Argonaute CSR-1 restricts holocentromere protein CENP-A/HCP-3 localization.

Chromosome segregation errors caused by centromere malfunction can lead to chromosome instability and aneuploidy. In Caenorhabditis elegans, the Argonaute protein CSR-1 is essential for proper chromosome segregation, though the specific mechanisms are not fully understood. Here we investigated how CSR-1 regulates centromere and kinetochore function in C. elegans embryos. We found that the depletion of CSR-1 results in defects in mitotic progression and chromosome positioning relative to the spindle pole. CSR-1 knockdown does not affect centromeric histone H3 variant CENP-A/HCP-3 mRNA and protein levels, but increases the localization of HCP-3 and some kinetochore proteins onto the mitotic chromosomes. Such elevation of chromatin HCP-3 localization depends on the CSR-1 RNAi pathway upstream factor EGO-1 and CSR-1's PIWI domain activity. Our results suggest that CSR-1 restricts HCP-3 level at the holocentromeres, prevents erroneous kinetochore assembly, and thereby promotes accurate chromosome segregation. Our work sheds light on CSR-1's role in regulating deposition of HCP-3 on chromatin and centromere function in the embryos.

RSU-1 regulates the integrity of dense bodies in muscle cells of aging Caenorhabditis elegans.

Muscle contraction is vital for animal survival, and the sarcomere is the fundamental unit for this process. However, the functions of many conserved sarcomere proteins remain unknown, as their mutants do not exhibit obvious defects. To address this, Caenorhabditis elegans was utilized as a model organism to investigate RSU-1 function in the body wall muscle. RSU-1 is found to colocalize with UNC-97 at the dense body and M-line, and it is particularly crucial for regulating locomotion in aging worms, rather than in young worms. This suggests that RSU-1 has a specific function in maintaining muscle function during aging. Furthermore, the interaction between RSU-1 and UNC-97/PINCH is essential for RSU-1 to modulate locomotion, preserve filament structure, and sustain the M-line and dense body throughout aging. Overall, these findings highlight the significant contribution of RSU-1, through its interaction with UNC-97, in maintaining proper muscle cell function in aging worms.

The Two-Year Results of Using Radiofrequency Ablation as a Novel Treatment for Persistent or Relapsed Graves' Disease: A Prospective Study.

Objectives: Graves' disease (GD) is the most common cause of hyperthyroidism. Antithyroid drugs (ATDs) are the first-line treatment, but when discontinued, >50% of patients experience relapses. Conventional definitive treatment options include surgery and radioiodine therapy (RAI), each with its own disadvantages. Radiofrequency ablation (RFA) achieved promising short-term remission rates in a previous pilot study. The current study reports our experience of using RFA to treat relapsed GD in the largest cohort of patients with a longer follow-up period. Methods: This single-arm prospective study recruited consecutive patients aged ≥18 with persistent/relapsed GD requiring ATD from two tertiary endocrine surgery centers. Those with compressive goiter, suspected thyroid malignancy, moderate-to-severe Graves' ophthalmopathy, preference for surgery/RAI, or pregnancy were excluded. Eligible patients received ultrasound-guided RFA to the entire bulk of the thyroid gland. ATDs were discontinued afterward, and thyroid function tests were monitored bimonthly. The primary outcome was the disease remission rate at 24 months follow-up after single-session RFA, defined as being biochemically euthyroid or hypothyroid without ATD. Secondary outcomes were complication rates. Results: Of the 100 patients considered, 30 (30.0%) patients were eligible and received RFA. Most were female patients (93.3%). The median total thyroid volume was 23 mL (15.9-34.5). All completed 24 months follow-up. After single-session RFA, disease remission rates were 60.0% at 12 months and 56.7% at 24 months. Among the 13 patients with relapse after RFA, 9 (69%) required a lower ATD dose than before RFA; 2 received surgery without complications. Total thyroid volume was the only significant factor associated with relapse after RFA (odds ratio 1.054, confidence interval 1.012-1.099, p = 0.012). At 24 months, RFA led to disease remission in 100% of the 9 patients with a total thyroid volume <20 mL and 35% of patients with a total thyroid volume ≥20 mL (p = 0.007). There was no vocal cord palsy, skin burn, hematoma, or thyroid storm after RFA. Conclusions: In a highly selected group of patients with relapsed GD and predominantly small thyroid glands, single-session RFA may achieve disease remission. Smaller total thyroid volume may be a favorable factor associated with disease remission after RFA. The results of this study need to be confirmed with a long-term clinical trial. Clinical Trial Registration: This study is registered at www.clinicaltrial.gov with identifier NCT06418919.