (Orthormyxoviridae). Whole or partial genomes for the toti-like virus, partiti-like virus, and one orthomyxo-like virus were assembled and analyzed phylogenetically. Multigenerational maintenance of these ISVs was confirmed orthogonally by RT-PCR in G0 and G7 mosquitoes, indicating vertical transmission as the mechanism for ISV sustentation. This study provides fundamental information regarding ISV ecology, persistence, and variation in A. aegypti in nature.
The B chromosome of Pseudococcus viburni: a selfish chromosome that exploits whole-genome meiotic drive
Authors: Vea Isabelle M. , de la Filia Andrés G. , Jaron Kamil S. , Mongue Andrew J. , Ruiz-Ruano Francisco J. , Barlow Scott E.J , Nelson Ross , Ross Laura 
Published: August 2021

AbstractMeiosis, the key process underlying sexual reproduction, is generally a fair process: each chromosome has a 50% chance of being included into each gamete. However in some organisms meiosis has become highly aberrant with some chromosomes having a higher chance of making it into gametes than others. Yet why and how such systems evolve remains unclear. Here we study the unusual reproductive genetics of mealybugs, in which only maternal-origin chromosomes are included into the gametes during male meiosis, while paternally-derived chromosomes degrade. This “whole genome meiotic drive” occurs in all males and is evolutionarily conserved. However one species - the obscure mealybug Pseudococcus viburni - has a segregating B chromosome that increases in frequency by escaping paternal genome elimination. Here we present whole-genome and gene expression data from laboratory lines with and without B chromosomes. These data allow us to identify B-linked sequences including >70 protein-coding genes as well as a B-specific satellite repeat that makes up a significant proportion of the chromosome. We also used these data to investigate the evolutionary origin of the B chromosome. The few paralogs between the B and the core genome are distributed throughout the genome, showing that it is unlikely that the B originated through a simple duplication of one of the autosomes. We also find that while many of the B-linked genes do not have paralogs within the P.viburni genome, but they do show orthology with genes in other hemipteran insects suggesting that the B might have originated from fission of one of the autosomes, possibly followed by further translocations of individual genes. Finally in order to understand the mechanisms by which the B is able to escape elimination when paternally-derived we generated gene expression data for males and females with and without B chromosomes. We find that at the developmental stage when meiosis is taking place only a small number of B-linked genes show significant expression. Only one gene was significantly over-expressed during male meiosis, which is when the drive occurs: a acetyltransferase involved in H3K56Ac, which has a putative role in meiosis and is therefore a promising candidate for further studies. Together, these results form a promising foundation for studying the mechanisms of meiotic drive in a system that is uniquely suited for this approach.
HIF-1α stabilization modified by glutaredoxin-1 is critical for intestinal angiogenesis in NEC pathogenesis
Authors: Zhang Yunfei , Zhang Xiao , Tian Bing , Ding Xionghui , Ye Cuilian , Guo Chunbao 
Published: August 2021

AbstractBackgroundHypoxia inducible factor (HIF-1α) are essential in the pathogenesis of necrotizing enterocolitis (NEC), which is stabilized by Grx1 deletion. Until now, the mechanism of HIF-1α in the intestinal microcirculation in NEC is not well defined. We intend to investigate the role of HIF-1α in the development of NEC in regulating the microcirculation and the following vasodilatory signal, VEGF.Materials and methodsExperimental NEC was induced in full-term C57BL/6 mouse and Grx1-/- pups through the formula gavage and hypoxia technique. The HIF-1α signal was blocked utilizing the HIF-1α inhibitor, YC-1. Intestinal tissues were collected at predetermined time points for the assessment of intestinal microcirculation and the HIF-1α activity involved signal.ResultsWe found that NEC inducement impaired the intestinal microcirculation, but intestinal blood flow and capillary density were ameliorated in Grx1-/- mice, which was associated with the GSH-protein adducts of HIF-1α in the intestinal tissue. Grx1 ablation could also promote vascular endothelial growth factor (VEGFA) production in the intestinal tissue. This intestinal microvascular improvement was not found in the HIF-1α inhibited mice, suggesting the HIF-1α dependent manner for intestinal microcirculatory perfusion.ConclusionThe current data demonstrated that HIF-1α signaling is involved in the intestinal microvascular modification during the pathogenesis of NEC, suggesting that targeting with HIF-1α might be a promising strategy for NEC treatment.
Apropos of Universal Epitope Discovery for COVID-19 Vaccines: A Framework for Targeted Phage Display-Based Delivery and Integration of New Evaluation Tools
Authors: Markosian Christopher , Staquicini Daniela I. , Dogra Prashant , Dodero-Rojas Esteban , Tang Fenny H. F. , Smith Tracey L. , Contessoto Vinícius G. , Libutti Steven K. , Wang Zhihui , Cristini Vittorio , Whitford Paul C. , Burley Stephen K. , Onuchic José N. , Pasqualini Renata , Arap Wadih 
Published: August 2021

AbstractTargeted bacteriophage (phage) particles are potentially attractive yet inexpensive platforms for immunization. Herein, we describe targeted phage capsid display of an immunogenically relevant epitope of the SARS-CoV-2 Spike protein that is empirically conserved, likely due to the high mutational cost among all variants identified to date. This observation may herald an approach to developing vaccine candidates for broad-spectrum, towards universal, protection against multiple emergent variants of coronavirus that cause COVID-19.
Selective cleavage of ncRNA and antiviral activity by human RNase2/EDN in a macrophage infection model
Authors: Lu Lu , Li Jiarui , Wei Ranlei , Guidi Irene , Cozzuto Luca , Ponomarenko Julia , Prats-Ejarque Guillem , Boix Ester 
Published: August 2021

