Biological Interest Research Articles

Mass Spectral Imaging to Map Plant-Microbe Interactions.

Plant-microbe interactions are of rising interest in plant sustainability, biomass production, plant biology, and systems biology. These interactions have been a challenge to detect until recent advancements in mass spectrometry imaging. Plants and microbes interact in four main regions within the plant, the rhizosphere, endosphere, phyllosphere, and spermosphere. This mini review covers the challenges within investigations of plant and microbe interactions. We highlight the importance of sample preparation and comparisons among time-of-flight secondary ion mass spectroscopy (ToF-SIMS), matrix-assisted laser desorption/ionization (MALDI), laser desorption ionization (LDI/LDPI), and desorption electrospray ionization (DESI) techniques used for the analysis of these interactions. Using mass spectral imaging (MSI) to study plants and microbes offers advantages in understanding microbe and host interactions at the molecular level with single-cell and community communication information. More research utilizing MSI has emerged in the past several years. We first introduce the principles of major MSI techniques that have been employed in the research of microorganisms. An overview of proper sample preparation methods is offered as a prerequisite for successful MSI analysis. Traditionally, dried or cryogenically prepared, frozen samples have been used; however, they do not provide a true representation of the bacterial biofilms compared to living cell analysis and chemical imaging. New developments such as microfluidic devices that can be used under a vacuum are highly desirable for the application of MSI techniques, such as ToF-SIMS, because they have a subcellular spatial resolution to map and image plant and microbe interactions, including the potential to elucidate metabolic pathways and cell-to-cell interactions. Promising results due to recent MSI advancements in the past five years are selected and highlighted. The latest developments utilizing machine learning are captured as an important outlook for maximal output using MSI to study microorganisms.

Assessing troglomorphic and phylogenetically informative traits in troglobionts: a new cave-dwelling centipede illuminates the evolution of a soil-dwelling lineage (Chilopoda: Geophilidae)

Cave-dwelling species are of special interest in evolutionary biology, because (i) many share particular traits associated with the cave habitat (troglomorphic traits), and (ii) some represent relict lineages that may conserve ancestral traits or possibly transitional traits, which may provide insights into the evolution of other highly derived species. However, these different kinds of characters are hard to assess thoroughly in troglobionts belonging to little known terrestrial arthropod groups. We describe a new species of centipedes from the Areias System caves, Brazil, namely, Plutogeophilus jurupariquibaba gen.n. sp.n., which adds to the few putative troglobionts known among Chilopoda Geophilomorpha. We analyzed a suite of characters in the light of a phylogenetic analysis and by direct comparison with epigean relatives, controlling for interindividual variation and its confounding sources. We found that: (i) troglomorphic traits of P. jurupariquibaba may include large body, elongate antennae, elongate legs and claws, and possibly also elongate setae and large coxal pores; (ii) the cave-dwelling Plutogeophilus is the sister lineage of the soil-dwelling Macronicophilus, whose morphology is highly derived and whose phylogenetic position remained unclear; (iii) compared with other extant geophilids, symplesiomorphic traits and apparently intermediate traits found in Plutogeophilus provide insights on the origin of the morphology of Macronicophilus, suggesting a stepwise modification of labrum, forcipular apparatus and ultimate legs, and the derivation of the unique rounded and spiny tip of the second maxillae from a pointed claw.

Nitroalkanes as thioacyl equivalents to access thioamides and thiopeptides

Thioamides are an important, but a largely underexplored class of amide bioisostere in peptides. Replacement of oxoamide units with thioamides in peptide therapeutics is a valuable tactic to improve biological activity and resistance to enzymatic hydrolysis. This tactic, however, has been hampered by insufficient methods to introduce thioamide bonds into peptide or protein backbones in a site-specific and stereo-retentive fashion. In this work, we developed an efficient and mild thioacylation method to react nitroalkanes with amines directly in the presence of elemental sulfur and sodium sulfide to form a diverse range of thioamides in high yields. Notably, this convenient method can be employed for the controlled thioamide coupling of multifunctionalized peptides without epimerization of stereocenters, including the late stage thioacylation of advanced compounds of biological and medicinal interest. Experimental interrogation of postulated mechanisms currently supports the intermediacy of thioacyl species.

