bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity
Authors: Thakare Aditi , Ghosh Chaitali , Alalamath Tejashwini , Kumar Naveen , Narang Himani , Whadgar Saurabh , Paul Kiran , Shrotri Shweta , Kumar Sampath , Soumya M , Rao Raksha , Chakraborty Mahul , Choudhary Bibha , Ghosh Susanta K. , Subramani Suresh , Swain Sunita , Srinivasan Subhashini 
Published: August 2021

ABSTRACTBackgroundAnopheles stephensi is the most menacing malaria vector to watch for in newly urbanizing parts of the world. The fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions of malaria vectors are implicated in adaptation.ResultsWe report the assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome completes the trilogy with respect to a 16 Mbp inversion (2Rb) in An. stephensi associated with adaptation to environmental heterogeneity. Comparative genome analysis revealed breakpoint structure and allowed extraction of 22,650 segregating SNPs for typing this inversion. Using whole genome sequencing of 82 individual mosquitoes, we conclude that one third of both wild and laboratory populations maintain heterozygous genotype of 2Rb. The large number of SNPs are tailored to assign inversion genotype directly from 1740 exonic SNPs 80% of which are expressed in various developmental stages.ConclusionsThe genome trilogy approach accelerates study of fine structure and typing of important inversions in malaria vectors putting the genome resources for the much understudied An. stephensi, on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse populations cluster with IndCh pointing to significant commerce between cities, perhaps, allowing for survival of the fittest strain.
CALANGO: a phylogeny-aware comparative genomics tool for discovering quantitative genotype-phenotype associations across species
Authors: Hongo Jorge Augusto , de Castro Giovanni Marques , Albuquerque Menezes Alison Pelri , Rios Picorelli Agnello César , da Silva Thieres Tayroni Martins , Imada Eddie Luidy , Marchionni Luigi , Del-Bem Luiz-Eduardo , Chaves Anderson Vieira , de Freitas Almeida Gabriel Magno , Campelo Felipe , Lobo Francisco Pereira 
Published: August 2021

ABSTRACTThe increasing availability of genomic, annotation, evolutionary and phenotypic data for species contrasts with the lack of studies that adequately integrate these heterogeneous data sources to produce biologically meaningful knowledge. Here, we present CALANGO, a phylogeny-aware comparative genomics tool that uncovers functional molecular convergences and homologous regions associated with quantitative genotypes and phenotypes across species, enabling the fast discovery of novel statistically sound, biologically relevant phenotype-genotype associations. We demonstrate the usefulness of CALANGO in two case studies. The first one unveils potential causal links between prophage density and the pathogenicity phenotype in Escherichia coli, and confidently demonstrates how CALANGO supports the investigation of basic causal relationships by enabling a level of counterfactual investigation of observed associations in the data. As a second case study, we used our tool to search for homologous regions associated with a complex phenotypic trait in a major group of eukaryotes: the evolution of maximum height in angiosperms. We confidently identify a previously unknown association between maximum plant height and the expansion of the self-incompatibility system, a molecular mechanism that prevents inbreeding and increases genetic diversity. Taller species also have lower rates of molecular evolution due to their longer generation times, a critical concern for their long-term viability. The new mechanism we report could counterbalance this fact, and have far-reaching consequences for fields as diverse as conservation biology and agriculture. CALANGO is provided as a fully operational R package that can be freely installed from CRAN.
From Text-based Genome, Population Variations, and Transcriptome Datafiles to SQLite Database and Web Application: A Bioinformatical Study on Alfalfa
Authors: Qiao Shichen , Shen Chen 
Published: August 2021

AbstractIn this study, a web database application with the Flask framework was developed to implement three types of queries and visualize the results over a bioinformatical dataset from Alfalfa (Medicago sativa). A backend SQLite database was constructed from genome FASTA, population variations, transcriptome, and annotation files with extensions “.fasta”, “.gff”, “vcf”, “.annotate”, etc. Further, a supplementary command-line-based Java application was also developed for faster access to the database without direct SQL programming. Overall, Python, Java, and HTML were the main programming languages used in this application. Those scripts and the development procedures are valuable for bioinformaticians to build online databases from similar raw datasets of other species.
Glial Nrf2 signaling mediates the neuroprotection exerted by Gastrodia elata Blume in Lrrk2-G2019S Parkinson’s disease
Authors: Lin Yu-En , Lin Chin-Hsien , Ho En-Peng , Ke Yi-Ci , Petridi Stavroula , Elliott Christopher J. H. , Sheen Lee-Yan , Chien Cheng-Ting 
Published: August 2021

