Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders.

Effective translation of rare disease diagnosis knowledge into therapeutic applications is achievable within a reasonable timeframe; where mutations are amenable to current antisense oligonucleotide technology. In our study, we identified five distinct types of abnormal splice-causing mutations in patients with rare genetic disorders and developed a tailored antisense oligonucleotide for each mutation type using phosphorodiamidate morpholino oligomers with or without octa-guanidine dendrimers and 2'-O-methoxyethyl phosphorothioate. We observed variations in treatment effects and efficiencies, influenced by both the chosen chemistry and the specific nature of the aberrant splicing patterns targeted for correction.

Adsorption of Cu(II) and Ni(II) from Aqueous Solutions Using Synthesized Alkali-Activated Foamed Zeolite Adsorbent: Isotherm, Kinetic, and Regeneration Study.

Water pollution, particularly from heavy metals, poses a significant threat to global health, necessitating efficient and environmentally friendly removal methods. This study introduces novel zeolite-based adsorbents, specifically alkali-activated foamed zeolite (AAFZ), for the effective adsorption of Cu(II) and Ni(II) ions from aqueous solutions. The adsorbents' capabilities were comprehensively characterized through kinetic and isotherm analyses.

Adsorption of Heavy Metals on Alkali-Activated Zeolite Foams.

Elevated concentrations of heavy metals in natural waters can cause significant ecological problems. It is therefore essential to ensure their removal from any water discharged into the environment immediately, especially in case of an accident, where there is a risk of releasing large quantities or high concentrations. The aim of this paper is to test a newly developed adsorbent for the removal of heavy metals from aqueous solutions-in particular, it is very fast adsorption, and thus efficiency, during clean-ups.

Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity.

Hereditary angioedema (HAE) is a rare genetic disorder with variable expressivity even in carriers of the same underlying genetic defect, suggesting other genetic and epigenetic factors participate in modifying HAE severity. Recent knowledge indicates the role of immune cells in several aspects of HAE pathogenesis, which makes monocytes and macrophages candidates to mediate these effects. Here we combined a search for HAE phenotype modifying gene variants with the characterization of selected genes' mRNA levels in monocyte and macrophages in a symptom-free period.

Short amplicon reverse transcription-polymerase chain reaction detects aberrant splicing in genes with low expression in blood missed by ribonucleic acid sequencing analysis for clinical diagnosis.

Use of blood RNA sequencing (RNA-seq) as a splicing analysis tool for clinical interpretation of variants of uncertain significance (VUSs) found via whole-genome and exome sequencing can be difficult for genes that have low expression in the blood due to insufficient read count coverage aligned to specific genes of interest. Here, we present a short amplicon reverse transcription-polymerase chain reaction(RT-PCR) for the detection of genes with low blood expression. Short amplicon RT-PCR, is designed to span three exons where an exon harboring a variant is flanked by one upstream and one downstream exon.

Hirata's Disease: Rare Cause of Hypoglycaemia in Caucasian Male.

Insulin autoimmune syndrome or Hirata's disease is an extremely rare condition leading to hypoglycaemia of variable severity due to autoantibodies against insulin. We present the first case documented in the Czech Republic.

Hydrotreating of Atmospheric Gas Oil and Co-Processing with Rapeseed Oil Using Sulfur-Free PMoCx/AlO Catalysts.

Sulfur-free molybdenum carbides have the potential to replace the conventional sulfided catalysts used for hydrotreating. For these catalysts, it is not necessary to add sulfur to maintain their activity. This fact makes it worthwhile to continue working on improving their hydrotreating efficiency.

Characterization of Modified Natural Minerals and Rocks for Possible Adsorption and Catalytic Use.

This study focused on natural materials such as clinoptilolite (CLI), metakaolin (MK), marlstone (MRL) and phonolite (PH). Clinoptilolite is one of the most known and common natural minerals (zeolites) with a unique porous structure, metakaolin is calcined kaolin clay, marlstone is a sedimentary rock and phonolite is an igneous rock composed of alkali feldspar and other minerals. These natural materials are mainly used in the building industry (additions for concrete mixtures, production of paving, gravels) or for water purification, but the modification of their chemical, textural and mechanical properties makes these materials potentially usable in other industries, especially in the chemical industry.

