Trinucleotide Repeat Expansion and RNA Dysregulation in Fragile X Syndrome: Emerging Therapeutic Approaches.

Fragile X Syndrome (FXS) is characterized by intellectual impairment caused by CGG repeat expansion in the FMR1 gene. When repeats exceed 200, they induce DNA methylation of the promoter and the repeat region, resulting in transcriptional silencing of the FMR1 gene and the subsequent loss of FMRP protein. In the past decade or so, research has focused on the role of FMRP as an RNA-binding protein involved in translation inhibition in the brain in FXS model mice, particularly by slowing or stalling ribosome translocation on mRNA.

FMRP deficiency leads to multifactorial dysregulation of splicing and mislocalization of MBNL1 to the cytoplasm.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is often modeled in Fmr1 knockout mice where the RNA-binding protein FMRP is absent. Here, we show that in Fmr1-deficient mice, RNA mis-splicing occurs in several brain regions and peripheral tissues. To assess molecular mechanisms of splicing mis-regulation, we employed N2A cells depleted of Fmr1.

The effects of herbal medicine (Jujadokseo-hwan) on quality of life in patients with mild cognitive impairment: Cost-effectiveness analysis alongside randomized controlled trial.

Background: Mild cognitive impairment (MCI), the early stage of dementia, requires effective intervention for symptom management and improving patients' quality of life (QoL). Jujadokseo-hwan (JDH) is a Korean herbal medicine prescription used to improve MCI symptoms, such as memory deficit. This study evaluates the improvement in QoL through JDH.

CPEB1 regulates the inflammatory immune response, phagocytosis, and alternative polyadenylation in microglia.

Microglia are myeloid cells of the central nervous system that perform tasks essential for brain development, neural circuit homeostasis, and neural disease. Microglia react to inflammatory stimuli by upregulating inflammatory signaling through several different immune cell receptors such as the Toll-like receptor 4 (TLR4), which signals to several downstream effectors including transforming growth factor beta-activated kinase 1 (TAK1). Here, we show that TAK1 levels are regulated by CPEB1, a sequence-specific RNA binding protein that controls translation as well as RNA splicing and alternative poly(A) site selection in microglia.

Oppositional poly(A) tail length regulation by FMRP and CPEB1.

Poly(A) tail length is regulated in both the nucleus and cytoplasm. One factor that controls polyadenylation in the cytoplasm is CPEB1, an RNA binding protein that associates with specific mRNA 3'UTR sequences to tether enzymes that add and remove poly(A). Two of these enzymes, the noncanonical poly(A) polymerases GLD2 (TENT2, PAPD4, Wispy) and GLD4 (TENT4B, PAPD5, TRF4, TUT3), interact with CPEB1 to extend poly(A).

FMRP links optimal codons to mRNA stability in neurons.

Fragile X syndrome (FXS) is caused by inactivation of the gene and loss of encoded FMRP, an RNA binding protein that represses translation of some of its target transcripts. Here we use ribosome profiling and RNA sequencing to investigate the dysregulation of translation in the mouse brain cortex. We find that most changes in ribosome occupancy on hundreds of mRNAs are largely driven by dysregulation in transcript abundance.

HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression.

Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). UCP1 increases the conductance of the inner mitochondrial membrane (IMM) for protons to make BAT mitochondria generate heat rather than ATP. HDAC6 is a cytosolic deacetylase for non-histone substrates to regulate various cellular processes, including mitochondrial quality control and dynamics.

HDAC6 deficiency induces apoptosis in mesenchymal stem cells through p53 K120 acetylation.

The acetylation of p53 is critical in modulating its pro-apoptotic roles. However, its regulatory mechanism and physiological significance are unclear. Here, we show HDAC6 negatively regulates pro-apoptotic acetylation of p53 at lysine residue 120 (K120) in mesenchymal stem cells (MSCs).

The DTL ERG electrode comes in different shapes and sizes: Are they all good?