AbstractThe most frequent missense mutations in familial Parkinson’s disease (PD) occur in the highly conserved LRRK2/PARK8 gene with G2019S mutation. We previously established a fly model of PD carrying the LRRK2-G2019S mutation that exhibited the parkinsonism-like phenotypes. An herbal medicine—Gastrodia elata Blume (GE), has been reported to have neuroprotective effects in toxin- induced PD models. However, the underpinning molecular mechanisms of GE beneficiary to G2019S- induced PD remain unclear. Here, we show that these G2019S flies treated with water extracts of GE (WGE) and its bioactive compounds, gastrodin and 4-HBA, displayed locomotion improvement and dopaminergic neuron protection. WGE suppressed the accumulation and hyperactivation of G2019S proteins in dopaminergic neurons, and activated the antioxidation and detoxification factor Nrf2 mostly in the astrocyte-like and ensheathing glia. Glial activation of Nrf2 antagonizes G2019S-induced Mad/Smad signaling. Moreover, we treated LRRK2-G2019S transgenic mice with WGE and found the locomotion declines, the loss of dopaminergic neurons, and the number of hyperactive microglia were restored. WGE also suppressed the hyperactivation of G2019S proteins and regulated the Smad2/3 pathways in the mice brains. We conclude that WGE prevents locomotion defects and the neuronal loss induced by G2019S mutation via glial Nrf2/Mad signaling, unveiling a potential therapeutic avenue for PD.
Anterior thalamic nuclei neurons sustain memory
Authors: Barnett S. C. , Parr-Brownlie L.C. , Perry B. A. L. , Young C. K. , Wicky H. E. , Hughes S. M. , McNaughton N. , Dalrymple-Alford J. C. 
Published: August 2021

AbstractA hippocampal-diencephalic-cortical network supports memory function. The anterior thalamic nuclei (ATN) form a key anatomical hub within this system. Consistent with this, injury to the mammillary body-ATN axis is associated with examples of clinical amnesia. However, there is only limited and indirect support that the output of ATN neurons actively enhances memory. Here, in rats, we first showed that mammillothalamic tract (MTT) lesions caused a persistent impairment in spatial working memory. MTT lesions also reduced rhythmic electrical activity across the memory system. Next, we introduced 8.5 Hz optogenetic theta-burst stimulation of the ATN glutamatergic neurons. The exogenously-triggered, regular pattern of stimulation produced an acute and substantial improvement of spatial working memory in rats with MTT lesions and enhanced rhythmic electrical activity. Neither behaviour nor rhythmic activity was affected by endogenous stimulation derived from the dorsal hippocampus. Analysis of immediate early gene activity, after the rats foraged for food in an open field, showed that exogenously-triggered ATN stimulation also increased Zif268 expression across memory-related structures. These findings provide clear evidence that increased ATN neuronal activity supports memory. They suggest that ATN-focused gene therapy may be feasible to counter clinical amnesia associated with dysfunction in the mammillary body-ATN axis.HighlightsThe mammillothalamic tract (MTT) supports neural activity in an extended memory system.Optogenetic activation of neurons in the anterior thalamus acutely improves memory after MTT lesions.Rescued memory associates with system-wide neuronal activation and enhanced EEG.Anterior thalamus actively sustains memory and is a feasible therapeutic target.Abstract FigureOptostimulation of anterior thalamus restores memory function after MTT lesionsCreated with BioRender.com
A local scale evaluation of spatial sampling bias in the Atlas of Australian Birds
Authors: Totterman Stephen L. 
Published: August 2021

ABSTRACTThe reliability of ‘citizen science’ datasets where volunteers are free to choose sampling locations is not clear. This study examined local (‘patch’) scale spatial sampling patterns in the Atlas of Australian Birds and then compared reporting rates, i.e. the proportion of sampling units in which a given species was present, from a sample of atlas points with those from a regular sample. Three sites that have been were surveyed sequentially between January–May 2017: Killawarra Forest, Victoria, Coolah Tops National Park and Pilliga Nature Reserve, New South Wales. Spatial bias in atlas sampling patterns was evident as clusters at tourist areas and special habitat features and linear patterns along roads and creek lines. Atlas samples overestimated reporting rates for species with spatial distributions that were concordant with those sampling patterns and vice versa. At least two-fold differences in atlas/regular sample reporting rate ratios were detected for between 13–15% of non-rare species (with reporting rates ≥ 0.08). Concerns are raised that spatial sampling bias is common in the atlas and affects a variety of species, that popular sites may not be representative of habitat patches and that a large proportion of surveys are being filtered out in data analyses.
Identifying Gene-wise Differences in Latent Space Projections Across Cell Types and Species in Single Cell Data using scProject
Authors: Baraban Asher , Clark Brian S. , Slosberg Jared , Fertig Elana J. , Goff Loyal A. , Stein-O’Brien Genevieve 
Published: August 2021

