Novel function of U7 snRNA in the repression of HERV1/LTR12s and lincRNAs in human cells.

U7 snRNA is part of the U7 snRNP complex, required for the 3' end processing of replication-dependent histone pre-mRNAs in S phase of the cell cycle. Here, we show that U7 snRNA plays another function in inhibiting the expression of a subset of long terminal repeats of human endogenous retroviruses (HERV1/LTR12s) and LTR12-containing long intergenic noncoding RNAs (lincRNAs), both bearing sequence motifs that perfectly match the 5' end of U7 snRNA. We demonstrate that U7 snRNA inhibits LTR12 and lincRNA transcription and propose a mechanism in which U7 snRNA hampers the binding/activity of the NF-Y transcription factor to CCAAT motifs within LTR12 elements.

Microscopic and Biopharmaceutical Evaluation of Emulsion and Self-Emulsifying Oil with Cyclosporine.

Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research was to conduct the microscopic and biopharmaceutical evaluation of two formulations, an emulsion (EM) and a self-emulsifying oil (SEO), both with 0.

Modulatory role of RNA helicases in MBNL-dependent alternative splicing regulation.

Muscleblind-like splicing regulators (MBNLs) activate or repress the inclusion of alternative splicing (AS) events, enabling the developmental transition of fetal mRNA splicing isoforms to their adult forms. Herein, we sought to elaborate the mechanism by which MBNLs mediate AS related to biological processes. We evaluated the functional role of DEAD-box (DDX) RNA helicases, DDX5 and DDX17 in MBNL-dependent AS regulation.

Imprinted small nucleolar RNAs: Missing link in development and disease?

The 14q32.2 (DLK1-DIO3) and 15q11-q13 (SNURF-SNRPN) imprinted gene loci harbor the largest known small nucleolar RNA clusters expressed from the respective maternal and paternal alleles. Recent studies have demonstrated significant roles for the 15q11-q13 located SNORD115-SNORD116 C/D box snoRNAs in Prader-Willi syndrome (PWS), a neurodevelopmental disorder.

FUS regulates a subset of snoRNA expression and modulates the level of rRNA modifications.

FUS is a multifunctional protein involved in many aspects of RNA metabolism, including transcription, splicing, translation, miRNA processing, and replication-dependent histone gene expression. In this work, we show that FUS depletion results in the differential expression of numerous small nucleolar RNAs (snoRNAs) that guide 2'-O methylation (2'-O-Me) and pseudouridylation of specific positions in ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). Using RiboMeth-seq and HydraPsiSeq for the profiling of 2'-O-Me and pseudouridylation status of rRNA species, we demonstrated considerable hypermodification at several sites in HEK293T and SH-SY5Y cells with FUS knockout (FUS KO) compared to wild-type cells.

Role of Long Intergenic Noncoding RNAs in Cancers with an Overview of MicroRNA Binding.

Long intergenic noncoding RNAs are transcripts originating from the regions without annotated coding genes. They are located mainly in the nucleus and regulate gene expression. Long intergenic noncoding RNAs can be also found in the cytoplasm acting as molecular sponges of certain microRNAs.

The Novel Role of hnRNP UL1 in Human Cell Nucleoli.

hnRNP UL1 plays an important role in cell nuclei, where it is recruited to DNA damage sites and is involved in the repair of DNA double-strand breaks. Furthermore, this protein is known as a transcriptional repressor of RNA polymerase II genes. In the present study, we have shown that hnRNP UL1 is also localized in the nucleoli of human cells.

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders.

Long intergenic noncoding RNAs (lincRNAs) are a class of independently transcribed molecules longer than 200 nucleotides that do not overlap known protein-coding genes. LincRNAs have diverse roles in gene expression and participate in a spectrum of biological processes. Dysregulation of lincRNA expression can abrogate cellular homeostasis, cell differentiation, and development and can also deregulate the immune and nervous systems.

Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs.

In recent functional genomics studies, a large number of non-coding RNAs have been identified. It has become increasingly apparent that noncoding RNAs are crucial players in a wide range of cellular and physiological functions. They have been shown to modulate gene expression on different levels, including transcription, post-transcriptional processing, and translation.

ALS-linked FUS mutants affect the localization of U7 snRNP and replication-dependent histone gene expression in human cells.

Genes encoding replication-dependent histones lack introns, and the mRNAs produced are a unique class of RNA polymerase II transcripts in eukaryotic cells that do not end in a polyadenylated tail. Mature mRNAs are thus formed by a single endonucleolytic cleavage that releases the pre-mRNA from the DNA and is the only processing event necessary. U7 snRNP is one of the key factors that determines the cleavage site within the 3'UTR of replication-dependent histone pre-mRNAs.

U7 snRNA: A tool for gene therapy.

Most U-rich small nuclear ribonucleoproteins (snRNPs) are complexes that mediate the splicing of pre-mRNAs. U7 snRNP is an exception in that it is not involved in splicing but is a key factor in the unique 3' end processing of replication-dependent histone mRNAs. However, by introducing controlled changes in the U7 snRNA histone binding sequence and in the Sm motif, it can be used as an effective tool for gene therapy.

Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.

Polyglutamine (polyQ) diseases are incurable neurological disorders caused by CAG repeat expansion in the open reading frames (ORFs) of specific genes. This type of mutation in the HTT gene is responsible for Huntington's disease (HD). CAG repeat-targeting artificial miRNAs (art-miRNAs) were shown as attractive therapeutic approach for polyQ disorders as they caused allele-selective decrease in the level of mutant proteins.