Emergence of Ag as a Catalyst of Choice for Fluorination and Trifluoromethylation Reactions

AbstractCarbon‐fluorine bond being highly polar in nature, its presence in pharmaceutically active molecules has huge impact on their chemical and physical properties. However, fluorine being highly electronegative and small in size, limits its nucleophilicity to the large extent; hence the incorporation of fluorine in the organic molecules is not an easy task. Due to this, demand for a suitable catalyst for fluorination reaction has been raised, which lowers the activation energy of these reactions and makes C−F/CF3 bond formation reaction kinetically more feasible. Silver being a late transition metal catalyst has been efficiently used to catalyze several reactions in the organic chemistry and has the substantial potential to catalyze the fluorination reactions. This Review shows the silver catalyzed fluorination and trifluoromethylation reactions for the synthesis of F/CF3 containing aromatic, aliphatic and heterocyclic compounds. All the sections have been elaborated using general discussion of the method, exploration of substrate scope, insight into the mechanistic studies and the shortcomings of the methods. After reading this Review article the readers can develop a detailed understanding of concept of silver metal catalyzed fluorination and trifluoromethylation reactions which can be explored for synthesizing molecules of biological interest.

Disproportionation and dimerisation of kynurenic acid under UV light

In this work, we report on the photo-induced oxidation of kynurenic acid (KNA) by the triplet-excited KNA in a neutral aqueous solution. This reaction is confirmed by two different time-resolved methods: optical spectroscopy and chemically induced dynamic nuclear polarization (CIDNP). The disproportionation reaction proceeds with the rate constant of (6.0 ± 1.2) × 107 M−1s−1 via the mechanism of H-atom transfer to the photoexcited KNA in the triplet state, yielding the reduced and oxidized forms of KNA, KNAH2− and KNA(-H)−, respectively. The formation of these radicals is confirmed by a good proportionality relationship between the calculated proton hyperfine coupling constants of both radicals and the signal intensities in 1H CIDNP spectra detected after the recombination of the geminate radical pairs formed immediately after the laser pulse. The oxidized forms of KNA recombine yielding dimeric KNA-KNA products crosslinked via different positions within aromatic systems. The oxidized form of KNA, KNA(-H)−, could be of high biological interest due to its ability to recombine with other electron-deficient radicals, including tryptophan and tyrosine radicals, unravelling a radical pathway for the covalent attachment of KNA to proteins in living tissues.

Extending the range of metal ions SERS detection using hybrid plasmonic/ZIF-8 particles

Nanosensors based on surface-enhanced Raman spectroscopy (SERS) have emerged as a class of promising optical tools for the ultrasensitive quantification of metal ions of environmental and biological interest. A central bottleneck in this field is the availability of suitable surface receptors able to convert the selective binding with these vibrationless analytes into measurable SERS signals. In this work, we tackle this issue by employing a hybrid substrate comprising a highly SERS-active plasmonic core and a ZIF-8 metal-organic framework (MOF) shell. The ZIF-8 shell firmly captures aromatic receptors close to the plasmonic structure regardless of their intrinsic affinity for the metallic surface and without altering their ability to coordinate metal ions. Furthermore, it imparts molecular sieving abilities enabling the direct use of the SERS sensing platform in complex media such as biological fluids. This was demonstrated by using different classes of chromogenic reagents (bathocuproine, a 2,6':2′,2″-terpyridine derivative, and Arsenazo III) which were exploited for the SERS detection of both transition and alkaline earth metal ions (i.e., divalent copper, cobalt and calcium ions). Notably, we successfully applied this approach for the detection of Cu(II) in untreated urine samples for Wilson's disease diagnosis. Overall, we believe this class of multifunctional hybrid substrates will serve as a valuable material for expanding the applicability of SERS spectroscopy in real-life environmental and biomedical metal ions analysis.

Redox regulation, thioredoxins and glutaredoxins in retrograde signalling and in gene transcription.

Integration of reactive oxygen species (ROS)-mediated signal transduction pathways via redox sensors and the thiol-dependent signalling network is of increasing interest in cell biology for their implications in plant growth and productivity. Redox regulation is an important point of control in the protein structure, interactions, cellular location and function, thioredoxins (TRXs) and glutaredoxins (GRXs) being key players in the maintenance of cellular redox homeostasis. The crosstalk between second messengers, ROS, thiol redox signalling and redox homeostasis-related genes, controls almost every aspect of plant development and stress response. We review the emerging roles of TRXs and GRXs in redox-regulated processes interacting with other cell signalling systems such as organellar retrograde communication and gene expression, especially in plants during their development and under stressful environments. This approach will throw light on the specific role of these proteins as redox signalling components, and their importance in different developmental processes during abiotic stress.

