The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Zinc Ion Coordinated Poly(Ionic Liquid) Antimicrobial Membranes for Wound Healing

Herein, a series of quaternary ammonium (Qa) or imidazolium (Im) cation-based poly­(ionic liquid) (PIL) membranes and their corresponding zinc ion coordinated PIL membranes were synthesized. The effects of chemical structure, including organic cations, alkyl side chain of substitution, and zinc atoms on the antimicrobial activities against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Candida albicans</i> were investigated. The Zn-containing PIL membranes show higher antibacterial activities compared to those of pristine PIL membranes due to the synergistic attributes of both organic cations (Qa or Im) and zinc atoms. A wound healing test using methicillin-resistant <i>S. aureus</i> infected mouse as the model further demonstrated that zinc ion coordinated PIL membranes were antibacterially active, biologically safe, and may have potential application as an antimicrobial wound dressing in a clinical setting

Metal-Containing Poly(ionic liquid) Membranes for Antibacterial Applications

Imidazolium-type metal-containing ionic liquid (IL) monomers and their corresponding poly­(ionic liquid) (PIL) membranes coordinated with CuCl₂ (PILM-Cu), FeCl₃ (PILM-Fe), or ZnCl₂ (PILM-Zn) were synthesized. The effect of metal ions on the antimicrobial activities against both <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and <i>Escherichia coli</i> (<i>E. coli</i>) was investigated. Compared with pristine PILM-Br membrane, PILM-Cu, PILM-Fe, and PILM-Zn membranes exhibit enhanced antibacterial activities due to the attributes of both imidazolium cations and metal-containing anions. Furthermore, all of the metal-containing PIL membranes present low hemolysis toward human red blood cell and high long-term antibacterial stability, even after immersion in water for 90 days, demonstrating clinical feasibility in topical applications

Systemic Metabolic Changes of Traumatic Critically III Patients Revealed by an NMR-Based Metabonomic Approach

Progression of critically ill patients from Systemic Inflammatory Response Syndrome (SIRS) to Multiple Organ Dysfunction Syndrome (MODS) accounts for more than 75% of deaths in adult surgical intensive care units. Currently, there is no practical clinical technique to predict the progression of SIRS or MODS. In this report, we describe an NMR-based metabonomic method to aid detection of these conditions based on abnormal metabolic signatures. We applied pattern recognition methods to analyze one-dimensional H-1 NMR spectra of SIRS and MODS patient sera. By using Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA), we could distinguish critically ill patients (n = 52) from healthy controls (n = 26). After noise reduction by Orthogonal Signal Correction (OSC), PLS-DA was also able to clearly discriminate SIRS and MODS patients. The corresponding coefficients indicated that spectra responsible for the discrimination were located in delta 3.06-3.86 NMR integral regions from SIRS, mainly composed of sugars, amino acids and glutamine signals, and delta 1.18-1.3 and delta 4.02-4.1 integral regions of MODS serum samples, principally consisted of various proton signals of fatty acyl chains and glycerol backbone of lipids, along with creatinine and lactate. Our results are consistent with the clinical observations that carbohydrate and amino acid levels changes in the early course of critical illness (SIRS stage) and significant disturbances in fat metabolism and development of organ abnormalities become the characteristics in the late stage (MODS). These data suggest that NMR-based metabonomic approach can be developed to diagnose the disease progress of critically ill patients.Department of Health, Jiangsu Provincial People's Government [H200872]; Nantong Social Development Project [S2007038]; Nantong University [08ZY004]; China Postdoctoral Science Foundation ; Open Lab Project of Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences [7152710]; National Natural Science Foundation of China [20705037, 30570352, 30730026

Structure–Antibacterial Activity Relationships of Imidazolium-Type Ionic Liquid Monomers, Poly(ionic liquids) and Poly(ionic liquid) Membranes: Effect of Alkyl Chain Length and Cations