The Level of Cytokines in the Vitreous Body of Severe Proliferative Diabetic Retinopathy Patients Undergoing Posterior Vitrectomy.

Objective: The objective of the study was to compare cytokine levels in the vitreous body of patients with proliferative diabetic retinopathy (PDR) undergoing posterior vitrectomy.

Patients And Methods: The study included 39 patients (39 eyes) undergoing pars plana vitrectomy (PPV). Patients were divided into three groups: patients with proliferative diabetic retinopathy (PDR) without aflibercept injection prior to the surgery, PDR patients administered aflibercept injection prior to the surgery, and patients without diabetes mellitus (control group).

Pilot Study of Eyesight Characteristics and Thickness of the Retinal Nerve Fiber and Ganglion Cell-inner Plexiform Layers in Adolescent Patients with Type one Diabetes Mellitus on an Insulin Pump.

Aim: Estimation of the ocular status in adolescents with diabetes mellitus type 1 (DM1) treated with continuous subcutaneous insulin infusion (CSII), assessment of the development of the diabetic retinopathy (DR) and nephropathy (DN) within 10 years.

Methods: 37 patients (74 eyes) aged 16-33 years, treated with CSII were enrolled to the study. Baseline, and a 10- year follow-up evaluation included: best corrected visual acuity (BCVA), tonometry, slit lamp exam and fluorescein angiography (FLA).

The Influence of Silicone Oil on the Ganglion Cell Complex After Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment.

Purpose: Pars plana vitrectomy (PPV) and silicone oil endotamponade have been used as a treatment in rhegmatogenous retinal detachment (RRD). Improvement in the modality of spectral-domain optical coherence tomography (SD-OCT) allows for the assessment of ganglion cell layer-inner plexiform layer (GCL-IPL) in the macular region. Information about the GCL-IPL status may be a response to the question as to why the visual recovery after PPV with silicone oil tamponade is incomplete.

Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression.

Background: Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this increment is achieved by both enhanced transcription and 3' end processing. In this paper, we described positive cofactor 4 (PC4) as a protein that contributes to the regulation of replication-dependent histone gene expression.

Ocular irritation and cyclosporine A distribution in the eye tissues after administration of Solid Lipid Microparticles in the rabbit model.

The aim of this study was to investigate the in vivo effect of Solid Lipid Microparticles (SLM), proposed for topical ocular administration of cyclosporine, on the rabbit eye. SLM carrier is an aqueous dispersion of lipid microparticles (20% w/w) with a size up to 15 μm. Cyclosporine was dissolved in the formulation in the concentration of 0.

A 10-year monitoring of the eyesight in patients after kidney transplantation.

A pilot study of a 10-year analysis of the eyesight characteristics in patients after renal transplantation with a view to a later wider study of the same population.The study encompassed 50 eyes in 25 patients who underwent renal transplantation in the years 2007 and 2008. All patients underwent: visual acuity measurement, tonometry, slit lamp examination, and spectroscopic optical coherence tomography.

FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors.

Replication-dependent histone genes are up-regulated during the G1/S phase transition to meet the requirement for histones to package the newly synthesized DNA. In mammalian cells, this increment is achieved by enhanced transcription and 3' end processing. The non-polyadenylated histone mRNA 3' ends are generated by a unique mechanism involving the U7 small ribonucleoprotein (U7 snRNP).

[Pigmented paravenous retinochoroidal atrophy--a case report].

Pigmented paravenous retinochoroidal atrophy is a rare dystrophy, which is usually asymptomatic and limited to the paravenous area. Due to the slow progression of eye fundus changes, typically without the macular involvement, pigmented paravenous retinochoroidal atrophy is not thought to be a vision-threatening ocular disease. We report a case of a 64-year-old man with sudden unilateral reduction of vision and binocular diplopia, diagnosed with bilateral pigmented paravenous retinochoroidal atrophy.

Five-month observation of persistent diabetic macular edema after intravitreal injection of Ozurdex implant.

Aims: This retrospective analysis was aimed at evaluating the effectiveness of treatment of persistent diabetic macular edema with intravitreal injections of 0.7 mg dexamethasone implant Ozurdex. The study comprised three male patients (6 eyes).

Evaluation of corneal endothelium in children and adolescents with type 1 diabetes mellitus.

Purpose: To evaluate the systemic and local factors that contribute to the damage of endothelial cells in diabetic patients and to compare the endothelial structure of the cornea in diabetic and nondiabetic patients.

Materials And Methods: The endothelial cell density (ECD) and central corneal thickness (CCT) were investigated in 123 eyes of type 1 diabetic patients and in 124 eyes of nondiabetic patients. The mean diabetic patients age was 15.

Biomarkers in diabetic retinopathy and the therapeutic implications.

The main problem both in type 1 (T1DM) and type 2 (T2DM) diabetes is the development of chronic vascular complications encompassing micro- as well as macrocirculation. Chronic complications lower the quality of life, lead to disability, and are the cause of premature death in DM patients. One of the chronic vascular complications is a diabetic retinopathy (DR) which leads to a complete loss of sight in DM patients.

Relationship between serum transforming growth factor β 1 concentrations and the duration of type 1 diabetes mellitus in children and adolescents.

The aim of this study was to evaluate the relationship between serum transforming growth factor β 1 (TGF- β 1) concentrations and the duration of type 1 diabetes mellitus (T1DM) in children and adolescents. One hundred and sixteen patients with T1DM and 19 healthy controls were examined. Serum TGF- β 1 concentrations were measured using the cytometric bead array (CBA).