Targets For Experimental Studies Research Articles

Machine learning approaches to predict TAS2R receptors for bitterants.

Bitter taste involves the detection of diverse chemical compounds by a family of G protein-coupled receptors, known as taste receptor type 2 (TAS2R). It is often linked to toxins and harmful compounds and in particular bitter taste receptors participate in the regulation of glucose homeostasis, modulation of immune and inflammatory responses, and may have implications for various diseases. Human TAS2Rs are characterized by their polymorphism and differ in localization and function. Different receptors can activate various signaling pathways depending on the tissue and the ligand. However, in vitro screening of possible TAS2R ligands is costly and time-consuming. For this reason, in silico methods to predict bitterant-TAS2R interactions could be powerful tools to help in the selection of ligands and targets for experimental studies and improve our knowledge of bitter receptor roles. Machine learning (ML) is a branch of artificial intelligence that applies algorithms to large datasets to learn from patterns and make predictions. In recent years, there has been a record of numerous taste classifiers in literature, especially on bitter/non-bitter or bitter/sweet classification. However, only a few of them exploit ML to predict which TAS2R receptors could be targeted by bitter molecules. Indeed, the shortage and incompleteness of data on receptor-ligand associations in literature make this task non-trivial. In this work, we provide an overview of the state of the art dealing with this specific investigation, focusing on three ML-based models, namely BitterX (2016), BitterSweet (2019) and BitterMatch (2022). This review aims to establish the foundation for future research endeavours focused on addressing the limitations and drawbacks of existing models.

Exploring the conservation of Alzheimer-related pathways between H. sapiens and C. elegans: a network alignment approach

Alzheimer disease (AD) is a neurodegenerative disorder with an –as of yet– unclear etiology and pathogenesis. Research to unveil disease processes underlying AD often relies on the use of neurodegenerative disease model organisms, such as Caenorhabditis elegans. This study sought to identify biological pathways implicated in AD that are conserved in Homo sapiens and C. elegans. Protein–protein interaction networks were assembled for amyloid precursor protein (APP) and Tau in H. sapiens—two proteins whose aggregation is a hallmark in AD—and their orthologs APL-1 and PTL-1 for C. elegans. Global network alignment was used to compare these networks and determine similar, likely conserved, network regions. This comparison revealed that two prominent pathways, the APP-processing and the Tau-phosphorylation pathways, are highly conserved in both organisms. While the majority of interactions between proteins in those pathways are known to be associated with AD in human, they remain unexamined in C. elegans, signifying the need for their further investigation. In this work, we have highlighted conserved interactions related to AD in humans and have identified specific proteins that can act as targets for experimental studies in C. elegans, aiming to uncover the underlying mechanisms of AD.

Novel solid $$^4$$He targets for experimental studies on nuclear reactions: $$^6$$Li + $$^4$$He differential cross-section measurement at incident energy of 5.5 MeV

A specially prepared Si/He thin solid film was investigated as a suitable target for experimental studies on nuclear reactions involving $$^4$$ He targets. For that purpose, the elastically scattered $$^4$$ He recoil coming from the reaction $$^6$$ Li + $$^4$$ He at incident energy of 5.5 MeV was measured. The differential cross section of $$^6$$ Li on $$^{4}$$ He has been found to be fully consistent with previous measurements in the literature. The prospective advantages of using these solid He targets in experiments at radioactive beam facilities are discussed.

An ectopic macrochaeta in the middle of a compound eye of a field-collected anthomyiid fly

Recording and describing animal 'monsters' collected in the field can still contribute to progress in developmental biology despite the uncontrolled conditions the specimen experienced throughout development. Comparison with model organisms and a sound phylogenetic analysis may offer a tentative explanation for the underlying developmental mechanism and suggest new targets for experimental studies. We describe a female specimen of the anthomyiid fly Hydrophoria sp. with an ectopic macrochaeta in the left eye and suggest tentative interpretations, including one in terms of a local expression, or derepression, of a proneural gene. The anthomyiid lineage has been estimated to have split ca. 65 million years ago from the dipteran clade containing Drosophila and ca. 140 million years ago from the clade containing Megaselia.

Within- and between-generation effects of temperature on life-history traits in a butterfly

Non-genetic parental effects may largely affect offspring phenotype, and such plasticity is potentially adaptive. Despite its potential importance, little is known about cross-generational effects of temperature, at least partly because parental effects were frequently considered a troublesome nuisance, rather than a target of experimental studies. We here investigate effects of parental, developmental and acclimation temperature on life-history traits in the butterfly Bicyclus anynana. Higher developmental temperatures reduced development times and egg size, increased egg number, but did not affect pupal mass. Between-generation temperature effects on larval time, pupal time, larval growth rate and egg size were qualitatively very similar to effects of developmental temperature, and additionally affected pupal mass but not egg number. Parental effects are important mediators of phenotypic plasticity in B. anynana, and partly yielded antagonistic effects on different components of fitness, which may constrain the evolution of cross-generational adaptive plasticity.

Theoretical designs for triplet ground-state carbenes: A target for experimental studies

A density functional study of triplet ground-state carbenes was carried out using the B3LYP/6-311G(d) and B3LYP/cc-PVTZ_DK methods. The structures of 10 model carbenes in their closed-shell singlet and open-shell triplet states were obtained. Both a valence electron model and our quantum calculations strongly suggest that a persistent triplet ground-state carbene occurs when the carbenic center is attached to two bulky substituents arranged in a perpendicular conformation. If the attached substituents bear aromatic rings, then their ortho positions must be occupied by other protecting groups. Moreover, if the attached atoms are less electronegative than the carbon atom, this can also lead to an increase in the singlet-triplet energy gap, and thus to further stabilization of the triplet state. The results obtained allow a number of predictions to be made.

The energy substrate switch during development of heart failure: gene regulatory mechanisms (Review).

During cardiac hypertrophy and in the failing heart, the chief myocardial energy substrate switches from fatty acids to glucose. In this review, we describe recent progress in the elucidation of the molecular regulatory events involved in the dramatic downregulation of the expression of fatty acid utilization enzymes during development of cardiac hypertrophy and failure. Much of this work has focused on the gene encoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyzes a pivotal step in the mitochondrial fatty acid -oxidation (FAO) cycle. In vivo ventricular pressure overload studies performed in mice transgenic for human MCAD promoter fragments linked to reporter genes have shown that transcription is markedly downregulated within seven days of pressure overload. The temporal pattern of this alteration in MCAD gene expression has also been characterized in a rat model of progressive pressure overload-induced left ventricular hypertrophy (LVH) and heart failure (HF) [SHHF/Mcc-facp (SHHF) rat]. MCAD mRNA levels are downregulated (>70%) during both the LVH and HF stages in the SHHF rats compared with controls. In contrast, the activity and immunodetectable levels of MCAD enzyme were not significantly reduced until the HF stage, indicating additional compensatory control at the translational or post-translational levels in the hypertrophied but non-failing ventricle. FAO enzyme expression was also shown to be downregulated in human subjects with dilated cardiomyopathy compared to age-matched controls. Taken together, these results have identified a gene regulatory program that is involved in the alterations in myocardial energy substrate utilization in the failing heart. The temporal correlation of diminished enzyme expression with onset of heart failure suggests that this alteration in lipid metabolism may play a role in the pathogenesis of pressure-overload induced heart failure. This gene regulatory pathway should be a useful target for experimental studies aimed at the molecular pathogenesis of the transition from stable cardiac hypertrophy to overt heart failure.