bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current sampling and sequencing biases of Lassa mammarenavirus limit inference from phylogeography and molecular epidemiology in Lassa Fever endemic regions
Authors: Arruda Liã Bárbara , Free Hayley Beth , Simons David , Ansumana Rashid , Elton Linzy , Haider Najmul , Honeyborne Isobella , Asogun Danny , McHugh Timothy D , Ntoumi Francine , Zumla Alimuddin , Kock Richard 
Published: June 2023

AbstractLassa fever (LF) is a potentially lethal viral haemorrhagic infection of humans caused byLassa mammarenavirus(LASV). It is an important endemic zoonotic disease in West Africa with growing evidence for increasing frequency and sizes of outbreaks. Phylogeographic and molecular epidemiology methods have projected expansion of the Lassa fever endemic zone in the context of future global change. The Natal multimammate mouse (Mastomys natalensis) is the predominant LASV reservoir, with few studies investigating the role of other animal species. To explore host sequencing biases, all LASV nucleotide sequences and associated metadata available on GenBank (n = 2,298) were retrieved. Most data originated from Nigeria (54%), Guinea (20%) and Sierra Leone (14%). Data from non-human hosts (n = 703) were limited and only 69 sequences encompassed complete genes. We found a strong positive correlation between the number of confirmed human cases and sequences at the country level (r= 0.93 (95% Confidence Interval = 0.71 - 0.98),p< 0.001) but no correlation exists between confirmed cases and the number of available rodent sequences (r= -0.019 (95% C.I. -0.71 - 0.69),p =0.96). Spatial modelling of sequencing effort highlighted current biases in locations of available sequences, with increased effort observed in Southern Guinea and Southern Nigeria. Phylogenetic analyses showed geographic clustering of LASV lineages, suggestive of isolated events of human-to-rodent transmission and the emergence of currently circulating strains of LASV from the year 1498 in Nigeria. Overall, the current study highlights significant geographic limitations in LASV surveillance, particularly, in non-human hosts. Further investigation of the non-human reservoir of LASV, alongside expanded surveillance, are required for precise characterisation of the emergence and dispersal of LASV. Accurate surveillance of LASV circulation in non-human hosts is vital to guide early detection and initiation of public health interventions for future Lassa fever outbreaks.
CLOCI:Unveiling cryptic gene clusters with generalized detection
Authors: Konkel Zachary , Kubatko Laura , Slot Jason C. 
Published: June 2023

ABSTRACTGene clusters are genomic loci that contain multiple genes that are functionally and genetically linked. Gene clusters collectively encode diverse functions, including small molecule biosynthesis, nutrient assimilation, metabolite degradation, and production of proteins essential for growth and development. Identifying gene clusters is a powerful tool for small molecule discovery and provides insight into the ecology and evolution of organisms. Current detection algorithms focus on canonical “core” biosynthetic functions many gene clusters encode, while overlooking uncommon or unknown cluster classes. These overlooked clusters are a potential source of novel natural products and comprise an untold portion of overall gene cluster repertoires. Unbiased,function-agnosticdetection algorithms therefore provide an opportunity to reveal novel classes of gene clusters and more precisely define genome organization. We presentCLOCI(Co-occurrence Locus and Orthologous Cluster Identifier), an algorithm that identifies gene clusters using multiple proxies of selection for coordinated gene evolution. Our approach generalizes gene cluster detection and gene cluster family circumscription, improves detection of multiple known functional classes, and unveils noncanonical gene clusters.CLOCIis suitable for genome-enabled small molecule mining, and presents an easily tunable approach for delineating gene cluster families and homologous loci.
Phantom oscillations in principal component analysis
Authors: Shinn Maxwell 
Published: June 2023

