The BCR-ABL fusion protein with dysregulated tyrosine kinase activity is the cause of chronic myelogenous leukemia (CML). Mutations in the P-loop, gatekeeper, catalytic and activation loop, within its kinase domain leads to drug resistance while treating CML. The mutation driven drug resistance mechanisms at the atomic level in BCR-ABL needs to be unravelled. This work aims to study the structural, dynamical, and functional effects of the P-loop point mutations on BCR-ABL kinase. In this work, the five main FDA approved drugs Imatinib, Dasatinib, Nilotinib, Ponatinib, Bosutinib and one investigational drug Rebastinib were analysed using molecular dynamics (MD), post-MD analyses and quantum chemical (QM) approaches. The P-loop residue L248 and its point mutations (L248R/V) forming direct interactions with the drug were validated. The root-mean-square deviation analysis suggests that Imatinib, Dasatinib and Nilotinib are promising drugs for L248 and L248R/V point mutations, followed by Rebastinib, Ponatinib, and Bosutinib, despite minor variations. The R and C-spines of the wild and mutant systems differ significantly, indicating that the protein backbone is directly affected by mutation. For all the considered wild and mutated amino acid-drug complexes, the interaction energy for L248R complexes is high compared to L248 and L248V complexes. The frontier molecular orbitals, HOMO-LUMO gap, and electrostatic potential maps were analysed. The MD simulations and QM studies suggest that L248 residue and its point mutations (L248R/V) are responsible for high affinity binding of BCR-ABL kinase with the drugs considered for the study.

Ri/rol transformation by Rhizobium rhizogenes is well known to alter plant architecture, including shoot compactness, branching and root development. However, its significance for plant responses to nitrogen limitation remains unclear. Here, we investigated developmental, physiological and hormonal responses of an interspecific Kalanchoë laciniata × K. blossfeldiana hybrid to nitrogen deficiency using complementary pot and hydroponic experiments. Nitrogen deficiency strongly reduced leaf area and total biomass in both wild-type (WT) and rol-transformed (Rol) plants. Nevertheless, rol transformation consistently produced a more compact, highly branched phenotype, with increased leaf number, greater side-shoot formation, higher specific leaf area, lower leaf dry matter content, and, in hydroponics, a striking increase in root mass allocation. Rol plants also maintained higher chlorophyll and carotenoid concentrations than WT and showed altered carbon partitioning, with lower soluble sugars but a higher relative proportion of sucrose. Under nitrogen deficiency, Rol plants maintained positive net photosynthesis and higher electron transport, whereas WT plants showed near-complete suppression of CO2 assimilation despite high intercellular CO2 concentration, pointing to strong non-stomatal limitation. Rol plants were characterized by lower ABA and PA concentrations, reduced auxin pools and enhanced leaf cytokinin status. Under low N, greater root allocation in Rol plants was not accompanied by reduced overall growth when root expansion was unrestricted, suggesting compensation through higher specific leaf area and maintenance of photosynthetic function. The strong shift towards root investment highlights a potential role of rol transformation in applications where belowground biomass and root development are especially relevant.

Internalizing problems are prevalent in childhood and are associated with exposure to adverse childhood experiences (ACEs); however, their co-development across childhood remains understudied. Prior research documents sociodemographic disparities (i.e., race/ethnicity, sex, income) in ACE exposure and internalizing problems. The current study examined individual and co-developing trajectories of ACEs and internalizing problems and sociodemographic disparities among 4,655 diverse at-risk youth at ages 3, 5, and 9. Participants were 52.2% boys and racially and ethnically diverse, with 44.7% Black, 22.5% Hispanic, 16.7% Other, and 16.2% White youth. Results showed various trajectories with stable levels of cumulative ACE exposure over time and internalizing problems trajectories that decreased or increased over time. Findings provide some evidence for a dose-response relationship between ACEs and internalizing problems. Youth of Color (φ = 0.26, 0.11, 0.19) and from low-income backgrounds (ϵ2 = 0.07-0.09, 0.02, 0.06-0.08) were more likely to be in worse trajectories of ACEs, internalizing problems, and joint trajectories across ages 3, 5, and 9, respectively. Findings underscore the need for culturally responsive trauma-informed interventions and policy-level efforts that target the root cause of inequities.

