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To clarify whether differential compartmentalization of Survivin impacts temozolomide (TMZ)-triggered end points, we established a well-defined glioblastoma cell model in vitro (LN229 and A172) and in vivo, distinguishing between its nuclear and cytoplasmic localization. Expression of nuclear export sequence (NES)-mutated Survivin (SurvNESmut-GFP) led to impaired colony formation upon TMZ. This was not due to enhanced cell death but rather due to increased senescence. Nuclear-trapped Survivin reduced homologous recombination (HR)-mediated double-strand break (DSB) repair, as evaluated by γH2AX foci formation and qPCR-based HR assay leading to pronounced induction of chromosome aberrations. Opposite, clones, expressing free-shuttling cytoplasmic but not nuclear-trapped Survivin, could repair TMZ-induced DSBs and evaded senescence. Mass spectrometry-based interactomics revealed, however, no direct interaction of Survivin with any of the repair factors. The improved TMZ-triggered HR activity in Surv-GFP was associated with enhanced mRNA and stabilized RAD51 protein expression, opposite to diminished RAD51 expression in SurvNESmut cells. Notably, cytoplasmic Survivin could significantly compensate for the viability under RAD51 knockdown. Differential Survivin localization also resulted in distinctive TMZ-triggered transcriptional pathways, associated with senescence and chromosome instability as shown by global transcriptome analysis. Orthotopic LN229 xenografts, expressing SurvNESmut exhibited diminished growth and increased DNA damage upon TMZ, as manifested by PCNA and γH2AX foci expression, respectively, in brain tissue sections. Consequently, those mice lived longer. Although tumors of high-grade glioma patients expressed majorly nuclear Survivin, they exhibited rarely NES mutations which did not correlate with survival. Based on our in vitro and xenograft data, Survivin nuclear trapping would facilitate glioma response to TMZ.

Six borazine-linked polymers (BLPs) have been synthesized through the thermolysis reaction of p -phenylenediamine, 1,3,5-tris-(4-aminophenyl)benzene, benzidine, or tetra-(4-aminophenyl)methane with boron tribromide or boron trichloride. Each product exists as an amorphous polymer whose chemical connectivity was confirmed by FT-IR and elemental analysis while thermogravimetric analysis revealed moderate thermal stabilities up to about 200 °C under nitrogen atmosphere. All BLPs possess high surface areas with chlorinated BLPs exhibiting higher values than brominated BLPs (1,174–1,569 vs. 503–849 m 2 /g, respectively). Gas storage capabilities were investigated as well. BLPs possess good hydrogen uptakes (0.68–1.75 wt% at 77 K) and zero-coverage isosteric heat of adsorption, Q st , (7.06–7.65 kJ/mol) as calculated by the virial method. The uptakes and heat of adsorption for carbon dioxide (51–141 mg/g at 273 K with Q st : 22.2–31.7 kJ/mol) are also attractive. BLPs do not, however, appear to exhibit significant methane storage capacities (1.9–15.2 mg/g at 273 K with Q st : 17.1–21.7 kJ/mol). Accordingly, CO 2 /CH 4 selectivity studies were performed using the ideal adsorbed solution theory and further supported by initial slope calculations. The results indicate that BLP-1(Br) and BLP-2(Br) exhibit very high CO 2 /CH 4 selectivities 23 and 26, respectively, which make them attractive for small gas separation applications.

Nephrotoxicity caused by drug or chemical exposure involves complex mechanisms as well as a temporal integration of injury and repair responses in different nephron segments. Distinct cellular transcriptional programs regulate the time-dependent tissue injury and regeneration responses. Whole kidney transcriptome analysis cannot dissect the complex spatio-temporal injury and regeneration responses in the different nephron segments. Here, we used laser capture microdissection of formalin-fixed paraffin embedded sections followed by whole genome targeted RNA-sequencing-TempO-Seq and co-expression gene-network (module) analysis to determine the spatial–temporal responses in rat kidney glomeruli (GM), cortical proximal tubules (CPT) and outer-medulla proximal tubules (OMPT) comparison with whole kidney, after a single dose of the nephrotoxicant cisplatin. We demonstrate that cisplatin induced early onset of DNA damage in both CPT and OMPT, but not GM. Sustained DNA damage response was strongest in OMPT coinciding with OMPT specific inflammatory signaling, actin cytoskeletal remodeling and increased glycolytic metabolism with suppression of mitochondrial activity. Later responses reflected regeneration-related cell cycle pathway activation and ribosomal biogenesis in the injured OMPT regions. Activation of modules containing kidney injury biomarkers was strongest in OMPT, with OMPT Clu expression highly correlating with urinary clusterin biomarker measurements compared the correlation of Kim1. Our findings also showed that whole kidney responses were less sensitive than OMPT. In conclusion, our LCM-TempO-Seq method reveals a detailed spatial mechanistic understanding of renal injury/regeneration after nephrotoxicant exposure and identifies the most representative mechanism-based nephron segment specific renal injury biomarkers. Graphical Abstract Highlights • Different nephron segments exhibit distinct transcriptomic perturbation with different degrees of sensitivity. • Sustained activation of DNA damage responses upon cisplatin exposure is linked to progressive outcomes of injured nephron regions. • Mechanistic kidney injury biomarkers such as urinary clusterin outperform conventional biomarkers in reflecting the condition of the damaged nephron segments.

