bluuebunny/crossref_metadata_2025_split huggingface dataset:
cycle_finder:de novoanalysis of tandem and interspersed repeats based on cycle-finding
Authors: Tanaka Yoshiki , Kajitani Rei , Itoh Takehiko 
Published: July 2023

AbstractRepeat sequences in the genome can be classified into interspersed and tandem repeats, both of which are important for understanding genome evolution and important traits such as disease. They are also noteworthy as regions of high frequency of genome rearrangement in somatic cells and high inter-individual diversity. Existing repeat detection tools have limitations in that they targets only one of the two types and/or require reference sequences. In this study, we developed a novel tool: cycle_finder, which constructs a graph structure (de Bruijn graph) from low-cost short-read data and constructs units of both types of repeats. The tool can detect cycles with branching and corresponding tandem repeats, and can also construct interspersed repeats by exploring non-cycle subgraphs. Furthermore, it can estimate sequences with large copy-number differences by using two samples as input. Benchmarking with simulations and actual data from the human genome showed that this tool had superior recall and precision values compared to existing methods. In a test on the roundworm data, in which large-scale deletions occur in somatic cells, the tool succeeded in detecting deletion sequences reported in previous studies. This tool is expected to enable low-cost analysis of repeat sequences that were previously difficult to construct.
Recognition of sounds by ensembles of proteinoids
Authors: Mougkogiannis Panagiotis , Adamatzky Andrew 
Published: July 2023

AbstractProteinoids are artificial polymers that imitate certain characteristics of natural proteins, including self-organization, catalytic activity, and responsiveness to external stimuli. This paper investigates the potential of proteinoids as organic audio signal processors. We convert sounds of English alphabet into waveforms of electrical potential, feed the waveforms into proteinoid solutions and record electrical responses of the proteinoids. We also undertake a detailed comparison of proteinoids’ electrical responses (frequencies, periods, and amplitudes) with original input signals. We found that responses of proteinoids are less regular, lower dominant frequency, wider distribution of proteinoids and less skewed distribution of amplitudes compared with input signals. We found that letter of English alphabet uniquely maps onto a pattern of electrical activity of a proteinoid ensemble, that is the proteinoid ensembles recognise spoken letters of English alphabet. The finding will be used in further designs of organic electronic devices, based on ensembles of proteinoids, for sound processing and speech recognition.
The MEK-ERK signaling pathway promotes maintenance of cardiac chamber identity
Authors: Yao Yao , Yelon Deborah 
Published: July 2023

ABSTRACTVentricular and atrial cardiac chambers have unique structural and contractile characteristics that underlie their distinct functions. Intriguingly, the maintenance of chamber-specific features requires active reinforcement, even in differentiated cardiomyocytes. Prior studies in zebrafish have shown that sustained FGF signaling acts upstream ofnkx2.5to maintain ventricular identity, but the rest of this maintenance pathway remains unclear. Here, we show that MEK1/2-ERK1/2 signaling acts downstream of FGF and upstream ofnkx2.5to promote ventricular maintenance. Inhibition of MEK signaling, like inhibition of FGF signaling, results in ectopic atrial gene expression and reduced ventricular gene expression in ventricular cardiomyocytes. FGF and MEK signaling both influence ventricular maintenance over a similar timeframe, when phosphorylated ERK (pERK) is present in the myocardium. However, the role of FGF-MEK activity seems to be context-dependent: some ventricular regions are more sensitive than others to inhibition of FGF-MEK signaling. Additionally, in the atrium, although endogenous pERK does not induce ventricular traits, heightened MEK signaling can provoke ectopic ventricular gene expression. Together, our data reveal chamber-specific roles of MEK-ERK signaling in the maintenance of ventricular and atrial identities.SUMMARY STATEMENTThe MEK-ERK signaling pathway plays distinct roles in the maintenance of ventricular and atrial cardiomyocyte identities.
Model connectivity: leveraging the power of encoding models to overcome the limitations of functional connectivity
Authors: Meschke Emily X. , Castello Matteo Visconti di Oleggio , Tour Tom Dupré la , Gallant Jack L. 
Published: July 2023

