Degnpolat5577

DJ-1/PARK7 mutations are linked with familial forms of early-onset Parkinson's disease (PD). We have studied the degradation of untagged DJ-1 wild type (WT) and missense mutants in mouse embryonic fibroblasts obtained from DJ-1-null mice, an approach closer to the situation in patients carrying homozygous mutations. The results showed that the mutants L10P, M26I, A107P, P158Δ, L166P, E163K, and L172Q are unstable proteins, while A39S, E64D, R98Q, A104T, D149A, A171S, K175E, and A179T are as stable as DJ-1 WT. Inhibition of proteasomal and autophagic-lysosomal pathways had little effect on their degradation. Immunofluorescence and biochemical fractionation studies indicated that M26I, A107P, P158Δ, L166P, E163K, and L172Q mutants associate with mitochondria. Silencing of mitochondrial matrix protease LonP1 produced a strong reduction of the degradation of the mitochondrial-associated DJ-1 mutants A107P, P158Δ, L166P, E163K, and L172Q but not of mutant L10P. These results demonstrated a mitochondrial pathway of degradation of those DJ-1 missense mutants implicated in PD pathogenesis.MLL is an aggressive subtype of leukemia with a poor prognosis that mostly affects pediatric patients. Wnt antagonist MLL-rearranged fusion proteins (MLLr) induce aberrant target gene expression resulting in leukemogenesis. MLL and its fusions are tethered to chromatin by LEDGF/p75, a transcriptional co-activator that specifically recognizes H3K36me2/3. LEDGF/p75 is ubiquitously expressed and associated with regulation of gene expression, autoimmune responses, and HIV replication. LEDGF/p75 was proven to be essential for leukemogenesis in MLL. Apart from MLL, LEDGF/p75 has been linked to lung, breast, and prostate cancer. Intriguingly, LEDGF/p75 interacts with Med-1, which co-localizes with BRD4. Both are known as co-activators of super-enhancers. Here, we describe LEDGF/p75-dependent chemoresistance of MLLr cell lines. Investigation of the underlying mechanism revealed a role of LEDGF/p75 in the cell cycle and in survival pathways and showed that LEDGF/p75 protects against apoptosis during chemotherapy. Remarkably, LEDGF/p75 levels also affected expression of BRD4 and Med1. Altogether, our data suggest a role of LEDGF/p75 in cancer survival, stem cell renewal, and activation of nuclear super enhancers.Photosynthesis is tightly regulated in order to withstand dynamic light environments. Under high light intensities, a mechanism known as non-photochemical quenching (NPQ) dissipates excess excitation energy, protecting the photosynthetic machinery from damage. An obstacle that lies in the way of understanding the molecular mechanism of NPQ is the large gap between in vitro and in vivo studies. On the one hand, the complexity of the photosynthetic membrane makes it challenging to obtain molecular information from in vivo experiments. On the other hand, a suitable in vitro system for the study of quenching is not available. Here we have developed a minimal NPQ system using proteoliposomes. With this, we demonstrate that the combination of low pH and PsbS is both necessary and sufficient to induce quenching in LHCII, the main antenna complex of plants. This proteoliposome system can be further exploited to gain more insight into how PsbS and other factors (e.g. zeaxanthin) influence the quenching mechanism observed in LHCII.Culex mosquitoes particularly Culex quinquefasciatus are important arboviral and filariasis vectors, however despite this important epidemiological role, there is still a paucity of data on their bionomics. The present study was undertaken to assess the insecticide resistance status of Cx. quinquefasciatus populations from four districts of Yaoundé (Cameroon). All Culex quinquefasciatus populations except one displayed high resistance to bendiocarb and malathion with mortalities ranging from 0 to 89% while high resistance intensity against both permethrin and deltamethrin was recorded. Molecular analyses revealed high frequencies of the ACE-1 G119S mutation (ranging from 0 to 33%) and kdr L1014F allele (ranging from 55 to 74%) in all Cx. quinquefasciatus populations. Significant overexpression was detected for cytochrome P450s genes CYP6AA7 and CYP6Z10, as well as for Esterase A and Esterase B genes. The total cuticular hydrocarbon content, a proxy of cuticular resistance, was significantly increased (compared to the S-lab strain) in one population. The study confirms strong insecticide resistance mediated by different mechanisms in Cx. quinquefasciatus populations from the city of Yaoundé. The expansion of insecticide resistance in Culex populations could affect the effectiveness of current vector control measures and stress the need for the implementation of integrated vector control strategies in urban settings.To imply the gravity of their impact on Christmas celebration, the term Christmas typhoon recently became more popular to refer to tropical cyclones (TC) in the Western North Pacific (WNP) during its less active season. The past 9 years from 2012 to 2020 saw more than 70% (210%) increases in Christmas typhoon occurrences in the WNP (Philippines). Furthermore, Mindanao Island, which is located in southern Philippines, has experienced an unprecedented 480% increase in TC passage in the same period. Here we show that the detected recent increase in Christmas typhoons are mainly associated with the shift of the Pacific Decadal Oscillation to its positive phase in early 2010s, which led to favorable changes in the large-scale environment for TC development such as higher relative vorticity, anomalous low-level westerlies, warmer sea surface temperatures in the central Pacific, and extended WNP subtropical high. We also found that the poleward shift of the Intertropical Convergence Zone and possibly, the recent recovery of the Siberian High contributed to such increased