Resource Discovery Research Articles

Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing

MicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for miRNA modulation using oligonucleotides and gene therapies are challenging, especially for neurological diseases, and none have yet gained clinical approval. We explore a different approach by screening a biodiverse library of small molecule compounds for their ability to modulate hundreds of miRNAs in human induced pluripotent stem cell-derived neurons. We demonstrate the utility of the screen by identifying cardiac glycosides as potent inducers of miR-132, a key neuroprotective miRNA downregulated in Alzheimer’s disease and other tauopathies. Coordinately, cardiac glycosides downregulate known miR-132 targets, including Tau, and protect rodent and human neurons against various toxic insults. More generally, our dataset of 1370 drug-like compounds and their effects on the miRNome provides a valuable resource for further miRNA-based drug discovery.

Arabian Gulf Academic Libraries’ Knowledge Representation Practices, Perspectives and Barriers

Knowledge representation through metadata is crucial to successful knowledge management and ensuring access. Libraries, especially those associated with universities and colleges, have been long engaged in important activities of developing, adapting, implementing, and managing descriptive and administrative metadata, bibliographic authority control, etc. A substantial amount of research exists in knowledge representation practices of libraries that operate in North America and Western Europe. However, some other regions of the world, in particular the Arabian Gulf region which includes Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates, are currently underrepresented in this research. The exploratory project presented in this paper aimed to address this gap with the goal of developing an understanding of the current state of knowledge representation (including descriptive metadata practices, identity management, use of knowledge organisation systems, and more) in academic libraries of Kuwait, Oman, and Qatar, as well as plans and preparedness of these institutions and their staff for future developments in this area to facilitate discovery of resources, specifically in the aggregated digital environment. The qualitative study used semi-structured interviews of metadata managers at a representative sample of regional university libraries. The findings provide insights into this previously under-researched area and contribute to understanding of related knowledge management barriers and perspectives on a global scale. Implications for practice and research are discussed.

Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra.

Human-associated bacteria secrete modified peptides to control host physiology and remodel the microbiota species composition. Here we scanned 2,229 Human Microbiome Project genomes of species colonizing skin, gastrointestinal tract, urogenital tract, mouth and trachea for gene clusters encoding RiPPs (ribosomally synthesized and post-translationally modified peptides). We found 218 lanthipeptides and 25 lasso peptides, 70 of which were synthesized and expressed in E. coli and 23 could be purified and functionally characterized. They were tested for activity against bacteria associated with healthy human flora and pathogens. New antibiotics were identified against strains implicated in skin, nasal and vaginal dysbiosis as well as from oral strains selectively targeting those in the gut. Extended- and narrow-spectrum antibiotics were found against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Mining natural products produced by human-associated microbes will enable the elucidation of ecological relationships and may be a rich resource for antimicrobial discovery.

Environmental impacts of shallow water mining in the Baltic Sea

The discovery of rare metal resources in international waters has raised seabed mining claims for large areas of the bottom. There is abundant scientific evidence of major negative consequences for the maritime environment, such as the destruction of natural landforms and the fauna that depend on them, as well as the production of enormous silt plumes that disrupt aquatic life. This study investigated the environmental risks of seabed mining for metal resources in the Baltic Sea using a combination of hydrodynamic, particle-tracking, and sediment-transport models. The models were applied for ten years i.e., 2000-2009 under prevailing conditions to simulate seabed mining operations. The focus was on sediment concentration near the seabed and its spread. The mean background concentrations were low with small seasonal bed-level variations throughout the Baltic Sea Basin. Late summer and early autumn periods were the most active. Seabed mining significantly alters the dynamics of sediment suspensions and bed level variations. The concentrations increase unsustainably to high levels, posing a serious threat to the ecological health of the Baltic Sea. The Gotland basins in the Baltic Sea are the most susceptible to mining. The bed level variations will be ten-fold, exposing the highly contaminated sediments at the seabed to the flow. In less than a year, 30-60% of the total particles released in each basin reached the thermocline layers. This study suggests that seabed mining in the Baltic Sea is not sustainable.

