Translation initiation factor eIF4G1 modulates assembly of the polypeptide exit tunnel region in yeast ribosome biogenesis.

eIF4G is an important eukaryotic translation initiation factor. In this study, eIF4G1, one of the eIF4G isoforms, was shown to directly participate in biogenesis of the large (60S) ribosomal subunit in Saccharomyces cerevisiae cells. Mutation of eIF4G1 decreased the amount 60S ribosomal subunits significantly. The C-terminal fragment of eIF4G1 could complement the function in 60S biogenesis. Analyses of its purified complex with mass spectrometry indicated that eIF4G1 associated with the pre-60S form directly. Strong genetic and direct protein-protein interactions were observed between eIF4G1 and Ssf1 protein. Upon deletion of eIF4G1, Ssf1, Rrp15, Rrp14 and Mak16 were abnormally retained on the pre-60S complex. This purturbed the loading of Arx1 and eL31 at the polypeptide exit tunnel (PET) site and the transition to a Nog2 complex. Our data indicate that eIF4G1 is important in facilitating PET maturation and 27S processing correctly. This article has an associated First Person interview with the first author of the paper.

Mutations of ribosomal protein genes induce overexpression of catalase in Saccharomyces cerevisiae.

Ribosome assembly defects result in ribosomopathies, primarily caused by inadequate protein synthesis and induced oxidative stress. This study aimed to investigate the link between deleting one ribosomal protein gene (RPG) paralog and oxidative stress response. Our results indicated that RPG mutants exhibited higher oxidant sensitivity than the wild type (WT). The concentrations of H2O2 were increased in the RPG mutants. Catalase and superoxide dismutase (SOD) activities were generally higher at the stationary phase, with catalase showing particularly elevated activity in the RPG mutants. While both catalase genes, CTT1 and CTA1, consistently exhibited higher transcription in RPG mutants, Ctt1 primarily contributed to the increased catalase activity. Stress-response transcription factors Msn2, Msn4, and Hog1 played a role in regulating these processes. Previous studies have demonstrated that H2O2 can cleave 25S rRNA via the Fenton reaction, enhancing ribosomes' ability to translate mRNAs associated with oxidative stress-related genes. The cleavage of 25S rRNA was consistently more pronounced, and the translation efficiency of CTT1 and CTA1 mRNAs was altered in RPG mutants. Our results provide evidence that the mutations in RPGs increase H2O2 levels in vivo and elevate catalase expression through both transcriptional and translational controls.

Exploring the multifaceted impact of lanthanides on physiological pathways in human breast cancer cells.

Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl3 or CeCl3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly.

Artificial neural network for predicting pathological stage of clinically localized prostate cancer in a Taiwanese population.

BACKGROUND: We developed an artificial neural network (ANN) model to predict prostate cancer pathological staging in patients prior to when they received radical prostatectomy as this is more effective than logistic regression (LR), or combined use of age, prostate-specific antigen (PSA), body mass index (BMI), digital rectal examination (DRE), trans-rectal ultrasound (TRUS), biopsy Gleason sum, and primary biopsy Gleason grade. METHODS: Our study evaluated 299 patients undergoing retro-pubic radical prostatectomy or robotic-assisted laparoscopic radical prostatectomy surgical procedures with pelvic lymph node dissection. The results were intended to predict the pathological stage of prostate cancer (T2 or T3) after radical surgery. The predictive ability of ANN was compared with LR and validation of the 2007 Partin Tables was estimated by the areas under the receiving operating characteristic curve (AUCs). RESULTS: Of the 299 patients we evaluated, 109 (36.45%) displayed prostate cancer with extra-capsular extension (ECE), and 190 (63.55%) displayed organ-confined disease (OCD). LR analysis showed that only PSA and BMI were statistically significant predictors of prostate cancer with capsule invasion. Overall, ANN outperformed LR significantly (0.795 ± 0.023 versus 0.746 ± 0.025, p = 0.016). Validation using the current Partin Tables for the participants of our study was assessed, and the predictive capacity of AUC for OCD was 0.695. CONCLUSION: ANN was superior to LR at predicting OCD in prostate cancer. Compared with the validation of current Partin Tables for the Taiwanese population, the ANN model resulted in larger AUCs and more accurate prediction of the pathologic stage of prostate cancer.

Non-planar and flexible chip technology for biomedical applications.

We report a novel non-planar flexible silicon chip technology by means of patterning thin films of high residual stress on top of shaped thin silicon substrate. High residual stresses of thin films make thin chip deform into designed three-dimensional shapes. In this study, a series of patterned stress films and "petal-like" chips were fabricated and analyzed. Large curvatures can also be formed and maintained by the packaging process bonding the chips to constraining elements such as thin-film polymer ring structures. As a demonstration, a CMOS image-sensing retina chip is made into a contact-lens shape conforming to a human eyeball 12.5 m in radius. This non-planar and flexible chip technology provides a desirable device surface interface to soft or non-planar bio surfaces and opens up possibilities for many biomedical applications.