CRISPR/Cas9-mediated exon skipping to restore premature translation termination in a DFNB4 mouse model.

SLC26A4 encodes pendrin, a crucial anion exchanger essential for maintaining hearing function. Mutations in SLC26A4, including the prevalent c.919-2 A > G splice-site mutation among East Asian individuals, can disrupt inner ear electrolyte balance, leading to syndromic and non-syndromic hearing loss, such as Pendred syndrome and DFNB4.

The composition of the maternal breastmilk microbiota influences the microbiota network structure during early infancy.

Background/purpose(s): Human breastmilk (BM) is important for microbiome maturation in infants across different body sites. Streptococcus and Staphylococcus are considered universally predominant genera in the BM microbiota. However, whether the differential abundance of Streptococcus and Staphylococcus in BM can differentially affect microbiome maturation in infants remains unclear.

Gene therapy with a synthetic adeno-associated viral vector improves audiovestibular phenotypes in Pjvk-mutant mice.

Recessive PJVK mutations that cause a deficiency of pejvakin, a protein expressed in both sensory hair cells and first-order neurons of the inner ear, are an important cause of hereditary hearing impairment. Patients with PJVK mutations garner limited benefits from cochlear implantation; thus, alternative biological therapies may be required to address this clinical difficulty. The synthetic adeno-associated viral vector Anc80L65, with its wide tropism and high transduction efficiency in various inner ear cells, may provide a solution.

Generation and pathological characterization of a transgenic mouse model carrying a missense PJVK mutation.

Hearing loss is the most prevalent hereditary sensory disorder in children. Approximately 2 in 1000 infants are affected by genetic hearing loss. The PJVK gene, which encodes the pejvakin protein, has been linked to autosomal recessive non-syndromic hearing loss DFNB59.

Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65.

Sensorineural hearing loss is one of the most common sensory disorders worldwide. Recent advances in vector design have paved the way for investigations into the use of adeno-associated vectors (AAVs) for hearing disorder gene therapy. Numerous AAV serotypes have been discovered to be applicable to inner ears, constituting a key advance for gene therapy for sensorineural hearing loss, where transduction efficiency of AAV in inner ear cells is critical for success.

Establishment of an induced pluripotent stem cell (iPSC) line from a 7-year-old male patient with profound hearing loss carrying c.235delC in GJB2 gene.

Gap junction protein beta 2 gene (GJB2) mutations are the most frequent cause of hereditary hearing impairment. The recessive c.235delC mutation in the GJB2 gene is the most common mutation causing severe to profound sensorineural hearing loss in the Asian population.

Different mechanisms involved in the berberine-induced antiproliferation effects in triple-negative breast cancer cell lines.

Background/aim: Berberine (BBR) is known to be effective at inhibiting cell proliferation and promoting apoptosis in various cancer cells. However, the effects of BBR on triple-negative breast cancer (TNBC) cells remain unclear. The aim of this study was to investigate the cell inhibition effects of BBR on different subtypes of TNBC cells.

The Deubiquitinase OTU5 Regulates Root Responses to Phosphate Starvation.

Phosphorus, taken up by plants as inorganic phosphate (Pi), is an essential but often growth-limiting mineral nutrient for plants. As part of an orchestrated response to improve its acquisition, insufficient Pi supply triggers alterations in root architecture and epidermal cell morphogenesis. Arabidopsis () mutants defective in the expression of the () exhibited a constitutive Pi deficiency root phenotype, comprising the formation of long and dense root hairs and attenuated primary root growth.

Deubiquitinating Enzyme OTU5 Contributes to DNA Methylation Patterns and Is Critical for Phosphate Nutrition Signals.

Phosphate (Pi) starvation induces a suite of adaptive responses aimed at recalibrating cellular Pi homeostasis. Plants harboring a mutation in () showed altered DNA methylation of root hair-related genes and altered Pi-responsive root traits. Unlike the wild type, homozygous mutants did not respond to Pi starvation by increased lateral root formation and increased root hair length but formed very short root hairs when grown on low-Pi media.

Systems-wide analysis of manganese deficiency-induced changes in gene activity of Arabidopsis roots.

Manganese (Mn) is pivotal for plant growth and development, but little information is available regarding the strategies that evolved to improve Mn acquisition and cellular homeostasis of Mn. Using an integrated RNA-based transcriptomic and high-throughput shotgun proteomics approach, we generated a comprehensive inventory of transcripts and proteins that showed altered abundance in response to Mn deficiency in roots of the model plant Arabidopsis. A suite of 22,385 transcripts was consistently detected in three RNA-seq runs; LC-MS/MS-based iTRAQ proteomics allowed the unambiguous determination of 11,606 proteins.

PFT1-controlled ROS balance is critical for multiple stages of root hair development in Arabidopsis.

Reactive oxygen species (ROS) have been shown to play key roles in cellular decision making and signal integration in multicellular organisms. In roots, ROS levels are managed by the action of peroxidases and NAPDH oxidases, resulting in a distinct spatial distribution of hydrogen peroxide (H₂O₂) and superoxide (O₂(-)) that is critical for the balance between cell proliferation and differentiation. In addition, ROS is required for the determination of the cell shape of root hairs.