AbstractPrincipal component analysis (PCA) is a dimensionality reduction technique that is known for being simple and easy to interpret. Principal components are often interpreted as low-dimensional patterns in high-dimensional data. However, this simple interpretation of PCA relies on several unstated assumptions that are difficult to satisfy. When these assumptions are violated, non-oscillatory data may have oscillatory principal components. Here, we show that two common properties of data violate these assumptions and cause oscillatory principal components: smooth-ness, and shifts in time or space. These two properties implicate almost all neuroscience data. We show how the oscillations that they produce, which we call “phantom oscillations”, impact data analysis. We also show that traditional cross-validation does not detect phantom oscillations, so we suggest procedures that do. Our findings are supported by a collection of mathematical proofs. Collectively, our work demonstrates that patterns which emerge from high-dimensional data analysis may not faithfully represent the underlying data.
Integration of eQTL and Machine Learning Methods to Dissect Causal Genes with Pleiotropic effects in Genetic Regulation Networks of Seed Cotton Yield
Authors: Zhao Ting , Wu Hongyu , Wang Xutong , Zhao Yongyan , Wang Luyao , Pan Jiaying , Mei Huan , Han Jin , Wang Siyuan , Lu Kening , Li Menglin , Gao Mengtao , Cao Zeyi , Zhang Hailin , Wan Ke , Li Jie , Zhang Tianzhen , Guan Xueying 
Published: June 2023

AbstractExpression quantitative trait loci (eQTL) provide a powerful means of investigating the biological basis of genome-wide association study (GWAS) results and exploring complex traits or phenotypes. In addition to identifying the causal gene incis, eQTL analysis also reveals a large number of trans-regulated genes located on different chromosomes, which form a gene regulatory network (GRN) that complements the GWAS locus. However, the dissection of a GRN and the crosstalk underlying multiple agronomical traits, along with prioritizing important genes in eQTL-derived GRNs, remains a major challenge. In this study, we generated 558 transcriptional profiles of lint-bearing ovules at one day post-anthesis (DPA) from a selective core cotton germplasm, from which we identified 12,207 eQTLs. By integrating with a GWAS catalog, we found that 66 out of 187 (35.29%) known phenotypic GWAS loci are colocalized with 1,090 eQTLs, forming 38 major functional GRNs predominantly (30 out of 38) associated with seed size-related phenotypes. Of the eGenes, 34 were shared between at least two functional GRNs, exhibiting pleiotropic effects, such asNF-YB3,GRDP1, andIDD7. Narrow-sense heritability analysis showed that the heritability increased with combining the eQTLs with GRNs compared to those with previous yield trait GWAS loci. The extreme gradient boosting (XGBoost) machine learning approach was then applied to predict seed cotton yield phenotypes based on gene expression. Top-ranking eGenes (NF-YB3,FLA2, andGRDP1) derived by XGBoost with pleiotropic effects on yield traits were validated, along with their potential roles by correlation analysis, domestication selection analysis, and transgenic plants. This study provides insights into the mining of GRNs in relation to the pleiotropy of phenotype. The combination of eQTL and machine learning approaches is efficient in improving the genetic dissection of agricultural traits.
Group or solitary dispersal: worker presence and number favour the success of colony foundation in ants
Authors: Finand Basile , Loeuille Nicolas , Bocquet Céline , Fédérici Pierre , Monnin Thibaud 
Published: June 2023

ABSTRACTDispersal strategies are highly variable. Any strategy is associated to costs and benefits, and understanding which factors favour or disfavour a strategy is a key issue in ecology and evolution. Ants exhibit different dispersal and colony foundation strategies. Some species have winged queens that disperse solitarily and far by flight, and that found new colonies alone. Others have apterous queens that disperse with workers over short walking distances, and found new colonies as a group (colony fission). The putative benefits conferred by workers have been little studied and quantified, because comparing the costs and benefits of solitary vs. group dispersal and foundation is difficult when comparing different species. We did this using the antMyrmecina graminicola, one of the few species that use both strategies. Young queens were mated and allowed to found new colonies in the laboratory, with either zero, two or four workers. We monitored the survival and growth of foundations over one year. The presence of workers increased both survival and growth, with more workers yielding higher growth. These results show the benefit of dispersing and founding in a group. The presence of few workers (as little as two workers) was sufficient to provide benefits, suggesting group foundation does not require a dramatic decrease in the number of propagules produced inM. graminicola. Our results support the hypothesis that the two strategies coexist along a competition-colonization trade-off, where solitary foundation offers a colonization advantage while group foundation has a competitive advantage.
Opportunistic bacteria of grapevine crown galls are equipped with the genomic repertoire for opine utilization
Authors: Faist Hanna , Ankenbrand Markus J. , Sickel Wiebke , Hentschel Ute , Keller Alexander , Deeken Rosalia 
Published: June 2023