Purpose: Although the DTL fiber electrode has been in use in the ERG field for more than four decades, its composition was never clearly defined. We compared five different types of conductive (DTL type) yarn (differing in terms of mass, number of filaments, and crimping degree) in order to determine whether we could identify one that would be better suited for the recording of ERGs.

Methods: Photopic flash ERGs were recorded from five subjects using the following DTL electrodes: 27/7, 22/1, 11/1, 11/1*2, and 22/1*2.

Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia.

Purpose: The purpose of this study was to investigate the effects of sildenafil on retinal injury following neonatal hypoxia-ischemia (HI) at term-equivalent age in rat pups.

Methods: Hypoxia-ischemia was induced in male Long-Evans rat pups at postnatal day 10 (P10) by a left common carotid ligation followed by a 2-hour exposure to 8% oxygen. Sham-operated rats served as the control group.

Impact of bronchopulmonary dysplasia on brain and retina.

Many premature newborns develop bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD.

Visual Impairments Following Term Neonatal Encephalopathy: Do Retinal Impairments Also Play a Role?

Purpose: We investigated the effects of term neonatal encephalopathy on retinal function and structure.

Methods: A rat model of term neonatal hypoxic-ischemic (HI) encephalopathy (Vannucci model) was used. Hypoxia-ischemia was induced by a left common carotid ligation followed by a 2-hour period of hypoxia (8% oxygen) in Long-Evans rat pups at postnatal day 10 (P10).

Solid solution cermet: (Ti,Nb)(CN)-Ni cermet.

Solid solution powders without W, (Ti,Nb)(CN) powders with a B1 structure (NaCl like), were synthesized by high energy milling and carbothermal reduction in nitrogen. The range of molar ratios of Ti/Nb for forming complete (Ti,Nb)(CN) phase was broader than that of Ti/W for the (Ti,W)(CN) phase because carbide or carbonitride of Nb had a B1 crystal structure identical to Ti(CN) while WC had a hexagonal crystal structure. The results revealed that the hardness of (Ti,Nb)(CN)-Ni cermets was higher than that of (Ti,W)(CN)-Ni cermets.

Targeted delivery of vaccine to dendritic cells by chitosan nanoparticles conjugated with a targeting peptide ligand selected by phage display technique.

The paper presents a novel dendritic cells (DC)-targeting peptide, TPAFRYS (TP) identified by phage display technique and conjugated to chitosan in order to develop an efficient DC-targeting vaccine delivery carrier. TP-conjugated chitosan nanoparticles (TPC-NPs) were prepared with ovalbumin (OVA) as a model vaccine by ionic gelation. Flow cytometry and immunocytochemistry studies demonstrated the higher targeting ability of TPC-NPs to DCs in compared to chitosan NPs.

Solid-solution nanocrystallite formation by high-energy milling.

Solid-solution nanocrystalline powders were prepared by the high-energy milling of Ti alloys with graphite. The B1 structure (NaCl-like structure) phases, (Ti, Cr)C and (Ti, Al)C, were formed during the milling process of Ti-Cr + graphite and Ti-Al + graphite, and the synthetic procedures were investigated in terms of the phase evolution from XRD data. The (Ti, Al)C phase was obtained after milling for 20 hr at BPR = 40:1 (under a more severe condition), while the (Ti, Cr)C phase formed after milling for 20 hr at BPR = 20:1 (a relatively soft condition).

Leptin and interleukin-6 alter the function of mesolimbic dopamine neurons in a rodent model of prenatal inflammation.

Maternal inflammation during critical stages of gestation is thought to underlie the link between prenatal infection and several neurodevelopmental psychiatric disorders in the offspring, including schizophrenia. Increased activity of mesolimbic dopamine (DA) neurons, a hallmark of psychosis, is found in offspring of rodents exposed to a prenatal inflammatory challenge but it is unclear how this effect is elicited. Using an experimental model of localized aseptic inflammation with turpentine oil (TURP) we sought to establish whether circulating interleukin-6 (IL-6) and leptin play a role in the effects of prenatal inflammation on DA neurons.