Chromosome classification via deep learning and its application to patients with structural abnormalities of chromosomes.

Background And Objective: Karyotyping is an important technique in cytogenetic practice for the early diagnosis of genetic diseases. Clinical karyotyping is tedious, time-consuming, and error-prone. The objective of our study was to develop a single-stage deep convolutional neural networks (DCNN)-based model to automatically classify normal and abnormal chromosomes in an end-to-end manner.

A novel variant in the FBP1 gene causes fructose-1,6-bisphosphatase deficiency through increased ubiquitination.

Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive disorder characterized by impaired gluconeogenesis caused by mutations in the fructose-1,6-bisphosphatase 1 (FBP1) gene. The molecular mechanisms underlying FBPase deficiency caused by FBP1 mutations require investigation. Herein, we report the case of a Chinese boy with FBPase deficiency who presented with hypoglycemia, ketonuria, metabolic acidosis, and repeated episodes of generalized seizures that progressed to epileptic encephalopathy.

Novel variant of ETFDH leading to multiple acyl-CoA dehydrogenase deficiency by promoting protein degradation via ubiquitin proteasome pathway.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive metabolic disease. Patients present with metabolic decompensation, muscle weakness, respiratory failure, and cardiomyopathy. Late-onset MADD is primarily caused by mutations in the ETFDH gene.

Nedd4-2 haploinsufficiency in mice causes increased seizure susceptibility and impaired Kir4.1 ubiquitination.

Neural precursor cell expressed developmentally down-regulated gene 4-like (NEDD4-2) encodes a ubiquitin E3 ligase that is involved in epileptogenesis with mechanisms needing further investigation. We constructed a novel Nedd4-2 mouse model with half level of both Nedd4-2 long and short isoforms in the brain. Nedd4-2 haploinsufficiency caused increased susceptibility and severity of pentylenetetrazole (PTZ)-induced seizures.

20-HETE downregulates Na/K-ATPase α1 expression via the ubiquitination pathway.

In this article, we found that 20-Hydroxyeicosatetraenoic acid (20-HETE) reduced Na/K-ATPase α1 expression via the ubiquitin-proteasome pathway. The ubiquitination level of Na/K-ATPase α1 protein was increased in 20-HETE-treated mouse cortical collecting duct cells and the kidney tissues of CYP4F2 transgenic mice. We also demonstrated that 20-HETE-induced high level phosphorylation of Na/K-ATPase α1 was necessary for its ubiquitination.

Neddylation-mediated Nedd4-2 activation regulates ubiquitination modification of renal NBCe1.

The sodium-coupled bicarbonate cotransporter 1 (NBCe1) plays an essential role in the maintenance of acid-base homeostasis in the human body. However, little research has been done regarding the modification of NBCe1. Nedd4-2 is one of the most important ubiquitin E3 ligases in the kidney where it is responsible for mediating the ubiquitylation level of many important ion channel proteins; therefore, influencing their expression and membrane localization.

Long non-coding RNA LINC00222 regulates GSK3β activity and promotes cell apoptosis in lung adenocarcinoma.

Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulating cellular processes such as differentiation, proliferation, metastasis and apoptosis. These lncRNAs are found to be dysregulated in a variety of cancers. However, the underlying mechanisms of lncRNAs action in lung adenocarcinoma remain unclear.

20-HETE regulated PSMB5 expression via TGF-β/Smad signaling pathway.

We previously found that 20-hydroxyeicosatetraeonic acid (20-HETE) showed an effect on proteasome activity in cytochrome P450 F2 (CYP4F2) transgenic mice. Proteasome subunit β5 (PSMB5) is a primary subunit of the proteasome. In the current study, we examine whether 20-HETE has any affect on PSMB5.

cMyBP-C was decreased via KLHL3-mediated proteasomal degradation in congenital heart diseases.

Cardiac myosin binding protein C (cMyBP-C) is a cardiac structural and regulatory protein; mutations of cMyBP-C are frequently associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Cardiac special transcription factors may regulate the expression of cMyBP-C. However, the role of cMyBP-C in congenital heart diseases (CHD) remains poorly understood.

miR-137 downregulates c-kit expression in acute myeloid leukemia.

The oncogene c-kit plays a vital role in the pathogenesis of acute myeloid leukemia (AML). However, the mechanism of microRNAs targeting c-kit in AML has not been determined in detail. Moreover, the role miR-137 in tumor cell proliferation remains controversial.

Role of NSD1 in H2O2-induced GSTM3 suppression.

Nuclear receptor-binding SET domain-containing protein 1 (NSD1) has been proved to act as a histone methyltransferase and a transcription co-factor to regulate gene expression. However, the role of NSD1 in oxidative stress remains poorly understood. In the present study, we focused on the NSD1 regulation of antioxidant enzyme gene glutathione S-transferase M3 (GSTM3) expression in response to oxidative stress.