AbstractYoung grapevines (Vitis vinifera) suffer and eventually can die from the crown gall (CG) disease caused by the plant pathogenAllorhizobium vitis (Rhizobiaceae). Virulent members ofA. vitisharbour a tumor-inducing (Ti) plasmid and induce formation of crown galls (CGs) due to the oncogenes encoded on the transfer-DNA (T-DNA). Expression of oncogenes in transformed host cells induce unregulated cell proliferation, metabolic and physiological changes. The CG produces opines uncommon to plants, which provide an important nutrient source forA. vitisharbouring opine catabolism enzymes. CGs host a distinct bacterial community and the mechanisms establishing a CG-specific bacterial community are currently unknown. Thus, we were interested in whether genes homologous to those of the Ti-plasmid coexist in the genomes of the microbial species coexisting in CGs.We isolated eight bacterial strains from grapevine CGs, sequenced their genomes and tested their virulence and opine utilization ability in bioassays. In addition, the eight genome sequences were compared to 34 published bacterial genomes, including closely related plant associated bacteria not from CGs. Homologous genes for virulence and opine anabolism were only present in the virulent Rhizobiaceae. By contrast, homologs of the opine catabolism genes were present in all strains including the non-virulent members of the Rhizobiaceae and non-Rhizobiaceae. Gene neighbourhood and sequence identity of the opine degradation cluster of virulent and non-virulent strains together with the results of the opine utilization assay support the important role of opine utilization for co-colonization in CGs, thereby shaping the CG community.Significance statementVirulentAllorhizobium vitiscauses crown galls on grapevines which reduce plant vigour, yield, and cannot be cured. Non-virulent agrobacteria have been used as biocontrol agents to reduce the virulence potential within a crown gall and disease symptoms. We wanted to know if and how in nature this biocontrol concept is accomplished. We found virulentAllorhizobiumalong with non-virulentAgrobacterium, orPseudomonasin the same tumours. Both harboured the catabolism genes in their genomes and metabolized thequorum sensingmolecule opine. Thus, in nature it seems common that virulent and non-virulent species coexist in a crown gall and that the avirulent members control the virulence potential of the crown gall community by reducing the opine levels.
FSCN1 is critical for HNSCC
Authors: Wei Xin 
Published: June 2023

AbstractBackgroundThe study of molecular markers for diagnosis and prognosis is of great clinical significance for HNSCC patients. In this study, we proposed that FSCN1 has a potential indication for prognosis and is essential for the migration of HNSCC.MethodsWe analyzed the expression and survival association of FSCN1 in HNSCC using TCGA data. We compared the expression of FSCN1 in tumors from primary and metastasis HNSCC patients using QPCR, western blotting, and immunochemistry staining. We determined the migration velocity of multiple HNSCC cell lines using a chemotaxis migration assay. We analyzed the correlation between FSCN1 expression and HNSCC cell migration. We also test the effect of FSCN1 knockdown and overexpression on HNSCC cell migration.ResultsFSCN1 was overexpressed in HNSCC than pair normal tissues and metastasis HNSCC than primary HNSCC. FSCN1 expression was associated with significantly poorer overall survival of HNSCC patients. FSCN1 was potentially associated with immune cell infiltration and migration-associated genes. FSCN1 level was correlated with the migration in HNSCC cell lines. Knockdown of FSCN1 reduced the migration and the overexpression of FSCN1 promoted the migration of HNSCC cell lines.ConclusionFSCN1 is a potential prognostic marker and a critical biomolecule for the migration of HNSCC
Accommodation and wavelength: the effect of longitudinal chromatic aberration on the stimulus-response curve
Authors: Fernandez-Alonso Maydel , Finch Abigail P. , Love Gordon D. , Read Jenny C. A. 
Published: June 2023

