A dataset of transcriptomic effects of camptothecin treatment on early zebrafish embryos.

Zebrafish () are a good model for cancer research including studies on chemotherapy treatments. We treated wild-type and deletion mutant zebrafish embryos at 24 h post-fertilization with 1 µM of the topoisomerase I inhibitor, camptothecin (CPT), for 4 h to catalogue gene expression changes induced by this DNA damage treatment and to understand if these changes are influenced by loss of miR-34a. The 4 sample groups of 3 independent biological samples consisting of 30 embryos each were analyzed by RNA-sequencing using the recently updated zebrafish transcriptome annotation based on GRCz11, which enabled a more complete and sensitive read mapping and gene assignment than standard annotations.

miR-34a is a tumor suppressor in zebrafish and its expression levels impact metabolism, hematopoiesis and DNA damage.

Li-Fraumeni syndrome is caused by inherited TP53 tumor suppressor gene mutations. MicroRNA miR-34a is a p53 target and modifier gene. Interestingly, miR-34 triple-null mice exhibit normal p53 responses and no overt cancer development, but the lack of miR-34 promotes tumorigenesis in cancer-susceptible backgrounds.

Application of annotation-agnostic RNA sequencing data analysis tools for biomarker discovery in liquid biopsy.

RNA sequencing analysis is an important field in the study of extracellular vesicles (EVs), as these particles contain a variety of RNA species that may have diagnostic, prognostic and predictive value. Many of the bioinformatics tools currently used to analyze EV cargo rely on third-party annotations. Recently, analysis of unannotated expressed RNAs has become of interest, since these may provide complementary information to traditional annotated biomarkers or may help refine biological signatures used in machine learning by including unknown regions.

A novel CHD3 variant in a patient with central precocious puberty: Expanded phenotype of Snijders Blok-Campeau syndrome?

Snijders Blok-Campeau syndrome is an autosomal dominant genetic disorder first described in 2018, mostly associated with de novo variants in the CHD3 gene that affects chromatin remodeling. This syndrome is characterized by developmental delay, speech delay, and intellectual disability, but only about 60 affected individuals have been reported to date. We report a de novo likely pathogenic CHD3 variant (c.

Pathogenic variants carrier screening in New Brunswick: Acadians reveal high carrier frequency for multiple genetic disorders.

Background: Founder populations that have recently undergone important genetic bottlenecks such as French-Canadians and Ashkenazi Jews can harbor some pathogenic variants at a higher carrier rate than the general population, putting them at a higher risk for certain genetic diseases. In these populations, there can be considerable benefit to performing ethnic-based or expanded preconception carrier screening, which can help in the prevention or early diagnosis and management of some genetic diseases. Acadians are descendants of French immigrants who settled in the Atlantic Coast of Canada in the seventeenth century.

Pax-5 Protein Expression Is Regulated by Transcriptional 3'UTR Editing.

The gene encodes a transcription factor that is essential for B-cell commitment and maturation. However, deregulation is associated with various cancer lesions, notably hematopoietic cancers. Mechanistically, studies have characterized genetic alterations within the -5 locus that result in either dominant oncogenic function or haploinsufficiency-inducing mutations leading to oncogenesis.

A multiparametric extraction method for Vn96-isolated plasma extracellular vesicles and cell-free DNA that enables multi-omic profiling.

Extracellular vesicles (EVs) have been recognized as a rich material for the analysis of DNA, RNA, and protein biomarkers. A remaining challenge for the deployment of EV-based diagnostic and prognostic assays in liquid biopsy testing is the development of an EV isolation method that is amenable to a clinical diagnostic lab setting and is compatible with multiple types of biomarker analyses. We have previously designed a synthetic peptide, known as Vn96 (ME kit), which efficiently isolates EVs from multiple biofluids in a short timeframe without the use of specialized lab equipment.

EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex.

PAX5 and EBF1 work synergistically to regulate genes that are involved in B lymphocyte differentiation. We used the KIS-1 diffuse large B cell lymphoma cell line, which is reported to have elevated levels of PAX5 expression, to investigate the mechanism of EBF1- and PAX5-regulated gene expression. We demonstrate the lack of expression of hallmark B cell genes, including CD19, CD79b, and EBF1, in the KIS-1 cell line.

Phenotypic spectrum associated with pathogenic mutation in the NRG1 gene in Acadian family.

NRG1 is a gene that encodes for a protein that binds to a receptor of the tyrosine kinase family which is essential for the survival of the central nervous system development during embryogenesis. Mutation of the NRG1 gene causes aganglionosis, which leads to Hirschsprung disease. Two brothers of Acadian descent presented with a history of Hirschsprung disease, in association with other anomalies including congenital heart disease, learning difficulties, developmental issues, and hypopigmented hair patch.

Peptide-Affinity Precipitation of Extracellular Vesicles and Cell-Free DNA Improves Sequencing Performance for the Detection of Pathogenic Mutations in Lung Cancer Patient Plasma.

Liquid biopsy is a minimally-invasive diagnostic method that may improve access to molecular profiling for non-small cell lung cancer (NSCLC) patients. Although cell-free DNA (cf-DNA) isolation from plasma is the standard liquid biopsy method for detecting DNA mutations in cancer patients, the sensitivity can be highly variable. Vn96 is a peptide with an affinity for both extracellular vesicles (EVs) and circulating cf-DNA.

Transcriptomics-Based Approach Identifies Spinosad-Associated Targets in the Colorado Potato Beetle, .

The Colorado potato beetle is an insect pest that threatens potato crops globally. The primary method to control its damage on potato plants is the use of insecticides, including imidacloprid, chlorantraniliprole and spinosad. However, insecticide resistance has been frequently observed in Colorado potato beetles.

