GPR15 in colon cancer development and anti-tumor immune responses.

Introduction: The chemoattractant receptor, G protein-coupled receptor 15 (GPR15), promotes colon homing of T cells in health and colitis. GPR15 function in colon cancer is largely unexplored, motivating our current studies.

Methods: In human study, immune cells were isolated from tumor tissues and healthy surgical tumor margins (STM), and their proportions as well as expression of GPR15 was analyzed by flow cytometry.

Integrating inflammatory biomarker analysis and artificial-intelligence-enabled image-based profiling to identify drug targets for intestinal fibrosis.

Intestinal fibrosis, often caused by inflammatory bowel disease, can lead to intestinal stenosis and obstruction, but there are no approved treatments. Drug discovery has been hindered by the lack of screenable cellular phenotypes. To address this, we used a scalable image-based morphology assay called Cell Painting, augmented with machine learning algorithms, to identify small molecules that could reverse the activated fibrotic phenotype of intestinal myofibroblasts.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

Background: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD.

Aims: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation.

Genome-wide CRISPR Screening to Identify Drivers of TGF-β-Induced Liver Fibrosis in Human Hepatic Stellate Cells.

Liver fibrosis progression in chronic liver disease leads to cirrhosis, liver failure, or hepatocellular carcinoma and often ends in liver transplantation. Even with an increased understanding of liver fibrogenesis and many attempts to generate therapeutics specifically targeting fibrosis, there is no approved treatment for liver fibrosis. To further understand and characterize the driving mechanisms of liver fibrosis, we developed a high-throughput genome-wide CRISPR/Cas9 screening platform to identify hepatic stellate cell (HSC)-derived mediators of transforming growth factor (TGF)-β-induced liver fibrosis.

Effects of family history of substance use disorder on reward processing in adolescents with and without attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) often develop early onset substance use disorder (SUD) and show poor treatment outcomes. Both disorders show similar reward-processing alterations, but it is unclear whether these are associated with familial vulnerability to SUD. Our aim was to investigate effects of family history of SUD (FH) on reward processing in individuals with and without ADHD, without substance misuse.

Effects of substance misuse and current family history of substance use disorder on brain structure in adolescents and young adults with attention-deficit/hyperactivity disorder.

Background: Alterations in brain structure in attention-deficit/hyperactivity disorder (ADHD) show considerable overlap with those observed in substance use disorder (SUD). These overlapping structural alterations in ADHD and SUD might be explained by family history (FH-trait) effects of SUD, and/or substance misuse (state) effects. Our aim was to investigate effects of 1) current parental SUD (SUD-FH) and 2) recent substance misuse (SM) on brain structure in a cohort of ADHD patients and controls.

Characterizing miRNA-lncRNA Interplay.

Long noncoding RNAs (lncRNAs) are noncoding transcripts, usually longer than 200 nt, that constitute one of the largest and significantly heterogeneous RNA families. The annotation of lncRNAs and the characterization of their function is a constantly evolving field. LncRNA interplay with microRNAs (miRNAs) is thoroughly studied in several physiological and disease states.

AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing.

AKT-phosphorylated IWS1 regulates alternative RNA splicing via a pathway that is active in lung cancer. RNA-seq studies in lung adenocarcinoma cells lacking phosphorylated IWS1, identified a exon 2-deficient U2AF2 splice variant. Here, we show that exon 2 inclusion in the U2AF2 mRNA is a cell cycle-dependent process that is regulated by LEDGF/SRSF1 splicing complexes, whose assembly is controlled by the IWS1 phosphorylation-dependent deposition of histone H3K36me3 marks in the body of target genes.

A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal Permeability.

Background & Aims: The limited availability of organoid systems that mimic the molecular signatures and architecture of human intestinal epithelium has been an impediment to allowing them to be harnessed for the development of therapeutics as well as physiological insights. We developed a microphysiological Organ-on-Chip (Emulate, Inc, Boston, MA) platform designed to mimic properties of human intestinal epithelium leading to insights into barrier integrity.

Methods: We combined the human biopsy-derived leucine-rich repeat-containing G-protein-coupled receptor 5-positive organoids and Organ-on-Chip technologies to establish a micro-engineered human Colon Intestine-Chip (Emulate, Inc, Boston, MA).

Effects of substance misuse on inhibitory control in patients with attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) are often diagnosed with comorbid substance misuse (SM), which is associated with poor treatment efficacy. Although literature indicates similar inhibitory control deficits in both conditions, it is unclear whether SM in ADHD exaggerates pre-existing deficits, with additive or distinct impairments in patients. Our aim was to examine SM effects on inhibitory control in ADHD.