Oceans of Ooze

Historians of science increasingly turn to ocean spaces, especially from the mid–twentieth century, when oceanography adopted new strategic and economic significance during and after World War II. Yet, the overdetermination of oceanography’s historiography by histories of conflict obscures the role that empire—its continuities and its ends—played in the transformation of ocean science and politics at the same time. This essay builds on recent work seeking to recover the role of empire’s endurance and its long shadows in the construction of mid-twentieth-century ocean science, politics, and law. Focusing on deep-sea sediments, I parse the work of H.M.S. Challenger (1872–1876) naturalist-cum-Challenger Office director John Murray alongside that of American economic geologist John Mero, who in the mid–twentieth century articulated all seabeds as storehouses of vast mineral wealth. Murray’s sedimentological taxonomies and representations as well as his collected data on global oozes, nodules included, formed much of the basis for Mero’s work. And, both Murray and Mero leveraged sediments to argue for proprietary positions premised on priority-in-time for resource discovery claims, and exclusive access based upon scientific knowledge and technical ability, both masked by tropes of equal access and opportunity. These data and practices helped Northern scientists build and maintain control over knowledge of the seabed and the value of its resources, as postcolonial and Cold War impetuses rearranged political and economic order at sea. Historicizing abyssal oozes illuminates the character of contemporary conflicts over the future of the international seabed, asking, who determines how the seabed will be valued?

Loving the Alien: The Contribution of the Wild in Securing the Breeding of Cultivated Hexaploid Wheat and Oats

Cereal production is of strategic importance to the world economy. Although the primary aim of breeding programs is to develop cultivars with improved agronomic performance, including high grain yield and grain quality, as well as disease and lodging resistance, nowadays the adaptability to changing environmental conditions seems to be an extremely important feature. The achievement of these breeding objectives in diploid cereal species such as rice, barley, or maize is straightforward. The genetic improvement of polyploid crops such as hexaploid wheat and oats for increased crop production is highly demanding. Progenitor species and wild relatives, including taxa at lower ploidy levels, have preserved a high degree of useful genetic variation. The world’s genebank collections of wheat and oat germplasm provide extremely rich resources for future breeding and utilization. This review highlights the immense potential of cultivated wild relatives as donors of genes for a wide range of biotic and abiotic traits and their impact on wheat and oat breeding. This review covers methods allowing access to these genetic resources, and it highlights the most (and most recently)-exploited related species for gene introgression in wheat and oats. Further, it will also deal with the impact of genomics and cloned genes on the advanced discovery, characterization, and utilization of genetic resources in these two cereals.

Exploring the visual distinguishability and topic autocorrelation of murals unearthed in China from the spatial perspective

Murals unearthed in China have outstanding regional characteristics and one of the largest period spans in scale and variety. To explore the visual distinguishability and topic autocorrelation of murals unearthed in China from the spatial perspective, multiple classification models are employed to classify murals unearthed in China through visual features. Then, the k-means is employed to mine topics, and they are analysed through topic intensities (TIs), Moran’s Index (MI) and spatial topic concentration degrees (STCDs). In addition, the characteristics of topic distribution and evolution are summarised and revealed in the spatial dimension. From a spatial perspective, it verifies the distinguishability of visual features of murals through ViT_BOW_GNB, and the precision of this model is 98.17%. Thirteen topics are clustered through k-means, and the distribution of mural topics is spatial autocorrelation according to MI. Besides, the topic evolves from the political centre to the surrounding area, and the topics with high intensities are highly concentrated in spatial. This study reveals the spatial characteristics of the mural at the level of visual features and semantics, which facilitates the digital management, conservation and knowledge discovery of cultural heritage resources.

The groundnut improvement network for Africa (GINA) germplasm collection: a unique genetic resource for breeding and gene discovery.

