BACKGROUND AND PURPOSE:VRSs are the perivascular spaces surrounding the deep perforating arteries in the brain. Although VRS variations with age and disease pathologies have been reported previously, the radiologic characteristics of the VRS in relation to AD are poorly understood. This study investigated the prevalence, spatial distribution, and severity of the VRS in AD, MCI, and older adults who were CN. It also investigated the relationship of the VRS to white matter changes.
The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60–70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.
The present study was to evaluate the diagnostic value of salivary total and oligomeric α-synuclein levels in PD. Furthermore, we sought to explore the relationship between salivary total α-synuclein and α-synuclein SNP variants levels. 201 PD patients and 67 controls were recruited, of which there also had the genetic information of two positive α-synuclein (SNCA) loci. Salivary total α-synuclein was assayed using a highly sensitive Luminex assay and oligomeric α-synuclein was quantified by the combination of Gel filtration chromatography and Western blot, respectively. From our analysis,No difference in salivary total α-synuclein levels was found between PD patients and healthy controls, it decreased with age in PD patients, and was closely associated with genotypic distribution of rs11931074 and rs894278 in PD, respectively. After controlled for age and genders, G allele of rs11931074 was correlated with lower salivary total α-synuclein levels, while G allele of rs894278 was also correlated with the higher levels. Simultaneously, the further study was shown that salivary oligomeric α-synuclein in PD patients significantly increased comparing to healthy controls. In conclusions,our study firstly demonstrated that salivary total α-synuclein levels could be manipulated by different α-synuclein SNPs and salivary oligomeric α-synuclein could be a potential diagnostic indicator of PD.
Skeletal muscle has a remarkable ability to regenerate owing to its resident stem cells (also called satellite cells, SCs). SCs are normally quiescent; when stimulated by damage, they activate and expand to form new fibers. The mechanisms underlying SC proliferative progression remain poorly understood. Here we show that DHX36, a helicase that unwinds RNA G-quadruplex (rG4) structures, is essential for muscle regeneration by regulating SC expansion. DHX36 (initially named RHAU) is barely expressed at quiescence but is highly induced during SC activation and proliferation. Inducible deletion of Dhx36 in adult SCs causes defective proliferation and muscle regeneration after damage. System-wide mapping in proliferating SCs reveals DHX36 binding predominantly to rG4 structures at various regions of mRNAs, while integrated polysome profiling shows that DHX36 promotes mRNA translation via 5′-untranslated region (UTR) rG4 binding. Furthermore, we demonstrate that DHX36 specifically regulates the translation of Gnai2 mRNA by unwinding its 5′ UTR rG4 structures and identify GNAI2 as a downstream effector of DHX36 for SC expansion. Altogether, our findings uncover DHX36 as an indispensable post-transcriptional regulator of SC function and muscle regeneration acting through binding and unwinding rG4 structures at 5′ UTR of target mRNAs.
BACKGROUND AND PURPOSE:The Brain Atrophy and Lesion Index combines several common, aging-related structural brain changes and has been validated for high-field MR imaging. In this study, we evaluated measurement properties of the Brain Atrophy and Lesion Index by use of T1WI and T2WI at 1.5T and 3T MR imaging to comprehensively assess the usefulness of the lower field-strength testing.
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