ABSTRACTLatent space techniques have emerged as powerful tools to identify genes and gene sets responsible for cell-type and species-specific differences in single-cell data. Transfer learning methods can compare learned latent spaces across biological systems. However, the robustness that comes from leveraging information across multiple genes in transfer learning is often attained at the sacrifice of gene-wise precision. Thus, methods are needed to identify genes, defined as important within a particular latent space, that significantly differ between contexts. To address this challenge, we have developed a new framework, scProject, and a new metric, projectionDrivers, to quantitatively examine latent space usage across single-cell experimental systems while concurrently extracting the genes driving the differential usage of the latent space between defined contrasts. Here, we demonstrate the efficacy, utility, and scalability of scProject with projectionDrivers and provide experimental validation for predicted species-specific differences between the developing mouse and human retina.
The E26 Transformation-Specific-family transcription factor Spi-C is dynamically regulated by external signals in B cells
Authors: Raczkowski Hannah L. , Xu Li S. , Wang Wei Cen , DeKoter Rodney P. 
Published: August 2021

AbstractSpi-C is an E26 transformation-specific transcription factor closely related to PU.1 and Spi-B. Spi-C has lineage-instructive functions important in antibody-generating responses, B cell development, and red pulp macrophage generation. Spi-C is inducible by heme- and NF-κB-dependent pathways in macrophages. The present research aimed to examine the regulation of Spi-C expression in B cells. RT-qPCR analysis revealed thatSpicexpression was reduced in B cells following addition of lipopolysaccharide, anti-IgM antibodies, CD40L, or cytokines BAFF + IL-4 + IL-5. Cytochalasin treatment partially prevented downregulation ofSpic. Unstimulated B cells upregulatedSpicover time in culture. To determine the mechanism ofSpicregulation, we examined theSpicpromoter and upstream regulatory elements. TheSpicpromoter had unidirectional activity, which was reduced by mutation of an NF-κB binding site.Spicwas repressed by an upstream regulatory region interacting with the heme-binding regulator Bach2. Taken together, these data indicate that Spi-C is dynamically regulated by external signals in B cells and provide insight into the mechanism of regulation.
The Enemy of my Enemy is my Friend: Immune-Mediated Facilitation Contributes to Fitness of Co-Infecting Helminths
Authors: Dagostin Francesca , Vanalli Chiara M. , Boag Brian , Casagrandi Renato , Gatto Marino , Mari Lorenzo , Cattadori Isabella M. 
Published: August 2021

AbstractOur conceptual understanding of immune-mediated interactions between parasites is rooted in the theory of community ecology. One of the limitations of this approach is that most of the theory and empirical evidence has focused on resource or immune-mediated parasite competition and yet, there is ample evidence of positive interactions between species that could be generated by immune-mediated facilitation. Here, we develop an immuno-epidemiological framework and apply it to longitudinal infection data of two gastrointestinal helminths that infect a population of free-living rabbits to investigate, through model testing, the mechanisms of immune-mediated facilitation in dual infections. Simulations show that weakened, species-specific IgA antibody responses and unequal, albeit low, IgA cross-reactions explain higher parasite intensities in dual compared to single infections, for both helminths. Simulations also show that rabbits with dual infections shed more free-living stages that survive fort longer in the environment, implying greater onward transmission than hosts with single infections. These findings support the hypothesis that the two helminths interact through immune-mediated facilitation which contributes to greater fitness and the long-term co-circulation of both species in the host population.
Locus-specific chromatin profiling of evolutionarily young transposable elements
Authors: Taylor Darren , Lowe Robert , Philippe Claude , Cheng Kevin C. L. , Grant Olivia A. , Zabet Nicolae Radu , Cristofari Gael , Branco Miguel R. 
Published: August 2021

ABSTRACTDespite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of HiChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we reveal previously unappreciated variation in the epigenetic profiles of young TE loci in mouse and human cells. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.
Using Conspecific Playbacks to Investigate Contact Calling in Southeast Alaskan Humpback Whales
Authors: Fournet Michelle E.H. , Matthews Leanna P. , Bartlett Annie , Mastick Natalie , Sharpe Fred , Doyle Laurance , McCowan Brenda , Crutchfield James P. , Mellinger David K. 
Published: August 2021