Cultivated peanut or groundnut (Arachis hypogaea L.) is a grain legume grown in many developing countries by smallholder farmers for food, feed, and/or income. The speciation of the cultivated species, that involved polyploidization followed by domestication, greatly reduced its variability at the DNA level. Mobilizing peanut diversity is a prerequisite for any breeding program for overcoming the main constraints that plague production and for increasing yield in farmer fields. In this study, the Groundnut Improvement Network for Africa assembled a collection of 1,049 peanut breeding lines, varieties, and landraces from 9 countries in Africa. The collection was genotyped with the Axiom_Arachis2 48K SNP array and 8,229 polymorphic single nucleotide polymorphism (SNP) markers were used to analyze the genetic structure of this collection and quantify the level of genetic diversity in each breeding program. A supervised model was developed using dapc to unambiguously assign 542, 35, and 172 genotypes to the Spanish, Valencia, and Virginia market types, respectively. Distance-based clustering of the collection showed a clear grouping structure according to subspecies and market types, with 73% of the genotypes classified as fastigiata and 27% as hypogaea subspecies. Using STRUCTURE, the global structuration was confirmed and showed that, at a minimum membership of 0.8, 76% of the varieties that were not assigned by dapc were actually admixed. This was particularly the case of most of the genotype of the Valencia subgroup that exhibited admixed genetic heritage. The results also showed that the geographic origin (i.e. East, Southern, and West Africa) did not strongly explain the genetic structure. The gene diversity managed by each breeding program, measured by the expected heterozygosity, ranged from 0.25 to 0.39, with the Niger breeding program having the lowest diversity mainly because only lines that belong to the fastigiata subspecies are used in this program. Finally, we developed a core collection composed of 300 accessions based on breeding traits and genetic diversity. This collection, which is composed of 205 genotypes of fastigiata subspecies (158 Spanish and 47 Valencia) and 95 genotypes of hypogaea subspecies (all Virginia), improves the genetic diversity of each individual breeding program and is, therefore, a unique resource for allele mining and breeding.

DNA sequencing, microbial indicators, and the discovery of buried kimberlites

Population growth and technological advancements are placing growing demand on mineral resources. New and innovative exploration technologies that improve detection of deeply buried mineralization and host rocks are required to meet these demands. Here we used diamondiferous kimberlite ore bodies as a test case and show that DNA amplicon sequencing of soil microbial communities resolves anomalies in microbial community composition and structure that reflect the surface expression of kimberlites buried under 10 s of meters of overburden. Indicator species derived from laboratory amendment experiments were employed in an exploration survey in which the species distributions effectively delineated the surface expression of buried kimberlites. Additional indicator species derived directly from field observations improved the blind discovery of kimberlites buried beneath similar overburden types. Application of DNA sequence-based analyses of soil microbial communities to mineral deposit exploration provides a powerful illustration of how genomics technologies can be leveraged in the discovery of critical new resources.

Transcriptome analysis reveals molecular signature and cell-type difference of Homo sapiens endothelial-to-mesenchymal transition.

Endothelial-to-mesenchymal transition (EndoMT), a specific form of epithelial-to-mesenchymal transition, drives a growing number of human (Homo sapiens) pathological conditions. This emerging knowledge opens a path to discovering novel therapeutic targets for many EndoMT-associated disorders. Here, we constructed an atlas of the endothelial-cell transcriptome and demonstrated EndoMT-induced global changes in transcriptional gene expression. Our gene ontology analyses showed that EndoMT could be a specific checkpoint for leukocyte chemotaxis, adhesion, and transendothelial migration. We also identified distinct gene expression signatures underlying EndoMT across arterial, venous, and microvascular endothelial cells. We performed protein-protein interaction network analyses, identifying a class of highly connected hub genes in endothelial cells from different vascular beds. Moreover, we found that the short-chain fatty acid acetate strongly inhibits the transcriptional program of EndoMT in endothelial cells from different vascular beds across tissues. Our results reveal the molecular signature and cell-type difference of EndoMT across distinct tissue- and vascular-bed-specific endothelial cells, providing a powerful discovery tool and resource value. These results suggest that therapeutically manipulating the endothelial transcriptome could treat an increasing number of EndoMT-associated pathological conditions.