Fostering Secondary School Students' interest in Biology Using Numbered Heads Together Cooperative Instructional Strategy

The study investigated the effect of numbered heads together cooperative instructional strategy (NHT) on secondary school students’ interest in biology in Awka Education Zone. Two research questions and three null hypotheses tested at 0.05 level of significance guided the study. The study is quasi-experimental research, adopting specifically the pretest posttest non-randomized control group of 2x2 factorial research design. 4755 senior secondary year two (SS2) students constituted the population. Multi-stage sampling procedure was employed to compose the sample size of 64 (21 males and 43 females) SS2 students. The sampled students who were in two intact classes were randomly assigned to experimental (23 girls and 10 boys) and control (20 girls and 11 boys) groups using a flip of a coin. A 20-item Biology students interest scale (BSIS), with five response options, developed by the researchers was used for data collection. The biology students interest scale was validated by three experts and with reliability index of 0.77 established using Cronbach alpha. Students in the experimental group was taught selected concepts in biology using NHT while those in the control group was taught the same concepts using Conventional Lecture Method (CLM). Mean and Standard deviation were used in answering the research questions while Analysis of Covariance (ANCOVA) was used to test the null hypotheses at 0.05 alpha level. The findings of the study revealed that NHT is more effective in fostering students’ interest in biology than CLM. Gender had no significant influence on students’ interest in biology. Also, there was no interaction effect of teaching methods and gender on students’ interest in biology. The study therefore concluded that NHT is a gender friendly approach that fosters students’ interest in biology as it involves the group working together and every member of the team taking accountability of the group. Based on the findings, recommendations were made among which include that NHT should be adopted by biology teachers in schools to foster students’ interest in biology.

MTG-Link: leveraging barcode information from linked-reads to assemble specific loci

BackgroundLocal assembly with short and long reads has proven to be very useful in many applications: reconstruction of the sequence of a locus of interest, gap-filling in draft assemblies, as well as alternative allele reconstruction of large Structural Variants. Whereas linked-read technologies have a great potential to assemble specific loci as they provide long-range information while maintaining the power and accuracy of short-read sequencing, there is a lack of local assembly tools for linked-read data.ResultsWe present MTG-Link, a novel local assembly tool dedicated to linked-reads. The originality of the method lies in its read subsampling step which takes advantage of the barcode information contained in linked-reads mapped in flanking regions. We validated our approach on several datasets from different linked-read technologies. We show that MTG-Link is able to assemble successfully large sequences, up to dozens of Kb. We also demonstrate that the read subsampling step of MTG-Link considerably improves the local assembly of specific loci compared to other existing short-read local assembly tools. Furthermore, MTG-Link was able to fully characterize large insertion variants and deletion breakpoints in a human genome and to reconstruct dark regions in clinically-relevant human genes. It also improved the contiguity of a 1.3 Mb locus of biological interest in several individual genomes of the mimetic butterfly Heliconius numata.ConclusionsMTG-Link is an efficient local assembly tool designed for different linked-read sequencing technologies. MTG-Link source code is available at https://github.com/anne-gcd/MTG-Link and as a Bioconda package.

N-Edited Guanine Isosteres.

Guanine is one out of five endogenous nucleobases and of key interest in drug discovery and chemical biology. Hitherto, the synthesis of guanine derivatives involves lengthy multistep sequential synthesis of low overall diversity, resulting in the quest for innovation. Using a "single-atom skeletal editing" approach, we designed 2-aminoimidazo[2,1-f][1,2,4]triazin-4(3H)-one as a guanine isostere, conserving the biologically important HBA-HBD-HBD (HBA = hydrogen bond acceptor; HBD = hydrogen bond donor) substructure. We realized our design by a simple one-pot two-step method combining the Groebke-Blackburn-Bienaymé reaction (GBB-3CR) and a deprotection reaction to assemble the innovative guanine isosteres in moderate to good yields. Our innovative, diverse, short, and reliable multicomponent reaction synthesis will add to the toolbox of guanine isostere syntheses.

A highly contiguous reference genome for the Steller's jay (Cyanocitta stelleri).

