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Transposable elements (TEs) have been implicated in autism spectrum disorder (ASD). However, our understanding of their roles is far from complete. Herein, we explored de novo TE insertions (dnTEIs) and de novo variants (DNVs) across the genomes of dizygotic twins with ASD and their parents. The neuronal regulatory elements had a tendency to harbor dnTEIs that were shared between twins, but ASD-risk genes had dnTEIs that were unique to each twin. The dnTEIs were 4.6-fold enriched in enhancers that are active in embryonic stem cell (ESC)-neurons (p < 0.001), but DNVs were 1.5-fold enriched in active enhancers of astrocytes (p = 0.0051). Our findings suggest that dnTEIs and DNVs play a role in ASD etiology by disrupting enhancers of neurons and astrocytes.

Bladder cancers are heterogeneous in nature, showing diverse molecular profiles and histopathological characteristics, which pose challenges for diagnosis and treatment. However, understanding the molecular basis of such heterogeneity has remained elusive. This study aimed to elucidate the molecular landscape of neuroendocrine‐like bladder tumors, focusing on the involvement of β‐catenin localization. Analyzing the transcriptome data and benefiting from the molecular classification tool, we undertook an in‐depth analysis of muscle‐invasive bladder cancers to uncover the molecular characteristics of the neuroendocrine‐like differentiation. The study explored the contribution of transcription factors and chromatin remodeling complexes to neuroendocrine differentiation in bladder cancer. The study revealed a significant correlation between β‐catenin localization and neuroendocrine differentiation in muscle‐invasive bladder tumors, highlighting the molecular complexity of neuroendocrine‐like tumors. Enrichment of YY1 transcription factor, E2F family members, and Polycomb repressive complex components in β‐catenin‐positive tumors suggest their potential contribution to neuroendocrine phenotypes. Our findings contribute valuable insights into the molecular complexity of neuroendocrine‐like bladder tumors. By identifying potential therapeutic targets and refining diagnostic strategies, this study advances our understanding of endocrinology in the context of bladder cancer. Further investigations into the functional implications of these molecular relationships are warranted to enhance our knowledge and guide future therapeutic interventions. [ABSTRACT FROM AUTHOR]

The glioma genome encompasses a complex array of dysregulatory events, presenting a formidable challenge in managing this devastating disease. Despite the widespread distribution of repeat and transposable elements across the human genome, their involvement in glioma's molecular pathology and patient survival remains largely unexplored. In this study, we aimed to characterize the links between the expressions of repeat/transposable elements with disease progression and survival in glioma patients. Hence, we analyzed the expression levels of satellite repeats and transposons along with genes in low-grade glioma (LGG) and high-grade glioma (HGG). Endogenous transposable elements LTR5 and HERV_a-int exhibited higher expression in HGG patients, along with immune response-related genes. Altogether, 16 transposable elements were associated with slower progression of disease in LGG patients. Conversely, 22 transposons and the HSAT5 satellite repeat were linked to a shorter event-free survival in HGG patients. Intriguingly, our weighted gene coexpression network analysis (WGCNA) disclosed that the HSAT5 satellite repeat resided in the same module network with genes implicated in chromosome segregation and nuclear division; potentially hinting at its contribution to disease pathogenesis. Collectively, we report for the first time that repeat and/or transposon expression could be related to disease progression and survival in glioma. The expressions of these elements seem to exert a protective effect during LGG-to-HGG progression, whereas they could have a detrimental impact once HGG is established. The results presented herein could serve as a foundation for further experimental work aimed at elucidating the molecular regulation of glioma genome. [ABSTRACT FROM AUTHOR]

Sialic acids are nine-carbon sugars that modify glycans on glycoconjugates and mediate important biological functions. While sialic acids have not been detected in insects (as it was considered that it is obtained from external sources), orthologs of sialic acid biosynthetic enzymes and insect ST6Gal sialyltransferases suggest ancestral sialylation pathways. Sialyltransferases contain conserved peptide regions called sialylmotifs (L, S, VS, III), participating in donor substrate binding and catalytic activity. We performed a computational analysis searching 27 insect proteomes for vertebrate sialylmotif sequences to identify putative novel insect sialyltransferases. Sialylmotif L sequences similar to mammalian ST3Gal IV and ST6GalNAc I were found in putative proteins from Galleria mellonella and Manduca sexta, respectively. Identifying sialyltransferase precursor genes in insects supports their evolutionary origin preceding vertebrate diversification. Despite the lack of sialic acid production, sialyltransferase genes in insects suggest an evolutionary perspective on conserved sialylation pathways. [ABSTRACT FROM AUTHOR]