SummaryFunctional connectivity (FC) is the most popular method for recovering functional networks of brain areas with fMRI. However, because FC is defined as temporal correlations in brain activity, FC networks are confounded by noise and lack a precise functional role. To overcome these limitations, we developed model connectivity (MC). MC is defined as similarities in encoding model weights, which quantify reliable functional activity in terms of interpretable stimulus- or task-related features. To compare FC and MC, both methods were applied to a naturalistic story listening dataset. FC recovered spatially broad networks that are confounded by noise, and that lack a clear role during natural language comprehension. By contrast, MC recovered spatially localized networks that are robust to noise, and that represent distinct categories of semantic concepts. Thus, MC is a powerful data-driven approach for recovering and interpreting the functional networks that support complex cognitive processes.
Climate and geography shape hybrid zone dynamics across space and time: insights fromPopulus trichocarpaxP. balsamifera
Authors: Bolte Constance E. , Phannareth Tommy , Fitzpatrick Matthew C. , Holliday Jason A. , Keller Stephen R. , Hamilton Jill A. 
Published: July 2023

SummaryQuantifying the mechanisms underlying hybrid zone formation requires an evaluation of both neutral and nonneutral evolutionary processes. Population demographic changes, alongside landscape heterogeneity and climate adaptation, can influence the timing, stability, and extent of introgression where species hybridize. Thus, quantifying interactions across diverged lineages, and the relative contributions of interspecific genetic exchange and selection to divergence at the genome-wide level is needed.We quantified the contributions of climate and geography to the genetic structure across replicate contact zones betweenPopulus trichocarpaandP. balsamifera,evaluating the demographic context of hybridization and the role of genetic connectivity over time.We found genomic structure differed among the seven latitudinally arrayed transects. While ancestry was strongly structured by climate, geography appears to have restricted gene flow in certain regions of the hybrid zone. The best fitting demographic model indicated high rates of gene flow alongside selection have likely influenced the establishment and maintenance of the hybrid zone.Our results point towards the importance of climate in structuring the contact zones betweenP. trichocarpaandP. balsamiferaand emphasize the value of sampling replicated zones of contact to understand how neutral and non-neutral processes influence hybrid zone formation across space and time.
C9orf72gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types
Authors: Broce Iris J. , Sirkis Daniel W. , Nillo Ryan M. , Bonham Luke W. , Lee Suzee E. , Miller Bruce , Castruita Patricia , Sturm Virginia E. , Sugrue Leo S. , Desikan Rahul S. , Yokoyama Jennifer S. 
Published: July 2023

AbstractIntroductionA hexanucleotide repeat expansion (HRE) intronic to chromosome 9 open reading frame 72 (C9orf72) is recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and ALS-FTD. Identifying genes that show similar regional co-expression patterns toC9orf72may help identify novel gene targets and biological mechanisms that mediate selective vulnerability to ALS and FTD pathogenesis.MethodsWe leveraged mRNA expression data in healthy brain from the Allen Human Brain Atlas to evaluateC9orf72co-expression patterns. To do this, we correlated averageC9orf72expression values in 51 regions across different anatomical divisions (cortex, subcortex, cerebellum) with average gene expression values for 15,633 protein-coding genes, including 50 genes known to be associated with ALS, FTD, or ALS-FTD. We then evaluated whether the identifiedC9orf72co-expressed genes correlated with patterns of cortical thickness in symptomaticC9orf72pathogenic HRE carriers (n=19). Lastly, we explored whether genes with significantC9orf72radiogenomic correlations (i.e., ‘C9orf72gene network’) were enriched in specific cell populations in the brain and enriched for specific biological and molecular pathways.ResultsA total of 1,748 genes showed an anatomical distribution of gene expression in the brain similar toC9orf72and significantly correlated with patterns of cortical thickness inC9orf72HRE carriers. ThisC9orf72gene network was differentially expressed in cell populations previously implicated in ALS and FTD, including layer 5b cells, cholinergic motor neurons in the spinal cord, and medium spiny neurons of the striatum, and was enriched for biological and molecular pathways associated with multiple neurotransmitter systems, protein ubiquitination, autophagy, and MAPK signaling, among others.ConclusionsConsidered together, we identified a network ofC9orf72-associated genes that may influence selective regional and cell-type-specific vulnerabilities in ALS/FTD.
Comparative metagenomic analysis of diarrheal and non-diarrheal gut microbiome delineating the prospective development of prognostic markers and probiotics to protect from diarrhea
Authors: De Rituparna , Kanungo Suman , Mukhopadhyay Asish K. , Dutta Shanta 
Published: July 2023