The Steller's jay is a familiar bird of western forests from Alaska south to Nicaragua. Here, we report a draft reference assembly for the species generated from PacBio HiFi long-read and Omni-C chromatin-proximity sequencing data as part of the California Conservation Genomics Project (CCGP). Sequenced reads were assembled into 352 scaffolds totaling 1.16 Gb in length. Assembly metrics indicate a highly contiguous and complete assembly with a contig N50 of 7.8 Mb, scaffold N50 of 25.8 Mb, and BUSCO completeness score of 97.2%. Repetitive elements span 16.6% of the genome including nearly 90% of the W chromosome. Compared with high-quality assemblies from other members of the family Corvidae, the Steller's jay genome contains a larger proportion of repetitive elements than 4 crow species (Corvus), but a lower proportion of repetitive elements than the California scrub-jay (Aphelocoma californica). This reference genome will serve as an essential resource for future studies on speciation, local adaptation, phylogeography, and conservation genetics in this species of significant biological interest.

Hierarchical structure in language and action: A formal comparison.

Since the cognitive revolution, language and action have been compared as cognitive systems, with cross-domain convergent views recently gaining renewed interest in biology, neuroscience, and cognitive science. Language and action are both combinatorial systems whose mode of combination has been argued to be hierarchical, combining elements into constituents of increasingly larger size. This structural similarity has led to the suggestion that they rely on shared cognitive and neural resources. In this article, we compare the conceptual and formal properties of hierarchy in language and action using set theory. We show that the strong compositionality of language requires a particular formalism, a magma, to describe the algebraic structure corresponding to the set of hierarchical structures underlying sentences. When this formalism is applied to actions, it appears to be both too strong and too weak. To overcome these limitations, which are related to the weak compositionality and sequential nature of action structures, we formalize the algebraic structure corresponding to the set of actions as a trace monoid. We aim to capture the different system properties of language and action in terms of the distinction between hierarchical sets and hierarchical sequences and discuss the implications for the way both systems could be represented in the brain. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emerging Role of Glioma Stem Cells in Mechanisms of Therapy Resistance.

Since their discovery at the beginning of this millennium, glioma stem cells (GSCs) have sparked extensive research and an energetic scientific debate about their contribution to glioblastoma (GBM) initiation, progression, relapse, and resistance. Different molecular subtypes of GBM coexist within the same tumor, and they display differential sensitivity to chemotherapy. GSCs contribute to tumor heterogeneity and recapitulate pathway alterations described for the three GBM subtypes found in patients. GSCs show a high degree of plasticity, allowing for interconversion between different molecular GBM subtypes, with distinct proliferative potential, and different degrees of self-renewal and differentiation. This high degree of plasticity permits adaptation to the environmental changes introduced by chemo- and radiation therapy. Evidence from mouse models indicates that GSCs repopulate brain tumors after therapeutic intervention, and due to GSC plasticity, they reconstitute heterogeneity in recurrent tumors. GSCs are also inherently resilient to standard-of-care therapy, and mechanisms of resistance include enhanced DNA damage repair, MGMT promoter demethylation, autophagy, impaired induction of apoptosis, metabolic adaptation, chemoresistance, and immune evasion. The remarkable oncogenic properties of GSCs have inspired considerable interest in better understanding GSC biology and functions, as they might represent attractive targets to advance the currently limited therapeutic options for GBM patients. This has raised expectations for the development of novel targeted therapeutic approaches, including targeting GSC plasticity, chimeric antigen receptor T (CAR T) cells, and oncolytic viruses. In this review, we focus on the role of GSCs as drivers of GBM and therapy resistance, and we discuss how insights into GSC biology and plasticity might advance GSC-directed curative approaches.

Undergraduate Internship on Yamuna River Exploration: Raising Awareness about SDG6

A semester-long internship was designed for undergraduate students at the University of Delhi, India. Teams comprising 30 students from all over the University were trained to carry out field exploration activities on the Yamuna River flowing in Delhi. The students were provided with portable kits to measure the physicochemical parameters at a selected bank of the Yamuna River. Students documented the invertebrate fauna in the riparian zone of the banks. At the same time, they noted the anthropogenic polluting activities on the bank of the Yamuna River. This internship educated students about the UN’s Sustainable Development Goals (SDGs). They all studied Ecology and Environmental Science in their undergraduate curriculum, but they all confessed that they were unaware of the 17 SDGs and the deteriorating health of the Yamuna River in the city. We educated students about the freshwater emergency recovery plan and the International Union for Conservation of Nature (IUCN) red list of ecosystems. This internship is a great example of an undergraduate-directed study or research experience that supported student constructivism and inquiry-based learning, and this research article elaborates on student reports and situational interest in freshwater biology to achieve SDG6.