Hierarchical Virtual Screening of Potential New Antibiotics from Polyoxygenated Dibenzofurans against Staphylococcus aureus Strains.

Staphylococcus aureus is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the S. aureus MRSA and VRSA strains. To achieve this goal, tetrahydroxybenzofuran, a promising antibacterial agent according to in vitro tests described in the literature, was adopted as the pivotal molecule and derivative molecules were considered to generate a pharmacophore model, which was used to perform virtual screening on the Pharmit platform. Through this result, twenty-four molecules were selected from the MolPort® database. Using the Tanimoto Index on the BindingDB web server, it was possible to select eighteen molecules with greater structural similarity in relation to commercial antibiotics (methicillin and oxacillin). Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the eighteen most similar molecules, showed that only three exhibited desired properties (LB255, LB320 and LB415). In the molecular docking study, the promising molecules LB255, LB320 and LB415 showed significant values in both molecular targets. LB320 presented better binding affinity to MRSA (-8.18 kcal/mol) and VRSA (-8.01 kcal/mol) targets. Through PASS web server, the three molecules, specially LB320, showed potential for antibacterial activity. Synthetic accessibility (SA) analysis performed on AMBIT and SwissADME web servers showed that LB255 and LB415 can be considered difficult to synthesize and LB320 is considered easy. In conclusion, the results suggest that these ligands, particularly LB320, may bind strongly to the studied targets and may have appropriate ADME/Tox properties in experimental studies.

Efficient IoT resource discovery approach based on P2P networks and Fog Computing

The Internet of Things (IoT) objects, their provided resources and services, as well as their users, and the requests for these resources, are increasing. Consequently, it is becoming extremely difficult for users to find a specific IoT resource that fits their needs. The sheer number and wide range of equipment in IoT, coupled with the lack of standardized and coherent resource descriptions, have a significant impact on resource discovery. In this context, we propose a Fog-based Distributed Semantic IoT resource discovery (FDS-RD) solution. FDS-RD leverages semantic technologies and two levels of peer-to-peer (P2P) networks to provide a semantic and scalable IoT resource discovery. Additionally, to support real-time applications, FDS-RD capitalizes on the Fog computing paradigm to reduce the discovery time. Experimental results demonstrate that the proposed solution enhances the performance of the discovery process by increasing the relevance of the discovered resources and reducing the response time.

Insights into the plant growth promotion properties of bacterial endophytes isolated from Alternanthera philoxeroides and Eichhornia crassipes from Bellandur lake, India

The presence of macrophytes such as Alternanthera philoxeroides and Eichhornia crassipes in Bellandur Lake, India, has been observed despite the high pollution levels. Our research aims to explore the potential role of endophytes in promoting the growth of these macrophytes in such heavily contaminated environments. In current study, we isolated 20 endophytic bacteria from various parts of A. philoxeroides (12) and E. crassipes (8) plants, including shoots, roots, leaves, and flowers. We found that a significant proportion of endophytes from A. philoxeroides (42 %) and E. crassipes (25 %) produced more than 100 µg/mL of indole acetic acid (IAA). Similarly, the majority of the isolates possessed other plant growth promoting traits like ammonia production, nitrogen fixation, phosphate and potassium solubilization, siderophore production, and ACC deaminase production. Many of these isolates demonstrated extracellular enzyme production and halotolerance properties. We identified Acinetobacter soli ON529869 and Bacillus licheniformis ON506048 as the most effective plant growth promoters among the isolates, which also displayed antifungal properties against Fusarium solani and Cladosporium tenuissimum in vitro. Furthermore, greenhouse trials using these two endophytes revealed their significant plant growth promotion abilities in Amaranthus viridis. The pigment indices were evaluated using CI-710 Leaf Spectrometer. In conclusion, our findings provide compelling evidence for exploring the endophytic microbiomes of macrophytes in polluted areas for sustainable agriculture and bioprospecting of unique traits. This research could lead to the discovery of new and valuable resources for agricultural practices and other applications.

