Laustsenjiang6340

R-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops, we mapped RNADNA hybrids, markers of replication fork stalling and DNA double-strand breaks along the human genome. This analysis indicates that transient replication fork pausing occurs at the transcription termination sites of highly expressed genes enriched in R-loops and prevents head-on conflicts with transcription, in a topoisomerase I-dependent manner.We have recently identified the MYC proto-oncogene, bHLH transcription factor (MYC, best known as c-Myc)-responsive pan-cancer lncRNA c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP) as an oncogenic driver. Our studies show that MILIP facilitates tumor protein p53 (TP53, best known as p53) turnover by reducing its SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2), thus promoting cell survival, proliferation, and tumorigenicity. MILIP may thus represent an anti-cancer target for counteracting the c-Myc axis.The inositol 1,4,5-triphosphate receptor (InsP3R)-mediated calcium (Ca2+) transfer to mitochondria is important to maintain mitochondrial respiration and bioenergetics in normal and cancer cells, even though cancer cells have defective oxidative phosphorylation (OXPHOS). Here, we discuss how tumor mitochondria could become a feasible therapeutic target to treat tumors that depend on reductive carboxylation.Chemotherapy-induced peripheral neuropathy is a debilitating toxicity that adversely affects patient quality and course of treatment. Recent findings have demonstrated that the etiology of peripheral neuropathy is dependent on transporter-mediated accumulation in dorsal root ganglia, and targeting this mechanism can afford neurological protection without compromising therapeutic efficacy.CRL and APC/C belong to the RING-finger-type E3 ligases, and both play important roles in cell cycle regulation. Recently, we found that SAG, a RING component of CRL, acts as an endogenous inhibitor of APC/C by competing with APC2 for E2s binding; while APC/CCDH1 targets SAG for ubiquitylation and degradation at G1 phase. The negative crosstalk between these two E3s ensures the orderly cell cycle progression.Abnormally increased signaling by the GTPase RAP1 favors progression of diverse tumors. We have characterized the auto-regulation and activation of C3G (RAPGEF1), an activator of RAP1. This led us to discover mutations in non-Hodgkin's lymphomas that activate C3G-RAP1 constitutively, suggesting that deregulation of C3G may favor the dissemination of tumor cells.Skeletal morbidities continue to cause acute and long-term burdens for B-ALL patients underscoring the need to identify the mechanisms underlying these processes and to develop effective therapies. Our recent findings demonstrated that B-ALL cells isolated at patient diagnosis can cause bone destruction and have identified the receptor activator of nuclear factor κ-B (RANK-RANKL) ligand axis as a critical effector of these effects.This study aimed to identify the high-impact details of play and movements with higher acceleration and their frequency during a female basketball match. Trunk acceleration was measured during a simulated basketball game with eight female players. The extracted instance was categorized, which generated at > 6 and 8 G resultant accelerations using a video recording and an accelerometer attached to the players' trunk, as details of play and movements. The frequency and ratio of the details of play and movements regarding all detected movements were calculated. A total of 1062 and 223 play actions were detected for the resultant acceleration thresholds of > 6 and 8 G, respectively. For these acceleration thresholds, in terms of details of play, positioning on the half-court was the most frequently observed (29.6 and 23.8%, respectively). In terms of movements, deceleration was the most frequently detected movement (21.5 and 23.3%, respectively), followed by landing (7.6 and 15.7%, respectively). Deceleration during positioning on the half-court and defense as well as landing mostly after a shot were detected as high-impact frequent basketball-specific movements. The results also showed that characteristics of movements or playing style and playing position may have an effect on acceleration patterns during a basketball game.Biological disasters endanger the lives of teachers and students, causing serious disturbances to schools, and forcing them to shut down for a short or long period of time. Over the last few decades, the Greater Athens area and Attica Prefecture in Greece have experienced several natural disasters. These events have highlighted problems and weaknesses in emergency planning for school communities at both local and regional level, and have shown the need for new precautionary measures and effective risk management for modern society and school communities. The present study reports an investigation of the perception of the risk posed by biological hazards to teacher safety. The investigation utilized a questionnaire survey of teachers working in the secondary education directorate in Western Attica, which was carried out between May and December 2019. The teachers' perceptions of the extent to which their safety was affected by biohazards (i.e., infectious diseases and weather-related diseases) were investigated using a 5-point scale ranging from affected a lot (- 2) to not affected at all (+ 2). A multivariate statistical technique-principal component analysis-was used to explore the results of the survey. The results showed that the teachers' feelings of safety were affected a lot (- 2) or affected enough (- 1) by biohazards. 61.5% (n = 72) of the participants reported that their feelings of safety were affected a lot or enough by infectious diseases, and 55.6% (n = 65) of the participants noted that their feelings of safety were affected a lot or enough by weather-related diseases. Compared to other natural, technological, or social hazards, biological hazards seem to have a greater impact on teachers' feelings of safety. click here These results could have implications for the design of risk management plans for school communities.