A histological analysis of coloration in the Peruvian mimic poison frog (Ranitomeya imitator).

Aposematism continues to be a phenomenon of central interest in evolutionary biology. The life history of the mimic poison frog, Ranitomeya imitator, relies heavily on aposematism. In order for aposematic signals to be effective, predators must be able to learn to avoid the associated phenotype. However, in R. imitator, aposematism is associated with four different color phenotypes that mimic a complex of congeneric species occurring across the mimic frog's geographic range. Investigations of the underlying mechanics of color production in these frogs can provide insights into how and why these different morphs evolved. We used histological samples to examine divergence in the color production mechanisms used by R. imitator to produce effective aposematic signals across its geographic range. We measured the coverage of melanophores and xanthophores (the area covered by chromatophores divided by total area of the skin section) in each color morph. We find that morphs that produce orange skin exhibit a higher coverage of xanthophores and lower coverage of melanophores than those that produce yellow skin. In turn, morphs that produce yellow skin exhibit a higher coverage of xanthophores and lower coverage of melanophores than those that produce green skin. Generally, across the morphs, a high ratio of xanthophores to melanophores is associated with colors of brighter spectral reflectance. Together, our results contribute to the understanding of color production in amphibians and document divergence in the histology of a species that is subject to divergent selection associated with aposematism.

Development of a Rapid, Targeted LC-IM-MS Method for Anabolic Steroids.

Anabolic steroids are of high biological interest due to their involvement in human development and disease progression. Additionally, they are banned in sport due to their performance-enhancing characteristics. Analytical challenges associated with their measurement stem from structural heterogeneity, poor ionization efficiency, and low natural abundance. Their importance in a variety of clinically relevant assays has prompted the consideration of integrating ion mobility spectrometry (IMS) into existing LC-MS assays, due primarily to its speed and structure-based separation capability. Herein we have optimized a rapid (2 min) targeted LC-IM-MS method for the detection and quantification of 40 anabolic steroids and their metabolites. First, a steroid-specific calibrant mixture was developed to cover the full range of retention time, mobility, and accurate mass. Importantly, this use of this calibrant mixture provided robust and reproducible measurements based on collision cross section (CCS) with interday reproducibility of <0.5%. Furthermore, the combined separation power of LC coupled to IM provided comprehensive differentiation of isomers/isobars within 6 different isobaric groups. Multiplexed IM acquisition also provided improved limits of detection, which were well below 1 ng/mL in almost all compounds measured. This method was also capable of steroid profiling, providing quantitative ratios (e.g., testosterone/epitestosterone, androsterone/etiocholanolone, etc.). Lastly, phase II steroid metabolites were probed in lieu of hydrolysis to demonstrate the ability to separate those analytes and provide information beyond total steroid concentration. This method has tremendous potential for rapid analysis of steroid profiles in human urine spanning a variety of applications from developmental disorders to doping in sport.

Inferring links in directed complex networks through feed forward loop motifs

Complex networks are mathematical abstractions of real-world systems using sets of nodes and edges representing the entities and their interactions. Prediction of unknown interactions in such networks is a problem of interest in biology, sociology, physics, engineering, etc. Most complex networks exhibit the recurrence of subnetworks, called network motifs. Within the realm of social science, link prediction (LP) models are employed to model opinions, trust, privacy, rumor spreading in social media, academic and corporate collaborations, liaisons among lawbreakers, and human mobility resulting in contagion. We present an LP metric based on a motif in directed complex networks, called feed-forward loop (FFL). Unlike nearest neighbor-based metrics and machine learning-based techniques that gauge the likelihood of a link based on node similarity, the proposed approach leverages a known dichotomy in the motif distribution of directed networks. Complex networks are sparse, causing most nodes and their associated links to have low motif participation. Yet, due to intrinsic network motif-richness, few links participate in many distinct motif substructures. Thus, the FFL-based metric combines the presence and absence of motifs as a signature to outperform baseline metrics on ten directed social and biological network datasets. We conclude with the future of the FFL-based metric in dynamic network inference as well as its use in designing combined metrics using network motifs of varying orders as features.

100 years of glucagon and 100 more.