At the 2013 Charleston Conference I presented my paper: “Less Is More: The University of Wisconsin–Stevens Point Collection Assessment Program.” For the first time in decades, the UWSP Albertson Library had started a weeding and collection assessment of our entire stacks print holdings. In 2012–2013, our seven-floor learning resource center faced a pending renovation project slated for 2017. Dutifully, we vetted and adopted a thorough collection assessment plan though our collection development committee. Weeding of the collection was initiated so collections occupied “less” space, while at the same time we set out to enhance the collection so that

The synthesis of highly porous organic polymers with predefined porosity has attracted considerable attention due to their potential in a wide range of applications. Of particular interest in porous organic polymers is their potential use in automotive applications as well as separation processes whereby advancements could result in a reduction in carbon dioxide emissions and the production of natural gas in a more economically friendly manner. Along these pursuits, seven borazine-linked polymers (BLPs) have been synthesized through the introduction of p-phenylenediamine, 1,3,5-tris-(4-aminophenyl)benzene, benzidine, or tetra-(4-aminophenyl)methane with boron tribromide or boron trichloride followed by the thermolysis reaction of the resulting in situ adduct. All resulting polymers exist as amorphous polymers whose chemical connectivity was confirmed through FT-IR, solid state 11B and 13C NMR, and elemental analysis while thermogravimetric analysis reveals moderate thermal stabilities up to about 200°C. To assess their textural properties, all BLPs were subjected to nitrogen sorption experiments at 77 K. In all cases, the polymers possess high surface areas with chlorinated BLPs exhibiting higher values than their brominated analogues (1174-1569 m2/g versus 503-849 m2/g, respectively). Gas storage capabilities of BLPs for hydrogen, carbon dioxide, and methane were investigated as well. BLPs possess good hydrogen uptakes (0.68-1.75 wt% at 77 K) and zero-coverage isosteric heat of adsorption, Qst, (7.06-7.65 kJ/mol) as calculated by the virial method. The uptakes and heats of adsorption for carbon dioxide (51-141 mg/g at 273 K with Qst: 22.2-31.7 kJ/mol) are also attractive. BLPs do not, however, appear to exhibit significant methane storage capabilities (1.9-15.2 mg/g at 273 K with Qst: 17.1-21.7 kJ/mol). In light of such a difference in storage between carbon dioxide and methane, CO2/CH4 selectivity was calculated for each polymer according to the ideal adsorbed solution theory (IAST). Three of the polymers, BLP-1(Br), BLP-2(Br), and BLP-10(Cl), possess excellent selectivity capabilities over 20 even at low pressures for all molar ratios. Additionally, these selectivity values increase further with increasing pressure. Selectivity was also investigated for benzimidazole-linked polymers. In such systems, the CO2/N2 selectivity values reach 73 at low pressure and exhibit an increasing trend with increasing pressure.

A bacterial isolate, tentatively identified as Pseudomonas sp. strain TR3, was found to utilize the diaryl ester phenylbenzoate as sole source of carbon and energy. This strain has the ability to productively degrade phenylbenzoate and some substituted derivatives by a catabolic sequence which was characterized biochemically. The biodegradation of phenylbenzoate is thus initiated by an inducible esterase, effectively hydrolyzing the diaryl esters to produce stoichiometric amounts of two monoaromatic metabolites, identified as benzoate and phenol in the case of phenylbenzoate. The diaryl ester p-tolylbenzoate was hydrolyzed to yield benzoate and 4-methylphenol while 4-chlorophenylbenzoate gave rise to the production of benzoate and 4-chlorophenol. These monoaromatic catabolites were further degraded via the oxoadipate pathway.

A bacterial isolate, tentatively identified as Pseudomonas sp. strain TR3, was found to utilize the diaryl ester phenylbenzoate as sole source of carbon and energy. This strain has the ability to productively degrade phenylbenzoate and some substituted derivatives by a catabolic sequence which was characterized biochemically. The biodegradation of phenylbenzoate is thus initiated by an inducible esterase, effectively hydrolyzing the diaryl esters to produce stoichiometric amounts of two monoaromatic metabolites, identified as benzoate and phenol in the case of phenylbenzoate. The diaryl ester p-tolylbenzoate was hydrolyzed to yield benzoate and 4-methylphenol while 4-chlorophenylbenzoate gave rise to the production of benzoate and 4-chlorophenol. These monoaromatic catabolites were further degraded via the oxoadipate pathway.