Bücherschau

Ohne Zusammenfassung VDI     

Partial Reduction in BRCA1 Gene Dose Modulates DNA Replication Stress Level and Thereby Contributes to Sensitivity or Resistance

BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1. How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1.     

Improved Bladder Tumor RNA Isolation from Archived Tissues Using Methylene Blue for Normalization,Multiplex RNA Hybridization,Sequencing and Subtyping

Methylene blue (MB) is a dye used for histology with clinical importance and intercalates into nucleic acids. After MB staining of formalin fixed paraffin embedded (FFPE) muscle invasive bladder cancer (MIBC) and normal urothelium, specific regions could be microdissected. It is not known if MB influences RNA used for gene expression studies. Therefore, we analyzed MIBC using five different RNA isolation methods comparing patient matched FFPE and fresh frozen (FF) tissues pre-stained with or without MB. We demonstrate a positive impact of MB on RNA integrity with FF tissues using real time PCR with no interference of its chemical properties. FFPE tissues showed no improvement of RNA integrity, which we propose is due to formalin induced nucleotide crosslinks. Using direct multiplex RNA hybridization the best genes for normalization of MIBC and control tissues were identified from 34 reference genes. In addition, 5SrRNA and 5.8SrRNA were distinctive reference genes detecting <200 bp fragments important for mRNA analyses. Using these normalized RNAs from MB stained MIBC and applying multiplex RNA hybridization and mRNA sequencing, a minimal gene expression panel precisely identified luminal and basal MIBC tumor subtypes, important for diagnosis, prognosis and chemotherapy response.     

Rare-earth diiodides and derivatives

The rare-earth diiodides, MI₂, may be synthesized from the corresponding triiodides, MI₃, by reduction with their metals at elevated temperatures or, alternatively, through so-called metallothermic reduction reactions with alkaline or alkaline-earth metals. In these cases, ternary iodides may be obtained that may be derived from the binary diiodides by either formal addition or substitution. Prominent formula types that are thus obtained are A^IMI₃, or the mixed-valent A^I₅M^II₂M^IIII₁₂ and A^IIMI₄ with A^I and A^II representing alkaline or alkaline-earth elements (and their analogues), respectively. Further iodides that are relevant in these systems are, for example, Pr₂I₅, Ba₆Pr₃I₁₉ and interstitially stabilized phases such as {Er₁₄(N₂)(C₂)₂}I₂₄, La₉O₄I₁₆ and Ba{Ce₄N₂}I₈.     

Differential responses to male and female depressive reactions.

Suggests that the commonly reported preponderance of female over male depression in incidence and prevalence studies requires further analysis. One explanation is that the social consequences of expression of depressive symptomatology are different for males and females. A comparison of 157 male and 189 female undergraduates' reactions to male and female case histories of common reactions to stress confirmed the hypothesis. Depression elicited more rejection of males than of females, and the sex difference in rejection of depression was more pronounced than for anxiety or flat affect-detached responses. A discriminant analysis suggested that depressed males are especially likely to be perceived as impaired in role functioning as compared with depressed females. Results suggest that depressed males are not rejected for expression of emotionality as such. Speculations about the causes and consequences of differential rejection of depression are noted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychological disease adjustment in breast cancer patients

In a prospective follow-up study, attention was focused on adjustment to disease in breast cancer patients one year after diagnosis. Prebioptic data was collected in the original patient group consisting of 95 women with mammary tissue findings that required clarification. Twenty-nine women with histological confirmation of breast cancer and 37 patients of the control group with benign histological findings were recontacted after an interval of one year. Data was collected by means of psychological test questionnaires (STAI, SVF, FPI, CIP-DS), the patients with breast cancer were given an additional problem-oriented questionnaire about coping with disease, compiled by the author. Most denied having disease-related fears-progression of the disease, premature death; instead, marked sleep disturbances, regularly, recurring nightmares, and depressed states of mind characterized the psychosomatic correlate of the mental burden. The psychological consequences of cancer are related to some extent to the stage of tumour growth at the time of diagnosis; the process of social reintegration appears to be facilitated in women whose biopsy operation did not involve removal of a breast. An clear characterization of breast cancer patients could not be established using psychological testing procedures one year after diagnosis of the disease.     

X-ray microbeam and recrystallization studies of plastic deformation around fatigue cracks

X-ray microbeam technique and recrystallization method were used to measure plastic zones around 20 kHz fatigue cracks in mild steel. Both methods render approximately the same extension of a plastic zone. In order to obtain the amount of deformation within a plastic zone measurements of integral line breadth and recrystallization temperature were calibrated by specimens deformed with known per cent static tension. But since static and cyclic loading cause different dislocation structures (especially the dislocation density is much more inhomogeneous in fatigued specimens) quantitative comparison is difficult. Furthermore the two methods display different values of the actual amount of deformation. X-ray line broadening indicates an average dislocation density, whereas recrystallization displays a maximum amount of deformation, which corresponds to the local dislocation concentrations.     

SNR enhancement in radial SSFP imaging using partial k-space averaging

The steady-state free precessing (SSFP) sequences, widely used in MRI today, acquire data only during a short fraction of the repetition time (TR). Thus, they exhibit a poor scan efficiency. In this paper, a novel approach to extending the acquisition window for a given TR without considerably modifying the basic sequence is explored for radial SSFP sequences. The additional data are primarily employed to increase the signal-to-noise ratio, rather than to improve the temporal resolution of the imaging. The approach is analyzed regarding its effect on the image SNR (signal to noise ratio) and the reconstruction algorithm. Results are presented for phantom experiments and cardiac functions studies. The gain in SNR is most notable in rapid imaging, since SNR enhancement for a constant repetition time may be used to compensate for the increase in noise resulting from angular undersampling.