Effects of substance misuse on reward-processing in patients with attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD.

Effects of Substance Misuse and Family History of Substance Use Disorder on Delay Discounting in Adolescents and Young Adults with Attention-Deficit/Hyperactivity Disorder.

Background: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) often co-occur. Both disorders are characterized by impulsive choice. However, little is known about the effects of substance misuse (SM) and family history of SUD (FH) on impulsive choice in ADHD-SUD comorbidity.

DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts.

DIANA-LncBase v3.0 (www.microrna.

The combination of knockdown and TNFα causes synthetic lethality via caspase-8 activation in human carcinoma cell lines.

Most normal and tumor cells are protected from tumor necrosis factor α (TNFα)-induced apoptosis. Here, we identify the MAP3 kinase tumor progression locus-2 (TPL2) as a player contributing to the protection of a subset of tumor cell lines. The combination of knockdown and TNFα gives rise to a synthetic lethality phenotype via receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-dependent and -independent mechanisms.

microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions.

Argonaute crosslinking and immunoprecipitation (CLIP) experiments are the most widely used high-throughput methodologies for miRNA targetome characterization. The analysis of Photoactivatable Ribonucleoside-Enhanced (PAR) CLIP methodology focuses on sequence clusters containing T-to-C conversions. Here, we demonstrate for the first time that the non-T-to-C clusters, frequently observed in PAR-CLIP experiments, exhibit functional miRNA-binding events and strong RNA accessibility.

DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA-gene interactions.

DIANA-TarBase v8 (http://www.microrna.gr/tarbase) is a reference database devoted to the indexing of experimentally supported microRNA (miRNA) targets.

BUFET: boosting the unbiased miRNA functional enrichment analysis using bitsets.

Background: A group of miRNAs can regulate a biological process by targeting genes involved in the process. The unbiased miRNA functional enrichment analysis is the most precise in silico approach to predict the biological processes that may be regulated by a given miRNA group. However, it is computationally intensive and significantly more expensive than its alternatives.

A perspective on AKT 25-plus years after its discovery.

Since its discovery more than 25 years ago, the kinase AKT has become a central figure in cell signaling. We highlight some of the landmark findings in those 25 years that contributed to our understanding of the regulation and function of AKT in directing cellular processes and behavior. Future progress toward fully understanding the roles of AKT in cell, tissue, and organismal biology will depend on technological innovations and the combination of in-depth reductionist analyses with systems-based strategies.

Neuronal ELAVL proteins utilize AUF-1 as a co-partner to induce neuron-specific alternative splicing of APP.

Aβ peptide that accumulates in Alzheimer's disease brain, derives from proteolytic processing of the amyloid precursor protein (APP) that exists in three main isoforms derived by alternative splicing. The isoform APP695, lacking exons 7 and 8, is predominately expressed in neurons and abnormal neuronal splicing of APP has been observed in the brain of patients with Alzheimer's disease. Herein, we demonstrate that expression of the neuronal members of the ELAVL protein family (nELAVLs) correlate with APP695 levels in vitro and in vivo.

RNAcentral: a comprehensive database of non-coding RNA sequences.

RNAcentral is a database of non-coding RNA (ncRNA) sequences that aggregates data from specialised ncRNA resources and provides a single entry point for accessing ncRNA sequences of all ncRNA types from all organisms. Since its launch in 2014, RNAcentral has integrated twelve new resources, taking the total number of collaborating database to 22, and began importing new types of data, such as modified nucleotides from MODOMICS and PDB. We created new species-specific identifiers that refer to unique RNA sequences within a context of single species.

The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species.

Background: The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control.

DIANA-TarBase and DIANA Suite Tools: Studying Experimentally Supported microRNA Targets.

microRNAs (miRNAs) are short non-coding RNAs (∼22 nts) present in animals, plants, and viruses. They are considered central post-transcriptional regulators of gene expression and are key components in a great number of physiological and pathological conditions. The accurate characterization of their targets is considered essential to a series of applications and basic or applied research settings.

DIANA-mirExTra v2.0: Uncovering microRNAs and transcription factors with crucial roles in NGS expression data.

Differential expression analysis (DEA) is one of the main instruments utilized for revealing molecular mechanisms in pathological and physiological conditions. DIANA-mirExTra v2.0 (http://www.