AbstractRNase2, also named the Eosinophil derived Neurotoxin (EDN), is one of the main proteins secreted by the eosinophil secondary granules. RNase2 is also expressed in other leukocyte cells and is the member of the human ribonuclease A family most abundant in macrophages. The protein is endowed with a high ribonucleolytic activity and participates in the host antiviral activity. Although RNase2 displays a broad antiviral activity, it is mostly associated to the targeting of single stranded RNA viruses. To explore RNase2 mechanism of action in antiviral host defence we knocked out RNase2 expression in the THP1 monocyte cell line and characterized the cell response to human Respiratory Syncytial Virus (RSV). We observed that RSV infection induced the RNase2 expression and protein secretion in THP1 macrophage-derived cells, whereas the knockout (KO) of RNase2 resulted in higher RSV burden and reduced cell viability. Next, by means of the cP-RNAseq methodology, which uniquely amplifies the RNA 2’3’cyclic-phosphate-end products released by an endonuclease cleavage, we compared the ncRNA population in native and RNase2-KO cell lines. Among the ncRNAs accumulated in WT versus KO cells, we found mostly tRNA-derived fragments and secondly miRNAs. Analysis of the differential sequence coverage of tRNAs molecules in native and KO cells identified fragments derived from only few parental tRNAs, revealing a predominant cleavage at anticodon loops and secondarily at D-loops. Inspection of cleavage region identified U/C and A, at 5’ and 3’ sides of cleavage sites respectively (namely RNase B1 and B2 base binding subsites). Likewise, only few selected miRNAs were significantly more abundant in WT versus RNase2-KO cells, with cleavage sites located at the end of stem regions with predominance for pyrimidines at B1 but following an overall less defined nucleotide specificity.Complementarily, by screening of a tRF&tiRNA PCR array we identified an enriched population of tRNA-derived fragments associated to RNase2 expression and RSV infection. The present results confirm the contribution of the protein in macrophage response against virus infection and provide the first evidence of its cleavage selectivity against ncRNA population. A better understanding of the mechanism of action of RNase2 recognition of cellular RNA during the antiviral host defence should pave the basis for the design of novel antiviral drugs.
Algal photosystem I dimer and high resolution model of PSI:plastocyanin complex
Authors: Naschberger Andreas , Mosebach Laura , Tobiasson Victor , Kuhlgert Sebastian , Scholz Martin , Perez-Boerema Annemarie , Ho Thi Thu Hoai , Vidal-Meireles Andre , Takahashi Yuichiro , Hippler Michael , Amunts Alexey 
Published: August 2021

AbstractPhotosystem I (PSI) enables photo-electron transfer and regulates photosynthesis in the bioenergetic membranes of cyanobacteria and chloroplasts. Being a multi-subunit complex, its macromolecular organization affects the dynamics of photosynthetic membranes. Here, we reveal a chloroplast PSI from the green alga Chlamydomonas reinhardtii that is organized as a homodimer, comprising 40 protein subunits with 118 transmembrane helices that provide scaffold for 568 pigments. Our cryo-EM structure identifies that the absence of PsaH and Lhca2 gives rise to a head-to-head relative orientation of the PSI-LHCI monomers in a way that is essentially different from the oligomer formation in cyanobacteria. The light-harvesting protein Lhca9 is the key element for mediating this dimerization. The interface between the monomers is lacking PsaH, and thus partially overlaps with the surface area that would bind one of the LHCII complexes in state transitions. We also define the most accurate available PSI-LHCI model at 2.3 Å resolution, including a flexibly bound electron donor plastocyanin, and assign correct identities and orientations of all the pigments, as well as 621 water molecules that affect energy transfer pathways.
Engineering yeast for de-novo synthesis of the insect repellent - nepetalactone
Authors: Davies Meghan E , Tsyplenkov Daniel , Martin Vincent J. J. 
Published: August 2021

ABSTRACTWhile nepetalactone, the active ingredient in catnip, is a potent insect repellent, its low in planta accumulation limits its commercial viability as an alternative repellent. Here we describe a platform for de novo nepetalactone production in Saccharomyces cerevisiae, enabling sustainable and scalable production. Nepetalactone production required introduction of eight exogenous genes including the cytochrome P450 geraniol-8-hydroxylase, which represented the bottleneck of the heterologous pathway. Combinatorial assessment of geraniol-8-hydroxylase and cytochrome P450 reductase variants, as well as copy-number variations were used to overcome this bottleneck. We found that several reductases improved hydroxylation activity, with a higher geraniol-8-hydroxylase ratio further increasing 8-hydroxygeraniol titers. Another roadblock was the accumulation of an unwanted metabolite that implied inefficient channeling of carbon through the pathway. With the native yeast old yellow enzymes previously shown to use monoterpene intermediates as substrates, both homologs were deleted. These deletions increased 8-hydroxygeraniol yield, resulting in a final de novo accumulation of 3.10 mg/L/OD600 of nepetalactone from simple sugar in microtiter plates. Our pathway optimization will aid in the development of high yielding monoterpene S. cerevisiae strains.