Hendricksmcmillan8785

Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM.Corynebacteriales are Actinobacteria that possess an atypical didermic cell envelope. One of the principal features of this cell envelope is the presence of a large complex made up of peptidoglycan, arabinogalactan and mycolic acids. This covalent complex constitutes the backbone of the cell wall and supports an outer membrane, called mycomembrane in reference to the mycolic acids that are its major component. The biosynthesis of the cell envelope of Corynebacteriales has been extensively studied, in particular because it is crucial for the survival of important pathogens such as Mycobacterium tuberculosis and is therefore a key target for anti-tuberculosis drugs. In this study, we explore the biogenesis of the cell envelope of Corynebacterium glutamicum, a non-pathogenic Corynebacteriales, which can tolerate dramatic modifications of its cell envelope as important as the loss of its mycomembrane. For this purpose, we used a genetic approach based on genome-wide transposon mutagenesis. We developed a highly e a better understanding of the biosynthesis of the envelope components of these bacteria.Chimpanzees (Pan troglodytes) are, along with bonobos, humans' closest living relatives. The advent of diffusion MRI tractography in recent years has allowed a resurgence of comparative neuroanatomical studies in humans and other primate species. Here we offer, in comparative perspective, the first chimpanzee white matter atlas, constructed from in vivo chimpanzee diffusion-weighted scans. Comparative white matter atlases provide a useful tool for identifying neuroanatomical differences and similarities between humans and other primate species. Until now, comprehensive fascicular atlases have been created for humans (Homo sapiens), rhesus macaques (Macaca mulatta), and several other nonhuman primate species, but never in a nonhuman ape. Information on chimpanzee neuroanatomy is essential for understanding the anatomical specializations of white matter organization that are unique to the human lineage.The critical demand for eco-friendly, renewable, and safe energy resources is essential issue encountering in the contemporary world. The catalytic transesterification of plant oils into biodiesel was assessed as promising technique to provide new forms of clean and safe fuels. Natural clinoptilolite was doped with Na+ ions by green chemical reactions suiting sodium nitrite and green tea extract producing novel modified structure (Na+/Clino). The Na+/Clino product is of enhanced total basicity (6.41 mmol OH/g), ion exchange capacity (387 meq/100g), and surface area (312.7 m2/g) which qualifies it as a potential basic catalyst for the transesterification of palm oil. The transesterification tests were assessed statistically by the response surface methodology and the central composite design. Considering the interaction effect of the affecting factors with each other, the synthetic Na+/Clino achieved 96.4 % as experimental biodiesel yield after 70 min at 100 oC in the presence of 2.75 wt., % catalyst loading, and 12.51 methanol/palm oil ratio. Based on the optimization function of the statistical model, the performance of Na+/Clino can be enhanced theoretically to increase the yield to 98.2 % by expanding the test time to 85 min and the loading value to 3 wt., %. The resulted product over Na+/ClinO is of adequate technical properties considering the international levels for standard biodiesel (EN 14214 and ASTM D-6751). Finally, the prepared green Na+ doped clinoptilolite is of excellent recyclability as a heterogeneous basic catalyst and displayed higher efficiency than several species of previously studied heterogeneous and homogenous catalysts.In this paper, Au nanoparticles (AuNPs) are prepared using wet chemical reduction transfer of dense AuNPs film by self-assembly to the surface of Ag grating, which is inverted from the inner DVD after evaporation. The Ag grating/AuNPs self-assembly hybrid substrate commonly used in surface-enhanced Raman scattering (SERS) research is produced. The coupling effect between AuNP-AuNP and AuNPs-Ag slugs can evidently enhance the local electric field. Experimental results show that the hybrid SERS substrate can detect 10-9 M Rh6G, and the enhancement factor reaches 4.4×105. This small, cheap hybrid substrate has enormous potential in the field of SERS sensing.The intrinsic poor solubility and limited load capacity of β-cyclodextrins (β-CDs) results in reduced bioavailability, rendering the material unsuitable in complex biological environments. In this work, a pair of β-CDs was methylated and covalently linked with acid-sensitive acylhydrazone and GSH-sensitive disulfide bonds to ensure a precise drug release pattern. The hydrophobic anticancer drug doxorubicin (Dox) was encapsulated inside the hydrophobic core of bis(β-CD) via hydrophobic association with loading capacity of 24% in weight and a hydrodynamic size of about 100 nm. When exposed to acidic and reductive environments, the acylhydrazone and disulfide bonds were found to be cleaved, resulting in Dox release. Using fluorescence imaging and flow cytometry analysis, the designed bis(β-CD) were determined to activate the drug release behavior by specific intracellular stimuli (pH and GSH). HSP (HSP90) inhibitor In vivo studies demonstrated specific drug delivery characteristics and controlled drug release behaviors in the tumor sites, giving rise to high antitumor activity and low toxicity.