Sagittal nasal dural arteriovenous fistula manifesting since unilateral singing retract paresis
Manganese overexposure can induce neurotoxicity, lead to manganism and result in clinical manifestations similar to those of parkinsonism. However, the underlying molecular mechanism is still unclear. This study demonstrated that MnCl
induces mitophagy and leads to neurotoxicity by promoting BNIP3-mediated reactive oxygen species (ROS) generation.
Human neuroblastoma SH-SY5Y cells were used throughout our experiments. Cell viability was detected by cell proliferation/toxicity test kits. Mitochondrial membrane potential was measured by flow cytometry. Selleckchem WM-8014 ROS generation was detected using a microplate reader. Protein levels were evaluated by Western blot. Transmission electron microscopy was used to evaluate mitochondrial morphology. Co-immunoprecipitation was used to verify the interaction between BNIP3 and LC3.
MnCl
led to loss of mitochondrial membrane potential and apoptosis of SH-SY5Y cells by enhancing expression of BNIP3 and conversion of LC3-I to LC3-II. Moreover, MnCl
reduced expression of the mitochondrial marker protein TOMM20 and promoted interaction between BNIP3 and LC3. The results also indicated that a decrease in BNIP3 expression reduced the mitochondrial membrane potential loss, attenuated apoptosis and reduced mitochondrial autophagosome formation in SH-SY5Y cells after MnCl
treatment. Finally, we found that manganese-induced ROS generation could be reversed by the antioxidant N-acetyl cysteine (NAC) or silencing BNIP3 expression.
BNIP3 mediates MnCl
-induced mitophagy and neurotoxicity in dopaminergic SH-SY5Y cells through ROS. Thus, BNIP3 contributes to manganese-induced neurotoxicity by functioning as a mitophagy receptor protein.
BNIP3 mediates MnCl2-induced mitophagy and neurotoxicity in dopaminergic SH-SY5Y cells through ROS. Thus, BNIP3 contributes to manganese-induced neurotoxicity by functioning as a mitophagy receptor protein.
During the Neolithic expansion, cattle accompanied humans and spread from their domestication centres to colonize the ancient world. In addition, European cattle occasionally intermingled with both indicine cattle and local aurochs resulting in an exclusive pattern of genetic diversity. Among the most ancient European cattle are breeds that belong to the so-called Podolian trunk, the history of which is still not well established. Here, we used genome-wide single nucleotide polymorphism (SNP) data on 806 individuals belonging to 36 breeds to reconstruct the origin and diversification of Podolian cattle and to provide a reliable scenario of the European colonization, through an approximate Bayesian computation random forest (ABC-RF) approach.
Our results indicate that European Podolian cattle display higher values of genetic diversity indices than both African taurine and Asian indicine breeds. Clustering analyses show that Podolian breeds share close genomic relationships, which suggests a likely common gdmixture as a driver of diversification in Italy, which could represent a melting pot for Podolian cattle.
Understanding the functional effects of non-coding variants is important as they are often associated with gene-expression alteration and disease development. Over the past few years, many computational tools have been developed to predict their functional impact. However, the intrinsic difficulty in dealing with the scarcity of data leads to the necessity to further improve the algorithms. In this work, we propose a novel method, employing a semi-supervised deep-learning model with pseudo labels, which takes advantage of learning from both experimentally annotated and unannotated data.
We prepared known functional non-coding variants with histone marks, DNA accessibility, and sequence context in GM12878, HepG2, and K562 cell lines. Applying our method to the dataset demonstrated its outstanding performance, compared with that of existing tools. Our results also indicated that the semi-supervised model with pseudo labels achieves higher predictive performance than the supervised model without pseudo labelal phenomena, including human diseases.Dendrimers are macromolecules with high-polymeric branching capable of undergoing major modifications. These characteristics make them an efficient nanocarrier capable of encapsulating and delivering drug, antibodies, or any therapeutic gene. The failure of conventional techniques to deliver drug with higher efficacy and reduced side effects has led to the use of nanomedicines including dendrimers. Dendrimers are novel drug carriers that are modified, complexed, and conjugated with different ligands and receptors to target the delivery of drug at the specific site without impacting any of the normal cells in surrounding. Moreover, the biocompatibility and safety of the dendrimers can be altered accordingly by the process of functionalization by PEGylation, acetylation, or amination. Various dendrimers have been designed to incorporate and deliver anticancer drug either in free form or as codelivery in conjugation with other drugs or therapeutic siRNA/DNA. Doxorubicin (DOX) is one such chemotherapeutic drug thdrimers and their compatibility with DOX (free/salt), the article was updated with all current insights.The goal of the study was to investigate the concentration of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in 84 samples of mussels, collected from supermarkets and fish markets in Serbia. Lead, cadmium, mercury and arsenic concentrations were determined using an inductive coupled plasma mass spectrometry method. Sixteen PAHs were determined using a gas chromatography-mass spectrometry method. Heavy metals in the mussels were in the range (mg/kg) of 0.01-0.74 for lead, 0.01-0.38 for cadmium, 0.01-0.15 for mercury and 1.12-5.87 for arsenic. Metals and PAHs levels in all analysed samples were under the legal European and Serbian legislation limits. The provisional tolerable intake values were calculated on the base of the obtainable values of heavy metals. Mussels are considered to be safe for human consumption. However, one should take care of the amount and frequency of mussel consumption, primarily due to consumer's cadmium and mercury burden.