occurrences. As opposed to the more active TC season, there is a wide research gap during the less active season. We aim to fill in this knowledge gap to gain better insights on TC risk reduction.The expansion of mosquito species worldwide is creating a powerful network for the spread of arboviruses. In addition to the destruction of breeding sites (prevention) and mass trapping, methods based on the sterile insect technique (SIT), the autodissemination of pyriproxyfen (ADT), and a fusion of elements from both of these known as boosted SIT (BSIT), are being developed to meet the urgent need for effective vector control. However, the comparative potential of these methods has yet to be explored in different environments. This is needed to propose and integrate informed guidelines into sustainable mosquito management plans. We extended a weather-dependent model of Aedes albopictus population dynamics to assess the effectiveness of these different vector control methods, alone or in combination, in a tropical (Reunion island, southwest Indian Ocean) and a temperate (Montpellier area, southern France) climate. Our results confirm the potential efficiency of SIT in temperate climates when performed early in the year (mid-March for northern hemisphere). In such a climate, the timing of the vector control action was the key factor in its success. In tropical climates, the potential of the combination of methods becomes more relevant. BSIT and the combination of ADT with SIT were twice as effective compared to the use of SIT alone.Individuals tend to approach positive stimuli and avoid negative stimuli. Furthermore, emotions influence whether individuals freeze or move more. These two kinds of motivated behavior refer to the approach/avoidance behavior and behavioral freezing/activation. Previous studies examined (e.g., using forced platforms) whether individuals' behavior depends on stimulus' valence; however, the results were mixed. Thus, we aimed to test whether emotions' effects on spontaneous whole-body behavior of standing individuals also occur in the seated position. We used a computer vision method to measure the head sway in video recordings that offers ease of use, replicability, and unobtrusiveness for the seated research participant. We analyzed behavior recorded in the laboratory during emotion manipulations across five studies totaling 932 participants. We observed that individuals leaned more forward and moved more when watching positive stimuli than when watching negative stimuli. However, individuals did not behave differently when watching positive or negative stimuli than in the neutral condition. Our results indicate that head movements extracted from seated individuals' video recordings can be useful in detecting robust differences in emotional behavior (positive vs. negative emotions).Anopheles mosquitoes transmit malaria, which affects one-fifth of the world population. A comprehensive understanding of mosquito behaviour is essential for the development of novel tools for vector control and surveillance. Despite abundant research on mosquito behaviour, little is known on the stimuli that drive malaria vectors during the landing phase of host-seeking. Using behavioural assays with a multimodal step approach we quantified both the individual and the combined effect of three host-associated stimuli in eliciting landing in Anopheles coluzzii females. We demonstrated that visual, olfactory and thermal sensory stimuli interact synergistically to increase the landing response. Furthermore, if considering only the final outcome (i.e. landing response), our insect model can bypass the absence of either a thermal or a visual stimulus, provided that at least one of these is presented simultaneously with the olfactory stimuli, suggesting that landing is the result of a flexible but accurate stimuli integration. These results have important implications for the development of mosquito control and surveillance tools.To investigate the influence of age on the function and morphology of patients with myopic choroidal neovascularization (mCNV) and to evaluate the effect and prognostic factors of recurrence of Conbercept treatment on mCNV patients over 50 years. A total of 64 patients (64 eyes) with mCNV were enrolled in this retrospective study. The differences in baseline best-corrected visual acuity (BCVA) and morphological features on imaging between the younger group (˂ 50 years) and the older group (≥ 50 years) were analyzed. Of all, 21 eyes of 21 mCNV patients aged over 50 years who received Conbercept injection were further analyzed. Between the younger and the older group, significant differences were shown in mean BCVA (0.58 ± 0.28 vs 0.77 ± 0.31), subfoveal choroidal thickness (SFCT) (108.17 ± 78.32 μm vs 54.68 ± 39.03 μm) and frequency of vitreoretinal interface abnormalities (VIA) (2 vs 13), respectively (P  less then  0.05). After treated with Conbercept, the mean BCVA of 21 older mCNV patients increased from 0.83 ± 0.30 at baseline to 0.49 ± 0.24 at one year. Baseline BCVA, external limiting membrane damage, CNV area and CNV location correlated with the visual acuity at the 1-year follow-up. There were 7 (33.3%) recurrent cases during the follow-up and the risk of recurrence in patients with baseline central macular thickness (CMT) ≥ 262.86 μm was 14 times greater than that of patients with CMT  less then  262.86 μm. The risk of recurrence increased 1.84 times for every 100-μm increment in the CMT. Patients over 50 years with mCNV had a worse BCVA, thinner choroid, and higher risk of VIA than young mCNV patients. The standard Conbercept treatment strategy was safe and effective in mCNV patients over 50 years. As patients over 50 years with a greater CMT have a high risk of recurrence, more attention should be paid on these patients by following them up closely.