Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.

BARD1 is an ATPase activating protein for OLA1.

OLA1 is a P-loop ATPase, implicated in centrosome duplication through the interactions with tumor suppressors BRCA1 and BARD1. Disruption of the interaction of OLA1 with BARD1 results in centrosome amplification. However, the molecular interplay and mechanism of the OLA1-BARD1 complex remain elusive. Here, we use a battery of biophysical, biochemical, and structural analyses to elucidate the molecular basis of the OLA1-BARD1 interaction. Our structural and enzyme kinetics analyses show this nucleotide-dependent interaction enhances the ATPase activity of OLA1 by increasing the turnover number (kcat). Unlike canonical GTPase activating proteins that act directly on the catalytic G domain, the BARD1 BRCT domain binds to the OLA1 TGS domain via a highly conserved BUDR motif. A cancer related mutation V695L on BARD1 is known to associate with centrosome abnormality. The V695L mutation reduces the BARD1 BRCT-mediated activation of OLA1. Crystallographic snapshot of the BRCT V695L mutant at 1.88 Å reveals this mutation perturbs the OLA1 binding site, resulting in reduced interaction. Altogether, our findings suggest the BARD1 BRCT domain serves as an ATPase activating protein to control OLA1 allosterically.

The remarkable activity and stability of a highly dispersive beta-brass Cu-Zn catalyst for the production of ethylene glycol.

Incorporation of Zn atoms into a nanosize Cu lattice is known to alter the electronic properties of Cu, improving catalytic performance in a number of industrially important reactions. However the structural influence of Zn on the Cu phase is not well studied. Here, we show that Cu nano-clusters modified with increasing concentration of Zn, derived from ZnO support doped with Ga(3+), can dramatically enhance their stability against metal sintering. As a result, the hydrogenation of dimethyl oxalate (DMO) to ethylene glycol, an important reaction well known for deactivation from copper nanoparticle sintering, can show greatly enhanced activity and stability with the CuZn alloy catalysts due to no noticeable sintering. HRTEM, nano-diffraction and EXAFS characterization reveal the presence of a small beta-brass CuZn alloy phase (body-centred cubic, bcc) which appears to greatly stabilise Cu atoms from aggregation in accelerated deactivation tests. DFT calculations also indicate that the small bcc CuZn phase is more stable against Cu adatom migration than the fcc CuZn phase with the ability to maintain a higher Cu dispersion on its surface.

The relationships of the pulmonary arteries to lung lesions aid in differential diagnosis using computed tomography.

The improvement of the resolution of rapid scanning in multidetector computed tomography (CT) has an increased accuracy that allows for the demonstration of the relationship of the pulmonary arteries and lung lesions, even in the peripheral lung. The purpose of this study is to evaluate the relationship between the pulmonary arteries and lung lesions by CT, and to use this relationship to distinguish between benign and malignant lung lesions. The relationships of the lung lesions and the adjacent pulmonary artery were recorded as encasement, displacement, penetration, in the margin, and disconnection. Statistical analyses were then performed to evaluate the relationship of the pulmonary arteries to each lesion with a focus toward the possibility of malignancy and the degree of pulmonary arterial encasement in the lesion. The relationship between the pulmonary arteries and lung lesions had a statistically significant difference between benignancy and malignancy (P < 0.001). Inter-observer agreement was substantial (κ = 0.639; 95% CI: 0.518-0.719). The average degrees of pulmonary arterial encasement in benign and malignant lesions were 52.1% ± 27.3% and 71.8% ± 18.8%, respectively (P = 0.011). The ROC curve showed that the degree of pulmonary arterial encasement had a moderate discriminating ability in diagnosing lung carcinoma, and the area under the curve was 0.738. The best cutoff value was 44.4%. The relationships of the pulmonary arteries to lung lesions and the degree of pulmonary arterial encasement could be used in differentiating benignancy from malignancy not only for central lung lesions but also peripheral lung lesions.

Subsequent Cancer Risk of Women Receiving Hysterosalpingography: A Nationwide Population-Based Retrospective Cohort Study.

The objective of this study was to estimate the subsequent cancer risk of women after receiving hysterosalpingography (HSG) by conducting a nationwide retrospective cohort study. We identified a study cohort of 4,371 patients who had had a HSG examination and a comparison cohort of 17,484 women without HSG examination between 1998 and 2005. Both cohorts were followed up with until the end of 2010 to measure the incidence of cancer. The risk of developing cancer for patients with HSG was assessed using the Cox proportional hazard model. In the multivariate analyses, the HSG cohort did not have a significantly greater risk of cancer (Hazard Ratio [HR] = 1.02, 95% CI = 0.79-1.31) than the non-HSG cohort. The HR was highest for genital cancer (HR = 1.32, 95% CI = 0.77-2.25), followed by urinary system cancer (HR = 1.11, 95% CI = 0.23-5.40), and abdominal cancer not involving the GU system (HR = 1.04, 95% CI = 0.53-2.03), all of which were non-significant elevations. The cancer incidence rates, especially that for urinary system cancer, were increased in the HSG cohort, but the increase in cancer incidence was small and not statistically significant.