The peptide hormone glucagon, discovered in late 1922, is secreted from pancreatic alpha cells and is an essential regulator of metabolic homeostasis. This review summarises experiences since the discovery of glucagon regarding basic and clinical aspects of this hormone and speculations on the future directions for glucagon biology and glucagon-based therapies. The review was based on the international glucagon conference, entitled 'A hundred years with glucagon and a hundred more', held in Copenhagen, Denmark, in November 2022. The scientific and therapeutic focus of glucagon biology has mainly been related to its role in diabetes. In type 1 diabetes, the glucose-raising properties of glucagon have been leveraged to therapeutically restore hypoglycaemia. The hyperglucagonaemia evident in type 2 diabetes has been proposed to contribute to hyperglycaemia, raising questions regarding underlying mechanism and the importance of this in the pathogenesis of diabetes. Mimicry experiments of glucagon signalling have fuelled the development of several pharmacological compounds including glucagon receptor (GCGR) antagonists, GCGR agonists and, more recently, dual and triple receptor agonists combining glucagon and incretin hormone receptor agonism. From these studies and from earlier observations in extreme cases of either glucagon deficiency or excess secretion, the physiological role of glucagon has expanded to also involve hepatic protein and lipid metabolism. The interplay between the pancreas and the liver, known as the liver-alpha cell axis, reflects the importance of glucagon for glucose, amino acid and lipid metabolism. In individuals with diabetes and fatty liver diseases, glucagon's hepatic actions may be partly impaired resulting in elevated levels of glucagonotropic amino acids, dyslipidaemia and hyperglucagonaemia, reflecting a new, so far largely unexplored pathophysiological phenomenon termed 'glucagon resistance'. Importantly, the hyperglucagonaemia as part of glucagon resistance may result in increased hepatic glucose production and hyperglycaemia. Emerging glucagon-based therapies show a beneficial impact on weight loss and fatty liver diseases and this has sparked a renewed interest in glucagon biology to enable further pharmacological pursuits.

PoliViews: A comprehensive and modular approach to the conceptual modeling of genomic data

The human genome complexity is captured by many signals, representing for instance DNA variations, the expression of gene activity, or DNA’s structural rearrangements; a rich set of data types and formats is used to record these signals. Conceptual models can support the description and explanation of the genome’s elaborate structure and behavior. Among others, the Conceptual Schema of the Human Genome (CSG) provides a concept-oriented, top-down representation of the genome behavior, which is independent of data formats. The Genomic Conceptual Model (GCM) provides instead a data-oriented, bottom-up representation, targeting a well-organized, unified description of these formats. In this research, we join the two approaches to achieve PoliViews, a comprehensive model that links (1) a concepts layer, describing genome elements and their conceptual connections, with (2) a data layer, describing datasets derived from genome sequencing with specific technologies. Their dynamic connection is established when specific genomic data types are chosen in the data layer, thereby triggering the selection of a view in the concepts layer. The benefit is mutual: data records can be semantically described by high-level concepts exploiting their links and, in turn, the continuously evolving abstract model can be extended thanks to the input provided by real datasets. PoliViews enables expressing queries that employ a holistic conceptual perspective on the genome, directly translated onto data-oriented terms and organization. Here, we demonstrate the approach by linking two major genomic data types, namely DNA variation and gene expression. For each type, we consider different eminent data sources; we describe their mapping with the corresponding view in the concepts layer, enabling an intra-data-type integration. Then, leveraging on the connections available in the concepts layer, we show how the distinct data types can be interoperated, enabling an inter-data-type integration. The PoliViews approach is shown through several examples of biological interest and can be further extended to any kind of genomic information.

Accuracy Meets Feasibility for the Structures and Rotational Constants of the Molecular Bricks of Life: A Joint Venture of DFT and Wave-Function Methods.

A fully unsupervised computational protocol is proposed with the aim of obtaining reliable structural properties for molecular bricks of life in the gas phase. The results of the new composite scheme approach spectroscopic accuracy at a moderate cost without any empirical parameter in addition to those of the underlying electronic structure method. The whole workflow is fully automated and provides optimized geometries and equilibrium rotational constants. Direct comparison with experimental ground state rotational constants can be performed thanks to the effective computation of vibrational corrections in the framework of second-order vibrational perturbation theory. The results for all the nucleic acid bases and several flexible molecules of biological or medicinal interest show that the accuracy of the new tool is close to that delivered by state-of-the-art composite wave function methods for small semirigid molecules.