One of the major issues in human health and disease is to find the basic physiology of various cellular processes and understand the root cause(s) of various diseases. It is true that various cellular processes are complex. It is estimated that in a single cell at any given point in time, a minimum of 1 trillion reactions or processes are occurring simultaneously. If this is true, it is almost mind-boggling to imagine how many processes or reactions are occurring in the whole body at a single point in time. Because it is nearly impossible to grasp all cellular or enzymatic reactions at once, researchers study individual reactions or processes in a specific cell or tissue at a given time, gradually piecing together the body's complex functions. Such an understanding is expected to, hopefully, help us to understand the most crucial cellular processes and thus try to decipher the pathological states of various diseases. Such an understanding of the various physiological processes and cellular reactions is expected to lead to the development of better diagnostic, therapeutic, and prognostic markers for various diseases. One such crucial endogenous chemical that follows a complex metabolic process with its involvement in various physiological and pathological processes is arachidonic acid (AA). In this section, a brief introduction to AA and its metabolism is provided.

Chromosomal rearrangement is a primary driver of speciation. The macroevolutionary forces governing diversification, however, remain poorly understood. This study aimed to elucidate the mechanisms of karyotypic evolution across Siluriformes (catfish), with an emphasis on the genomic plasticity of Clarias. Using a dataset of 88 species, we integrated continuous and discrete evolutionary models to evaluate the ancestral chromosomal states and tempo of karyotypic diversification. Our results revealed a basal Siluriform karyotype of n = 27, followed by 13 phylogenetic rate shifts that caused saltational transitions in diploid chromosome numbers (24 to 100) and fundamental chromosome numbers (NF = 40 to 136). Phylogenetic generalized least squares and Ornstein-Uhlenbeck modeling indicated that karyotypic trait evolution in Siluriformes is better described by an Ornstein-Uhlenbeck process than by neutral Brownian motion, indicating a tendency toward a model-inferred optimum. We identified a transition of haploid chromosome numbers from 27 to 28 in the African Clarias root, consistent with the hypothesis that chromosomal rearrangements may act as a recombination suppressor and facilitate semipermeable reproductive barriers in Clarias. This result indicates that fertile interspecific hybrid occurs between species with different karyotypes in Clarias, supporting a model of speciation with gene flow. By reconciling speciational bursts with selective constraints, this study provides a robust framework for understanding the complex genomic landscapes of teleosts and highlights the ecological role of karyotypic diversity in shaping catfish diversification.

A compelling new study on the evolution of plant cell types shows that the root endodermis has evolved independently twice. These two paths have led to identical structures (Casparian strips) that share no conserved molecular mechanisms.

Using cultured Glycyrrhiza glabra roots, we identified a new prenyltransferase involved in the formation of a variety of flavonoids, thereby revealing novel prenylated isoflavonoid pathways in licorice. Prenylated isoflavonoids are widely distributed specialized metabolites within the Fabaceae and contribute to various characteristic biological activities in both plants and humans. Several aromatic prenyltransferases (PTs) have been identified in Glycyrrhiza species, which are the most widely consumed crude drugs in traditional Chinese medicine. However, these enzymes do not sufficiently explain the structural diversity of prenylated flavonoids produced by the Glycyrrhiza genus. To identify additional novel PTs, we used elicited cultured Glycyrrhiza glabra roots as source material, where elicitor treatment increased the accumulation of multiple prenylated flavonoids. To identify the responsible enzyme, PT candidates were screened using G. uralensis transcriptomes, currently the sole publicly available transcriptomic resource within the genus, and a homolog designated GgBSPT1 (BSPT; a broad-substrate prenyltransferase) was subsequently isolated from elicited cultured G. glabra roots. GgBSPT1 differed from previously identified Glycyrrhiza PTs in both amino acid sequence and enzymatic properties. GgBSPT1 displayed unusually broad substrate acceptance across 20 distinct flavonoid structures and catalyzed regiospecific 3'-prenylation of isoliquiritigenin and 6-prenylation of five flavonoids. Overall, elicited cultured G. glabra roots enabled the identification of a previously unrecognized PT that is functionally distinct from earlier reported Glycyrrhiza PTs. This study provides new insights into the metabolic plasticity of Glycyrrhiza species and expands the enzymatic toolkit for future metabolic engineering of prenylated phytochemicals through the unusually broad substrate specificity of GgBSPT1.