TAZ functions as a tumor suppressor in multiple myeloma by downregulating MYC.

Multiple myeloma (MM) is an incurable blood cancer that is often characterized by amplification and overexpression of the MYC oncogene. Despite efforts, direct targeting of MYC is not yet possible; therefore, alternative strategies to inhibit MYC activity are necessary. TAZ is a transcriptional coactivator downstream of the Hippo-signaling pathway that functions as an oncogene in many solid tumors.

A novel missense mutation in the MYH7 gene causes an uncharacteristic phenotype of myosin storage myopathy: a case report.

Background: Few manuscripts have reported phenotypes of skeletal muscle myopathies caused by mutations in the head region of slow/cardiac beta-myosin heavy chain (MyHCI). Among the patients, some of them showed the phenotype of skeletal muscle weakness with the obvious clinical features of cardiomyopathy while others showed pure skeletal muscle weakness with no symptoms of cardiac involvement. Genotype-phenotype relationship regarding the effect of a mutation on MyHCI is complex.

A new case of spastic paraplegia type 64 due to a missense mutation in the gene.

Spastic paraplegia type 64 (SPG64; OMIM 615683) is a complicated form of hereditary spastic paraplegia (HSP) recently identified in individuals diagnosed with suspected neurodegenerative disease. Affected patients carry homozygous mutations in the ectonucleoside triphosphate diphosphohydrolase 1 gene (). Although they share common characteristics, affected individuals show slight discrepancies in some clinical aspects.

Identification of a circulating miRNA signature in extracellular vesicles collected from amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with the progressive death of motor neurons. Mean survival for a patient diagnosed with ALS is between 2 and 5 years. Early and efficient diagnosis of the various forms of ALS remains a significant challenge, resulting in a need to identify clinically-relevant biomarkers in readily accessible body fluids.

Pax-5 Inhibits Breast Cancer Proliferation Through MiR-215 Up-regulation.

Background/aim: In breast cancer, Pax-5 promotes pro-epithelial features and suppresses malignant cancer processes. However, the molecular mechanism of this antitumor activity remains largely unknown. This study aimed to identify the cellular roles of Pax-5-regulated miRNAs in breast cancer progression.

Pax-5 Inhibits NF-κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors.

Pax-5, an essential transcription factor in B cell development, is aberrantly expressed in various B cell cancer lesions and solid tumors such as breast carcinoma. We have recently shown that Pax-5 regulates NF-κB activity which lead to the modulation of breast cancer phenotypic features (EMT-MET). NF-κB is known as a central mediator in inflammation, stress response as well as being a gatekeeper of pro-tumorigenic activity.

Identification of Differentially Expressed miRNAs in Colorado Potato Beetles (Leptinotarsa decemlineata (Say)) Exposed to Imidacloprid.

The Colorado potato beetle ( (Say)) is a significant pest of potato plants that has been controlled for more than two decades by neonicotinoid imidacloprid. can develop resistance to this agent even though the molecular mechanisms underlying this resistance are not well characterized. MicroRNAs (miRNAs) are short ribonucleic acids that have been linked to response to various insecticides in several insect models.

hace1 Influences zebrafish cardiac development via ROS-dependent mechanisms.

Background: In this study, we reveal a previously undescribed role of the HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) tumor suppressor protein in normal vertebrate heart development using the zebrafish (Danio rerio) model. We examined the link between the cardiac phenotypes associated with hace1 loss of function to the expression of the Rho small family GTPase, rac1, which is a known target of HACE1 and promotes ROS production via its interaction with NADPH oxidase holoenzymes.

Results: We demonstrate that loss of hace1 in zebrafish via morpholino knockdown results in cardiac deformities, specifically a looping defect, where the heart is either tubular or "inverted".

Pax-5 is a potent regulator of E-cadherin and breast cancer malignant processes.

Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes.

Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways.

The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues inversely correlate with those of the Focal Adhesion Kinase (FAK), a potent activator of breast cancer malignancy.

Characterization of cold-associated microRNAs in the freeze-tolerant gall fly Eurosta solidaginis using high-throughput sequencing.

Significant physiological and biochemical changes are observed in freeze-tolerant insects when confronted with cold temperatures. These insects have adapted to winter by retreating into a hypometabolic state of diapause and implementing cryoprotective mechanisms that allow them to survive whole body freezing. MicroRNAs (miRNAs), a family of short ribonucleic acids, are emerging as likely molecular players underlying the process of cold adaptation.

Identification and profiling of miRNAs in the freeze-avoiding gall moth Epiblema scudderiana via next-generation sequencing.

The rapid development of high-throughput next-generation sequencing approaches in recent years has facilitated large-scale discovery and expression analysis of non-coding RNAs, including miRNAs, in traditional and non-traditional animal models. Such an approach has been leveraged to amplify, identify, and quantify miRNAs in several models of cold adaptation. The present study is the first to investigate the status of these small RNAs in an insect species that uses the freeze avoidance strategy of cold hardiness, the gall moth Epiblema scudderiana.

Rapid isolation of extracellular vesicles from cell culture and biological fluids using a synthetic peptide with specific affinity for heat shock proteins.

Recent studies indicate that extracellular vesicles are an important source material for many clinical applications, including minimally-invasive disease diagnosis. However, challenges for rapid and simple extracellular vesicle collection have hindered their application. We have developed and validated a novel class of peptides (which we named venceremin, or Vn) that exhibit nucleotide-independent specific affinity for canonical heat shock proteins.