Long non-coding RNA exchange during the oocyte-to-embryo transition in mice.

The oocyte-to-embryo transition (OET) transforms a differentiated gamete into pluripotent blastomeres. The accompanying maternal-zygotic RNA exchange involves remodeling of the long non-coding RNA (lncRNA) pool. Here, we used next generation sequencing and de novo transcript assembly to define the core population of 1,600 lncRNAs expressed during the OET (lncRNAs).

Production of small RNAs by mammalian Dicer.

MicroRNA (miRNA) and RNA interference (RNAi) pathways employ RNase III Dicer for the biogenesis of small RNAs guiding post-transcriptional repression. Requirements for Dicer activity differ in the two pathways. The biogenesis of miRNAs requires a single Dicer cleavage of a short hairpin precursor to produce a small RNA with a precisely defined sequence, while small RNAs in RNAi come from a processive cleavage of a long double-stranded RNA (dsRNA) into a pool of small RNAs with different sequences.

The key role of insulin-like growth factor I in limbal stem cell differentiation and the corneal wound-healing process.

Limbal stem cells (LSC), which reside in the basal layer of the limbus, are thought to be responsible for corneal epithelial healing after injury. When the cornea is damaged, LSC start to proliferate, differentiate, and migrate to the site of injury. To characterize the signaling molecules ensuring communication between the cornea and LSC, we established a mouse model of mechanical corneal damage.

Differential interaction of the two related fungal species Candida albicans and Candida dubliniensis with human neutrophils.

Candida albicans, the most common facultative human pathogenic fungus is of major medical importance, whereas the closely related species Candida dubliniensis is less virulent and rarely causes life-threatening, systemic infections. Little is known, however, about the reasons for this difference in pathogenicity, and especially on the interactions of C. dubliniensis with the human immune system.

Factor h: a complement regulator in health and disease, and a mediator of cellular interactions.

Complement is an essential part of innate immunity as it participates in host defense against infections, disposal of cellular debris and apoptotic cells, inflammatory processes and modulation of adaptive immune responses. Several soluble and membrane-bound regulators protect the host from the potentially deleterious effects of uncontrolled and misdirected complement activation. Factor H is a major soluble regulator of the alternative complement pathway, but it can also bind to host cells and tissues, protecting them from complement attack.

Role of pH-regulated antigen 1 of Candida albicans in the fungal recognition and antifungal response of human neutrophils.

Candida albicans is an opportunistic human-pathogenic fungus, which can cause superficial but also life-threatening invasive infections. The pH-regulated antigen 1 (Pra1) of C. albicans is a surface-associated and secreted protein highly expressed in the hyphal form.

Cyclosporine A-loaded and stem cell-seeded electrospun nanofibers for cell-based therapy and local immunosuppression.

Cyclosporine A (CsA), a potent immunosuppressive drug with low water solubility, was dissolved in poly(L-lactic acid) (PLA) solution, and nanofibers were fabricated from this mixture by electrospinning technology. The addition of CsA into the PLA solution and the conditions of the electrospinning process did not influence the structure of the nanofibers nor affect the pharmacological activity of CsA. Study of the CsA release behavior in culture medium showed a release for at least 96 h.

The role of mouse mesenchymal stem cells in differentiation of naive T-cells into anti-inflammatory regulatory T-cell or proinflammatory helper T-cell 17 population.

Bone marrow-derived mesenchymal stem cells (MSCs) modulate immune response and can produce significant levels of transforming growth factor-β (TGF-β) and interleukin-6 (IL-6). These 2 cytokines represent the key factors that reciprocally regulate the development and polarization of naive T-cells into regulatory T-cell (Treg) population or proinflammatory T helper 17 (Th17) cells. In the present study we demonstrate that MSCs and their products effectively regulate expression of transcription factors Foxp3 and RORγt and control the development of Tregs and Th17 cells in a population of alloantigen-activated mouse spleen cells or purified CD4(+)CD25(-) T-cells.