In-silico study of antisense oligonucleotide antibiotics.

Background: The rapid emergence of antibiotic-resistant bacteria directly contributes to a wave of untreatable infections. The lack of new drug development is an important driver of this crisis. Most antibiotics today are small molecules that block vital processes in bacteria.

Electrocardiogram analysis of post-stroke elderly people using one-dimensional convolutional neural network model with gradient-weighted class activation mapping.

Stroke is the second leading cause of death globally after ischemic heart disease, also a risk factor of cardioembolic stroke. Thus, we postulate that heartbeats encapsulate vital signals related to stroke. With the rapid advancement of deep neural networks (DNNs), it emerges as a powerful tool to decipher intriguing heartbeat patterns associated with post-stroke patients.

Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury.

Injuries to the central nervous system (CNS) such as stroke, brain, and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration. The brain has a surprising intrinsic capability of recovering itself after injury. However, the hostile extrinsic microenvironment significantly hinders axon regeneration.

Identification of Blood Circular RNAs as Potential Biomarkers for Acute Ischemic Stroke.

Many hospitals lack facilities for accurate diagnosis of acute ischemic stroke (AIS). Circular RNA (circRNA) is highly expressed in the brain and is closely associated with stroke. In this study, we examined whether the blood-borne circRNAs could be promising candidates as adjunctive diagnostic biomarkers and their pathophysiological roles after stroke.

Overexpressed HSF1 cancer signature genes cluster in human chromosome 8q.

Background: HSF1 (heat shock factor 1) is a transcription factor that is found to facilitate malignant cancer development and proliferation. In cancer cells, HSF1 mediates a set of genes distinct from heat shock that contributes to malignancy. This set of genes is known as the HSF1 Cancer Signature genes or simply HSF1-CanSig genes.

gb4gv: a genome browser for .

Background: Geminiviruses (family ) are prevalent plant viruses that imperil agriculture globally, causing serious damage to the livelihood of farmers, particularly in developing countries. The virus evolves rapidly, attributing to its single-stranded genome propensity, resulting in worldwide circulation of diverse and viable genomes. Genomics is a prominent approach taken by researchers in elucidating the infectious mechanism of the virus.

U1 Adaptors Suppress the Oncogenic Axis in Human Pancreatic Cancer Xenografts.

Targeting KRAS and MYC has been a tremendous challenge in cancer drug development. Genetic studies in mouse models have validated the efficacy of silencing expression of both KRAS and MYC in mutant KRAS-driven tumors. We investigated the therapeutic potential of a new oligonucleotide-mediated gene silencing technology (U1 Adaptor) targeting KRAS and MYC in pancreatic cancer.

IDICAP: A Novel Tool for Integrating Drug Intervention Based on Cancer Panel.

Cancer is a heterogeneous disease afflicting millions of people of all ages and their families worldwide. Tremendous resources have been and continue to be devoted to the development of cancer treatments that target the unique mutation profiles of patients, namely targeted cancer therapy. However, the sheer volume of drugs coupled with cancer heterogeneity becomes a challenge for physicians to prescribe effective therapies targeting patients' unique genetic mutations.

Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for FLT3-ITD acute myeloid leukemia.

An in vitro drug-screening platform on patient samples was developed and validated to design personalized treatment for relapsed/refractory acute myeloid leukemia (AML). Unbiased clustering and correlation showed that homoharringtonine (HHT), also known as omacetaxine mepesuccinate, exhibited preferential antileukemia effect against AML carrying internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD). It worked synergistically with FLT3 inhibitors to suppress leukemia growth in vitro and in xenograft mouse models.

Bioinformatic analysis reveals genome size reduction and the emergence of tyrosine phosphorylation site in the movement protein of New World bipartite begomoviruses.

Begomovirus (genus Begomovirus, family Geminiviridae) infection is devastating to a wide variety of agricultural crops including tomato, squash, and cassava. Thus, understanding the replication and adaptation of begomoviruses has important translational value in alleviating substantial economic loss, particularly in developing countries. The bipartite genome of begomoviruses prevalent in the New World and their counterparts in the Old World share a high degree of genome homology except for a partially overlapping reading frame encoding the pre-coat protein (PCP, or AV2).

U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo.

U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2) and metabotropic glutamate receptor 1 (GRM1), in a human melanoma cell xenograft mouse model system.

A multispecies polyadenylation site model.

Background: Polyadenylation is present in all three domains of life, making it the most conserved post-transcriptional process compared with splicing and 5'-capping. Even though most mammalian poly(A) sites contain a highly conserved hexanucleotide in the upstream region and a far less conserved U/GU-rich sequence in the downstream region, there are many exceptions. Furthermore, poly(A) sites in other species, such as plants and invertebrates, exhibit high deviation from this genomic structure, making the construction of a general poly(A) site recognition model challenging.

Long conserved fragments upstream of Mammalian polyadenylation sites.

Polyadenylation is a cotranscriptional nuclear RNA processing event involving endonucleolytic cleavage of the nascent, emerging pre-messenger RNA (pre-mRNA) from the RNA polymerase, immediately followed by the polymerization of adenine ribonucleotides, called the poly(A) tail, to the cleaved 3' end of the polyadenylation site (PAS). This apparently simple molecular processing step has been discovered to be connected to transcription and splicing therefore increasing its potential for regulation of gene expression. Here, through a bioinformatic analysis of cis-PAS-regulatory elements in mammals that includes taking advantage of multiple evolutionary time scales, we find unexpected selection pressure much further upstream, up to 200 nt, from the PAS than previously thought.

iTriplet, a rule-based nucleic acid sequence motif finder.

Background: With the advent of high throughput sequencing techniques, large amounts of sequencing data are readily available for analysis. Natural biological signals are intrinsically highly variable making their complete identification a computationally challenging problem. Many attempts in using statistical or combinatorial approaches have been made with great success in the past.

Mutational analysis of a Dcp2-binding element reveals general enhancement of decapping by 5'-end stem-loop structures.

mRNA decapping is a critical step in the control of mRNA stability and gene expression and is carried out by the Dcp2 protein. Dcp2 is an RNA-binding protein that must bind the RNA in order to recognize the cap for hydrolysis. We previously demonstrated that a 60 nucleotide (nt) element at the 5' end of the mRNA encoding Rrp41 is preferentially bound and decapped by Dcp2.

A bipartite U1 site represses U1A expression by synergizing with PIE to inhibit nuclear polyadenylation.

U1A protein negatively autoregulates itself by polyadenylation inhibition of its own pre-mRNA by binding as two molecules to a 3'UTR-located Polyadenylation Inhibitory Element (PIE). The (U1A)2-PIE complex specifically blocks U1A mRNA biosynthesis by inhibiting polyA tail addition, leading to lower mRNA levels. U1 snRNP bound to a 5'ss-like sequence, which we call a U1 site, in the 3'UTRs of certain papillomaviruses leads to inhibition of viral late gene expression via a similar mechanism.