The structure–antibacterial activity relationship between the small molecular compounds and polymers are still elusive. Here, imidazolium-type ionic liquid (IL) monomers and their corresponding poly­(ionic liquids) (PILs) and poly­(ionic liquid) membranes were synthesized. The effect of chemical structure, including carbon chain length of substitution at the N3 position and charge density of cations (mono- or bis-imidazolium) on the antimicrobial activities against both <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>) was investigated by determination of minimum inhibitory concentration (MIC). The antibacterial activities of both ILs and PILs were improved with the increase of the alkyl chain length and higher charge density (bis-cations) of imidazolium cations. Moreover, PILs exhibited lower MIC values relative to the IL monomers. However, the antibacterial activities of PIL membranes showed no correlation to those of their analogous small molecule IL monomers and PILs, which increased with the charge density (bis-cations) while decreasing with the increase of alkyl chain length. The results indicated that antibacterial property studies on small molecules and homopolymers may not provide a solid basis for evaluating that in corresponding polymer membranes

Intrinsically Antibacterial Poly(ionic liquid) Membranes: The Synergistic Effect of Anions

The development of materials with intrinsically antimicrobial activities has attracted great interest. Herein, we report the synthesis of free-standing and robust poly­(ionic liquid) (PIL) membranes with high antibacterial activities by in situ photo-cross-linking of an ionic liquid monomer and followed by anion-exchange with an amino acid (l-proline (Pro) or l-tryptophan (Trp)). The resultant PIL-based membranes with excellent robustness exhibit high antimicrobial properties against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) and present no significant hemolysis and cytotoxicity toward human red blood and skin fibroblast cells, as well as low adsorption of bovine serum albumin. The synthesized PIL-Trp membranes exhibit the highest antibacterial efficiency due to the synergistic attributes of both imidazolium cation and Trp^– anion. Furthermore, all the PIL-based membranes exhibit long-term antibacterial stability, which demonstrates clinical feasibility in topical applications

In-depth characterization of the pituitary transcriptome in Simmental and Chinese native cattle

The pituitary gland is a key endocrine organ responsible for growth and development. To get closer to understanding important molecular mechanisms at work in the bovine pituitary and identifying the core genes controlling growth, in the present study we have analyzed the transcriptome profiling of the pituitary glands of two cattle breeds (Wenshan and Simmental cattle) with extreme growth differences using high-throughput RNA sequencing. Our study revealed that the overall gene expression levels are quite similar between the two breeds. A total of 18,065 annotated genes were identified, which accounted for 85% of the annotated genes in cattle. The five most abundant hormone genes (GH, PRL, POMC, CGA, and LHB) were relatively stable in both breeds, indicating their pivotal roles in maintaining the basic functions of the pituitary. In addition, 105 genes were identified as differentially expressed between Wenshan and Simmental pituitary glands, including 83 known and 22 novel genes. Functional association analyses of the differentially expressed genes between the breeds revealed 60 enriched gene ontology terms and 3 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Interestingly, the most enriched KEGG pathway, cell adhesion molecules, can modulate pituitary hormone secretion by cell-cell contact. Our findings demonstrated that SYTL2, SLC38A4, and NCAM2 are new candidates for crucial functions in the secretory pathways of the pituitary gland. These results will further understanding of the important molecular mechanisms at work in the bovine pituitary

Pathological Features of <i>Staphylococcus aureus</i> Induced Mastitis in Dairy Cows and Isobaric-Tags-for-Relative-and-Absolute-Quantitation Proteomic Analyses

In part as a result of the production of an enterotoxin, <i>Staphylococcus aureus</i> is a highly infectious pathogen and is a considerable threat to food hygiene and safety. Clinical mastitis models were established by <i>S. aureus</i> nipple-tube perfusion. The influence of mastitis on the mammary-gland-tissue proteomic profile was investigated using isobaric tags for relative and absolute quantitation. In this study, healthy and mastitic tissues from different mammary-gland areas of the same dairy cows were screened, and differentially expressed proteins were identified. Bioinformatic analysis identified proteins related to the inflammation and immunization of dairy cows. Histology, immunoblotting, and immunohistochemical-staining analyses were used to determine the expression of PGLYRP1 and PTX3 proteins in the acquired mammary-gland-tissue samples. PGLYRP1 and PTX3 in mastitic mammary glands may be associated with tissue damage and immune responses to late stages of infection. This further contributes to the understanding of the molecular theory of the treatment of mastitis caused by <i>S. aureus</i>