Integrated Volatile Metabolome and Transcriptome Analyses Provide Insights into the Formation of Benzenoid–Phenylpropanoid Aroma Substance Eugenol in the Rosa hybrida ‘Lanxing’ Flowering

Scent is the key character of the horticultural ornamental plant rose, and benzenoid–phenylpropanoid compounds are the main source of scent. However, the underlying biosynthesis mechanism of these benzenoid–phenylpropanoid scent metabolites during Rosa flowering is poorly understood. In this study, the volatile metabolome and transcriptome conjoint analysis was conducted on the six stages petals of the variety ‘Lanxing’ to investigate the synthesis of benzenoid–phenylpropanoid metabolites. A total of 25 benzenoid–phenylpropanoid volatile compounds were identified, of which eugenol possessed the highest content. Meanwhile, transcriptome analysis produced 87.9 million clean reads and 22,004 differentially expressed genes (DEGs). Group pairwise comparison of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis found DEGs were enriched into phenylpropanoid compound synthesis related pathway. Weighted gene co-expression network analysis (WGCNA) found a MEgreenyellow gene module (650 DEGs) correlated with phenylpropanoid compounds. Based on the eugenol content variation and gene spatio-temporal expression, a key candidate gene RcEGS32 related to the synthesis of eugenol was identified. Co-expression network analysis found that five transcription factors, RcMYB1, RcBES1, RcERF2, RcbHLH1, and RcTUB, may act as regulators in the eugenol synthesis process by directly binding to RcEGS32 or forming a complex unit. This study provided key insights into the formation of the scent substance eugenol during flowering, offering a valuable volatile metabolome and transcriptome resource for the future target trait-related gene discovery of roses.

Repurposing Normal Chromosomal Microarray Data to Harbor Genetic Insights into Congenital Heart Disease.

About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered by their nominal association with a CHD diagnosis, the expression level in the fetal heart, and the deleteriousness of a loss-of-function mutation. The subsequent enrichment for CHD genes was assessed using the presence of known or potentially novel genes implicated by a large whole-exome sequencing study of CHD. The unreported microdeletions were modestly enriched for both known CHD genes and those of unknown significance identified using their de novo mutation in CHD patients. Our results show that readily available "normal" CMA data can be a fruitful resource for genetic discovery and that smaller deletions should receive more attention in clinical evaluation.

Single-nucleus transcriptomic mapping uncovers targets for traumatic brain injury.

The subventricular zone (SVZ) is a neurogenic niche that contributes to homeostasis and repair after brain injury. However, the effects of mild traumatic brain injury (mTBI) on the divergence of the regulatory DNA landscape within the SVZ and its link to functional alterations remain unexplored. In this study, we mapped the transcriptome atlas of murine SVZ and its responses to mTBI at the single-cell level. We observed cell-specific gene expression changes following mTBI and unveiled diverse cell-to-cell interaction networks that influence a wide array of cellular processes. Moreover, we report novel neurogenesis lineage trajectories and related key transcription factors, which we validate through loss-of-function experiments. Specifically, we validate the role of Tcf7l1, a cell cycle gene regulator, in promoting neural stem cell differentiation toward the neuronal lineage after mTBI, providing a potential target for regenerative medicine. Overall, our study profiles an SVZ transcriptome reference map, which underlies the differential cellular behavior in response to mTBI. The identified key genes and pathways that may ameliorate brain damage or facilitate neural repair serve as a comprehensive resource for drug discovery in the context of mTBI.