AbstractThe longitudinal chromatic aberration (LCA) of the eye creates a chromatic blur on the retina that is an important cue for accommodation. While this mechanism can work optimally in broadband illuminants such as daylight, it is not clear how the system responds to the narrowband illuminants used by many modern displays. Here, we measured pupil and accommodative responses as well as visual acuity under narrowband LED illuminants of different peak wavelengths. Observers were able to accommodate under narrowband light and compensate for the LCA of the eye, with no difference in the variability of the steady-state accommodation response between narrowband and broadband illuminants. Intriguingly, our subjects compensated more fully for LCA at nearer distances. That is, the difference in accommodation to different wavelengths became larger when the object was placed nearer the observer, causing the slope of the accommodation response curve to become shallower for shorter wavelengths and steeper for longer ones. Within the accommodative range of observers, accommodative errors were small and visual acuity normal. When comparing between illuminants, when accommodation was accurate, visual acuity was worst for blue narrowband light. This cannot be due to the sparser spacing for S-cones, since our stimuli had equal luminance and thus activated M-cones roughly equally. It is likely because ocular LCA changes more rapidly at shorter wavelength, and so the finite spectral bandwidth of LEDs corresponds to a greater dioptric range at shorter wavelengths. This effect disappears for larger accommodative errors, due to the increased depth-of-focus of the eye.
The impact of ROI extraction method for MEG connectivity estimation: practical recommendations for the study of resting state data
Authors: Brkić Diandra , Sommariva Sara , Schuler Anna-Lisa , Pascarella Annalisa , Belardinelli Paolo , Isabella Silvia L. , Di Pino Giovanni , Zago Sara , Ferrazzi Giulio , Rasero Javier , Arcara Giorgio , Marinazzo Daniele , Pellegrino Giovanni 
Published: June 2023

AbstractMagnetoencephalography and electroencephalography (M/EEG) seed-based connectivity analysis requires the extraction of measures from regions of interest (ROI). M/EEG ROI-derived source activity can be treated in different ways. It is possible, for instance, to average each ROI’s time series prior to calculating connectivity measures. Alternatively, one can compute connectivity maps for each element of the ROI prior to dimensionality reduction to obtain a single map. The impact of these different strategies on connectivity results is still unclear.Here, we address this question within a large MEG resting state cohort (N=113) and within simulated data. We consider 68 ROIs (Desikan-Kiliany atlas), two measures of connectivity (phase locking value-PLV, and its imaginary counterpart- ciPLV), three frequency bands (theta 4-8 Hz, alpha 9-12 Hz, beta 15-30 Hz). We compare four extraction methods: (i) mean, or (ii) PCA of the activity within the seed or ROIbeforecomputing connectivity, map of the (iii) average, or (iv) maximum connectivityaftercomputing connectivity for each element of the seed. Hierarchical clustering in then applied to compare connectivity outputs across multiple strategies, followed by direct contrasts across extraction methods. Finally, the results are validated by using a set of realistic simulations.We show that ROI-based connectivity maps vary remarkably across strategies in terms of connectivity magnitude and spatial distribution. Dimensionality reduction procedures conductedaftercomputing connectivity are more similar to each-other, while PCA before approach is the most dissimilar to other approaches. Although differences across methods are consistent across frequency bands, they are influenced by the connectivity metric and ROI size. Greater differences were observed for ciPLV than PLV, and in larger ROIs. Realistic simulations confirmed thatafteraggregation procedures are generally more accurate but have lower specificity (higher rate of false positive connections). Though computationally demanding,afterdimensionality reduction strategies should be preferred when higher sensitivity is desired. Given the remarkable differences across aggregation procedures, caution is warranted in comparing results across studies applying different methods.
SRC family kinase inhibition rescues molecular and behavioral phenotypes, but not protein interaction network dynamics, in a mouse model of Fragile X syndrome
Authors: Stamenkovic Vera , Lautz Jonathan D. , Harsh Felicia M. , Smith Stephen E.P. 
Published: June 2023

