Search Results (6)

To complement classical methods for identifying Japanese, Chinese, and Western dietary styles, this study aimed to develop a machine learning model. This study utilized 604 features from 8183 cooking recipes based on a Japanese recipe site. The data were randomly divided into training, validation, and test sets for each dietary style at a 60:20:20 ratio. Six machine learning models were developed in this study to effectively classify cooking recipes according to dietary styles. The evaluation indicators were above 0.8 for all models in each dietary style. The top ten features were extracted from each model, and the features common to three or more models were employed as the best predictive features. Five well-predicted features were indicated for the following seasonings: soy sauce, miso (fermented soy beans), and mirin (sweet cooking rice wine) in the Japanese diet; oyster sauce and doubanjiang (chili bean sauce) in the Chinese diet; and olive oil in the Western diet. Predictions by broth were indicated in each diet, such as dashi in the Japanese diet, chicken soup in the Chinese diet, and consommé in the Western diet. The prediction model suggested that seasonings and broths could be used to predict dietary styles. Full article

Pine-green moss forests on Podzols exhibit high susceptibility to fire. Subsequent to wildfire, soot and charcoal enter the soil profile and accumulate in the upper part of the podzolic horizon (E). This process results in the development of a greying pyrogenic podzol horizon (Epyr). The maximum concentration of pyrogenic components accumulates in the surface layer of Epyr, which is 1 to 4 cm thick and the darkest in colour. The comprehensive soil descriptions showed the existence of a fine pyrogenic layer between the forest floor and mineral horizon. This layer was not analysed. The current shift in science towards assessing the environmental aspects of soil organic matter dynamics requires a more detailed study of the soil profile. We suggest distinguishing the pyrogenic organic mineral sub-horizon of the Eopyr as the upper Epyr layer. Our results show this sub-horizon contains sand, humus, detritus, and charcoal. It forms around 6%–22% of the entire organic matter pools in the biologically active part of the soil (0–30 cm). Further research is needed to obtain reliable qualitative and quantitative data on Eopyr. Full article

The MRE11 nuclease is essential during DNA damage recognition, homologous recombination, and replication. BRCA2 plays important roles during homologous recombination and replication. Here, we show that effecting an MRE11 blockade using a prototypical inhibitor (Mirin) induces synthetic lethality (SL) in BRCA2-deficient ovarian cancer cells, HeLa cells, and 3D spheroids compared to BRCA2-proficient controls. Increased cytotoxicity was associated with double-strand break accumulation, S-phase cell cycle arrest, and increased apoptosis. An in silico analysis revealed Mirin docking onto the active site of MRE11. While Mirin sensitises DT40 MRE11^+/− cells to the Top1 poison SN-38, it does not sensitise nuclease-dead MRE11 cells to this compound confirming that Mirin specifically inhibits Mre11 nuclease activity. MRE11 knockdown reduced cell viability in BRCA2-deficient PEO1 cells but not in BRCA2-proficient PEO4 cells. In a Mirin-resistant model, we show the downregulation of 53BP1 and DNA repair upregulation, leading to resistance, including in in vivo xenograft models. In a clinical cohort of human ovarian tumours, low levels of BRCA2 expression with high levels of MRE11 co-expression were linked with worse progression-free survival (PFS) (p = 0.005) and overall survival (OS) (p = 0.001). We conclude that MRE11 is an attractive SL target, and the pharmaceutical development of MRE11 inhibitors for precision oncology therapeutics may be of clinical benefit. Full article

Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 exonuclease activity), albeit with ~40% reduced efficiency compared to normal cells. Editing in the absence of XRCC4 or MRE11 exonuclease was robust, with little difference between the indel profiles amongst any of the groups. Reviewing the transcriptional profiles of the mirin-treated XRCC4 knockout cells showed 307 uniquely differentially expressed genes, a number far greater than for either of the other cell lines (the HeLa XRCC4 knockout sample had 83 genes, and the mirin-treated HeLa cells had 30 genes uniquely differentially expressed). Pathways unique to the XRCC4 knockout+mirin group included differential expression of p53 downstream pathways, and metabolic pathways indicating cell adaptation for energy regulation and stress response. In conclusion, our study showed that TALEN-induced DSBs are repaired, even when a key DSB repair protein or protein function is not operational, without a change in indel profiles. However, transcriptional profiles indicate the induction of unique cellular responses dependent upon the DNA repair protein(s) hampered. Full article

Cancer stem cells (CSCs) drive not only tumor initiation and expansion, but also therapeutic resistance and tumor relapse. Therefore, CSC eradication is required for effective cancer therapy. In preclinical models, CSCs demonstrated high capability to tolerate even extensive genotoxic stress, including replication stress, because they are endowed with a very robust DNA damage response (DDR). This favors the survival of DNA-damaged CSCs instead of their inhibition via apoptosis or senescence. The DDR represents a unique CSC vulnerability, but the abrogation of the DDR through the inhibition of the ATR-CHK1 axis is effective only against some subtypes of CSCs, and resistance often emerges. Here, we analyzed the impact of druggable DDR players in the response of patient-derived colorectal CSCs (CRC-SCs) to CHK1/2 inhibitor prexasertib, identifying RAD51 and MRE11 as sensitizing targets enhancing prexasertib efficacy. We showed that combined inhibition of RAD51 and CHK1 (via B02+prexasertib) or MRE11 and CHK1 (via mirin+prexasertib) kills CSCs by affecting multiple genoprotective processes. In more detail, these two prexasertib-based regimens promote CSC eradication through a sequential mechanism involving the induction of elevated replication stress in a context in which cell cycle checkpoints usually activated during the replication stress response are abrogated. This leads to uncontrolled proliferation and premature entry into mitosis of replication-stressed cells, followed by the induction of mitotic catastrophe. CRC-SCs subjected to RAD51+CHK1 inhibitors or MRE11+CHK1 inhibitors are eventually eliminated, and CRC-SC tumorspheres inhibited or disaggregated, via a caspase-dependent apoptosis. These results support further clinical development of these prexasertib-based regimens in colorectal cancer patients. Full article

We report that an ErAs quantum-dot array in a GaAs matrix under 1550 nm pulsed excitation produces cooperative spontaneous emission—Dicke superradiance—in the terahertz frequency region at room temperature. Two key points pertain to the experimental evidence: (i) the pulsed THz emission power is much greater than the continuous wave (CW) photomixing power; and (ii) the ultrafast time-domain waveform displays ringing cycles. A record of ~117 μW pulsed THz power was obtained, with a 1550 nm-to-THz power conversion efficiency of ~0.2%. Full article