Cold acclimation of young maize plants induced a light-dependent, organ-specific reprogramming at the metabolomic and gene expression levels, which significantly altered responses to salinity. It has been shown that light plays a decisive role in cold acclimation in plants. The core objective of the present work was to elucidate how light conditions during cold acclimation affect subsequent salt stress responses by co-regulating various processes among organs maize (Zea mays L.). Plants were cold-acclimated under sufficient light or shade and subsequently exposed to severe cold or salinity. Organ-specific analyses of leaves, stems, and roots combined chlorophyll fluorescence measurements with targeted and untargeted metabolomics, hormone and polyamine profiling, and stress-related gene expression were studied. Cold acclimation under sufficient light established organ-specific metabolic and transcriptional reprogramming that substantially altered subsequent salt stress responses. Light-acclimated plants showed coordinated, pathway-level metabolic adjustments across organs and distinct regulation of key stress-responsive genes, particularly in leaves and roots. Analyses indicated systemic, rather than isolated, metabolic rearrangements. These findings demonstrate that cold acclimation, depending on light intensity, establishes an organ-coordinated acclimated state that modulates subsequent salinity responses, highlighting the importance of environmental history and inter-organ regulation in stress adaptation. This study is the first to systematically reveal the organ-specific and systemic regulatory network underlying the light-temperature-salt interaction in maize.

The Wisconsin Department of Health Services received notice of an unusual number of cases of retinoblastoma in a small geographic area. Retinoblastoma is a rare pediatric eye cancer that strikes children aged <5 years. The reporters of these cases were concerned that they may be part of a cancer cluster. Cancer clusters are unusual numbers of cases in a defined geographic area over a defined period of time. They are believed to be caused by shared environmental or occupational risk factors. It is not known to what extent these risk factors play a role in retinoblastoma incidence.

Notopterygium incisum is not only a traditional Chinese medicine but also an endemic herb. Artificial domestication and large-scale cultivation are crucial for resolving the crisis of wild resources and the supply-demand imbalance of N. incisum, yet current techniques have failed to stably provide the herb medicine in good quality. Metagenomic analyses revealed significant differences in the rhizomicrobiota between wild and cultivated N. incisum, particularly in microbial composition, gene functions, and community assembly. The rhizomicrobiota of the wild N. incisum from 3 different sites with an altitude drop over 1400 m had a similar composition when being compared with the cultivated samples. The wild N. incisum had higher abundances of beneficial microbes, particularly Hyphomicrobiales (Rhizobiales) (21.27% on average). In contrast, the rhizosphere microbial communities of the cultivated N. incisum showed a high prevalence of functional genes involved in the pathways of DNA repair and recombination proteins, replication and repair, peptidases and inhibitors, DNA replication proteins, and transfer RNA biogenesis. The co-occurrence networks analysis indicated that the stability of the wild samples' network remained significantly more robust when nodes were proportionally removed, as the wild samples' network had approximately the same positive and negative links while the cultivated samples' network had nearly all positive links and many fewer connectors. This is related to the conclusion that wild N. incisum exhibits superior efficacy, as reported in previous studies. Additionally, it can be observed from the sampling images that the root surface of wild N. incisum has more pronounced tiny protrusions, which may be associated with rhizobial attachment, thereby enhancing the nitrogen fixation process. Importantly, the observed shifts in rhizosphere microbial communities, particularly the enrichment of beneficial rhizobia in wild plants, are closely linked to enhanced accumulation of bioactive secondary metabolites such as coumarins and volatile oils. These microbiome-driven differences are likely associated with the superior medicinal quality of wild N. incisum compared to cultivated counterparts, highlighting the pivotal role of rhizosphere microbes in shaping therapeutic efficacy.