AbstractA cross-sectional gut microbiome analysis of 23 non-diarrheal and 5 diarrheal fecal samples was conducted by employing 16s rRNA amplicon sequencing and subsequent analysis for taxonomic profiling of OTUs and abundance interpretation of reads. Significant differences in the structural composition of the two groups were observed. In both Firmicutes was the most abundant phylum in majority of the samples. B/F ratio was consistently <1 in all diarrheal samples. Significant difference in mean B/F ratio of the two groups was found. Proteobacteria was significantly more abundant in the diarrheal group.Prevotellaceaewas the most abundant family in non-diarrheal samples and was suppressed significantly in diarrheal samples.Streptococcaceaewas the most abundant family in 60% diarrheal samples and whereStreptococcaceaewas suppressed,BacteroideaceaeandNocardeaceaewere the most abundant. In non-diarrheal samples whereStreptococcaceaewas almost completely suppressedBifidobacteriaceaewas the most abundant and suppressed other families significantly. A negative correlation was observed betweenPrevotellaceaeandBacteroideaceaein the non-diarrheal group.Prevotella copriwas the most abundant species in 70% non-diarrheal samples and was significantly suppressed in diarrheal samples.Proteus mirabiliswas identified in all the non-diarrheal samples while they were absent in diarrheal samples. The OTUs associated with diarrheal dysbiosis can serve as prognostic markers. This is the first report on the comparative analysis of diarrheal and non-diarrheal microbiome, to our knowledge, and distinctly addressing the gut microbiome dysbiosis from the context that can lead to the development of prognostic markers and probiotics for protecting the endemic population from diarrhea.
The gut microbiome of the healthy population in Kolkata, India, is a reservoir of antimicrobial resistance genes emphasizing the need of enforcing antimicrobial stewardship
Authors: De Rituparna , Kanungo Suman , Mukhopadhyay Asish Kumar , Dutta Shanta 
Published: July 2023

AbstractAntimicrobial resistance (AMR) alleviation warrants antimicrobial stewardship (AS) entailing indispensability of epidemiological surveillance. We undertook a small-scale surveillance in Kolkata to detect the presence of antimicrobial resistance genes (ARGs) in the healthy gut microbiome. We found that it was a reservoir of ARGs against common antibiotics. A targeted PCR and sequencing-based ARGs detection against tetracyclines, macrolides, trimethoprim, sulfamethoxazole, aminoglycosides, amphenicol and mobile genetic element (MGE) markers was deployed in twenty-five fecal samples. Relative abundance and frequency of ARGs was calculated. We detected markers against all these classes of antibiotics. 100% samples carried aminoglycoside resistance marker andint1U. A comparison with our previously published diarrheal resistome from the same spatial and temporal frame revealed that a higher diversity of ARGs were detected in the community and a higher rate of isolation oftetC, msrA, tmpandsul-2was found. The presence of common markers in the two cohorts proves that the gut microbiome has been contaminated with ARGs and which are being disseminated among different ecosystems. This is an issue of discerning concern for public health. The study raises an alarming picture of the AMR crisis in low-middle and emergent economies. It emphasizes the strict enforcement of AS in the community.
A nearly complete and phased genome assembly of a ColombianTrypanosoma cruziTcI strain and the evolution of gene families
Authors: Hoyos Sanchez Maria Camila , Ospina Zapata Hader Sebastian , Suarez Brayhan Dario , Ospina Carlos , Barbosa Hamilton Julian , Carranza Martinez Julio Cesar , Vallejo Gustavo Adolfo , Montes Daniel Urrea , Duitama Jorge 
Published: July 2023

