In the human genome, there are several genes whose primary transcripts are both canonically and non-canonically spliced to generate mRNAs and RNA circles, respectively. These RNA circles are a novel ...class of long non-coding RNAs that became known as circular RNAs (circRNAs). Recently, a new type of circRNA was discovered and called read-through circRNAs (rt-circRNAs). They are hybrid circles that include coding exons from two adjacent and similarly oriented genes. The function of rt-circRNAs, as well as the impact of read-through transcription in our transcriptome, remains to be elucidated. Although we have just begun to scratch it, here I discussed some insights that these fascinating circRNAs are already giving us about the plasticity of RNA processing in our cells.
Apoptosis is one of the main types of regulated cell death, a complex process that can be triggered by external or internal stimuli, which activate the extrinsic or the intrinsic pathway, ...respectively. Among various factors involved in apoptosis, several genes and their interactive networks are crucial regulators of the outcomes of each apoptotic phase. Furthermore, mitochondria are key players in determining the way by which cells will react to internal stress stimuli, thus being the main contributor of the intrinsic pathway, in addition to providing energy for the whole process. Other factors that have been reported as important players of this intricate molecular network are miRNAs, which regulate the genes involved in the apoptotic process. Imbalance in any of these mechanisms can lead to the development of several illnesses, hence, an overall understanding of these processes is essential for the comprehension of such situations. Although apoptosis has been widely studied, the current literature lacks an updated and more general overview on this subject. Therefore, here, we review and discuss the mechanisms of apoptosis, highlighting the roles of genes, miRNAs, and mitochondria involved in this type of cell death.
Mitochondria are organelles responsible for several functions involved in cellular balance, including energy generation and apoptosis. For decades now, it has been well-known that mitochondria have ...their own genetic material (mitochondrial DNA), which is different from nuclear DNA in many ways. More recently, studies indicated that, much like nuclear DNA, mitochondrial DNA is regulated by epigenetic factors, particularly DNA methylation and non-coding RNAs (ncRNAs). This field is now called mitoepigenetics. Additionally, it has also been established that nucleus and mitochondria are constantly communicating to each other to regulate different cellular pathways. However, little is known about the mechanisms underlying mitoepigenetics and nuclei-mitochondria communication, and also about the involvement of the ncRNAs in mitochondrial functions and related diseases. In this context, this review presents the state-of-the-art knowledge, focusing on ncRNAs as new players in mitoepigenetic regulation and discussing future perspectives of these fields.
Gastric cancer (GC) represents a notable amount of morbidity and mortality worldwide. Understanding the molecular basis of CG will offer insight into its pathogenesis in an attempt to identify new ...molecular biomarkers to early diagnose this disease. Therefore, studies involving small non-coding RNAs have been widely explored. Among these, PIWI-interacting RNAs (piRNAs) are an emergent class that can play important roles in carcinogenesis. In this study, small-RNA sequencing was used to identify the global piRNAs expression profile (piRNome) of gastric cancer patients. We found 698 piRNAs in gastric tissues, 14 of which were differentially expressed (DE) between gastric cancer (GC), adjacent to gastric cancer (ADJ), and non-cancer tissues (NC). Moreover, three of these DE piRNAs (piR-48966*, piR-49145, piR-31335*) were differently expressed in both GC and ADJ samples in comparison to NC samples, indicating that the tumor-adjacent tissue was molecularly altered and should not be considered as a normal control. These three piRNAs are potential risk biomarkers for GC, especially piR-48966* and piR-31335*. Furthermore, an in-silico search for mRNAs targeted by the differentially expressed piRNAs revealed that these piRNAs may regulate genes that participate in cancer-related pathways, suggesting that these small non-coding RNAs may be directly and indirectly involved in gastric carcinogenesis.
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in ...non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (
= 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.