AbstractGlutamatergic synapses encode information from extracellular inputs using dynamic protein interaction networks (PINs) that undergo widespread reorganization following synaptic activity, allowing cells to distinguish between signaling inputs and generate coordinated cellular responses. Here, we investigated how Fragile X Messenger Ribonucleoprotein (FMRP) deficiency disrupts signal transduction through a glutamatergic synapse PIN. In cultured cortical neurons or acute cortical slices from P7, P17 and P60 FMR1-/ymice, the unstimulated protein interaction networks state resembled that of wildtype littermates stimulated with neurotransmitter agonists, demonstrating resting state pre-activation of signaling networks. We identified the Src family kinase (SFK) Fyn as a network hub, because many interactions involving Fyn were pre-activated. We tested whether targeting Fyn in FMR1-/ymice could modify disease phenotypes, and found that Saracatinib (AZD-0530), an SFK inhibitor, normalized elevated basal protein synthesis, novel object recognition memory and social behavior in FMR1-/ymice. However, SCB treatment did not normalize the PIN to a wild-type-like statein vitroorin vivo, but rather induced extensive changes to protein complexes containing Shank3, NMDARs and Fyn. We conclude that targeting abnormal nodes of a PIN can identify potential disease-modifying drugs, but behavioral rescue does not correlate with PIN normalization.
Architecture of the vertebrate egg coat and structural basis of the ZP2 block to polyspermy
Authors: Nishio Shunsuke , Emori Chihiro , Wiseman Benjamin , Fahrenkamp Dirk , Dioguardi Elisa , Zamora-Caballero Sara , Bokhove Marcel , Han Ling , Stsiapanava Alena , Lu Yonggang , Kodani Mayo , Bainbridge Rachel E. , Komondor Kayla M. , Carlson Anne E. , Landreh Michael , de Sanctis Daniele , Yasumasu Shigeki , Ikawa Masahito , Jovine Luca 
Published: June 2023

SUMMARYPost-fertilization cleavage of glycoprotein ZP2, a major subunit of egg zona pellucida (ZP) filaments, is crucial for mammalian reproduction by irreversibly blocking polyspermy. ZP2 processing is thought to inactivate a sperm-binding activity located upstream of the protein’s cleavage site; however, its molecular consequences and connection with ZP hardening are unknown. Here we report X-ray crystallographic, cryo-EM and biochemical studies showing that cleavage of ZP2 triggers its oligomerization. Deletion of the ZP-N1 domain that precedes the cleavage site of mouse ZP2 allows it to homodimerize even without processing, and animals homozygous for this variant are subfertile by having a semi-hardened ZP that allows sperm attachment but hinders penetration. Combined with the structure of a native egg coat filament, which reveals the molecular basis of heteromeric ZP subunit interaction, this suggests that oligomerization of cleaved ZP2 cross-links the ZP, rigidifying it and making it physically impenetrable to sperm.
Ryanodine Receptor Stabilization Therapy Suppresses Ca2+-Based Arrhythmias in a Novel Model of Metabolic HFpEF
Authors: Kaplan Aaron D. , Boyman Liron , Ward Christopher W. , Lederer W. Jonathan , Greiser Maura 
Published: June 2023

AbstractHeart Failure with preserved ejection fraction (HFpEF) is the most prevalent form of heart failure worldwide and its significant mortality is associated with a high rate of sudden cardiac death (SCD; 30% - 40%). Chronic metabolic stress is an important driver of HFpEF, and clinical data show metabolic stress as a significant risk factor for ventricular arrhythmias in HFpEF patients. The mechanisms of SCD and ventricular arrhythmia in HFpEF remain critically understudied and empirical treatment is ineffective. To address this important knowledge gap, we developed a novel preclinical model of metabolic-stress induced HFpEF using Western diet (High fructose and fat) and hypertension induced by nitric oxide synthase inhibition (with L-NAME) in wildtype C57BL6/J mice. After 5 months, mice display all clinical characteristics of HFpEF and present with stress-induced sustained ventricular tachycardia (VT). Mechanistically, we found a novel pattern of arrhythmogenic intracellular Ca2+handling that is distinct from the well-characterized changes pathognomonic for heart failure with reduced ejection fraction. In addition, we show that the transverse tubular system remains intact in HFpEF and that arrhythmogenic, intracellular Ca2+mobilization becomes hyper-sensitive to ß- adrenergic activation. Finally, in proof-of-concept experiments we showin vivothat the clinically used intracellular calcium stabilizer dantrolene, which acts on the Ca2+release channels of the sarcoplasmic reticulum (SR), the ryanodine receptors, acutely prevents stress-induced VT in HFpEF mice. Therapeutic control of SR Ca2+leak may present a novel mechanistic treatment approach in metabolic HFpEF.