AbstractChagas is an endemic disease in tropical regions of Latin America, caused by the parasiteTrypanosoma cruzi. High intraspecies variability and genome complexity have been challenges for the development of genomic variation databases, needed to conduct studies in evolution, population genomics, and identification of genomic elements related to virulence and drug resistance inT. cruzi. Here we present a chromosome-level phased assembly of aT. cruzistrain (Dm25), isolated from a reservoir of the speciesDidelphis marsupialislocated at the Tolima department in Colombia, and belonging to the TcI DTU. We obtained a primary haplotype composed of 32 chromosomes, 30 of them assembled in a single contig, and one complete copy of the maxicircle. While 29 chromosomes show a large collinearity with the assembly of the Brazil A4 strain, three chromosomes with a high density of repeat elements show a large divergence, compared to the Brazil A4 assembly. Considering that the distribution of heterozygous sites suggest that Dm25 is diploid, we assembled a second haplotype for 31 chromosomes, achieving an average of three contigs per chromosome. Nucleotide and protein evolution statistics indicate thatT. cruziMarinkellei separated before the diversification ofT. cruziin the known DTUs. Interchromosomal paralogs of dispersed gene families and histones appeared before but at the same time have a more strict purifying selection, compared to other repeat families. Previously unreported large tandem arrays of protein kinases and histones were identified in this assembly. Over one million variants obtained from Illumina reads aligned to the primary assembly clearly separate the main DTUs. We expect that this new assembly will be a valuable resource for further studies on evolution and functional genomics ofTrypanosomatids.
Mutation of theVinv5′ UTR regulatory region reduces acrylamide levels in processed potato to reach EU food-safety standards
Authors: Shumbe Leonard , Soares Emanoella , Muhovski Yordan , Smit Inga , Vanderschuren Hervé 
Published: July 2023

AbstractProtein-coding regions of genes have so far been the preferred targets for trait improvement using CRISPR-Cas9 genome editing in plants. Alteration of the reading frame can result in termination of transcription or translation, hence, loss of function of the encoded protein. 5’ UTR sequences also represent a practical target region to alter gene expression and protein abundance. However, editing of 5’ UTRs has so far been scarcely used to engineer trait in crop plants. Here, we demonstrate that insertion of a single adenine nucleotide mediated by Cas9 in the 5’ UTR region of two alleles from the Vacuolar invertase gene (VInv) of the tetraploid potato variety Lady Rosetta (LaRo) is sufficient to substantially lower the content of reducing sugars in the potato under cold-storage conditions. Moreover, the acrylamide content generated during processing of the edited potato lines into crisps was more than three folds lower than the current EU-regulated maximum level of 750 μg/kg in crisps. This gene-editing approach represents a durable strategy to improve food safety of potatoes in varieties widely preferred by the consumers and the industry.
Evolving Membrane-Associated Accessory Protein Variants for Improved Adeno-associated Virus Production
Authors: Schieferecke Adam J. , Lee Hyuncheol , Chen Aleysha , Kilaru Vindhya , Williams Justin Krish , Schaffer David. V. 
Published: July 2023

AbstractManufacturing sufficient Adeno-Associated Virus (AAV) to meet current and projected clinical needs is a significant hurdle to the growing gene therapy industry. The recently discovered membrane-associated accessory protein (MAAP) is encoded by an alternative open reading frame in the AAVcapgene that is found in all presently reported natural serotypes. Recent evidence has emerged supporting a functional role of MAAP in AAV egress, though the underlying mechanisms of MAAP function remain unknown. Here, we show that inactivation of MAAP from AAV2 by a single point mutation that is silent in the VP1 ORF (AAV2-ΔMAAP) decreased exosome-associated and secreted vector genome production. We hypothesized that novel MAAP variants could be evolved to increase AAV production and thus subjected a library encoding over 1E6 MAAP protein variants to five rounds of packaging selection into the AAV2-ΔMAAP capsid. Between each successive packaging round, we observed a progressive increase in both overall titer and ratio of secreted vector genomes conferred by the bulk selected MAAP library population. Next-generation sequencing uncovered enriched mutational features, and a resulting selected MAAP variant containing missense mutations and a novel C-terminal domain increased overall GFP transgene packaging in AAV2, AAV6, and AAV9 capsids.
Eugenol mimics exercise to promote skeletal muscle fiber remodeling and myokine IL-15 expression by activating TRPV1 channel
Authors: Huang Tengteng , Chen Xiaoling , He Jun , Zheng Ping , Luo Yuheng , Wu Aimin , Yan Hui , Yu Bing , Chen Daiwen , Huang Zhiqing 
Published: July 2023

