SUMMARY We report the construction and analysis of 4,836 heterozygous diploid deletion mutants covering 98.4% of the fission yeast genome. This resource provides a powerful tool for biotechnological and eukaryotic cell biology research. Comprehensive gene dispensability comparisons with budding yeast, the first time such studies have been possible between two eukaryotes, revealed that 83% of single copy orthologues in the two yeasts had conserved dispensability. Gene dispensability differed for certain pathways between the two yeasts, including mitochondrial translation and cell cycle checkpoint control. We show that fission yeast has more essential genes than budding yeast and that essential genes are more likely than non-essential genes to be single copy, broadly conserved and to contain introns. Growth fitness analyses determined sets of haploinsufficient and haploproficient genes for fission yeast, and comparisons with budding yeast identified specific ribosomal proteins and RNA polymerase subunits, which may act more generally to regulate eukaryotic cell growth.

PurposeThis study was designed to investigate quality of life (QOL) differences between younger (<50 years) and older (≥50 years) breast cancer survivors and to determine the unique effect of age on QOL after adjusting age-correlated variables.MethodsOne thousand two hundred fifty patients were enrolled. Clinicopatholgical and social parameters were reviewed and Functional Assessment of Cancer Therapy-Breast cancer instrument (FACT-B) and the Ladder of Life scale were used to measure the QOL. Among 1,250 eligible patients, 1,094 patients completed the questionnaire and were used for analysis. Chi-square test, t-test and a series of multiple regression analyses were conducted to verify age-related differences in QOL between two groups and to evaluate the unique contribution of age variable on QOL of breast cancer patients.ResultsSignificant socio-demographic and clinical differences existed based on age categories, including education, job, time since surgery, chemotherapy and daily activity. Also, there were significant age-related differences in FACT-B total, physical well-being, social/family well-being, functional well-being and breast cancer subscale and in subjective QOL. Older patients ≥50 years showed significantly lower QOL than younger patients <50 years. However, after controlling for age-correlated variables including job, education, time since surgery, chemotherapy, and daily activity, there was no unique age difference in QOL among breast cancer survivors.ConclusionOur study results suggest that older women with breast carcinoma suffered significantly lower QOL, even though the unique age effect was not found. Therefore, various interventions for enhancing QOL for women with breast carcinoma should be provided to older age group.

Developing and mature chondrocytes constantly interact with and remodel the surrounding extracellular matrix (ECM). Recent research indicates that integrin-ECM interaction is differentially regulated during cartilage formation (chondrogenesis). Integrin signaling is also a key source of the catabolic reactions responsible for joint destruction in both rheumatoid arthritis and osteoarthritis. However, we do not understand how chondrocytes dynamically regulate integrin signaling in such an ECM-rich environment. Here, we found that developing chondrocytes express integrin-β–like 1 (Itgbl1) at specific stages, inhibiting integrin signaling and promoting chondrogenesis. Unlike cytosolic integrin inhibitors, ITGBL1 is secreted and physically interacts with integrins to down-regulate activity. We observed that Itgbl1 expression was strongly reduced in the damaged articular cartilage of patients with osteoarthritis (OA). Ectopic expression of Itgbl1 protected joint cartilage against OA development in the destabilization of the medial meniscus–induced OA mouse model. Our results reveal ITGBL1 signaling as an underlying mechanism of protection against destructive cartilage disorders and suggest the potential therapeutic utility of targeting ITGBL1 to modulate integrin signaling in human disease.

Pseudoprogression is a major diagnostic dilemma in current treatment protocols for malignant gliomas that involve concurrent chemoradiotherapy. We hypothesized that methylation-specific multiplex ligation probe amplification (MS-MLPA), an assay that permits semiquantitative evaluation of promoter methylation, may be used to diagnose pseudoprogression based on the quantification of the methylation status of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter. We examined the methylation ratio of the MGMT promoter with MS-MLPA in 48 samples from glioblastoma patients. The results were compared with those from methylation-specific polymerase chain reaction (MSP), and protein levels were confirmed by immunohistochemical staining. We then evaluated the correlation between those molecular signatures and clinical outcomes. With regard to radiological progression after chemoradiotherapy, the diagnostic accuracy of the MS-MLPA method was 80% (using a cut-off value of 0.2). These results are better than those obtained with MSP (diagnostic accuracy of 68%). Combining the MS-MLPA and MSP methods resulted in a diagnostic accuracy of 93% for the identification of pseudoprogression among patients to whom these results were coherent. These results demonstrate that MS-MLPA is a useful method to predict radiological progression vs pseudoprogression in glioblastoma patients and that the interpretation of these results in combination with MSP results will provide good practical guidelines for clinical decision making in glioblastoma treatment.