On petrological principles of allocation of promising diamond-bearing areas for geological prospection in the northern Russian Platform

A comprehensive study of all magmatic manifestations of the Zimny Bereg kimberlite district (about 100 bodies) revealed a regular petrological zonality of the district, demonstrating both the central and linear types of the symmetry of distribution of the volcanites different in their composition and diamond-bearing potential. Elements of various petrological zonality are also noted for other areas of the northern Russian Platform: for the Tersk coast of the Kola Peninsula, the Nenok district of the Onega Peninsula, the Umba district of the Middle Timan, as well as for the entire White Sea region as a whole. These features can be used to identify the prospecting sites most promising for discovery of diamond deposits. The other most interesting districts of the northern Russian Platform are the Ust-Yansk diamond-bearing districts of the southern Arkhangelsk Region (that is characterized by a spatial coincidence of all favorable prerequisites and features, including the determined diamond-bearing potential of Quaternary deposits), as well as the Onega Peninsula and Timan Ridge. For more expeditious discovery of new diamond deposits, the intellectual, informational, industrial, and administrative resources of the individual subsoil users and scientific and governmental organizations are to be consolidated.

Conversational assistants in academic libraries: enhancing reference services through Bing Chat

Purpose This research aims to explore the integration of Bing Chat, an artificial intelligence (AI)-powered conversational assistant, into academic libraries and its potential impact on reference services. Design/methodology/approach This study analyzes existing literature to investigate the integration of Bing Chat in academic libraries. This research focuses on its features, capabilities and implications for enhancing user experiences and addressing information needs. Findings The findings highlight that Bing Chat’s conversational interface facilitates more dynamic and context-aware reference interactions, fostering user empowerment and personalized learning pathways. The integration of Bing Chat with existing library resources enhances resource discovery, navigational assistance and engagement with visual content. However, challenges related to accuracy, privacy and algorithmic bias require careful consideration. Originality/value This research contributes to the literature by providing an in-depth exploration of Bing Chat’s integration into academic libraries, emphasizing its transformative potential for reference services. This study addresses ethical and social dimensions associated with AI-driven tools in library environments, offering insights into ensuring fairness, privacy and user trust.

Recent progress in the reprogramming of nonribosomal peptide synthetases.

Nonribosomal peptide synthetases (NRPSs) biosynthesize nonribosomal peptide (NRP) natural products, which belong to the most promising resources for drug discovery and development because of their wide range of therapeutic applications. The results of genetic, biochemical, and bioinformatics analyses have enhanced our understanding of the mechanisms of the NRPS machinery. A major goal in NRP biosynthesis is to reprogram the NRPS machinery to enable the biosynthetic production of designed peptides. Reprogramming strategies for the NRPS machinery have progressed considerably in recent years, thereby increasing the yields and generating modified peptides. Here, the recent progress in NRPS reprogramming and its application in peptide synthesis are described.

Odor cues rather than personality affect tadpole deposition in a neotropical poison frog.

Animals constantly need to evaluate available external and internal information to make appropriate decisions. Identifying, assessing, and acting on relevant cues in contexts such as mate choice, intra-sexual competition, and parental care is particularly important for optimizing individual reproductive success. Several factors can influence decision-making, such as external environmental cues and the animal's own internal state, yet, we have limited knowledge on how animals integrate available information. Here, we used an entire island population (57 males, 53 females, and 1,109 tadpoles) of the neotropical brilliant-thighed poison frog Allobates femoralis to investigate how 2 factors (olfactory cues and personality traits) influence the ability of males to find and use new resources for tadpole deposition. We experimentally manipulated the location of tadpole deposition sites and their associated olfactory cues, and repeatedly measured exploration and boldness in adult males. We further reconstructed tadpole deposition choices via inferred parent-offspring relationships of adult frogs and tadpoles deposited in our experimental pools using molecular parentage analysis. We found that the discovery and use of new rearing sites were heavily influenced by olfactory cues; however, we did not find an effect of the measured behavioral traits on resource discovery and use. We conclude that in highly dynamic environments such as tropical rainforests, reliable external cues likely take priority over personality traits, helping individuals to discover and make use of reproductive resources.