Ophthalmic diseases affect many people, causing partial or total loss of vision and a reduced quality of life. The anterior segment of the eye accounts for nearly half of all visual impairment that can lead to blindness. Therefore, there is a growing demand for ocular research and regenerative medicine that specifically targets the anterior segment to improve vision quality. This study aims to generate a microfluidic platform for investigating the formation of the anterior segment of the eye derived from human induced pluripotent stem cells (hiPSC) under various spatial‐mechanoresponsive conditions. Microfluidic platforms are developed to examine the effects of dynamic conditions on the generation of hiPSCs‐derived ocular organoids. The differentiation protocol is validated, and mechanoresponsive genes are identified through transcriptomic analysis. Several culture strategies is implemented for the anterior segment of eye cells in a microfluidic chip. hiPSC‐derived cells showed anterior eye cell characteristics in mRNA and protein expression levels under dynamic culture conditions. The expression levels of yes‐associated protein and transcriptional coactivator PDZ binding motif (YAP/TAZ) and PIEZO1, varied depending on the differentiation and growth conditions of the cells, as well as the metabolomic profiles under dynamic culture conditions. [ABSTRACT FROM AUTHOR]

Since the start of COVID‐19 pandemic, a huge effort has been devoted to understanding the Spike (SARS‐CoV‐2)–ACE2 recognition mechanism. To this end, two deep mutational scanning studies traced the impact of all possible mutations across receptor binding domain (RBD) of Spike and catalytic domain of human ACE2. By concentrating on the interface mutations of these experimental data, we benchmarked six commonly used structure‐based binding affinity predictors (FoldX, EvoEF1, MutaBind2, SSIPe, HADDOCK, and UEP). These predictors were selected based on their user‐friendliness, accessibility, and speed. As a result of our benchmarking efforts, we observed that none of the methods could generate a meaningful correlation with the experimental binding data. The best correlation is achieved by FoldX (R = −0.51). When we simplified the prediction problem to a binary classification, that is, whether a mutation is enriching or depleting the binding, we showed that the highest accuracy is achieved by FoldX with a 64% success rate. Surprisingly, on this set, simple energetic scoring functions performed significantly better than the ones using extra evolutionary‐based terms, as in Mutabind and SSIPe. Furthermore, we demonstrated that recent AI approaches, mmCSM‐PPI and TopNetTree, yielded comparable performances to the force field‐based techniques. These observations suggest plenty of room to improve the binding affinity predictors in guessing the variant‐induced binding profile changes of a host–pathogen system, such as Spike–ACE2. To aid such improvements we provide our benchmarking data at https://github.com/CSB-KaracaLab/RBD-ACE2-MutBench with the option to visualize our mutant models at https://rbd-ace2-mutbench.github.io/. [ABSTRACT FROM AUTHOR]

Novel transcript discovery through RNA sequencing has substantially improved our understanding of the transcriptome dynamics of biological systems. Endogenous target mimicry (eTM) transcripts, a novel class of regulatory molecules, bind to their target microRNAs (miRNAs) by base pairing and block their biological activity. The objective of this study was to provide a computational analysis framework for the prediction of putative eTM sequences in plants, and as an example, to discover previously un-annotated eTMs in Prunus persica (peach) transcriptome. Therefore, two public peach transcriptome libraries downloaded from Sequence Read Archive (SRA) and a previously published set of long non-coding RNAs (lncRNAs) were investigated with multi-step analysis pipeline, and 44 putative eTMs were found. Additionally, an eTM-miRNA-mRNA regulatory network module associated with peach fruit organ development was built via integration of the miRNA target information and predicted eTM-miRNA interactions. My findings suggest that one of the most widely expressed miRNA families among diverse plant species, miR156, might be potentially sponged by seven putative eTMs. Besides, the study indicates eTMs potentially play roles in the regulation of development processes in peach fruit via targeting specific miRNAs. In conclusion, by following the step-by step instructions provided in this study, novel eTMs can be identified and annotated effectively in public plant transcriptome libraries.

Hyperhydricity is a syndrome that causes morpho-physiological malformations in tissue culture plantlets. Micro-RNAs (miRNA) are small non-coding RNAs that play important regulatory roles in plant development, stress response, and adaptation to environmental conditions. In this study, differential expression analysis indicated that miRNAs play an underlying role in the responses to the hyperhydricity syndrome in peach Prunus persica (L.) leaves. 24 known and three novel potential miRNAs were characterized in hyperhydric and non-hyperhydric transcriptome libraries. The miRNA-target transcript analyses indicated that transport, plant cuticle development, intracellular part, and stress response are regulated by miRNAs in hyperhydric leaves. It is also suggested that miR5021 and miRnovel2 might play critical regulatory roles in hyperhydricity regarding miRNA-based response to stress. This study went one step further to advance understanding of molecular miRNA-based regulatory mechanisms regarding responses to hyperhydricity in peach.