Though emerging evidence indicates that the pathogenesis of Parkinson's disease is strongly correlated to the accumulation and transmission of α-synuclein (α-syn) aggregates in the midbrain, no anti-aggregation agents have been successful at treating the disease in the clinic. Here, we show that graphene quantum dots (GQDs) inhibit fibrillization of α-syn and interact directly with mature fibrils, triggering their disaggregation. Moreover, GQDs can rescue neuronal death and synaptic loss, reduce Lewy body and Lewy neurite formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of α-syn pathology provoked by α-syn preformed fibrils. We observe, in vivo, that GQDs penetrate the blood-brain barrier and protect against dopamine neuron loss induced by α-syn preformed fibrils, Lewy body/Lewy neurite pathology and behavioural deficits.

Graphene quantum dots (GQDs) have been considered as a novel material because their electronic and optoelectronic properties can be tuned by controlling the size and the functional groups of GQDs. Here we report the synthesis of reduction-controlled GQDs and their application to bulk heterojunction (BHJ) solar cells with enhanced power conversion efficiency (PCE). Three different types of GQDs--graphene oxide quantum dots (GOQDs), 5 h reduced GQDs, and 10 h reduced GQDs--were tested in BHJ solar cells, and the results indicate that GQDs play an important role in increasing optical absorptivity and charge carrier extraction of the BHJ solar cells. The enhanced optical absorptivity by rich functional groups in GOQDs increases short-circuit current, while the improved conductivity of reduced GQDs leads to the increase of fill factors. Thus, the reduction level of GQDs needs to be intermediate to balance the absorptivity and conductivity. Indeed, the partially reduced GQDs yielded the outstandingly improved PCE of 7.60% in BHJ devices compared to a reference device without GQDs (6.70%).

DNA analysis of various body fluid stains at crime scenes facilitates the identification of individuals but does not currently determine the type and origin of the biological material. Recent advances in whole genome epigenetic analysis indicate that chromosome pieces called tDMRs (tissue-specific differentially methylated regions) show different DNA methylation profiles according to the type of cell or tissue. We examined the potential of tissue-specific differential DNA methylation for body fluid identification. Five tDMRs for the genes DACT1, USP49, HOXA4, PFN3, and PRMT2 were selected, and DNA methylation profiles for these tDMRs were produced by bisulfite sequencing using pooled DNA from blood, saliva, semen, menstrual blood, and vaginal fluid. The tDMRs for DACT1 and USP49 showed semen-specific hypomethylation, and the tDMRs for HOXA4, PFN3, and PRMT2 displayed varying degrees of methylation according to the type of body fluid. Preliminary tests using methylation-specific PCR for the DACT1 and USP49 tDMRs showed that these two markers could be used successfully to identify semen samples including sperm cells. Body fluid-specific differential DNA methylation may be a promising indicator for body fluid identification. Because DNA methylation profiling uses the same biological source of DNA for individual identification profiling, the determination of more body fluid-specific tDMRs and the development of convenient tDMR analysis methods will facilitate the broad implementation of body fluid identification in forensic casework.

Background: PTTG1 is an oncogene with its expression levels correlating with tumor development and metastasis. Results: Modulation of PTTG1 expression levels revealed that PTTG1 promotes invasive and migratory properties and expansion of CD44 high CD24 low cell population via AKT activation in breast cancer cells. Conclusion: PTTG1 induces EMT and promotes cancer stem cells via activation of AKT. Significance: PTTG1 represents a potential target for therapeutic intervention against the spread of breast cancer.

Claudins are identified as members of the tetraspanin family of proteins, which are integral to the structure and function of tight junction. Recent studies showed an increase in expression of claudins during tumorigenesis, which is associated with loss of cell-cell contact, dedifferentiation, and invasiveness. However, the molecular basis for the causal relationship between claudin expression and cancer progression is not fully understood yet. In this study, we show that claudin-1 plays a causal role in the acquisition of invasive capacity in human liver cells and that c-Abl-protein kinase C␦ (PKC␦) signaling is critical for Metastasis is the spread of cancer from its primary site to other places in the body, a process that is common in the late stages of cancer (1-4). It is a multistep process that involves migration of cancer cells from the primary tumor site, penetration into the vascular or lymphatic system, dispersal through the circulation, and extravasation and growth of malignant cells in the target organ (2, 3, 5). However, little is known about how malignant cells leave the primary site and begin to grow at distant sites; moreover, how the process of metastatic progression develops in cells is unknown. Thus, understanding the molecular basis for the spread of cancer, especially the development of invasive properties, is one of the most important issues in cancer research.Claudins (CLDs) 2 are a family of integral membrane proteins central to the formation of tight junctions, structures that are critical for the maintenance of cellular polarity, and are involved in paracellular transport and cellular growth and differentiation (6 -8). Recent studies have provided evidence that claudins are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs) (9 -11), and are associated with the development and progression of cancer. In this context, it has been shown that decreased or abnormal expression of claudin-4 (CLD4) or claudin-7 (CLD7) is correlated with liver metastases (12)(13)(14). Moreover, downregulation of claudin-2 (CLD2) has been implicated in the development and progression of breast carcinomas (4). Other reports, however, have suggested that increased CLD4 expression is associated with poor prognosis and high tumor grade in human breast cancer (15). In addition, overexpression of claudin-1 (CLD1) is associated with advanced stage disease in oral squamous cell carcinomas (16,17) and with angiolymphatic and perineural invasion, consistent with an aggressive tumor phenotype (16 -19). Moreover, CLD2, in combination with the epidermal growth factor receptor, has been shown to participate in tumor colonization in non-small cell lung cancer (20). These results indicate that the expression and functional significance of claudins may be highly specific for tumor cell type and depend on tumor grade.

Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. .

No abstract

No abstract