AbstractHumpback whales (Megaptera novaeangliae) produce calls across age and sex class and throughout their migratory range. Despite growing interest in calling behavior, the function of most calls is unknown. Among identified call types, the ‘whup’ is ubiquitous, and innate, and may serve as a contact call. We conducted an acoustic playback experiment combined with passive acoustic monitoring and visual observations to test the function of the whup on a Southeast Alaskan foraging ground. Using a before-during-after design, we broadcasted either a control sound or a unique whup call sequence. We investigated the change in whup rates (whups/whale/10 minutes) in response to treatment (whup or control) and period (before, during, or after). In 100% of the conspecific trials, whup rates increased during broadcasts, and whup rates were significantly higher than in before or after periods. There was no significant difference in whup rates between before and after periods during conspecific trials. In control trials, there were no significant differences in whup rates between before, during, or after periods. Neither whups nor control playbacks elicited an approach response. Humpback whale vocal responses to whup playbacks suggest that whups function as a contact call, but not necessarily as an aggregation signal.
Neural Basis of Acoustic Species Recognition in a Cryptic Species Complex
Authors: Gupta Saumya , Alluri Rishi K. , Rose Gary J. , Bee Mark A. 
Published: August 2021

ABSTRACTSexual traits that promote species recognition are important drivers of reproductive isolation, especially among closely related species. Identifying neural processes that shape species differences in recognition is crucial for understanding the causal mechanisms of reproductive isolation. Temporal patterns are salient features of sexual signals that are widely used in species recognition by several taxa, including anurans. Recent advances in our understanding of temporal processing by the anuran auditory system provide an excellent opportunity to investigate the neural basis of species-specific recognition. The anuran inferior colliculus (IC) consists of neurons that are selective for temporal features of calls. Of potential relevance are auditory neurons known as interval-counting neurons (ICNs) that are often selective for the pulse rate of conspecific advertisement calls. Here, we took advantage of a species differences in temporal selectivity for pulsatile advertisement calls exhibited by two cryptic species of gray treefrog (Hyla chrysoscelis and Hyla versicolor) to test the hypothesis that ICNs mediate acoustic species recognition. We tested this hypothesis by examining the extent to which the threshold number of pulses required to elicit behavioral responses from females and neural responses from ICNs was similar within each species but potentially different between the two species. In support of our hypothesis, we found that a species difference in behavioral pulse number thresholds corresponded closely to a parallel species difference in neural pulse number thresholds. However, this relationship held only for ICNs that exhibited band-pass tuning for conspecific pulse rates. Together, these findings suggest that differences in temporal processing of a subset of ICNs provide a mechanistic explanation for reproductive isolation between two cryptic and syntopically breeding treefrog species.Summary StatementTemporal processing by a subset of midbrain auditory neurons plays key roles in decoding information about species identity in anurans.
An automatic diagnostic system for pediatric genetic disorders by linking genotype and phenotype information
Authors: Dong Xinran , Wu Bingbing , Wang Huijun , Yang Lin , Chen Xiang , Ni Qi , Wang Yaqiong , Liu Bo , Lu Yulan , Zhou Wenhao 
Published: August 2021

AbstractBackgroundQuantitatively describe the phenotype spectrum of pediatric disorders has remarkable power to assist genetic diagnosis. Here, we developed a matrix which provide this quantitative description of genomic-phenotypic association and constructed an automatic system to assist the diagnose of pediatric genetic disorders.Results20,580 patients with genetic diagnostic conclusions from the Children’s Hospital of Fudan University during 2015 to 2019 were reviewed. Based on that, a phenotype spectrum matrix -- cGPS (clinical Gene’s Preferential Synopsis) -- was designed by Naïve Bayes model to quantitatively describe genes’ contribution to clinical phenotype categories. Further, for patients who have both genomic and phenotype data, we designed a ConsistencyScore based on cGPS. ConsistencyScore aimed to figure out genes that were more likely to be the genetic causal of the patient’s phenotype and to prioritize the causal gene among all candidates. When using the ConsistencyScore in each sample to predict the causal gene for patients, the AUC could reach 0.975 for ROC (95% CI 0.972-0.976 and 0.575 for precision-recall curve (95% CI 0.541-0.604). Further, the performance of ConsistencyScore was evaluated on another cohort with 2,323 patients, which could rank the causal gene of the patient as the first for 75.00% (95% CI 70.95%-79.07%) of the 296 positively genetic diagnosed patients. The causal gene of 97.64% (95% CI 95.95%-99.32%) patients could be ranked within top 10 by ConsistencyScore, which is much higher than existing algorithms (p <0.001).ConclusionscGPS and ConsistencyScore offer useful tools to prioritize disease-causing genes for pediatric disorders and show great potential in clinical applications.