Subsequent cancer risk of children receiving post voiding cystourethrography: a nationwide population-based retrospective cohort study.

BACKGROUND: To estimate the subsequent cancer risk of children receiving post voiding cystourethrography (VCUG), a nationwide population-based retrospective cohort study with the data from the Taiwan National Health Insurance Research Database (NHIRD) were used for the analysis. METHODS: In the VCUG cohort, 31,908 participants younger than 18 years of age who underwent VCUG between 1997 and 2008 were identified from the NHIRD. A comparison cohort, the non-VCUG cohort, was randomly selected among children without VCUG examination histories during 1997-2008, frequency matched for age (every 5 years), sex, geographic region area, parents' occupation, and index year based on a 1:4 ratio. Cox's proportional hazard regression analysis was conducted to estimate the subsequent cancer risk of children receiving VCUG. RESULTS: The overall cancer risk of the VCUG cohort is 1.92-fold (95 % CI = 1.34-2.74) higher than that of the non-VCUG cohort with statistical significance. The genital cancer and urinary system cancer risks of the VCUG cohort are respectively 6.19-fold (95 % CI = 1.37-28.0) and 5.8-fold (95 % CI = 1.54-21.9) higher than those of the non-VCUG cohort with statistical significance. The hazard ratios are higher in genital cancer, urinary system cancer (the major radiation exposure area), and cancer of the abdomen, except for the genitourinary system (the minor radiation exposure area), in sequence. CONCLUSIONS: Pediatric VCUG is associated with increased subsequent cancer risk, especially in the genitourinary system.

Reproducibility of corticospinal diffusion tensor tractography in normal subjects and hemiparetic stroke patients.

PURPOSE: The reproducibility of corticospinal diffusion tensor tractography (DTT) for a guideline is important before longitudinal monitoring of the therapy effects in stroke patients. This study aimed to establish the reproducibility of corticospinal DTT indices in healthy subjects and chronic hemiparetic stroke patients. MATERIALS AND METHODS: Written informed consents were obtained from 10 healthy subjects (mean age 25.8 ± 6.8 years), who underwent two scans in one session plus the third scan one week later, and from 15 patients (mean age 47.5 ± 9.1 years, 6-60 months after the onset of stroke, NIHSS scores between 9 and 20) who were scanned thrice on separate days within one month. Diffusion-tensor imaging was performed at 3T with 25 diffusion directions. Corticospinal tracts were reconstructed using fiber assignment by continuous tracking without and with motion/eddy-current corrections. Intra- and inter-rater as well as intra- and inter-session variations of the DTT derived indices (fiber number, apparent diffusion coefficient (ADC), and fractional anisotropy (FA)) were assessed. RESULTS: Intra-session and inter-session coefficients of variations (CVs) are small for FA (1.13-2.09%) and ADC (0.45-1.64%), but much larger for fiber number (8.05-22.4%). Inter-session CVs in the stroke side of patients (22.4%) are higher than those in the normal sides (18.0%) and in the normal subjects (14.7%). Motion/eddy-current correction improved inter-session reproducibility only for the fiber number of the infarcted corticospinal tract (CV reduced from 22.4% to 14.1%). CONCLUSION: The fiber number derived from corticospinal DTT shows substantially lower precision than ADC and FA, with infarcted tracts showing lower reproducibility than the healthy tissues.

Automated feature set selection and its application to MCC identification in digital mammograms for breast cancer detection.

We propose a fully automated algorithm that is able to select a discriminative feature set from a training database via sequential forward selection (SFS), sequential backward selection (SBS), and F-score methods. We applied this scheme to microcalcifications cluster (MCC) detection in digital mammograms for early breast cancer detection. The system was able to select features fully automatically, regardless of the input training mammograms used. We tested the proposed scheme using a database of 111 clinical mammograms containing 1,050 microcalcifications (MCs). The accuracy of the system was examined via a free response receiver operating characteristic (fROC) curve of the test dataset. The system performance for MC identifications was Az = 0.9897, the sensitivity was 92%, and 0.65 false positives (FPs) were generated per image for MCC detection.

Dependent pooling: a contrast-enhanced sign of cardiac arrest during CT.

OBJECTIVE: The purpose of this study is to describe the imaging features of cardiac arrest that occur during CT. CONCLUSION: CT features of cardiac arrest are characterized by a pooling of contrast agent in the dependent parts of the right side of the body, including the venous system and the right lobe of the liver. If medical professionals are aware of these specific imaging features, prompt cardiac resuscitation can be initiated to avoid permanent brain damage and death.