Background: Parkinson’s disease (PD) is currently the second most common neurodegenerative disorder, burdening about 10 million elderly individuals worldwide. The multifactorial nature of PD poses a ...difficult obstacle for understanding the mechanisms involved in its onset and progression. Currently, diagnosis depends on the appearance of clinical signs, some of which are shared among various neurologic disorders, hindering early diagnosis. There are no effective tools to prevent PD onset, detect the disease in early stages or accurately report the risk of disease progression. Hence, there is an increasing demand for biomarkers that may identify disease onset and progression, as treatment-based medicine may not be the best approach for PD. Over the last few decades, the search for molecular markers to predict susceptibility, aid in accurate diagnosis and evaluate the progress of PD have intensified, but strategies aimed to improve individualized patient care have not yet been established. Conclusions: Genomic variation, regulation by epigenomic mechanisms, as well as the influence of the host gut microbiome seem to have a crucial role in the onset and progress of PD, thus are considered potential biomarkers. As such, the human nuclear and mitochondrial genome, epigenome, and the host gut microbiome might be the key elements to the rise of personalized medicine for PD patients.
In this work we study the decidability of a class of global modal logics arising from Kripke frames evaluated over certain residuated lattices, known in the literature as modal many-valued logics. We ...exhibit a large family of these modal logics which are undecidable, in contrast with classical modal logic and propositional logics defined over the same classes of algebras. This family includes the global modal logics arising from Kripke frames evaluated over the standard Łukasiewicz and Product algebras. We later refine the previous result, and prove that global modal Łukasiewicz and Product logics are not even recursively axiomatizable. We conclude by closing negatively the open question of whether each global modal logic coincides with its local modal logic closed under the unrestricted necessitation rule.
This paper is focused on the study of modal logics defined from valued Kripke frames, and particularly, on computability and expressivity questions of modal logics of transitive Kripke frames ...evaluated over certain residuated lattices. It is shown that a large family of those logics -including the ones arising from the standard MV and Product algebras- yields an undecidable consequence relation. Later on, the behavior of transitive modal Łukasiewicz logic is compared with that of its non-transitive counterpart, exhibiting some particulars concerning computability and equivalence with other logics. We conclude the article by showing the undecidability of the validity and the local SAT questions over transitive models when the Δ operation is added to the logic.
Clausal Forms in MaxSAT and MinSAT Li, Chu Min; Manyà, Felip; Soler, Joan Ramon ...
International journal of computational intelligence systems,
11/2022, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We tackle the problem of reducing non-clausal MaxSAT and MinSAT to clausal MaxSAT and MinSAT. Our motivation is twofold: (i) the clausal form transformations used in SAT are unsound for MaxSAT and ...MinSAT, because they do not preserve the minimum or maximum number of unsatisfied clauses, and (ii) the state-of-the-art MaxSAT and MinSAT solvers require as input a multiset of clauses. The main contribution of this paper is the definition of three different cost-preserving transformations. Two transformations extend the usual equivalence preserving transformation used in SAT to MaxSAT and MinSAT. The third one extends the well-known Tseitin transformation. Furthermore, we report on an empirical comparison of the performance of the proposed transformations when solved with a state-of-the-art MaxSAT solver.
Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the ...etiology of the disease, genetic and epigenetic factors are also required for its progression. Among the epigenetic factors are included the long noncoding RNAs (lncRNAs), transcripts of more than 200 nucleotides (nt) that generally do not code for proteins and have been associated with diverse functions such as the regulation of transcription, translation, RNA metabolism, as well as stem cell maintenance and differentiation, cell autophagy and apoptosis. Recently, studies have begun to characterize the aberrant regulation of lncRNAs in CC cells and tissues, including Homeobox transcript antisense RNA (HOTAIR), H19, Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), Cervical Carcinoma High-Expressed 1 (CCHE1), Antisense noncoding RNA in the inhibitors of cyclin-dependent kinase 4 (ANRIL), Growth arrest special 5 (GAS5) and Plasmacytoma variant translocation 1 (PVT1). They have been associated with several disease-related processes such as cell growth, cell proliferation, cell survival, metastasis and invasion as well as therapeutic resistance, and are novel potential biomarkers for diagnosis and prognosis in CC. In this review, we summarize the current literature regarding the knowledge we have about the roles and mechanisms of the lncRNAs in cervical neoplasia.
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