AbstractMetabolic disorders are highly prevalent in modern society. Exercise mimetics are defined as pharmacologic compounds that can produce the beneficial effects of fitness. Recently, there has been increased interest in the role of eugenol and transient receptor potential vanilloid 1 (TRPV1) in improving metabolic health. The aim of this study was to investigate whether eugenol acts as an exercise mimetic by activating TRPV1. Here, we showed that eugenol improved endurance capacity, caused the conversion of fast to slow muscle fibers, and promoted white fat browning and lipolysis in mice. Mechanistically, eugenol promoted muscle fiber type transformation by activating TRPV1-mediated CaN signaling pathway. Subsequently, we identified IL-15 as a myokine that is regulated by the CaN/Nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Moreover, we found that TRPV1-mediated CaN/NFATc1 signaling, activated by eugenol, controlled IL-15 levels in C2C12 myotubes. Our results suggest that eugenol may act as an exercise mimetic to improve metabolic health via activating the TRPV1-mediated CaN signaling pathway.
Multiple axes of visual system diversity in Ithomiini, an ecologically diverse tribe of mimetic butterflies
Authors: Wainwright J. Benito , Schofield Corin , Conway Max , Phillips Daniel , Martin-Silverstone Elizabeth , Brodrick Emelie A. , Cicconardi Francesco , How Martin J. , Roberts Nicholas W. , Montgomery Stephen H. 
Published: July 2023

AbstractThe striking structural variation seen in arthropod visual systems can be explained by the overall quantity and spatio-temporal structure of light within habitats coupled with developmental and physiological constraints. However, little is currently known about how fine-scale variation in visual structures arise across shorter evolutionary and ecological scales. In this study, we characterise patterns of interspecific (between species), intraspecific (between sexes) and intraindividual (between eye regions) variation in the visual system of four ithomiine butterfly species. These species are part of a diverse 26-Myr-old Neotropical radiation where changes in mimetic colouration are associated with fine-scale shifts in ecology, such as microhabitat preference. By using a combination of selection analyses on visual opsin sequences, in-vivo ophthalmoscopy, micro-computed tomography (micro-CT), immunohistochemistry, confocal microscopy, and neural tracing, we quantify and describe physiological, anatomical, and molecular traits involved in visual processing. Using these data, we provide evidence of substantial variation within the visual systems of Ithomiini, including: i) relaxed selection on visual opsins, perhaps mediated by habitat preference, ii) interspecific shifts in visual system physiology and anatomy, and iii) extensive sexual dimorphism, including the complete absence of a butterfly-specific optic neuropil in the males of some species. We conclude that considerable visual system variation can exist within diverse insect radiations, hinting at the evolutionary lability of these systems to rapidly develop specialisations to distinct visual ecologies, with selection acting at both the perceptual, processing, and molecular level.Summary statementPhysiological, anatomical, and molecular evidence of extensive visual system variation within a diverse butterfly radiation, hinting at the lability of visual systems to evolve specialisations to distinct visual environments.
Genetic associations of dimensional autistic phenotypes
Authors: Eriksson Tore , Nakamori Chiaki , Iwamoto Kazunari 
Published: July 2023

AbstractSince there is a large variation in the symptoms shown by persons affected with ASD, analyzing genetics data using a case-control design is not straightforward. To avoid the difficult problem of defining heterogeneous groups, we used four different methods to compute a latent representation of a merged set of three psychometric tests. Computing the genetic contribution of each representation using a subset of participants with genetic data, we showed that factor analysis as well as variable autoencoders separates information contained in psychometric tests into genetically distinct phenotypic domains. Using the individual-level loadings of the domains as quantitative phenotypes in genome-wide association studies we detected statistically significant genetic associations in the domain related to insistence on routine, as well as suggestive genetic signals in other domains. We hope that these results can suggest possible domain-specific interventions in the future.