Rio1 downregulates centromeric RNA levels to promote the timely assembly of structurally fit kinetochores.

Kinetochores assemble on centromeres via histone H3 variant CENP-A and low levels of centromere transcripts (cenRNAs). The latter are ensured by the downregulation of RNA polymerase II (RNAPII) activity, and cenRNA turnover by the nuclear exosome. Using S. cerevisiae, we now add protein kinase Rio1 to this scheme. Yeast cenRNAs are produced either as short (median lengths of 231 nt) or long (4458 nt) transcripts, in a 1:1 ratio. Rio1 limits their production by reducing RNAPII accessibility and promotes cenRNA degradation by the 5'-3'exoribonuclease Rat1. Rio1 similarly curtails the concentrations of noncoding pericenRNAs. These exist as short transcripts (225 nt) at levels that are minimally two orders of magnitude higher than the cenRNAs. In yeast depleted of Rio1, cen- and pericenRNAs accumulate, CEN nucleosomes and kinetochores misform, causing chromosome instability. The latter phenotypes are also observed with human cells lacking orthologue RioK1, suggesting that CEN regulation by Rio1/RioK1 is evolutionary conserved.

Breast MRI in patients with unilateral bloody and serous-bloody nipple discharge: a comparison with galactography.

PURPOSE: Assessing the role of breast MRI compared to galactography in patients with unilateral bloody or serous-bloody nipple discharge. MATERIALS AND METHODS: Retrospective study including 53 unilateral discharge patients who performed galactography and MRI. We evaluated the capability of both techniques in identifying pathology and distinguishing between nonmalignant and malignant lesions. Lesions BIRADS 1/2 underwent follow-up, while the histological examination after surgery has been the gold standard to assess pathology in lesions BIRADS 3/4/5. The ROC analysis was used to test diagnostic MRI and galactography ability. RESULTS: After surgery and follow-up, 8 patients had no disease (15%), 23 papilloma (43%), 11 papillomatosis (21%), 5 ductal cancer in situ (10%), and 6 papillary carcinoma (11%) diagnoses. Both techniques presented 100% specificity; MRI sensitivity was 98% versus 49% of galactography. Considering MRI, we found a statistical association between mass enhancement and papilloma (P < 0.001; AUC 0.957; CI 0.888-1.025), ductal enhancement and papillomatosis (P < 0.001; AUC 0.790; CI 0.623-0.958), segmental enhancement and ductal cancer in situ (P = 0.007; AUC 0.750; CI 0.429-1.071), and linear enhancement and papillary cancer (P = 0.011). CONCLUSIONS: MRI is a valid tool to detect ductal pathologies in patients with suspicious bloody or serous-bloody discharge showing higher sensitivity and specificity compared to galactography.

Breast MRI: Are T2 IR sequences useful in the evaluation of breast lesions?

AIM: To evaluate the potential role of signal intensities calculated in T2 images as an adjunctive parameter in the analysis of mass-like enhancements classified as BIRADS (Breast Imaging Reporting and Data System) assessment categories 2, 3, 4 or 5 with the standard T1 criteria. MATERIALS AND METHODS: After a retrospective review of 338-breast Magnetic Resonance Imaging (MRI) performed for the evaluation of a suspicious lesion we selected a group of 65 mass-like enhancements ranging from 5 to 20mm, classified as BIRADS assessment categories 2, 3, 4 or 5, histologically proved. In all cases we calculated the ratio between the signal intensity (SI) of the nodule and the pectoralis major muscle (LMSIR, lesion to muscle signal intensity ratio) with a multiROIs (region of interest) analysis on T2 images. A ROC analysis was performed to test the ability of the two diagnostic parameters separately considered (BIRADS and LMSIR) and combined in a new mono-dimensional variable obtained by a computerized discriminant function. RESULTS: Histological examination assessed 34 malignant lesions (52.3%) and 31 benign lesions (47.7%). The evaluation of ROC curves gave the following results: BIRADS area under the curve (AUC) 0.913, S.E. 0.0368, LMSIR AUC 0.854, S.E. 0.0487, combined BIRADS-LMSIR AUC 0.965, S.E. 0.0191 with a definitive increase in the AUC between the overall ROC area and those of the two diagnostic modalities separately considered. DISCUSSION: T2-weighted SI assessment with LMSIR measurement improves the diagnostic information content of standard breast MRI and can be considered a promising potential tool in the differential diagnosis of mass-like enhancements judged as borderline lesions (BIRADS 3 and 4).